PESTICIDAL COMPOSITION COMPRISING CryIF CHIMERIC AND CryIA(c) CHIMERIC BACILLUS THURINGIENSIS DELTA-ENDOTOXIN

Abstract: Disclosed are compositions and processes for controlling lepidopteran pests. These compositions comprise synergistic combinations of a CryIF chimeric and CryIA(c) chimeric Bacillus thuringiensis delta -endotoxin. These compositions have been found to exhibit excellent activity against lepidopteran pests.

Description: PESΗCIDAL COMPOSITION COMPRISING CiylF CHIMERIC AND CιyΙA(c) CHIMERIC BACIL¬ LUS THURINGIENSIS DELTA-ENDOTOXIN Background of the Invention The soil microbe Bacillus thuringiensis (B.t.) is a Gram-positive, spore-forming bacterium characterized by parasporal crystalline protein inclusions. These inclusions often appear microscopically as distinctively shaped crystals. The proteins can be highly toxic to pests and specific in their toxic activity. Certain B.t. toxin genes have been isolated and sequenced, and recombinant DNA-based B.t. products have been produced and approved for use. In addition, with the use of genetic engineering techniques, new approaches for delivering these B.t. endotoxins to agricultural environments are under development, including the use of plants genetically engineered with endotoxin genes for insect resistance and the use of stabilized intact microbial cells as B.t. endotoxin delivery vehicles (Gaertner, F.H., L. Kim [1988] T1BTECH 6:S -S7). Thus, isolated B.t. endotoxin genes are becoming commercially valuable. Until the last ten years, commercial use of B.t. pesticides has been largely restricted to a narrow range of lepidopteran (caterpillar) pests. Preparations of the spores and crystals of B. thuringiensis subsp. kurstaki have been used for many years as commercial insecticides for lepidopteran pests. For example, B. thuringiensis var. kurstaki HD-1 produces a crystal called a δ -endotoxin which is toxic to die larvae of a number of lepidopteran insects. In recent years, however, investigators have discovered B.t. pesticides with specificities for a much broader range of pests. For example, other species of B.t., namely israelensis and tenebrionis (a.k.a. B.t. M-7, a.k.a. B.t. san diego), have been used commercially to control insects of the orders Diptera and Coleoptera, respectively (Gaertner, F.H. [1989] "Cellular Delivery Systems for Insecticidal Proteins: Living and Non-Living Microorganisms," in Controlled Delivery of Crop Protection Agents. R.M. Wilkins, ed., Taylor and Francis, New York and London, 1990, pp. 245-255). See also Couch, T.L. (1980) "Mosquito Pathogenicity of Bacillus thuringiensis var. israelensis " Developments in Industrial Microbiology 22:61-76; Beegle, C.C, (1978) "Use of Entomogenous Bacteria in Agroecosystems," Developments in Industrial Microbiology 20:97-104. Krieg, A-, A.M. Huger, G.A. Langenbruch, W. Schnetter (1983) Z ang. Ent. 96:500-508, describe Bacillus thuringiensis var. tenebrionis, which is reportedly active against two beetles in the order Coleoptera. These are the Colorado potato beetle, Leptinotarsa decemlineata, and Agelastica alni. Recently, new subspecies of B.t. have been identified, and genes responsible for active δ- endotoxin proteins have been isolated (Hόfte, H., H.R. Whitelev [1989] Microbiological Reviews 52(2):242-255). Hόfte and Whitelev classified B.t. crystal protein genes into 4 major classes. The classes were Cryl (Lepidoptera-specific), CiyE. (Lepidoptera- and Diptera-specific), Crylll (Coleoptera-specific), and Cry-V (Diptera-specific). The discovery of strains specifically toxic to other pests has been reported. (Feitelson. J.S.. J. Payne. L. Kim [1992] Bio/Technology 10:271-275). The cloning and expression of a B.t. crystal protein gene in Escherichia coli has been described in the published literature (Schnepf, H.E., H.R. Whiteley [1981] Proc. Natl. Acad. Sci. USA 78:2893- 2897). U.S. Patent No. 4,448,885 and U.S. Patent No. 4,467,036 both disclose the expression of a B.t. crystal protein in E. coli. Hybrid B.t. crystal protein genes have been constructed that exhibit increased toxicity and display an expanded host range to a target pest. See U.S. Patent Nos. 5,128,130 and 5,055,294. U.S. Patent Nos. 4,797,276 and 4,853,331 disclose B. thuringiensis strain san diego (a.k.a. B.t. tenebrionis, a.k.a. M-7) which can be used to control coleopteran pests in various environments. U.S. Patent No. 4,918,006 discloses B.t. toxins having activity against dipterans. U.S. Patent No. 4.849,217 discloses B.t. isolates which have activity against the alfalfa weevil. U.S. Patent No. 5,151,363 and U.S. Patent No. 4,948,734 disclose certain isolates of B.t. which have activity against nematodes. As a result of extensive research and investment of resources, other patents have issued for new B.t. isolates and new uses of B.t. isolates. However, the discovery of new B.t. isolates and new uses of known B.t. isolates remains an empirical, unpredictable art. A majority of Bacillus thuringiensis δ-endotoxin crystal protein molecules are composed of two functional segments. The protease -resistant core toxin is the first segment and corresponds to about the first half of the protein molecule. The three-dimensional structure of a core segment of a crylllA B.t. δ- endotoxin is known and it is proposed that all related toxins have that same overall structure (Li, J., J. Carroll, D.J. Ellar [1991] Nature 353:815-821). The second half of the molecule is the second segment. For purposes of this application, this second segment will be referred to herein as the "protoxin segment." The protoxin segment is believed to participate in toxin crystal formation (Arvidson, H., P.E. Dunn, S. Strand. Al. Aronson [19&9] Molecular Microbiology 3:1533-1534; Choma, C.T., W.K. Surewicz, P.R. Carey. M. Pozsgay, T. Raynor. H. Kaplan [1990] Eur. J. Biochem. 189:523-527). The full 130 kDa toxin molecule is rapidly processed to the resistant core segment by protease in the insect gut. The protoxin segment may thus convey a partial insect specificity for the toxin by limiting the accessibility of the core to the insect by reducing the protease processing of the toxin molecule (Haider, M.Z., B.H. Knowles, D.J. Ellar [1986] Eur. J. Biochem. 156:531-540) or by reducing toxin solubility (Aronson, A.I., E S. Han, W. McGaughey, D. Johnson [1991] Appl. Environ. Microbiol. 57:981-986). Chimeric proteins joined within the toxin domains have been reported between CrylC and CryΙA(b) (Honee, G.. D. Convents, J. Van Rie. S. Jansens, M. Perferoen, B. Visser [1991] Mot. Microbiol. 5:2799-2806); however, the activity of these chimeric proteins was either much less, or undetectable. when compared to CrylC on a relevant insect. Honee et al. (Honee, G, W. Vriezen. B. Visser [1990] Appl. Environ. Microbiol. 56:823-825) also reported making a chimeric fusion protein by linking tandem toxin domains of CrylC and CryIA(b). The resulting protein had an increased spectrum of activity equivalent to the combined activities of the individual toxins: however, the activity of the chimeric was not increased toward any one of the target insects. When toxins or biologically active agents are blended together, the biological activity of the resulting mixture can be affected in several ways. The resultant biological activity can be the sum of the activity of each of the toxins. Biological activity of the mixture may be less than the sum of the activity of each of the agents, or the resultant activity may be greater than the sum of the activity of each of the agents. A nucleotide β-exotoxin produced by a particular B.t. strain was found to act in synergy with the protein δ-endotoxins in B.t. var. kurstaki to yield increased activity against the lepidopteran pest Spodoptera exigua (Moar, W.J., W.L.A. Osbrink, J.T> Trumble [1986] J. Econ. Entomol. 79:1443- 1446). Enhanced toxicity to mosquito larvae occurs with the mixture of the 27 kDa and the 65 or 130 kDa proteins from B.t. var. israelensis (Chilcott, C.N., D.J. Ellar [1988] J. Gen. Microbiology 132:2551-2558; Yuetal, 1987; Wu, D., F.N. Chang [1985] FEBS 190(2):232-236). The CrylVA and CrylVB toxins from B.t. var. israelensis have also been used together (Angsuthanasomat, C, N. Crickmore, D.J. Ellar [1992] FEMS Microbiol. Lett. 94:63-68). Brief Summary of the Invention The subject invention concerns the discovery of advantageous increased activity against lepidopteran pests achieved by the combination of two Bacillus thuringiensis (B.t.) δ -endotoxin proteins. More specifically, a CryEF chimeric toxin combined with a CryΙA(c) chimeric toxin act in synergy to yield unexpected enhanced toxicity to lepidopteran pests. The synergistic effect of the subject invention may be achieved by combining, as in a mixture, isolates that each produce one of d e toxin proteins. Recombinant hosts engineered to express both of die toxins of the subject invention can also be used to achieve the synergistic effect. Suitable recombinant hosts include prokaryotes and lower eukaryotes, as well as plants. Chimeric CryEF genes useful according to the subject invention can be assembled d at substitute a heterologous protoxin segment for all or part of the native crylF protoxin segment. In particular, all or part of the protoxin-encoding region of a cryIA(b) gene can be used in place of all or part of the region which encodes the protoxin for a native crylF toxin. Similarly, a chimeric gene can be constructed wherein the region encoding all or part of the protoxin of a crylF toxin is replaced by DNA encoding all or part of the protoxin of a c_yIA(c)/cryIA(b) chimeric gene. In a specific embodiment, the cryIA(c)/cryIA(b) chimeric gene is that which has been denoted 436 and which is described in U.S. Patent No. 5, 128, 130. This gene can be obtained from the plasmid in P. βuorescens MR436. The chimeric gene can be introduced into a wide variety of microbial or plant hosts. A transformed host expressing the chimeric gene can be used to produce the lepidopteran-active toxins of the subject invention. Transformed hosts can be used to produce the insecticidal toxins or, in the case of a plant cell transformed to produce die toxins, die plant will become resistant to insect attack. The subject invention further pertains to the use of the chimeric toxins, or hosts containing the genes encoding die chimeric toxins, in med ods for controlling lepidopteran pests. Still further, die invention includes combinations of substantially intact treated B t cells, or recombinant cells expressmg the genes and producmg the toxins of the invention The cells can be treated to prolong the pesucidal activity when the substantially intact cells are applied to the environment of the target pest Such treatment can be by chemical or physical means, or a combination of chemical and physical means, so long as die technique does not deleteπously affect the synergistic properties of the pesticides, nor diminish the cellular capability m protectmg the pesticides The treated cell acts as a protective coatmg for die pesϋcidal toxins The toxins become available to act as such upon ingestion by a target pest Bnef Description of the Drawings Figure 1 - The BamUl site is removed from pMYC1050 by a fill-in reaction with Klenow polymerase to give plasmid pMYC1050Δ_tømHI To facilitate cloning, an Nstl DNA fragment that contains most of the toxin open reading frame is cloned into pGEM5 The resulting plasmid is called pGEMtox C=C/αI, H=_ ./.dIII Figure 2 - BamRl or Pvul cloning sites were introduced into toxin DNA by the technique of Splice Overlap Extension (SOE) DNA fragments with die new sites are used to replace homologous DNA fragments in pGEMtox The resulting plasmids are pGEMtoxδαmHl or pGEMtox/VuI The letters A through G below the arrows correspond to oligonucleotide primers in die text Letters above vertical lines correspond to restnction enzyme sites Figure 3 - The DNA fragment containing d e BamW mutation is used to replace the homologous fragment in pGEMtoxPvwI The resulting plasmid which contains both clomng sites is pGEMtox-BαmHI/Pvt-I To construct an expression plasmid, d e toxin-containing Nsil fragment is excised for clomng into die pTJS260 broad host-range vector B=_3omHI, C=Clal, H=/_ wdin, ?=Pvul Figure 4 - The Nsil toxin-containing fragment with die new restriction sites is ligated to d e vector-containing DNA from pMYC 1050Δ_tømHI to give pMYC2244 A BamHl-Pvul PCR-derived D A fragment containing die crylF toxin is exchanged for the equivalent fragment in pMYC2244 The resulting chimera is called pMYC2239 B=βαmHI, C=C/αI, H=_/mdIII, N=N_;I, ?=Pvul Figure 5 - The small Apal DΝA fragment of pMYC2047 is substituted for the homologous region of pMYC2239 to give plasmid pMYC2244 This chimera consists of crylF in the toxin region and cr IA(b) m d e protoxin Figure 6 - Silent codon changes are introduced mto die cry IF toxin by SOE The Spel-Kpnl PCR DΝA fragment wid the changes is substituted for the homologous toxin-containing fragment in pMYC2047 The resulting plasmid is pMYC2243 Letters H through K below the arrow s correspond to oligonucleotide primers in die text Figure 7 - Silent codon changes are introduced mto pMYC2244 bv substitution of the homologous fragment with the small Apal DΝA fragment of pMYC2243 The final plasmid is pMYC2523 ?=Pvul Figure 8 - A chimeric toxin containing the 436 protoxin is constructed by substituting a PCR- generated _°vuI-B-tEII protoxin DNA for the homologous fragment in pMYC2523. The final plasmid is pMYC2254. Letters F and M below die arrows correspond to oligonucleotide primers in die text. Figure 9 - A CryIF/C-y-A(b) chimeric protein sequence and residue-by-residue substitutions. The 'Cons' line shows a CryIF/CryIA(b) chimeric sequence. The 'Alt' lines show residue-by-residue substitutions found in the 436 protein, CryIA(b) variant proteins and Cry F protoxins. Brief Description of the Sequences SEQ ID NO. 1 is oligonucleotide primer "A" SEQ ID NO. 2 is oligonucleotide primer "B" SEQ ID NO. 3 is oligonucleotide primer "C" SEQ ID NO.4 is oligonucleotide primer "D" SEQ ID NO. 5 is oligonucleotide primer "E" SEQ ID NO. 6 is oligonucleotide primer T" SEQ ID NO. 7 is oligonucleotide primer "G" SEQ ID NO. 8 is oligonucleotide primer "L" SEQ ID NO. 9 is oligonucleotide primer "N" SEQ ID NO. 10 is oligonucleotide primer "O" SEQ ID NO. 11 is oligonucleotide primer "H" SEQ ID NO. 12 is oligonucleotide primer "I" SEQ ID NO. 13 is oligonucleotide primer T SEQ ID NO. 14 is oligonucleotide primer "K" SEQ ID NO. 15 is oligonucleotide primer "P" SEQ ID NO. 16 is oligonucleotide primer "Q" SEQ ID NO. 17 is oligonucleotide primer "M" SEQ ID NO. 18 shows die toxin-encoding DNA sequence of pMYC2224. SEQ ID NO. 19 shows die predicted amino acid sequence of the toxin encoded by pMYC2224. SEQ ID NO. 20 shows the toxin-encoding DNA sequence of pMYC2239. SEQ ID NO. 21 shows the predicted amino acid sequence of die toxin encoded by pMYC2239 SEQ ID NO. 22 shows die toxin-encoding DNA sequence of pMYC2244, which encodes a crylF/cry IA(b) chimeric toxin. SEQ ID NO.23 shows the predicted amino acid sequence of die cryIF/cryIA(b) chimeric toxin encoded by pMYC2244. SEQ ID NO. 24 shows the toxin-encoding DNA sequence of pMYC2243. SEQ ID NO.25 shows the predicted amino acid sequence of d e toxin encoded by pMYC2243. SEQ ID NO. 26 shows the toxin-encoding DNA sequence of pMYC2523, which encodes a cryIF/cryIA(b) chimenc toxm with codon rework SEQ ID NO.27 shows the predicted ammo acid sequence of the toxm encoded by pMYC2523 SEQ ID NO. 28 shows the toxin-encoding DNA sequence of pMYC2254, which encodes a cryEF/436 chimenc toxm SEQ ID NO.29 shows d e predicted ammo acid sequence of d e toxin encoded by pMYC2254 SEQ ID NO.30 is a characteπs tic sequence of cry I toxins This sequence ends at residue 601 of SEQ ID NO 23 SEQ ID NO. 31 is die eight ammo acids preceding ammo acid 1043 m SEQ ED NO 23 SEQ ID NO.32 shows die ammo acid sequence of a native cryIF/cryIA(b) toxin SEQ ID NO.33 shows the ammo acid sequence of a native cryIA(b) toxin SEQ ID NO. 34 shows die ammo acid sequence of a cryIA(c)/cryIA(b) toxm Detailed Disclosure of the Invention The subject invention concerns the unexpected enhanced pesticidal activity resulting from the combination of a CryEF chimeπc toxm and a CryIA(c) chimenc toxm The combmation surpπsmgly has increased activity against lepidopteran pests Preparations of combinations of isolates that produce the two chimenc toxins can be used to practice the subject invention Pseudomonas fluorescens cells transformed idi B t genes can serve as one source of the toxins of die subject invention For example, a lactose-inducible P fluorescens strain compnsmg a gene encodmg a Cry IF/CryIA(b) toxm, and P fluorescens MR436, which comprises a gene encodmg a CryIA(c)/CryIA(b) chimenc toxin, can be used to practice die subject invention These two Pseudomonas strains can be combmed m a physical blend diat exhibits adv antageous enhanced pesticidal activity Genes encodmg die toxins of the v ention can be used to transform smtable hosts so that a smgle host will produce d e two toxins providmg d e advantageous effect Bactena harboring plasnuds useful accordmg to the subject invention are the following Culture Repository No U S Patent No P fluorescens (pM3, 130-7) NRRL B-18332 5,055,294 P fluorescens MR436 NRRL B- 18292 5.128,130 (pM2.16-l l. aka pMYC436) E coh NM522 (pMYC 1603) NRRL B-18517 5,188,960 It should be understood that die availability of a deposit does not constitute a license to practice die subject v ention in derogation of patent nghts granted by governmental action In accordance ith die subject invention, it has been discovered diat products compnsmg die two chimenc toxins have been discovered to require a lower total protem content for product application, d us providmg die user greater economy Insects which are less susceptible to die action of a smgle toxm will be more greatlv affected bv die combination of toxins of die subject invention, rendering a product containing the two toxins more efficacious tiian products containing a single toxin. Additionally, pests are less likely to develop a rapid resistance to a product containing the two toxins, than to products containing a single toxin. Combinations of die toxins described in die invention can be used to control lepidopteran pests. Adult lepidopterans, i.e., butterflies and modis, primarily feed on flower nectar and are a significant effector of pollination- The larvae, i.e., caterpillars, nearly all feed on plants, and many are serious pests. Caterpillars feed on or inside foliage or on the roots or stem of a plant, depriving