Methods For Producing Heterologous Polypeptides In Mutants Of Trichoderma

Abstract

The present invention relates to mutants of a parent Trichoderma strain, comprising a polynucleotide encoding a polypeptide and one or more genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more of the enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions. The present invention also relates to methods of producing a polypeptide in such mutants and methods for producing such mutants.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a divisional application of U.S. application Ser. No. 14/652,755 filed on Jun. 16, 2015, which is a 35 U.S.C. .sctn. 371 national application of PCT/US2013/076977 filed on Dec. 20, 2013, which claims priority or the benefit under 35 U.S.C. .sctn. 119 of U.S. Provisional Application No. 61/745,165 filed on Dec. 21, 2012, the contents of which are fully incorporated herein by reference.

REFERENCE TO A SEQUENCE LISTING

[0002] This application contains a Sequence Listing in computer readable form, which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

Field of the Invention

[0003] The present invention relates to Trichoderma mutant strains deficient in the production of secondary metabolites, methods of obtaining the Trichoderma mutant strains, and methods of producing heterologous polypeptides in the Trichoderma mutant strains.

Description of the Related Art

[0004] Trichoderma has been shown to be useful as a host cell for the recombinant production of polypeptides having biological activity (WO 96/00787 and WO 97/26330). Trichoderma hosts with the desirable traits of increased protein expression and secretion may not necessarily have the most desirable characteristics for successful fermentation. The fermentation may not be optimal because of the production of biological substances detrimental to the production, recovery, or application of a particular polypeptide of interest.

[0005] Peptaibols are synthesized by large multidomain enzymes known as non-ribosomal peptide synthetases that assemble compounds from a range of precursors (including nonproteinogenic amino acids and hydroxy or carboxyl acids), which can be N-methylated, acylated, reduced, or epimerized (Marahiel et al., 1997, Chem. Rev. 97: 2651-2674; Zocher and Keller, 1997, Adv. Microb. Physiol. 38: 85-131). The synthetases have a modular structure in which each module is a semiautonomous unit that recognizes, activates, and modifies a single residue of the final peptide. Each module can be further partitioned into distinct adenylation, thiolation, and condensation domains, which together represent a minimal repeating unit of such a synthetase (Stein et al., 1996, Journal of Biological Chemistry 271: 15428-15435).

[0006] Mukherjee et al., 2012, Microbiology 158: 35-45, describe secondary metabolism in Trichoderma. Mukherjee et al., 2011, Journal of Biological Chemistry 286: 4544-4554, disclose two classes of new peptaibols synthesized by a single non-ribosomal peptide synthetase of Trichoderma virens. Kubicek et al., 2011, Genome Biology 12: R40, describe a comparative genome sequence analysis underscoring mycoparasitism as the ancestral life style of Trichoderma. Neohof et al., 2007, Microbiology 153: 3417-3437, describe intact-cell MALDI-TOF mass spectrometry analysis of peptaibol formation by the genus Trichoderma.

[0007] Mukherjee et al., 2012, supra, also describe that several Trichoderma spp. strains produce terpenoids synthesized from five-carbon isopentenyl units by the action of terpene cyclases. The T. virens genome harbors six terpene cyclases, while T. atroviride and T. reesei have three each.

[0008] The present invention relates to improved Trichoderma hosts that combine the capacity for expression of commercial quantities of a polypeptide of interest while being deficient in the production of peptaibol(s) and terpene(s) that can complicate production, recovery, or application of the polypeptide.

SUMMARY OF THE INVENTION

[0009] The present invention relates to mutants of a parent Trichoderma strain, comprising a polynucleotide encoding a heterologous polypeptide and one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0010] The present invention also relates to methods of producing a heterologous polypeptide, comprising:

[0011] (a) cultivating a mutant of a parent Trichoderma strain in a medium for the production of the heterologous polypeptide, wherein the mutant strain comprises a polynucleotide encoding the heterologous polypeptide and one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions; and optionally

[0012] (b) recovering the heterologous polypeptide from the cultivation medium.

[0013] The present invention further relates to methods of obtaining mutants of a parent Trichoderma strain, comprising:

[0014] (a) modifying one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene; and

[0015] (b) identifying a mutant strain from step (a) wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

BRIEF DESCRIPTION OF THE FIGURES

[0016] FIG. 1 shows a restriction map of pJyHi002.

[0017] FIG. 2 shows a restriction map of pJyHi001.

DEFINITIONS

[0018] Allelic variant: The term "allelic variant" means any of two or more alternative forms of a gene occupying the same chromosomal locus. Allelic variation arises naturally through mutation, and may result in polymorphism within populations. Gene mutations can be silent (no change in the encoded polypeptide) or may encode polypeptides having altered amino acid sequences. An allelic variant of a polypeptide is a polypeptide encoded by an allelic variant of a gene.

[0019] Aspartic protease: The term "aspartic protease" means a protease that uses an aspartate residue(s) for catalyzing the hydrolysis of peptide bonds in peptides and proteins. Aspartic proteases are a family of protease enzymes that use an aspartate residue for catalysis of their peptide substrates. In general, they have two highly-conserved aspartates in the active site and are optimally active at acidic pH (Szecsi, 1992, Scand. J. Clin. Lab. In vest. Suppl. 210: 5-22). For purposes of the present invention, aspartic protease activity is determined according to the procedure described in WO 2011/075677.

[0020] cDNA: The term "cDNA" means a DNA molecule that can be prepared by reverse transcription from a mature, spliced, mRNA molecule obtained from a eukaryotic cell. cDNA lacks intron sequences that may be present in the corresponding genomic DNA. The initial, primary RNA transcript is a precursor to mRNA that is processed through a series of steps, including splicing, before appearing as mature spliced mRNA.

[0021] Coding sequence: The term "coding sequence" means a polynucleotide, which directly specifies the amino acid sequence of a polypeptide. The boundaries of the coding sequence are generally determined by an open reading frame, which begins with a start codon such as ATG, GTG, or TTG and ends with a stop codon such as TAA, TAG, or TGA. The coding sequence may be a genomic DNA, cDNA, synthetic DNA, or a combination thereof.

[0022] Control sequences: The term "control sequences" means nucleic acid sequences necessary for expression of a polynucleotide encoding a polypeptide. Each control sequence may be native (i.e., from the same gene) or foreign (i.e., from a different gene) to the polynucleotide encoding the polypeptide or native or foreign to each other. Such control sequences include, but are not limited to, a leader, polyadenylation sequence, propeptide sequence, promoter, signal peptide sequence, and transcription terminator. At a minimum, the control sequences include a promoter, and transcriptional and translational stop signals. The control sequences may be provided with linkers for the purpose of introducing specific restriction sites facilitating ligation of the control sequences with the coding region of the polynucleotide encoding a polypeptide.

[0023] Deficient: The term "deficient" means a Trichoderma mutant strain that produces no detectable activity of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions, or, in the alternative, produces preferably at least 25% less, more preferably at least 50% less, even more preferably at least 75% less, and most preferably at least 95% less of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase than the parent Trichoderma strain when cultivated under identical conditions. The level of peptaibol, paracelsin, or terpenoid produced by a Trichoderma mutant strain of the present invention may be determined using methods described by Neuhof et al., 2007, Microbiology 153: 3417-3437 or Degenkolb et al., 2012, Chemistry & Biodiversity 9: 499-535.

[0024] Expression: The term "expression" includes any step involved in the production of a polypeptide including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion.

[0025] Expression vector: The term "expression vector" means a linear or circular DNA molecule that comprises a polynucleotide encoding a polypeptide and is operably linked to control sequences that provide for its expression.

[0026] High stringency conditions: The term "high stringency conditions" means for probes of at least 100 nucleotides in length, prehybridization and hybridization at 42.degree. C. in 5.times.SSPE, 0.3% SDS, 200 micrograms/ml sheared and denatured salmon sperm DNA, and 50% formamide, following standard Southern blotting procedures for 12 to 24 hours. The carrier material is finally washed three times each for 15 minutes using 0.2.times.SSC, 0.2% SDS at 65.degree. C.

[0027] Host cell: The term "host cell" means any cell type that is susceptible to transformation, transfection, transduction, or the like with a nucleic acid construct or expression vector comprising a polynucleotide. The term "host cell" encompasses any progeny of a parent cell that is not identical to the parent cell due to mutations that occur during replication.

[0028] Isolated: The term "isolated" means a substance in a form or environment that does not occur in nature. Non-limiting examples of isolated substances include (1) any non-naturally occurring substance, (2) any substance including, but not limited to, any enzyme, variant, nucleic acid, protein, peptide or cofactor, that is at least partially removed from one or more or all of the naturally occurring constituents with which it is associated in nature; (3) any substance modified by the hand of man relative to that substance found in nature; or (4) any substance modified by increasing the amount of the substance relative to other components with which it is naturally associated (e.g., recombinant production in a host cell; multiple copies of a gene encoding the substance; and use of a stronger promoter than the promoter naturally associated with the gene encoding the substance).

[0029] Low stringency conditions: The term "low stringency conditions" means for probes of at least 100 nucleotides in length, prehybridization and hybridization at 42.degree. C. in 5.times.SSPE, 0.3% SDS, 200 micrograms/ml sheared and denatured salmon sperm DNA, and 25% formamide, following standard Southern blotting procedures for 12 to 24 hours. The carrier material is finally washed three times each for 15 minutes using 0.2.times.SSC, 0.2% SDS at 50.degree. C.

