PATENT ABSTRACT
The present invention relates to protein disulfide isomerases which are encoded by a nucleic acid sequence which hybridizes with (i) the DNA sequence of SEQ ID NO:1 or (ii) the DNA sequence of SEQ ID NO:2, under the following conditions: presoaking in 5×SSC and prehybridizing for 1 h at ˜40° C. in a solution of 5×SSC, 5×Denhardt&#39;s solution, 50 mM sodium phosphate, pH 6.8, and 50 μg of denatured sonicated calf thymus DNA, followed by hybridization in the same solution supplemented with 50 μCi 32-P-dCTP labelled probe for 18 h at ˜40° C. followed by washing three times in 2×SSC, 0.2% SDS at 40° C. for 30 minutes; and fragments thereof. The present invention also relates to DNA sequences encoding the protein disulfide isomerases, compositions comprising said protein disulfide isomerases and methods of use thereof.

PATENT DESCRIPTION
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of U.S. Ser. No. 08/557,122 filed Dec. 11, 1995, now U.S. Pat. No. 5,879,664 which is a 35 U.S.C. 371 national application of PCT/DK94/00266 filed Jun. 28, 1994 and claims priority under 35 U.S.C. 119 of Danish application 0768/93 filed Jun. 28, 1993, the contents of which are fully incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to an active recombinant fungal protein disulfide isomerase, compositions comprising said fungal protein disulfide isomerase, and methods for their use; a DNA construct comprising a DNA sequence encoding said fungal protein disulfide isomerase, and a vector and cell harbouring the DNA construct. Furthermore, the present invention relates to a method of preparing the fungal protein disulfide isomerase by use of both traditional and recombinant DNA techniques. 
     BACKGROUND OF THE INVENTION 
     The use of protein disulfide redox agents such as protein disulfide isomerases (PDI), and thioredoxins (TRX) for various purposes has been known for some time. 
     Protein disulfide redox agents catalyse the general reaction: 
     
       
         R 1 —SH+R 2 —SH+Enz ox ⇄R 1 —S—S—R 2 +Enz red   (reaction I) 
       
     
     where R 1  and R 2  represent protein entities which are the same or different, either within the same polypeptide or in two polypeptides, Enz ox  is a protein disulfide redox agent in the oxidised state, and Enz red  is a protein disulfide redox agent in the reduced state. EC 5.3.4.1 refers to an enzyme capable of capable of catalysing the rearrangement of —S—S— bonds in proteins and EC 1.6.4.4 and EC 1.8.4.2 is an example of enzymes catalysing the reaction with NAD(P)H and glutathione as a mediator, respectively. 
     This type of activity has been designated as protein disulfide isomerase, sulfhydryl oxidase, protein disulfide reductase, disulfide isomerase, protein disulfide transhydrogenase, and sulfhydryl oxidase. 
     Disulfide linkages in proteins are formed between cysteine residues and have the general function of stabilising the three dimensional structure of the proteins. They can be formed between cysteine residues of the same or different polypeptides. 
     Disulfide linkages are present in many types of proteins such as enzymes, structural proteins, etc. Enzymes are catalytic proteins such as proteases, amylases, etc., while structural proteins can be scleroproteins such as keratin, etc. Protein material in hair, wool, skin, leather, hides, food, fodder, stains, and human tissue contains disulfide linkages. Treatment of some of these materials with PDI and TRX, and a redox partner have been described previously. 
     The use of TRX for waving, straightening, removing and softening of human and animal hair was described by Pigiet et al. (EP 183506 and WO 8906122). Pigiet (U.S. Pat. No. 4,771,036) also describes the use of TRX for prevention and reversal of cataracts. Schreiber (DE 2141763 and DE 2141764) describes the use of protein disulfide transhydrogenase for changing the form of human hair. Pigiet (EP 225156) describes the use of TRX for refolding denatured proteins. Use of TRX to prevent metal catalysed oxidative damage in biological reactions is described by Pigiet et al. (EP 237189). 
     Toyoshima et al. (EP 277563 and EP 293793) describes the use of PDI to catalyse renaturation of proteins having reduced disulfide linkages or unnatural oxidised disulfide linkages, in particular in connection with renaturation of recombinantly produced proteins. Brockway (EP 272781), and King and Brockway (EP 276547) describe the use of PDI for reconfiguration of human hair, and for treatment of wool, respectively. Sulfhydryl oxidase for the treatment of Ultra-high temperature sterilized milk is described in U.S. Pat. Nos. 4,894,340, 4,632,905, 4,081,328 and 4,053,644. Schreiber (DE 2141763 and DE 2141764) describes the use of protein disulfide transhydrogenase for changing the form of human hair. 
     The uses of such enzymes have all been connected with reduction of protein disulfide linkages to free protein sulhydryl groups and/or the oxidation of protein sylfhydryl groups to protein disulfide linkages, and/or the rearrangement of disulfide linkages in the same or between different polypeptides, and sometimes to the use of these processes in sequence. 
     Protein disulfide redox agents can be divided into two main groups of enzymes, thioredoxin type (TRX), and protein disulfide isomerase type (PDI). 
     Both these can be modified to obtain protein engineered derivatives, chemical modifications and hybrids of TRX and/or PDI (ENG). 
     TRX is a 12-kDa protein having a redox-active disulfide/dithiol and catalysing thiol-disulfide exchange reactions (Edman et al., Nature 317:267-270, 1985; Holmgren, Ann. Rev. Biochem. 54:237-271, 1985; Holmgren, J. Biol. Chem. 264:13963-13966, 1989). PDI consists of two subunits, each consisting of two domains which are homologous to TRX. 
     TRX and PDI can be obtained from a number of sources: PDI: protein disulfide isomerases have mainly been identified from mammalian sources, such as Bovine (Yamauchi et al., Biochem. Biophys. Res. Commun. 146:1485-1492, 1987), Chicken (Parkkonen et al., Biochem. J. 256:1005-1011, 1988), Human (Rapilajaniemi et al. EMBO J. 6:643-649, 1987), Mouse (Gong, et al., Nucleic Acids Res. 16:1203, 1988), Rabbit (Fliegel et al., J. Biol. Chem. 265:15496-15502, 1990), and Rat (Edman et al., Nature 317:267-270, 1985). PDI has furthermore been isolated from yeast (Tachikawa et al., J. Biochem. 110:306-313). 
     TRX: Thioredoxin has been identified from bacteriophages, bacteria such as  Escherichia coli  (Wallace and Kusher, Gene 32:399-408, 1984) and  Bacillus subtilis  (Chen et al. J. Biol Chem. 262:8787-8798, 1987) and eukaryotes. 
     It would be desirable to facilitate the production of protein disulfide isomerase (PDI), to be able of producing both larger amounts of the enzyme and to produce it in a more economical manner than what is possible by the prior art methods. 
     Engineered variants (ENG) with improved properties for particular applications are also highly desirable and can be prepared by a variety of methods based on standard recombinant DNA technology: 
     1) by using site-directed or random mutagenesis to modify the genes encoding TRX or PDI in order to obtain ENG with one or few amino acid changes, 
     2) by inhibiting or otherwise avoiding dimerisation of the subunits of PDI, thus giving rise to PDI monomers, 
     3) by producing partial monomers of PDI or TRX, in which regions of the NH2- or COOH termini of PDI or TRX are lacking, 
     4) by creating hybrids of PDI, TRX and/or ENG, 
     5) by chemically or enzymatically modifying the products of 1)-4), 
     6) by a combination of any of 1)-5). 
     ENG produced according to 1) were described by Lundström et al. (J. Biol. Chem. 267:9047-9052, 1992) and by a combination of 3) and 5) by Pigiet (WO 8906122). 
     PDI, and TRX can, apart from their natural sources, be obtained by expression of recombinant DNA encoding plant, animal, human or microbial PDI, or TRX, in various hosts, such as microorganisms followed by purification of PDI, or TRX from extracts or supernatants of said host organisms. This goes also for ENG. Preparation of Trx from natural sources is described by Luthman and Holmgren (Biochem. 121:6628-6633, 1982), Wada and Buchanan (in “Thioredoxins, structure and function” (Gadal, Ed.) Editions du Centre National de la Recherche Scientifique), Porque et al. (J. Biol. Chem. 245:2362-2379, 1970) and by Laurent et al. (J. Biol. Chem. 239:3436-3445), whereas recombinant production of TRX is described by Krause et al. (J. Biol. Chem. 266:9494-9500). PDI or sulfhydryl oxidase has been prepared from natural sources by Lambert and Freedman (Biochem J. 213:225-234, 1983), Starnes et al. (U.S. Pat. No. 4,632,905) and Hammer et al. (U.S. Pat. No. 4,894,340), and by recombinant technology by among others Yamauchi et al. (Biochem. Biophys. Res. Commun. 146:1485-1492, 1987). Finally, recombinant production of an ENG is described by Lundström et al. (J. Biol. Chem. 267:9047-9052, 1992). 
     SUMMARY OF THE INVENTION 
     The present inventors have succeeded in cloning a DNA sequence encoding a fungal protein disulfide isomerase from filamentous fungi and in obtaining expression of an active protein disulfide isomerase from said DNA sequence, both in the same species and in other organisms, especially microorganisms, and preferably in fungi. 
     Accordingly, in a first aspect the present invention relates to an active protein disulfide isomerase obtainable from filamentous fungi, specifically fungi belonging to the genus Aspergillus, and especially a protein disulfide isomerase obtainable from  A. oryzae,  or  A. niger,  which enzyme is immunologically reactive with an antibody raised against a purified protein disulfide isomerase derived from  Aspergillus oryzae,  IFO 4177, or  Aspergillus niger,  A524. 
     From the sequence of the isolated enzyme it can be seen that the protein disulfide isomerase has two -Cys-X-Y-Cys- subunits in positions 58-61 and 393-396. The invention consequently also comprises active truncated forms of the enzymes of the invention, wherein at least one subunit is retained. Examples hereof could be an enzyme having an amino acid sequence corresponding to the residues 20 to 100, residues 330 to 450, or residues 360 to 430 of the appended SEQ ID No. 3, or the corresponding sequence of the enzyme of the invention in question. 
     Under this aspect, the invention specifically relates to enzymes exhibiting protein disulfide isomerase activity comprising the amino acid residues 1-131, 1-141, 1-143, 1-163, 1-174, or 1-281, of the amino acid sequence shown in the appended SEQ ID No. 3, or variants thereof exhibiting a protein disulfide isomerase activity. Further specific enzymes are enzymes exhibiting protein disulfide isomerase activity comprising the amino acid residues 1-115, of the amino acid sequence shown in the appended SEQ ID No. 3 extended with the following sequence: Leu-Ile-Arg-Glu-Leu-Leu-Gln-Glu-Leu-Val-Asn-Lys-His-Leq (SEQ ID NO. 11); and an enzyme comprising the amino acid residues 1-511, of the amino acid sequence shown in the appended SEQ ID No. 3, and wherein the amino acid residue in position 511 is changed from Glu to Ala. 
     In the present context, the term “derived from” is intended not only to indicate a protein disulfide isomerase produced by strains IFO 4177 or A524, but also a protein disulfide isomerase encoded by a DNA sequence isolated from these strains such as indicated in SEQ ID No. 1 and SEQ ID No. 2, or a sequence homologous thereto encoding a polypeptide with protein disulfide isomerase activity and produced in a host organism transformed with said DNA sequence. 
     Accordingly, the present invention thus relates to an enzyme exhibiting protein disulfide isomerase activity, which enzyme is immunologically reactive with an antibody raised against a purified protein disulfide isomerase derived from  Aspergillus oryzae,  IFO 4177. 
     In the present context, the term “homologue” is intended to indicate a polypeptide encoded by DNA which hybridizes to the same probe as the DNA coding for the protein disulfide isomerase enzyme under certain specified conditions (such as presoaking in 5×SSC and prehybridizing for 1 h at ˜40° C. in a solution of 5×SSC, 5×Denhardt&#39;s solution, 50 mM sodium phosphate, pH 6.8, and 50 μg of denatured sonicated calf thymus DNA, followed by hybridization in the same solution supplemented with 50 μCi 32-P-dCTP labelled probe for 18 h at ˜40° C. followed by washing three times in 2×SSC, 0.2% SDS at 40° C. for 30 minutes). More specifically, the term is intended to refer to a DNA sequence which is at least 70% homologous to the sequences indicated above encoding the protein disulfide isomerase of the invention. The term is intended to include modifications of the DNA sequences indicated above, such as nucleotide substitutions which do not give rise to another amino acid sequence of the protein disulfide isomerase but which correspond to the codon usage of the host organism into which the DNA construct is introduced or nucleotide substitutions which do give rise to a different amino acid sequence and therefore, possibly, a different protein structure which might give rise to a protein disulfide isomerase mutant with different properties than the native enzyme. Other examples of possible modifications are insertion of one or more nucleotides into the sequence, addition of one or more nucleotides at either end of the sequence, or deletion of one or more nucleotides at either end or within the sequence. 
     In the present context the term active protein disulfide isomerase is intended to indicate an enzyme having an activity similar to that of protein disulfide isomerase, i.e. an enzyme capable of catalysing reaction I. The activity may be determined in an assay based on oxidative refolding of reduced Bowman-Birk soya bean inhibitor, e.g. as described in the Materials and Methods section below. 
     The term “recombinant” as used about the protein disulfide isomerase of the invention is intended to indicate that it is produced by a cell transformed with a DNA sequence encoding the protein disulfide isomerase. Thus, the recombinant protein disulfide isomerase may be produced by either its parent organism or another organism. 
     In a further aspect the present invention relates to a DNA construct comprising a DNA sequence encoding an active recombinant protein disulfide isomerase of the invention as defined above. Such a DNA construct may comprise introns (an example thereof is shown in the appended SEQ ID No. 1) and/or regulatory elements native to the parts coding for the mature protein disulfide isomerase of the invention, or be a cDNA construct comprising only that part coding for the mature protein disulfide isomerase (an example being the appended SEQ ID No.2). 
     In still further aspects the present invention relates to a recombinant expression vector harbouring the DNA construct of the invention, to a cell which either harbours the DNA construct or the expression vector of the invention, and to a process for the production of a protein disulfide isomerase of the invention, wherein a cell of the invention as described above is cultured under conditions conducive to the production of the protein disulfide isomerase, and the protein disulfide isomerase is subsequently recovered from the culture. 
     Finally, the present invention relates to compositions comprising the active protein disulfide isomerase of the invention and methods for their use in various applications. 
    