die plant of nutrients and often destroying die plant's physical support structure. Additionally, caterpillars feed on fruit, fabrics, and stored grains and flours, ruining diese products for sale or severely diminishing their value. As used herein, reference to lepidopteran pests refers to various life stages of the pest, including larval stages. The chimeric toxins of the subject invention comprise a full core N-teπninal toxin portion of a B.t. toxin and, at some point past die end of die toxin portion, die protein has a transition to a heterologous protoxin sequence. The N-terminal toxin portion of a B.t. toxin is refererred to herein as the "core" toxin. The transition to die heterologous protoxin segment can occur at approximately the toxin/ protoxin junction or, in die alternative, a portion of the native protoxin (extending past the toxin portion) can be retained widi die transition to die heterologous protoxin occurring downstream. As an example, one chimeric toxin of die subject invention has die full toxin portion of crylF (amino acids 1- 601) and a heterologous protoxin (amino acids 602 to die C-terminus). In a preferred embodiment, die heterologous portion of the protoxin is derived from a cryIA(b) or 436 toxin. A person skilled in diis art will appreciate that B.t. toxins, even within a certain class such as crylF, will vary to some extent in lengdi and die precise location of the transition from toxin portion to protoxin portion. Typically, die cryIA(b) and crylF toxins are about 1150 to about 1200 amino acids in lengdi. The transition from toxin portion to protoxin portion will typically occur at between about 50% to about 60% of the full length toxin. The chimeric toxin of the subject invention will include d e fidl expanse of iis core N-terminal toxin portion- Thus, the chimeric toxin will comprise at least about 50% of d e full lengdi cryEF B.t. toxin. This will typically be at least about 590 amino acids. Widi regard to die protoxin portion, die full expanse of die cryIA(b) protoxin portion extends from die end of die toxin portion to the C-terminus of die molecule. It is die last about 100 to 150 amino acids of diis portion which are most critical to include in die chimeric toxin of the subject invention. In a chimeric toxin specifically exemplified herein, at least amino acids 1043 (of SEQ ID NO. 23) to die C-terminus of the cryIA(b) molecule are utilized. Amino acid 1043 in SEQ ID NO. 23 is preceded by die sequence TVT Pro Asn Asn Thr Val Thr Cys (SEQ ID NO. 31). This amino acid sequence marks the location in die protoxin segment of die molecule beyond which heterologous amino acids will always occur in the chimeric toxin. In another example, d e peptide shown as SEQ ID NO. 31 occurs at amino acids 1061 to 1068. In this case, amino acids 1069 to die C-terminus are preferably heterologous (SEQ ID NO. 29). The peptide shown in SEQ ID NO. 31 can be found at positions 1061 to 1068 in Figure 9. Thus, it is at least the last approximately 5 to 10% of d e overall B.t. protein which should comprise heterologous DNA (compared to the cryEF core N-terminal toxm portion) m the chimenc toxin of the subject invention In die specific examples contained herem, heterologous protoxm sequences occur from ammo acid 640 to the C-terminus Thus, a preferred embodiment of the subject invention is a chimenc B t toxm of about 1150 to about 1200 ammo acids in length, wherein the chimenc toxm compnses a cry F core N-terminal toxm portion of at least about 50 to 60% of a full cryEF molecule, but no more dian about 90 to 95% of d e full molecule The chimenc toxm further compnses a cryIA(b) or a 436 protoxm C-teπmnal portion which compnses at least about 5 to 10% of die cryEA ) or 436 molecule The transition from crylF to cryIA(b) or 436 sequence thus occurs within the protoxm segment (or at the junction of the toxm and protoxm segments) between about 50% and about 95% of the wav through the molecule In die specific examples provided herem, the transitions from the crvIF sequence to die heterologous proto m sequences occur pπor to the end of die peptide sequence shown in SEQ ID NO 31 A specific embodiment of die subject invention is the chimenc toxin shown m Figure 9 Other constructs mav be made and used by tiiose skilled in tius art havmg the benefit of die teachmgs provided herem The core toxm segment of cryl proteins characteristically ends widi the sequence Val/Leu Tyr/Ile De Asp Arg/Lys Ile/Phe Glu Ile/Phe/Leu Ile/Leu/Val Pro/Leu Ala/Val Glu/Thr/Asp (SEQ ID NO 30), which ends at residue 601 of SEQ ID NO 23 Additionally, the protoxm segments of d e cryl toxins (which follow residue 601) bear more sequence similanty dian die toxm segments Because of dus sequence similanty, the transition pomt m die protoxm segment for making a chimenc protem between the crvEF sequence and die crvIA(b) or 436 sequence can be readilv determined bv one skilled in die art From studies of data regarding the partial proteolysis of Cryl genes, the heterogeneity and least-conserved amino acid regions are found after the conserved cryl protoxin sequence, positions 1061 - 1068 of Figure 9 Therefore a chimenc toxm of the subject invention can compnse the full cr IF toxin and a portion of d e crvIF protoxin, transiQoning to the corresponding cr IA(b) or 436 sequence at any position between die end of die toxm segment (as defined above) and die end of d e peptide sequence shown in SEQ ED NO 31 Preferabl , the ammo acid sequence of die C-terminus of die chimenc tox compnses a crvIA(b) sequence or a sequence from die 436 gene or an equivalent of one of these sequences are well known in the art CrvIF genes and toxins hav e been descnbed m. for example Chambers et al (1991) J Bacteriol 173 3966 CrvIA(b) genes and toxins have been descnbed m, for example. Hofte et al (1986) Eur J Biochem 161 273 Geiser et al (1986) Gene 48 109, and Haider et al (1988) Nucleic Acids Res 16 10927 The skilled artisan havmg d e benefit of die teachmgs contained herem could readilv identify and use DNA which encodes die toxm N-terminal portion of a cr IF molecule and die C-teπrunal protoxm portion of d e crvIA(b) toxins Figure 9 provides examples of ammo acid substitutions which can be used in die to ins of d e subject invention It is also well known m the art that vaπous mutations can be made m a toxm sequence without changing die activity of a toxm Furthermore, due to d e degeneracy of die genetic code, a vanety of DNA sequences can be used to encode a particular toxm These alternative DNA and ammo acid sequences can be used accordmg to the subject invention by a person skilled m this art The protoxm substitution techniques of d e subject invention can be used widi other classes of B t endotoxins to enhance expression of the toxin The technique would be most applicable to other B t toxins which have die charactenstic sequence shown in SEQ ID NO 30 The flow charts of Figures 1-8 provide a general overview of vector construction diat can be earned out accordmg to the subject invention BamHl and Pvul clomng sites can be introduced mto a cryIA(c)/cryIA(b) chimenc toxm gene by mutagenesis usmg die PCR technique of Splice Overlap Extension (SOE) (Horton, R M , H D Hunt, S N Ho, J K Pullen, L R Pease [1989] Gene 11 61-68) to give plasmid pMYC2224 A region of the crylF gene from a crv/ -contaimng plasmid such as pMYC1260 can be generated by PCR and substituted for the BamHl-Pvul cryIA(c)/ctyIA(b) gene fragment of pMYC2224 The new plasmid, which we designated pMYC2239, consisted of a short segment of cryΙA(c) followed by cry IF to the toxin/protoxin segment junction Thus, die protoxm segment was now deπved from cryl A(b) (pMYC 1050) An Apal fragment denved from the cry IF clone (pMYC2047) was substituted for the Apal fragment m pMYC2239 The resulting clone (pMYC2244) consisted of cryEF from the initiator methiomne to die toxin/protoxin segment junction and cryIA(b) to the end of die coding region Clone pMYC2243 was constructed by SOE to introduce sdent codon changes m a limited region The Apal fragment from pMYC2243 that contained the silent changes was substituted for the Apal fragment m pMYC2244 to give clone pMYC2523 The chimeπc pMYC2523 showed an expression improvement over pMYC2243, which contains unchanged crylF protem sequence A crvIF/436 chimera can be assembled by substituting die A -.I--__.EII protem segment- containing fragment of pMYC2523 with an eqmvalent fragment generated by PCR from a plasmid containing a cryIA(c)/cryIA(b) gene One such gene is die 436 gene (e g , pMYC467. as disclosed m U S Patent Nos 5,055,294 and 5,169.760) This construction also results m improved expression compared to the native crylF protem sequence Genes and toxins The genes and toxins useful accordmg to the subject invention mclude not onlv d e full lengdi sequences disclosed but also fragments of these sequences, aπants mutants and fusion proteins which retain die charactenstic pesticidal activity of die to ins specificalh exemplified herem As used herein, the terms "vanants" or "vaπations" of genes refer to nucleotide sequences which encode die same toxins or which encode eqmvalent toxins havmg pesticidal activitv As used herein, the term "eqmvalent toxins" refers to toxins havmg die same or essentially the same biological activity against the target pests as the claimed toxins It should be apparent to a person skilled m tins art diat genes encodmg active toxins can be identified and obtamed dirough several means The specific genes or gene portions exemplified herem mav be obtamed from die isolates deposited at a culture depository as descnbed abov e These genes, or portions or variants thereof, may also be constructed synthetically, for example, by use of a gene synthesizer. Variations of genes may be readily constructed using standard techniques for making point mutations. Also, fragments of these genes can be made using commercially available exonucleases or endonucleases according to standard procedures. For example, enzymes such as BaB 1 or site-directed mutagenesis can be used to systematically cut off nucleotides from die ends of these genes. Also, genes which encode active fragments may be obtained using a variety of restriction enzymes. Proteases may be used to direcdy obtain active fragments of tiiese toxins. Fragments and equivalents which retain the pesticidal activity of the exemplified toxins would be widiin the scope of die subject invention. Also, because of die redundancy of die genetic code, a variety of different DNA sequences can encode die amino acid sequences disclosed herein. It is well within die skill of a person trained in die art to create these alternative DNA sequences encoding die same, or essentially the same, toxins. These variant DNA sequences are within die scope of the subject invention. As used herein, reference to ' essentially die same" sequence refers to sequences which have amino acid substitutions, deletions, additions, or insertions which do not materially affect pesticidal activity. Fragments retaining pesticidal activity are also included in this definition. A further method for identifying die toxins and gene portions useful according to die subject invention is dirough die use of oligonucleotide probes. These probes are detectable nucleotide sequences. These sequences may be detectable by virtue of an appropriate label or may be made inherently fluorescent as described in International Application No. WO93/16094. As is well known in die art, if the probe molecule and nucleic acid sample hybridize by forming a strong bond between the two molecules, it can be reasonably assumed diat the probe and sample have substantial homology . Preferably . hybridization is conducted under stringent conditions by techniques well-known in die art, as described, for example, in Keller, G.H., M.M. Manak (1987) DNA Probes, Stockton Press, New York, NY., pp. 169-170. Detection of die probe provides a means for determining in a known manner whether hybridization has occurred. Such a probe analysis provides a rapid method for identifying toxin-encoding genes of the subject invention. The nucleotide segments which are used as probes according to die invention can be syndiesized using DNA syndiesizer and standard procedures. These nucleotide sequences can also be used as PCR primers to amplify- genes of die subject invention. Certain toxins of die subject invention have been specifically exemplified herein. Since these toxins are merely exemplary of the toxins of die subject invention, it should be readily apparent that the subject invention comprises variant or equivalent toxins (and nucleotide sequences coding for equivalent toxins) having the same or similar pesticidal activity of the exemplified toxin. Equivalent toxins will have amino acid homology widi an exemplified toxi - This amino acid homology will typicall be greater dian 75%. preferably be greater than 90%, and most preferably be greater than 95%. The amino acid homology will be highest in critical regions of die toxin which account for biological activity or are involved in the determination of three-dimensional configuration which ultimately is responsible for the biological activit '. In this regard, certain amino acid substitutions are acceptable and can be expected if tiiese substitutions are m regions which are not cπϋcal to activity or are conservative ammo acid substitutions which do not affect die tiiree-dimensional configuration of the molecule For example, ammo acids may be placed m die following classes non-polar, uncharged polar, basic, and acidic Conservative substitutions whereby an ammo acid of one class is replaced widi another amino acid of the same type fall within the scope of die subject invention so long as the substitution does not materially alter the biological activity of die compound Table 1 provides a listing of examples of ammo acids belonging to each class Table 1. Class of Ammo Acid Examples of Ammo Acids Nonpolar Ala, Val, Leu, He, Pro, Met, Phe, Trp Uncharged Polar Gly, Ser, Thr, Cys, Tyr, Asn, Gin Acidic Asp, Glu Basic Lys, Arg, His In some instances, non-conservative substitutions can also be made The cntical factor is that tiiese substitutions must not significa ly detract from die biological activity of the toxm Recombinant hosts The genes encodmg die toxins of die subject invention can be introduced mto a wide vaπety of microbial or plant hosts Expression of the toxm gene results, directly or lndirettly, m the intracellular production and mamtenance of die pesticide Conjugal transfer and recombinant transfer can be used to create a B t strain that e presses both toxins of the subject invention Other host organisms mav also be transformed with one or both of die toxin genes en used to accomplish die svnergistic effect Widi suitable microbial hosts, e , Pseudomonas, the microbes can be applied to die situs of die pest, where they will proliferate and be mgested The result is control of the pest Alternativel , die microbe hosting die toxm gene can be treated under conditions diat prolong die activity of the toxm and stabilize die cell The treated cell, which retams the toxic activity, then can be applied to the environment of the target pest Where the B t toxm gene is introduced v la a smtable vector mto a microbial host, and said host is applied to die environment m a living state, it is essential diat certain host microbes be used Microorganism hosts are selected which are known to occupy die "phytosphere" (phv lloplane, phvllosphere. rhizosphere, and/or rhizoplane) of one or more crops of mterest These microorganisms are selected so as to be capable of successfully competing m die particular environment (crop and odier msect habitats) widi die wild-type πucroorgamsms, provide for stable mamtenance and expression of the gene expressing the polypeptide pesticide, and, desirably, provide for unproved protection of the pesticide from environmental degradation and inactivation A large number of microorganisms are known to inhabit the phylloplane (the surface of the plant leaves) and/or die rhizosphere (die soil surrounding plant roots) of a wide vanety of important crops These microorganisms include bacteria, algae, and fungi Of particular interest are πucroorgamsms, such as bactena, e g , genera Pseudomonas, Erwinia, Serratia, Klebsiella, Xanthomonas, Streptomyces, Rhizobium, Rhodopseudomonas, Methylophilius, Agrobactenum, Acetobacter, Lactobacillus, Arthrobacter, Azotobacter, Leuconostoc, and Alca genes, fungi, particularly yeast, e g , genera Saccharomyces, Cryptococcus, Kluyveromyces, Sporobolomvces, Rhodotorula, and Aureobasidium Of particular mterest are such phytosphere bactenal species as Pseudomonas synngae, Pseudomonas fluorescens, Serratia marcescens, Acetobacter xylinum, Agrobactenum tumefaciens, Rhodopseudomonas spheroides, Xanthomonas campestris, Rhizobium me oti, Alca genes entrophus, and Azotobacter vinlandit, and phytosphere veast species such as Rhodotorula rubra. R gluttnis, R marina. R aurantiaca, Cryptococcus albidus, C diflluens, C laurentn, Saccharomyces rosei, S pretonensis, S cerevisiae, Sporobolomvces roseus, S odorus, Kluyveromyces veronae, and Aureobasidium pollulans Of particular mterest are the pigmented microorganisms A wide vanety of wavs are available for introducing a B t gene encodmg a toxm mto a microorganism host under conditions which allow for stable mamtenance and expression of the gene These methods are well known to diose skilled m die art and are descnbed, for example, m United States Patent No 5,135,867, which is incorporated herem bv reference Treatment of cells Bacillus thuringiensis or recombinant cells expressing the B t toxins can be treated to prolong the toxm activity and stabilize the cell The pesticide microcapsule diat is formed compnses die B t toxm or toxins within a cellular structure that has been stabilized and will protect die toxin when die microcapsule is applied to the environment of the target pest Smtable host cells mav include either prokaryotes or eukaryotes, normally bemg limited to tiiose cells which do not produce substances toxic to higher organisms, such as mammals However, organisms which produce substances toxic to higher organisms could be used where die toxic substances are unstable or die level of application sufficientlv low as to avoid am possibility of toxicity to a mammalian host As hosts of particular mterest will be die prokarvotes and die lo er eukaryotes, such as fiingi The cell will usuallv be intact and be substantially m die proliferative form when treated radier dian m a spore form although m