[0030] Mature polypeptide: The term "mature polypeptide" means a polypeptide in its final form following translation and any post-translational modifications, such as N-terminal processing, C-terminal truncation, glycosylation, phosphorylation, etc.

[0031] Mature polypeptide coding sequence: The term "mature polypeptide coding sequence" means a polynucleotide that encodes a mature polypeptide having enzyme activity.

[0032] Medium stringency conditions: The term "medium stringency conditions" means for probes of at least 100 nucleotides in length, prehybridization and hybridization at 42.degree. C. in 5.times.SSPE, 0.3% SDS, 200 micrograms/ml sheared and denatured salmon sperm DNA, and 35% formamide, following standard Southern blotting procedures for 12 to 24 hours. The carrier material is finally washed three times each for 15 minutes using 0.2.times.SSC, 0.2% SDS at 55.degree. C.

[0033] Medium-high stringency conditions: The term "medium-high stringency conditions" means for probes of at least 100 nucleotides in length, prehybridization and hybridization at 42.degree. C. in 5.times.SSPE, 0.3% SDS, 200 micrograms/ml sheared and denatured salmon sperm DNA, and 35% formamide, following standard Southern blotting procedures for 12 to 24 hours. The carrier material is finally washed three times each for 15 minutes using 0.2.times.SSC, 0.2% SDS at 60.degree. C.

[0034] Modification: The term "modification" means introduction, substitution, or removal of one or more (e.g., several) nucleotides in a gene or a control sequence required for the transcription or translation thereof, or gene disruption, gene conversion, gene deletion, or random or specific mutagenesis of a gene, e.g., a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, a third terpene cyclase gene, or a combination thereof. The deletion of one or more (e.g., several) of the peptaibol synthetase gene, the paracelsin synthetase gene, the first terpene cyclase gene, the second terpene cyclase gene, and the third terpene cyclase gene may be partial or complete. The modification results in a decrease in or elimination (inactivation) of expression of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, the third terpene cyclase, or a combination thereof. In a preferred aspect, one or more (e.g., several) of the peptaibol synthetase gene, the paracelsin synthetase gene, the first terpene cyclase gene, the second terpene cyclase gene, and the third terpene cyclase gene are inactivated.

[0035] Non-ribosomal peptide synthetases: The term "non-ribosomal peptide synthetases" means enzymes involved in the biosynthesis of a class of non-ribosomally synthesized peptides known as peptaibols, containing non-proteinogenic amino acids (particularly alpha-aminoisobutyric acid).

[0036] Nucleic acid construct: The term "nucleic acid construct" means a nucleic acid molecule, either single- or double-stranded, which is isolated from a naturally occurring gene or is modified to contain segments of nucleic acids in a manner that would not otherwise exist in nature or which is synthetic, which comprises one or more control sequences.

[0037] Operably linked: The term "operably linked" means a configuration in which a control sequence is placed at an appropriate position relative to the coding sequence of a polynucleotide such that the control sequence directs expression of the coding sequence.

[0038] Paracelsin: The term "paracelsin" means a peptide antibiotic containing alpha-aminoisobutyric acid. Paracelsin is a peptaibol characterized by the presence of phenylalaninol as the C-terminal amino alcohol and by the specific amino acid content and sequence of peptaibols (Przybylski et al., 1984, Biomed. Mass Spectrometry 11, 569; Bruckner et al., 1983, Experientia 39: 528-530; Bruckner et al., 1984, Experientia 40: 1189-1197; Ritieni et al., 1995, Journal of Natural Products 58: 1745-1748; Pocsfalvi et al., 1997, Rapid Commun. Mass Spectrometry 11: 922-930).

[0039] Paracelsin synthetase: The term "paracelsin synthetase" means a peptaibol synthetase that catalyzes the formation of paracelsin.

[0040] Peptaibol: The term "peptaibol" means peptides characterized by short linear chain lengths (.ltoreq.20 residues), C-terminal alcohol residues, and high levels of non-standard amino acids, principally alpha-aminoisobutyric acid, isovaline, and the imino acid hydroxyproline. Peptaibol subfamilies 1, 4, 5 and 9 have been described (Szekeres et al., 2005, Acta. Microbiol. Immunol. Hung. 52: 137-168). Subfamily 1 (SF1) comprises about half of the known structures and includes peptides ranging from 18 to 20 residues in length. All of these peptides have partial sequence identities or similarities. Subfamily 4 (SF4) is comprised of peptides of 11-14 residues, also sharing sequence similarities, but having no sequence relationship to SF1. Subfamilies 5 and 9 (SF5 and SF9) have only a few members and comprise peptides with 11 or 6 and 7 residues, respectively, again with no sequence similarities to the other subfamilies (Neuhof et al., 2007, Microbiology 153: 3417-3427; Whitmore et al., 2004, Nucleic Acids Research 32 D593-D594; Mukherjee et al., 2011, J. Biol. Chem. 286: 4544-4554).

[0041] Peptaibol synthetase: The term "peptaibol synthetase" means a non-ribosomal peptide synthetase that is involved in the synthesis of one or more peptaibol(s).

[0042] Polypeptide fragment: The term "polypeptide fragment" means a polypeptide having one or more (e.g., several) amino acids deleted from the amino and/or carboxyl terminus of a polypeptide, wherein the fragment has enzyme activity, e.g., paracelsin synthetase, peptaibol synthetase, or terpene cyclase activity. In one aspect, a fragment contains at least 85% of the amino acid residues, e.g., at least 90% of the amino acid residues or at least 95% of the amino acid residues of a peptaibol synthetase, a paracelsin synthetase, or a terpene cyclase, such as SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 10; or homologous sequences thereof.

[0043] Sequence identity: The relatedness between two amino acid sequences or between two nucleotide sequences is described by the parameter "sequence identity".

[0044] For purposes of the present invention, the sequence identity between two amino acid sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch, 1970, J. Mol. Biol. 48: 443-453) as implemented in the Needle program of the EMBOSS package (EMBOSS: The European Molecular Biology Open Software Suite, Rice et al., 2000, Trends Genet. 16: 276-277), preferably version 5.0.0 or later. The parameters used are a gap open penalty of 10, a gap extension penalty of 0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix. The output of Needle labeled "longest identity" (obtained using the -nobrief option) is used as the percent identity and is calculated as follows:

(Identical Residues.times.100)/(Length of Alignment-Total Number of Gaps in Alignment)

[0045] For purposes of the present invention, the sequence identity between two deoxyribonucleotide sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch, 1970, supra) as implemented in the Needle program of the EMBOSS package (EMBOSS: The European Molecular Biology Open Software Suite, Rice et al., 2000, supra), preferably version 5.0.0 or later. The parameters used are a gap open penalty of 10, a gap extension penalty of 0.5, and the EDNAFULL (EMBOSS version of NCBI NUC4.4) substitution matrix. The output of Needle labeled "longest identity" (obtained using the -nobrief option) is used as the percent identity and is calculated as follows:

(Identical Deoxyribonucleotides.times.100)/(Length of Alignment-Total Number of Gaps in Alignment)

[0046] Subsequence: The term "subsequence" means a nucleotide sequence having one or more (e.g., several) nucleotides deleted from the 5' and/or 3' end of a polypeptide coding sequence, wherein the subsequence encodes a polypeptide fragment having enzyme activity, e.g., paracelsin synthetase, peptaibol synthetase, or terpene synthase activity. In one aspect, a subsequence contains at least 85% of the nucleotides, e.g., at least 90% of the nucleotides or at least 95% of the nucleotides of a polynucleotide encoding a peptaibol synthetase, a paracelsin synthetase, or a terpene cyclase, such as SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or SEQ ID NO: 9; or homologous sequences thereof.

[0047] Subtilisin-like serine protease: The term "subtilisin-like serine protease" means a protease with a substrate specificity similar to subtilisin that uses a serine residue for catalyzing the hydrolysis of peptide bonds in peptides and proteins. Subtilisin-like proteases (subtilases) are serine proteases characterized by a catalytic triad of the three amino acids aspartate, histidine, and serine. The arrangement of these catalytic residues is shared with the prototypical subtilisin from Bacillus licheniformis (Siezen and Leunissen, 1997, Protein Science 6: 501-523). For purposes of the present invention, subtilisin-like serine protease activity is determined according to the procedure described in WO 2011/075677.

[0048] Terpene cyclase: The term "terpene cyclase" means an enzyme that catalyzes the formation of cyclic terpenes through the cyclization of linear terpenes (e.g., isopentenyl-pyrophosphate, geranyl-pyrophosphate, farnesyl-pyrophosphate, and geranylgeranyl-pyrophosphate) containing varying numbers of isoprene units. The T. virens genome harbors six terpene cyclases, while T. atroviride and T. reesei have three each.

[0049] Terpene: The term "terpene" means a group of natural products composed of several isoprene units, which are synthesized from isopentenyl pyrophosphate. A terpene is also known as a terpenoid or an isoprenoid.

[0050] Trypsin-like serine protease: The term "trypsin-like serine protease" means a protease with a substrate specificity similar to trypsin that uses a serine residue for catalyzing the hydrolysis of peptide bonds in peptides and proteins. For purposes of the present invention, trypsin-like serine protease activity is determined according to the procedure described by WO 2011/075677.