    
     BRIEF DESCRIPTION OF THE TABLES AND DRAWING 
     The invention is further illustrated in the accompanying tables and drawing, in which 
     Table 1 shows an alignment of published eukaryotic PDI amino acid sequences: Bovine ( Bos taurus ) (Yamauchi et al., Biochem. Biophys. Res. Commun. 146:1485-1492, 1987), chicken ( Gallus gallus ) (Parkkonen et al., Biochem. J. 256:1005-1011, 1988), human ( Homo sapiens ) (Rapilajaniemi et al. EMBO J. 6:643-649, 1987), mouse ( Mus musculus ) (Gong, et al., Nucleic Acids Res. 16:1203, 1988), rabbit ( Oryctolagus cuniculus ) (Fliegel et al., J. Biol. Chem. 265:15496-15502, 1990), rat ( Rattus norvegicus ) (Edman et al., Nature 317:267-270, 1985), and yeast ( Sacchaaromyces cerevisiae ) (Tachikawa et al., J. Biochem. 110:306-313). 
     Table 2 shows an alignment of PDI amino acid sequences: Alfalfa ( Medicago sativa ) (Shorrosh and Dixon, Plant. Mol. Bio. 19:319-321, 1992),  A. oryzae  (this invention), yeast ( Saccharomyces cerevisiae ) (Tachikawa et al., J. Biochem. 110:306-313), bovine ( Bos taurus ) (Yamauchi et al., Biochem. Biophys. Res. Commun. 146:1485-1492, 1987), rat ( Rattus norvegicus ) (Edman et al., Nature 317:267-270, 1985), and mouse ( Mus musculus ) (Gong, et al., Nucleic Acids Res. 16:1203, 1988), and 
     FIG. 1 illustrates the construction of the expression plasmids pCaHj431, pCaHj432, pCaHj433, and pCaHj434 further described in Example 1. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The amino acid sequence of the protein disulfide isomerase of the invention, which was isolated from a strain of the  A. oryzae,  has been aligned with that of protein disulfide isomerases of other origins and have been shown to have a degree of identity of about 38% with that of  Saccharomyces cerevisiae  (GenBank Acc. No. M62815) and 30% with that of Alfalfa (GenBank Acc. No. 11499). 
     These homologies are taken to indicate that some kind of evolutionary relationship exists between protein disulfide isomerases, and that the protein disulfide isomerase of the invention may represent a distinct class of protein disulfide isomerase. It is contemplated that the protein disulfide isomerase of the invention or DNA encoding the protein disulfide isomerase may be isolated from other organisms, including animals, especially a mammal, an insect, a plant or a microorganism. In the present context, especially interesting origins are bacteria and fungi, including yeasts and filamentous fungi. 
     As indicated above the sequence of the isolated enzyme shows that the protein disulfide isomerase of the invention has two -Cys-X-Y-Cys- subunits in positions 58-61 and 393-396. 
     The invention consequently also comprises active truncated forms of the enzymes of the invention, wherein at least one subunit is retained. Examples hereof could be an enzyme having an amino acid sequence corresponding to the residues 20 to 100, residues 330 to 450, or residues 360 to 430 of the appended SEQ ID No. 3, or the corresponding sequence of the enzyme of the invention in question. 
     Under this aspect, the invention specifically relates to enzymes exhibiting protein disulfide isomerase activity comprising the amino acid residues 1-131 (SEQ ID No. 10), 1-141 (SEQ ID No.9), 1-143 (SEQ ID No. 8), 1-163 (SEQ ID No. 7), 1-174 (SEQ ID No. 6), 1-281 (SEQ ID No. 5), or 25-225 (SEQ ID No. 12) of the amino acid sequence shown in the appended SEQ ID No. 3, or variants/derivatives thereof exhibiting a protein disulfide isomerase activity. Further specific enzymes are enzymes exhibiting protein disulfide isomerase activity comprising the amino acid residues 1-115, of the amino acid sequence shown in the appended SEQ ID No. 3 extended with the following sequence: 
     Leu-Ile-Arg-Glu-Leu-Leu-Gln-Glu-Leu-Val-Asn-Lys-His-Leu (SEQ ID No. 11); and an enzyme comprising the amino acid residues 1-511, of the amino acid sequence shown in the appended SEQ ID No. 3, and wherein the amino acid residue in position 511 is changed from Glu to Ala (SEQ ID No. 4). 
     The DNA sequence of the DNA construct of the invention encoding a recombinant protein disulfide isomerase enzyme as defined above is preferably as shown in the appended SEQ ID No. 1 (genomic DNA) or SEQ ID No. 2 (cDNA). Analogues of said sequences, which differ in one or more codons, but which encodes the recombinant protein disulfide isomerase are also within the invention. 
     Similar DNA sequences coding for the truncated forms of the protein disulfide isomerases of the invention are also part of the invention. DNA sequences therefore can be taken from SEQ ID No. 1, or preferably SEQ ID No. 2. 
     The DNA sequence of the DNA construct of the invention may be isolated by well-known methods. Thus, the DNA sequence may, for instance, be isolated by establishing a cDNA or genomic library from an organism expected to harbour the sequence, and screening for positive clones by conventional procedures. Examples of such procedures are hybridization to oligonucleotide probes synthesized on the basis of the full amino acid sequence shown in SEQ ID No. 3, or a subsequence thereof in accordance with standard techniques (cf. Sambrook et al., 1989), and/or selection for clones expressing a protein disulfide isomerase activity as defined above, and/or selection for clones producing a protein which is reactive with an antibody raised against the protein disulfide isomerase comprising the amino acid sequence shown in SEQ ID No. 3 and in particular amino acid residues 1-143 thereof as shown in SEQ ID No. 8. 
     A preferred method of isolating a DNA construct of the invention from a cDNA or genomic library is by use of polymerase chain reaction (PCR) using degenerate oligonucleotide probes prepared on the basis of the amino acid sequence of the protein disulfide isomerase of the invention comprising amino acid residues 1-515 of SEQ ID No. 3. For instance, the PCR may be carried out using the techniques described in U.S. Pat. No. 4,683,202 or by R. K. Saiki et al. (1988). 
     Alternatively, the DNA sequence of the DNA construct of the invention may be prepared synthetically by established standard methods, e.g. the phosphoamidite method described by Beaucage and Caruthers (1981), or the method described by Matthes et al. (1984). According to the phosphoamidite method, oligonucleotides are synthesized, e.g. in an automatic DNA synthesizer, purified, annealed, ligated and cloned in appropriate vectors. 
     Finally, the DNA construct may be of mixed genomic and synthetic, mixed synthetic and cDNA or mixed genomic and cDNA origin prepared by ligating fragments of synthetic, genomic or cDNA origin (as appropriate), the fragments corresponding to various parts of the entire recombinant DNA molecule, in accordance with standard techniques. 
     DNA constructs coding for the truncated forms of the enzyme of the invention may naturally be made in corresponding ways. 
     The recombinant expression vector carrying the DNA construct of the invention may be any vector which may conveniently be subjected to recombinant DNA procedures, and the choice of vector will often depend on the host cell into which it is to be introduced. Thus, the vector may be an autonomously replicating vector, i.e. a vector which exists as an extrachromosomal entity, the replication of which is independent of chromosomal replication, e.g. a plasmid, a bacteriophage or an extrachromosomal element, minichromosome or an artificial chromosome. Alternatively, the vector may be one which, when introduced into a host cell, is integrated into the host cell genome and replicated together with the chromosome(s) into which it has been integrated. 
     In the vector, the DNA sequence should be operably connected to a suitable promoter sequence. The promoter may be any DNA sequence which shows transcriptional activity in the host cell of choice and may be derived from genes encoding proteins either homologous or heterologous to the host cell. Examples of suitable promoters for directing the transcription of the DNA construct of the invention, especially in a bacterial host, are the promoter of the lac operon of  E. coli,  the  Streptomyces coelicolor  agarase gene dagA promoters, the promoters of the  Bacillus lichenifornis  α-amylase gene (amyL), the promoters of the  Bacillus stearothermophilus  maltogenic amylase gene (amyM), the promoters of the  Bacillus Amyloliquefaciens  α-amylase (amyQ), the promoters of the Bacillus subtilis xylA and xylB genes etc. For transcription in a fungal host, examples of useful promoters are those derived from the gene encoding  A. oryzae  TAKA amylase,  Rhizomucor miehei  aspartic proteinase,  A. niger  neutral α-amylase,  A. niger  acid stable a-amylase,  A. niger  glucoamylase,  Rhizomucor miehei  lipase,  A. oryzae  alkaline protease,  A. oryzae  triose phosphate isomerase or  A. nidulans  acetamidase. 
     The expression vector of the invention may also comprise a suitable transcription terminator and, in eukaryotes, polyadenylation sequences operably connected to the DNA sequence encoding the recombinant protein disulfide isomerase of the invention. Termination and polyadenylation sequences may suitably be derived from the same sources as the promoter. 
     The vector may further comprise a DNA sequence enabling the vector to replicate in the host cell in question. Examples of such sequences are the origins of replication of plasmids pUC19, pACYC177, pUB110, pE194, pAMB1 and pIJ702. 
     The vector may also comprise a selectable marker, e.g. a gene the product of which complements a defect in the host cell, such as the dal genes from  B. subtilis  or  B. licheniformis,  or one which confers antibiotic resistance such as ampicillin, kanamycin, chloramphenicol or tetracyclin resistance. Examples of Aspergillus selection markers include amdS, argB, niaD and sC, a marker giving rise to hygromycin resistance. Furthermore, the selection may be accomplished by co-transformation, e.g. as described in WO 91/17243. 
     While intracellular expression may be advantageous in some respects, e.g. when using certain bacteria as host cells, it is generally preferred that the expression is extracellular. The protein disulfide isomerase of the invention or truncated forms thereof comprising the amino acid sequences shown in the SEQ ID Nos. 3 to 12 may furthermore comprise a preregion permitting secretion of the expressed protein disulfide isomerase into the culture medium. If desirable, this preregion may be native to the protein disulfide isomerase of the invention or substituted with a different preregion or signal sequence, conveniently accomplished by substitution of the DNA sequences encoding the respective preregions. 
     The procedures used to ligate the DNA construct of the invention, the promoter, terminator and other elements, respectively, and to insert them into suitable vectors containing the information necessary for replication, are well known to persons skilled in the art (cf., for instance, Sambrook et al. (1989)). 
     The cell of the invention either comprising a DNA construct or an expression vector of the invention as defined above is advantageously used as a host cell in the recombinant production of a polypeptide of the invention. The cell may be transformed with the DNA construct of the invention, conveniently by integrating the DNA construct in the host chromosome. This integration is generally considered to be an advantage as the DNA sequence is more likely to be stably maintained in the cell. Integration of the DNA constructs into the host chromosome may be performed according to conventional methods, e.g. by homologous or heterologous recombination. Alternatively, the cell may be transformed with an expression vector as described above in connection with the different types of host cells. 
     The cell of the invention may be a cell of a higher organism such as a mammal, an avian, an insect, or a plant cell, but is preferably a microbial cell, e.g. a bacterial or a fungal (including yeast) cell. 
     Examples of suitable bacteria are gram positive bacteria such as  Bacillus subtilis, Bacillus licheniformis, Bacillus lentus, Bacillus brevis, Bacillus stearothermophilus, Bacillus alkalophilus, Bacillus amyloliquefaciens, Bacillus coagulans, Bacillus circulans, Bacillus lautus, Bacillus megaterium, Bacillus thuringiensis,  or  Streptomyces lividans  or  Streptomyces murinus,  or gram negative bacteria such as  E. coli.  The transformation of the bacteria may for instance be effected by protoplast transformation or by using competent cells in a manner known per se. 
     The yeast organism may favourably be selected from a species of Saccharomyces or Schizosaccharomyces, e.g.  Saccharomyces cerevisiae.  The filamentous fungus may advantageously belong to a species of Aspergillus, e.g.  Aspergillus oryzae  or  Aspergillus niger.  Alternatively, a strain of a Fusarium species, e.g.  F. oxysporum,  can be used as a host cell. Fungal cells may be. transformed by a process involving protoplast formation and transformation of the protoplasts followed by regeneration of the cell wall in a manner known per se. A suitable procedure for transformation of Aspergillus host cells is described in EP 238 023. A suitable method of transforming Fusarium species is described by Malardier et al., 1989. 
     In a yet further aspect, the present invention relates to a method of producing a recombinant protein disulfide isomerase of the invention, which method comprises cultivating a host cell as described above under conditions conducive to the production of the protein disulfide isomerase and recovering the protein disulfide isomerase from the cells and/or culture medium. 
     The medium used to cultivate the cells may be any conventional medium suitable for growing the host cell in question and obtaining expression of the protein disulfide isomerase of the invention. Suitable media are available from commercial suppliers or may be prepared according to published recipes (e.g. in catalogues of the American Type Culture Collection). 
     The resulting protein disulfide isomerase may be recovered from the medium by conventional procedures including separating the cells from the medium by centrifugation or filtration, if necessary after disruption of the cells, precipitating the proteinaceous components of the supernatant or filtrate by means of a salt, e.g. ammonium sulphate, followed by purification by a variety of chromatographic procedures, e.g. ion exchange chromatography, affinity chromatography, or the like. 
     It is of course also possible to produce the protein disulfide isomerases of the invention by culturing the filamentous fungal natural host or parent organism of interest and recovering the protein disulfide isomerase from the culture broth in traditional ways. 
     The present invention also relates to compositions comprising the protein disulfide isomerase of the invention. 
     The compositions may suitably contain 0.01-200 mg of enzyme protein per gram, preferably 0.01-20 mg of enzyme protein per gram, especially 0.01-2 mg of enzyme protein per gram, or alternatively 0.02-0.2 mg of enzyme protein per gram, or 0.01-0.2 mg of enzyme protein per gram. 
     The compositions of the invention may contain other ingredients known in the art as e.g. excipients, stabilizers, fillers, detergents, etc. 
     The compositions of the invention may be formulated in any convenient form, e.g. as a powder, paste, liquid or in granular form. The enzyme may be stabilized in a liquid by inclusion of enzyme stabilizers. Usually, the pH of a solution of the composition of the invention will be 5-10 and in some instances 7.0-8.5. Other enzymes such as proteases, cellulases, oxidases, peroxidases, amylases or lipases may be included in the compositions of the invention, either separately or in a combined additive. 
     The compositions of the invention can be used for the treatment or degradation of scleroproteins, especially hair, skin and wool, dehairing and softening of hides, treatment and cleaning of fabrics, as additives to detergents, thickening and gelation of food and fodder, strengthening of gluten in bakery or pastry products, and as pharmaceuticals for the alleviation of eye sufferings. 
     The present invention is further illustrated in the following examples which should not, in any manner, be considered to limit the scope of the present invention. 
     Materials and Methods 
     Strains 
       Aspergillus oryzae  IFO 4177 available from Institute for Fermentation, Osaka; 17-25 Juso Hammachi 2-Chome Yodogawa-Ku, Osaka, Japan. 
       Aspergillus niger  A524 (ATCC 16882) 
       Aspergillus niger  TSA 1. 
       E. coli  DH5αF′ 
     Determination of PDI Activity 
     The PDI is assayed using the insulin reduction assay described by James et al., Cell 67:581-589, 1991. 
     Plasmids 
     pUC 19, pMT 1560, pToC 90 
     EXAMPLES 
     Example 1 
     Cloning of  Aspergillus oryzae  and  Aspergillus niger  PDI Encoding Genes 
     1.1. Design of Oligo Nucleotides for PCR Amplification 
     PDI from different organisms are highly homologous especially near the active site residues. In FIG. 1, the following 7 PDI gene products are aligned: 
     Bovine ( Bos taurus ) PDI (Yamauchi et al., Biochem. Biophys. Res. Commun. 146:1485-1492, 1987), Chicken ( Gallus gallus ) PDI (Parkkonen et al., Biochem. J. 256:1005-1011, 1988), Human ( Homo sapiens ) PDI (Rapilajaniemi et al. EMBO J. 6:643-649, 1987), Mouse ( Mus musculus ) PDI (Gong, et al., Nucleic Acids Res. 16:1203, 1988), Rabbit ( Oryctolaqus cuniculus ) PDI (Fliegel et al., J. Biol. Chem. 265:15496-15502, 1990), Rat ( Rattus norvegicus ) PDI (Edman et al., Nature 317:267-270, 1985), Yeast ( Saccharomyces cerevisiae ) PDI (Tachikawa et al., J. Biochem. 110:306-313). 
     Each subunit contains two active centres (Freedman et al., Cell 57:1069-1072, 1989) and the homology in the surroundings of these active centres are particularly strong. A consensus amino acid sequence for the active centre closest to the N-terminus was determined from the alignment as -APWCGHCK-, and an oligo aeoxyribonucleotide encoding the peptide -WCGHCK- and extended with an EcoRI site in the 5′ end, was synthesized: 
     5′ TGGAATTCTGGTGYGGNCAYTGYAA3′ (primer 4762, 25 nucleotides, 32 species, SEQ ID No. 13) (Y=C or T; R=A or G; N=A, T, C, or G). 
     A consensus amino acid sequence for the active centre closest to the C-terminus was determined: -YAPWCGHCK-, and an oligo deoxyribonucleotide encoding the peptide -YAPWCG- in antisense and extended with a BamHI site in the 5′ end was synthesized: 
     5′ TGGGATCCRCACCANGGNGCRTA3′ (primer 4763, 23 nucleotides, 64 species, SEQ ID NO. 14). 
     These oligo deoxyribonucleotides (primers 4762 and 4763) were used as primers in a PCR reaction to amplify PDI-encoding gene fragments from genomic DNA from  A. oryzae  and  A. niger.    
     1.2 Amplification and Cloning of Fragments of PDI-encoding Genes 
     Genomic DNA was prepared from  Aspergillus oryzae  IFO 4177 and  Aspergillus niger  A524 as described by Yelton et al. (Proc. Natl. Acad. Sci. USA 81:1470-1474, 1984). 
     PCR reaction mixtures contained Taq DNA polymerase buffer supplied by Clontech laboratories Inc. and diluted as described, 250 μM of each of dATP, dCTP, dGTP, and, dTTP, 100 pmol of each of primers 4762 and 4763, and 0.5 μg of genomic DNA of either  A. niger  or  A. oryzae.  The total reaction volume was 0.1 ml, and it was covered with 0.05 ml paraffin oil. 
     The following program was run on a Cetus Perkin Elmer thermal cycler: 
     1. cycle: 94° C. for 2 min., (when the temperature reached 94° C. 2.5 U of Taq DNA polymerase supplied by Clontech laboratories Inc. was added). 
     10 cycles: 94° C. for 1 min., 50° C. for 1 min., and 72° C. for 2 min. 
     30 cycles: 94° C. for 1 min., 55° C. for 1 min., and 72° C. for 2 min. 
     1 cycle: 72° C. for 5 min. 
     The reaction mixtures were loaded on an agarose gel, and both the  A. oryzae  and the  A. niger  DNA produced fragments of approximately 1.1 kb. 
     The fragments were digested with EcoRI and BamHI and ligated to pUC19 (Yanisch-Perron et al., Gene 33:103-119, 1985). The ligation mixture was transformed into  E. coli  DH5αF′ (Woodcock et al., Nucleic Acids Res. (1989) 17:3469-3478). Recombinant plasmids were subjected to sequence analysis using the Sequenase™ kit (United States Biochemical) and a M13 universal primer following the manufacturers instructions. The analysis confirmed that both in the case of  A. oryzae  and in that of  A. niger  sequences homologous to other PDI genes were amplified and cloned. 
     1.3 Genome Cloning of the  A. oryzae  PDI-encoding Gene 
     Genomic DNA from  A. oryzae  was digested with the following restriction enzymes supplied by New England Biolabs Inc.: HindIII, BamHI, BamHI+HindIII, EcoRI, EcoRI+HindIII, SalI, SalI+HindIII, BglII, BglII+HindIII, PstI and PstI+HindIII. After digestion, the reaction mixtures were run on a 1% agarose gel and then blotted onto an Immobilon N™ membrane (Millipore Corporation) following the manufacturers instructions. The membrane was probed with the cloned  A. oryzae  PCR product isolated as a BamHI-EcoRI fragment and radio labelled with  32 p, After stringent washes the membrane was subjected to autoradiography. 
     Genomic DNA from  A. niger  was digested with the following restriction enzymes: BglII, BamlHI, BamHI+BglII, EcoRI, EcoRI+BglII, SalI, SalI+BglII, HindIII, HindIII+BglII, PstI and PstI+BglII. The Southern blot was made as described with  A. oryzae,  only the  A. niger  PCR product was used as probe. 
     1.4 Construction of Genomic  A. oryzae  Library 
     Southern analysis indicated that the  A. oryzae  PDI gene was located on a 6.8 kb BglII fragment. Genomic  A. oryzae  DNA was digested with BglII and fragments ranging from 5 kb to 8.5 kb were isolated from an agarose gel. Subcloning thereof and Southern analysis indicated that the  A. oryzae  PDI gene was located on a 2.3 kb BamH I, Hind III fragment. Genomic  A. oryzae  DNA was digested with BamH I and Hind III and fragments ranging from 1.9-3 kb were isolated from an agarose gel. This mixture of fragments was ligated to pUC19 digested with BamHI and Hind III. The ligation mixture was used to transform  E. coli  DH5αF′. The transformed  E. coli  cells were spread onto 10 agar plates using ampicillin selection. 
     1.5 Screening of the  A. oryzae  Genomic Library 
     The libraries were screened using the filter colony hybridization method described by Gergen et al. (Nucleic Acids Res. 7:2115-2136, 1979). The probe that was used for the Southern blot was also used for the colony hybridization. Positive clones were isolated and confirmed by sequence analysis using sequencing primers designed from the sequences of the PDI fragments. One of the plasmids containing the desired fragment was termed pCaHj 425. 
     1.6 Sequence of the Gene 
     The gene was sequenced using the Tag DyeDeoxy™ Terminator cycle sequencing kit supplied by Applied Biosystems following the manufacturer&#39;s instructions. The sequence reactions were run on an Applied Biosystems 373A DNA sequencer and the data were evaluated using the Macintosh computer program SegEd version 1.0 supplied by Applied Biosystems. 
     The sequence of the  A. oryzae  gene is shown in the appended SEQ ID No 1. 
     The amino acid composition of the purified PDI obtained as described in Example 2 was in accordance with the composition deduced from the DNA-sequence shown in SEQ ID No. 1. From homology to other PDI genes and consensus splicing sequences a CDNA sequence as shown in SEQ ID no. 2 was suggested. The derived protein sequence is as shown in SEQ ID No. 3. 
     Example 2 
     Expression of Truncated Forms of the  A. oryzae  PDI Gene 
     2.1 Construction of Expression Plasmids 
     The PDI gene of  A. oryzae  was truncated at various positions by introduction stop codons. This was done by PCR amplification of the PDI gene using a 5′ PCR primer harbouring a BamH I site at its 5′ end and 8 different 3′ primers corresponding to 8 different truncations each harbouring a Hind III site. The sequence of the 5′ primer was: 
     
       
         
               
               
               
             
           
               
                 5′ TTCGGATCCACCATGCGGACTTTCGCACC 3′ 
                 5205. (SEQ ID No. 15) 
                   
               
               
                   
               
               
                 The sequences of the eight 3′primers were: 
               
               
                   
               
               
                 5′ CCAAGCTTTAGAGATGCTTGTTGACAAGCTCCTG 
               
               
                    GAGGAGCTCCCTGATAAGCTT 3′ 
                 5215. (SEQ ID No. 16) 
               
               
                   
               
               
                 5′ CCAAGCTTTAGACCATGTATGACACAATCGCCTCG 
               
               
                    GTCTGACGAG 3′ 
                 5397. (SEQ ID No. 17) 
               
               
                   
               
               
                 5′ CCAAGCTTTAGACAGGGGACACAGCAGGTAG 3′ 
                 5895. (SEQ ID No. 18) 
               
               
                   
               
               
                 5′ CCAAGCTTTATGGGGTGACAGGGGACA 3′ 
                 5399. (SEQ ID No. 19) 
               
               
                   
               
               
                 5′ CCAAGCTTTAAGACGCGATATAACCAATAAC 3′ 
                 5894. (SEQ ID No. 20) 
               
               
                   
               
               
                 5′ CCAAGCTTTAAGTGGTGAATATATCATTGGC 3′ 
                 5893. (SEQ ID No. 21) 
               
               
                   
               
               
                 5′ CCAAGCTTAGTGTTTCTCGGCGATGAACTT 3′ 
                 6314. (SEQ ID No. 22) 
               
               
                   
               
               
                 5′ CCAAGCTTTACGCAGACTTGTCATCGCTAGT 3′ 
                 5204. (SEQ ID No. 23) 
               
             
          
         
       