some instances spores mav be employed Treatment of the microbial cell, e . a microbe containing the B t toxm gene or genes can be bv chemical or physical means, or by a combmation of chemical and/or physical means so long as the techmque does not deletenouslv affect die properties of the toxm nor diminish die cellular capability of protectmg the toxm Examples of chemical reagents are halogenatmg agents particularly halogens of atomic no 17-80 More particularly iodine can be used under mild conditions and for sufficient time to achiev e die desired results Other suitable techniques mclude treatment with aldehydes, such as glutaraldeh de, anti-infectives, such as zephiran chlonde and cetylpyndinium chlonde. alcohols, such as isopropyl and etiianol, vanous histologic fixatives, such as Lugol iodine, Bourn's fixative, vanous acids and Helly's fixative (See Humason, Gretchen L., Animal Tissue Techniques, W H Freeman and Company, 1967), or a combmation of physical (heat) and chemical agents that preserve and prolong the activity of the toxm produced in the cell when the cell is administered to the host environment Examples of physical means are short wavelengtii radiation such as gamma-radiation and X -radiation, freezing, UV irradiation, lyophilization, and die like Metiiods for treatment of microbial cells are disclosed United States Patent Nos 4,695,455 and 4,695,462, which are incorporated herem by reference The cells generally will have enhanced structural stability which will enhance resistance to environmental conditions Where the pesticide is m a proform, the metiiod of cell treatment should be selected so as not to inhibit processing of the proform to the mature form of the pesticide by die target pest pathogen For example, formaldehyde will crosslink proteins and could inhibit processing of the proform of a polypeptide pesticide The method of treatment should retain at least a substantial portion of the bio-availability or bioactivity of the toxm Charactenstics of particular mterest m selecting a host cell for purposes of production mclude ease of mtroducmg the B t gene or genes mto the host, availability of expression systems, efficiency of expression, stability of the pesticide m die host, and die presence of auxiliary genetic capabilities Charactenstics of mterest for use as a pesticide microcapsule mclude protective qualities for die pesticide, such as duck cell walls, pigmentation, and intracellular packaging or formation of inclusion bodies, survival aqueous environments, lack of mammalian toxicity , attractiveness to pests for lngestion, ease of killmg and fixmg widiout damage to me toxin, and die hke Otiier considerations mclude ease of formulation and handling, economics, storage stability, and die like Growth of cells The cellular host containing die B t insecticidal gene or genes mav be grown in anv convenient nutnent medium, where the DNA construct provides a selective advantage, providmg for a selective medium so that substantially all or all of the cells retain the B t gene These cells may dien be harvested in accordance widi conventional way s Alternatively , the cells can be treated pπor to harvesting The B t cells producmg die toxins of the mvention can be cultured usmg standard art media and fermentation techniques Upon compleϋon of the fermentation c cle the bacteπa can be harvested by first separating the B t spores and crystals from the fermentation broth bv means well known m the art The recovered B t spores and crystals can be formulated mto a wettable powder, liquid concentrate, granules or other formulations bv the addition of surfactants, dispersants, inert earners, and otiier components to facilitate handling and application for particular target pests These formulations and application procedures are all ell known in the art Formulations Formulated bait granules containing an attractant and spores, crystals, and toxins of the _? f isolates, or recombinant microbes compnsmg the genes obtainable from die B t isolates disclosed herein, can be applied to die soil Formulated product can also be applied as a seed-coatmg or root treatment or total plant treatment at later stages of the crop cycle Plant and sod treatments of B.t cells may be employed as wettable powders, granules or dusts, by mixing with vanous inert materials, such as inorganic minerals (phyllosilicates, carbonates, sulfates, phosphates, and die like) or botanical materials (powdered corncobs, nee hulls, walnut shells, and die like) The formulations may mclude spreader-sticker adjuvants, stabilizing agents, other pesticidal additives, or surfactants Liquid formulations may be aqueous-based or non-aqueous and employed as foams, gels, suspensions, emulsifiable concentrates, or die like The ingredients may mclude theological agents, surfactants, emulsifiers, dispersants, or polymers As would be appreciated by a person skilled m die art, the pesticidal concentration will vary widely dependmg upon the nature of the particular formulation, particularly whether it is a concentrate or to be used direcdy The pesticide will be present m at least 1% by weight and may be 100% by weight The dry formulations will hav e from about 1-95% by weight of die pesticide while die liquid formulations will generally be from about 1-60% by weight of the solids m die liquid phase The formulations will generally have from about 10 2 to about 10 4 cells/mg These formulations will be administered at about 50 mg (hq d or dry) to 1 kg or more per hectare The formulations can be applied to die environment of the lepidopteran pest, e g , foliage or sod, by spraying, dusting, sprinkling, or the Id e Matenals and Mediods NACS (Bediesda Research Labs, Gaithersburg, MD) column chromatography was used for purification of electioeluted DNA It was performed accordmg to die manufacturer's directions, except that the buffers were modified to 0.5X TBE 0 2 M NaCl for binding, and 0 5X TBE 2 0 M NaCl for elution Random pruning labeling of DNA with α-[ 3J P]dATP was done wtth a kit (Boehπnger- Mannheim Biochemicals, Indianapolis, IN) accordmg to the manufacturer's directions Gel purification refers to sequential application of agarose-TBE gel electrophoresis. electroelutioa and NACS column chromatography for purification of selected DNA fragments, mediods which are well known m the art Polvmerase chain reaction (PCR) amplification of DNA was done for 25 cycles on a Perkin Elmer (Norwalk. CT) thermal cycler with die following c cle parameters 94 °C for 1 minute, 37 C for 2 minutes, 72 °C for 3 minutes (each 72 °C cycle has a 5 second extension time) PCR DNA products were proteinase K treated to improve clo ng efficiency (Crowe, J S , Cooper, H J , Srmdi. M A Suns, M J , Parker, D , Gewert, D [1991] Nucl Acids Res 19 184) Oligodeoxynbonucleotides (oligonucleotides) were synthesized on an Applied Biosystems (Foster City , CA) model 381 A DNA synthesizer Purification was done widi Nensorb columns (New England Nuclear-Dupont, Wilmington. DE). if necessary, accordmg to die manufacturer's instructions Electroporation of Pseudomonas fluorescens was done widi log-phase cells grown in L-broth (LB) at 30 °C on a rotary shaker. Cells were washed 2 to 3 times with ice-cold sterile distilled water and concentrated to 0.03x starting volume in distilled water. DNA in 1-20 μl was mixed widi 50-300 μl of cells. Parameters selected for the Biorad Gene Pulser (Bio-Rad, Richmond, CA) were 200 ohms, 25 microfarads, and 2.25 kϋovolts in a cuvette widi a 0.2 cm electrode gap. Following electroporation, one milliliter of LB was added and cells were held on ice for at least 2 minutes. Cells were then incubated for 2 hours to overnight at 30°C without shaking. B. t. toxin expression in P. fluorescens was done in the recommended medium found in the Manual of Methods for General Bacteriology (P. Gerhardt et al., 1981, American Society for Microbiology, Washington, D.C.). Glycerol was substituted for glucose. The recipe was made widi tap water and the pH adjusted to 7.2. Seed flasks were made from L-broth. The following recipes apply: Base Medium (for 1 liter) glycerol 65 g (NH 4 ) 2 S0 4 1.0 g Na 2 HP0 4 5.24 g KH 2 P0 4 2.77 g Yeast extract 5.0 g Casamino acids 1.0 g Metals 44 (for 100 ml) EDTA 250 mg ZnSO_-7H : 0 1095 mg FeS0 4 -7H_0 500 mg MnS0 4 H 2 0 154 mg CuS0 4 -5H 2 0 39.2 mg Co(N0 3 ) 2 -6H 2 0 24.8 mg Na 2 B,O. 10H,O 17.7 mg Add a few drops of 6 N H 2 S0 4 to retard precipitation. Huntner's M eral Mix (for 1 liter) Nitnloacetic acid (dissolved and neutrahzed with KOH) 10 g MgS0 4 -7H 2 0 14 45 g CaCl 2 -2H 2 0 3.33 g (NH 4 ) 6 Mo 7 0 24 -4H 2 0 9 25 g FeS0 4 -7H 2 0 99 mg Metals 44 50 ml pH adjusted to 6 6-6 8 At inoculation for analysis of B t toxm expression, 4 ml of Huntner's Mmeral Mix was added per 200 ml of broth Flasks were then given a 2% inoculum, by volume, of an overnight culture Cultures were allowed to grow for 24 hours at 32 °C at _ 200 m At this pomt, they were mduced widi 075 mM IPTG and supplemented widi 2 g east extract Protem gels were run on samples pulled at 48 and 72 hours The 130 kDa protem was quantified by laser densitometry Following are examples which dlustrate procedures, including die best mode, for practicing the invention These examples should not be construed as limiting All percentages are by weight and all solvent mixture proportions are by volume unless otiierwise noted Example 1 - Expression Vector Modification bv Splice Overlap Extension (SOE) A clomng vector can be constructed based on pTJS260 a broad host-range plasmid deπved from RSF1010 (pTJS260 can be obtamed from Dr Donald Helinski, U C San Diego) An example of the svstem used in die vector construction can be found m EPO patent application 0 471 564 A cry lA(c)/crvIA(b) gene, refeπed to herem as the 436 gene and toxm, are descnbed m U S Patent No 5 055,294 A plasmid designated pMYC1050 contains the 436 gene pMYC1050 was constructed re-cloning the toxm gene and promoter of pM3.130-7 (disclosed m U S Patent No 5 055,294) mto a pTJS260-based vector such as pMYC467 (disclosed m U S Patent No 5,169.760) bv mediods well known in die art In particular, the pM3, 130-7 promoter and toxm gene can be obtamed as a BamHl to Ndcl fragment and placed mto die pMYC467 plasmid replacmg a fragment bounded bv die same sites (Bam HI near base 12100 and Ndel near base 8000) The unproved vector ideally contains a unique BamHl clomng site The plasmid BamHl site located upstream from die lac promoter (Ptac), can be removed by blunting witii Klenow and re gating (Figure 1) Absence of the site can be confirmed b restnction digestion A plasmid produced accordmg to tins procedure was called pMYC1050Δ__αmHI The construct can now have a BamHl site added to die plasmid by SOE mutagenesis SOE mutagenesis can be facilitated bv subcloning an Nsil tox n- containing DNA fragment mto the smaller pGEM5 (Promega Coφ Madison WI) vector which uses die ampicillin resistance (b la) gene as a selectable marker (Figure 1). The fragment can be oriented by restriction digestion. A plasmid produced according to diis procedure was called pGEMtox. DNA in die toxin coding region can be mutated by die PCR-mediated technique of SOE to introduce restriction enzyme cloning sites as shown in Figure 2. Oligonucleotides useful as primers are shown below: "A" (SEQ ID NO. 1) 5' GCATACTAGTAGGAGATTTCCATGGATAACAATCCGAAC 3' "B" (SEQ ID NO. 2) 5' GGATCCGCTTCCCAGTCT 3' "C" (SEQ ID NO. 3) 5' AGAGAGTGGGAAGCGGATCCTACTAATCC 3' "D" (SEQ ID NO. 4) 5 ' TGGATACTCGATCGATATGATAATCCGT 3 ' "E" (SEQ ID NO. 5) 5 ' TAATAAGAGCTCCTATGT 3 ' "F" (SEQ ID NO. 6) 5 ' TATCATATCGATCGAGTATCC AATTTAG 3 ' "G" (SEQ ID NO. 7) 5 ' GTC ACATAGCCAGCTGGT 3 ' pMYClOSO DNA was used as the template for PCR amplification usmg primer sets A/B, C D, E D. and F/G Amplified DNA fragments were named AB, CD, ED, and FG Amplified DNAs were purified by agarose-TBE gel electrophoresis, electroelution, and NACS column chromatography. mediods all well- known in the art. Purified template DNAs were used in a second set of PCR reactions Fragments AB and CD were mixed and amplified widi primers A and D. In a separate reaction, fragments ED and FG were mixed and amplified widi primers E and G Amplified DNA was resolved by agarose-TBE gel electrophoresis and die fragments widi the corresponding increase m size were excised, electioeluted. and purified over NACS columns by means well known in die art Amplified DNA fragments are called AD or EG for reference. DNA fragments AD or EG with die new restriction enzyme sites were incoφorated mto the toxin-containing DNA by several subcloning procedures (Figures 2 and 3). pGEMtox was digested with Clal or Hindlll Vector-containing DNA was gel-purified. Fragment AD was digested widi Clal and ligated to C/αl-digested pGEMtox vector DNA. Fragment EG was digested widi Hindlll and ligated to -V.rtdlll-digested pGEMtox vector DNA. E. coli strain NM522 was transformed widi gation mixes Correctly assembled constructs were identified by restriction enzyme digestion of plasmid DNA from isolated colonies. The plasmid widi die new BamHl site was called pGEM tox BamHl The plasmid widi die new Pvul site was called pGEMtox Pvul. The Clal fragment containing die BamHl site from plasmid pGEMtox BamHl was ligated to die phosphatased Clal vector-containing fragment from pGEMtox Pvul. E. coli strain NM522 was transformed widi ligation mixes. Correctly assembled constructs were identified by PCR analysis with primer set C/D, and by restriction digestion. The plasmid widi bodi new restriction enzyme sites was called pGEMtox BamHl/Pvul. A completed expression vector was assembled widi insert from pGEMtox BamHl/Pvul and vector from pMYC1050Δ_5omHI (Figures 3 and 4). Gel-purified insert was prepared from pGEMtox BamHl/Pvul by Nsil digestion, and S al digestion (to remove contaminating vector). It was ligated to gel-purified Ns/I-digested vector-containing pMYC1050Δ5αmHI DΝA. E. coli strain ΝM522 was transformed widi die ligation mixes, and transformation mixes were plated on LB agar containing tetracycline at 12 μg/ml. Colonies containing the Nsil insert were identified by colony hybridization and autoradiography. Inserts were oriented by PCR, using primer set A D, which bridges an Nsil cloning site, and agarose-TBE gel electrophoresis. The correcdy assembled plasmid is called pMYC2224. DNA and protein sequences of the toxin are found in SEQ ID NOS. 18 and 19, respectively. A lactose-inducible P. fluorescens strain was electroporated with correctly assembled plasmid DN Transformation mixes were plated on LB agar containing tetracycline at 20 μg ml. Plasmid DNA was prepared from P. fluorescens for use in subsequent cloning experiments. Example 2 - Subcloning die crvIF Hvpervariable Region into pMYC2224 A DNA fragment containing die hypervariable region from cryEF (pMYC 1260) was exchanged for the BamHl-Pnil toxin-containing DNA fragment from pMYC2224 (Figure 4). Since the coding sequence contains a preexisting BamHl site, BgUl was chosen for cloning. The 4-base overhangs of BamHl and BgUl are compatible, permitting ligation while eliminating bodi sites from die junction. It was necessary to synthesize a new primer for PCR: "L" (SEQ ID NO. 8) 5 ' GAGTGGGAAGC AGATCTTAATAATGCAC AATTAAGG 3 ' A toxin-containing DNA fragment was generated by PCR widi primers L/D on template pMYC 1260. The DNA was digested widi BglU and Pvul for subcloning. Since the telAR locus contains multiple sites, it was necessary to isolate the vector-containing DNA on two separate fragments. To obtain die first fragment, pMYC2224 was digested widi BamHl x BstEll. and die large DNA fragment containing the Ptac-tetAR locus-rep functions was gel-purified. To obtain die second fragment. pMYC2224 was digested widi BstEll x Pvul, and die DNA fragment containing the vector-proto in module was gel-purified. A diree-piece ligation was set up and used for E. coli strain NM522 transformation. Grossly conect plasmids were identified by PCR analysis and agarose-TBE gel electrophoresis using die primer set N/O, which bridges die BamHl/Bgfll fusion junction. "N" (tac promoter) (SEQ ID NO. 9) 5 ' TTAATCATCGGCTCGTA 3 ' "O" (SEQ ID NO. 10) 5' ACTCGATCGATATGATA(GA)TCCGT 3' The correct plasmid was named pMYC2239. It consists of cιyIA(c) at the ammo-terminus, cryEF up to die toxinprotoxin junction, and cryIA(b) through the protoxm segment. The toxm DNA and protem sequences are in SEQ ID NOS. 20 and 21, respectively. Example 3 - Construction of the P. fluorescens Expression Plasmids pMYC1260 and pMYC2047 The cloned toxm gene crylF can be modified for expression in P fluorescens in the following way: 1 A plasmid containing the pKK223-3 rrnB termination sequences in the pTJS260- deπved vector (Dr Donald Helinsla, U C. San Diego) can be made by ligating die BamHl-Scal fragment containing die Ptac promoter and rrnB terminator from pKK223-3 (Pharmacia E. coli vector) mto the BamHl to blunted Kpnl vector fragment of pMYCl 197 (descnbed in EP 0 417 564). The assembled plasmid is recovered following transformation of E. coli and growth under tetracycline selection 2. A plasmid containing die Ptoc-promoted cryEF toxm gene can be made by ligating toxin gene-containing Ndel-Nde-l fragment (with ends blunted using DNA polymerase and dNTPs) of about 3800 bp from pMYC1603 (from NRRL B-18517) into the blunted EcoRI and Hindlll sites of pKK223- 3 The /toe-promoted crylF toxm plasmid can be recovered following transformation of E. coli, grown under ampicilhn selection, and screening for plasmids widi inserts in die proper oπentation for expression from die Ptac promoter by techniques well known m the art 3 The / .ore-promoted crylF toxin can be assembled mto die pTJS260-deπved vector m a three-piece ligation usmg the 2 4 kb DNA fragment having BamHl and Apal ends from die plasmid pTJS260, Apal to Hmd l fragment of 8.5 kb containmg the replication region of die plasmid from step 1 above, and a Hindlll to partial BamHl fragment containing die Ptac promoter and cry IF toxm gene from step 2 above The resulting pTJS260-denved crylF toxm expression plasmid (pMYC1260) can be introduced mto P. fluorescens by electroporation. 