[0051] Very high stringency conditions: The term "very high stringency conditions" means for probes of at least 100 nucleotides in length, prehybridization and hybridization at 42.degree. C. in 5.times.SSPE, 0.3% SDS, 200 micrograms/ml sheared and denatured salmon sperm DNA, and 50% formamide, following standard Southern blotting procedures for 12 to 24 hours. The carrier material is finally washed three times each for 15 minutes using 0.2.times.SSC, 0.2% SDS at 70.degree. C.

[0052] Very low stringency conditions: The term "very low stringency conditions" means for probes of at least 100 nucleotides in length, prehybridization and hybridization at 42.degree. C. in 5.times.SSPE, 0.3% SDS, 200 micrograms/ml sheared and denatured salmon sperm DNA, and 25% formamide, following standard Southern blotting procedures for 12 to 24 hours. The carrier material is finally washed three times each for 15 minutes using 0.2.times.SSC, 0.2% SDS at 45.degree. C.

DETAILED DESCRIPTION OF THE INVENTION

[0053] The present invention relates to mutants of a parent Trichoderma strain, comprising a polynucleotide encoding a heterologous polypeptide and one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0054] The present invention also relates to methods of producing a heterologous polypeptide, comprising: (a) cultivating a mutant of a parent Trichoderma strain in a medium for the production of the heterologous polypeptide, wherein the mutant strain comprises a polynucleotide encoding the heterologous polypeptide and one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions; and optionally (b) recovering the heterologous polypeptide from the cultivation medium.

[0055] The present invention further relates to methods of obtaining mutants of a parent Trichoderma strain, comprising: (a) modifying one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene; and (b) identifying a mutant strain from step (a) wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more (e.g., several) enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0056] The terms "a peptaibol synthetase gene" and "a paracelsin synthetase gene" can also be referred to herein as "a first peptaibol synthetase gene" and "a second peptaibol synthetase gene", respectively. The terms "a peptaibol synthetase" and "a paracelsin synthetase" can also be referred to herein as "a first peptaibol synthetase" and "a second peptaibol synthetase", respectively.

[0057] An advantage of the present invention is elimination or reduction of one or more (e.g., several) enzyme activities, which may be detrimental to the production, recovery, and/or application of a particular polypeptide of interest.

[0058] In the methods of the present invention, the parent Trichoderma strain may be any Trichoderma strain such as a wild-type Trichoderma strain or a mutant thereof. The parent Trichoderma strain may be Trichoderma harzianum, Trichoderma koningii, Trichoderma longibrachiatum, Trichoderma reesei, or Trichoderma viride; or the alternative sexual form thereof, i.e., Hypocrea.

[0059] In another aspect, the parent Trichoderma strain is Trichoderma harzianum. In another aspect, the parent Trichoderma strain is Trichoderma koningii. In another aspect, the parent Trichoderma strain is Trichoderma longibrachiatum. In another aspect, the parent Trichoderma strain is Trichoderma reesei. In another aspect, the parent Trichoderma strain is Trichoderma viride.

[0060] In another aspect, the parent Trichoderma reesei strain is Trichoderma reesei RutC30. In another aspect, the parent Trichoderma reesei strain is a mutant of Trichoderma reesei. In another aspect, the parent Trichoderma reesei strain is a mutant of Trichoderma reesei RutC30. In another aspect, the parent Trichoderma reesei strain is a morphological mutant of Trichoderma reesei (WO 97/26330).

[0061] A Trichoderma mutant strain of the present invention may be constructed by reducing or eliminating expression of one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene using methods well known in the art, such as insertions, disruptions, replacements, or deletions. A portion of the gene can be modified such as the coding region or a control sequence required for expression of the coding region. Such a control sequence of the gene may be a promoter sequence or a functional part thereof, i.e., a part that is sufficient for affecting expression of the gene. For example, a promoter sequence may be inactivated resulting in no expression or a weaker promoter may be substituted for the native promoter sequence to reduce expression of the coding sequence. Other control sequences for possible modification include, but are not limited to, a leader, propeptide sequence, signal sequence, transcription terminator, and transcriptional activator.

[0062] The Trichoderma mutant strains may be constructed by gene deletion techniques to eliminate or reduce expression of the genes. Gene deletion techniques enable the partial or complete removal of the gene thereby eliminating their expression. In such methods, deletion of the gene is accomplished by homologous recombination using a plasmid that has been constructed to contiguously contain the 5' and 3' regions flanking the gene.

[0063] The Trichoderma mutant strains may also be constructed by introducing, substituting, and/or removing one or more (e.g., several) nucleotides in the gene or a control sequence thereof required for the transcription or translation thereof. For example, nucleotides may be inserted or removed, e.g., for the introduction of a stop codon, the removal of the start codon, or a frame-shift of the open reading frame. Such a modification may be accomplished by site-directed mutagenesis or PCR generated mutagenesis in accordance with methods known in the art. See, for example, Botstein and Shortle, 1985, Science 229: 4719; Lo et al., 1985, Proceedings of the National Academy of Sciences USA 81: 2285; Higuchi et al., 1988, Nucleic Acids Research 16: 7351; Shimada, 1996, Meth. Mol. Biol. 57: 157; Ho et al., 1989, Gene 77: 61; Horton et al., 1989, Gene 77: 61; and Sarkar and Sommer, 1990, BioTechniques 8: 404.

[0064] The Trichoderma mutant strains may also be constructed by gene disruption techniques by inserting into the gene a disruptive nucleic acid construct comprising a nucleic acid fragment homologous to the gene that will create a duplication of the region of homology and incorporate construct DNA between the duplicated regions. Such a gene disruption can eliminate gene expression if the inserted construct separates the promoter of the gene from the coding region or interrupts the coding sequence such that a non-functional gene product results. A disrupting construct may be simply a selectable marker gene accompanied by 5' and 3' regions homologous to the gene. The selectable marker enables identification of transformants containing the disrupted gene.

[0065] The Trichoderma mutant strains may also be constructed by the process of gene conversion (see, for example, Iglesias and Trautner, 1983, Molecular General Genetics 189: 73-76). For example, in the gene conversion method, a nucleotide sequence corresponding to the gene is mutagenized in vitro to produce a defective nucleotide sequence, which is then transformed into the parent Trichoderma strain to produce a defective gene. By homologous recombination, the defective nucleotide sequence replaces the endogenous gene. It may be desirable that the defective nucleotide sequence also comprises a marker for selection of transformants containing the defective gene.

[0066] The Trichoderma mutant strains may also be constructed by established anti-sense techniques using a nucleotide sequence complementary to the nucleotide sequence of the gene (Parish and Stoker, 1997, FEMS Microbiology Letters 154: 151-157). More specifically, expression of the gene by a Trichoderma strain may be reduced or inactivated by introducing a nucleotide sequence complementary to the nucleotide sequence of the gene, which may be transcribed in the strain and is capable of hybridizing to the mRNA produced in the strain. Under conditions allowing the complementary anti-sense nucleotide sequence to hybridize to the mRNA, the amount of protein translated is thus reduced or eliminated.

[0067] The Trichoderma mutant strains may also be constructed by established RNA interference (RNAi) techniques (see, for example, WO 2005/056772 and WO 2008/080017).

[0068] The Trichoderma mutant strains may be further constructed by random or specific mutagenesis using methods well known in the art, including, but not limited to, chemical mutagenesis (see, for example, Hopwood, The Isolation of Mutants in Methods in Microbiology (J. R. Norris and D. W. Ribbons, eds.) pp. 363-433, Academic Press, New York, 1970). Modification of the gene may be performed by subjecting the parent strain to mutagenesis and screening for mutant strains in which expression of the gene has been reduced or inactivated. The mutagenesis, which may be specific or random, may be performed, for example, by use of a suitable physical or chemical mutagenizing agent, use of a suitable oligonucleotide, or subjecting the DNA sequence to PCR generated mutagenesis. Furthermore, the mutagenesis may be performed by use of any combination of these mutagenizing methods.

[0069] Examples of a physical or chemical mutagenizing agent suitable for the present purpose include ultraviolet (UV) irradiation, hydroxylamine, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N'-nitrosoguanidine (NTG) O-methyl hydroxylamine, nitrous acid, ethyl methane sulphonate (EMS), sodium bisulphite, formic acid, and nucleotide analogues. When such agents are used, the mutagenesis is typically performed by incubating the parent strain to be mutagenized in the presence of the mutagenizing agent of choice under suitable conditions, and selecting for mutants exhibiting reduced or no expression of the gene.

[0070] In one aspect, the modification results in the inactivation of one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the modification results in a decrease in expression of one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the modification results in expression of one or more (e.g., several) genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene being decreased, inactivated, or a combination thereof.

[0071] In another aspect, the mutant comprises a modification of a peptaibol synthetase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene. In another aspect, the mutant comprises a modification of a first terpene cyclase gene. In another aspect, the mutant comprises a modification of a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a third terpene cyclase gene.

[0072] In another aspect, the mutant comprises a modification of a peptaibol synthetase gene and a paracelsin synthetase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene and a first terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene and a first terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a first terpene cyclase gene and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a first terpene cyclase gene and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a second terpene cyclase gene and a third terpene cyclase gene.

[0073] In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, and a first terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene, a first terpene cyclase gene, and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene, a first terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a first terpene cyclase gene, and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a first terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene.