     
     Primer 5215 directed an extension of the PDI gene amino acid 1-115 with the sequence Leu-Ile-Arq-Glu-Leu-Leu-Gln-Glu-Leu-Val-Asn-Lys-His-Leu (SEQ ID NO. 11): followed by a stop codon. 
     Primer 5397 introduced a stop codon after amino acid 131. 
     Primer 5895 introduced a stop codon after amino acid 141. 
     Primer 5399 introduced a stop codon after amino acid 143. 
     Primer 5894 introduced a stop codon after amino acid 163. 
     Primer 5893 introduced a stop codon after amino acid 174. 
     Primer 6314 introduced a stop codon after amino acid 281. 
     Primer 5204 introduced the mutation E511A (meaning substituting and a stop codon after amino acid 511. 
     The expression plasmids were constructed by PCR amplification using primer 5205 in combination with either 5215, 5397, 5895, 5399, 5894, 5893, 6314 or 5204 and pCaHj 425 as template using standard PCR conditions. The generated PCR fragments were digested with BamH I and Hind III and inserted into pMT 1560 (described in e.g. PCT/DK94/00138) digested with the same enzymes (See FIG.  3 ). The constructed plasmids were named pCaHj 432 (from primer 5215), pCaHj 433 (from primer 5397), PCaHj 441 (from primer 5895), pCaHj 434 (from primer 5399), pCaHj 440 (from primer 5894), pCaHj 439 (from primer 5893), pCaHj 445 (from primer 6314) and pCaHj 431 (from primer 5204). 
     2.2 Transformation of  A. oryzae  IFO 4177 
     Each of the plasmids pCaHj 432, pCaHj 433, PCaHj 441, pCaHj 434, pCaHj 440, pCaHj 439, pCaHj 445 and pCaHj 431 were transformed into  A. oryzae  IFO 4177 by cotransformation with the amds selection plasmid pToC 90 (described in W091/17243) following the procedure described in the published EP patent application No. 238 023. 
     A number of transformants of each plasmid were evaluated. 
     2.3 Transformation of  A. niger  TSA 1 
     Each of the plasmids PCaHj 441, pCaHj 434, pCaHj 440 and pCaHj 439 were transformed into  A. niger  TSA 1 by the same procedure as with  A. oryzae.    
     A number of transformants of each plasmid were evaluated. 
     Example 3 
     Fermentation Purification and Characterization of the  Aspergillus oryzae  PDI Truncations 
     3.1  A. oryzae  IFO 4177 Transformants 
     Crude truncated PDI preparation was isolated from supernatants obtained by fermentation of the  A. oryzae  or  A. niger  pCaHj 432, pCaHj 433, PCaHj 441, pCaHj 434, pCaHj 440, pCaHj 439, pCaHj 445 or pCaHj 431 transformants in shake flasks containing YPM medium (1 liter: 5 g Difco Yeast extract, 10 g Difco peptone, 20 g maltose). The supernatant was recovered by filtration. The PDI truncation gene products were partially purified using a 1 ml HiTrap Q™ anion exchanger from Pharmacia LKB Biotechnology AB Uppsala, Sweden following the manufacturers instructions. Fractions were collected and analyzed by measuring the disulphide isomerase activity and by SDS PAGE. 
     The pCaHj 434 transformants secreted a protein of approx 14 kD (SDS PAGE) not present in supernatants of the untransformed strain. Enrichment of this protein by ion exchange was followed by increased disulphide isomerase activity. The approx. 14 kD band was blotted from an SDS Page gel and subjected to N-terminal amino acid sequence determination using an Applied Biosystems 473A protein sequencer. A sequence of 7 amino acids could unambiguously be determined as: Thr-Ala-Glu-Ala-Pro-Ser-Asp. This sequence corresponds to residue 24-30 of the  A. oryzae  protein sequence. The size of the truncation expected from the amino acid sequence is thus 13.2 kD. So it can be concluded that the pCaHj 434 gene product is secreted to the supernatant, that it has the expected size and that it is catalytic active. 
     The pCaHj 441 transformants secreted a protein of the same size as the pCaHj 434 transformants. Also for this truncation enrichment of the protein was followed by increased disulphide isomerase activity demonstrating that the pCaHj 441 gene product is a catalytic active secreted protein. 
     The pCaHj 440 transformants secreted a protein of approx 16 kD not present in the untransformed strain. The expected size is 15.7 kD assuming the same N-terminal sequence as the pCaHj 434 product. Enrichment of the protein by ion exchange was followed by increased disulphide isomerase activity demonstrating that also the pCaHj 440 gene product is a catalytic active secreted protein. 
     The pCaHj 445 transformants secreted a protein of approx 30 kD not present in the untransformed strain. The expected size is 28.6 kD assuming the same N-terminal sequence as the pCaHj 434 product. Enrichment of the protein by ion exchange was followed by increased disulphide isomerase activity demonstrating that the pCaHj 440 gene product is a catalytic active secreted protein. 
     3.2  A. niger  TSA 1 Transformants 
     Transformants of PCaHj 441, pCaHj 434, pCaHj 440 and pCaHj 439 were evaluated in the same way as the corresponding  A. oryzae  transformants with the exception that the N-terminal amino acid sequence was not determined for any of the proteins secreted by  A. niger.    
     In all other aspects the same results were obtained with the  A. niger  transformants as with the  A. oryzae  transformants. However the fermentation yield of the truncations were generally lower in  A. niger  than in  A. oryzae.   
     
       
         
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
             
             
               
                   
                 1                                                   50 
               
               
                 Pdi_Mouse 
                 .......MLS RALLCLALAW AARVGADALE EEDNVLVLKK SNFEEALAAH 
               
               
                 Pdi_Rat 
                 .......MLS RALLCLAAAW AARVGADALE EEDNVLVLKK SNFAEALAAH 
               
               
                 Pdi_Bovin 
                 .......MLR RALLCLALTA LFRAGAGAPD EEDHVLVLHK GNFDEALLAH 
               
               
                 Pdi_Human 
                 .......MLR RALLCLAVAA LVR..ADAPE EEDHVLVLRK SNFAEALAAH 
               
               
                 Pdi_Rabit 
                 .......MLR RAVLCLALAV TA.GWAWAAE EEDNVLVLKS SNFAEELAAH 
               
               
                 Pdi_Chick 
                 .......... .......... ......EPLE EEDGVLVLRA ANFEQALAAH 
               
               
                 Pdi_Yeast 
                 MKFSAGAVLS WSSLLLASSV FAQQEAVAPE DSA.VVKLAT DSFNEYIQSH 
               
               
                   
               
               
                   
                 51                                                 100 
               
               
                 Pdi_Mouse 
                 KYLLVEFYAP WCGHCKALAP EYAKRAAKLK AEGSEIRLAK VDATEESDLA 
               
               
                 Pdi_Rat 
                 NYLLVEFYAP WCGHCKALAP EYAKAAAKLK AEGSEIRLAK VDATEESDLA 
               
               
                 Pdi_Bovin 
                 KYLLVEFYAP WCGHCKALAP EYAKAAGKLK AEGSEIRLAK VDATEESDLA 
               
               
                 Pdi_Human 
                 KYLLVEFYAP WCGHCKALAP EYAKAAGKLK AEGSEIRLAK VDATEESDLA 
               
               
                 Pdi_Rabit 
                 KHLLVEFYAP WCGHCKALAP EYAKAAGKLK AEGSDIRLAK VDATEESDLA 
               
               
                 Pdi_Chick 
                 RHLLVEFYAP WCGHCKALAP EYAKAAAQLK AEGSEIRLAK VDATEEAELA 
               
               
                 Pdi_Yeast 
                 DLVLAEFFAP WCGHCKNMAP EYVKAAETL. .VEKNITLAQ IDCTENQDLC 
               
               
                   
               
               
                   
                 101                                                150 
               
               
                 Pdi_Mouse 
                 QQYGVRGYPT IKFFKNGDTA SPKEYTAGRE ADDIVNWLKK RTGPAATTLS 
               
               
                 Pdi_Rat 
                 QQYGVRGYPT IKFFKNGDTA SPKEYTAGRE ADDIVWWLKK RTGPAATTLS 
               
               
                 Pdi_Bovin 
                 QQYGVRGYPT IKFFKNGDTA SPKEYTAGRE ADDIVNWLKK RTGPAASTLS 
               
               
                 Pdi_Human 
                 QQYGVRGYPT ZKFFRNGDTA SPKEYTAGRE ADDIVNWLKK RTGPAATLLR 
               
               
                 Pdi_Rabit 
                 QQYGVRGYPT ZKFFKNGDTA SPKEYTAGRE ADDIVNWLKK RTGPAATTLA 
               
               
                 Pdi_Chick 
                 QQFGVRGYPT ZKFFRNGDKA APREYTAGRE ADDIVSWLKK RTGPAATTLT 
               
               
                 Pdi_Yeast 
                 MEHNIPGFPS LKIFKNSDVN NSIDYEGPRT AEAIVQFMIK QSQPAVAVVA 
               
               
                   
               
               
                   
                 151                                                200 
               
               
                 Pdi_Mouse 
                 DTAAAESLVD SSEVTVIGFF KDVESDSAKQ FLLAAEAIDD IPFGITSNSG 
               
               
                 Pdi_Rat 
                 DTAAAESLVD SSEVTVIGFF KDAGSDSAKQ FLLAAEAVDD IPFGITSNSD 
               
               
                 Pdi_Bovin 
                 DGAAAEALVE SSEVAVIGFF KDMESDSAKQ FFLAAEVIDD IPFGITSNSD 
               
               
                 Pdi_Human 
                 DGAAAESLVE SSEVAVZGFF KDVESDSAKQ FLQAAZAZDD IPFGITSNSD 
               
               
                 Pdi_Rabit 
                 DSAAAESLVE SSEVAVZGFF KDVESDAAKQ FLLAAEATDD IPFGITSNSD 
               
               
                 Pdi_Chick 
                 DAAAAETLVD SSEVVVIGFF KDVTSDAAKE FLLAAESVDD IPFGISSSAD 
               
               
                 Pdi_Yeast 
                 DLPAYLANET FVTPVIVQSG KIDADFNATF YDFVSAENAD YDFVSAENAD 
               
               
                   
               
               
                   
                 201                                                250 
               
               
                 Pdi_Mouse 
                 VFSKYQLDKD GVVLFKKFDE GR..NNFEGE ITKEKLLD.F IKHNQLPLVI 
               
               
                 Pdi_Rat 
                 VFSKYQLDKD GVVLFKKFDE GR..NNFEGE ITKEKLLD.F IKHNQLPLVI 
               
               
                 Pdi_Bovin 
                 VFSKYQLDKD GVVLFKKFDE GR..NNFEGE VTKEKLLD.F IKHNQLPLVI 
               
               
                 Pdi_Human 
                 VFSKYQLDKD GVVLFKKFDE GR..NNFEGE VTKENLLD.F IKHNQLPLVI 
               
               
                 Pdi_Rabit 
                 VFSRYQVHQD GVVLFKKFDE GR..NNFEGE VTKEKLLD.F IKHNQLPLVI 
               
               
                 Pdi_Chick 
                 VFSKYQLSQD GVVLFKKFDE GR..NNFEGD LTKDNLLN.F IKSNQLPLVI 
               
               
                 Pdi_Yeast 
                 ..DDFKL... SIYLPSAMDE PVVYNGKKAD IADADVFEKW LQVEALPYFG 
               
               
                   
               
               
                   
                 251                                                300 
               
               
                 Pdi_Mouse 
                 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSSFKRA AEGF..KGKI 
               
               
                 Pdi_Ra 
                 EFTEQTAPKI FGGEZKTHIL LFLPKSVSDY DGKLSNFKKA AEGF..KGKI 
               
               
                 Pdi_Bovin 
                 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY EGKLSNFKKA AESF..KGKI 
               
               
                 Pdi_Human 
                 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSNFKTA AESF..KGKI 
               
               
                 Pdi_Rabit 
                 EFTEQTAPKI FGGEIKTHIL LFLPRSAADH DGKLSGFKQA AEGF..KGKI 
               
               
                 Pdi_Chick 
                 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY EGKLDNFKTA AGNF..KGKI 
               
               
                 Pdi_Yeast 
                 EIDGSVFAQY VESGLPLGLY FY......ND EEELEEYKPL FTELAKKNRG 
               
               
                   
               
               
                   
                 301                                                350 
               
               
                 Pdi_Mouse 
                 LFIFIDSDHT DNQRILEFFG LKKEECPAVR LITLEEEM.. .......TKY 
               
               
                 Pdi_Rat 
                 LFIFIDSDHT DNQRILEFFG LKKEECPAVR LITLEEEM.. .......TKY 
               
               
                 Pdi_Bovin 
                 LFIFIDSDHT DNQRILEFFG LKKEECPAVR LITLEEEM.. .......TKY 
               
               
                 Pdi_Human 
                 LFIFIDSDHT DNQRILEFFG LKKEECPAVR LITLEEEM.. .......TKY 
               
               
                 Pdi_Rabit 
                 LFIFIDSDHT DNQRILEFFG LKKEECPAVR LITLEEEM.. .......TKY 
               
               
                 Pdi_Chick 
                 LFIFIDSDHT DNQRILEFFG LKKEECPAVR LITLEEEM.. .......TKY 
               
               
                 Pdi_Yeast 
                 LMNFVSIDAR KFGRMAGNLN M.KEQFPLFA IHDMTEDLKY GLPQLSEEAF 
               
               
                   
               
               
                   
                 351////////////////////////////////////////////////400 
               
               
                 Pdi_Mouse 
                 KPESDELTAE K..ITEFCHR FLEGKIKPHL MSQEVPEDWD KQPVKVLVGA 
               
               
                 Pdi_Rat 
                 KPESDELTAE K..ITQFCHH FLEGKIKPHL MSQELPEDWD KQPVKVLVGK 
               
               
                 Pdi_Bovin 
                 KPESDELTAE K..ITEFCHR FLEGKIKPHL MSQELPDDWD KQPVKVLVGK 
               
               
                 Pdi_Human 
                 KPESEELTAE R..ITEFCHR FLEGKIKPHL MSQERAGDWD KQPVKVPVGK 
               
               
                 Pdi_Rabit 
                 KPESDELTAE G..ITEFCQR FLEGKIKPHL MSQELPEDWD RQPVKVLVGK 
               
               
                 Pdi_Chick 
                 KPESDDLTAD K..IKEFCNK FLEGKIKPHL MSQDLPEDWD KQPVKVLVGK 
               
               
                 Pdi_Yeast 
                 DELSDKZVLE SKAIESLVKD FLKGDASPZV KSQEIFENQD S.SVFQLVGK 
               
               
                   
               
               
                   
                 401                                                450 
               
               
                 Pdi_Mouse 
                 NFEEAAFDEK KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                 Pdi_Rat 
                 NFEEVAFDEK KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                 Pdi_Bovin 
                 NFEEVAFDEK KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                 Pdi_Human 
                 NFEDVAFDEK KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                 Pdi_Rabit 
                 NFEEVAFDEK KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                 Pdi_Chick 
                 NFEEVAFDEN KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                 Pdi_Yeast 
                 NHDEIVNDPK KNVFVEFYAP WCGHCKQLAP IWDKLGETY. KDHENIIIAK 
               
               
                   
               
               
                   
                 451                                                500 
               
               
                 Pdi_Mouse 
                 MDSTANEVEA VKVHSFPTLK FFPASADRTV IDYNGERTLD GFKKFLESGG 
               
               
                 Pdi_Rat 
                 MDSTANEVEA VKVHSFPTLK FFPASADRTV IDYNGERTLD GFKKFLESGG 
               
               
                 Pdi_Bovin 
                 MDSTANEVEA VKVHSFPTLK FFPASADRTV IDYNGERTLD GFKKFLESGG 
               
               
                 Pdi_Human 
                 MDSTANEVEA VKVHSFPTLK FFPASADRTV IDYNGERTLD GFKKFLESGG 
               
               
                 Pdi_Rabit 
                 MDSTANEVEA VKVHSFPTLK FFPASADRTV IDYNGERTLD GFKKFLESGG 
               
               
                 Pdi_Chick 
                 MDSTANEVEA VKVHSFPTLK FFPASADRTV IDYNGERTLD GFKKFLESGG 
               
               
                 Pdi_Yeast 
                 LDHTENDVRG VVIEGYPTIV LYPGGKKSES VVYQGSRSLD SLFDFIKENG 
               
               
                   
               
               
                   
                 501                                   538 
               
               
                 Pdi_Mouse 
                 QDGAGDDEDL .DLEE..ALE PDMEE..DDD QKAVKDEL 
               
               
                 Pdi_Rat 
                 QDGAGDNDDL .DLEE..ALE PDMEE..DDD QKAVKDEL 
               
               
                 Pdi_Bovin 
                 QDGAGDDDDL EDLEE..AEE PDLEE..DDD QKAVKDEL 
               
               
                 Pdi_Human 
                 QDGAGDDDDL EDLEE..AEE PDMEE..DDD QKAVKDEL 
               
               
                 Pdi_Rabit 
                 QDGAGDEDGL EDLEE..AEE PDLEE..DDD QKAVRDEL 
               
               
                 Pdi_Chick 
                 QDGAAADDDL EDLET..DEE TDLEEGDDDE QKIQKDEL 
               
               
                 Pdi_Yeast 
                 HFDVDGKALY EEAQEKAAEE ADADAELADE EDAIHDEL 
               
               
                   
               
             
          
         
       
     
     
       
         
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
             
             
               
                 Alfalfa 
                 M-AKNVAIFG LLFSLLLLVP SQIFA----- -------EES STDAKE---- 
               
               
                 Oryzae 
                 MRTFAPWIL- --SLLGASA- --VAS----- ------AADA TAEAPS---- 
               
               
                 Yeast 
                 MKFSAGAVLS WSSLLLASS- --VFA----- ------QQEA VAPEDS---- 
               
               
                 Bovine 
                 M-LRRA-LLC --LALTALF- --RVG----- -------AGA PDEEDH---- 
               
               
                 Rat 
                 M-LSRA-LLC --LALAWAA- --RVG----- -------ADA LEEEDN---- 
               
               
                 Mouse 
                 MKLRKAWLLV LLLALTQLLA AASAGDAQED TSDTENATEE EEEEDDDDLE 
               
               
                   
               
               
                   
                 ---------- ---------- ----FVL--- ---------- ---------- 
               
               
                   
                 ---------- ---------- ----DVV--- ---------- ---------- 
               
               
                   
                 ---------- ---------- ----AVV--- ---------- ---------- 
               
               
                   
                 ---------- ---------- -----VL--- ---------- ---------- 
               
               
                   
                 ---------- ---------- -----VL--- ---------- ---------- 
               
               
                   
                 VKEENGVWVL NDGNFDNFVA DKDTVLLEFY APWCGHCKQF APEYEKIAST 
               
               
                   
               
               
                   
                 ---------- ---------- ---------- ----TLDNT- ---------- 
               
               
                   
                 ---------- ---------- ---------- ----SLTGD- ---------- 
               
               
                   
                 ---------- ---------- ---------- ----KLATD- ---------- 
               
               
                   
                 ---------- ---------- ---------- ----VLHKG- ---------- 
               
               
                   
                 ---------- ---------- ---------- ----VLKKS- ---------- 
               
               
                   
                 LKDNDPPIAV AKIDATSASM LASKFDVSGY PTIKILKKGQ AVDYDGSRTQ 
               
               
                   
               
               
                   
                 ---------- ---------- --------NF HDTVKKHDFI VVEFYAPWCG 
               
               
                   
                 ---------- ---------- --------TF ETFVKEHDLV LAEFFAPWCG 
               
               
                   
                 ---------- ---------- --------SF NEYIQSHDLV LAEFFAPWCG 
               
               
                   
                 ---------- ---------- --------NF DEALAAHKYL VEFY-APWCG 
               
               
                   
                 ---------- ---------- --------NF AEPAAHNYLL VEFY-APWCG 
               
               
                   
                 EEIVAKVREV SQPDWTPPPE VTLSLTKDNF DDVVNNADII LVEFYAPWCG 
               
               
                   
               
               
                   
                 HCKKLAPEYE KAASILSTHE PPVVLAKVDA NEEHNKDLAS ENDVKGFPTI 
               
               
                   
                 HCKALAPEYE QAATELKEKN IPL--VKVDC TEEEA--LCR DQGVEGYPTL 
               
               
                   
                 HCKNMAPEYV KAAETLVEKN ITL--AQIDC TENQD--LCM EHNIPGFPSL 
               
               
                   
                 HCKALAPEYA KAAGKLKAEG SEIRLAKVDA TEESD--LAQ QYGVRGYPTI 
               
               
                   