4 pMYC2047 can be constructed by ligating an Spel to Kpnl fragment obtamed dirough PCR of a suitable cry IF template with primers H and K followed by digestion widi Spel and Kpnl and gel purification, an Apal to Kpnl fragment of a 10 kb from die plasmid of step 3. and die Apal to Spe I fragment of ca 2600 bp from pMYC1197 containing the Ptac promoter The coπect cry IF toxin expression plasmids are determmed by restπction enzyme digestion of plasmids following electroporation mto Pseudomonas fluorescens Example 4 - Construction of a crvIF/crvIA(b) Chimera The cryIA(c) segment at the aπuno-teπrunus can be replaced by die crylF coding sequence by a simple, straightforward swap (Figure 5) Both the tetAR locus and crylF coding sequence contain an Apal site A small Apal fragment containing a portion of the tetAR genes and die anuno-termmus of crylF can be isolated from pMYC2047 and ligated to die large Apal vector-containing fragment from pMYC2239 A P fluorescens lactose-inducible strain can be electroporated with die ligaαon mix and plated on LB agar containmg tetracycline at 20 μg/ml. Lactose-inducible strains are known to diose skilled m the art and are descnbed, for example, m U.S Patent No. 5,169,760. Correct onentation of the Apal fragment reconstitutes tetracycline resistance. A clone produced m tins manner was shown to be grossly coπect by restnction enzyme digestion, and it was named pMYC2244 The toxm DNA sequence is shown in SEQ ID NO 22, and die predicted protem sequence is shown m SEQ ID NO 23 Example 5 - Construction of a Limited Codon Rework of crvIF Codon usage m Pseudomonas spp favors G or C m the wobble position of triplet codons, as determmed by analysis of genes in die GenBankEMBL sequence libranes A limited region of the crylF gene was reworked by SOE to incoφorate favored wobble position changes diat were sdent (Figure 6) Oligos used are shown below "H" (SEQ ID NO 11) 5' GGACTAGTAAAAAGGAGATAACCATGGAAAATAATATTCAAAATC 3' "I" (SEQ ID NO. 12) 5' TCCAC GGCAC -CGGCCGGTGCTGCGTTCTTCGTTCAGTATTTCTACT TCAGGATTATTTAAAC 3' "J" (SEQ ID NO. 13) 5 ' AACGCAGCACCGGCCGCCTGCCGCTGGACATCAGCCTGAGCCTTACAC GTTTCCTTTTGAGTGAA 3' "K" (SEQ ID NO. 14) 5 CATCAAAGGTACCTGGT 3' Two separate PCR reactions were done on pMYC2047 template with primer sets H/l or J/K Amplified DNA fragments were called HI or JK A second PCR reaction was set up by mixing fragments HI and JK and PCR amplifying w di pπmer set H/K The larger SOE DNA was gel-purified and digested widi Spel x Kpnl A tiiree-piece ligation was set up vvitii Spel-Apal Plac-teiAR locus DNA Apal-Kpnl vector-protoxin module DNA and Spel-Kpnl PCR DNA A P fluorescens lactose-inducible strain can be electroporated with die ligation mix Grossly' coπect clones can be identified by PCR analv sis using die primer set P/Q and agarose-TBE gel electrophoresis Oligo P (SEQ ID NO 15) was designed to discriminate between the v\ lid-type and codon-reworked gene "P" (SEQ ID NO 15) 5 ' TGCCGCTGGACATCAGCCTGAG 3 ' "Q" (SEQ ID NO. 16) 5 ' TCTAGAGCGGCCGCTTATAC(CT)CGATCGATATGATA(GA)TCCGT 3 ' The complete plasmid was named pMYC2243 The toxm DNA sequence is shown m SEQ ID NO 24 The toxm protem sequence is predicted to be unchanged, and is shown m SEQ ID NO 25 Example 6 - Construction of the cryEF/cryIA(b) Chimera Containing the Limited Codon Rework The construct was assembled (Figure 7) using die same Apal fragment exchange strategy as for pMYC2244 (cιyIF/c_yIA(b)) above The small, toxm-tetAR locus Apal DNA fragment was gel-purified from pMYC2243 The larger vector-protoxin module Apal DNA fragment was gel-purified from pMYC2244 The completed plasmid was named pMYC2523 Predicted DNA and protem sequences are m SEQ ID NOS 26 and 27, respectively Example 7 - Comparative Expression of Toxms from pMYC2244 and pMYC2523 Toxm expression m P fluorescens was analyzed as descnbed above At 24 and 48 hours post- induction, die pMYC2523-contaιnιng strain produced more toxm dian die pMYC2244-contaιnιng strain Toxin specific activity on Spodoptera exigua was statistically unchanged Example 8 - Construction of the cryIF/436 Chimera Containing die Limited Codon Rework A second type of chimeπc toxm was assembled by substituting the 436 protoxm module for the cryIA(b) protoxm m pMYC2523 (Figure 8) The 436 protoxm sequence consists of crylA(c) sequence except at the very C-termmus (See U S Patent Nos 5,128,130 and 5,169,760, mcoφorated herem by reference m their entirety) Proto m DNA for clo ng was generated by PCR widi die pnmer set F M using a plasmid such as pMYC467 (U S Patent No 5,169,760) as a template "M" (SEQ ID NO 17) 5' AGGCTTCCATAGATACCTTGTGCG 3' PCR DNA was digested widi Pvul x jSs.EII A three-piece ligation was set up widi Spe -Pvul toxm DNA from pMYC2523, Spel-BstEU vector DNA from pMYC2523. and Pvul-BstEll PCR protoxin module DNA A lactose-inducible P fluorescens strain was electroporated widi die ligation mix Grossly coπect plasmids were identified by PCR witii pnmer set F/G and screenmg for slight size mcrease by agarose-TBE gel electrophoresis The construct was named pMYC2254 Predicted DNA and protem sequences are found m SEQ ID NOS 28 and 29, respectively Example 9 - Comparative Expression of Toxins from pMYC2243 and PMYC2254 Toxin expression in P. fluorescens was analyzed as described above. Toxin expression from pMYC2254 was improved over pMYC2243 expression. Example 10 - Analysis for Synergy Between CrvIF Chimeric Toxin and CryIA(c) Chimeric Toxin Against the Corn Earworm. Heliothis zea Twenty-four Heliothis zea first instar larvae were exposed to agar diet containing various concentiations of toxin- At 7 days post treatment, assays were graded for growth inhibition. Larvae were inhibited if the molt from first to second instar was inhibited. Calculations for estimating synergy factor (SF) and expected activity (E[exp]) are shown below. SF = E(obs)fE(exp) where, SF = synergy factor E(ob s) = observed mortality E(exp) - expected mortality E(exp) = a + b - (ab/100) where, a = activity from compound A b = activity from compound B Table 2. % INHIBITION crylF/ cryΙA(c)/ Rate cryIA(b) cryIA(b) 1 1 mix of the two chimenc toxins μg toxin/ g diet a b E(exp) E(obs) SF 50 0 - - 50 78 1 6 25 0 13 23 22 62 2 8 12 5 9 14 22 31 1 4 6 25 9 14 ~ - - An SF greater than 1 indicates synergy fl_evy, Y , M Benderly, Y Cohen, U Gisi. D Bassard [1986] Bulletin OEPP/EPPO Bulletin 16 651-657) Abbott. W S (1925) J Economic Entomology 18.265-267 Example 11 - Analysis for Synergy Between CrvIF Chimenc Toxm and CryΙA(c) Chimenc Toxm Agamst die Corn Earworm. Heliothis zea Twenty-four Heliothis zea first mstar larvae were exposed to agar diet containmg vanous concentrations of toxm At 7 days post treatment, assays were graded for growth inhibition Larv ae were inhibited rfdie molt from first to second mstar was mhibited The dosage reqiured to inhibit 50 percent of die populations (ΕD X ) was estimated usmg standard probit analysis techmques Calculations for estimating svnergy factor (SF) and expected effective dosages (ED[exp]) are shown below SF = ED(exp) ED(obs) where, ED(exp) = expected effective dose of a mixture ED(obs) = observed effective dose of a mixture ED(exp) = (a + b)/a ED A + b ED B where, a = proportion of compound A m mixture b = proportion of compound B m mixture ED A and ED B = equally effective doses of A and B m mixture Table 3. ED(obs) ED(exp) Treatment (μg toxin g diet) SF cryIA(c)/cryIA(b) (A) 36 - - cryIF/cryIA(b) (B) 135 - - A:B (1:1) 21 57 2.6 A:B (3:1) 14 44 3.1 A:B (1:3) 35 80 2.3 A SF greater than 1 indicates synergy (Levy et al. [1986], supra). [CITE for Wadley method] It should be understood diat die examples and embodiments described herein are for illustrative puφoses only and diat various modifications or changes in light thereof will be suggested to persons skilled in die art and are to be included widiin the spirit and purview of this application and die scope of die appended claims. SEQUENCE LISTING ( 1 ) GENERAL INFORMATION : ( i ) APPLICANT : Applicant Name ( s ) : MYCOGEN CORPORATION Street address : 5501 Oberlin Drive City : San Diego State/Province: California Country: US Postal code/Zip: 92121 Phone number: (619) 453-8030 Fax number: (619) 453-6991 (ii) TITLE OF INVENTION: Novel Pesticidal Compositions (iii) NUMBER OF SEQUENCES: 34 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: David R. Saliwanchik (B) STREET: 2421 N.W. 41st Street, Suite A-l (C) CITY: Gainesville (D) STATE: FL (E) COUNTRY: USA (F) ZIP: 32606 (V) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.25 (Vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: US (B) FILING DATE: (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Saliwanchik, David R. (B) REGISTRATION NUMBER: 31,794 (C) REFERENCE/DOCKET NUMBER: MA86 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: 904-375-8100 (B) TELEFAX: 904-372-5800 (2) INFORMATION FOR SEQ ID Nθ:l: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 39 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:l: GCATACTAGT AGGAGATTTC CATGGATAAC AATCCGAAC 39 (2) INFORMATION FOR SEQ ID Nθ:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: GGATCCGCTT CCCAGTCT 18 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: AGAGAGTGGG AAGCGGATCC TACTAATCC 29 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: TGGATACTCG ATCGATATGA TAATCCGT 28 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: TAATAAGAGC TCCTATGT 18 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: TATCATATCG ATCGAGTATC CAATTTAG 28 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) ( i) SEQUENCE DESCRIPTION: SEQ ID NO:7: GTCACATAGC CAGCTGGT 18 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: GAGTGGGAAG CAGATCTTAA TAATGCACAA TTAAGG 36 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: TTAATCATCG GCTCGTA 17 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 23 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: ACTCGATCGA TATGATARTC CGT 23 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 45 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: Single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: GGACTAGTAA AAAGGAGATA ACCATGGAAA ATAATATTCA AAATC 45 (2) INFORMATION FOR SEQ ID NO: 12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 64 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: TCCAGCGGCA GGCGGCCGGT GCTGCGTTCT TCGTTCAGTA TTTCTACTTC AGGATTATTT 60 AAAC 64 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 65 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: AACGCAGCAC CGGCCGCCTG CCGCTGGACA TCAGCCTGAG CCTTACACGT TTCCTTTTGA 60 GTGAA 65 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: CATCAAAGGT ACCTGGT 17 (2) INFORMATION FOR SEQ ID NO: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (Xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:15: TGCCGCTGGA CATCAGCCTG AG 22 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 41 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: TCTAGAGCGG CCGCTTATAC YCGATCGATA TGATARTCCG T 41 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 bases (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (synthetic) (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: AGGCTTCCAT AGATACCTTG TGCG 24 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3465 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: ATGGATAACA ATCCGAACAT CAATGAATGC ATTCCTTATA ATTGTTTAAG TAACCCTGAA 60 GTAGAAGTAT TAGGTGGAGA AAGAATAGAA ACTGGTTACA CCCCAATCGA TATTTCCTTG 120 TCGCTAACGC AATTTCTTTT GAGTGAATTT GTTCCCGGTG CTGGATTTGT GTTAGGACTA 180 GTTGATATAA TATGGGGAAT TTTTGGTCCC TCTCAATGGG ACGCATTTCT TGTACAAATT 240 GAACAGTTAA TTAACCAAAG AATAGAAGAA TTCGCTAGGA ACCAAGCCAT TTCTAGATTA 300 GAAGGACTAA GCAATCTTTA TCAAATTTAC GCAGAATCTT TTAGAGAGTG GGAAGCGGAT 360 CCTACTAATC CAGCATTAAG AGAAGAGATG CGTATTCAAT TCAATGACAT GAACAGTGCC 420 CTTACAACCG CTATTCCTCT TTTTGCAGTT CAAAATTATC AAGTTCCTCT TTTATCAGTA 480 TATGTTCAAG CTGCAAATTT ACATTTATCA GTTTTGAGAG ATGTTTCAGT GTTTGGACAA 540 AGGTGGGGAT TTGATGCCGC GACTATCAAT AGTCGTTATA ATGATTTAAC TAGGCTTATT 600 GGCAACTATA CAGATTATGC TGTACGCTGG TACAATACGG GATTAGAACG TGTATGGGGA 660 CCGGATTCTA GAGATTGGGT AAGGTATAAT CAATTTAGAA GAGAATTAAC ACTAACTGTA 720 TTAGATATCG TTGCTCTGTT CCCGAATTAT GATAGTAGAA GATATCCAAT TCGAACAGTT 780 TCCCAATTAA CAAGAGAAAT TTATACAAAC CCAGTATTAG AAAATTTTGA TGGTAGTTTT 840 CGAGGCTCGG CTCAGGGCAT AGAAAGAAGT ATTAGGAGTC CACATTTGAT GGATATACTT 900 AACAGTATAA CCATCTATAC GGATGCTCAT AGGGGTTATT ATTATTGGTC AGGGCATCAA 960 ATAATGGCTT CTCCTGTAGG GTTTTCGGGG CCAGAATTCA CTTTTCCGCT ATATGGAACT 1020 ATGGGAAATG CAGCTCCACA ACAACGTATT GTTGCTCAAC TAGGTCAGGG CGTGTATAGA 1080 ACATTATCGT CCACTTTATA TAGAAGACCT TTTAATATAG GGATAAATAA TCAACAACTA 11 0 TCTGTTCTTG ACGGGACAGA ATTTGCTTAT GGAACCTCCT CAAATTTGCC ATCCGCTGTA 1200 TACAGAAAAA GCGGAACGGT AGATTCGCTG GATGAAATAC CGCCACAGAA TAACAACGTG 1260 CCACCTAGGC AAGGATTTAG TCATCGATTA AGCCATGTTT CAATGTTTCG TTCAGGCTTT 1320 AGTAATAGTA GTGTAAGTAT AATAAGAGCT CCTATGTTCT CTTGGATACA TCGTAGTGCT 1380 GAATTTAATA ATATAATTCC TTCATCACAA ATTACACAAA TACCTTTAAC AAAATCTACT 1440 AATCTTGGCT CTGGAACTTC TGTCGTTAAA GGACCAGGAT TTACAGGAGG AGATATTCTT 1500 CGAAGAACTT CACCTGGCCA GATTTCAACC TTAAGAGTAA ATATTACTGC ACCATTATCA 1560 CAAAGATATC GGGTAAGAAT TCGCTACGCT TCTACCACAA ATTTACAATT CCATACATCA 1620 ATTGACGGAA GACCTATTAA TCAGGGGAAT TTTTCAGCAA CTATGAGTAG TGGGAGTAAT 1680 TTACAGTCCG GAAGCTTTAG GACTGTAGGT TTTACTACTC CGTTTAACTT TTCAAATGGA 1740 TCAAGTGTAT TTACGTTAAG TGCTCATGTC TTCAATTCAG GCAATGAAGT TTATATAGAT 1800 CGAATTGAAT TTGTTCCGGC AGAAGTAACC TTTGAGGCAG AATATGATTT AGAAAGAGCA 1860 CAAAAGGCGG TGAATGAGCT GTTTACTTCT TCCAATCAAA TCGGGTTAAA AACAGATGTG 1920 ACGGATTATC ATATCGATCG AGTATCCAAT TTAGTTGAGT GTTTATCTGA TGAATTTTGT 1980 CTGGATGAAA AAAAAGAATT GTCCGAGAAA GTCAAACATG CGAAGCGACT TAGTGATGAG 2040 CGGAATTTAC TTCAAGATCC AAACTTTAGA GGGATCAATA GACAACTAGA CCGTGGCTGG 2100 AGAGGAAGTA CGGATATTAC CATCCAAGGA GGCGATGACG TATTCAAAGA GAATTACGTT 2160 ACGCTATTGG GTACCTTTGA TGAGTGCTAT CCAACGTATT TATATCAAAA AATAGATGAG 2220 TCGAAATTAA AAGCCTATAC CCGTTACCAA TTAAGAGGGT ATATCGAAGA TAGTCAAGAC 2280 TTAGAAATCT ATTTAATTCG CTACAATGCC AAACACGAAA CAGTAAATGT GCCAGGTACG 2340 GGTTCCTTAT GGCCGCTTTC AGCCCCAAGT CCAATCGGAA AATGTGCCCA TCATTCCCAT 2400 CATTTCTCCT TGGACATTGA TGTTGGATGT ACAGACTTAA ATGAGGACTT AGGTGTATGG 2460 GTGATATTCA AGATTAAGAC GCAAGATGGC CATGCAAGAC TAGGAAATCT AGAATTTCTC 2520 GAAGAGAAAC CATTAGTAGG AGAAGCACTA GCTCGTGTGA AAAGAGCGGA GAAAAAATGG 2580 AGAGACAAAC GTGAAAAATT GGAATGGGAA ACAAATATTG TTTATAAAGA GGCAAAAGAA 2640 TCTGTAGATG CTTTATTTGT AAACTCTCAA TATGATAGAT TACAAGCGGA TACCAACATC 2700 GCGATGATTC ATGCGGCAGA TAAACGCGTT CATAGCATTC GAGAAGCTTA TCTGCCTGAG 2760 CTGTCTGTGA TTCCGGGTGT CAATGCGGCT ATTTTTGAAG AATTAGAAGG GCGTATTTTC 2820 ACTGCATTCT CCCTATATGA TGCGAGAAAT GTCATTAAAA ATGGTGATTT TAATAATGGC 2880 TTATCCTGCT GGAACGTGAA AGGGCATGTA GATGTAGAAG AACAAAACAA CCACCGTTCG 2940 GTCCTTGTTG TTCCGGAATG GGAAGCAGAA GTGTCACAAG AAGTTCGTGT CTGTCCGGGT 3000 CGTGGCTATA TCCTTCGTGT CACAGCGTAC AAGGAGGGAT ATGGAGAAGG TTGCGTAACC 3060 ATTCATGAGA TCGAGAACAA TACAGACGAA CTGAAGTTTA GCAACTGTGT AGAAGAGGAA 3120 GTATATCCAA ACAACACGGT AACGTGTAAT GATTATACTG CGACTCAAGA AGAATATGAG 3180 GGTACGTACA CTTCTCGTAA TCGAGGATAT GACGGAGCCT ATGAAAGCAA TTCTTCTGTA 3240 CCAGCTGATT ATGCATCAGC CTATGAAGAA AAAGCATATA CAGATGGACG AAGAGACAAT 3300 CCTTGTGAAT CTAACAGAGG ATATGGGGAT TACACACCAC TACCAGCTGG CTATGTGACA 3360 AAAGAATTAG AGTACTTCCC AGAAACCGAT AAGGTATGGA TTGAGATCGG AGAAACGGAA 3420 GGAACATTCA TCGTGGACAG CGTGGAATTA CTTCTTATGG AGGAA 3465 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1155 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19: Met Asp Asn Asn Pro Asn lie Asn Glu Cys lie Pro Tyr Asn Cys Leu 1 5 10 15 Ser Asn Pro Glu Val Glu Val Leu Gly Gly Glu Arg lie Glu Thr Gly 20 25 30 Tyr Thr Pro lie Asp lie Ser Leu ser Leu Thr Gin Phe Leu Leu Ser 35 40 45 Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly Leu Val Asp lie He 50 55 60 Trp Gly He Phe Gly Pro Ser Gin Trp Asp Ala Phe Leu Val Gin He 65 70 75 80 Glu Gin Leu He Asn Gin Arg He Glu Glu Phe Ala Arg Asn Gin Ala 85 90 95 He Ser Arg Leu Glu Gly Leu Ser Asn Leu Tyr Gin He Tyr Ala Glu 100 105 110 Ser Phe Arg Glu Trp Glu Ala Asp Pro Thr Asn Pro Ala Leu Arg Glu 115 120 125 Glu Met Arg He Gin Phe Asn Asp Met Asn Ser Ala Leu Thr Thr Ala 130 135 140 He Pro Leu Phe Ala Val Gin Asn Tyr Gin Val Pro Leu Leu Ser Val 145 150 155 160 Tyr Val Gin Ala Ala Asn Leu His Leu ser Val Leu Arg Asp Val Ser 165 170 175 Val Phe Gly Gin Arg Trp Gly Phe Asp Ala Ala Thr He Asn Ser Arg 180 185 190 Tyr Asn Asp Leu Thr Arg Leu He Gly Asn Tyr Thr Asp Tyr Ala Val 195 200 205 Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp Gly Pro Asp Ser Arg 210 215 220 Asp Trp Val Arg Tyr Asn Gin Phe Arg Arg Glu Leu Thr Leu Thr Val 225 230 235 240 Leu Asp He Val Ala Leu Phe Pro Asn Tyr Asp Ser Arg Arg Tyr Pro 245 250 255 He Arg Thr Val Ser Gin Leu Thr Arg Glu He Tyr Thr Asn Pro Val 260 265 270 Leu Glu Asn Phe Asp Gly Ser Phe Arg Gly Ser Ala Gin Gly He Glu 275 280 285 Arg Ser He Arg ser Pro His Leu Met Asp He Leu Asn Ser He Thr 290 295 300 He Tyr Thr Asp Ala His Arg Gly Tyr Tyr Tyr Trp Ser Gly His Gin 305 310 315 320 He Met Ala Ser Pro Val Gly Phe Ser Gly Pro Glu Phe Thr Phe Pro 325 330 335 Leu Tyr Gly Thr Met Gly Asn Ala Ala Pro Gin Gin Arg He Val Ala 340 345 350 Gin Leu Gly Gin Gly Val Tyr Arg Thr Leu Ser ser Thr Leu Tyr Arg 355 360 365 Arg Pro Phe Asn He Gly He Asn Asn Gin Gin Leu Ser Val Leu Asp 370 375 380 Gly Thr Glu Phe Ala Tyr Gly Thr Ser Ser Asn Leu Pro Ser Ala Val 385 390 395 400 Tyr Arg Lys Ser Gly Thr val Asp Ser Leu Asp Glu He Pro Pro Gin 405 410 415 Asn Asn Asn Val Pro Pro Arg Gin Gly Phe ser His Arg Leu Ser His 420 425 430 Val Ser Met Phe Arg Ser Gly Phe Ser Asn Ser Ser Val Ser He He 435 440 445 Arg Ala Pro Met Phe Ser Trp He His Arg Ser Ala Glu Phe Asn Asn 450 455 460 He He Pro Ser Ser Gin He Thr Gin He Pro Leu Thr Lys Ser Thr 465 470 475 480 Asn Leu Gly Ser Gly Thr Ser Val Val Lys Gly Pro Gly Phe Thr Gly 485 490 495 Gly Asp He Leu Arg Arg Thr Ser Pro Gly Gin He Ser Thr Leu Arg 500 505 510 Val Asn He Thr Ala Pro Leu Ser Gin Arg Tyr Arg Val Arg He Arg 515 520 525 Tyr Ala Ser Thr Thr Asn Leu Gin Phe His Thr Ser He Asp Gly Arg 530 535 540 Pro He Asn Gin Gly Asn Phe Ser Ala Thr Met Ser Ser Gly Ser Asn 545 550 555 560 Leu Gin Ser Gly Ser Phe Arg Thr Val Gly Phe Thr Thr Pro Phe Asn 565 570 575 Phe Ser Asn Gly Ser Ser Val Phe Thr Leu ser Ala His Val Phe Asn 580 585 590 Ser Gly Asn Glu val Tyr He Asp Arg He Glu Phe Val Pro Ala Glu 595 600 605 Val Thr Phe Glu Ala Glu Tyr Asp Leu Glu Arg Ala Gin Lys Ala Val 610 615 620 Asn Glu Leu Phe Thr Ser Ser Asn Gin He Gly Leu Lys Thr Asp Val 625 630 635 640 Thr Asp Tyr His He Asp Arg Val ser Asn Leu Val Glu Cys Leu Ser 645 650 655 Asp Glu Phe cys Leu Asp Glu Lys Lys Glu Leu Ser Glu Lys val Lys 660 665 670 His Ala Lys Arg Leu Ser Asp Glu Arg Asn Leu Leu Gin Asp Pro Asn 675 680 685 Phe Arg Gly He Asn Arg Gin Leu Asp Arg Gly Trp Arg Gly Ser Thr 690 695 700 Asp He Thr He Gin Gly Gly Asp Asp Val Phe Lys Glu Asn Tyr Val 705 710 715 720 Thr Leu Leu Gly Thr Phe Asp Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin 725 730 735 Lys He Asp Glu Ser Lys Leu Lys Ala Tyr Thr Arg Tyr Gin Leu Arg 740 745 750 Gly Tyr He Glu Asp Ser Gin Asp Leu Glu He Tyr Leu