[0074] In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, and a second terpene cyclase gene. In another aspect, the mutant comprises a modification of a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, a second terpene cyclase gene, and a third terpene cyclase gene. In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, and a third terpene cyclase gene.

[0075] In another aspect, the mutant comprises a modification of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene.

[0076] In one aspect, the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2. In another aspect, the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity comprising or consisting of SEQ ID NO: 2.

[0077] In another aspect, the peptaibol synthetase gene comprises a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1 or the cDNA sequence thereof. In another aspect, the peptaibol synthetase gene comprises a polynucleotide comprising or consisting of SEQ ID NO: 1.

[0078] In another aspect, the peptaibol synthetase gene comprises a polynucleotide that hybridizes under very low stringency conditions, low stringency conditions, medium stringency conditions, medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 1 or the cDNA sequence thereof; or the full-length complement thereof.

[0079] In another aspect, the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 4. In another aspect, the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity comprising or consisting of SEQ ID NO: 4.

[0080] In another aspect, the paracelsin synthetase gene comprises a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 3. In another aspect, the paracelsin synthetase gene comprises a polynucleotide comprising or consisting of SEQ ID NO: 3.

[0081] In another aspect, the paracelsin synthetase gene comprises a polynucleotide that hybridizes under very low stringency conditions, low stringency conditions, medium stringency conditions, medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 3 or the cDNA sequence thereof; or the full-length complement thereof.

[0082] In another aspect, the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6. In another aspect, the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 6.

[0083] In another aspect, the first terpene cyclase gene comprises a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 5 or the genomic DNA sequence thereof. In another aspect, the first terpene cyclase gene comprises a polynucleotide comprising or consisting of SEQ ID NO: 5.

[0084] In another aspect, the first terpene cyclase gene comprises a polynucleotide that hybridizes under very low stringency conditions, low stringency conditions, medium stringency conditions, medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 5 or the genomic DNA sequence thereof; or the full-length complement thereof.

[0085] In another aspect, the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8. In another aspect, the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 8.

[0086] In another aspect, the second terpene cyclase gene comprises a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 7 or the genomic DNA sequence thereof. In another aspect, the second terpene cyclase gene comprises a polynucleotide comprising or consisting of SEQ ID NO: 7.

[0087] In another aspect, the second terpene cyclase gene comprises a polynucleotide that hybridizes under very low stringency conditions, low stringency conditions, medium stringency conditions, medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 7 or the genomic DNA sequence; or the full-length complement thereof.

[0088] In another aspect, the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 10. In another aspect, the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 10.

[0089] In another aspect, the third terpene cyclase gene comprises a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9 or the genomic DNA sequence thereof. In another aspect, the third terpene cyclase gene comprises a polynucleotide comprising or consisting of SEQ ID NO: 9.

[0090] In another aspect, the third terpene cyclase gene comprises a polynucleotide that hybridizes under very low stringency conditions, low stringency conditions, medium stringency conditions, medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 9 or the genomic DNA sequence thereof; or the full-length complement thereof.

[0091] The nucleotide sequences disclosed herein or subsequences thereof, as well as the amino acid sequences thereof or fragments thereof, may be used to design nucleic acid probes to identify and clone homologous DNA of the genes described above from strains of different genera or species according to methods well known in the art. In particular, such probes can be used for hybridization with the genomic DNA or cDNA of the genus or species of interest, following standard Southern blotting procedures, in order to identify and isolate the corresponding gene therein. Such probes can be considerably shorter than the entire sequence, but should be at least 14, e.g., at least 25, at least 35, or at least 70 nucleotides in length. Preferably, the nucleic acid probe is at least 100 nucleotides in length, e.g., at least 200 nucleotides, at least 300 nucleotides, at least 400 nucleotides, at least 500 nucleotides, at least 600 nucleotides, at least 700 nucleotides, at least 800 nucleotides, or at least 900 nucleotides in length. Both DNA and RNA probes can be used. The probes are typically labeled for detecting the corresponding gene (for example, with .sup.32P, .sup.3H, .sup.35S, biotin, or avidin).

[0092] Thus, a genomic DNA or cDNA library prepared from such other organisms may be screened for DNA that hybridizes with the probes described above. Genomic or other DNA from such other organisms may be separated by agarose or polyacrylamide gel electrophoresis, or other separation techniques. DNA from the libraries or the separated DNA may be transferred to and immobilized on nitrocellulose or other suitable carrier material. In order to identify a clone or DNA that is homologous with the nucleotide sequences disclosed herein or subsequences thereof, the carrier material is used in a Southern blot. For purposes of the present invention, hybridization indicates that the nucleic acid sequence hybridizes to a labeled nucleic acid probe corresponding to the nucleotide sequences disclosed herein, its complementary strand, or a subsequence thereof, under very low to very high stringency conditions. Molecules to which the nucleic acid probe hybridizes under these conditions are detected using X-ray film.

[0093] For short probes of about 15 nucleotides to about 70 nucleotides in length, stringency conditions are defined as prehybridization and hybridization at about 5.degree. C. to about 10.degree. C. below the calculated T.sub.m using the calculation according to Bolton and McCarthy (1962, Proc. Natl. Acad. Sci. USA 48:1390) in 0.9 M NaCl, 0.09 M Tris-HCl pH 7.6, 6 mM EDTA, 0.5% NP-40, 1.times.Denhardt's solution, 1 mM sodium pyrophosphate, 1 mM sodium monobasic phosphate, 0.1 mM ATP, and 0.2 mg of yeast RNA per ml following standard Southern blotting procedures for 12 to 24 hours optimally. The carrier material is finally washed once in 6.times.SCC plus 0.1% SDS for 15 minutes and twice each for 15 minutes using 6.times.SSC at 5.degree. C. to 10.degree. C. below the calculated T.sub.m.

[0094] A nucleotide sequence homologous or complementary to a gene described herein may be used from other microbial sources to modify the corresponding gene in a Trichoderma strain of choice.

[0095] In another aspect, the modification of a gene in the Trichoderma mutant strain is unmarked with a selectable marker. Removal of the selectable marker gene may be accomplished by culturing the mutants on a counter-selection medium. Where the selectable marker gene contains repeats flanking its 5' and 3' ends, the repeats will facilitate the looping out of the selectable marker gene by homologous recombination when the mutant strain is submitted to counter-selection. The selectable marker gene may also be removed by homologous recombination by introducing into the mutant strain a nucleic acid fragment comprising 5' and 3' regions of the defective gene, but lacking the selectable marker gene, followed by selecting on a counter-selection medium. By homologous recombination, the defective gene containing the selectable marker gene is replaced with the nucleic acid fragment lacking the selectable marker gene. Other methods known in the art may also be used.

[0096] It will be understood that the methods of the present invention are not limited to a particular order for obtaining the Trichoderma mutant strain. The modification of a gene may be introduced into the parent strain at any step in the construction of the strain for the production of a polypeptide of interest. It is preferred that the Trichoderma mutant strain has already been made peptaibol, paracelsin, and/or terpene-deficient prior to such a construction.

[0097] In a further aspect of the present invention, the mutants of Trichoderma strains may contain additional modifications, e.g., deletions or disruptions, of other genes, which may encode substances detrimental to the production, recovery, or application of a polypeptide of interest.

[0098] In one aspect, the Trichoderma strain further comprises a modification, e.g., disruption or deletion, of one or more (e.g., several) genes encoding a proteolytic activity selected from the group consisting of an aminopeptidase, dipeptidylaminopeptidase, tripeptidylaminopeptidase, carboxypeptidase, metalloprotease, cysteine protease, and vacuolar protease.

[0099] In a preferred aspect, the Trichoderma strain further comprises a modification, e.g., disruption or deletion, of one or more (e.g., several) genes selected from the group consisting of a first subtilisin-like serine protease gene, a first aspartic protease gene, a trypsin-like serine protease gene, a second subtilisin-like serine protease gene, and a second aspartic protease gene, as described in WO 2011/075677, which is incorporated herein by reference in its entirety.

[0100] In another aspect, the Trichoderma strain further comprises a modification, e.g., disruption or deletion, of one or more (e.g., several) additional genes encoding enzymes selected from the group consisting of an oxidoreductase, a transferase, a hydrolase, a lyase, an isomerase, or a ligase.

[0101] In another aspect, the Trichoderma strain further comprises a modification, e.g., disruption or deletion, of one or more (e.g., several) additional genes encoding enzymes selected from the group consisting of an acetylmannan esterase, acetylxylan esterase, aminopeptidase, alpha-amylase, arabinanase, arabinofuranosidase, carbohydrase, carboxypeptidase, catalase, cellobiohydrolase, cellulase, cellulose inducing protein, chitinase, coumaric acid esterase, cyclodextrin glycosyltransferase, cutinase, cyclodextrin glycosyltransferase, deoxyribonuclease, endoglucanase, esterase, expansin, feruloyl esterase, AA9 (GH61) polypeptide, alpha-galactosidase, beta-galactosidase, glucocerebrosidase, glucose oxidase, alpha-glucosidase, beta-glucosidase, glucuronidase, glucuronoyl esterase, haloperoxidase, hemicellulase, invertase, isomerase, laccase, ligase, lipase, mannanase, mannosidase, mutanase, oxidase, pectinolytic enzyme, peroxidase, phospholipase, phytase, phenoloxidase, polyphenoloxidase, proteolytic enzyme, ribonuclease, swollenin, alpha-1,6-transglucosidase, transglutaminase, urokinase, xylanase, or beta-xylosidase.