                 HCKALAPEYA KAAAKLKAEG SEIRLAKVDA TEESD--LAQ QYGVRGYPTI 
               
               
                   
                 HCKKLAPEYE KAAKELSKRS PPIPLAKVDA TEQTD--LAK RFDVSGYPTL 
               
               
                   
               
               
                   
                 KIFRNGG-KN IQEYKGPREA EGIVEYLKKQ SGPAS-TEIK SADDATAFVG 
               
               
                   
                 KIFRGLDAVK P--YQGARQT EAIVSYMVKQ SLPAV-SPVT DQGVEGYPTL 
               
               
                   
                 KIFKNRDVNN SIDYEGPRTA EAIVQFMIKQ SQPAV-AVVA DLPAYL-ANE 
               
               
                   
                 KFFKNGDTAS PKEYTAGREA DDIVNWLKKR TGPAA-STLS DGAAAEALVE 
               
               
                   
                 KFFKNGDTAS PKEYTAGREA DDIVNWLKKR TGPAA-TTLS DTAAAESLVD 
               
               
                   
                 KIFRKG---R PFDYNGPREK YGIVDYMIEQ SGPPSKEILT LKQVQEFLKD 
               
               
                   
               
               
                   
                 DNKVVIVGVG PKFSGEEYDN FIALAEKLRS DYDFAHTLNA KHLPKGDSSV 
               
               
                   
                 MDKIVVIGYI ASDDQTANDI FTTFAESQRD NYLFAATSDA SI--AKAEGV 
               
               
                   
                 TFVTPVIVQS GKIDADFNAT FYSMANKHFN DYDFVSAENA DD--DFKLSI 
               
               
                   
                 SSEVAVIGFF KDMESDSAKQ FFLAAEVI-D DIPFGITSNS DV--FSKYQL 
               
               
                   
                 SSEVTVIGFF KDAGSDSAKQ FLLAAEAV-D DIPFGITSNS DV--FSKYQL 
               
               
                   
                 GDDVVIIGLF QGDGDPAYLQ YQDAANNLRE DYKFHHTFSP EIAKFLKVSL 
               
               
                   
               
               
                   
                 SGPVVRLFKP FDELFVDS-- -KDFNVEALE KFIEESSTPI VTVFNNEPSN 
               
               
                   
                 KQPSIVLYKD FDEKKATYDG EIEQDALLSW VKTASTPLVG ELGPETYSGY 
               
               
                   
                 YLPSAM--DE PVVYNGKKAD IADADVFEKW LQVEALPYFG EIDGSVFAQY 
               
               
                   
                 DKDGVVLFKK FD---EGR-- -NNFEGEVTK EKLLDFIKHN QLPLVIEFTE 
               
               
                   
                 DKDGVVLFKK FD---EGR-- -NNFEGEVTK EKLLDFIKHN QLPLVIEFTE 
               
               
                   
                 GKLVLTHPEK FQSKYEPRFH VMDVQGSTEA SAIKDYVVKH ALPLVGHRKT 
               
               
                   
               
               
                   
                 HRFVVKFFNS PNAKAMLFIN FTTEGAESFK TKYHEVAEQY KQQGV-SFLV 
               
               
                   
                 ITAGIPLAYI FAETKEEREQ FTEEFKFIAE KHKGSINIVT IDAKLYGAHA 
               
               
                   
                 VESGLPLGYL FYNDEEELEE YKPLFTELAK KNRGLMNFVS IDARKFGRHA 
               
               
                   
                 QTAPKIFGGE IKTHILLFLP KSVSDYDGKL SNFKKAAEGF KGKILFIFID 
               
               
                   
                 QTAPKIFGGE IKTHILLFLP KSVSDYDGKL SNFKKAAEGF KGKILFIFID 
               
               
                   
                 SNDAKRYSKR PLVVVYYSVD FSFDYRAATQ FWRNKVLEVA KDFPEYTFAI 
               
               
                   
               
               
                   
                 GDVESSQGAF QYFGLKEEQV PLI--IIQHN DGKKFFKPN- --LELDQLPT 
               
               
                   
                 GNLNLDPSKF PAFAIQDPEK NAKY------ --PYDQSKE- --VKAKDIGK 
               
               
                   
                 GNLNMK-EQF PLFAIHDMTE DLKYGLPQLS EEAFDELSDK IVLESKAIES 
               
               
                   
                 SDHTDNQRIL EFFGLKKEEC PAVR-LITLE EEMTKYKPES DELTAEKITE 
               
               
                   
                 SDHTDNQRIL EFFGLKKEEC PAVR-LITLE EEMTKYKPES DELTAEKITE 
               
               
                   
                 ADEEDYATEV KDLGL-SESG EDVN-AAILD ESGKKFAMEP EEFDSDTLRE 
               
               
                   
               
               
                   
                 WLKAYKDGKV EPFVKSEPIP ETNN-EPVKV VVGQTLEDVV FKSGKNVLIE 
               
               
                   
                 FIQDVLDDKV EPSIKSEAIP ETQE-GPVTV VVAHSYKDLV LDNEKDVLLE 
               
               
                   
                 LVKDFLKGDA SPIVKSQEIF ENQD-SSVFQ LVGKNHDEIV NDPKKDVLVL 
               
               
                   
                 FCHRFLEGKI KPHLMSQELP DDWDKQPVKV LVGKNFEEVA FDEKKNVFVE 
               
               
                   
                 FCHRFLEGKI KPHLMSQELP EDWDKQPVKV LVGKNFEEVA FDEKKNVFVE 
               
               
                   
                 FVTAFKKGKL KPVIKSQPVP KN-NKGPVKV VVGKTFDAIV MDPKKDVLIE 
               
               
                   
               
               
                   
                 FYAPWCGHCK QLAPILDEVA VSFQS-DADV VIAKLDATAN DIPTDTFDVQ 
               
               
                   
                 FYAPWCGHCK ALAPKYEELA SLYKD-IPEV TIAKIDATAN DV--PD-SIT 
               
               
                   
                 YYAPWCGHCK RLAPTYQELA DTYANATSDV LIAKLDHTEN DV--RGVVIE 
               
               
                   
                 FYAPWCGHCK QLAPIWDKLG ETYKD-HENI VIAKMDSTAN EV--EAVKVH 
               
               
                   
                 FYAPWCGHCK QLAPIWDKLG ETYKD-HENI VIAKMDSTAN EV--EAVKVH 
               
               
                   
                 FYAPWCKHCK QLEPIYTSLG KKYKG-QKDL VIAKMDATAN DITNDQYKVE 
               
               
                   
               
               
                   
                 GYPTLYFRSA SGK--LSQYD GGRTKEDIIE FIE------K NKDKTGAAHQ 
               
               
                   
                 GFPTIKLFAA GAKDSPVEYE GSRTVEDLAN FVK------E NGKHKVDALE 
               
               
                   
                 GYPTIVLYPG GKKSESVVYQ GSRSLDSLFD FIK------E NGHFDVDGKA 
               
               
                   
                 SFPTLKFFPA SADRTVIDYN GERTLDGFKK GLESGGQDGA GDDDDLEDLE 
               
               
                   
                 SFPTLKFFPA SADRTVIDYN GERTLDGFKK GLESGGQDGA GDDDDLEDLE 
               
               
                   
                 GFPTIYFAPS GDKKNPI--- ---------K F--------E GGNRDLEHLS 
               
               
                   
               
               
                   
                 EVEQPKAAAQ PE-------- ---------- AEQPKDEL 
               
               
                   
                 VDPKKEQESG DATETRAASD ETETPAATSD DKSEHDEL 
               
               
                   
                 LYEEAQEKAA EEAEADAEAE ADADAELADE EDAIHDEL 
               
               
                   
                 EAEEPDLEED DD-------- ---------- QKAVKDEL 
               
               
                   
                 EAEEPDLEED DD-------- ---------- QKAVKDEL 
               
               
                   
                 KF--ID-EHA TK-------- ---------- RSRTKEEL 
               
             
          
         
       
     
     REFERENCES CITED IN THE SPECIFICATION 
     Sambrook, J., Fritsch, E. F. &amp; Maniatis, T. 1989. Molecular Cloning: A Laboratory Manual. 2. edition. Cold Spring Harbor Lab., Cold Spring Harbor, N.Y. 
     U.S. Pat. No. 4,683,202. 
     Hudson et al, 1989, Practical Immunology, Third edition, Blackwell Scientific Publications. 
     Beaucage and Caruthers, 1981, Tetrahedron Letters 22, 1981, pp. 1859-1869. 
     Matthes et al., 1984, The EMBO J. 3, 1984, pp. 801-805. 
     R. K. Saiki et al., 1988, Science 239, pp. 487-491. 
     WO 91/17243. 
     EP 238 023. 
     Malardier et al. Gene 78 (1989), pp. 147-156. 
     Woodcock et al., Nucleic Acids Res. (1989) 17:3469-3478. 
     
       
         
               
             
           
               
                   
               
               
                                                SEQUENCE LISTING 
               
               
                   
               
               
                   
               
               
                 (1) GENERAL INFORMATION: 
               
               
                   
               
               
                    (iii) NUMBER OF SEQUENCES: 38 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 1: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 1953 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: DNA (genomic) 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE: 
               
               
                           (A) ORGANISM: Aspergillus oryzae 
               
               
                           (B) STRAIN: IFO 4177 
               
               
                   
               
               
                     (ix) FEATURE: 
               
               
                           (A) NAME/KEY: CDS 
               
               
                           (B) LOCATION: join(71..445, 503..880, 962..1402, 
               
               
                                1479..1829) 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1: 
               
               
                   
               
               
                 CCCTGCTGTC CCCATAGACA GTACACACGT CATCCTTTGA TATTGTCACA CTTGACAAAT     60 
               
               
                   
               
               
                 TCCCGACACC ATG CGG ACT TTC GCA CCT TGG ATC TTG AGC CTT CTA GGG       109 
               
               
                            Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly 
               
               
                              1               5                  10 
               
               
                   
               
               
                 GCT TCT GCT GTA GCT TCT GCT GCC GAT GCG ACT GCC GAA GCT CCC TCC      157 
               
               
                 Ala Ser Ala Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser 
               
               
                      15                  20                  25 
               
               
                   
               
               
                 GAT GTG GTC TCG CTC ACC GGG GAC ACA TTC GAA ACT TTC GTC AAG GAG      205 
               
               
                 Asp Val Val Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu 
               
               
                  30                  35                  40                  45 
               
               
                   
               
               
                 CAT GAC CTA GTT TTG GCC GAG TTT TTT GCT CCC TGG TGT GGC CAT TGC      253 
               
               
                 His Asp Leu Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys 
               
               
                                  50                  55                  60 
               
               
                   
               
               
                 AAG GCT CTC GCT CCG AAA TAC GAG CAG GCC GCC ACT GAG TTA AAG GAA      301 
               
               
                 Lys Ala Leu Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu 
               
               
                              65                  70                  75 
               
               
                   
               
               
                 AAG AAC ATT CCG CTG GTC AAG GTT GAT TGC ACC GAG GAA GAG GCT CTT      349 
               
               
                 Lys Asn Ile Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu 
               
               
                          80                  85                  90 
               
               
                   
               
               
                 TGT AGG GAC CAA GGT GTT GAA GGT TAC CCC ACG CTG AAG ATT TTC CGT      397 
               
               
                 Cys Arg Asp Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg 
               
               
                      95                 100                 105 
               
               
                   
               
               
                 GGC CTT GAC GCT GTT AAG CCT TAT CAG GGA GCT CGT CAG ACC GAG GCG      445 
               
               
                 Gly Leu Asp Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala 
               
               
                 110                 115                 120                 125 
               
               
                   
               
               
                 GTAAGTGTCA CCTGTTTGTT AGCCTTGCTC AAATAATATT GACCGCTAGT ATCATAG       502 
               
               
                   
               
               
                 ATT GTT TCA TAC ATG GTC AAG CAG TCA CTA CCT GCT GTG TCC CCT GTC      550 
               
               
                 Ile Val Ser Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val 
               
               
                                 130                 135                 140 
               
               
                   
               
               
                 ACC CCA GAA AAC CTC GAA GAG ATC AAG ACT ATG GAC AAG ATT GTC GTT      598 
               
               
                 Thr Pro Glu Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val 
               
               
                             145                 150                 155 
               
               
                   
               
               
                 ATT GGT TAT ATC GCG TCT GAC GAC CAG ACT GCC AAT GAT ATA TTC ACC      646 
               
               
                 Ile Gly Tyr Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr 
               
               
                         160                 165                 170 
               
               
                   
               
               
                 ACT TTT GCC GAG TCA CAG AGA GAC AAC TAC CTC TTC GCC GCC ACA AGT      694 
               
               
                 Thr Phe Ala Glu Ser Gln Arg Asp Asn Tyr Leu Phe Ala Ala Thr Ser 
               
               
                     175                 180                 185 
               
               
                   
               
               
                 GAT GCA TCG ATC GCT AAG GCA GAA GGT GTT AAG CAA CCT TCG ATT GTT      742 
               
               
                 Asp Ala Ser Ile Ala Lys Ala Glu Gly Val Lys Gln Pro Ser Ile Val 
               
               
                 190                 195                 200                 205 
               
               
                   
               
               
                 CTC TAT AAA GAC TTC GAT GAA AAG AAA GCT ACT TAT GAT GGA GAG ATT      790 
               
               
                 Leu Tyr Lys Asp Phe Asp Glu Lys Lys Ala Thr Tyr Asp Gly Glu Ile 
               
               
                                 210                 215                 220 
               
               
                   
               
               
                 GAA CAG GAT GCC CTC CTC AGT TGG GTC AAG ACT GCC AGT ACC CCC TTG      838 
               
               
                 Glu Gln Asp Ala Leu Leu Ser Trp Val Lys Thr Ala Ser Thr Pro Leu 
               
               
                             225                 230                 235 
               
               
                   
               
               
                 GTG GGC GAG CTG GGC CCA GAG ACT TAC TCC GGA TAT ATA ACG              880 
               
               
                 Val Gly Glu Leu Gly Pro Glu Thr Tyr Ser Gly Tyr Ile Thr 
               
               
                         240                 245                 250 
               
               
                   
               
               
                 GTATGTCACA AGACACAATC TCAATATCGC TTCACAACGT TTAGTAAATA ATCATGAGTT    940 
               
               
                   
               
               
                 TCTGACATGG GTTTGGTTAA G GCT GGC ATT CCA CTG GCG TAC ATT TTC GCC      991 
               
               
                                         Ala Gly Ile Pro Leu Ala Tyr Ile Phe Ala 
               
               
                                                     255                 260 
               
               
                   
               
               
                 GAA ACC AAA GAA GAG CGT GAG CAG TTC ACC GAG GAG TTC AAG TTC ATC     1039 
               
               
                 Glu Thr Lys Glu Glu Arg Glu Gln Phe Thr Glu Glu Phe Lys Phe Ile 
               
               
                             265                 270                 275 
               
               
                   
               
               
                 GCC GAG AAA CAC AAG GGT TCC ATC AAT ATT GTC ACC ATT GAC GCC AAG     1087 
               
               
                 Ala Glu Lys His Lys Gly Ser Ile Asn Ile Val Thr Ile Asp Ala Lys 
               
               
                         280                 285                 290 
               
               
                   
               
               
                 TTG TAC GGC GCT CAT GCA GGC AAT CTC AAC CTT GAC CCC TCC AAG TTC     1135 
               
               
                 Leu Tyr Gly Ala His Ala Gly Asn Leu Asn Leu Asp Pro Ser Lys Phe 
               
               
                     295                 300                 305 
               
               
                   
               
               
                 CCT GCA TTC GCT ATT CAA GAC CCT GAA AAG AAC GCC AAG TAT CCT TAT     1183 
               
               
                 Pro Ala Phe Ala Ile Gln Asp Pro Glu Lys Asn Ala Lys Tyr Pro Tyr 
               
               
                 310                 315                 320                 325 
               
               
                   
               
               
                 GAC CAG TCG AAG GAA GTC AAG GCC AAG GAT ATC GGT AAA TTC ATC CAA     1231 
               
               
                 Asp Gln Ser Lys Glu Val Lys Ala Lys Asp Ile Gly Lys Phe Ile Gln 
               
               
                                 330                 335                 340 
               
               
                   
               
               
                 GAC GTT CTT GAT GAT AAA GTA GAG CCA AGC ATT AAG TCT GAG GCT ATT     1279 
               
               
                 Asp Val Leu Asp Asp Lys Val Glu Pro Ser Ile Lys Ser Glu Ala Ile 
               
               
                             345                 350                 355 
               
               
                   
               
               
                 CCT GAG ACT CAG GAA GGT CCT GTT ACT GTT GTT GTC GCG CAT TCC TAT     1327 
               
               
                 Pro Glu Thr Gln Glu Gly Pro Val Thr Val Val Val Ala His Ser Tyr 
               
               
                         360                 365                 370 
               
               
                   
               
               
                 AAG GAT CTC GTC CTT GAC AAC GAG AAG GAC GTC CTT CTC GAA TTT TAT     1375 
               
               
                 Lys Asp Leu Val Leu Asp Asn Glu Lys Asp Val Leu Leu Glu Phe Tyr 
               
               
                     375                 380                 385 
               
               
                   
               
               
                 GCG CCA TGG TGC GGA CAC TGC AAG GCC  GTAAGTTTTC CCCCTCTTTC          1422 
               
               
                 Ala Pro Trp Cys Gly His Cys Lys Ala 
               
               
                 390                 395 
               
               
                   
               
               
                 TCTACAACGA ATTATATCCA CTCTCGCTTG CGAATACCTA ATTAAACCTT GAATAG       1478 
               
               
                   
               
               
                 CTT GCC CCG AAG TAC GAG GAA CTT GCA AGC CTT TAC AAG GAT ATT CCT     1526 
               
               
                 Leu Ala Pro Lys Tyr Glu Glu Leu Ala Ser Leu Tyr Lys Asp Ile Pro 
               
               
                     400                 405                 410 
               
               
                   
               
               
                 GAA GTT ACC ATC GCC AAA ATT GAC GCA ACG GCC AAC GAT GTC CCC GAC     1574 
               
               
                 Glu Val Thr Ile Ala Lys Ile Asp Ala Thr Ala Asn Asp Val Pro Asp 
               
               
                 415                 420                 425                 430 
               
               
                   
               
               
                 TCC ATT ACA GGA TTT CCT ACT ATT AAG CTC TTC GCT GCC GGC GCC AAG     1622 
               
               
                 Ser Ile Thr Gly Phe Pro Thr Ile Lys Leu Phe Ala Ala Gly Ala Lys 
               
               
                                 435                 440                 445 
               
               
                   
               
               
                 GAC TCC CCA GTT GAA TAT GAA GGC TCT CGC ACG GTG GAG GAC CTC GCC     1670 
               
               
                 Asp Ser Pro Val Glu Tyr Glu Gly Ser Arg Thr Val Glu Asp Leu Ala 
               
               
                             450                 455                 460 
               
               
                   
               
               
                 AAC TTC GTC AAG GAG AAT GGC AAG CAC AAG GTC GAT GCT CTT GAA GTT     1718 
               
               
                 Asn Phe Val Lys Glu Asn Gly Lys His Lys Val Asp Ala Leu Glu Val 
               
               
                         465                 470                 475 
               
               
                   
               
               
                 GAT CCG AAG AAA GAA CAG GAG AGT GGC GAT GCC ACC GAG ACT CGG GCC     1766 
               
               
                 Asp Pro Lys Lys Glu Gln Glu Ser Gly Asp Ala Thr Glu Thr Arg Ala 
               
               
                     480                 485                 490 
               
               
                   
               
               
                 GCC TCT GAC GAG ACC GAA ACT CCT GCT GCT ACT AGC GAT GAC AAG TCT     1814 
               
               
                 Ala Ser Asp Glu Thr Glu Thr Pro Ala Ala Thr Ser Asp Asp Lys Ser 
               
               
                 495                 500                 505                 510 
               
               
                   
               
               