He Arg Tyr 755 760 765 Asn Ala Lys His Glu Thr Val Asn Val Pro Gly Thr Gly Ser Leu Trp 770 775 780 Pro Leu Ser Ala Pro Ser Pro He Gly Lys Cys Ala His His Ser His 785 790 795 800 His Phe Ser Leu Asp He Asp Val Gly Cys Thr Asp Leu Asn Glu Asp 805 810 815 Leu Gly Val Trp Val He Phe Lys He Lys Thr Gin Asp Gly His Ala 820 825 830 Arg Leu Gly Asn Leu Glu Phe Leu Glu Glu Lys Pro Leu Val Gly Glu 835 840 845 Ala Leu Ala Arg Val Lys Arg Ala Glu Lys Lys Trp Arg Asp Lys Arg 850 855 860 Glu Lys Leu Glu Trp Glu Thr Asn He Val Tyr Lys Glu Ala Lys Glu 865 870 875 880 Ser Val Asp Ala Leu Phe Val Asn Ser Gin Tyr Asp Arg Leu Gin Ala 885 890 895 Asp Thr Asn He Ala Met He His Ala Ala Asp Lys Arg Val His Ser 900 905 910 He Arg Glu Ala Tyr Leu Pro Glu Leu Ser Val He Pro Gly Val Asn 915 920 925 Ala Ala He Phe Glu Glu Leu Glu Gly Arg He Phe Thr Ala Phe Ser 930 935 940 Leu Tyr Asp Ala Arg Asn Val He Lys Asn Gly Asp Phe Asn Asn Gly 945 950 955 960 Leu Ser Cys Trp Asn Val Lys Gly His Val Asp Val Glu Glu Gin Asn 965 970 975 Asn His Arg Ser Val Leu Val Val Pro Glu Trp Glu Ala Glu Val Ser 980 985 990 Gin Glu Val Arg Val Cys Pro Gly Arg Gly Tyr He Leu Arg Val Thr 995 1000 1005 Ala Tyr Lys Glu Gly Tyr Gly Glu Gly Cys Val Thr He His Glu He 1010 1015 1020 Glu Asn Asn Thr Asp Glu Leu Lys Phe Ser Asn cys Val Glu Glu Glu 1025 1030 1035 1040 Val Tyr Pro Asn Asn Thr Val Thr Cys Asn Asp Tyr Thr Ala Thr Gin 1045 1050 1055 Glu Glu Tyr Glu Gly Thr Tyr Thr Ser Arg Asn Arg Gly Tyr Asp Gly 1060 1065 1070 Ala Tyr Glu Ser Asn Ser Ser Val Pro Ala Asp Tyr Ala ser Ala Tyr 1075 1080 1085 Glu Glu Lys Ala Tyr Thr Asp Gly Arg Arg Asp Asn Pro Cys Glu Ser 1090 1095 1100 Asn Arg Gly Tyr Gly Asp Tyr Thr Pro Leu Pro Ala Gly Tyr Val Thr 1105 1110 1115 1120 Lys Glu Leu Glu Tyr Phe Pro Glu Thr Asp Lys Val Trp He Glu He 1125 1130 1135 Gly Glu Thr Glu Gly Thr Phe He Val Asp Ser Val Glu Leu Leu Leu 1140 1145 1150 Met Glu Glu 1155 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3450 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: ATGGATAACA ATCCGAACAT CAATGAATGC ATTCCTTATA ATTGTTTAAG TAACCCTGAA 60 GTAGAAGTAT TAGGTGGAGA AAGAATAGAA ACTGGTTACA CCCCAATCGA TATTTCCTTG 120 TCGCTAACGC AATTTCTTTT GAGTGAATTT GTTCCCGGTG CTGGATTTGT GTTAGGACTA 180 GTTGATATAA TATGGGGAAT TTTTGGTCCC TCTCAATGGG ACGCATTTCT TGTACAAATT 240 GAACAGTTAA TTAACCAAAG AATAGAAGAA TTCGCTAGGA ACCAAGCCAT TTCTAGATTA 300 GAAGGACTAA GCAATCTTTA TCAAATTTAC GCAGAATCTT TTAGAGAGTG GGAAGCGGAT 360 CTTAATAATG CACAATTAAG GGAAGATGTG CGTATTCGAT TTGCTAATAC AGACGACGCT 420 TTAATAACAG CAATAAATAA TTTTACACTT ACAAGTTTTG AAATCCCTCT TTTATCGGTC 480 TATGTTCAAG CGGCGAATTT ACATTTATCA CTATTAAGAG ACGCTGTATC GTTTGGGCAG 540 GGTTGGGGAC TGGATATAGC TACTGTTAAT AATCATTATA ATAGATTAAT AAATCTTATT 600 CATAGATATA CGAAACATTG TTTGGACACA TACAATCAAG GATTAGAAAA CTTAAGAGGT 660 ACTAATACTC GACAATGGGC AAGATTCAAT CAGTTTAGGA GAGATTTAAC ACTTACTGTA 720 TTAGATATCG TTGCTCTTTT TCCGAACTAC GATGTTAGAA CATATCCAAT TCAAACGTCA 780 TCCCAATTAA CAAGGGAAAT TTATACAAGT TCAGTAATTG AGGATTCTCC AGTTTCTGCT 840 AATATACCTA ATGGTTTTAA TAGGGCGGAA TTTGGAGTTA GACCGCCCCA TCTTATGGAC 900 TTTATGAATT CTTTGTTTGT AACTGCAGAG ACTGTTAGAA GTCAAACTGT GTGGGGAGGA 960 CACTTAGTTA GTTCACGAAA TACGGCTGGT AACCGTATAA ATTTCCCTAG TTACGGGGTC 1020 TTCAATCCTG GTGGCGCCAT TTGGATTGCA GATGAGGATC CACGTCCTTT TTATCGGACA 1080 TTATCAGATC CTGTTTTTGT CCGAGGAGGA TTTGGGAATC CTCATTATGT ACTGGGGCTT 1140 AGGGGAGTAG CATTTCAACA AACTGGTACG AACCACACCC GAACATTTAG AAATAGTGGG 1200 ACCATAGATT CTCTAGATGA AATCCCACCT CAGGATAATA GTGGGGCACC TTGGAATGAT 1260 TATAGTCATG TATTAAATCA TGTTACATTT GTACGATGGC CAGGTGAGAT TTCAGGAAGT 1320 GATTCATGGA GAGCTCCAAT GTTTTCTTGG ACGCACCGTA GTGCAACCCC TACAAATACA 1380 ATTGATCCGG AGAGGATTAC TCAAATACCA TTGGTAAAAG CACATACACT TCAGTCAGGT 1440 ACTACTGTTG TAAGAGGGCC CGGGTTTACG GGAGGAGATA TTCTTCGACG AACAAGTGGA 1500 GGACCATTTG CTTATACTAT TGTTAATATA AATGGGCAAT TACCCCAAAG GTATCGTGCA 1560 AGAATACGCT ATGCCTCTAC TACAAATCTA AGAATTTACG TAACGGTTGC AGGTGAACGG 1620 ATTTTTGCTG GTCAATTTAA CAAAACAATG GATACCGGTG ACCCATTAAC ATTCCAATCT 1680 TTTAGTTACG CAACTATTAA TACAGCTTTT ACATTCCCAA TGAGCCAGAG TAGTTTCACA 1740 GTAGGTGCTG ATACTTTTAG TTCAGGGAAT GAAGTTTATA TAGACAGATT TGAATTGATT 1800 CCAGTTACTG CAACATTTGA AGCAGAATAT GATTTAGAAA GAGCACAAAA GGCGGTGAAT 1860 GCGCTGTTTA CTTCTATAAA CCAAATAGGG ATAAAAACAG ATGTGACGGA TTATCATATC 1920 GATCGAGTAT CCAATTTAGT TGAGTGTTTA TCTGATGAAT TTTGTCTGGA TGAAAAAAAA 1980 GAATTGTCCG AGAAAGTCAA ACATGCGAAG CGACTTAGTG ATGAGCGGAA TTTACTTCAA 2040 GATCCAAACT TTAGAGGGAT CAATAGACAA CTAGACCGTG GCTGGAGAGG AAGTACGGAT 2100 ATTACCATCC AAGGAGGCGA TGACGTATTC AAAGAGAATT ACGTTACGCT ATTGGGTACC 2160 TTTGATGAGT GCTATCCAAC GTATTTATAT CAAAAAATAG ATGAGTCGAA ATTAAAAGCC 2220 TATACCCGTT ACCAATTAAG AGGGTATATC GAAGATAGTC AAGACTTAGA AATCTATTTA 2280 ATTCGCTACA ATGCCAAACA CGAAACAGTA AATGTGCCAG GTACGGGTTC CTTATGGCCG 2340 CTTTCAGCCC CAAGTCCAAT CGGAAAATGT GCCCATCATT CCCATCATTT CTCCTTGGAC 2 00 ATTGATGTTG GATGTACAGA CTTAAATGAG GACTTAGGTG TATGGGTGAT ATTCAAGATT 2460 AAGACGCAAG ATGGCCATGC AAGACTAGGA AATCTAGAAT TTCTCGAAGA GAAACCATTA 2520 GTAGGAGAAG CACTAGCTCG TGTGAAAAGA GCGGAGAAAA AATGGAGAGA CAAACGTGAA 2580 AAATTGGAAT GGGAAACAAA TATTGTTTAT AAAGAGGCAA AAGAATCTGT AGATGCTTTA 2640 TTTGTAAACT CTCAATATGA TAGATTACAA GCGGATACCA ACATCGCGAT GATTCATGCG 2700 GCAGATAAAC GCGTTCATAG CATTCGAGAA GCTTATCTGC CTGAGCTGTC TGTGATTCCG 2760 GGTGTCAATG CGGCTATTTT TGAAGAATTA GAAGGGCGTA TTTTCACTGC ATTCTCCCTA 2820 TATGATGCGA GAAATGTCAT TAAAAATGGT GATTTTAATA ATGGCTTATC CTGCTGGAAC 2880 GTGAAAGGGC ATGTAGATGT AGAAGAACAA AACAACCACC GTTCGGTCCT TGTTGTTCCG 2940 GAATGGGAAG CAGAAGTGTC ACAAGAAGTT CGTGTCTGTC CGGGTCGTGG CTATATCCTT 3000 CGTGTCACAG CGTACAAGGA GGGATATGGA GAAGGTTGCG TAACCATTCA TGAGATCGAG 3060 AACAATACAG ACGAACTGAA GTTTAGCAAC TGTGTAGAAG AGGAAGTATA TCCAAACAAC 3120 ACGGTAACGT GTAATGATTA TACTGCGACT CAAGAAGAAT ATGAGGGTAC GTACACTTCT 3180 CGTAATCGAG GATATGACGG AGCCTATGAA AGCAATTCTT CTGTACCAGC TGATTATGCA 3240 TCAGCCTATG AAGAAAAAGC ATATACAGAT GGACGAAGAG ACAATCCTTG TGAATCTAAC 3300 AGAGGATATG GGGATTACAC ACCACTACCA GCTGGCTATG TGACAAAAGA ATTAGAGTAC 3360 TTCCCAGAAA CCGATAAGGT ATGGATTGAG ATCGGAGAAA CGGAAGGAAC ATTCATCGTG 3420 GACAGCGTGG AATTACTTCT TATGGAGGAA 3450 (2) INFORMATION FOR SEQ ID Nθ:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1150 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single ( D ) TOPOLOGY : linear ( ii ) MOLECULE TYPE : protein ( i ) SEQUENCE DESCRIPTION : SEQ ID NO : 21 : Met Asp Asn Asn Pro Asn He Asn Glu Cys He Pro Tyr Asn Cys Leu 1 5 10 15 Ser Asn Pro Glu Val Glu Val Leu Gly Gly Glu Arg He Glu Thr Gly 20 25 30 Tyr Thr Pro He Asp He Ser Leu ser Leu Thr Gin Phe Leu Leu ser 35 40 45 Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly Leu Val Asp He He 50 55 60 Trp Gly He Phe Gly Pro Ser Gin Trp Asp Ala Phe Leu Val Gin He 65 70 75 80 Glu Gin Leu He Asn Gin Arg He Glu Glu Phe Ala Arg Asn Gin Ala 85 90 95 He Ser Arg Leu Glu Gly Leu Ser Asn Leu Tyr Gin He Tyr Ala Glu 100 105 110 Ser Phe Arg Glu Trp Glu Ala Asp Leu Asn Asn Ala Gin Leu Arg Glu 115 120 125 Asp Val Arg He Arg Phe Ala Asn Thr Asp Asp Ala Leu He Thr Ala 130 135 140 He Asn Asn Phe Thr Leu Thr Ser Phe Glu He Pro Leu Leu Ser Val 145 150 155 160 Tyr Val Gin Ala Ala Asn Leu His Leu Ser Leu Leu Arg Asp Ala Val 165 170 175 Ser Phe Gly Gin Gly Trp Gly Leu Asp He Ala Thr Val Asn Asn His 180 185 190 Tyr Asn Arg Leu He Asn Leu He His Arg Tyr Thr Lys His Cys Leu 195 200 205 Asp Thr Tyr Asn Gin Gly Leu Glu Asn Leu Arg Gly Thr Asn Thr Arg 210 215 220 Gin Trp Ala Arg Phe Asn Gin Phe Arg Arg Asp Leu Thr Leu Thr Val 225 230 235 240 Leu Asp He Val Ala Leu Phe Pro Asn Tyr Asp Val Arg Thr Tyr Pro 245 250 255 He Gin Thr Ser Ser Gin Leu Thr Arg Glu He Tyr Thr Ser Ser Val 260 265 270 He Glu Asp Ser Pro Val ser Ala Asn He Pro Asn Gly Phe Asn Arg 275 280 285 Ala Glu Phe Gly Val Arg Pro Pro His Leu Met Asp Phe Met Asn Ser 290 295 300 Leu Phe Val Thr Ala Glu Thr Val Arg Ser Gin Thr Val Trp Gly Gly 305 310 315 320 His Leu Val Ser Ser Arg Asn Thr Ala Gly Asn Arg He Asn Phe Pro 325 330 335 ser Tyr Gly Val Phe Asn Pro Gly Gly Ala He Trp He Ala Asp Glu 340 345 350 Asp Pro Arg Pro Phe Tyr Arg Thr Leu Ser Asp Pro Val Phe Val Arg 355 360 365 Gly Gly Phe Gly Asn Pro His Tyr Val Leu Gly Leu Arg Gly Val Ala 370 375 380 Phe Gin Gin Thr Gly Thr Asn His Thr Arg Thr Phe Arg Asn ser Gly 385 390 395 400 Thr He Asp Ser Leu Asp Glu He Pro Pro Gin Asp Asn Ser Gly Ala 405 410 415 Pro Trp Asn Asp Tyr Ser His Val Leu Asn His Val Thr Phe Val Arg 420 425 430 Trp Pro Gly Glu He Ser Gly Ser Asp Ser Trp Arg Ala Pro Met Phe 435 440 445 Ser Trp Thr His Arg Ser Ala Thr Pro Thr Asn Thr He Asp Pro Glu 450 455 460 Arg He Thr Gin He Pro Leu Val Lys Ala His Thr Leu Gin Ser Gly 465 470 475 480 Thr Thr Val Val Arg Gly Pro Gly Phe Thr Gly Gly Asp He Leu Arg 485 490 495 Arg Thr Ser Gly Gly Pro Phe Ala Tyr Thr He Val Asn He Asn Gly 500 505 510 Gin Leu Pro Gin Arg Tyr Arg Ala Arg He Arg Tyr Ala Ser Thr Thr 515 520 525 Asn Leu Arg He Tyr Val Thr Val Ala Gly Glu Arg He Phe Ala Gly 530 535 540 Gin Phe Asn Lys Thr Met Asp Thr Gly Asp Pro Leu Thr Phe Gin Ser 545 550 555 560 Phe ser Tyr Ala Thr He Asn Thr Ala Phe Thr Phe Pro Met Ser Gin 565 570 575 Ser Ser Phe Thr Val Gly Ala Asp Thr Phe Ser Ser Gly Asn Glu Val 580 585 590 Tyr He Asp Arg Phe Glu Leu He Pro Val Thr Ala Thr Phe Glu Ala 595 600 605 Glu Tyr Asp Leu Glu Arg Ala Gin Lys Ala Val Asn Ala Leu Phe Thr 610 615 620 Ser He Asn Gin He Gly He Lys Thr Asp Val Thr Asp Tyr His He 625 630 635 640 Asp Arg Val Ser Asn Leu Val Glu Cys Leu Ser Asp Glu Phe Cys Leu 645 650 655 Asp Glu Lys Lys Glu Leu Ser Glu Lys Val Lys His Ala Lys Arg Leu 660 665 670 Ser Asp Glu Arg Asn Leu Leu Gin Asp Pro Asn Phe Arg Gly He Asn 675 680 685 Arg Gin Leu Asp Arg Gly Trp Arg Gly. Ser Thr Asp He Thr He Gin 690 695 700 Gly Gly Asp Asp Val Phe Lys Glu Asn Tyr Val Thr Leu Leu Gly Thr 705 710 715 720 Phe Asp Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin Lys He Asp Glu Ser 725 730 735 Lys Leu Lys Ala Tyr Thr Arg Tyr Gin Leu Arg Gly Tyr He Glu Asp 740 745 750 Ser Gin Asp Leu Glu He Tyr Leu He Arg Tyr Asn Ala Lys His Glu 755 760 765 Thr Val Asn Val Pro Gly Thr Gly ser Leu Trp Pro Leu Ser Ala Pro 770 775 780 Ser Pro He Gly Lys Cys Ala His His Ser His His Phe Ser Leu Asp 785 790 795 800 He Asp val Gly Cys Thr Asp Leu Asn Glu Asp Leu Gly Val Trp Val 805 810 815 He Phe Lys He Lys Thr Gin Asp Gly His Ala Arg Leu Gly Asn Leu 820 825 830 Glu Phe Leu Glu Glu Lys Pro Leu Val Gly Glu Ala Leu Ala Arg Val 835 840 845 Lys Arg Ala Glu Lys Lys Trp Arg Asp Lys Arg Glu Lys Leu Glu Trp 850 855 860 Glu Thr Asn He Val Tyr Lys Glu Ala Lys Glu Ser Val Asp Ala Leu 865 870 875 880 Phe Val Asn Ser Gin Tyr Asp Arg Leu Gin Ala Asp Thr Asn He Ala 885 890 895 Met He His Ala Ala Asp Lys Arg Val His Ser He Arg Glu Ala Tyr 900 905 910 Leu Pro Glu Leu Ser Val He Pro Gly Val Asn Ala Ala He Phe Glu 915 920 925 Glu Leu Glu Gly Arg He Phe Thr Ala Phe Ser Leu Tyr Asp Ala Arg 930 935 940 Asn Val He Lys Asn Gly Asp Phe Asn Asn Gly Leu Ser Cys Trp Asn 945 950 955 960 Val Lys Gly His Val Asp Val Glu Glu Gin Asn Asn His Arg ser Val 965 970 975 Leu Val Val Pro Glu Trp Glu Ala Glu val Ser Gin Glu Val Arg Val 980 985 990 Cys Pro Gly Arg Gly Tyr He Leu Arg Val Thr Ala Tyr Lys Glu Gly 995 1000 1005 Tyr Gly Glu Gly Cys Val Thr He His Glu He Glu Asn Asn Thr Asp 1010 1015 1020 Glu Leu Lys Phe Ser Asn Cys Val Glu Glu Glu Val Tyr Pro Asn Asn 1025 1030 1035 1040 Thr Val Thr cys Asn Asp Tyr Thr Ala Thr Gin Glu Glu Tyr Glu Gly 1045 1050 1055 Thr Tyr Thr Ser Arg Asn Arg Gly Tyr Asp Gly Ala Tyr Glu Ser Asn 1060 1065 1070 Ser Ser Val Pro Ala Asp Tyr Ala ser Ala Tyr Glu Glu Lys Ala Tyr 1075 1080 1085 Thr Asp Gly Arg Arg Asp Asn Pro Cys Glu ser Asn Arg Gly Tyr Gly 1090 1095 1100 Asp Tyr Thr Pro Leu Pro Ala Gly Tyr Val Thr Lys Glu Leu Glu Tyr 1105 1110 1115 1120 Phe Pro Glu Thr Asp Lys Val Trp He Glu He Gly Glu Thr Glu Gly 1125 1130 1135 Thr Phe He Val Asp Ser Val Glu Leu Leu Leu Met Glu Glu 1140 1145 1150 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3444 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: ATGGAGAATA ATATTCAAAA TCAATGCGTA CCTTACAATT GTTTAAATAA TCCTGAAGTA 60 GAAATATTAA ATGAAGAAAG AAGTACTGGC AGATTACCGT TAGATATATC CTTATCGCTT 120 ACACGTTTCC TTTTGAGTGA ATTTGTTCCA GGTGTGGGAG TTGCGTTTGG ATTATTTGAT 180 TTAATATGGG GTTTTATAAC TCCTTCTGAT TGGAGCTTAT TTCTTTTACA GATTGAACAA 240 TTGATTGAGC AAAGAATAGA AACATTGGAA AGGAACCGGG CAATTACTAC ATTACGAGGG 300 TTAGCAGATA GCTATGAAAT TTATATTGAA GCACTAAGAG AGTGGGAAGC AAATCCTAAT 360 AATGCACAAT TAAGGGAAGA TGTGCGTATT CGATTTGCTA ATACAGACGA CGCTTTAATA 420 ACAGCAATAA ATAATTTTAC ACTTACAAGT TTTGAAATCC CTCTTTTATC GGTCTATGTT 480 CAAGCGGCGA ATTTACATTT ATCACTATTA AGAGACGCTG TATCGTTTGG GCAGGGTTGG 540 GGACTGGATA TAGCTACTGT TAATAATCAT TATAATAGAT TAATAAATCT TATTCATAGA 600 TATACGAAAC ATTGTTTGGA CACATACAAT CAAGGATTAG AAAACTTAAG AGGTACTAAT 660 ACTCGACAAT GGGCAAGATT CAATCAGTTT AGGAGAGATT TAACACTTAC TGTATTAGAT 720 ATCGTTGCTC TTTTTCCGAA CTACGATGTT AGAACATATC CAATTCAAAC GTCATCCCAA 780 TTAACAAGGG AAATTTATAC AAGTTCAGTA ATTGAGGATT CTCCAGTTTC TGCTAATATA 840 CCTAATGGTT TTAATAGGGC GGAATTTGGA GTTAGACCGC CCCATCTTAT GGACTTTATG 900 AATTCTTTGT TTGTAACTGC AGAGACTGTT AGAAGTCAAA CTGTGTGGGG AGGACACTTA 960 GTTAGTTCAC GAAATACGGC TGGTAACCGT ATAAATTTCC CTAGTTACGG GGTCTTCAAT 1020 CCTGGTGGCG CCATTTGGAT TGCAGATGAG GATCCACGTC CTTTTTATCG GACATTATCA 1080 GATCCTGTTT TTGTCCGAGG AGGATTTGGG AATCCTCATT ATGTACTGGG GCTTAGGGGA 1140 GTAGCATTTC AACAAACTGG TACGAACCAC ACCCGAACAT TTAGAAATAG TGGGACCATA 1200 GATTCTCTAG ATGAAATCCC ACCTCAGGAT AATAGTGGGG CACCTTGGAA TGATTATAGT 1260 CATGTATTAA ATCATGTTAC ATTTGTACGA TGGCCAGGTG AGATTTCAGG AAGTGATTCA 1320 TGGAGAGCTC CAATGTTTTC TTGGACGCAC CGTAGTGCAA CCCCTACAAA TACAATTGAT 1380 CCGGAGAGGA TTACTCAAAT ACCATTGGTA AAAGCACATA CACTTCAGTC AGGTACTACT 1440 GTTGTAAGAG GGCCCGGGTT TACGGGAGGA GATATTCTTC GACGAACAAG TGGAGGACCA 1500 TTTGCTTATA CTATTGTTAA TATAAATGGG CAATTACCCC AAAGGTATCG TGCAAGAATA 1560 CGCTATGCCT CTACTACAAA TCTAAGAATT TACGTAACGG TTGCAGGTGA ACGGATTTTT 1620 GCTGGTCAAT TTAACAAAAC AATGGATACC GGTGACCCAT TAACATTCCA ATCTTTTAGT 1680 TACGCAACTA TTAATACAGC TTTTACATTC CCAATGAGCC AGAGTAGTTT CACAGTAGGT 1740 GCTGATACTT TTAGTTCAGG GAATGAAGTT TATATAGACA GATTTGAATT GATTCCAGTT 1800 ACTGCAACAT TTGAAGCAGA ATATGATTTA GAAAGAGCAC AAAAGGCGGT GAATGCGCTG 1860 TTTACTTCTA TAAACCAAAT AGGGATAAAA ACAGATGTGA CGGATTATCA TATCGATCGA 1920 GTATCCAATT TAGTTGAGTG TTTATCTGAT GAATTTTGTC TGGATGAAAA AAAAGAATTG 1980 TCCGAGAAAG TCAAACATGC GAAGCGACTT AGTGATGAGC GGAATTTACT TCAAGATCCA 2040 AACTTTAGAG GGATCAATAG ACAACTAGAC CGTGGCTGGA GAGGAAGTAC GGATATTACC 2100 ATCCAAGGAG GCGATGACGT ATTCAAAGAG AATTACGTTA CGCTATTGGG TACCTTTGAT 2160 GAGTGCTATC CAACGTATTT ATATCAAAAA ATAGATGAGT CGAAATTAAA AGCCTATACC 2220 CGTTACCAAT TAAGAGGGTA TATCGAAGAT AGTCAAGACT TAGAAATCTA TTTAATTCGC 2280 TACAATGCCA AACACGAAAC AGTAAATGTG CCAGGTACGG GTTCCTTATG GCCGCTTTCA 2340 GCCCCAAGTC CAATCGGAAA ATGTGCCCAT CATTCCCATC ATTTCTCCTT GGACATTGAT 2400 GTTGGATGTA CAGACTTAAA TGAGGACTTA GGTGTATGGG TGATATTCAA GATTAAGACG 2460 CAAGATGGCC ATGCAAGACT AGGAAATCTA GAATTTCTCG AAGAGAAACC ATTAGTAGGA 2520 GAAGCACTAG CTCGTGTGAA AAGAGCGGAG AAAAAATGGA GAGACAAACG TGAAAAATTG 2580 GAATGGGAAA CAAATATTGT TTATAAAGAG GCAAAAGAAT CTGTAGATGC TTTATTTGTA 2640 AACTCTCAAT ATGATAGATT ACAAGCGGAT ACCAACATCG CGATGATTCA TGCGGCAGAT 2700 AAACGCGTTC ATAGCATTCG AGAAGCTTAT CTGCCTGAGC TGTCTGTGAT TCCGGGTGTC 2760 AATGCGGCTA TTTTTGAAGA ATTAGAAGGG CGTATTTTCA CTGCATTCTC CCTATATGAT 2820 GCGAGAAATG TCATTAAAAA TGGTGATTTT AATAATGGCT TATCCTGCTG GAACGTGAAA 2880 GGGCATGTAG ATGTAGAAGA ACAAAACAAC CACCGTTCGG TCCTTGTTGT TCCGGAATGG 2940 GAAGCAGAAG TGTCACAAGA AGTTCGTGTC TGTCCGGGTC GTGGCTATAT CCTTCGTGTC 3000 ACAGCGTACA AGGAGGGATA TGGAGAAGGT TGCGTAACCA TTCATGAGAT CGAGAACAAT 3060 ACAGACGAAC TGAAGTTTAG CAACTGTGTA GAAGAGGAAG TATATCCAAA CAACACGGTA 3120 ACGTGTAATG ATTATACTGC GACTCAAGAA GAATATGAGG GTACGTACAC TTCTCGTAAT 3180 CGAGGATATG ACGGAGCCTA TGAAAGCAAT TCTTCTGTAC CAGCTGATTA TGCATCAGCC 3240 TATGAAGAAA AAGCATATAC AGATGGACGA AGAGACAATC CTTGTGAATC TAACAGAGGA 3300 TATGGGGATT ACACACCACT ACCAGCTGGC TATGTGACAA AAGAATTAGA GTACTTCCCA 3360 GAAACCGATA AGGTATGGAT TGAGATCGGA GAAACGGAAG GAACATTCAT CGTGGACAGC 3420 GTGGAATTAC TTCTTATGGA GGAA 3444 [2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1148 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: Met Glu Asn Asn lie Gin Asn Gin Cys Val Pro Tyr Asn Cys Leu Asn 1 5 10 15 Asn Pro Glu Val Glu He Leu Asn Glu Glu Arg Ser Thr Gly Arg Leu 20 25 30 Pro Leu Asp lie Ser Leu Ser Leu Thr Arg Phe Leu Leu Ser Glu Phe 35 40 45 Val Pro Gly Val Gly Val Ala Phe Gly Leu Phe Asp Leu He Trp Gly 50 55 60 Phe He Thr Pro Ser Asp Trp Ser Leu Phe Leu Leu Gin He Glu Gin 65 70 75 80 Leu He Glu Gin Arg He Glu Thr Leu Glu Arg Asn Arg Ala He Thr 85 90 95 Thr Leu Arg Gly Leu Ala Asp Ser Tyr Glu He Tyr He Glu Ala Leu 100 105 110 Arg Glu Trp Glu Ala Asn Pro Asn Asn Ala Gin Leu Arg Glu Asp Val 115 120 125 Arg He Arg Phe Ala Asn Thr Asp Asp Ala Leu He Thr Ala He Asn 130 135 140 Asn Phe Thr Leu Thr Ser Phe Glu He Pro Leu Leu Ser Val Tyr Val 145 150 155 160 Gin Ala Ala Asn Leu His Leu Ser Leu Leu Arg Asp Ala Val Ser Phe 165 170 175 Gly Gin Gly Trp Gly Leu Asp He Ala Thr Val Asn Asn His Tyr Asn 180 185 190 Arg Leu He Asn Leu He His Arg Tyr Thr Lys His Cys Leu Asp Thr 195 200 205 Tyr Asn Gin Gly Leu Glu Asn Leu Arg Gly Thr Asn Thr Arg Gin Trp 210 215 220 Ala Arg Phe Asn Gin Phe Arg Arg Asp Leu Thr Leu Thr Val Leu Asp 225 230 235 240 He Val Ala Leu Phe Pro Asn Tyr Asp Val Arg Thr Tyr Pro He Gin 245 250 255 Thr Ser Ser Gin Leu Thr Arg Glu He Tyr Thr Ser ser Val He Glu 260 265 270 Asp ser Pro Val Ser Ala Asn He Pro Asn Gly Phe Asn Arg Ala Glu 275 280 285 Phe Gly Val Arg Pro Pro His Leu Met Asp Phe Met Asn Ser Leu Phe 290 295 300 Val Thr Ala Glu Thr Val Arg Ser Gin Thr Val Trp Gly Gly His Leu 305 310 315 320 Val Ser Ser Arg Asn Thr Ala Gly Asn Arg He Asn Phe Pro Ser Tyr 325 330 335 Gly Val Phe Asn Pro Gly Gly Ala He Trp He Ala Asp Glu Asp Pro 340 345 350 Arg Pro Phe Tyr Arg Thr Leu Ser Asp Pro Val Phe Val Arg Gly Gly 355 360 365 Phe Gly Asn Pro His Tyr Val Leu Gly Leu Arg Gly Val Ala Phe Gin 370 375 380 Gin Thr Gly Thr Asn His Thr Arg Thr Phe Arg Asn Ser Gly Thr He 385 390 395 400 Asp Ser Leu Asp Glu He Pro Pro Gin Asp Asn Ser Gly Ala Pro Trp 405 410 415 Asn Asp Tyr Ser His Val Leu Asn His val Thr Phe Val Arg Trp Pro 420 425 430 Gly Glu lie Ser Gly Ser Asp Ser Trp Arg Ala Pro Met Phe Ser Trp 435 440 445 Thr His Arg Ser Ala Thr Pro Thr Asn Thr He Asp Pro Glu Arg He 450 455 460 Thr Gin He Pro Leu Val Lys Ala His Thr Leu Gin Ser Gly Thr Thr 465 470 475 480 Val Val Arg Gly Pro Gly Phe Thr Gly Gly Asp He Leu Arg Arg Thr 485 490 495 Ser Gly Gly Pro Phe Ala Tyr Thr He Val Asn He Asn Gly Gin Leu 500 505 510 Pro Gin Arg Tyr Arg Ala Arg He Arg Tyr Ala ser Thr Thr Asn Leu 515 520 525 Arg He Tyr Val Thr Val Ala Gly Glu Arg He Phe Ala Gly Gin Phe 530 535 540 Asn Lys Thr Met Asp Thr