[0102] In another aspect, the Trichoderma strain further comprises a modification, e.g., disruption or deletion, of one or more (e.g., several) additional genes encoding enzymes selected from the group consisting of an endoglucanase, a cellobiohydrolase, and a beta-glucosidase,

[0103] In the methods of the present invention, the Trichoderma mutant strain preferably produces at least the same amount of a heterologous polypeptide of interest as the corresponding parent Trichoderma strain when cultured under identical production conditions. In another aspect, the mutant strain produces at least 5% more, e.g., at least 10% more, at least 25% more, at least 50% more, at least 75% more, and at least 100% more of the heterologous polypeptide than the corresponding parent Trichoderma strain when cultured under identical production conditions.

[0104] The Trichoderma mutant strains are cultivated in a nutrient medium for production of the heterologous polypeptide of interest using methods known in the art. For example, the strain may be cultivated by shake flask cultivation or small-scale or large-scale fermentation (including continuous, batch, fed-batch, or solid state fermentations) in laboratory or industrial fermentors performed in a suitable medium and under conditions allowing the polypeptide to be expressed and/or isolated. The cultivation takes place in a suitable nutrient medium comprising carbon and nitrogen sources and inorganic salts, using procedures known in the art. Suitable media are available from commercial suppliers or may be prepared according to published compositions (e.g., in catalogues of the American Type Culture Collection). The secreted polypeptide can be recovered directly from the medium. If the polypeptide is not secreted, it may be obtained from cell lysates. A whole broth comprising a heterologous polypeptide of interest can also be recovered.

[0105] The polypeptide of interest may be detected using methods known in the art that are specific for the polypeptide. These detection methods may include use of specific antibodies, high performance liquid chromatography, capillary chromatography, formation of an enzyme product, disappearance of an enzyme substrate, or SDS-PAGE. For example, an enzyme assay may be used to determine the activity of an enzyme. Procedures for determining enzyme activity are known in the art for many enzymes (see, for example, D. Schomburg and M. Salzmann (eds.), Enzyme Handbook, Springer-Verlag, New York, 1990).

[0106] The resulting polypeptide may be isolated by methods known in the art. For example, a polypeptide of interest may be isolated from the cultivation medium by conventional procedures including, but not limited to, centrifugation, filtration, extraction, spray-drying, evaporation, or precipitation. The isolated polypeptide may then be further purified by a variety of procedures known in the art including, but not limited to, chromatography (e.g., ion exchange, affinity, hydrophobic, chromatofocusing, and size exclusion), electrophoretic procedures (e.g., preparative isoelectric focusing (IEF), differential solubility (e.g., ammonium sulfate precipitation), or extraction (see, e.g., Protein Purification, J.-C. Janson and Lars Ryden, editors, VCH Publishers, New York, 1989).

[0107] The heterologous polypeptide of interest may be any polypeptide foreign to the Trichoderma strain. The polypeptide may be encoded by a single gene or two or more genes. The term "polynucleotide encoding the polypeptide" will be understood to encompass one or more (e.g., several) genes involved in the production of the polypeptide. The term "heterologous polypeptide" is defined herein as a polypeptide that is not native to the host strain; a native polypeptide in which structural modifications have been made to alter the native polypeptide, e.g., the protein sequence of a native polypeptide; or a native polypeptide whose expression is quantitatively altered as a result of a manipulation of the polynucleotide or host strain by recombinant DNA techniques, e.g., a stronger promoter, multiple copies of a DNA encoding the polypeptide. Thus, the present invention also encompasses, within the scope of the term "heterologous polypeptides," such recombinant production of native polypeptides, to the extent that such expression involves the use of genetic elements not native to the Trichoderma strain, or use of native elements that have been manipulated to function in a manner that do not normally occur in the host strain.

[0108] The heterologous polypeptide may be any polypeptide having a biological activity of interest. The term "polypeptide" is not meant herein to refer to a specific length of the encoded product and, therefore, encompasses peptides, oligopeptides, and proteins. The term "polypeptide" also includes naturally occurring allelic and engineered variations of a polypeptide. The term "polypeptide" further encompasses hybrid and fusion polypeptides.

[0109] A hybrid polypeptide comprises a combination of partial polypeptide sequences obtained from at least two different polypeptides wherein one or more (e.g., several) may be heterologous to the Trichoderma strain.

[0110] A fusion polypeptide or cleavable fusion polypeptide comprises a polypeptide fused at the N-terminus or the C-terminus of another polypeptide. A fusion polypeptide is produced by fusing a polynucleotide encoding one polypeptide to a polynucleotide encoding another polypeptide. Techniques for producing fusion polypeptides are known in the art, and include ligating the coding sequences encoding the polypeptides so that they are in frame and that expression of the fusion polypeptide is under control of the same promoter(s) and terminator. Fusion polypeptides may also be constructed using intein technology in which fusion polypeptides are created post-translationally (Cooper et al., 1993, EMBO J. 12: 2575-2583; Dawson et al., 1994, Science 266: 776-779).

[0111] A fusion polypeptide can further comprise a cleavage site between the two polypeptides. Upon secretion of the fusion protein, the site is cleaved releasing the two polypeptides. Examples of cleavage sites include, but are not limited to, the sites disclosed in Martin et al., 2003, J. Ind. Microbiol. Biotechnol. 3: 568-576; Svetina et al., 2000, J. Biotechnol. 76: 245-251; Rasmussen-Wilson et al., 1997, Appl. Environ. Microbiol. 63: 3488-3493; Ward et al., 1995, Biotechnology 13: 498-503; and Contreras et al., 1991, Biotechnology 9: 378-381; Eaton et al., 1986, Biochemistry 25: 505-512; Collins-Racie et al., 1995, Biotechnology 13: 982-987; Carter et al., 1989, Proteins: Structure, Function, and Genetics 6: 240-248; and Stevens, 2003, Drug Discovery World 4: 35-48.

[0112] In one aspect, the polypeptide is an antibody, an antigen, an antimicrobial peptide, an enzyme, a growth factor, a hormone, an immunodilator, a neurotransmitter, a receptor, a reporter protein, a structural protein, or a transcription factor.

[0113] In another aspect, the polypeptide is an oxidoreductase, a transferase, a hydrolase, a lyase, an isomerase, or a ligase. In another aspect, the polypeptide is an acetylmannan esterase, acetylxylan esterase, aminopeptidase, alpha-amylase, arabinanase, arabinofuranosidase, carbohydrase, carboxypeptidase, catalase, cellobiohydrolase, cellulase, cellulose inducing protein, chitinase, coumaric acid esterase, cyclodextrin glycosyltransferase, cutinase, cyclodextrin glycosyltransferase, deoxyribonuclease, endoglucanase, esterase, expansin, feruloyl esterase, AA9 (GH61) polypeptide, alpha-galactosidase, beta-galactosidase, glucocerebrosidase, glucose oxidase, alpha-glucosidase, beta-glucosidase, glucuronidase, glucuronoyl esterase, haloperoxidase, hemicellulase, invertase, isomerase, laccase, ligase, lipase, mannanase, mannosidase, mutanase, oxidase, pectinolytic enzyme, peroxidase, phospholipase, phytase, phenoloxidase, polyphenoloxidase, proteolytic enzyme, ribonuclease, swollenin, alpha-1,6-transglucosidase, transglutaminase, urokinase, xylanase, or beta-xylosidase.

[0114] In another aspect, the polypeptide is an albumin, a collagen, a tropoelastin, an elastin, or a gelatin.

[0115] In another aspect, the polypeptide is an endoglucanase. In another aspect, the polypeptide is a cellobiohydrolase. In another aspect, the polypeptide is a beta-glucosidase.

[0116] In another aspect, the polypeptide is an AA9 (GH61) polypeptide. In another aspect, the polypeptide is a xylanase. In another aspect, the polypeptide is a beta-xylosidase. In another aspect, the polypeptide is an acetylxylan esterase. In another aspect, the polypeptide is a feruloyl esterase. In another aspect, the polypeptide is an arabinofuranosidase. In another aspect, the polypeptide is a glucuronidase. In another aspect, the polypeptide is an acetylmannan esterase. In another aspect, the polypeptide is an arabinanase. In another aspect, the polypeptide is a coumaric acid esterase. In another aspect, the polypeptide is a galactosidase. In another aspect, the polypeptide is a glucuronoyl esterase. In another aspect, the polypeptide is a mannanase. In another aspect, the polypeptide is a mannosidase. In another aspect, the polypeptide is a cellulose inducing protein. In another aspect, the polypeptide is an expansin. In another aspect, the polypeptide is a Swollenin.

[0117] In the methods of the present invention, the mutant of the Trichoderma strain is a recombinant strain, comprising a polynucleotide encoding a heterologous polypeptide, which is advantageously used in the recombinant production of the polypeptide. The strain is preferably transformed with a vector comprising the polynucleotide encoding the heterologous polypeptide followed by integration of the vector into the chromosome. "Transformation" means introducing a vector comprising the polynucleotide into a host strain so that the vector is maintained as a chromosomal integrant or as a self-replicating extra-chromosomal vector. Integration is generally considered to be an advantage as the polynucleotide is more likely to be stably maintained in the strain. Integration of the vector into the chromosome can occur by homologous recombination, non-homologous recombination, or transposition.