                 GAG CAT GAT GAA TTG TAAATTTCAT TTGGCCTGAT AGTTTGATCC ATATTTATGT     1869 
               
               
                 Glu His Asp Glu Leu 
               
               
                                 515 
               
               
                   
               
               
                 GAATTCTTGT ATTCTACCAG CAGTTTGAGC AATCGCAGCT ACTTCCGGCT TAGGAAACTG   1929 
               
               
                   
               
               
                 TTGTTCTATC CTAGTGGGAA GCTT                                          1953 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 2: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 1547 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: cDNA 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE: 
               
               
                           (A) ORGANISM: Aspergillus oryzae 
               
               
                           (B) STRAIN: IFO 4177 
               
               
                   
               
               
                     (ix) FEATURE: 
               
               
                           (A) NAME/KEY: CDS 
               
               
                           (B) LOCATION: 1..1547 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: 
               
               
                   
               
               
                 ATG CGG ACT TTC GCA CCT TGG ATC TTG AGC CTT CTA GGG GCT TCT GCT       48 
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 GTA GCT TCT GCT GCC GAT GCG ACT GCC GAA GCT CCC TCC GAT GTG GTC       96 
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 TCG CTC ACC GGG GAC ACA TTC GAA ACT TTC GTC AAG GAG CAT GAC CTA      144 
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 GTT TTG GCC GAG TTT TTT GCT CCC TGG TGT GGC CAT TGC AAG GCT CTC      192 
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 GCT CCG AAA TAC GAG CAG GCC GCC ACT GAG TTA AAG GAA AAG AAC ATT      240 
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 CCG CTG GTC AAG GTT GAT TGC ACC GAG GAA GAG GCT CTT TGT AGG GAC      288 
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 CAA GGT GTT GAA GGT TAC CCC ACG CTG AAG ATT TTC CGT GGC CTT GAC      336 
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 GCT GTT AAG CCT TAT CAG GGA GCT CGT CAG ACC GAG GCG ATT GTT TCA      384 
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 TAC ATG GTC AAG CAG TCA CTA CCT GCT GTG TCC CCT GTC ACC CCA GAA      432 
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 AAC CTC GAA GAG ATC AAG ACT ATG GAC AAG ATT GTC GTT ATT GGT TAT      480 
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 ATC GCG TCT GAC GAC CAG ACT GCC AAT GAT ATA TTC ACC ACT TTT GCC      528 
               
               
                 Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr Thr Phe Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 GAG TCA CAG AGA GAC AAC TAC CTC TTC GCC GCC ACA AGT GAT GCA TCG      576 
               
               
                 Glu Ser Gln Arg Asp Asn Tyr Leu Phe Ala Ala Thr Ser Asp Ala Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 ATC GCT AAG GCA GAA GGT GTT AAG CAA CCT TCG ATT GTT CTC TAT AAA      624 
               
               
                 Ile Ala Lys Ala Glu Gly Val Lys Gln Pro Ser Ile Val Leu Tyr Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 GAC TTC GAT GAA AAG AAA GCT ACT TAT GAT GGA GAG ATT GAA CAG GAT      672 
               
               
                 Asp Phe Asp Glu Lys Lys Ala Thr Tyr Asp Gly Glu Ile Glu Gln Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 GCC CTC CTC AGT TGG GTC AAG ACT GCC AGT ACC CCC TTG GTG GGC GAG      720 
               
               
                 Ala Leu Leu Ser Trp Val Lys Thr Ala Ser Thr Pro Leu Val Gly Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 CTG GGC CCA GAG ACT TAC TCC GGA TAT ATA ACG GCT GGC ATT CCA CTG      768 
               
               
                 Leu Gly Pro Glu Thr Tyr Ser Gly Tyr Ile Thr Ala Gly Ile Pro Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 GCG TAC ATT TTC GCC GAA ACC AAA GAA GAG CGT GAG CAG TTC ACC GAG      816 
               
               
                 Ala Tyr Ile Phe Ala Glu Thr Lys Glu Glu Arg Glu Gln Phe Thr Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 GAG TTC AAG TTC ATC GCC GAG AAA CAC AAG GGT TCC ATC AAT ATT GTC      864 
               
               
                 Glu Phe Lys Phe Ile Ala Glu Lys His Lys Gly Ser Ile Asn Ile Val 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 ACC ATT GAC GCC AAG TTG TAC GGC GCT CAT GCA GGC AAT CTC AAC CTT      912 
               
               
                 Thr Ile Asp Ala Lys Leu Tyr Gly Ala His Ala Gly Asn Leu Asn Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 GAC CCC TCC AAG TTC CCT GCA TTC GCT ATT CAA GAC CCT GAA AAG AAC      960 
               
               
                 Asp Pro Ser Lys Phe Pro Ala Phe Ala Ile Gln Asp Pro Glu Lys Asn 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 GCC AAG TAT CCT TAT GAC CAG TCG AAG GAA GTC AAG GCC AAG GAT ATC     1008 
               
               
                 Ala Lys Tyr Pro Tyr Asp Gln Ser Lys Glu Val Lys Ala Lys Asp Ile 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 GGT AAA TTC ATC CAA GAC GTT CTT GAT GAT AAA GTA GAG CCA AGC ATT     1056 
               
               
                 Gly Lys Phe Ile Gln Asp Val Leu Asp Asp Lys Val Glu Pro Ser Ile 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 AAG TCT GAG GCT ATT CCT GAG ACT CAG GAA GGT CCT GTT ACT GTT GTT     1104 
               
               
                 Lys Ser Glu Ala Ile Pro Glu Thr Gln Glu Gly Pro Val Thr Val Val 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 GTC GCG CAT TCC TAT AAG GAT CTC GTC CTT GAC AAC GAG AAG GAC GTC     1152 
               
               
                 Val Ala His Ser Tyr Lys Asp Leu Val Leu Asp Asn Glu Lys Asp Val 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 CTT CTC GAA TTT TAT GCG CCA TGG TGC GGA CAC TGC AAG GCC CTT GCC     1200 
               
               
                 Leu Leu Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 CCG AAG TAC GAG GAA CTT GCA AGC CTT TAC AAG GAT ATT CCT GAA GTT     1248 
               
               
                 Pro Lys Tyr Glu Glu Leu Ala Ser Leu Tyr Lys Asp Ile Pro Glu Val 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 ACC ATC GCC AAA ATT GAC GCA ACG GCC AAC GAT GTC CCC GAC TCC ATT     1296 
               
               
                 Thr Ile Ala Lys Ile Asp Ala Thr Ala Asn Asp Val Pro Asp Ser Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 ACA GGA TTT CCT ACT ATT AAG CTC TTC GCT GCC GGC GCC AAG GAC TCC     1344 
               
               
                 Thr Gly Phe Pro Thr Ile Lys Leu Phe Ala Ala Gly Ala Lys Asp Ser 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 CCA GTT GAA TAT GAA GGC TCT CGC ACG GTG GAG GAC CTC GCC AAC TTC     1392 
               
               
                 Pro Val Glu Tyr Glu Gly Ser Arg Thr Val Glu Asp Leu Ala Asn Phe 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 GTC AAG GAG AAT GGC AAG CAC AAG GTC GAT GCT CTT GAA GTT GAT CCG     1440 
               
               
                 Val Lys Glu Asn Gly Lys His Lys Val Asp Ala Leu Glu Val Asp Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 AAG AAA GAA CAG GAG AGT GGC GAT GCC ACC GAG ACT CGG GCC GCC TCT     1488 
               
               
                 Lys Lys Glu Gln Glu Ser Gly Asp Ala Thr Glu Thr Arg Ala Ala Ser 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 GAC GAG ACC GAA ACT CCT GCT GCT ACT AGC GAT GAC AAG TCT GAG CAT     1536 
               
               
                 Asp Glu Thr Glu Thr Pro Ala Ala Thr Ser Asp Asp Lys Ser Glu His 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 GAT GAA TTG TA                                                      1547 
               
               
                 Asp Glu Leu 
               
               
                         515 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 3: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 515 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr Thr Phe Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Glu Ser Gln Arg Asp Asn Tyr Leu Phe Ala Ala Thr Ser Asp Ala Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Ala Lys Ala Glu Gly Val Lys Gln Pro Ser Ile Val Leu Tyr Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Asp Phe Asp Glu Lys Lys Ala Thr Tyr Asp Gly Glu Ile Glu Gln Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ala Leu Leu Ser Trp Val Lys Thr Ala Ser Thr Pro Leu Val Gly Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Leu Gly Pro Glu Thr Tyr Ser Gly Tyr Ile Thr Ala Gly Ile Pro Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Tyr Ile Phe Ala Glu Thr Lys Glu Glu Arg Glu Gln Phe Thr Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Glu Phe Lys Phe Ile Ala Glu Lys His Lys Gly Ser Ile Asn Ile Val 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Thr Ile Asp Ala Lys Leu Tyr Gly Ala His Ala Gly Asn Leu Asn Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Asp Pro Ser Lys Phe Pro Ala Phe Ala Ile Gln Asp Pro Glu Lys Asn 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Ala Lys Tyr Pro Tyr Asp Gln Ser Lys Glu Val Lys Ala Lys Asp Ile 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Gly Lys Phe Ile Gln Asp Val Leu Asp Asp Lys Val Glu Pro Ser Ile 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Ser Glu Ala Ile Pro Glu Thr Gln Glu Gly Pro Val Thr Val Val 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Ala His Ser Tyr Lys Asp Leu Val Leu Asp Asn Glu Lys Asp Val 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Leu Leu Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Pro Lys Tyr Glu Glu Leu Ala Ser Leu Tyr Lys Asp Ile Pro Glu Val 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Thr Ile Ala Lys Ile Asp Ala Thr Ala Asn Asp Val Pro Asp Ser Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Thr Gly Phe Pro Thr Ile Lys Leu Phe Ala Ala Gly Ala Lys Asp Ser 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Val Glu Tyr Glu Gly Ser Arg Thr Val Glu Asp Leu Ala Asn Phe 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Val Lys Glu Asn Gly Lys His Lys Val Asp Ala Leu Glu Val Asp Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Lys Lys Glu Gln Glu Ser Gly Asp Ala Thr Glu Thr Arg Ala Ala Ser 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Asp Glu Thr Glu Thr Pro Ala Ala Thr Ser Asp Asp Lys Ser Glu His 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Asp Glu Leu 
               
               
                         515 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 4: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 511 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr Thr Phe Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Glu Ser Gln Arg Asp Asn Tyr Leu Phe Ala Ala Thr Ser Asp Ala Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Ala Lys Ala Glu Gly Val Lys Gln Pro Ser Ile Val Leu Tyr Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Asp Phe Asp Glu Lys Lys Ala Thr Tyr Asp Gly Glu Ile Glu Gln Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ala Leu Leu Ser Trp Val Lys Thr Ala Ser Thr Pro Leu Val Gly Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Leu Gly Pro Glu Thr Tyr Ser Gly Tyr Ile Thr Ala Gly Ile Pro Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Tyr Ile Phe Ala Glu Thr Lys Glu Glu Arg Glu Gln Phe Thr Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Glu Phe Lys Phe Ile Ala Glu Lys His Lys Gly Ser Ile Asn Ile Val 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Thr Ile Asp Ala Lys Leu Tyr Gly Ala His Ala Gly Asn Leu Asn Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Asp Pro Ser Lys Phe Pro Ala Phe Ala Ile Gln Asp Pro Glu Lys Asn 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Ala Lys Tyr Pro Tyr Asp Gln Ser Lys Glu Val Lys Ala Lys Asp Ile 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Gly Lys Phe Ile Gln Asp Val Leu Asp Asp Lys Val Glu Pro Ser Ile 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Ser Glu Ala Ile Pro Glu Thr Gln Glu Gly Pro Val Thr Val Val 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Ala His Ser Tyr Lys Asp Leu Val Leu Asp Asn Glu Lys Asp Val 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Leu Leu Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Pro Lys Tyr Glu Glu Leu Ala Ser Leu Tyr Lys Asp Ile Pro Glu Val 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Thr Ile Ala Lys Ile Asp Ala Thr Ala Asn Asp Val Pro Asp Ser Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Thr Gly Phe Pro Thr Ile Lys Leu Phe Ala Ala Gly Ala Lys Asp Ser 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Val Glu Tyr Glu Gly Ser Arg Thr Val Glu Asp Leu Ala Asn Phe 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Val Lys Glu Asn Gly Lys His Lys Val Asp Ala Leu Glu Val Asp Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Lys Lys Glu Gln Glu Ser Gly Asp Ala Thr Glu Thr Arg Ala Ala Ser 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Asp Glu Thr Glu Thr Pro Ala Ala Thr Ser Asp Asp Lys Ser Ala 
               
               
                             500                 505                 510 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 5: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 281 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr Thr Phe Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Glu Ser Gln Arg Asp Asn Tyr Leu Phe Ala Ala Thr Ser Asp Ala Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Ala Lys Ala Glu Gly Val Lys Gln Pro Ser Ile Val Leu Tyr Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Asp Phe Asp Glu Lys Lys Ala Thr Tyr Asp Gly Glu Ile Glu Gln Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ala Leu Leu Ser Trp Val Lys Thr Ala Ser Thr Pro Leu Val Gly Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Leu Gly Pro Glu Thr Tyr Ser Gly Tyr Ile Thr Ala Gly Ile Pro Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Tyr Ile Phe Ala Glu Thr Lys Glu Glu Arg Glu Gln Phe Thr Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Glu Phe Lys Phe Ile Ala Glu Lys His 
               
               
                         275                 280 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 6: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 174 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr Thr 
               
               
                                 165                 170 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 7: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 163 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ile Ala Ser 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 8: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 143 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro 
               
               
                     130                 135                 140 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 9: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 141 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val 
               
               
                     130                 135                 140 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 10: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 131 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val 
               
               
                     130 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 11: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 129 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Leu Ile Arg Glu Leu Leu Gln Glu Leu Val Asn Lys His 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Leu 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 12: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 200 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: protein 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12: 
               
               
                   
               
               
                 Ala Glu Ala Pro Ser Asp Val Val Ser Leu Thr Gly Asp Thr Phe Glu 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Thr Phe Val Lys Glu His Asp Leu Val Leu Ala Glu Phe Phe Ala Pro 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Trp Cys Gly His Cys Lys Ala Leu Ala Pro Lys Tyr Glu Gln Ala Ala 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Thr Glu Leu Lys Glu Lys Asn Ile Pro Leu Val Lys Val Asp Cys Thr 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Glu Glu Glu Ala Leu Cys Arg Asp Gln Gly Val Glu Gly Tyr Pro Thr 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Leu Lys Ile Phe Arg Gly Leu Asp Ala Val Lys Pro Tyr Gln Gly Ala 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Arg Gln Thr Glu Ala Ile Val Ser Tyr Met Val Lys Gln Ser Leu Pro 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Ser Pro Val Thr Pro Glu Asn Leu Glu Glu Ile Lys Thr Met 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Asp Lys Ile Val Val Ile Gly Tyr Ile Ala Ser Asp Asp Gln Thr Ala 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Asp Ile Phe Thr Thr Phe Ala Glu Ser Gln Arg Asp Asn Tyr Leu 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Phe Ala Ala Thr Ser Asp Ala Ser Ile Ala Lys Ala Glu Gly Val Lys 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Gln Pro Ser Ile Val Leu Tyr Lys Asp Phe Asp Glu Lys Lys Ala Thr 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Tyr Asp Gly Glu Ile Glu Gln Asp 
               
               
                         195                 200 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 13: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 25 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 4762 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: 
               
               
                   
               
               
                 TGGAATTCTG GTGYGGNCAY TGYAA                                           25 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 14: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 23 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 4763 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14: 
               
               
                   
               
               
                 TGGGATCCRC ACCANGGNGC RTA                                             23 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 15: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 29 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5205 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15: 
               
               
                   
               
               
                 TTCGGATCCA CCATGCGGAC TTTCGCACC                                       29 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 16: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 55 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5215 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16: 
               
               
                   
               
               
                 CCAAGCTTTA GAGATGCTTG TTGACAAGCT CCTGGAGGAG CTCCCTGATA AGCTT          55 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 17: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 45 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5397 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17: 
               
               
                   
               
               
                 CCAAGCTTTA GACCATGTAT GACACAATCG CCTCGGTCTG ACGAG                     45 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 18: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 31 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5895 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: 
               
               
                   
               
               
                 CCAAGCTTTA GACAGGGGAC ACAGCAGGTA G                                    31 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 19: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 27 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5399 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19: 
               
               
                   
               
               
                 CCAAGCTTTA TGGGGTGACA GGGGACA                                         27 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 20: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 31 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5894 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20: 
               
               
                   
               
               
                 CCAAGCTTTA AGACGCGATA TAACCAATAA C                                    31 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 21: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 31 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5893 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21: 
               
               
                   
               
               
                 CCAAGCTTTA AGTGGTGAAT ATATCATTGG C                                    31 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 22: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 30 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 6314 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22: 
               
               
                   
               
               
                 CCAAGCTTAG TGTTTCTCGG CGATGAACTT                                      30 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 23: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 31 base pairs 
               
               
                           (B) TYPE: nucleic acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: primer 5204 
               
               
                   
               
               
                    (iii) HYPOTHETICAL: YES 
               
               
                   
               
               
                    (iii) ANTI-SENSE: NO 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23: 
               
               
                   
               
               
                 CCAAGCTTTA CGCAGACTTG TCATCGCTAG T                                    31 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:24: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 8 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: 
               
               
                   
               
               
                 Ala Pro Trp Cys Gly His Cys Lys 
               
               
                 1               5 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:25: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 7 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: 
               
               
                   
               
               
                 Thr Ala Glu Ala Pro Ser Asp 
               
               
                 1               5 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:26: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 3052 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: 
               
               
                   
               
               
                 Met Leu Ser Arg Ala Leu Leu Cys Leu Ala Leu Ala Trp Ala Ala Arg 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Val Gly Ala Asp Ala Leu Glu Glu Glu Asp Asn Val Leu Val Leu Lys 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Lys Ser Asn Phe Ala Glu Ala Leu Ala Ala His Met Leu Arg Arg Ala 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Leu Leu Cys Leu Ala Leu Thr Ala Leu Phe Arg Ala Gly Ala Gly Ala 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Pro Asp Glu Glu Asp His Val Leu Val Leu His Lys Gly Asn Phe Asp 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Glu Ala Leu Ala Ala His Met Leu Arg Arg Ala Leu Leu Cys Leu Ala 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Val Ala Ala Leu Val Arg Ala Asp Ala Pro Glu Glu Glu Asp His Val 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Leu Val Leu Arg Lys Ser Asn Phe Ala Glu Ala Leu Ala Ala His Met 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Leu Arg Arg Ala Val Leu Cys Leu Ala Leu Ala Val Thr Ala Gly Trp 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Ala Trp Ala Ala Glu Glu Glu Asp Asn Val Leu Val Leu Lys Ser Ser 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Asn Phe Ala Glu Glu Leu Ala Ala His Glu Pro Leu Glu Glu Glu Asp 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Gly Val Leu Val Leu Arg Ala Ala Asn Phe Glu Gln Ala Leu Ala Ala 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 His Met Lys Phe Ser Ala Gly Ala Val Leu Ser Trp Ser Ser Leu Leu 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Leu Ala Ser Ser Val Phe Ala Gln Gln Glu Ala Val Ala Pro Glu Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ser Ala Val Val Lys Leu Ala Thr Asp Ser Phe Asn Glu Tyr Ile Gln 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Ser His Asn Tyr Leu Leu Val Glu Phe Tyr Ala Pro Trp Cys Gly His 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Cys Lys Ala Leu Ala Pro Glu Tyr Ala Lys Ala Ala Ala Lys Leu Lys 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Ala Glu Gly Ser Glu Ile Arg Leu Ala Lys Val Asp Ala Thr Glu Glu 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Ser Asp Leu Ala Lys Tyr Leu Leu Val Glu Phe Tyr Ala Pro Trp Cys 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Gly His Cys Lys Ala Leu Ala Pro Glu Tyr Ala Lys Ala Ala Gly Lys 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu Ala Lys Val Asp Ala Thr 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Glu Glu Ser Asp Leu Ala Lys Tyr Leu Leu Val Glu Phe Tyr Ala Pro 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr Ala Lys Ala Ala 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Gly Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu Ala Lys Val Asp 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Ala Thr Glu Glu Ser Asp Leu Ala Lys Tyr Leu Leu Val Glu Phe Tyr 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr Ala Lys 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Ala Ala Gly Lys Leu Lys Ala Glu Gly Ser Asp Ile Arg Leu Ala Lys 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Arg His Leu Leu Val Glu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Ala Lys Ala Ala Ala Gln Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Ala Lys Val Asp Ala Thr Glu Glu Ala Glu Leu Ala Asp Leu Val Leu 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Asn Met Ala Pro 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Glu Tyr Val Lys Ala Ala Glu Thr Leu Val Glu Lys Asn Ile Thr Leu 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Ala Gln Ile Asp Cys Thr Glu Asn Gln Asp Leu Cys Gln Gln Tyr Gly 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp Thr Ala 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val Asn 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Ser Gln Gln 
               