Gly Asp Pro Leu Thr Phe Gin Ser Phe Ser 545 550 555 560 Tyr Ala Thr He Asn Thr Ala Phe Thr Phe Pro Met Ser Gin Ser ser 565 570 575 Phe Thr Val Gly Ala Asp Thr Phe ser ser Gly Asn Glu Val Tyr He 580 585 590 Asp Arg Phe Glu Leu He Pro Val Thr Ala Thr Phe Glu Ala Glu Tyr 595 600 605 Asp Leu Glu Arg Ala Gin Lys Ala Val Asn Ala Leu Phe Thr Ser He 610 615 620 Asn Gin He Gly He Lys Thr Asp Val Thr Asp Tyr His He Asp Arg 625 630 635 640 Val Ser Asn Leu Val Glu Cys Leu Ser Asp Glu Phe Cys Leu Asp Glu 645 650 655 Lys Lys Glu Leu Ser Glu Lys Val Lys His Ala Lys Arg Leu Ser Asp 660 665 670 Glu Arg Asn Leu Leu Gin Asp Pro Asn Phe Arg Gly He Asn Arg Gin 675 680 685 Leu Asp Arg Gly Trp Arg Gly Ser Thr Asp He Thr He Gin Gly Gly 690 695 700 Asp Asp Val Phe Lys Glu Asn Tyr Val Thr Leu Leu Gly Thr Phe Asp 705 710 715 720 Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin Lys He Asp Glu Ser Lys Leu 725 730 735 Lys Ala Tyr Thr Arg Tyr Gin Leu Arg Gly Tyr He Glu Asp Ser Gin 740 745 750 Asp Leu Glu He Tyr Leu lie Arg Tyr Asn Ala Lys His Glu Thr Val 755 760 765 Asn val Pro Gly Thr Gly ser Leu Trp Pro Leu Ser Ala Pro ser Pro 770 775 780 He Gly Lys Cys Ala His His Ser His His Phe Ser Leu Asp He Asp 785 790 795 800 Val Gly Cys Thr Asp Leu Asn Glu Asp Leu Gly Val Trp val He Phe 805 810 815 Lys He Lys Thr Gin Asp Gly His Ala Arg Leu Gly Asn Leu Glu Phe 820 825 830 Leu Glu Glu Lys Pro Leu Val Gly Glu Ala Leu Ala Arg val Lys Arg 835 840 845 Ala Glu Lys Lys Trp Arg Asp Lys Arg Glu Lys Leu Glu Trp Glu Thr 850 855 860 Asn He Val Tyr Lys Glu Ala Lys Glu Ser Val Asp Ala Leu Phe Val 865 870 875 880 Asn Ser Gin Tyr Asp Arg Leu Gin Ala Asp Thr Asn He Ala Met He 885 890 895 His Ala Ala Asp Lys Arg Val His ser He Arg Glu Ala Tyr Leu Pro 900 905 910 Glu Leu Ser Val He Pro Gly Val Asn Ala Ala He Phe Glu Glu Leu 915 920 925 Glu Gly Arg He Phe Thr Ala Phe Ser Leu Tyr Asp Ala Arg Asn Val 930 935 940 He Lys Asn Gly Asp Phe Asn Asn Gly Leu ser Cys Trp Asn Val Lys 945 950 955 960 Gly His Val Asp val Glu Glu Gin Asn Asn His Arg Ser Val Leu Val 965 970 975 Val Pro Glu Trp Glu Ala Glu Val ser Gin Glu Val Arg Val Cys Pro 980 985 990 Gly Arg Gly Tyr He Leu Arg Val Thr Ala Tyr Lys Glu Gly Tyr Gly 995 1000 1005 Glu Gly Cys Val Thr He His Glu He Glu Asn Asn Thr Asp Glu Leu 1010 1015 1020 Lys Phe Ser Asn Cys Val Glu Glu Glu Val Tyr Pro Asn Asn Thr Val 1025 1030 1035 1040 Thr Cys Asn Asp Tyr Thr Ala Thr Gin Glu Glu Tyr Glu Gly Thr Tyr 1045 1050 1055 Thr Ser Arg Asn Arg Gly Tyr Asp Gly Ala Tyr Glu Ser Asn Ser ser 1060 1065 1070 Val Pro Ala Asp Tyr Ala ser Ala Tyr Glu Glu Lys Ala Tyr Thr Asp 1075 1080 1085 Gly Arg Arg Asp Asn Pro Cys Glu Ser Asn Arg Gly Tyr Gly Asp Tyr 1090 1095 1100 Thr Pro Leu Pro Ala Gly Tyr Val Thr Lys Glu Leu Glu Tyr Phe Pro 1105 1110 1115 1120 Glu Thr Asp Lys Val Trp He Glu He Gly Glu Thr Glu Gly Thr Phe 1125 1130 1135 He Val Asp Ser Val Glu Leu Leu Leu Met Glu Glu 1140 1145 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3522 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: ATGGAAAATA ATATTCAAAA TCAATGCGTA CCTTACAATT GTTTAAATAA TCCTGAAGTA 60 GAAATACTGA ACGAAGAACG CAGCACCGGC CGCCTGCCGC TGGACATCAG CCTGAGCCTT 120 ACACGTTTCC TTTTGAGTGA ATTTGTTCCA GGTGTGGGAG TTGCGTTTGG ATTATTTGAT 180 TTAATATGGG GTTTTATAAC TCCTTCTGAT TGGAGCTTAT TTCTTTTACA GATTGAACAA 240 TTGATTGAGC AAAGAATAGA AACATTGGAA AGGAACCGGG CAATTACTAC ATTACGAGGG 300 TTAGCAGATA GCTATGAAAT TTATATTGAA GCACTAAGAG AGTGGGAAGC AAATCCTAAT 360 AATGCACAAT TAAGGGAAGA TGTGCGTATT CGATTTGCTA ATACAGACGA CGCTTTAATA 420 ACAGCAATAA ATAATTTTAC ACTTACAAGT TTTGAAATCC CTCTTTTATC GGTCTATGTT 480 CAAGCGGCGA ATTTACATTT ATCACTATTA AGAGACGCTG TATCGTTTGG GCAGGGTTGG 540 GGACTGGATA TAGCTACTGT TAATAATCAT TATAATAGAT TAATAAATCT TATTCATAGA 600 TATACGAAAC ATTGTTTGGA CACATACAAT CAAGGATTAG AAAACTTAAG AGGTACTAAT 660 ACTCGACAAT GGGCAAGATT CAATCAGTTT AGGAGAGATT TAACACTTAC TGTATTAGAT 720 ATCGTTGCTC TTTTTCCGAA CTACGATGTT AGAACATATC CAATTCAAAC GTCATCCCAA 780 TTAACAAGGG AAATTTATAC AAGTTCAGTA ATTGAGGATT CTCCAGTTTC TGCTAATATA 840 CCTAATGGTT TTAATAGGGC GGAATTTGGA GTTAGACCGC CCCATCTTAT GGACTTTATG 900 AATTCTTTGT TTGTAACTGC AGAGACTGTT AGAAGTCAAA CTGTGTGGGG AGGACACTTA 960 GTTAGTTCAC GAAATACGGC TGGTAACCGT ATAAATTTCC CTAGTTACGG GGTCTTCAAT 1020 CCTGGTGGCG CCATTTGGAT TGCAGATGAG GATCCACGTC CTTTTTATCG GACATTATCA 1080 GATCCTGTTT TTGTCCGAGG AGGATTTGGG AATCCTCATT ATGTACTGGG GCTTAGGGGA 1140 GTAGCATTTC AACAAACTGG TACGAACCAC ACCCGAACAT TTAGAAATAG TGGGACCATA 1200 GATTCTCTAG ATGAAATCCC ACCTCAGGAT AATAGTGGGG CACCTTGGAA TGATTATAGT 1260 CATGTATTAA ATCATGTTAC ATTTGTACGA TGGCCAGGTG AGATTTCAGG AAGTGATTCA 1320 TGGAGAGCTC CAATGTTTTC TTGGACGCAC CGTAGTGCAA CCCCTACAAA TACAATTGAT 1380 CCGGAGAGGA TTACTCAAAT ACCATTGGTA AAAGCACATA CACTTCAGTC AGGTACTACT 1440 GTTGTAAGAG GGCCCGGGTT TACGGGAGGA GATATTCTTC GACGAACAAG TGGAGGACCA 1500 TTTGCTTATA CTATTGTTAA TATAAATGGG CAATTACCCC AAAGGTATCG TGCAAGAATA 1560 CGCTATGCCT CTACTACAAA TCTAAGAATT TACGTAACGG TTGCAGGTGA ACGGATTTTT 1620 GCTGGTCAAT TTAACAAAAC AATGGATACC GGTGACCCAT TAACATTCCA ATCTTTTAGT 1680 TACGCAACTA TTAATACAGC TTTTACATTC CCAATGAGCC AGAGTAGTTT CACAGTAGGT 1740 GCTGATACTT TTAGTTCAGG GAATGAAGTT TATATAGACA GATTTGAATT GATTCCAGTT 1800 ACTGCAACAT TTGAAGCAGA ATATGATTTA GAAAGAGCAC AAAAGGCGGT GAATGCGCTG 1860 TTTACTTCTA TAAACCAAAT AGGGATAAAA ACAGATGTGA CGGATTATCA TATTGATCAA 1920 GTATCCAATT TAGTGGATTG TTTATCAGAT GAATTTTGTC TGGATGAAAA GCGAGAATTG 1980 TCCGAGAAAG TCAAACATGC GAAGCGACTC AGTGATGAGC GGAATTTACT TCAAGATCCA 040 AACTTCAAAG GCATCAATAG GCAACTAGAC CGTGGTTGGA GAGGAAGTAC GGATATTACC 2100 ATCCAAAGAG GAGATGACGT ATTCAAAGAA AATTATGTCA CACTACCAGG TACCTTTGAT 2160 GAGTGCTATC CAACGTATTT ATATCAAAAA ATAGATGAGT CGAAATTAAA ACCCTATACT 2220 CGTTATCAAT TAAGAGGGTA TATCGAGGAT AGTCAAGACT TAGAAATCTA TTTGATCCGC 2280 TATAATGCAA AACACGAAAC AGTAAATGTG CTAGGTACGG GTTCTTTATG GCCGCTTTCA 2340 GTCCAAAGTC CAATCAGAAA GTGTGGAGAA CCGAATCGAT GCGCGCCACA CCTTGAATGG 2400 AATCCTGATC TAGATTGTTC CTGCAGAGAC GGGGAAAAAT GTGCACATCA TTCGCATCAT 2460 TTCTCCTTGG ACATTGATGT TGGATGTACA GACTTAAATG AGGACTTAGA TGTATGGGTG 2520 ATATTCAAGA TTAAGACGCA AGATGGCCAT GCAAGACTAG GAAATCTAGA GTTTCTCGAA 2580 GAGAAACCAT TAGTCGGGGA AGCACTAGCT CGTGTGAAAA GAGCAGAGAA AAAATGGAGA 2640 GATAAACGTG AAAAATTGGA ATTGGAAACA AATATTGTTT ATAAAGAGGC AAAAGAATCT 2700 GTAGATGCTT TATTTGTAAA CTCTCAATAT GATCAATTAC AAGCGGATAC GAATATTGCC 2760 ATGATTCATG CGGCAGATAA ACGTGTTCAT AGAATTCGGG AAGCGTATCT TCCAGAGTTA 2820 TCTGTGATTC CGGGTGTAAA TGTAGACATT TTCGAAGAAT TAAAAGGGCG TATTTTCACT 2880 GCATTCTTCC TATATGATGC GAGAAATGTC ATTAAAAACG GTGATTTCAA TAATGGCTTA 2940 TCATGCTGGA ACGTGAAAGG GCATGTAGAT GTAGAAGAAC AAAACAACCA CCGTTCGGTC 3000 CTTGTTGTTC CGGAATGGGA AGCAGAAGTG TCACAAGAAG TTCGTGTCTG TCCGGGTCGT 3060 GGCTATATCC TTCGTGTCAC AGCGTACAAG GAGGGATATG GAGAAGGTTG CGTAACCATT 3120 CATGAGATCG AGAACAATAC AGACGAACTG AAGTTTAGCA ACTGCGTAGA AGAGGAAGTC 3180 TATCCAAACA ACACGGTAAC GTGTAATGAT TATACTGCAA ATCAAGAAGA ATACGGGGGT 32 0 GCGTACACTT CCCGTAATCG TGGATATGAC GAAACTTATG GAAGCAATTC TTCTGTACCA 3300 GCTGATTATG CGTCAGTCTA TGAAGAAAAA TCGTATACAG ATGGACGAAG AGACAATCCT 3360 TGTGAATCTA ACAGAGGATA TGGGGATTAC ACACCACTAC CAGCTGGCTA TGTGACAAAA 3420 GAATTAGAGT ACTTCCCAGA AACCGATAAG GTATGGATTG AGATCGGAGA AACGGAAGGA 3480 ACATTCATCG TGGACAGCGT GGAATTACTC CTTATGGAGG AA 3522 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1174 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: Met Glu Asn Asn He Gin Asn Gin cys Val Pro Tyr Asn cys Leu Asn 1 5 10 15 Asn Pro Glu Val Glu lie Leu Asn Glu Glu Arg Ser Thr Gly Arg Leu 20 25 30 Pro Leu Asp lie Ser Leu Ser Leu Thr Arg Phe Leu Leu Ser Glu Phe 35 40 45 Val Pro Gly Val Gly Val Ala Phe Gly Leu Phe Asp Leu He Trp Gly 50 55 60 Phe He Thr Pro Ser Asp Trp Ser Leu Phe Leu Leu Gin He Glu Gin 65 70 75 80 Leu He Glu Gin Arg He Glu Thr Leu Glu Arg Asn Arg Ala He Thr 85 90 95 Thr Leu Arg Gly Leu Ala Asp Ser Tyr Glu He Tyr He Glu Ala Leu 100 105 110 Arg Glu Trp Glu Ala Asn Pro Asn Asn Ala Gin Leu Arg Glu Asp Val 115 120 125 Arg He Arg Phe Ala Asn Thr Asp Asp Ala Leu He Thr Ala He Asn 130 135 140 Asn Phe Thr Leu Thr ser Phe Glu He Pro Leu Leu Ser Val Tyr Val 145 150 155 160 Gin Ala Ala Asn Leu His Leu Ser Leu Leu Arg Asp Ala Val Ser Phe 165 170 175 Gly Gin Gly Trp Gly Leu Asp He Ala Thr Val Asn Asn His Tyr Asn 180 185 190 Arg Leu He Asn Leu He His Arg Tyr Thr Lys His Cys Leu Asp Thr 195 200 205 Tyr Asn Gin Gly Leu Glu Asn Leu Arg Gly Thr Asn Thr Arg Gin Trp 210 215 220 Ala Arg Phe Asn Gin Phe Arg Arg Asp Leu Thr Leu Thr Val Leu Asp 225 230 235 240 He Val Ala Leu Phe Pro Asn Tyr Asp Val Arg Thr Tyr Pro He Gin 245 250 255 Thr Ser Ser Gin Leu Thr Arg Glu He Tyr Thr Ser Ser Val He Glu 260 265 270 Asp Ser Pro Val Ser Ala Asn He Pro Asn Gly Phe Asn Arg Ala Glu 275 280 285 Phe Gly Val Arg Pro Pro His Leu Met Asp Phe Met Asn Ser Leu Phe 290 295 300 Val Thr Ala Glu Thr Val Arg Ser Gin Thr Val Trp Gly Gly His Leu 305 310 315 320 Val Ser Ser Arg Asn Thr Ala Gly Asn Arg He Asn Phe Pro Ser Tyr 325 330 335 Gly Val Phe Asn Pro Gly Gly Ala He Trp He Ala Asp Glu Asp Pro 340 345 350 Arg Pro Phe Tyr Arg Thr Leu ser Asp Pro Val Phe Val Arg Gly Gly 355 360 365 Phe Gly Asn Pro His Tyr Val Leu Gly Leu Arg Gly Val Ala Phe Gin 370 375 380 Gin Thr Gly Thr Asn His Thr Arg Thr Phe Arg Asn Ser Gly Thr lie 385 390 395 400 Asp Ser Leu Asp Glu He Pro Pro Gin Asp Asn Ser Gly Ala Pro Trp 405 410 415 Asn Asp Tyr Ser His Val Leu Asn His Val Thr Phe Val Arg Trp Pro 420 425 430 Gly Glu He Ser Gly Ser Asp Ser Trp Arg Ala Pro Met Phe Ser Trp 435 440 445 Thr His Arg Ser Ala Thr Pro Thr Asn Thr He Asp Pro Glu Arg He 450 455 460 Thr Gin He Pro Leu Val Lys Ala His Thr Leu Gin Ser Gly Thr Thr 465 470 475 480 Val Val Arg Gly Pro Gly Phe Thr Gly Gly Asp He Leu Arg Arg Thr 485 490 495 Ser Gly Gly Pro Phe Ala Tyr Thr He Val Asn lie Asn Gly Gin Leu 500 505 510 Pro Gin Arg Tyr Arg Ala Arg He Arg Tyr Ala Ser Thr Thr Asn Leu 515 520 525 Arg He Tyr Val Thr Val Ala Gly Glu Arg He Phe Ala Gly Gin Phe 530 535 540 Asn Lys Thr Met Asp Thr Gly Asp Pro Leu Thr Phe Gin Ser Phe Ser 545 550 555 560 Tyr Ala Thr He Asn Thr Ala Phe Thr Phe Pro Met Ser Gin Ser Ser 565 570 575 Phe Thr Val Gly Ala Asp Thr Phe Ser Ser Gly Asn Glu Val Tyr He 580 585 590 Asp Arg Phe Glu Leu He Pro Val Thr Ala Thr Phe Glu Ala Glu Tyr 595 600 605 Asp Leu Glu Arg Ala Gin Lys Ala Val Asn Ala Leu Phe Thr Ser He 610 615 620 Asn Gin He Gly lie Lys Thr Asp Val Thr Asp Tyr His lie Asp Gin 625 630 635 640 Val Ser Asn Leu Val Asp cys Leu Ser Asp Glu Phe Cys Leu Asp Glu 645 650 655 Lys Arg Glu Leu Ser Glu Lys Val Lys His Ala Lys Arg Leu Ser Asp 660 665 670 Glu Arg Asn Leu Leu Gin Asp Pro Asn Phe Lys Gly He Asn Arg Gin 675 680 685 Leu Asp Arg Gly Trp Arg Gly ser Thr Asp He Thr He Gin Arg Gly 690 695 700 Asp Asp Val Phe Lys Glu Asn Tyr Val Thr Leu Pro Gly Thr Phe Asp 705 710 715 720 Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin Lys He Asp Glu Ser Lys Leu 725 730 735 Lys Pro Tyr Thr Arg Tyr Gin Leu Arg Gly Tyr He Glu Asp Ser Gin 740 745 750 Asp Leu Glu He Tyr Leu He Arg Tyr Asn Ala Lys His Glu Thr Val 755 760 765 Asn Val Leu Gly Thr Gly ser Leu Trp Pro Leu Ser Val Gin Ser Pro 770 775 780 He Arg Lys Cys Gly Glu Pro Asn Arg Cys Ala Pro His Leu Glu Trp 785 790 795 800 Asn Pro Asp Leu Asp Cys Ser Cys Arg Asp Gly Glu Lys Cys Ala His 805 810 815 His ser His His Phe Ser Leu Asp He Asp Val Gly Cys Thr Asp Leu 820 825 830 Asn Glu Asp Leu Asp Val Trp Val He Phe Lys He Lys Thr Gin Asp 835 840 845 Gly His Ala Arg Leu Gly Asn Leu Glu Phe Leu Glu Glu Lys Pro Leu 850 855 860 Val Gly Glu Ala Leu Ala Arg Val Lys Arg Ala Glu Lys Lys Trp Arg 865 870 875 880 Asp Lys Arg Glu Lys Leu Glu Leu Glu Thr Asn He Val Tyr Lys Glu 885 890 895 Ala Lys Glu Ser Val Asp Ala Leu Phe Val Asn Ser Gin Tyr Asp Gin 900 905 910 Leu Gin Ala Asp Thr Asn He Ala Met He His Ala Ala Asp Lys Arg 915 920 925 Val His Arg He Arg Glu Ala Tyr Leu Pro Glu Leu ser Val He Pro 930 935 940 Gly Val Asn Val Asp He Phe Glu Glu Leu Lys Gly Arg He Phe Thr 945 950 955 960 Ala Phe Phe Leu Tyr Asp Ala Arg Asn Val He Lys Asn Gly Asp Phe 965 970 975 Asn Asn Gly Leu Ser Cys Trp Asn Val Lys Gly His Val Asp Val Glu 980 985 990 Glu Gin Asn Asn His Arg Ser Val Leu Val Val Pro Glu Trp Glu Ala 995 1000 1005 Glu Val Ser Gin Glu Val Arg Val Cys Pro Gly Arg Gly Tyr He Leu 1010 1015 1020 Arg Val Thr Ala Tyr Lys Glu Gly Tyr Gly Glu Gly Cys Val Thr He 1025 1030 1035 1040 His Glu He Glu Asn Asn Thr Asp Glu Leu Lys Phe Ser Asn Cys Val 1045 1050 1055 Glu Glu Glu Val Tyr Pro Asn Asn Thr Val Thr cys Asn Asp Tyr Thr 1060 1065 1070 Ala Asn Gin Glu Glu Tyr Gly Gly Ala Tyr Thr Ser Arg Asn Arg Gly 1075 1080 1085 Tyr Asp Glu Thr Tyr Gly Ser Asn Ser ser Val Pro Ala Asp Tyr Ala 1090 1095 1100 Ser Val Tyr Glu Glu Lys Ser Tyr Thr Asp Gly Arg Arg Asp Asn Pro 1105 1110 1115 1120 Cys Glu ser Asn Arg Gly Tyr Gly Asp Tyr Thr Pro Leu Pro Ala Gly 1125 1130 1135 Tyr Val Thr Lys Glu Leu Glu Tyr Phe Pro Glu Thr Asp Lys Val Trp 1140 1145 1150 He Glu He Gly Glu Thr Glu Gly Thr Phe He Val Asp Ser Val Glu 1155 1160 1165 Leu Leu Leu Met Glu Glu 1170 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3444 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: ATGGAAAATA ATATTCAAAA TCAATGCGTA CCTTACAATT GTTTAAATAA TCCTGAAGTA 60 GAAATACTGA ACGAAGAACG CAGCACCGGC CGCCTGCCGC TGGACATCAG CCTGAGCCTT 120 ACACGTTTCC TTTTGAGTGA ATTTGTTCCA GGTGTGGGAG TTGCGTTTGG ATTATTTGAT 180 TTAATATGGG GTTTTATAAC TCCTTCTGAT TGGAGCTTAT TTCTTTTACA GATTGAACAA 240 TTGATTGAGC AAAGAATAGA AACATTGGAA AGGAACCGGG CAATTACTAC ATTACGAGGG 300 TTAGCAGATA GCTATGAAAT TTATATTGAA GCACTAAGAG AGTGGGAAGC AAATCCTAAT 360 AATGCACAAT TAAGGGAAGA TGTGCGTATT CGATTTGCTA ATACAGACGA CGCTTTAATA 420 ACAGCAATAA ATAATTTTAC ACTTACAAGT TTTGAAATCC CTCTTTTATC GGTCTATGTT 480 CAAGCGGCGA ATTTACATTT ATCACTATTA AGAGACGCTG TATCGTTTGG GCAGGGTTGG 540 GGACTGGATA TAGCTACTGT TAATAATCAT TATAATAGAT TAATAAATCT TATTCATAGA 600 TATACGAAAC ATTGTTTGGA CACATACAAT CAAGGATTAG AAAACTTAAG AGGTACTAAT 660 ACTCGACAAT GGGCAAGATT CAATCAGTTT AGGAGAGATT TAACACTTAC TGTATTAGAT 720 ATCGTTGCTC TTTTTCCGAA CTACGATGTT AGAACATATC CAATTCAAAC GTCATCCCAA 780 TTAACAAGGG AAATTTATAC AAGTTCAGTA ATTGAGGATT CTCCAGTTTC TGCTAATATA 8 0 CCTAATGGTT TTAATAGGGC GGAATTTGGA GTTAGACCGC CCCATCTTAT GGACTTTATG 900 AATTCTTTGT TTGTAACTGC AGAGACTGTT AGAAGTCAAA CTGTGTGGGG AGGACACTTA 960 GTTAGTTCAC GAAATACGGC TGGTAACCGT ATAAATTTCC CTAGTTACGG GGTCTTCAAT 1020 CCTGGTGGCG CCATTTGGAT TGCAGATGAG GATCCACGTC CTTTTTATCG GACATTATCA 1080 GATCCTGTTT TTGTCCGAGG AGGATTTGGG AATCCTCATT ATGTACTGGG GCTTAGGGGA 1140 GTAGCATTTC AACAAACTGG TACGAACCAC ACCCGAACAT TTAGAAATAG TGGGACCATA 1200 GATTCTCTAG ATGAAATCCC ACCTCAGGAT AATAGTGGGG CACCTTGGAA TGATTATAGT 1260 CATGTATTAA ATCATGTTAC ATTTGTACGA TGGCCAGGTG AGATTTCAGG AAGTGATTCA 1320 TGGAGAGCTC CAATGTTTTC TTGGACGCAC CGTAGTGCAA CCCCTACAAA TACAATTGAT 1380 CCGGAGAGGA TTACTCAAAT ACCATTGGTA AAAGCACATA CACTTCAGTC AGGTACTACT 1440 GTTGTAAGAG GGCCCGGGTT TACGGGAGGA GATATTCTTC GACGAACAAG TGGAGGACCA 1500 TTTGCTTATA CTATTGTTAA TATAAATGGG CAATTACCCC AAAGGTATCG TGCAAGAATA 1560 CGCTATGCCT CTACTACAAA TCTAAGAATT TACGTAACGG TTGCAGGTGA ACGGATTTTT 1620 GCTGGTCAAT TTAACAAAAC AATGGATACC GGTGACCCAT TAACATTCCA ATCTTTTAGT 1680 TACGCAACTA TTAATACAGC TTTTACATTC CCAATGAGCC AGAGTAGTTT CACAGTAGGT 1740 GCTGATACTT TTAGTTCAGG GAATGAAGTT TATATAGACA GATTTGAATT GATTCCAGTT 1800 ACTGCAACAT TTGAAGCAGA ATATGATTTA GAAAGAGCAC AAAAGGCGGT GAATGCGCTG 1860 TTTACTTCTA TAAACCAAAT AGGGATAAAA ACAGATGTGA CGGATTATCA TATCGATCGA 1920 GTATCCAATT TAGTTGAGTG TTTATCTGAT GAATTTTGTC TGGATGAAAA AAAAGAATTG 1980 TCCGAGAAAG TCAAACATGC GAAGCGACTT AGTGATGAGC GGAATTTACT TCAAGATCCA 2040 AACTTTAGAG GGATCAATAG ACAACTAGAC CGTGGCTGGA GAGGAAGTAC GGATATTACC 2100 ATCCAAGGAG GCGATGACGT ATTCAAAGAG AATTACGTTA CGCTATTGGG TACCTTTGAT 2160 GAGTGCTATC CAACGTATTT ATATCAAAAA ATAGATGAGT CGAAATTAAA AGCCTATACC 2220 CGTTACCAAT TAAGAGGGTA TATCGAAGAT AGTCAAGACT TAGAAATCTA TTTAATTCGC 2280 TACAATGCCA AACACGAAAC AGTAAATGTG CCAGGTACGG GTTCCTTATG GCCGCTTTCA 2340 GCCCCAAGTC CAATCGGAAA ATGTGCCCAT CATTCCCATC ATTTCTCCTT GGACATTGAT 2400 GTTGGATGTA CAGACTTAAA TGAGGACTTA GGTGTATGGG TGATATTCAA GATTAAGACG 2460 CAAGATGGCC ATGCAAGACT AGGAAATCTA GAATTTCTCG AAGAGAAACC ATTAGTAGGA 2520 GAAGCACTAG CTCGTGTGAA AAGAGCGGAG AAAAAATGGA GAGACAAACG TGAAAAATTG 2580 GAATGGGAAA CAAATATTGT TTATAAAGAG GCAAAAGAAT CTGTAGATGC TTTATTTGTA 2640 AACTCTCAAT ATGATAGATT ACAAGCGGAT ACCAACATCG CGATGATTCA TGCGGCAGAT 2700 AAACGCGTTC ATAGCATTCG AGAAGCTTAT CTGCCTGAGC TGTCTGTGAT TCCGGGTGTC 2760 AATGCGGCTA TTTTTGAAGA ATTAGAAGGG CGTATTTTCA CTGCATTCTC CCTATATGAT 2820 GCGAGAAATG TCATTAAAAA TGGTGATTTT AATAATGGCT TATCCTGCTG GAACGTGAAA 2880 GGGCATGTAG ATGTAGAAGA ACAAAACAAC CACCGTTCGG TCCTTGTTGT TCCGGAATGG 2940 GAAGCAGAAG TGTCACAAGA AGTTCGTGTC TGTCCGGGTC GTGGCTATAT CCTTCGTGTC 3000 ACAGCGTACA AGGAGGGATA TGGAGAAGGT TGCGTAACCA TTCATGAGAT CGAGAACAAT 3060 ACAGACGAAC TGAAGTTTAG CAACTGTGTA GAAGAGGAAG TATATCCAAA CAACACGGTA 3120 ACGTGTAATG ATTATACTGC GACTCAAGAA GAATATGAGG GTACGTACAC TTCTCGTAAT 3180 CGAGGATATG ACGGAGCCTA TGAAAGCAAT TCTTCTGTAC CAGCTGATTA TGCATCAGCC 3240 TATGAAGAAA AAGCATATAC AGATGGACGA AGAGACAATC CTTGTGAATC TAACAGAGGA 3300 TATGGGGATT ACACACCACT ACCAGCTGGC TATGTGACAA AAGAATTAGA GTACTTCCCA 3360 GAAACCGATA AGGTATGGAT TGAGATCGGA GAAACGGAAG GAACATTCAT CGTGGACAGC 3420 GTGGAATTAC TTCTTATGGA GGAA 3444 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1148 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: Met Glu Asn Asn He Gin Asn Gin Cys Val Pro Tyr Asn Cys Leu Asn 1 5 10 15 Asn Pro Glu Val Glu He Leu Asn Glu Glu Arg Ser Thr Gly Arg Leu 20 25 30 Pro Leu Asp He Ser Leu Ser Leu Thr Arg Phe Leu Leu Ser Glu Phe 35 40 45 Val Pro Gly Val Gly Val Ala Phe Gly Leu Phe Asp Leu He Trp Gly 50 55 60 Phe He Thr Pro Ser Asp Trp ser Leu Phe Leu Leu Gin He Glu Gin 65 70 75 80 Leu He Glu Gin Arg He Glu Thr Leu Glu Arg Asn Arg Ala He Thr 85 90 95 Thr Leu Arg Gly Leu Ala Asp Ser Tyr Glu He Tyr He Glu Ala Leu 100 105 110 Arg Glu Trp Glu Ala Asn Pro Asn Asn Ala Gin Leu Arg Glu Asp Val 115 120 125 Arg He Arg Phe Ala Asn Thr Asp Asp Ala Leu He Thr Ala He Asn 130 135 140 Asn Phe Thr Leu Thr Ser Phe Glu lie Pro Leu Leu Ser Val Tyr Val 145 150 155 160 Gin Ala Ala Asn Leu His Leu Ser Leu Leu Arg Asp Ala Val Ser Phe 165 170 175 Gly Gin Gly Trp Gly Leu Asp He Ala Thr Val Asn Asn His Tyr Asn 180 185 190 Arg Leu He Asn Leu He His Arg Tyr Thr Lys His Cys Leu Asp Thr 195 200 205 Tyr Asn Gin Gly Leu Glu Asn Leu Arg Gly Thr Asn Thr Arg Gin Trp 210 215 220 Ala Arg Phe Asn Gin Phe Arg Arg Asp Leu Thr Leu Thr Val Leu Asp 225 230 235 240 He Val Ala Leu Phe Pro Asn Tyr Asp Val Arg Thr Tyr Pro He Gin 245 250 255 Thr Ser ser Gin Leu Thr Arg Glu He Tyr Thr Ser Ser Val He Glu 260 265 270 Asp Ser Pro val Ser Ala Asn He Pro Asn Gly Phe Asn Arg Ala Glu 275 280 285 Phe Gly Val Arg Pro Pro His Leu Met Asp Phe Met Asn Ser Leu Phe 290 295 300 Val Thr Ala Glu Thr Val Arg Ser Gin Thr Val Trp Gly Gly His Leu 305 310 315 320 Val Ser Ser Arg Asn Thr Ala