[0118] The polynucleotide encoding a heterologous polypeptide may be obtained from any prokaryotic, eukaryotic, or other source, e.g., archaeabacteria. For purposes of the present invention, the term "obtained from" as used herein in connection with a given source shall mean that the polypeptide is produced by the source or by a strain in which a gene from the source has been inserted.

[0119] In the methods of the present invention, a mutant Trichoderma strain of the present invention may also be used for the recombinant production of a polypeptide that is native to the Trichoderma strain. The native polypeptide may be produced by recombinant means by, for example, placing a gene encoding the polypeptide under the control of a different promoter to enhance expression of the substance, expediting its export outside the strain by use of, for example, a signal sequence, or increasing the copy number of a gene encoding the polypeptide normally produced by the Trichoderma strain.

[0120] The techniques used to isolate or clone a polynucleotide encoding a polypeptide of interest are known in the art and include isolation from genomic DNA, preparation from cDNA, or a combination thereof. The cloning of such a polynucleotide from such genomic DNA can be effected, e.g., by using the well-known polymerase chain reaction (PCR). See, for example, Innis et al., 1990, PCR Protocols: A Guide to Methods and Application, Academic Press, New York. The cloning procedures may involve excision and isolation of a desired nucleic acid fragment comprising the polynucleotide encoding the polypeptide, insertion of the fragment into a vector molecule, and incorporation of the recombinant vector into a mutant Trichoderma strain of the present invention where multiple copies or clones of the polynucleotide will be replicated. The polynucleotide may be of genomic, cDNA, RNA, semisynthetic, synthetic origin, or any combinations thereof.

[0121] An isolated polynucleotide encoding a heterologous polypeptide may be manipulated in a variety of ways to provide for expression of the polypeptide in a mutant Trichoderma strain of the present invention. Manipulation of the polynucleotide's sequence prior to its insertion into a vector may be desirable or necessary depending on the expression vector. The techniques for modifying polynucleotide sequences utilizing recombinant DNA methods are well known in the art.

[0122] A nucleic acid construct comprising a polynucleotide encoding a polypeptide may be operably linked to one or more (e.g., several) control sequences capable of directing expression of the coding sequence in a mutant Trichoderma strain of the present invention under conditions compatible with the control sequences.

[0123] The control sequence may be an appropriate promoter, a nucleotide sequence that is recognized by a mutant Trichoderma strain of the present invention for expression of the polynucleotide encoding the polypeptide. The promoter contains transcriptional control sequences that mediate expression of the polypeptide. The promoter may be any nucleotide sequence that shows transcriptional activity in the mutant Trichoderma strain, including mutant, truncated, and hybrid promoters, and may be obtained from genes encoding extracellular or intracellular polypeptides either native or heterologous (foreign) to the mutant Trichoderma strain.

[0124] Examples of suitable promoters for directing the transcription of the nucleic acid constructs in the methods of the present invention are promoters obtained from the genes for Aspergillus nidulans acetamidase, Aspergillus niger neutral alpha-amylase, Aspergillus niger acid stable alpha-amylase, Aspergillus niger or Aspergillus awamori glucoamylase (glaA), Aspergillus oryzae TAKA amylase, Aspergillus oryzae alkaline protease, Aspergillus oryzae triose phosphate isomerase, Fusarium oxysporum trypsin-like protease (WO 96/00787), Fusarium venenatum amyloglucosidase (WO 00/56900), Fusarium venenatum Daria (WO 00/56900), Fusarium venenatum Quinn (WO 00/56900), Rhizomucor miehei lipase, Rhizomucor miehei aspartic proteinase, Trichoderma reesei beta-glucosidase, Trichoderma reesei cellobiohydrolase I, Trichoderma reesei cellobiohydrolase II, Trichoderma reesei endoglucanase I, Trichoderma reesei endoglucanase II, Trichoderma reesei endoglucanase III, Trichoderma reesei endoglucanase V, Trichoderma reesei xylanase I, Trichoderma reesei xylanase II, Trichoderma reesei xylanase III, Trichoderma reesei beta-xylosidase, Trichoderma reesei glyceraldehyde-6 phosphate dehydrogenase, and Trichoderma reesei translation elongation factor, as well as the NA2-tpi promoter (a modified promoter from an Aspergillus neutral alpha-amylase gene in which the untranslated leader has been replaced by an untranslated leader from an Aspergillus triose phosphate isomerase gene; non-limiting examples include modified promoters from an Aspergillus niger neutral alpha-amylase gene in which the untranslated leader has been replaced by an untranslated leader from an Aspergillus nidulans or Aspergillus oryzae triose phosphate isomerase gene); and mutant, truncated, and hybrid promoters thereof. Other promoters are described in U.S. Pat. No. 6,011,147.

[0125] The control sequence may also be a transcription terminator, which is recognized by a host cell to terminate transcription. The terminator is operably linked to the 3'-terminus of the polynucleotide encoding the polypeptide. Any terminator that is functional in a Trichoderma strain may be used in the present invention.

[0126] Preferred terminators are obtained from the genes for Aspergillus nidulans acetamidase, Aspergillus nidulans anthranilate synthase, Aspergillus niger glucoamylase, Aspergillus niger alpha-glucosidase, Aspergillus oryzae TAKA amylase, Fusarium oxysporum trypsin-like protease, Trichoderma reesei beta-glucosidase, Trichoderma reesei cellobiohydrolase I, Trichoderma reesei cellobiohydrolase II, Trichoderma reesei endoglucanase I, Trichoderma reesei endoglucanase II, Trichoderma reesei endoglucanase III, Trichoderma reesei endoglucanase V, Trichoderma reesei xylanase I, Trichoderma reesei xylanase II, Trichoderma reesei xylanase III, Trichoderma reesei beta-xylosidase, and Trichoderma reesei translation elongation factor.

[0127] The control sequence may also be a leader, a nontranslated region of an mRNA that is important for translation by a mutant Trichoderma strain of the present invention. The leader is operably linked to the 5'-terminus of the polynucleotide encoding the polypeptide. Any leader that is functional in the mutant Trichoderma strain may be used in the present invention.

[0128] Preferred leaders for filamentous fungal host cells are obtained from the genes for Aspergillus oryzae TAKA amylase and Aspergillus nidulans triose phosphate isomerase.

[0129] The control sequence may also be a polyadenylation sequence, a sequence operably linked to the 3' terminus of the nucleotide sequence and, when transcribed, is recognized by the mutant Trichoderma strain as a signal to add polyadenosine residues to transcribed mRNA. Any polyadenylation sequence that is functional in the mutant Trichoderma strain may be used in the present invention.

[0130] Preferred polyadenylation sequences for filamentous fungal host cells are obtained from the genes for Aspergillus oryzae TAKA amylase, Aspergillus niger glucoamylase, Aspergillus nidulans anthranilate synthetase, Fusarium oxysporum trypsin-like protease, and Aspergillus niger alpha-glucosidase.

[0131] The control sequence may also be a signal peptide coding region that encodes a signal peptide linked to the N-terminus of a polypeptide and directs the polypeptide into the cell's secretory pathway. The 5'-end of the coding sequence of the polynucleotide may inherently contain a signal peptide coding sequence naturally linked in translation reading frame with the segment of the coding sequence that encodes the polypeptide. Alternatively, the 5'-end of the coding sequence may contain a signal peptide coding sequence that is foreign to the coding sequence. A foreign signal peptide coding sequence may be required where the coding sequence does not naturally contain a signal peptide coding sequence. Alternatively, a foreign signal peptide coding sequence may simply replace the natural signal peptide coding sequence in order to enhance secretion of the polypeptide. However, any signal peptide coding sequence that directs the expressed polypeptide into the secretory pathway of the mutant Trichoderma strain, i.e., secreted into a culture medium, may be used in the present invention.

[0132] Effective signal peptide coding regions for the mutant Trichoderma strains are the signal peptide coding regions obtained from the genes for Aspergillus niger neutral amylase, Aspergillus niger glucoamylase, Aspergillus oryzae TAKA amylase, Humicola insolens cellulase, Humicola insolens endoglucanase V, Humicola lanuginosa lipase, and Rhizomucor miehei aspartic proteinase.

[0133] The control sequence may also be a propeptide coding sequence that encodes a propeptide positioned at the N-terminus of a polypeptide. The resultant polypeptide is known as a proenzyme or propolypeptide (or a zymogen in some cases). A propolypeptide is generally inactive and can be converted to an active polypeptide by catalytic or autocatalytic cleavage of the propeptide from the propolypeptide. The propeptide coding region may be obtained from genes for Saccharomyces cerevisiae alpha-factor, Rhizomucor miehei aspartic proteinase, and Myceliophthora thermophila laccase (WO 95/33836).

[0134] Where both signal peptide and propeptide sequences are present, the propeptide sequence is positioned next to the N-terminus of a polypeptide and the signal peptide sequence is positioned next to the N-terminus of the propeptide sequence.