               
                             580                 585                 590 
               
               
                   
               
               
                 Tyr Gly Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp 
               
               
                         595                 600                 605 
               
               
                   
               
               
                 Thr Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile 
               
               
                     610                 615                 620 
               
               
                   
               
               
                 Val Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Ser Thr Leu Ser 
               
               
                 625                 630                 635                 640 
               
               
                   
               
               
                 Gln Gln Tyr Gly Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Arg Asn 
               
               
                                 645                 650                 655 
               
               
                   
               
               
                 Gly Asp Thr Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp 
               
               
                             660                 665                 670 
               
               
                   
               
               
                 Asp Ile Val Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr 
               
               
                         675                 680                 685 
               
               
                   
               
               
                 Leu Arg Gln Gln Tyr Gly Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe 
               
               
                     690                 695                 700 
               
               
                   
               
               
                 Lys Asn Gly Asp Thr Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu 
               
               
                 705                 710                 715                 720 
               
               
                   
               
               
                 Ala Asp Asp Ile Val Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala 
               
               
                                 725                 730                 735 
               
               
                   
               
               
                 Thr Thr Leu Ala Gln Gln Tyr Gly Val Arg Gly Tyr Pro Thr Ile Lys 
               
               
                             740                 745                 750 
               
               
                   
               
               
                 Phe Phe Arg Asn Gly Asp Lys Ala Ala Pro Arg Glu Tyr Thr Ala Gly 
               
               
                         755                 760                 765 
               
               
                   
               
               
                 Arg Glu Ala Asp Asp Ile Val Ser Trp Leu Lys Lys Arg Thr Gly Pro 
               
               
                     770                 775                 780 
               
               
                   
               
               
                 Ala Ala Thr Thr Leu Thr Met Glu His Asn Ile Pro Gly Phe Pro Ser 
               
               
                 785                 790                 795                 800 
               
               
                   
               
               
                 Leu Lys Ile Phe Lys Asn Ser Asp Val Asn Asn Ser Ile Asp Tyr Glu 
               
               
                                 805                 810                 815 
               
               
                   
               
               
                 Gly Pro Arg Thr Ala Glu Ala Val Gln Phe Met Ile Lys Gln Ser Gln 
               
               
                             820                 825                 830 
               
               
                   
               
               
                 Pro Ala Val Ala Val Val Ala Asp Thr Ala Ala Ala Glu Ser Leu Val 
               
               
                         835                 840                 845 
               
               
                   
               
               
                 Asp Ser Ser Glu Val Thr Val Ile Gly Phe Phe Lys Asp Ala Gly Ser 
               
               
                     850                 855                 860 
               
               
                   
               
               
                 Asp Ser Ala Lys Gln Phe Leu Leu Ala Ala Glu Ala Val Asp Asp Ile 
               
               
                 865                 870                 875                 880 
               
               
                   
               
               
                 Pro Phe Gly Ile Thr Ser Asn Ser Asp Asp Gly Ala Ala Ala Glu Ala 
               
               
                                 885                 890                 895 
               
               
                   
               
               
                 Leu Val Glu Ser Ser Glu Val Ala Val Ile Gly Phe Phe Lys Asp Met 
               
               
                             900                 905                 910 
               
               
                   
               
               
                 Glu Ser Asp Ser Ala Lys Gln Phe Phe Leu Ala Ala Glu Val Ile Asp 
               
               
                         915                 920                 925 
               
               
                   
               
               
                 Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser Asp Asp Gly Ala Ala Ala 
               
               
                     930                 935                 940 
               
               
                   
               
               
                 Glu Ser Leu Val Glu Ser Ser Glu Val Ala Val Ile Gly Phe Phe Lys 
               
               
                 945                 950                 955                 960 
               
               
                   
               
               
                 Asp Val Glu Ser Asp Ser Ala Lys Gln Phe Leu Gln Ala Ala Glu Ala 
               
               
                                 965                 970                 975 
               
               
                   
               
               
                 Ile Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser Asp Asp Ser Ala 
               
               
                             980                 985                 990 
               
               
                   
               
               
                 Ala Ala Glu Ser Leu Val Glu Ser Ser Glu Val Ala Val Ile Gly Phe 
               
               
                         995                 1000                1005 
               
               
                   
               
               
                 Phe Lys Asp Val Glu Ser Asp Ala Ala Lys Gln Phe Leu Leu Ala Ala 
               
               
                     1010                1015                1020 
               
               
                   
               
               
                 Glu Ala Thr Asp Asp Ile Pro Phe Gly Leu Thr Ala Ser Ser Asp Asp 
               
               
                 1025                1030                1035                1040 
               
               
                   
               
               
                 Ala Ala Ala Ala Glu Thr Leu Val Asp Ser Ser Glu Val Val Val Ile 
               
               
                                 1045                1050                1055 
               
               
                   
               
               
                 Gly Phe Phe Lys Asp Val Thr Ser Asp Ala Ala Lys Glu Phe Leu Leu 
               
               
                             1060                1065                1070 
               
               
                   
               
               
                 Ala Ala Glu Ser Val Asp Asp Ile Pro Phe Gly Ile Ser Ser Ser Ala 
               
               
                         1075                1080                1085 
               
               
                   
               
               
                 Asp Asp Leu Pro Ala Tyr Leu Ala Asn Glu Thr Phe Val Thr Pro Val 
               
               
                     1090                1095                1100 
               
               
                   
               
               
                 Ile Val Gln Ser Gly Lys Ile Asp Ala Asp Phe Asn Ala Thr Phe Tyr 
               
               
                 1105                1110                1115                1120 
               
               
                   
               
               
                 Ser Met Ala Asn Lys His Phe Asn Asp Tyr Asp Phe Val Ser Ala Glu 
               
               
                                 1125                1130                1135 
               
               
                   
               
               
                 Asn Ala Asp Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val 
               
               
                             1140                1145                1150 
               
               
                   
               
               
                 Leu Phe Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Ile 
               
               
                         1155                1160                1165 
               
               
                   
               
               
                 Thr Lys Glu Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu 
               
               
                     1170                1175                1180 
               
               
                   
               
               
                 Val Ile Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu 
               
               
                 1185                1190                1195                1200 
               
               
                   
               
               
                 Phe Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr 
               
               
                                 1205                1210                1215 
               
               
                   
               
               
                 Lys Glu Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val 
               
               
                             1220                1225                1230 
               
               
                   
               
               
                 Ile Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe 
               
               
                         1235                1240                1245 
               
               
                   
               
               
                 Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys 
               
               
                     1250                1255                1260 
               
               
                   
               
               
                 Glu Asn Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile 
               
               
                 1265                1270                1275                1280 
               
               
                   
               
               
                 Val Phe Ser Arg Tyr Gln Val His Gln Asp Gly Val Val Leu Phe Lys 
               
               
                                 1285                1290                1295 
               
               
                   
               
               
                 Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys Glu 
               
               
                             1300                1305                1310 
               
               
                   
               
               
                 Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile Val 
               
               
                         1315                1320                1325 
               
               
                   
               
               
                 Phe Ser Lys Tyr Gln Leu Ser Gln Asp Gly Val Val Leu Phe Lys Lys 
               
               
                     1330                1335                1340 
               
               
                   
               
               
                 Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Asp Leu Thr Lys Asp Asn 
               
               
                 1345                1350                1355                1360 
               
               
                   
               
               
                 Leu Leu Asn Phe Ile Lys Ser Asn Gln Leu Pro Leu Val Ile Asp Asp 
               
               
                                 1365                1370                1375 
               
               
                   
               
               
                 Phe Lys Leu Ser Ile Tyr Leu Pro Ser Ala Met Asp Glu Pro Val Val 
               
               
                             1380                1385                1390 
               
               
                   
               
               
                 Tyr Asn Gly Lys Lys Ala Asp Ile Ala Asp Ala Asp Val Phe Glu Lys 
               
               
                         1395                1400                1405 
               
               
                   
               
               
                 Trp Leu Gln Val Glu Ala Leu Pro Tyr Phe Gly Glu Phe Thr Glu Gln 
               
               
                     1410                1415                1420 
               
               
                   
               
               
                 Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His Ile Leu Leu 
               
               
                 1425                1430                1435                1440 
               
               
                   
               
               
                 Phe Leu Pro Lys Ser Val Ser Asp Tyr Asp Gly Lys Leu Ser Asn Phe 
               
               
                                 1445                1450                1455 
               
               
                   
               
               
                 Lys Lys Ala Ala Glu Gly Phe Lys Gly Lys Ile Glu Phe Thr Glu Gln 
               
               
                             1460                1465                1470 
               
               
                   
               
               
                 Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His Ile Leu Leu 
               
               
                         1475                1480                1485 
               
               
                   
               
               
                 Phe Leu Pro Lys Ser Val Ser Asp Tyr Glu Gly Lys Leu Ser Asn Phe 
               
               
                     1490                1495                1500 
               
               
                   
               
               
                 Lys Lys Ala Ala Glu Ser Phe Lys Gly Lys Ile Glu Phe Thr Glu Gln 
               
               
                 1505                1510                1515                1520 
               
               
                   
               
               
                 Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His Ile Leu Leu 
               
               
                                 1525                1530                1535 
               
               
                   
               
               
                 Phe Leu Pro Lys Ser Val Ser Asp Tyr Asp Gly Lys Leu Ser Asn Phe 
               
               
                             1540                1545                1550 
               
               
                   
               
               
                 Lys Thr Ala Ala Glu Ser Phe Lys Gly Lys Ile Glu Phe Thr Glu Gln 
               
               
                         1555                1560                1565 
               
               
                   
               
               
                 Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His Ile Leu Leu 
               
               
                     1570                1575                1580 
               
               
                   
               
               
                 Phe Leu Pro Arg Ser Ala Ala Asp His Asp Gly Lys Leu Ser Gly Phe 
               
               
                 1585                1590                1595                1600 
               
               
                   
               
               
                 Lys Gln Ala Ala Glu Gly Phe Lys Gly Lys Ile Glu Phe Thr Glu Gln 
               
               
                                 1605                1610                1615 
               
               
                   
               
               
                 Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His Ile Leu Leu 
               
               
                             1620                1625                1630 
               
               
                   
               
               
                 Phe Leu Pro Lys Ser Val Ser Asp Tyr Glu Gly Lys Leu Asp Asn Phe 
               
               
                         1635                1640                1645 
               
               
                   
               
               
                 Lys Thr Ala Ala Gly Asn Phe Lys Gly Lys Ile Glu Ile Asp Gly Ser 
               
               
                     1650                1655                1660 
               
               
                   
               
               
                 Val Phe Ala Gln Tyr Val Glu Ser Gly Leu Pro Leu Gly Tyr Leu Phe 
               
               
                 1665                1670                1675                1680 
               
               
                   
               
               
                 Tyr Asn Asp Glu Glu Glu Leu Glu Glu Tyr Lys Pro Leu Phe Thr Glu 
               
               
                                 1685                1690                1695 
               
               
                   
               
               
                 Leu Ala Lys Lys Asn Arg Gly Leu Phe Ile Phe Ile Asp Ser Asp His 
               
               
                             1700                1705                1710 
               
               
                   
               
               
                 Thr Asp Asn Gln Arg Ile Leu Glu Phe Phe Gly Leu Lys Lys Glu Glu 
               
               
                         1715                1720                1725 
               
               
                   
               
               
                 Cys Pro Ala Val Arg Leu Ile Thr Leu Glu Glu Glu Met Thr Lys Tyr 
               
               
                     1730                1735                1740 
               
               
                   
               
               
                 Leu Phe Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu 
               
               
                 1745                1750                1755                1760 
               
               
                   
               
               
                 Glu Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile 
               
               
                                 1765                1770                1775 
               
               
                   
               
               
                 Thr Leu Glu Glu Glu Met Thr Lys Tyr Leu Phe Ile Phe Ile Asp Ser 
               
               
                             1780                1785                1790 
               
               
                   
               
               
                 Asp His Thr Asp Asn Gln Arg Ile Leu Glu Phe Phe Gly Leu Lys Lys 
               
               
                         1795                1800                1805 
               
               
                   
               
               
                 Glu Glu Cys Pro Ala Val Arg Leu Ile Thr Leu Glu Glu Glu Met Thr 
               
               
                     1810                1815                1820 
               
               
                   
               
               
                 Lys Tyr Leu Phe Ile Phe Ile Asp Ser Asp His Ala Asp Asn Gln Arg 
               
               
                 1825                1830                1835                1840 
               
               
                   
               
               
                 Ile Leu Glu Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg 
               
               
                                 1845                1850                1855 
               
               
                   
               
               
                 Leu Ile Thr Leu Glu Glu Glu Met Thr Lys Tyr Leu Phe Ile Phe Ile 
               
               
                             1860                1865                1870 
               
               
                   
               
               
                 Asp Ser Asp His Ser Asp Asn Gln Arg Ile Leu Glu Phe Phe Gly Leu 
               
               
                         1875                1880                1885 
               
               
                   
               
               
                 Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile Thr Leu Glu Glu Glu 
               
               
                     1890                1895                1900 
               
               
                   
               
               
                 Met Thr Lys Tyr Leu Met Asn Phe Val Ser Ile Asp Ala Arg Lys Phe 
               
               
                 1905                1910                1915                1920 
               
               
                   
               
               
                 Gly Arg His Ala Gly Asn Leu Asn Met Lys Glu Gln Phe Pro Leu Phe 
               
               
                                 1925                1930                1935 
               
               
                   
               
               
                 Ala Ile His Asp Met Thr Glu Asp Leu Lys Tyr Gly Leu Pro Gln Leu 
               
               
                             1940                1945                1950 
               
               
                   
               
               
                 Ser Glu Glu Ala Phe Lys Pro Glu Ser Asp Glu Leu Thr Ala Glu Lys 
               
               
                         1955                1960                1965 
               
               
                   
               
               
                 Ile Thr Gln Phe Cys His His Phe Leu Glu Gly Lys Ile Lys Pro His 
               
               
                     1970                1975                1980 
               
               
                   
               
               
                 Leu Met Ser Gln Glu Leu Pro Glu Asp Trp Asp Lys Gln Pro Val Lys 
               
               
                 1985                1990                1995                2000 
               
               
                   
               
               
                 Val Leu Val Gly Lys Lys Pro Glu Ser Asp Glu Leu Thr Ala Glu Lys 
               
               
                                 2005                2010                2015 
               
               
                   
               
               
                 Ile Thr Glu Phe Cys His Arg Phe Leu Glu Gly Lys Ile Lys Pro His 
               
               
                             2020                2025                2030 
               
               
                   
               
               
                 Leu Met Ser Gln Glu Leu Pro Asp Asp Trp Asp Lys Gln Pro Val Lys 
               
               
                         2035                2040                2045 
               
               
                   
               
               
                 Val Leu Val Gly Lys Lys Pro Glu Ser Glu Glu Leu Thr Ala Glu Arg 
               
               
                     2050                2055                2060 
               
               
                   
               
               
                 Ile Thr Glu Phe Cys His Arg Phe Leu Glu Gly Lys Ile Lys Pro His 
               
               
                 2065                2070                2075                2080 
               
               
                   
               
               
                 Leu Met Ser Gln Glu Arg Ala Asp Gly Asp Trp Asp Lys Gln Pro Val 
               
               
                                 2085                2090                2095 
               
               
                   
               
               
                 Lys Val Pro Val Gly Lys Lys Pro Glu Ser Asp Glu Leu Thr Ala Glu 
               
               
                             2100                2105                2110 
               
               
                   
               
               
                 Gly Ile Thr Glu Phe Cys Gln Arg Phe Leu Glu Gly Lys Ile Lys Pro 
               
               
                         2115                2120                2125 
               
               
                   
               
               
                 His Leu Met Ser Gln Glu Leu Pro Asp Glu Asp Trp Asp Arg Gln Pro 
               
               
                     2130                2135                2140 
               
               
                   
               
               
                 Val Lys Val Leu Val Gly Lys Lys Pro Glu Ser Asp Asp Leu Thr Ala 
               
               
                 2145                2150                2155                2160 
               
               
                   
               
               
                 Asp Lys Ile Lys Glu Phe Cys Asn Lys Phe Leu Glu Gly Lys Ile Lys 
               
               
                                 2165                2170                2175 
               
               
                   
               
               
                 Pro His Leu Met Ser Gln Asp Leu Pro Glu Asp Trp Asp Lys Gln Pro 
               
               
                             2180                2185                2190 
               
               
                   
               
               
                 Val Lys Val Leu Val Gly Lys Asp Glu Leu Ser Asp Lys Ile Val Leu 
               
               
                         2195                2200                2205 
               
               
                   
               
               
                 Glu Ser Lys Ala Ile Glu Ser Leu Asx Lys Asp Phe Leu Lys Gly Asp 
               
               
                     2210                2215                2220 
               
               
                   
               
               
                 Ala Ser Pro Ile Val Lys Ser Gln Glu Ile Phe Glu Asn Gln Asp Ser 
               
               
                 2225                2230                2235                2240 
               
               
                   
               
               
                 Ser Val Phe Gln Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe Asp 
               
               
                                 2245                2250                2255 
               
               
                   
               
               
                 Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly His 
               
               
                             2260                2265                2270 
               
               
                   
               
               
                 Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr Lys 
               
               
                         2275                2280                2285 
               
               
                   
               
               
                 Asp His Glu Asn Ile Ile Ile Ala Lys Asn Phe Glu Glu Val Ala Phe 
               
               
                     2290                2295                2300 
               
               
                   
               
               
                 Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly 
               
               
                 2305                2310                2315                2320 
               
               
                   
               
               
                 His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr 
               
               
                                 2325                2330                2335 
               
               
                   
               
               
                 Lys Asp His Glu Asn Ile Ile Ile Ala Lys Asn Phe Glu Asp Val Ala 
               
               
                             2340                2345                2350 
               
               
                   
               
               
                 Phe Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys 
               
               
                         2355                2360                2365 
               
               
                   
               
               
                 Gly His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr 
               
               
                     2370                2375                2380 
               
               
                   
               
               
                 Tyr Lys Asp His Glu Asn Ile Ile Ile Ala Lys Asn Phe Glu Glu Val 
               
               
                 2385                2390                2395                2400 
               
               
                   
               
               
                 Ala Phe Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp 
               
               
                                 2405                2410                2415 
               
               
                   
               
               
                 Cys Gly His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu 
               
               
                             2420                2425                2430 
               
               
                   
               
               
                 Thr Tyr Lys Glu His Gln Asp Ile Val Ile Ala Lys Asn Phe Glu Glu 
               
               
                         2435                2440                2445 
               
               
                   
               
               
                 Val Ala Phe Asp Glu Asn Lys Asn Val Phe Val Glu Phe Tyr Ala Pro 
               
               
                     2450                2455                2460 
               
               
                   
               
               
                 Trp Cys Gly His Cys Lys Gln Leu Ala Pro Ala Trp Asp Lys Leu Gly 
               
               
                 2465                2470                2475                2480 
               
               
                   
               
               