Gly Asn Arg He Asn Phe Pro Ser Tyr 325 330 335 Gly Val Phe Asn Pro Gly Gly Ala He Trp He Ala Asp Glu Asp Pro 340 345 350 Arg Pro Phe Tyr Arg Thr Leu Ser Asp Pro Val Phe Val Arg Gly Gly 355 360 365 Phe Gly Asn Pro His Tyr Val Leu Gly Leu Arg Gly Val Ala Phe Gin 370 375 380 Gin Thr Gly Thr Asn His Thr Arg Thr Phe Arg Asn Ser Gly Thr He 385 390 395 400 Asp Ser Leu Asp Glu He Pro Pro Gin Asp Asn Ser Gly Ala Pro Trp 405 410 415 Asn Asp Tyr Ser His Val Leu Asn His Val Thr Phe Val Arg Trp Pro 420 425 430 Gly Glu He Ser Gly Ser Asp Ser Trp Arg Ala Pro Met Phe Ser Trp 435 440 445 Thr His Arg Ser Ala Thr Pro Thr Asn Thr He Asp Pro Glu Arg He 450 455 460 Thr Gin He Pro Leu Val Lys Ala His Thr Leu Gin ser Gly Thr Thr 465 470 475 480 Val Val Arg Gly Pro Gly Phe Thr Gly Gly Asp He Leu Arg Arg Thr 485 490 495 Ser Gly Gly Pro Phe Ala Tyr Thr He Val Asn He Asn Gly Gin Leu 500 505 510 Pro Gin Arg Tyr Arg Ala Arg He Arg Tyr Ala Ser Thr Thr Asn Leu 515 520 525 Arg He Tyr Val Thr Val Ala Gly Glu Arg He Phe Ala Gly Gin Phe 530 535 540 Asn Lys Thr Met Asp Thr Gly Asp Pro Leu Thr Phe Gin Ser Phe Ser 545 550 555 560 Tyr Ala Thr He Asn Thr Ala Phe Thr Phe Pro Met Ser Gin Ser Ser 565 570 575 Phe Thr Val Gly Ala Asp Thr Phe Ser Ser Gly Asn Glu Val Tyr He 580 585 590 Asp Arg Phe Glu Leu He Pro Val Thr Ala Thr Phe Glu Ala Glu Tyr 595 600 605 Asp Leu Glu Arg Ala Gin Lys Ala Val Asn Ala Leu Phe Thr Ser He 610 615 620 Asn Gin He Gly He Lys Thr Asp Val Thr Asp Tyr His He Asp Arg 625 630 635 640 Val Ser Asn Leu Val Glu Cys Leu ser Asp Glu Phe cys Leu Asp Glu 645 650 655 Lys Lys Glu Leu Ser Glu Lys Val Lys His Ala Lys Arg Leu Ser Asp 660 665 670 Glu Arg Asn Leu Leu Gin Asp Pro Asn Phe Arg Gly He Asn Arg Gin 675 680 685 Leu Asp Arg Gly Trp Arg Gly ser Thr Asp He Thr He Gin Gly Gly 690 695 700 Asp Asp Val Phe Lys Glu Asn Tyr Val Thr Leu Leu Gly Thr Phe Asp 705 710 715 720 Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin Lys He Asp Glu Ser Lys Leu 725 730 735 Lys Ala Tyr Thr Arg Tyr Gin Leu Arg Gly Tyr He Glu Asp Ser Gin 740 745 750 Asp Leu Glu He Tyr Leu He Arg Tyr Asn Ala Lys His Glu Thr Val 755 760 765 Asn Val Pro Gly Thr Gly ser Leu Trp Pro Leu Ser Ala Pro Ser Pro 770 775 780 He Gly Lys Cys Ala His His Ser His His Phe Ser Leu Asp He Asp 785 790 795 800 Val Gly Cys Thr Asp Leu Asn Glu Asp Leu Gly Val Trp Val He Phe 805 810 815 Lys He Lys Thr Gin Asp Gly His Ala Arg Leu Gly Asn Leu Glu Phe 820 825 830 Leu Glu Glu Lys Pro Leu Val Gly Glu Ala Leu Ala Arg Val Lys Arg 835 840 845 Ala Glu Lys Lys Trp Arg Asp Lys Arg Glu Lys Leu Glu Trp Glu Thr 850 855 860 Asn He Val Tyr Lys Glu Ala Lys Glu Ser Val Asp Ala Leu Phe Val 865 870 875 880 Asn ser Gin Tyr Asp Arg Leu Gin Ala Asp Thr Asn He Ala Met He 885 890 895 His Ala Ala Asp Lys Arg Val His Ser He Arg Glu Ala Tyr Leu Pro 900 905 910 Glu Leu Ser Val He Pro Gly Val Asn Ala Ala He Phe Glu Glu Leu 915 920 925 Glu Gly Arg He Phe Thr Ala Phe Ser Leu Tyr Asp Ala Arg Asn Val 930 935 940 He Lys Asn Gly Asp Phe Asn Asn Gly Leu Ser Cys Trp Asn Val Lys 945 950 955 960 Gly His Val Asp Val Glu Glu Gin Asn Asn His Arg Ser Val Leu Val 965 970 975 Val Pro Glu Trp Glu Ala Glu Val Ser Gin Glu Val Arg Val Cys Pro 980 985 990 Gly Arg Gly Tyr He Leu Arg Val Thr Ala Tyr Lys Glu Gly Tyr Gly 995 1000 1005 Glu Gly Cys Val Thr He His Glu He Glu Asn Asn Thr Asp Glu Leu 1010 1015 1020 Lys Phe Ser Asn cys Val Glu Glu Glu Val Tyr Pro Asn Asn Thr Val 1025 1030 1035 1040 Thr Cys Asn Asp Tyr Thr Ala Thr Gin Glu Glu Tyr Glu Gly Thr Tyr 1045 1050 1055 Thr Ser Arg Asn Arg Gly Tyr Asp Gly Ala Tyr Glu ser Asn Ser ser 1060 1065 1070 Val Pro Ala Asp Tyr Ala Ser Ala Tyr Glu Glu Lys Ala Tyr Thr Asp 1075 1080 1085 Gly Arg Arg Asp Asn Pro Cys Glu Ser Asn Arg Gly Tyr Gly Asp Tyr 1090 1095 1100 Thr Pro Leu Pro Ala Gly Tyr Val Thr Lys Glu Leu Glu Tyr Phe Pro 1105 1110 1115 1120 Glu Thr Asp Lys Val Trp He Glu He Gly Glu Thr Glu Gly Thr Phe 1125 1130 1135 He Val Asp Ser Val Glu Leu Leu Leu Met Glu Glu 1140 1145 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3522 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: ATGGAAAATA ATATTCAAAA TCAATGCGTA CCTTACAATT GTTTAAATAA TCCTGAAGTA 60 GAAATACTGA ACGAAGAACG CAGCACCGGC CGCCTGCCGC TGGACATCAG CCTGAGCCTT 120 ACACGTTTCC TTTTGAGTGA ATTTGTTCCA GGTGTGGGAG TTGCGTTTGG ATTATTTGAT 180 TTAATATGGG GTTTTATAAC TCCTTCTGAT TGGAGCTTAT TTCTTTTACA GATTGAACAA 240 TTGATTGAGC AAAGAATAGA AACATTGGAA AGGAACCGGG CAATTACTAC ATTACGAGGG 300 TTAGCAGATA GCTATGAAAT TTATATTGAA GCACTAAGAG AGTGGGAAGC AAATCCTAAT 360 AATGCACAAT TAAGGGAAGA TGTGCGTATT CGATTTGCTA ATACAGACGA CGCTTTAATA 420 ACAGCAATAA ATAATTTTAC ACTTACAAGT TTTGAAATCC CTCTTTTATC GGTCTATGTT 480 CAAGCGGCGA ATTTACATTT ATCACTATTA AGAGACGCTG TATCGTTTGG GCAGGGTTGG 5 0 GGACTGGATA TAGCTACTGT TAATAATCAT TATAATAGAT TAATAAATCT TATTCATAGA 600 TATACGAAAC ATTGTTTGGA CACATACAAT CAAGGATTAG AAAACTTAAG AGGTACTAAT 660 ACTCGACAAT GGGCAAGATT CAATCAGTTT AGGAGAGATT TAACACTTAC TGTATTAGAT 720 ATCGTTGCTC TTTTTCCGAA CTACGATGTT AGAACATATC CAATTCAAAC GTCATCCCAA 780 TTAACAAGGG AAATTTATAC AAGTTCAGTA ATTGAGGATT CTCCAGTTTC TGCTAATATA 840 CCTAATGGTT TTAATAGGGC GGAATTTGGA GTTAGACCGC CCCATCTTAT GGACTTTATG 900 AATTCTTTGT TTGTAACTGC AGAGACTGTT AGAAGTCAAA CTGTGTGGGG AGGACACTTA 960 GTTAGTTCAC GAAATACGGC TGGTAACCGT ATAAATTTCC CTAGTTACGG GGTCTTCAAT 1020 CCTGGTGGCG CCATTTGGAT TGCAGATGAG GATCCACGTC CTTTTTATCG GACATTATCA 1080 GATCCTGTTT TTGTCCGAGG AGGATTTGGG AATCCTCATT ATGTACTGGG GCTTAGGGGA 1140 GTAGCATTTC AACAAACTGG TACGAACCAC ACCCGAACAT TTAGAAATAG TGGGACCATA 1200 GATTCTCTAG ATGAAATCCC ACCTCAGGAT AATAGTGGGG CACCTTGGAA TGATTATAGT 1260 CATGTATTAA ATCATGTTAC ATTTGTACGA TGGCCAGGTG AGATTTCAGG AAGTGATTCA 1320 TGGAGAGCTC CAATGTTTTC TTGGACGCAC CGTAGTGCAA CCCCTACAAA TACAATTGAT 1380 CCGGAGAGGA TTACTCAAAT ACCATTGGTA AAAGCACATA CACTTCAGTC AGGTACTACT 1440 GTTGTAAGAG GGCCCGGGTT TACGGGAGGA GATATTCTTC GACGAACAAG TGGAGGACCA 1500 TTTGCTTATA CTATTGTTAA TATAAATGGG CAATTACCCC AAAGGTATCG TGCAAGAATA 1560 CGCTATGCCT CTACTACAAA TCTAAGAATT TACGTAACGG TTGCAGGTGA ACGGATTTTT 1620 GCTGGTCAAT TTAACAAAAC AATGGATACC GGTGACCCAT TAACATTCCA ATCTTTTAGT 1680 TACGCAACTA TTAATACAGC TTTTACATTC CCAATGAGCC AGAGTAGTTT CACAGTAGGT 1740 GCTGATACTT TTAGTTCAGG GAATGAAGTT TATATAGACA GATTTGAATT GATTCCAGTT 1800 ACTGCAACAT TTGAAGCAGA ATATGATTTA GAAAGAGCAC AAAAGGCGGT GAATGCGCTG 1860 TTTACTTCTA TAAACCAAAT AGGGATAAAA ACAGATGTGA CGGATTATCA TATCGATCGA 1920 GTGTCCAATT TAGTTACGTA TTTATCGGAT GAATTTTGTC TGGATGAAAA GCGAGAATTG 1980 TCCGAGAAAG TCAAACATGC GAAGCGACTC AGTGATGAAC GCAATTTACT CCAAGATTCA 2040 AATTTCAAAG ACATTAATAG GCAACCAGAA CGTGGGTGGG GCGGAAGTAC AGGGATTACC 2100 ATCCAAGGAG GGGATGACGT ATTTAAAGAA AATTACGTCA CACTATCAGG TACCTTTGAT 2160 GAGTGCTATC CAACATATTT GTATCAAAAA ATCGATGAAT CAAAATTAAA AGCCTTTACC 2220 CGTTATCAAT TAAGAGGGTA TATCGAAGAT AGTCAAGACT TAGAAATCTA TTTAATTCGC 2280 TACAATGCAA AACATGAAAC AGTAAATGTG CCAGGTACGG GTTCCTTATG GCCGCTTTCA 2340 GCCCAAAGTC CAATCGGAAA GTGTGGAGAG CCGAATCGAT GCGCGCCACA CCTTGAATGG 2400 AATCCTGACT TAGATTGTTC GTGTAGGGAT GGAGAAAAGT GTGCCCATCA TTCGCATCAT 2460 TTCTCCTTAG ACATTGATGT AGGATGTACA GACTTAAATG AGGACCTAGG TGTATGGGTG 2520 ATCTTTAAGA TTAAGACGCA AGATGGGCAC GCAAGACTAG GGAATCTAGA GTTTCTCGAA 2580 GAGAAACCAT TAGTAGGAGA AGCGCTAGCT CGTGTGAAAA GAGCGGAGAA AAAATGGAGA 2640 GACAAACGTG AAAAATTGGA ATGGGAAACA AATATCGTTT ATAAAGAGGC AAAAGAATCT 2700 GTAGATGCTT TATTTGTAAA CTCTCAATAT GATCAATTAC AAGCGGATAC GAATATTGCC 2760 ATGATTCATG CGGCAGATAA ACGTGTTCAT AGCATTCGAG AAGCTTATCT GCCTGAGCTG 2820 TCTGTGATTC CGGGTGTCAA TGCGGCTATT TTTGAAGAAT TAGAAGGGCG TATTTTCACT 2880 GCATTCTCCC TATATGATGC GAGAAATGTC ATTAAAAATG GTGATTTTAA TAATGGCTTA 2940 TCCTGCTGGA ACGTGAAAGG GCATGTAGAT GTAGAAGAAC AAAACAACCA CCGTTCGGTC 3000 CTTGTTGTTC CGGAATGGGA AGCAGAAGTG TCACAAGAAG TTCGTGTCTG TCCGGGTCGT 3060 GGCTATATCC TTCGTGTCAC AGCGTACAAG GAGGGATATG GAGAAGGTTG CGTAACCATT 3120 CATGAGATCG AGAACAATAC AGACGAACTG AAGTTTAGCA ACTGTGTAGA AGAGGAAGTA 3180 TATCCAAACA ACACGGTAAC GTGTAATGAT TATACTGCGA CTCAAGAAGA ATATGAGGGT 3240 ACGTACACTT CTCGTAATCG AGGATATGAC GGAGCCTATG AAAGCAATTC TTCTGTACCA 3300 GCTGATTATG CATCAGCCTA TGAAGAAAAA GCATATACAG ATGGACGAAG AGACAATCCT 3360 TGTGAATCTA ACAGAGGATA TGGGGATTAC ACACCACTAC CAGCTGGCTA TGTGACAAAA 3420 GAATTAGAGT ACTTCCCAGA AACCGATAAG GTATGGATTG AGATCGGAGA AACGGAAGGA 3480 ACATTCATCG TGGACAGCGT GGAATTACTT CTTATGGAGG AA 3522 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1174 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: Met Glu Asn Asn He Gin Asn Gin Cys Val Pro Tyr Asn Cys Leu Asn 1 5 10 15 Asn Pro Glu Val Glu He Leu Asn Glu Glu Arg Ser Thr Gly Arg Leu 20 25 30 Pro Leu Asp He Ser Leu Ser Leu Thr Arg Phe Leu Leu Ser Glu Phe 35 40 45 Val Pro Gly Val Gly Val Ala Phe Gly Leu Phe Asp Leu He Trp Gly 50 55 60 Phe He Thr Pro Ser Asp Trp Ser Leu Phe Leu Leu Gin He Glu Gin 65 70 75 80 Leu He Glu Gin Arg He Glu Thr Leu Glu Arg Asn Arg Ala He Thr 85 90 95 Thr Leu Arg Gly Leu Ala Asp Ser Tyr Glu He Tyr He Glu Ala Leu 100 105 110 Arg Glu Trp Glu Ala Asn Pro Asn Asn Ala Gin Leu Arg Glu Asp Val 115 120 125 Arg He Arg Phe Ala Asn Thr Asp Asp Ala Leu He Thr Ala He Asn 130 135 140 Asn Phe Thr Leu Thr Ser Phe Glu He Pro Leu Leu Ser Val Tyr Val 145 150 155 160 Gin Ala Ala Asn Leu His Leu Ser Leu Leu Arg Asp Ala Val Ser Phe 165 170 175 Gly Gin Gly Trp Gly Leu Asp He Ala Thr Val Asn Asn His Tyr Asn 180 185 190 Arg Leu He Asn Leu He His Arg Tyr Thr Lys His Cys Leu Asp Thr 195 200 205 Tyr Asn Gin Gly Leu Glu Asn Leu Arg Gly Thr Asn Thr Arg Gin Trp 210 215 220 Ala Arg Phe Asn Gin Phe Arg Arg Asp Leu Thr Leu Thr Val Leu Asp 225 230 235 240 He Val Ala Leu Phe Pro Asn Tyr Asp Val Arg Thr Tyr Pro He Gin 245 250 255 Thr Ser Ser Gin Leu Thr Arg Glu He Tyr Thr ser ser Val He Glu 260 265 270 Asp Ser Pro Val Ser Ala Asn He Pro Asn Gly Phe Asn Arg Ala Glu 275 280 285 Phe Gly Val Arg Pro Pro His Leu Met Asp Phe Met Asn Ser Leu Phe 290 295 300 Val Thr Ala Glu Thr Val Arg Ser Gin Thr Val Trp Gly Gly His Leu 305 310 315 320 Val ser ser Arg Asn Thr Ala Gly Asn Arg He Asn Phe Pro Ser Tyr 325 330 335 Gly Val Phe Asn Pro Gly Gly Ala He Trp He Ala Asp Glu Asp Pro 340 345 350 Arg Pro Phe Tyr Arg Thr Leu Ser Asp Pro Val Phe Val Arg Gly Gly 355 360 365 Phe Gly Asn Pro His Tyr Val Leu Gly Leu Arg Gly Val Ala Phe Gin 370 375 380 Gin Thr Gly Thr Asn His Thr Arg Thr Phe Arg Asn Ser Gly Thr He 385 390 395 400 Asp Ser Leu Asp Glu He Pro Pro Gin Asp Asn Ser Gly Ala Pro Trp 405 410 415 Asn Asp Tyr Ser His Val Leu Asn His Val Thr Phe Val Arg Trp Pro 420 425 430 Gly Glu He Ser Gly ser Asp ser Trp Arg Ala Pro Met Phe Ser Trp 435 440 445 Thr His Arg Ser Ala Thr Pro Thr Asn Thr He Asp Pro Glu Arg He 450 455 460 Thr Gin He Pro Leu Val Lys Ala His Thr Leu Gin Ser Gly Thr Thr 465 470 475 480 Val Val Arg Gly Pro Gly Phe Thr Gly Gly Asp He Leu Arg Arg Thr 485 490 495 Ser Gly Gly Pro Phe Ala Tyr Thr He Val Asn He Asn Gly Gin Leu 500 505 510 Pro Gin Arg Tyr Arg Ala Arg He Arg Tyr Ala Ser Thr Thr Asn Leu 515 520 525 Arg He Tyr Val Thr Val Ala Gly Glu Arg He Phe Ala Gly Gin Phe 530 535 540 Asn Lys Thr Met Asp Thr Gly Asp Pro Leu Thr Phe Gin Ser Phe Ser 545 550 555 560 Tyr Ala Thr He Asn Thr Ala Phe Thr Phe Pro Met Ser Gin Ser Ser 565 570 575 Phe Thr Val Gly Ala Asp Thr Phe Ser Ser Gly Asn Glu Val Tyr He 580 585 590 Asp Arg Phe Glu Leu He Pro Val Thr Ala Thr Phe Glu Ala Glu Tyr 595 600 605 Asp Leu Glu Arg Ala Gin Lys Ala Val Asn Ala Leu Phe Thr Ser He 610 615 620 Asn Gin He Gly He Lys Thr Asp Val Thr Asp Tyr His He Asp Arg 625 630 635 640 Val Ser Asn Leu Val Thr Tyr Leu Ser Asp Glu Phe cys Leu Asp Glu 645 650 655 Lys Arg Glu Leu Ser Glu Lys Val Lys His Ala Lys Arg Leu Ser Asp 660 665 670 Glu Arg Asn Leu Leu Gin Asp Ser Asn Phe Lys Asp He Asn Arg Gin 675 680 685 Pro Glu Arg Gly Trp Gly Gly Ser Thr Gly He Thr He Gin Gly Gly 690 695 700 Asp Asp Val Phe Lys Glu Asn Tyr Val Thr Leu Ser Gly Thr Phe Asp 705 710 715 720 Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin Lys He Asp Glu Ser Lys Leu 725 730 735 Lys Ala Phe Thr Arg Tyr Gin Leu Arg Gly Tyr He Glu Asp Ser Gin 740 745 750 Asp Leu Glu He Tyr Leu He Arg Tyr Asn Ala Lys His Glu Thr Val 755 760 765 Asn Val Pro Gly Thr Gly ser Leu Trp Pro Leu Ser Ala Gin Ser Pro 770 775 780 He Gly Lys Cys Gly Glu Pro Asn Arg Cys Ala Pro His Leu Glu Trp 785 790 795 800 Asn Pro Asp Leu Asp Cys Ser Cys Arg Asp Gly Glu Lys Cys Ala His 805 810 815 His Ser His His Phe Ser Leu Asp He Asp Val Gly Cys Thr Asp Leu 820 825 830 Asn Glu Asp Leu Gly Val Trp Val He Phe Lys He Lys Thr Gin Asp 835 840 845 Gly His Ala Arg Leu Gly Asn Leu Glu Phe Leu Glu Glu Lys Pro Leu 850 855 860 Val Gly Glu Ala Leu Ala Arg Val Lys Arg Ala Glu Lys Lys Trp Arg 865 870 875 880 Asp Lys Arg Glu Lys Leu Glu Trp Glu Thr Asn He Val Tyr Lys Glu 885 890 895 Ala Lys Glu Ser Val Asp Ala Leu Phe Val Asn Ser Gin Tyr Asp Gin 900 905 910 Leu Gin Ala Asp Thr Asn He Ala Met He His Ala Ala Asp Lys Arg 915 920 925 Val His Ser He Arg Glu Ala Tyr Leu Pro Glu Leu Ser Val He Pro 930 935 940 Gly Val Asn Ala Ala He Phe Glu Glu Leu Glu Gly Arg He Phe Thr 945 950 955 960 Ala Phe Ser Leu Tyr Asp Ala Arg Asn Val He Lys Asn Gly Asp Phe 965 970 975 Asn Asn Gly Leu Ser cys Trp Asn Val Lys Gly His Val Asp Val Glu 980 985 990 Glu Gin Asn Asn His Arg Ser Val Leu Val Val Pro Glu Trp Glu Ala 995 1000 1005 Glu Val Ser Gin Glu Val Arg Val Cys Pro Gly Arg Gly Tyr He Leu 1010 1015 1020 Arg Val Thr Ala Tyr Lys Glu Gly Tyr Gly Glu Gly cys Val Thr He 1025 1030 1035 1040 His Glu He Glu Asn Asn Thr Asp Glu Leu Lys Phe Ser Asn Cys Val 1045 1050 1055 Glu Glu Glu Val Tyr Pro Asn Asn Thr Val Thr Cys Asn Asp Tyr Thr 1060 1065 1070 Ala Thr Gin Glu Glu Tyr Glu Gly Thr Tyr Thr Ser Arg Asn Arg Gly 1075 1080 1085 Tyr Asp Gly Ala Tyr Glu Ser Asn Ser Ser Val Pro Ala Asp Tyr Ala 1090 1095 1100 Ser Ala Tyr Glu Glu Lys Ala Tyr Thr Asp Gly Arg Arg Asp Asn Pro 1105 1110 1115 1120 Cys Glu Ser Asn Arg Gly Tyr Gly Asp Tyr Thr Pro Leu Pro Ala Gly 1125 1130 1135 Tyr val Thr Lys Glu Leu Glu Tyr Phe Pro Glu Thr Asp Lys Val Trp 1140 1145 1150 He Glu He Gly Glu Thr Glu Gly Thr Phe He Val Asp Ser Val Glu 1155 1160 1165 Leu Leu Leu Met Glu Glu 1170 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Xaa Xaa lie Asp Xaa Xaa Glu Xaa Xaa Xaa Xaa Xaa 5 10 (2) INFORMATION FOR SEQ ID NO:31: (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:31: Tyr Pro Asn Asn Thr Val Thr cys 5 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1174 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: Met Glu Asn Asn He Gin Asn Gin cys Val Pro Tyr Asn Cys Leu Asn 1 5 10 15 Asn Pro Glu Val Glu He Leu Asn Glu Glu Arg ser Thr Gly Arg Leu 20 25 30 Pro Leu Asp He Ser Leu ser Leu Thr Arg Phe Leu Leu Ser Glu Phe 35 40 45 Val Pro Gly Val Gly Val Ala Phe Gly Leu Phe Asp Leu He Trp Gly 50 55 60 Phe He Thr Pro Ser Asp Trp Ser Leu Phe Leu Leu Gin He Glu Gin 65 70 75 80 Leu He Glu Gin Arg He Glu Thr Leu Glu Arg Asn Arg Ala He Thr 85 90 95 Thr Leu Arg Gly Leu Ala Asp Ser Tyr Glu He Tyr He Glu Ala Leu 100 105 110 Arg Glu Trp Glu Ala Asn Pro Asn Asn Ala Gin Leu Arg Glu Asp Val 115 120 125 Arg He Arg Phe Ala Asn Thr Asp Asp Ala Leu He Thr Ala He Asn 130 135 140 Asn Phe Thr Leu Thr Ser Phe Glu He Pro Leu Leu ser Val Tyr Val 145 150 155 160 Gin Ala Ala Asn Leu His Leu Ser Leu Leu Arg Asp Ala Val Ser Phe 165 170 175 Gly Gin Gly Trp Gly Leu Asp He Ala Thr Val Asn Asn His Tyr Asn 180 185 190 Arg Leu He Asn Leu He His Arg Tyr Thr Lys His cys Leu Asp Thr 195 200 205 Tyr Asn Gin Gly Leu Glu Asn Leu Arg Gly Thr Asn Thr Arg Gin Trp 210 215 220 Ala Arg Phe Asn Gin Phe Arg Arg Asp Leu Thr Leu Thr Val Leu Asp 225 230 235 240 He Val Ala Leu Phe Pro Asn Tyr Asp Val Arg Thr Tyr Pro He Gin 245 250 255 Thr ser Ser Gin Leu Thr Arg Glu He Tyr Thr Ser Ser Val He Glu 260 265 270 Asp Ser Pro Val Ser Ala Asn He Pro Asn Gly Phe Asn Arg Ala Glu 275 280 285 Phe Gly Val Arg Pro Pro His Leu Met Asp Phe Met Asn Ser Leu Phe 290 295 300 Val Thr Ala Glu Thr Val Arg Ser Gin Thr Val Trp Gly Gly His Leu 305 310 315 320 Val Ser Ser Arg Asn Thr Ala Gly Asn Arg He Asn Phe Pro Ser Tyr 325 330 335 Gly Val Phe Asn Pro Gly Gly Ala He Trp He Ala Asp Glu Asp Pro 340 345 350 Arg Pro Phe Tyr Arg Thr Leu Ser Asp Pro Val Phe Val Arg Gly Gly 355 360 365 Phe Gly Asn Pro His Tyr Val Leu Gly Leu Arg Gly Val Ala Phe Gin 370 375 380 Gin Thr Gly Thr Asn His Thr Arg Thr Phe Arg Asn ser Gly Thr He 385 390 395 400 Asp ser Leu Asp Glu He Pro Pro Gin Asp Asn Ser Gly Ala Pro Trp 405 410 415 Asn Asp Tyr Ser His Val Leu Asn His Val Thr Phe Val Arg Trp Pro 420 425 430 Gly Glu He ser Gly Ser Asp Ser Trp Arg Ala Pro Met Phe Ser Trp 435 440 445 Thr His Arg Ser Ala Thr Pro Thr Asn Thr He Asp Pro Glu Arg He 450 455 460 Thr Gin He Pro Leu Val Lys Ala His Thr Leu Gin Ser Gly Thr Thr 465 470 475 480 Val Val Arg Gly Pro Gly Phe Thr Gly Gly Asp He Leu Arg Arg Thr 485 490 495 Ser Gly Gly Pro Phe Ala Tyr Thr He Val Asn He Asn Gly Gin Leu 500 505 510 Pro Gin Arg Tyr Arg Ala Arg He Arg Tyr Ala Ser Thr Thr Asn Leu 515 520 525 Arg He Tyr Val Thr Val Ala Gly Glu Arg He Phe Ala Gly Gin Phe 530 535 540 Asn Lys Thr Met Asp Thr Gly Asp Pro Leu Thr Phe Gin Ser Phe ser 545 550 555 560 Tyr Ala Thr He Asn Thr Ala Phe Thr Phe Pro Met Ser Gin ser Ser 565 570 575 Phe Thr Val Gly Ala Asp Thr Phe Ser Ser Gly Asn Glu Val Tyr He 580 585 590 Asp Arg Phe Glu Leu lie Pro Val Thr Ala Thr Phe Glu Ala Glu Tyr 595 600 605 Asp Leu Glu Arg Ala Gin Lys Ala Val Asn Ala Leu Phe Thr ser He 610 615 620 Asn Gin He Gly He Lys Thr Asp Val Thr Asp Tyr His He Asp Gin 625 630 635 640 Val Ser Asn Leu Val Asp Cys Leu Ser Asp Glu Phe Cys Leu Asp Glu 645 650 655 Lys Arg Glu Leu ser Glu Lys Val Lys His Ala Lys Arg Leu Ser Asp 660 665 670 Glu Arg Asn Leu Leu Gin Asp Pro Asn Phe Lys Gly He Asn Arg Gin 675 680 685 Leu Asp Arg Gly Trp Arg Gly Ser Thr Asp He Thr He Gin Arg Gly 690 695 700 Asp Asp Val Phe Lys Glu Asn Tyr Val Thr Leu Pro Gly Thr Phe Asp 705 710 715 720 Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin Lys He Asp Glu Ser Lys Leu 725 730 735 Lys Pro Tyr Thr Arg Tyr Gin Leu Arg Gly Tyr He Glu Asp Ser Gin 740 745 750 Asp Leu Glu He Tyr Leu He Arg Tyr Asn Ala Lys His Glu Thr Val 755 760 765 Asn Val Leu Gly Thr Gly Ser Leu Trp Pro Leu Ser Val Gin ser Pro 770 775 780 He Arg Lys Cys Gly Glu Pro Asn Arg Cys Ala Pro His Leu Glu Trp 785 790 795 800 Asn Pro Asp Leu Asp Cys Ser Cys Arg Asp Gly Glu Lys Cys Ala His 805 810 815 His Ser His His Phe Ser Leu Asp He Asp Val Gly Cys Thr Asp Leu 820 825 830 Asn Glu Asp Leu Asp Val Trp Val He Phe Lys He Lys Thr Gin Asp 835 840 845 Gly His Ala Arg Leu Gly Asn Leu Glu Phe Leu Glu Glu Lys Pro Leu 850 855 860 Val Gly Glu Ala Leu Ala Arg Val Lys Arg Ala Glu Lys Lys Trp Arg 865 870 875 880 Asp Lys Arg Glu Lys Leu Glu Leu Glu Thr Asn He Val Tyr Lys Glu 885 890 895 Ala Lys Glu Ser Val Asp Ala Leu Phe Val Asn Ser Gin Tyr Asp Gin 900 905 910 Leu Gin Ala Asp Thr Asn He Ala Met He His Ala Ala Asp Lys Arg 915 920 925 val His Arg He Arg