[0135] It may also be desirable to add regulatory sequences that regulate expression of the polypeptide relative to the growth of the mutant Trichoderma strain. Examples of regulatory sequences are those that cause expression of the gene to be turned on or off in response to a chemical or physical stimulus, including the presence of a regulatory compound. Regulatory systems in filamentous fungi such as the Aspergillus niger glucoamylase promoter, Aspergillus oryzae TAKA alpha-amylase promoter, and Aspergillus oryzae glucoamylase promoter, Trichoderma reesei cellobiohydrolase I promoter, and Trichoderma reesei cellobiohydrolase II promoter may be used. Other examples of regulatory sequences are those that allow for gene amplification. In eukaryotic systems, these regulatory sequences include the dihydrofolate reductase gene that is amplified in the presence of methotrexate, and the metallothionein genes that are amplified with heavy metals. In these cases, the polynucleotide encoding the polypeptide would be operably linked to the regulatory sequence.

[0136] In the methods of the present invention, a recombinant expression vector comprising a polynucleotide encoding a polypeptide of interest, a promoter, and transcriptional and translational stop signals may be used for the recombinant production of the polypeptide of interest. The various nucleotide and control sequences may be joined together to produce a recombinant expression vector that may include one or more convenient restriction sites to allow for insertion or substitution of the polynucleotide encoding the polypeptide at such sites. Alternatively, the polynucleotide may be expressed by inserting the polynucleotide or a nucleic acid construct comprising the polynucleotide into an appropriate vector for expression. In creating the expression vector, the coding sequence is located in the vector so that the coding sequence is operably linked with the appropriate control sequences for expression.

[0137] The recombinant expression vector may be any vector (e.g., a plasmid or virus) that can be conveniently subjected to recombinant DNA procedures and can bring about expression of the nucleotide sequence. The choice of the vector will typically depend on its compatibility with the mutant Trichoderma strain into which the vector is to be introduced. The vector may be a linear or closed circular plasmid.

[0138] The recombinant expression vector may be any vector (e.g., a plasmid or virus) that can be conveniently subjected to recombinant DNA procedures and can bring about expression of the polynucleotide. The choice of the vector will typically depend on the compatibility of the vector with the host cell into which the vector is to be introduced. The vector may be a linear or closed circular plasmid.

[0139] The vector may be an autonomously replicating vector, i.e., a vector that exists as an extrachromosomal entity, the replication of which is independent of chromosomal replication, e.g., a plasmid, an extrachromosomal element, a minichromosome, or an artificial chromosome. The vector may contain any means for assuring self-replication. Alternatively, the vector may be one that, when introduced into the host cell, is integrated into the genome and replicated together with the chromosome(s) into which it has been integrated. Furthermore, a single vector or plasmid or two or more vectors or plasmids that together contain the total DNA to be introduced into the genome of the host cell, or a transposon, may be used.

[0140] The vector preferably contains one or more selectable markers that permit easy selection of transformed, transfected, transduced, or the like cells. A selectable marker is a gene the product of which provides for biocide or viral resistance, resistance to heavy metals, prototrophy to auxotrophs, and the like.

[0141] Selectable markers for use in a filamentous fungal host cell include, but are not limited to, adeA (phosphoribosylam inoimidazole-succinocarboxam ide synthase), adeB (phosphoribosyl-aminoimidazole synthase), amdS (acetamidase), argB (ornithine carbamoyltransferase), bar (phosphinothricin acetyltransferase), hph (hygromycin phosphotransferase), niaD (nitrate reductase), pyrG (orotidine-5'-phosphate decarboxylase), sC (sulfate adenyltransferase), and trpC (anthranilate synthase), as well as equivalents thereof. Preferred for use in a Trichoderma cell are adeA, adeB, amdS, hph, and pyrG genes.

[0142] The selectable marker may be a dual selectable marker system as described in WO 2010/039889. In one aspect, the dual selectable marker is an hph-tk dual selectable marker system.

[0143] The vector preferably contains an element(s) that permits integration of the vector into the host cell's genome or autonomous replication of the vector in the cell independent of the genome.

[0144] For integration into the host cell genome, the vector may rely on the polynucleotide's sequence encoding the polypeptide or any other element of the vector for integration into the genome by homologous or non-homologous recombination. Alternatively, the vector may contain additional polynucleotides for directing integration by homologous recombination into the genome of the host cell at a precise location(s) in the chromosome(s). To increase the likelihood of integration at a precise location, the integrational elements should contain a sufficient number of nucleic acids, such as 100 to 10,000 base pairs, 400 to 10,000 base pairs, and 800 to 10,000 base pairs, which have a high degree of sequence identity to the corresponding target sequence to enhance the probability of homologous recombination. The integrational elements may be any sequence that is homologous with the target sequence in the genome of the host cell. Furthermore, the integrational elements may be non-encoding or encoding polynucleotides. On the other hand, the vector may be integrated into the genome of the host cell by non-homologous recombination.

[0145] For autonomous replication, the vector may further comprise an origin of replication enabling the vector to replicate autonomously in the host cell in question. The origin of replication may be any plasmid replicator mediating autonomous replication that functions in a cell. The term "origin of replication" or "plasmid replicator" means a polynucleotide that enables a plasmid or vector to replicate in vivo.

[0146] Examples of origins of replication useful in a filamentous fungal cell are AMA1 and ANSI (Gems et al., 1991, Gene 98: 61-67; Cullen et al., 1987, Nucleic Acids Res. 15: 9163-9175; WO 00/24883). Isolation of the AMA1 gene and construction of plasmids or vectors comprising the gene can be accomplished according to the methods disclosed in WO 00/24883.

[0147] More than one copy of a polynucleotide may be inserted into a host cell to increase production of a polypeptide. An increase in the copy number of the polynucleotide can be obtained by integrating at least one additional copy of the sequence into the host cell genome or by including an amplifiable selectable marker gene with the polynucleotide where cells containing amplified copies of the selectable marker gene, and thereby additional copies of the polynucleotide, can be selected for by cultivating the cells in the presence of the appropriate selectable agent.

[0148] The procedures used to ligate the elements described above to construct the recombinant expression vectors of the present invention are well known to one skilled in the art (see, e.g., Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, 2d edition, Cold Spring Harbor, New York).

[0149] A vector comprising the nucleotide sequence can be introduced, e.g., by transformation, into the mutant Trichoderma strain so that the vector is maintained as a chromosomal integrant or as a self-replicating extra-chromosomal vector. Integration is generally considered to be an advantage as the nucleotide sequence is more likely to be stably maintained in the strain. Integration of the vector into the chromosome occurs by homologous recombination, non-homologous recombination, or transposition.

[0150] The introduction of an expression vector into the mutant Trichoderma strain may involve a process consisting of protoplast formation, transformation of the protoplasts, and regeneration of the strain wall in a manner known per se. Suitable procedures for transformation of Trichoderma strains are described in Malardier et al., 1989, Gene 78: 147-156, and WO 96/00787.

[0151] The present invention is further described by the following examples that should not be construed as limiting the scope of the invention.

EXAMPLES

Strains

[0152] Trichoderma reesei strain 981-O-8 (D4) is a mutagenized strain of Trichoderma reesei RutC30 (Montenecourt and Eveleigh, 1979, Adv. Chem. Ser. 181: 289-301. Trichoderma reesei strain AgJg115-104-7B1 is a ku70 disrupted strain of Trichoderma reesei RutC30.

Media and Solutions

[0153] Overlay PDA medium was composed of 39 g of Potato Dextrose Agar (Difco) and deionized water to 1 liter supplemented with 100 .mu.g of hygromycin B per ml.

[0154] PDA plates were composed of 39 g of Potato Dextrose Agar (Difco) and deionized water to 1 liter.

[0155] PEG buffer was composed of 500 g of PEG 4000, 10 mM CaCl.sub.2, 10 mM Tris-HCl pH 7.5, and deionized water to 1 liter; filter sterilized.

[0156] SOC medium was composed of 20 g of tryptone, 5 g of yeast extract, 0.5 g of NaCl, 10 ml of 20 mM KCl, and deionized water to 1 liter.

[0157] STC was composed of 0.8 M or 1 M sorbitol, 10 mM or 25 mM CaCl.sub.2, and 10 mM or 25 mM Tris-HCl, pH 7.5 or pH 8; filter sterilized.

[0158] TAE buffer was composed of 4.82 g of Tris Base, 1.14 ml of Glacial acetic acid, 2 ml of 0.5 M EDTA pH 8.0, and deionized water to 1 liter.

[0159] TBE buffer was composed of 10.8 g of Tris base, 5.5 g of boric acid, 4 ml of 0.5 M EDTA pH 8.0, and deionized water to 1 liter.

[0160] TE buffer was composed of 10 mM Tris-0.1 mM EDTA pH 8.0.

[0161] 2XYT plus ampicillin plates were composed of 16 g of tryptone, 10 g of yeast extract, 5 g of NaCl, 15 g of Bacto agar, 1 ml of 100 mg/ml ampicillin stock, and deionized water to 1 liter.

[0162] YEG medium was composed of 5 g of yeast extract, 20 g of glucose, and deionized water to 1 liter.

[0163] YP medium was composed of 10 g of yeast extract, 20 g of Bacto peptone, and deionized water to 1 liter.

Example 1: Trichoderma reesei Strain 981-O-8 Genomic DNA Extraction

[0164] Trichoderma reesei strain 981-O-8 was grown in 50 ml of YEG medium in a baffled shake flask at 28.degree. C. for 2 days with agitation at 200 rpm. Mycelia were harvested by filtration using MIRACLOTH.RTM. (Calbiochem, La Jolla, Calif., USA), washed twice in deionized water, and frozen under liquid nitrogen. Frozen mycelia were ground, by mortar and pestle, to a fine powder, and total DNA was isolated using a DNEASY.RTM. Plant Maxi Kit (QIAGEN Inc., Valencia, Calif., USA).