                 Pro Thr Tyr Arg Asp His Glu Asn Ile Val Ile Ala Lys Asn His Asp 
               
               
                                 2485                2490                2495 
               
               
                   
               
               
                 Glu Ile Val Asn Asp Pro Lys Lys Asp Val Leu Val Leu Tyr Tyr Ala 
               
               
                             2500                2505                2510 
               
               
                   
               
               
                 Pro Trp Cys Gly His Cys Lys Arg Leu Ala Pro Thr Tyr Gln Glu Leu 
               
               
                         2515                2520                2525 
               
               
                   
               
               
                 Ala Asp Thr Tyr Ala Asn Ala Thr Ser Asp Val Leu Ile Ala Lys Met 
               
               
                     2530                2535                2540 
               
               
                   
               
               
                 Asp Ser Thr Ala Asn Glu Val Glu Ala Val Lys Val His Ser Phe Pro 
               
               
                 2545                2550                2555                2560 
               
               
                   
               
               
                 Thr Leu Lys Phe Phe Pro Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr 
               
               
                                 2565                2570                2575 
               
               
                   
               
               
                 Asn Gly Glu Arg Thr Leu Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly 
               
               
                             2580                2585                2590 
               
               
                   
               
               
                 Gly Met Asp Ser Thr Ala Asn Glu Val Glu Ala Val Lys Val His Ser 
               
               
                         2595                2600                2605 
               
               
                   
               
               
                 Phe Pro Thr Leu Lys Phe Phe Pro Ala Ser Ala Asp Arg Thr Val Ile 
               
               
                     2610                2615                2620 
               
               
                   
               
               
                 Asp Tyr Asn Gly Glu Arg Thr Leu Asp Gly Phe Lys Lys Phe Leu Glu 
               
               
                 2625                2630                2635                2640 
               
               
                   
               
               
                 Ser Gly Gly Met Asp Ser Thr Ala Asn Glu Val Glu Ala Val Lys Val 
               
               
                                 2645                2650                2655 
               
               
                   
               
               
                 His Ser Phe Pro Thr Leu Lys Phe Phe Pro Ala Ser Ala Asp Arg Thr 
               
               
                             2660                2665                2670 
               
               
                   
               
               
                 Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu Asp Gly Phe Lys Lys Phe 
               
               
                         2675                2680                2685 
               
               
                   
               
               
                 Leu Glu Ser Gly Gly Met Asp Ser Thr Ala Asn Glu Val Glu Ala Val 
               
               
                     2690                2695                2700 
               
               
                   
               
               
                 Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe Pro Ala Gly Pro Gly 
               
               
                 2705                2710                2715                2720 
               
               
                   
               
               
                 Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu Asp Gly Phe Lys 
               
               
                                 2725                2730                2735 
               
               
                   
               
               
                 Lys Phe Leu Glu Ser Gly Gly Met Asp Ser Thr Ala Asn Glu Val Glu 
               
               
                             2740                2745                2750 
               
               
                   
               
               
                 Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe Pro Ala Gly 
               
               
                         2755                2760                2765 
               
               
                   
               
               
                 Ser Gly Arg Asn Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu Glu Gly 
               
               
                     2770                2775                2780 
               
               
                   
               
               
                 Phe Lys Lys Phe Leu Glu Ser Gly Gly Leu Asp His Thr Glu Asn Asp 
               
               
                 2785                2790                2795                2800 
               
               
                   
               
               
                 Val Arg Gly Val Val Ile Glu Gly Tyr Pro Thr Ile Val Leu Tyr Pro 
               
               
                                 2805                2810                2815 
               
               
                   
               
               
                 Gly Gly Lys Lys Ser Glu Ser Val Val Tyr Gln Gly Ser Arg Ser Leu 
               
               
                             2820                2825                2830 
               
               
                   
               
               
                 Asp Ser Leu Phe Asp Phe Ile Lys Glu Asn Gly Gln Asp Gly Ala Gly 
               
               
                         2835                2840                2845 
               
               
                   
               
               
                 Asp Asn Asp Asp Leu Asp Leu Glu Glu Ala Leu Glu Pro Asp Met Glu 
               
               
                     2850                2855                2860 
               
               
                   
               
               
                 Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu Gln Asp Gly Ala 
               
               
                 2865                2870                2875                2880 
               
               
                   
               
               
                 Gly Asp Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala Glu Glu Pro Asp 
               
               
                                 2885                2890                2895 
               
               
                   
               
               
                 Leu Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu Gln Asp 
               
               
                             2900                2905                2910 
               
               
                   
               
               
                 Gly Ala Gly Asp Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala Glu Glu 
               
               
                         2915                2920                2925 
               
               
                   
               
               
                 Pro Asp Met Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 
               
               
                     2930                2935                2940 
               
               
                   
               
               
                 Gln Asp Gly Ala Gly Asp Glu Asp Gly Leu Glu Asp Leu Glu Glu Ala 
               
               
                 2945                2950                2955                2960 
               
               
                   
               
               
                 Glu Glu Pro Asp Leu Glu Glu Asp Asp Asp Gln Lys Ala Val Arg Asp 
               
               
                                 2965                2970                2975 
               
               
                   
               
               
                 Glu Leu Gln Asp Gly Ala Ala Ala Asp Asp Asp Leu Glu Asp Leu Glu 
               
               
                             2980                2985                2990 
               
               
                   
               
               
                 Thr Asp Glu Glu Thr Asp Leu Glu Glu Gly Asp Asp Asp Glu Gln Lys 
               
               
                         2995                3000                3005 
               
               
                   
               
               
                 Ile Gln Lys Asp Glu Leu His Phe Asp Val Asp Gly Lys Ala Leu Tyr 
               
               
                     3010                3015                3020 
               
               
                   
               
               
                 Glu Glu Ala Gln Glu Lys Ala Ala Glu Glu Ala Asp Ala Asp Ala Glu 
               
               
                 3025                3030                3035                3040 
               
               
                   
               
               
                 Leu Ala Asp Glu Glu Asp Ala Ile His Asp Glu Leu 
               
               
                                 3045                3050 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:27: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 509 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: 
               
               
                   
               
               
                 Met Leu Ser Arg Ala Leu Leu Cys Leu Ala Leu Ala Trp Ala Ala Arg 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Val Gly Ala Asp Ala Leu Glu Glu Glu Asp Asn Val Leu Val Leu Lys 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Lys Ser Asn Phe Ala Glu Ala Leu Ala Ala His Asn Tyr Leu Leu Val 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Tyr Ala Lys Ala Ala Ala Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Leu Ala Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Gly Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp Thr 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Ser Asp 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Thr Ala Ala Ala Glu Ser Leu Val Asp Ser Ser Glu Val Thr Val Ile 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Gly Phe Phe Lys Asp Ala Gly Ser Asp Ser Ala Lys Gln Phe Leu Leu 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ala Ala Glu Ala Val Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Asp Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Ile Thr Lys 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Glu Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Glu Phe Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Thr His Ile Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Asp Gly 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Lys Leu Ser Asn Phe Lys Lys Ala Ala Glu Gly Phe Lys Gly Lys Ile 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Leu Phe Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Glu Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Thr Leu Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Asp Glu Leu 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Thr Ala Glu Lys Ile Thr Gln Phe Cys His His Phe Leu Glu Gly Lys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Ile Lys Pro His Leu Met Ser Gln Glu Leu Pro Glu Asp Trp Asp Lys 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Gln Pro Val Lys Val Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Lys Asp His Glu Asn Ile Ile Ile Ala Lys Met Asp Ser Thr Ala Asn 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Glu Val Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Leu Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Gly Asp Asn Asp Asp Leu Asp Leu Glu Glu Ala Leu Glu Pro Asp Met 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 
               
               
                             500                 505 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:28: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 510 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: 
               
               
                   
               
               
                 Met Leu Arg Arg Ala Leu Leu Cys Leu Ala Leu Thr Ala Leu Phe Arg 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Ala Gly Ala Gly Ala Pro Asp Glu Glu Asp His Val Leu Val Leu His 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Lys Gly Asn Phe Asp Glu Ala Leu Ala Ala His Lys Tyr Leu Leu Val 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Tyr Ala Lys Ala Ala Gly Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Leu Ala Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Gly Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp Thr 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Ser Thr Leu Ser Asp 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Gly Ala Ala Ala Glu Ala Leu Val Glu Ser Ser Glu Val Ala Val Ile 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Gly Phe Phe Lys Asp Met Glu Ser Asp Ser Ala Lys Gln Phe Phe Leu 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ala Ala Glu Val Ile Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Asp Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Glu Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Glu Phe Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Thr His Ile Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Glu Gly 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Lys Leu Ser Asn Phe Lys Lys Ala Ala Glu Ser Phe Lys Gly Lys Ile 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Leu Phe Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Glu Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Thr Leu Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Asp Glu Leu 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Thr Ala Glu Lys Ile Thr Glu Phe Cys His Arg Phe Leu Glu Gly Lys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Ile Lys Pro His Leu Met Ser Gln Glu Leu Pro Asp Asp Trp Asp Lys 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Gln Pro Val Lys Val Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Lys Asp His Glu Asn Ile Ile Ile Ala Lys Met Asp Ser Thr Ala Asn 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Glu Val Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Leu Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Gly Asp Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala Glu Glu Pro Asp 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Leu Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:29: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 509 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: 
               
               
                   
               
               
                 Met Leu Arg Arg Ala Leu Leu Cys Leu Ala Val Ala Ala Leu Val Arg 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Ala Asp Ala Pro Glu Glu Glu Asp His Val Leu Val Leu Arg Lys Ser 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Asn Phe Ala Glu Ala Leu Ala Ala His Lys Tyr Leu Leu Val Glu Phe 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr Ala 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Lys Ala Ala Gly Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu Ala 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr Gly Val 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Arg Gly Tyr Pro Thr Ile Lys Phe Phe Arg Asn Gly Asp Thr Ala Ser 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val Asn Trp 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Arg Asp Gly Ala 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Ala Ala Glu Ser Leu Val Glu Ser Ser Glu Val Ala Val Ile Gly Phe 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Phe Lys Asp Val Glu Ser Asp Ser Ala Lys Gln Phe Leu Gln Ala Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Glu Ala Ile Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser Asp Val 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe Lys Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys Glu Asn 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile Glu Phe 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ile Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Asp Gly Lys Leu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Ser Asn Phe Lys Thr Ala Ala Glu Ser Phe Lys Gly Lys Ile Leu Phe 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu Glu Phe 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile Thr Leu 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Glu Glu Leu Thr Ala 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Glu Arg Ile Thr Glu Phe Cys His Arg Phe Leu Glu Gly Lys Ile Lys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Pro His Leu Met Ser Gln Glu Arg Ala Asp Gly Asp Trp Asp Lys Gln 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Pro Val Lys Val Pro Val Gly Lys Asn Phe Glu Asp Val Ala Phe Asp 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly His 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr Lys 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Asp His Glu Asn Ile Ile Ile Ala Lys Met Asp Ser Thr Ala Asn Glu 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Val Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe Pro 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala Gly 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Asp Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala Glu Glu Pro Asp Met 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 
               
               
                             500                 505 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:30: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 510 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: 
               
               
                   
               
               
                 Met Leu Arg Arg Ala Val Leu Cys Leu Ala Leu Ala Val Thr Ala Gly 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Trp Ala Trp Ala Ala Glu Glu Glu Asp Asn Val Leu Val Leu Lys Ser 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Ser Asn Phe Ala Glu Glu Leu Ala Ala His Lys Tyr Leu Leu Val Glu 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Ala Lys Ala Ala Gly Lys Leu Lys Ala Glu Gly Ser Asp Ile Arg Leu 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Ala Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr Gly 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp Thr Ala 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val Asn 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Ala Asp Ser 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Ala Ala Ala Glu Ser Leu Val Glu Ser Ser Glu Val Ala Val Ile Gly 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Phe Phe Lys Asp Val Glu Ser Asp Ala Ala Lys Gln Phe Leu Leu Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ala Glu Ala Thr Asp Asp Ile Pro Phe Gly Leu Thr Ala Ser Ser Asp 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Val Phe Ser Arg Tyr Gln Val His Gln Asp Gly Val Val Leu Phe Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys Glu 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Phe Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 His Ile Leu Leu Phe Leu Pro Arg Ser Ala Ala Asp His Asp Gly Lys 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Leu Ser Gly Phe Lys Gln Ala Ala Glu Gly Phe Lys Gly Lys Ile Leu 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Phe Ile Phe Ile Asp Ser Asp His Ala Asp Asn Gln Arg Ile Leu Glu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile Thr 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Leu Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Asp Glu Leu Thr 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Ala Glu Gly Ile Thr Glu Phe Cys Gln Arg Phe Leu Glu Gly Lys Ile 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Pro His Leu Met Ser Gln Glu Leu Pro Asp Glu Asp Trp Asp Arg 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Gln Pro Val Lys Val Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Lys Glu His Gln Asp Ile Val Ile Ala Lys Met Asp Ser Thr Ala Asn 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Glu Val Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Ala Gly Pro Gly Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Leu Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Gly Asp Glu Asp Gly Leu Glu Asp Leu Glu Glu Ala Glu Glu Pro Asp 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Leu Glu Glu Asp Asp Asp Gln Lys Ala Val Arg Asp Glu Leu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:31: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 493 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: 
               
               
                   
               
               
                 Glu Pro Leu Glu Glu Glu Asp Gly Val Leu Val Leu Arg Ala Ala Asn 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Phe Glu Gln Ala Leu Ala Ala His Arg His Leu Leu Val Glu Phe Tyr 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr Ala Lys 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Ala Ala Ala Gln Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu Ala Lys 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Val Asp Ala Thr Glu Glu Ala Glu Leu Ala Gln Gln Phe Gly Val Arg 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Gly Tyr Pro Thr Ile Lys Phe Phe Arg Asn Gly Asp Lys Ala Ala Pro 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Arg Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val Ser Trp Leu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Thr Asp Ala Ala Ala 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Ala Glu Thr Leu Val Asp Ser Ser Glu Val Val Val Ile Gly Phe Phe 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Lys Asp Val Thr Ser Asp Ala Ala Lys Glu Phe Leu Leu Ala Ala Glu 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ser Val Asp Asp Ile Pro Phe Gly Ile Ser Ser Ser Ala Asp Val Phe 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ser Lys Tyr Gln Leu Ser Gln Asp Gly Val Val Leu Phe Lys Lys Phe 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Asp Glu Gly Arg Asn Asn Phe Glu Gly Asp Leu Thr Lys Asp Asn Leu 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Leu Asn Phe Ile Lys Ser Asn Gln Leu Pro Leu Val Ile Glu Phe Thr 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His Ile 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Glu Gly Lys Leu Asp 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Asn Phe Lys Thr Ala Ala Gly Asn Phe Lys Gly Lys Ile Leu Phe Ile 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Phe Ile Asp Ser Asp His Ser Asp Asn Gln Arg Ile Leu Glu Phe Phe 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile Thr Leu Glu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Asp Asp Leu Thr Ala Asp 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Lys Ile Lys Glu Phe Cys Asn Lys Phe Leu Glu Gly Lys Ile Lys Pro 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 His Leu Met Ser Gln Asp Leu Pro Glu Asp Trp Asp Lys Gln Pro Val 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Val Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe Asp Glu Asn 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Gln Leu Ala Pro Ala Trp Asp Lys Leu Gly Pro Thr Tyr Arg Asp His 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Glu Asn Ile Val Ile Ala Lys Met Asp Ser Thr Ala Asn Glu Val Glu 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Ala Val Lys Ile His Ser Phe Pro Thr Leu Lys Phe Phe Pro Ala Gly 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Ser Gly Arg Asn Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu Glu Gly 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala Ala Ala Asp 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Asp Asp Leu Glu Asp Leu Glu Thr Asp Glu Glu Thr Asp Leu Glu Glu 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Gly Asp Asp Asp Glu Gln Lys Ile Gln Lys Asp Glu Leu 
               
               
                                 485                 490 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:32: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 521 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: 
               
               
                   
               
               
                 Met Lys Phe Ser Ala Gly Ala Val Leu Ser Trp Ser Ser Leu Leu Leu 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Ala Ser Ser Val Phe Ala Gln Gln Glu Ala Val Ala Pro Glu Asp Ser 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Ala Val Val Lys Leu Ala Thr Asp Ser Phe Asn Glu Tyr Ile Gln Ser 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 His Asp Leu Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Lys Asn Met Ala Pro Glu Tyr Val Lys Ala Ala Glu Thr Leu Val Glu 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Lys Asn Ile Thr Leu Ala Gln Ile Asp Cys Thr Glu Asn Gln Asp Leu 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Cys Met Glu His Asn Ile Pro Gly Phe Pro Ser Leu Lys Ile Phe Lys 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Asn Ser Asp Val Asn Asn Ser Ile Asp Tyr Glu Gly Pro Arg Thr Ala 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Glu Ala Val Gln Phe Met Ile Lys Gln Ser Gln Pro Ala Val Ala Val 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Val Ala Asp Leu Pro Ala Tyr Leu Ala Asn Glu Thr Phe Val Thr Pro 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Val Ile Val Gln Ser Gly Lys Ile Asp Ala Asp Phe Asn Ala Thr Phe 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Tyr Ser Met Ala Asn Lys His Phe Asn Asp Tyr Asp Phe Val Ser Ala 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Glu Asn Ala Asp Asp Asp Phe Lys Leu Ser Ile Tyr Leu Pro Ser Ala 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Met Asp Glu Pro Val Val Tyr Asn Gly Lys Lys Ala Asp Ile Ala Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ala Asp Val Phe Glu Lys Trp Leu Gln Val Glu Ala Leu Pro Tyr Phe 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Gly Glu Ile Asp Gly Ser Val Phe Ala Gln Tyr Val Glu Ser Gly Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Pro Leu Gly Tyr Leu Phe Tyr Asn Asp Glu Glu Glu Leu Glu Glu Tyr 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Lys Pro Leu Phe Thr Glu Leu Ala Lys Lys Asn Arg Gly Leu Met Asn 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Phe Val Ser Ile Asp Ala Arg Lys Phe Gly Arg His Ala Gly Asn Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Asn Met Lys Glu Gln Phe Pro Leu Phe Ala Ile His Asp Met Thr Glu 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Asp Leu Lys Tyr Gly Leu Pro Gln Leu Ser Glu Glu Ala Phe Asp Glu 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Leu Ser Asp Lys Ile Val Leu Glu Ser Lys Ala Ile Glu Ser Leu Asx 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Asp Phe Leu Lys Gly Asp Ala Ser Pro Ile Val Lys Ser Gln Glu 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Ile Phe Glu Asn Gln Asp Ser Ser Val Phe Gln Leu Val Gly Lys Asn 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 His Asp Glu Ile Val Asn Asp Pro Lys Lys Asp Val Leu Val Leu Tyr 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Tyr Ala Pro Trp Cys Gly His Cys Lys Arg Leu Ala Pro Thr Tyr Gln 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Glu Leu Ala Asp Thr Tyr Ala Asn Ala Thr Ser Asp Val Leu Ile Ala 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Lys Leu Asp His Thr Glu Asn Asp Val Arg Gly Val Val Ile Glu Gly 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Tyr Pro Thr Ile Val Leu Tyr Pro Gly Gly Lys Lys Ser Glu Ser Val 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Val Tyr Gln Gly Ser Arg Ser Leu Asp Ser Leu Phe Asp Phe Ile Lys 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Glu Asn Gly His Phe Asp Val Asp Gly Lys Ala Leu Tyr Glu Glu Ala 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Gln Glu Lys Ala Ala Glu Glu Ala Asp Ala Asp Ala Glu Leu Ala Asp 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Glu Glu Asp Ala Ile His Asp Glu Leu 
               
               
                         515                 520 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:33: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 512 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: 
               
               
                   
               
               