Glu Ala Tyr Leu Pro Glu Leu ser Val He Pro 930 935 940 Gly Val Asn Val Asp He Phe Glu Glu Leu Lys Gly Arg He Phe Thr 945 950 955 960 Ala Phe Phe Leu Tyr Asp Ala Arg Asn Val He Lys Asn Gly Asp Phe 965 970 975 Asn Asn Gly Leu ser Cys Trp Asn Val Lys Gly His Val Asp Val Glu 980 985 990 Glu Gin Asn Asn His Arg Ser Val Leu Val Val Pro Glu Trp Glu Ala 995 1000 1005 Glu Val Ser Gin Glu val Arg Val Cys Pro Gly Arg Gly Tyr He Leu 1010 1015 1020 Arg Val Thr Ala Tyr Lys Glu Gly Tyr Gly Glu Gly Cys Val Thr He 1025 1030 1035 1040 His Glu He Glu Asn Asn Thr Asp Glu Leu Lys Phe Ser Asn Cys Val 1045 1050 1055 Glu Glu Glu Val Tyr Pro Asn Asn Thr Val Thr Cys Asn Asp Tyr Thr 1060 1065 1070 Ala Asn Gin Glu Glu Tyr Gly Gly Ala Tyr Thr ser Arg Asn Arg Gly 1075 1080 1085 Tyr Asp Glu Thr Tyr Gly Ser Asn Ser Ser Val Pro Ala Asp Tyr Ala 1090 1095 1100 Ser Val Tyr Glu Glu Lys Ser Tyr Thr Asp Gly Arg Arg Asp Asn Pro 1105 1110 1115 1120 Cys Glu Ser Asn Arg Gly Tyr Gly Asp Tyr Thr Pro Leu Pro Ala Gly 1125 1130 1135 Tyr Val Thr Lys Glu Leu Glu Tyr Phe Pro Glu Thr Asp Lys Val Trp 1140 1145 1150 He Glu He Gly Glu Thr Glu Gly Thr Phe He Val Asp Ser Val Glu 1155 1160 1165 Leu Leu Leu Met Glu Glu 1170 (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1155 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: Met Asp Asn Asn Pro Asn He Asn Glu Cys He Pro Tyr Asn cys Leu 1 5 10 15 Ser Asn Pro Glu Val Glu Val Leu Gly Gly Glu Arg He Glu Thr Gly 20 25 30 Tyr Thr Pro He Asp He Ser Leu Ser Leu Thr Gin Phe Leu Leu Ser 35 40 45 Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly Leu Val Asp He He 50 55 60 Trp Gly He Phe Gly Pro Ser Gin Trp Asp Ala Phe Leu Val Gin He 65 70 75 80 Glu Gin Leu He Asn Gin Arg He Glu Glu Phe Ala Arg Asn Gin Ala 85 90 95 He Ser Arg Leu Glu Gly Leu ser Asn Leu Tyr Gin He Tyr Ala Glu 100 105 110 Ser Phe Arg Glu Trp Glu Ala Asp Pro Thr Asn Pro Ala Leu Arg Glu 115 120 125 Glu Met Arg He Gin Phe Asn Asp Met Asn Ser Ala Leu Thr Thr Ala 130 135 140 He Pro Leu Phe Ala Val Gin Asn Tyr Gin Val Pro Leu Leu Ser Val 145 150 155 160 Tyr Val Gin Ala Ala Asn Leu His Leu Ser Val Leu Arg Asp Val Ser 165 170 175 Val Phe Gly Gin Arg Trp Gly Phe Asp Ala Ala Thr He Asn Ser Arg 180 185 190 Tyr Asn Asp Leu Thr Arg Leu He Gly Asn Tyr Thr Asp His Ala Val 195 200 205 Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp Gly Pro Asp Ser Arg 210 215 220 Asp Trp He Arg Tyr Asn Gin Phe Arg Arg Glu Leu Thr Leu Thr Val 225 230 235 240 Leu Asp He Val Ser Leu Phe Pro Asn Tyr Asp Ser Arg Thr Tyr Pro 245 250 255 He Arg Thr Val Ser Gin Leu Thr Arg Glu He Tyr Thr Asn Pro Val 260 265 270 Leu Glu Asn Phe Asp Gly Ser Phe Arg Gly Ser Ala Gin Gly He Glu 275 280 285 Gly Ser He Arg Ser Pro His Leu Met Asp He Leu Asn Ser He Thr 290 295 300 He Tyr Thr Asp Ala His Arg Gly Glu Tyr Tyr Trp Ser Gly His Gin 305 310 315 320 He Met Ala ser Pro Val Gly Phe Ser Gly Pro Glu Phe Thr Phe Pro 325 330 335 Leu Tyr Gly Thr Met Gly Asn Ala Ala Pro Gin Gin Arg He Val Ala 340 345 350 Gin Leu Gly Gin Gly Val Tyr Arg Thr Leu Ser Ser Thr Leu Tyr Arg 355 360 365 Arg Pro Phe Asn He Gly He Asn Asn Gin Gin Leu Ser Val Leu Asp 370 375 380 Gly Thr Glu Phe Ala Tyr Gly Thr Ser ser Asn Leu Pro Ser Ala Val 385 390 395 400 Tyr Arg Lys ser Gly Thr Val Asp Ser Leu Asp Glu He Pro Pro Gin 405 410 415 Asn Asn Asn Val Pro Pro Arg Gin Gly Phe ser His Arg Leu Ser His 420 425 430 Val ser Met Phe Arg Ser Gly Phe Ser Asn Ser ser Val Ser He He 435 440 445 Arg Ala Pro Met Phe Ser Trp He His Arg Ser Ala Glu Phe Asn Asn 450 455 460 He He Pro ser ser Gin lie Thr Gin He Pro Leu Thr Lys ser Thr 465 470 475 480 Asn Leu Gly Ser Gly Thr Ser Val Val Lys Gly Pro Gly Phe Thr Gly 485 490 495 Gly Asp lie Leu Arg Arg Thr Ser Pro Gly Gin He ser Thr Leu Arg 500 505 510 Val Asn He Thr Ala Pro Leu Ser Gin Arg Tyr Arg Val Arg He Arg 515 520 525 Tyr Ala ser Thr Thr Asn Leu Gin Phe His Thr Ser He Asp Gly Arg 530 535 540 Pro He Asn Gin Gly Asn Phe Ser Ala Thr Met ser Ser Gly Ser Asn 545 550 555 560 Leu Gin Ser Gly Ser Phe Arg Thr Val Gly Phe Thr Thr Pro Phe Asn 565 570 575 Phe Ser Asn Gly Ser Ser Val Phe Thr Leu Ser Ala His Val Phe Asn 580 585 590 Ser Gly Asn Glu Val Tyr He Asp Arg He Glu Phe Val Pro Ala Glu 595 600 605 Val Thr Phe Glu Ala Glu Tyr Asp Leu Glu Arg Ala Gin Lys Ala Val 610 615 620 Asn Glu Leu Phe Thr Ser Ser Asn Gin He Gly Leu Lys Thr Asp Val 625 630 635 640 Thr Asp Tyr His He Asp Gin Val Ser Asn Leu Val Glu Cys Leu Ser 645 650 655 Asp Glu Phe Cys Leu Asp Glu Lys Lys Glu Leu Ser Glu Lys Val Lys 660 665 670 His Ala Lys Arg Leu Ser Asp Glu Arg Asn Leu Leu Gin Asp Pro Asn 675 680 685 Phe Arg Gly He Asn Arg Gin Leu Asp Arg Gly Trp Arg Gly Ser Thr 690 695 700 Asp He Thr He Gin Gly Gly Asp Asp Val Phe Lys Glu Asn Tyr Val 705 710 715 720 Thr Leu Leu Gly Thr Phe Asp Glu Cys Tyr Pro Thr Tyr Leu Tyr Gin 725 730 735 Lys He Asp Glu Ser Lys Leu Lys Ala Tyr Thr Arg Tyr Gin Leu Arg 740 745 750 Gly Tyr He Glu Asp Ser Gin Asp Leu Glu He Tyr Leu He Arg Tyr 755 760 765 Asn Ala Lys His Glu Thr Val Asn Val Pro Gly Thr Gly Ser Leu Trp 770 775 780 Pro Leu Ser Ala Pro Ser Pro He Gly Lys Cys Ala His His Ser His 785 790 795 800 His Phe Ser Leu Asp He Asp Val Gly Cys Thr Asp Leu Asn Glu Asp 805 810 815 Leu Gly Val Trp Val He Phe Lys He Lys Thr Gin Asp Gly His Ala 820 825 830 Arg Leu Gly Asn Leu Glu Phe Leu Glu Glu Lys Pro Leu Val Gly Glu 835 840 845 Ala Leu Ala Arg Val Lys Arg Ala Glu Lys Lys Trp Arg Asp Lys Arg 850 855 860 Glu Lys Leu Glu Trp Glu Thr Asn He Val Tyr Lys Glu Ala Lys Glu 865 870 875 880 Ser Val Asp Ala Leu Phe Val Asn ser Gin Tyr Asp Arg Leu Gin Ala 885 890 895 Asp Thr Asn He Ala Met He His Ala Ala Asp Lys Arg Val His Ser 900 905 910 He Arg Glu Ala Tyr Leu Pro Glu Leu Ser Val He Pro Gly Val Asn 915 920 925 Ala Ala He Phe Glu Glu Leu Glu Gly Arg He Phe Thr Ala Phe Ser 930 935 940 Leu Tyr Asp Ala Arg Asn Val He Lys Asn Gly Asp Phe Asn Asn Gly 945 950 955 960 Leu Ser Cys Trp Asn Val Lys Gly His Val Asp Val Glu Glu Gin Asn 965 970 975 Asn His Arg ser Val Leu Val Val Pro Glu Trp Glu Ala Glu Val Ser 980 985 990 Gin Glu Val Arg Val Cys Pro Gly Arg Gly Tyr He Leu Arg Val Thr 995 1000 1005 Ala Tyr Lys Glu Gly Tyr Gly Glu Gly Cys Val Thr He His Glu He 1010 1015 1020 Glu Asn Asn Thr Asp Glu Leu Lys Phe ser Asn Cys Val Glu Glu Glu 1025 1030 1035 1040 Val Tyr Pro Asn Asn Thr val Thr Cys Asn Asp Tyr Thr Ala Thr Gin 1045 1050 1055 Glu Glu Tyr Glu Gly Thr Tyr Thr Ser Arg Asn Arg Gly Tyr Asp Gly 1060 1065 1070 Ala Tyr Glu Ser Asn Ser Ser Val Pro Ala Asp Tyr Ala Ser Ala Tyr 1075 1080 1085 Glu Glu Lys Ala Tyr Thr Asp Gly Arg Arg Asp Asn Pro Cys Glu Ser 1090 1095 1100 Asn Arg Gly Tyr Gly Asp Tyr Thr Pro Leu Pro Ala Gly Tyr Val Thr 1105 1110 1115 1120 Lys Glu Leu Glu Tyr Phe Pro Glu Thr Asp Lys Val Trp He Glu He 1125 1130 1135 Gly Glu Thr Glu Gly Thr Phe He Val Asp ser Val Glu Leu Leu Leu 1140 1145 1150 Met Glu Glu 1155 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1182 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: 1inear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: Met Asp Asn Asn Pro Asn He Asn Glu Cys He Pro Tyr Asn Cys Leu 1 5 10 15 Ser Asn Pro Glu Val Glu Val Leu Gly Gly Glu Arg He Glu Thr Gly 20 25 30 Tyr Thr Pro He Asp He Ser Leu Ser Leu Thr Gin Phe Leu Leu Ser 35 40 45 Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly Leu Val Asp He He 50 55 60 Trp Gly He Phe Gly Pro Ser Gin Trp Asp Ala Phe Leu Val Gin He 65 70 75 80 Glu Gin Leu He Asn Gin Arg He Glu Glu Phe Ala Arg Asn Gin Ala 85 90 95 He Ser Arg Leu Glu Gly Leu Ser Asn Leu Tyr Gin He Tyr Ala Glu 100 105 110 Ser Phe Arg Glu Trp Glu Ala Asp Pro Thr Asn Pro Ala Leu Arg Glu 115 120 125 Glu Met Arg He Gin Phe Asn Asp Met Asn ser Ala Leu Thr Thr Ala 130 135 140 He Pro Leu Phe Ala Val Gin Asn Tyr Gin Val Pro Leu Leu ser Val 145 150 155 160 Tyr Val Gin Ala Ala Asn Leu His Leu Ser Val Leu Arg Asp Val Ser 165 170 175 Val Phe Gly Gin Arg Trp Gly Phe Asp Ala Ala Thr He Asn Ser Arg 180 185 190 Tyr Asn Asp Leu Thr Arg Leu He Gly Asn Tyr Thr Asp Tyr Ala Val 195 200 205 Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp Gly Pro Asp Ser Arg 210 215 220 Asp Trp Val Arg Tyr Asn Gin Phe Arg Arg Glu Leu Thr Leu Thr Val 225 230 235 240 Leu Asp He Val Ala Leu Phe Pro Asn Tyr Asp Ser Arg Arg Tyr Pro 245 250 255 He Arg Thr Val Ser Gin Leu Thr Arg Glu He Tyr Thr Asn Pro Val 260 265 270 Leu Glu Asn Phe Asp Gly Ser Phe Arg Gly Ser Ala Gin Gly He Glu 275 280 285 Arg Ser He Arg Ser Pro His Leu Met Asp He Leu Asn Ser He Thr 290 295 300 He Tyr Thr Asp Ala His Arg Gly Tyr Tyr Tyr Trp ser Gly His Gin 305 310 315 320 He Met Ala Ser Pro Val Gly Phe ser Gly Pro Glu Phe Thr Phe Pro 325 330 335 Leu Tyr Gly Thr Met Gly Asn Ala Ala Pro Gin Gin Arg He Val Ala 340 345 350 Gin Leu Gly Gin Gly Val Tyr Arg Thr Leu ser ser Thr Leu Tyr Arg 355 360 365 Arg Pro Phe Asn He Gly He Asn Asn Gin Gin Leu Ser Val Leu Asp 370 375 380 Gly Thr Glu Phe Ala Tyr Gly Thr Ser ser Asn Leu Pro Ser Ala Val 385 390 395 400 Tyr Arg Lys Ser Gly Thr Val Asp Ser Leu Asp Glu He Pro Pro Gin 405 410 415 Asn Asn Asn Val Pro Pro Arg Gin Gly Phe Ser His Arg Leu Ser His 420 425 430 Val Ser Met Phe Arg Ser Gly Phe Ser Asn Ser Ser Val Ser lie He 435 440 445 Arg Ala Pro Met Phe Ser Trp He His Arg Ser Ala Glu Phe Asn Asn 450 455 460 He He Ala Ser Asp Ser He Thr Gin lie Pro Ala Val Lys Gly Asn 465 470 475 480 Phe Leu Phe Asn Gly Ser Val He Ser Gly Pro Gly Phe Thr Gly Gly 485 490 495 Asp Leu Val Arg Leu Asn Ser Ser Gly Asn Asn He Gin Asn Arg Gly 500 505 510 Tyr He Glu Val Pro He His Phe Pro Ser Thr Ser Thr Arg Tyr Arg 515 520 525 Val Arg Val Arg Tyr Ala ser Val Thr Pro He His Leu Asn Val Asn 530 535 540 Trp Gly Asn Ser Ser He Phe Ser Asn Thr Val Pro Ala Thr Ala Thr 545 550 555 560 Ser Leu Asp Asn Leu Gin Ser Ser Asp Phe Gly Tyr Phe Glu Ser Ala 565 570 575 Asn Ala Phe Thr Ser Ser Leu Gly Asn He Val Gly Val Arg Asn Phe 580 585 590 Ser Gly Thr Ala Gly Val He He Asp Arg Phe Glu Phe He Pro Val 595 600 605 Thr Ala Thr Leu Glu Ala Glu Tyr Asn Leu Glu Arg Ala Gin Lys Ala 610 615 620 Val Asn Ala Leu Phe Thr Ser Thr Asn Gin Leu Gly Leu Lys Thr Asn 625 630 635 640 Val Thr Asp Tyr His He Asp Gin Val Ser Asn Leu Val Thr Tyr Leu 645 650 655 Ser Asp Glu Phe Cys Leu Asp Glu Lys Arg Glu Leu Ser Glu Lys Val 660 665 670 Lys His Ala Lys Arg Leu Ser Asp Glu Arg Asn Leu Leu Gin Asp Ser 675 680 685 Asn Phe Lys Asp He Asn Arg Gin Pro Glu Arg Gly Trp Gly Gly Ser 690 695 700 Thr Gly He Thr He Gin Gly Gly Asp Asp Val Phe Lys Glu Asn Tyr 705 710 715 720 Val Thr Leu Ser Gly Thr Phe Asp Glu Cys Tyr Pro Thr Tyr Leu Tyr 725 730 735 Gin Lys He Asp Glu ser Lys Leu Lys Ala Phe Thr Arg Tyr Gin Leu 740 745 750 Arg Gly Tyr He Glu Asp Ser Gin Asp Leu Glu He Tyr Leu He Arg 755 760 765 Tyr Asn Ala Lys His Glu Thr Val Asn Val Pro Gly Thr Gly Ser Leu 770 775 780 Trp Pro Leu Ser Ala Gin ser Pro He Gly Lys Cys Gly Glu Pro Asn 785 790 795 800 Arg cys Ala Pro His Leu Glu Trp Asn Pro Asp Leu Asp Cys Ser Cys 805 810 815 Arg Asp Gly Glu Lys Cys Ala His His Ser His His Phe Ser Leu Asp 820 825 830 He Asp Val Gly Cys Thr Asp Leu Asn Glu Asp Leu Gly Val Trp Val 835 840 845 He Phe Lys He Lys Thr Gin Asp Gly His Ala Arg Leu Gly Asn Leu 850 855 860 Glu Phe Leu Glu Glu Lys Pro Leu Val Gly Glu Ala Leu Ala Arg Val 865 870 875 880 Lys Arg Ala Glu Lys Lys Trp Arg Asp Lys Arg Glu Lys Leu Glu Trp 885 890 895 Glu Thr Asn He Val Tyr Lys Glu Ala Lys Glu Ser Val Asp Ala Leu 900 905 910 Phe Val Asn Ser Gin Tyr Asp Gin Leu Gin Ala Asp Thr Asn He Ala 915 920 925 Met He His Ala Ala Asp Lys Arg Val His Ser He Arg Glu Ala Tyr 930 935 940 Leu Pro Glu Leu ser Val He Pro Gly Val Asn Ala Ala He Phe Glu 945 950 955 960 Glu Leu Glu Gly Arg He Phe Thr Ala Phe Ser Leu Tyr Asp Ala Arg 965 970 975 Asn Val He Lys Asn Gly Asp Phe Asn Asn Gly Leu Ser cys Trp Asn 980 985 990 Val Lys Gly His Val Asp Val Glu Glu Gin Asn Asn His Arg Ser Val 995 1000 1005 Leu Val Val Pro Glu Trp Glu Ala Glu val Ser Gin Glu val Arg Val 1010 1015 1020 Cys Pro Gly Arg Gly Tyr He Leu Arg Val Thr Ala Tyr Lys Glu Gly 1025 1030 1035 1040 Tyr Gly Glu Gly Cys Val Thr lie His Glu He Glu Asn Asn Thr Asp 1045 1050 1055 Glu Leu Lys Phe Ser Asn cys val Glu Glu Glu Val Tyr Pro Asn Asn 1060 1065 1070 Thr Val Thr Cys Asn Asp Tyr Thr Ala Thr Gin Glu Glu Tyr Glu Gly 1075 1080 1085 Thr Tyr Thr Ser Arg Asn Arg Gly Tyr Asp Gly Ala Tyr Glu Ser Asn 1090 1095 1100 Ser Ser Val Pro Ala Asp Tyr Ala Ser Ala Tyr Glu Glu Lys Ala Tyr 1105 1110 1115 1120 Thr Asp Gly Arg Arg Asp Asn Pro Cys Glu Ser Asn Arg Gly Tyr Gly 1125 1130 1135 Asp Tyr Thr Pro Leu Pro Ala Gly Tyr Val Thr Lys Glu Leu Glu Tyr 1140 1145 1150 Phe Pro Glu Thr Asp Lys Val Trp He Glu He Gly Glu Thr Glu Gly 1155 1160 1165 Thr Phe He Val Asp Ser Val Glu Leu Leu Leu Met Glu Glu 1170 1175 1180

Claims: Claims 1 A composition for controlling lepidopteran pests compnsmg a CrylF chimenc core toxin- containmg protem and a CryLA(c) chimenc core toxin-containing protem, or cells which express these proteins 2 The composition, accordmg to claim 1 , compnsmg a cell expressmg a CrylF chimenc core toxin-containing protem and a cell expressmg a CryΙA(c) chimenc core toxin-containing protem 3 The composition, accordmg to claim 1, compnsmg a cell expressmg a CrylF chimenc core to vui-containing protem and a CryΙA(c) chimenc core toxin-containing protem 4 The composition, accordmg to claim 1, wherem said CrylF chimenc core toxin-containing protem compnses a Cr lF core N-terminal protem portion and a heterologous C-terminal toxm portion from a CrvIA(b) toxm or CryIA(b)/CryIA(c) chimeπc toxm 5 The composition, accordmg to claim 4, wherem said CrylF chimenc core toxin-containing protem has approximately 1150 to 1200 ammo acids and compnses a CrylF core N-terminal sequence of at least about 590 ammo acids and no more than about 1100 ammo acids, wherem said CryIA(b) or CryIA(c)/CrvIA(b) proto m portion compnses at least 100 ammo acids at die C-termmus of said protem 6 The composition, accordmg to claim 4, wherem the transition from Cry IF core N-terminal toxm portion to heterologous protoxm portion occurs after the sequence shown m SEQ ID NO 30 and before the end of die peptide sequence of SEQ ID NO 31 7 The composition, accordmg to claim 6, wherem said core toxm portion compnses the first about 601 ammo acids of a CrylF toxm and wherem said C-terminal protoxm portion compnses the CrvIA(b) or CrvIA(c)/CrvIA(b) ammo acid sequence which follows the peptide sequence shown m SEQ ID NO 31 8 The composition, accordmg to claim 6, wherem said core toxin-containing protem consists essentially of the ammo acid sequence shown m SEQ ID NO 23 9 The composition, accordmg to claim 6. wherem said core to in-containing protem consists essentially of the ammo acid sequence shown m SEQ ID NO 29 10. The composition, according to claim 6, wherein said CrylF chimeric core toxin-containing protein consists essentially of die amino acid sequence shown in Figure 9. 11. The composition, according to claim 1, wherein said CryIA(c) chimeric core toxin- containing protein has an amino acid sequence consisting essentially of die sequence shown in SEQ ID NO. 34. 12. The composition, according to claim 3, wherein said CryEF chimeric and CryIA(c) chimeric core toxin-containing proteins are produced by a host cell transformed to express SEQ ID NO. 23 and SEQ ID NO. 34. 13. The composition, according to claim 3, wherein said CrylF chimeric and CryΙA(c) chimeric core toxin-containing proteins are produced by a host cell transformed to express SEQ ID NO. 29 and SEQ ID NO. 34. 14. A host transformed to express both a CrylF chimeric core toxin-containing protein and a CryΙA(c) chimeric core toxin-containing protein. 15. A method for controlling lepidopteran pests comprising contacting said pests, or die environment of said pests, with an effective amount of a composition comprising a CrylF chimeric core toxin-containing protein and a CryΙA(c) chimeric core toxin-containing protein, or cells which produce tiiese proteins. 16. The method, according to claim 15, wherein said composition comprises a cell expressmg a CrvIF chimeric core toxin-containing protein and a cell expressing a CryΙA(c) chimeric core toxin- containing protein. 17. The method, according to claim 15, wherein said composition comprises a cell expressmg a CrvIF chimeric core toxin-containing protein and a CryΙA(c) chimeric core toxin-containing protein 18. The method, according to claim 15, wherein said Cr lF chimeric core toxin-containing protein comprises a CryEF core N-terminal toxin portion and a heterologous C-terminal protoxin portion from a CryIA(b) toxin or CryIA(b)/CryIA(c) chimeric toxin. 19. The method, according to claim 18. wherein said CrylF chimeric core toxin-containing protein has approximately 1150 to 1200 amino acids and comprises a CrylF core N-terminal sequence of at least about 590 ammo acids and no more than about 1100 ammo acids, wherem said CryIA(b) or CryIA(c)/CryIA(b) protoxm portion comprises at least 100 ammo acids at die C-terminus of said protem 20 The method, accordmg to claim 18, wherem die transition from CrylF core N-terminal toxm portion to heterologous protoxm portion occurs after the sequence shown m SEQ ID NO 30 and before the end of die peptide sequence of SEQ ID NO 31 21 The method, accordmg to claim 20, wherem said core toxm portion compnses die first about 601 ammo acids of a CrylF toxm and wherem said C-terminal protoxm portion compnses die CryIA(b) or CryIA(c)/CryIA(b) ammo acid sequence which follows the peptide sequence shown m SEQ ID NO 31 22 The method, accordmg to claim 20, wherem said core toxm-contaimng protem consists essentially of the ammo acid sequence shown in SEQ ID NO 23 23 The method, accordmg to claim 20, wherem said core toxin-containing protem consists essentially of die ammo acid sequence shown m SEQ ID NO 29 24 The method, accordmg to claim 20, wherem said CrylF chimenc core toxin-containing protem consists essentially of an ammo acid sequence shown m Figure 9 25 The mediod, accordmg to claim 18, wherem said CryΙA(c) chimeπc core toxin-containing protem has an ammo acid sequence consisting essentially of die sequence shown m SEQ ID NO 34 26 The mediod, accordmg to claim 18, wherem said Cπ IF chimeπc and CryIA(c) chimenc core toxin-containing protems are from a host cell transformed to express SEQ ID NO 23 and SEQ ID NO 34 27 The mediod. accordmg to claim 13. wherem said CrvIF chimeπc and CryΙA(c) chimenc core are from a host cell transformed to express SEQ ID NO 29 and SEQ ID NO 34

Inventors: BRADFISCH GREGORY A, SCHWAB GEORGE E, THOMPSON MARK, BRADFISCH, GREGORY, A., SCHWAB, GEORGE, E., THOMPSON, MARK
Applicants: MYCOGEN CORP, MYCOGEN CORPORATION
Application year: 1995
Main classification: C12N15
IPC codes: A01N37, A01N63, C07K7, C07K14, C12N1, C12N15, C12P21, C12R1