                 Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Leu 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Leu Val Pro Ser Gln Ile Phe Ala Glu Glu Ser Ser Thr Asp Ala Lys 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Glu Phe Val Leu Thr Leu Asp Asn Thr Asn Phe His Asp Thr Val Lys 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Lys His Asp Phe Ile Val Val Glu Phe Tyr Ala Pro Trp Cys Gly His 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Cys Lys Lys Leu Ala Pro Glu Tyr Glu Lys Ala Ala Ser Ile Leu Ser 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Thr His Glu Pro Pro Val Val Leu Ala Lys Val Asp Ala Asn Glu Glu 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 His Asn Lys Asp Leu Ala Ser Glu Asn Asp Val Lys Gly Phe Pro Thr 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ile Lys Ile Phe Arg Asn Gly Gly Lys Asn Ile Gln Glu Tyr Lys Gly 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Pro Arg Glu Ala Glu Gly Ile Val Glu Tyr Leu Lys Lys Gln Ser Gly 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Pro Ala Ser Thr Glu Ile Lys Ser Ala Asp Asp Ala Thr Ala Phe Val 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Gly Asp Asn Lys Val Val Ile Val Gly Val Phe Pro Lys Phe Ser Gly 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Glu Glu Tyr Asp Asn Phe Ile Ala Leu Ala Glu Lys Leu Arg Ser Asp 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Tyr Asp Phe Ala His Thr Leu Asn Ala Lys His Leu Pro Lys Gly Asp 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Ser Ser Val Ser Gly Pro Val Val Arg Leu Phe Lys Pro Phe Asp Glu 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Leu Phe Val Asp Ser Lys Asp Phe Asn Val Glu Ala Leu Glu Lys Phe 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Ile Glu Glu Ser Ser Thr Pro Ile Val Thr Val Phe Asn Asn Glu Pro 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ser Asn His Pro Phe Val Val Lys Phe Phe Asn Ser Pro Asn Ala Lys 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Ala Met Leu Phe Ile Asn Phe Thr Thr Glu Gly Ala Glu Ser Phe Lys 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Thr Lys Tyr His Glu Val Ala Glu Gln Tyr Lys Gln Gln Gly Val Ser 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Phe Leu Val Gly Asp Val Glu Ser Ser Gln Gly Ala Phe Gln Tyr Phe 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Gly Leu Lys Glu Glu Gln Val Pro Leu Ile Ile Ile Gln His Asn Asp 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Gly Lys Lys Phe Phe Lys Pro Asn Leu Glu Leu Asp Gln Leu Pro Thr 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Trp Leu Lys Ala Tyr Lys Asp Gly Lys Val Glu Pro Phe Val Lys Ser 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Glu Pro Ile Pro Glu Thr Asn Asn Glu Pro Val Lys Val Val Val Gly 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Gln Thr Leu Glu Asp Val Val Phe Lys Ser Gly Lys Asn Val Leu Ile 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Gln Leu Ala Pro Ile 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Leu Asp Glu Val Ala Val Ser Phe Gln Ser Asp Ala Asp Val Val Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Ala Lys Leu Asp Ala Thr Ala Asn Asp Ile Pro Thr Asp Thr Phe Asp 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Val Gln Gly Tyr Pro Thr Leu Tyr Phe Arg Ser Ala Ser Gly Lys Leu 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Ser Gln Tyr Asp Gly Gly Arg Thr Lys Glu Asp Ile Ile Glu Phe Ile 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Glu Lys Asn Lys Asp Lys Thr Gly Ala Ala His Gln Glu Val Glu Gln 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Pro Lys Ala Ala Ala Gln Pro Glu Ala Glu Gln Pro Lys Asp Glu Leu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:34: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 515 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: 
               
               
                   
               
               
                 Met Arg Thr Phe Ala Pro Trp Ile Leu Ser Leu Leu Gly Ala Ser Ala 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Val Ala Ser Ala Ala Asp Ala Thr Ala Glu Ala Pro Ser Asp Val Val 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Ser Leu Thr Gly Asp Thr Phe Glu Thr Phe Val Lys Glu His Asp Leu 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Ala Leu 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Ala Pro Lys Tyr Glu Gln Ala Ala Thr Glu Leu Lys Glu Lys Asn Ile 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Pro Leu Val Lys Val Asp Cys Thr Glu Glu Glu Ala Leu Cys Arg Asp 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Gln Gly Val Glu Gly Tyr Pro Thr Leu Lys Ile Phe Arg Gly Leu Asp 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Val Lys Pro Tyr Gln Gly Ala Arg Gln Thr Glu Ala Ile Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Tyr Met Val Lys Gln Ser Leu Pro Ala Val Ser Pro Val Thr Pro Glu 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asn Leu Glu Glu Ile Lys Thr Met Asp Lys Ile Val Val Ile Gly Tyr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ile Ala Ser Asp Asp Gln Thr Ala Asn Asp Ile Phe Thr Thr Phe Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Glu Ser Gln Arg Asp Asn Tyr Leu Phe Ala Ala Thr Ser Asp Ala Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Ala Lys Ala Glu Gly Val Lys Gln Pro Ser Ile Val Leu Tyr Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Asp Phe Asp Glu Lys Lys Ala Thr Tyr Asp Gly Glu Ile Glu Gln Asp 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ala Leu Leu Ser Trp Val Lys Thr Ala Ser Thr Pro Leu Val Gly Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Leu Gly Pro Glu Thr Tyr Ser Gly Tyr Ile Thr Ala Gly Ile Pro Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Tyr Ile Phe Ala Glu Thr Lys Glu Glu Arg Glu Gln Phe Thr Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Glu Phe Lys Phe Ile Ala Glu Lys His Lys Gly Ser Ile Asn Ile Val 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Thr Ile Asp Ala Lys Leu Tyr Gly Ala His Ala Gly Asn Leu Asn Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Asp Pro Ser Lys Phe Pro Ala Phe Ala Ile Gln Asp Pro Glu Lys Asn 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Ala Lys Tyr Pro Tyr Asp Gln Ser Lys Glu Val Lys Ala Lys Asp Ile 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Gly Lys Phe Ile Gln Asp Val Leu Asp Asp Lys Val Glu Pro Ser Ile 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Ser Glu Ala Ile Pro Glu Thr Gln Glu Gly Pro Val Thr Val Val 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Ala His Ser Tyr Lys Asp Leu Val Leu Asp Asn Glu Lys Asp Val 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Leu Leu Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Pro Lys Tyr Glu Glu Leu Ala Ser Leu Tyr Lys Asp Ile Pro Glu Val 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Thr Ile Ala Lys Ile Asp Ala Thr Ala Asn Asp Val Pro Asp Ser Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Thr Gly Phe Pro Thr Ile Lys Leu Phe Ala Ala Gly Ala Lys Asp Ser 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Val Glu Tyr Glu Gly Ser Arg Thr Val Glu Asp Leu Ala Asn Phe 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Val Lys Glu Asn Gly Lys His Lys Val Asp Ala Leu Glu Val Asp Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Lys Lys Glu Gln Glu Ser Gly Asp Ala Thr Glu Thr Arg Ala Ala Ser 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Asp Glu Thr Glu Thr Pro Ala Ala Thr Ser Asp Asp Lys Ser Glu His 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Asp Glu Leu 
               
               
                         515 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:35: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 530 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: 
               
               
                   
               
               
                 Met Lys Phe Ser Ala Gly Ala Val Leu Ser Trp Ser Ser Leu Leu Leu 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Ala Ser Ser Val Phe Ala Gln Gln Glu Ala Val Ala Pro Glu Asp Ser 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Ala Val Val Lys Leu Ala Thr Asp Ser Phe Asn Glu Tyr Ile Gln Ser 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 His Asp Leu Val Leu Ala Glu Phe Phe Ala Pro Trp Cys Gly His Cys 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Lys Asn Met Ala Pro Glu Tyr Val Lys Ala Ala Glu Thr Leu Val Glu 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Lys Asn Ile Thr Leu Ala Gln Ile Asp Cys Thr Glu Asn Gln Asp Leu 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Cys Met Glu His Asn Ile Pro Gly Phe Pro Ser Leu Lys Ile Phe Lys 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Asn Arg Asp Val Asn Asn Ser Ile Asp Tyr Glu Gly Pro Arg Thr Ala 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Glu Ala Ile Val Gln Phe Met Ile Lys Gln Ser Gln Pro Ala Val Ala 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Val Val Ala Asp Leu Pro Ala Tyr Leu Ala Asn Glu Thr Phe Val Thr 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Pro Val Ile Val Gln Ser Gly Lys Ile Asp Ala Asp Phe Asn Ala Thr 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Phe Tyr Ser Met Ala Asn Lys His Phe Asn Asp Tyr Asp Phe Val Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ala Glu Asn Ala Asp Asp Asp Phe Lys Leu Ser Ile Tyr Leu Pro Ser 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Ala Met Asp Glu Pro Val Val Tyr Asn Gly Lys Lys Ala Asp Ile Ala 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Asp Ala Asp Val Phe Glu Lys Trp Leu Gln Val Glu Ala Leu Pro Tyr 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Phe Gly Glu Ile Asp Gly Ser Val Phe Ala Gln Tyr Val Glu Ser Gly 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Leu Pro Leu Gly Tyr Leu Phe Tyr Asn Asp Glu Glu Glu Leu Glu Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Tyr Lys Pro Leu Phe Thr Glu Leu Ala Lys Lys Asn Arg Gly Leu Met 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Asn Phe Val Ser Ile Asp Ala Arg Lys Phe Gly Arg His Ala Gly Asn 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Leu Asn Met Lys Glu Gln Phe Pro Leu Phe Ala Ile His Asp Met Thr 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Glu Asp Leu Lys Tyr Gly Leu Pro Gln Leu Ser Glu Glu Ala Phe Asp 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Glu Leu Ser Asp Lys Ile Val Leu Glu Ser Lys Ala Ile Glu Ser Leu 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Val Lys Asp Phe Leu Lys Gly Asp Ala Ser Pro Ile Val Lys Ser Gln 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Glu Ile Phe Glu Asn Gln Asp Ser Ser Val Phe Gln Leu Val Gly Lys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Asn His Asp Glu Ile Val Asn Asp Pro Lys Lys Asp Val Leu Val Leu 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Tyr Tyr Ala Pro Trp Cys Gly His Cys Lys Arg Leu Ala Pro Thr Tyr 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Gln Glu Leu Ala Asp Thr Tyr Ala Asn Ala Thr Ser Asp Val Leu Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Ala Lys Leu Asp His Thr Glu Asn Asp Val Arg Gly Val Val Ile Glu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Gly Tyr Pro Thr Ile Val Leu Tyr Pro Gly Gly Lys Lys Ser Glu Ser 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Val Val Tyr Gln Gly Ser Arg Ser Leu Asp Ser Leu Phe Asp Phe Ile 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Lys Glu Asn Gly His Phe Asp Val Asp Gly Lys Ala Leu Tyr Glu Glu 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Ala Gln Glu Lys Ala Ala Glu Glu Ala Glu Ala Asp Ala Glu Ala Glu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Ala Asp Ala Asp Ala Glu Leu Ala Asp Glu Glu Asp Ala Ile His Asp 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Glu Leu 
               
               
                     530 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:36: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 510 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: 
               
               
                   
               
               
                 Met Leu Arg Arg Ala Leu Leu Cys Leu Ala Leu Thr Ala Leu Phe Arg 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Ala Gly Ala Gly Ala Pro Asp Glu Glu Asp His Val Leu Val Leu His 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Lys Gly Asn Phe Asp Glu Ala Leu Ala Ala His Lys Tyr Leu Leu Val 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Tyr Ala Lys Ala Ala Gly Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Leu Ala Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Gly Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp Thr 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Ser Thr Leu Ser Asp 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Gly Ala Ala Ala Glu Ala Leu Val Glu Ser Ser Glu Val Ala Val Ile 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Gly Phe Phe Lys Asp Met Glu Ser Asp Ser Ala Lys Gln Phe Phe Leu 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ala Ala Glu Val Ile Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Asp Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Glu Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Glu Phe Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Thr His Ile Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Glu Gly 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Lys Leu Ser Asn Phe Lys Lys Ala Ala Glu Ser Phe Lys Gly Lys Ile 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Leu Phe Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Glu Phe Glu Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Thr Leu Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Asp Glu Leu 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Thr Ala Glu Lys Ile Thr Glu Phe Cys His Arg Phe Leu Glu Gly Lys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Ile Lys Pro His Leu Met Ser Gln Glu Leu Pro Asp Asp Trp Asp Lys 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Gln Pro Val Lys Val Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Lys Asp His Glu Asn Ile Val Ile Ala Lys Met Asp Ser Thr Ala Asn 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Glu Val Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Pro Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Leu Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Gly Asp Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala Glu Glu Pro Asp 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Leu Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:37: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 508 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: 
               
               
                   
               
               
                 Met Leu Ser Arg Ala Leu Leu Cys Leu Ala Leu Ala Trp Ala Ala Arg 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Val Gly Ala Asp Ala Leu Glu Glu Glu Asp Asn Val Leu Val Leu Lys 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Lys Ser Asn Phe Ala Glu Pro Ala Ala His Asn Tyr Leu Leu Val Glu 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Ala Lys Ala Ala Ala Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Ala Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr Gly 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Val Arg Gly Tyr Pro Thr Ile Lys Phe Phe Lys Asn Gly Asp Thr Ala 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val Asn 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Ser Asp Thr 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Ala Ala Ala Glu Ser Leu Val Asp Ser Ser Glu Val Thr Val Ile Gly 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Phe Phe Lys Asp Ala Gly Ser Asp Ser Ala Lys Gln Phe Leu Leu Ala 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ala Glu Ala Val Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser Asp 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Val Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe Lys 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Ile Thr Lys Glu 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Lys Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile Glu 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Phe Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 His Ile Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Asp Gly Lys 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Leu Ser Asn Phe Lys Lys Ala Ala Glu Gly Phe Lys Gly Lys Ile Leu 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Phe Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu Glu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile Thr 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Leu Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Asp Glu Leu Thr 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Ala Glu Lys Ile Thr Gln Phe Cys His His Phe Leu Glu Gly Lys Ile 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Lys Pro His Leu Met Ser Gln Glu Leu Pro Glu Asp Trp Asp Lys Gln 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Pro Val Lys Val Leu Val Gly Lys Asn Phe Glu Glu Val Ala Phe Asp 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly His 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr Lys 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Asp His Glu Asn Ile Val Ile Ala Lys Met Asp Ser Thr Ala Asn Glu 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Val Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe Pro 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Arg Gln Asp Gly Ala Gly 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Asp Asn Asp Asp Leu Asp Leu Glu Glu Ala Leu Glu Pro Asp Met Glu 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 
               
               
                             500                 505 
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO:38: 
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS: 
               
               
                           (A) LENGTH: 638 amino acids 
               
               
                           (B) TYPE: amino acid 
               
               
                           (C) STRANDEDNESS: single 
               
               
                           (D) TOPOLOGY: linear 
               
               
                   
               
               
                     (ii) MOLECULE TYPE: peptide 
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: 
               
               
                   
               
               
                 Met Lys Leu Arg Lys Ala Trp Leu Leu Val Leu Leu Leu Ala Leu Thr 
               
               
                 1               5                   10                  15 
               
               
                   
               
               
                 Gln Leu Leu Ala Ala Ala Ser Ala Gly Asp Ala Gln Glu Asp Thr Ser 
               
               
                             20                  25                  30 
               
               
                   
               
               
                 Asp Thr Glu Asn Ala Thr Glu Glu Glu Glu Glu Glu Asp Asp Asp Asp 
               
               
                         35                  40                  45 
               
               
                   
               
               
                 Leu Glu Val Lys Glu Glu Asn Gly Val Trp Val Leu Asn Asp Gly Asn 
               
               
                     50                  55                  60 
               
               
                   
               
               
                 Phe Asp Asn Phe Val Ala Asp Lys Asp Thr Val Leu Leu Glu Phe Tyr 
               
               
                 65                  70                  75                  80 
               
               
                   
               
               
                 Ala Pro Trp Cys Gly His Cys Lys Gln Phe Ala Pro Glu Tyr Glu Lys 
               
               
                                 85                  90                  95 
               
               
                   
               
               
                 Ile Ala Ser Thr Leu Lys Asp Asn Asp Pro Pro Ile Ala Val Ala Lys 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Ile Asp Ala Thr Ser Ala Ser Met Leu Ala Ser Lys Phe Asp Val Ser 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Gly Tyr Pro Thr Ile Lys Ile Leu Lys Lys Gly Gln Ala Val Asp Tyr 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Asp Gly Ser Arg Thr Gln Glu Glu Ile Val Ala Lys Val Arg Glu Val 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Ser Gln Pro Asp Trp Thr Pro Pro Pro Glu Val Thr Leu Ser Leu Thr 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Lys Asp Asn Phe Asp Asp Val Val Asn Asn Ala Asp Ile Ile Leu Val 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Lys Leu Ala Pro Glu 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Tyr Glu Lys Ala Ala Lys Glu Leu Ser Lys Arg Ser Pro Pro Ile Pro 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Leu Ala Lys Val Asp Ala Thr Glu Gln Thr Asp Leu Ala Lys Arg Phe 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Asp Val Ser Gly Tyr Pro Thr Leu Lys Ile Phe Arg Lys Gly Arg Pro 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Phe Asp Tyr Asn Gly Pro Arg Glu Lys Tyr Gly Ile Val Asp Tyr Met 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Ile Glu Gln Ser Gly Pro Pro Ser Lys Glu Ile Leu Thr Leu Lys Gln 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Val Gln Glu Phe Leu Lys Asp Gly Asp Asp Val Val Ile Ile Gly Leu 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Phe Gln Gly Asp Gly Asp Pro Ala Tyr Leu Gln Tyr Gln Asp Ala Ala 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Asn Asn Leu Arg Glu Asp Tyr Lys Phe His His Thr Phe Ser Pro Glu 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Ile Ala Lys Phe Leu Lys Val Ser Leu Gly Lys Leu Val Leu Thr His 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Pro Glu Lys Phe Gln Ser Lys Tyr Glu Pro Arg Phe His Val Met Asp 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Gln Gly Ser Thr Glu Ala Ser Ala Ile Lys Asp Tyr Val Val Lys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 His Ala Leu Pro Leu Val Gly His Arg Lys Thr Ser Asn Asp Ala Lys 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Arg Tyr Ser Lys Arg Pro Leu Val Val Val Tyr Tyr Ser Val Asp Phe 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Ser Phe Asp Tyr Arg Ala Ala Thr Gln Phe Trp Arg Asn Lys Val Leu 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Glu Val Ala Lys Asp Phe Pro Glu Tyr Thr Phe Ala Ile Ala Asp Glu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Glu Asp Tyr Ala Thr Glu Val Lys Asp Leu Gly Leu Ser Glu Ser Gly 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Glu Asp Val Asn Ala Ala Ile Leu Asp Glu Ser Gly Lys Lys Phe Ala 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Met Glu Pro Glu Glu Phe Asp Ser Asp Thr Leu Arg Glu Phe Val Thr 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Ala Phe Lys Lys Gly Lys Leu Lys Pro Val Ile Lys Ser Gln Pro Val 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Pro Lys Asn Asn Lys Gly Pro Val Lys Val Val Val Gly Lys Thr Phe 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Asp Ala Ile Val Met Asp Pro Lys Lys Asp Val Leu Ile Glu Phe Tyr 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 Ala Pro Trp Cys Gly His Cys Lys Gln Leu Glu Pro Ile Tyr Thr Ser 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 Leu Gly Lys Lys Tyr Lys Gly Gln Lys Asp Leu Val Ile Ala Lys Met 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 Asp Ala Thr Ala Asn Asp Ile Thr Asn Asp Gln Tyr Lys Val Glu Gly 
               
               
                             580                 585                 590 
               
               
                   
               
               
                 Phe Pro Thr Ile Tyr Phe Ala Pro Ser Gly Asp Lys Lys Asn Pro Ile 
               
               
                         595                 600                 605 
               
               
                   
               
               
                 Lys Phe Glu Gly Gly Asn Arg Asp Leu Glu His Leu Ser Lys Phe Ile 
               
               
                     610                 615                 620 
               
               
                   
               
               
                 Asp Glu His Ala Thr Lys Arg Ser Arg Thr Lys Glu Glu Leu 
               
               
                 625                 630                 635