Example 2: Trichoderma reesei Protoplast Generation and Transformation

[0165] Protoplast preparation and transformation were performed using a modification of the protocol described by Penttila et al., 1987, Gene 61: 155-164. Briefly, Trichoderma reesei strain AgJg115-104-7B1 was cultivated in 25 ml of YP medium supplemented with 2% (w/v) glucose at 28.degree. C. for 17 hours with gentle agitation at 90 rpm. Mycelia were collected by filtration using a Millipore Vacuum Driven Disposable Filtration System (Millipore, Bedford, Mass., USA) and washed twice with deionized water and twice with 1.2 M sorbitol. Protoplasts were generated by suspending the washed mycelia in 30 ml of 1.2 M sorbitol containing 15 mg of GLUCANEX.RTM. 200 G (Novozymes A/S, Bagsvaerd, Denmark) per ml and 0.36 units of chitinase (Sigma Chemical Co., St. Louis, Mo., USA) per ml for 15-25 minutes at 34.degree. C. with gentle shaking at 90 rpm. Protoplasts were collected by centrifugation at 400.times.g for 7 minutes and washed twice with cold 1.2 M sorbitol. The protoplasts were counted using a hemacytometer and re-suspended to a final concentration of 1.times.10.sup.8 protoplasts per ml in STC. Excess protoplasts were stored in a Cryo 1.degree. C. Freezing Container (Nalgene, Rochester, N.Y., USA) at -80.degree. C.

[0166] Approximately 2 .mu.g of each of the deletion cassettes described in the following Examples were digested with Pme I. Each digestion reaction was purified by 0.8% agarose gel electrophoresis using TBE buffer where a DNA band was excised from the gel and extracted using a NUCLEOSPIN.RTM. Gel and PCR Cleanup kit (Macherey-Nagel GmbH & Co. KG, Duren, Germany). The resulting purified DNA was added to 100 .mu.l of the protoplast solution and mixed gently. PEG buffer (250 .mu.l) was added and mixed, and then the mixture was incubated at 34.degree. C. for 30 minutes. STC (3 ml) was then added and mixed, and the mixture was spread onto PDA plates supplemented with 1 M sucrose. After incubation at 28.degree. C. for 16 hours, 15 ml of overlay PDA medium supplemented with 100 .mu.g of hygromycin B per ml were added to each plate. The plates were incubated at 28.degree. C. for 4-6 days.

Example 3: Construction of a Peptaibol Synthetase Gene Deletion Vector

[0167] The 5' flanking sequence of the Trichoderma reesei strain 981-O-8 peptaibol synthetase gene (Trirre2:123786; SEQ ID NO: 1 for the genomic DNA sequence and SEQ ID NO: 2 for the deduced amino acid sequence) was amplified from genomic DNA of T. reesei strain 981-O-8 using the gene-specific forward and reverse primers shown below. Forward primer (1201181): 5'-tcacatggtttaaacggcgcgccGACCCGAAAGAACGCAAAAGTCCAT-3' (SEQ ID NO: 11) Reverse primer (1201182): 5'-agccttgttttgtcGTGTCAAGAACTTGGATCTCCTAGGAG-3' (SEQ ID NO: 12)

[0168] The underlined portion is an Asc I site introduced for cloning and the region in italics represents an introduced extension corresponding to a homologous region of the site of vector insertion necessary for cloning.

[0169] The amplification reaction was composed of 137 ng of T. reesei 981-O-8 genomic DNA, 200 .mu.m dNTP's, 0.4 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2 (New England Biolabs, Inc., Ipswich, Mass., USA), and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase (New England Biolabs, Inc., Ipswich, Mass., USA) in a final volume of 50 .mu.l. The amplification reaction was performed in a ROBOCYCLER.RTM. (Agilent Technologies, Santa Clara, Calif., USA) programmed for 1 cycle at 98.degree. C. for 3 minutes; 35 cycles each at 98.degree. C. for 10 seconds, 55.degree. C. for 30 seconds, and 72.degree. C. for 1.5 minutes; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 2.4 kb product was observed. The 2.4 kb PCR product was excised from the gel and purified using a MINELUTE.RTM. Gel Extraction Kit (QIAGEN Inc., Valencia, Calif., USA) according to the manufacturer's protocol.

[0170] The 2.4 kb PCR product was inserted into Asc I-digested pJfyS1579-41-11 (WO 2011/075677) using an IN-FUSION.RTM. HD ADVANTAGE.RTM. PCR Cloning Kit (Clontech, Palo Alto, Calif., USA) according to the manufacturer's protocol. The reaction was composed of 100 ng of pJfyS1579-41-11, 60 ng of the PCR product, and 2 .mu.l of IN-FUSION.RTM. HD Enzyme Premix (Clontech, Palo Alto, Calif., USA) in a 10 .mu.l reaction volume. The reaction was incubated for 15 minutes at 50.degree. C. Two and a half .mu.l were used to transform SOLOPACK.RTM. Gold Supercompetent (Agilent, Santa Clara, Calif., USA) cells. The DNA was added to the cells and incubated for 30 minutes on ice followed by a heat-shock at 42.degree. C. for 30 seconds. Then SOC medium (250 .mu.l) was added and incubated at 37.degree. C. for 1 hour. The reaction was spread onto 2XYT plus ampicillin plates and incubated overnight at 37.degree. C. Plasmid DNA was purified from several transformants using a BIOROBOT.RTM. 9600 (QIAGEN Inc., Valencia, Calif., USA) and analyzed by DNA sequencing using a 3130XL Genetic Analyzer (Life Technologies, Carlsbad, Calif., USA) to identify a plasmid containing the desired insert. One clone containing the insert was identified and designated plasmid pJyHi002A. Plasmid pJyHi002A was used to insert the 3' flank of the peptaibol synthetase gene.

[0171] The 3' peptaibol synthetase gene flanking sequence was amplified from T. reesei 981-O-8 genomic DNA using PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase (New England Biolabs, Inc., Ipswich, Mass., USA) and the gene-specific forward and reverse primers shown below.

TABLE-US-00001 Forward Primer (1201183): (SEQ ID NO: 13) 5'-cctagttggagtattcctgcaggTCCTCATCTGTGGCTCATATTAGG T-3' Reverse primer (1201524): (SEQ ID NO: 14) 5'-tggccatatttaaatcctgcagggtttaaacCAAGGCGGGATAGTGT CGGTTCTT-3'

[0172] The underlined portion is a Sbf I site introduced for cloning, the region in italics represents an introduced extension corresponding to a homologous region of the site of vector insertion necessary for cloning, and the bold portion is an introduced Pme I site for later removal of the bacterial propagation portion of the plasmid.

[0173] The amplification reaction was composed of 137 ng of T. reesei 981-O-8 genomic DNA, 200 .mu.m dNTP's, 0.4 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2, and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase in a final volume of 50 .mu.l. The amplification reaction was performed in an ROBOCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 3 minutes; 35 cycles each at 98.degree. C. for 10 seconds, 55.degree. C. for 30 seconds, and 72.degree. C. for 1 minute; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 2.0 kb fragment was excised from the gel and agarose was extracted using a NUCLEOSPIN.RTM. Extract II Kit (Clontech, Palo Alto, Calif., USA) according to the manufacturer's protocol.

[0174] The 2.0 kb PCR product was inserted into Sbf 1-digested pJyHi002A using an IN-FUSION.RTM. HD ADVANTAGE.RTM. PCR Cloning Kit according to the manufacturer's protocol. The reaction was composed of 100 ng of pJyHi002A, 50 ng of the 2.0 kb PCR product, and 2 .mu.l of IN-FUSION.RTM. Enzyme (Clontech, Palo Alto, Calif., USA) in a 10 .mu.l reaction volume. The reaction was incubated for 15 minutes at 50.degree. C. Forty .mu.l of TE buffer were added to the reaction and 2.5 .mu.l were used to transform SOLOPACK.RTM. Gold Supercompetent cells according to the manufacturer's protocol. The DNA was added to the cells and incubated for 30 minutes on ice followed by a heat-shock at 42.degree. C. for 30 seconds. Then SOC medium (250 .mu.l) was added and incubated at 37.degree. C. for 1 hour. The reaction was spread onto 2XYT plus ampicillin plates and incubated overnight at 37.degree. C. Plasmid DNA was purified from several transformants using a BIOROBOT.RTM. 9600 and analyzed by DNA sequencing using a 3130XL Genetic Analyzer to identify a plasmid containing the desired insert. One clone containing the insert was identified and designated plasmid pJyHi002 (FIG. 1). Plasmid pJyHi002 was used to delete the peptaibol synthetase gene.

Example 4: Generation of Peptaibol Synthetase Gene Deleted Trichoderma reesei Strain

[0175] Trichoderma reesei strain AgJg115-104-7B1 was transformed as described in Example 2 with plasmid pJyHi002. Transformants were transferred from PDA plates supplemented with 1 M sucrose with sterile inoculation loops to new PDA plates and grown at 28.degree. C. for 7 days.

[0176] Transformants of Trichoderma reesei strain AgJg115-104-7B1 containing the pJyHi002 deletion vector in the peptaibol synthetase locus, thereby deleting the peptaibol synthetase gene, were screened by fungal spore PCR using a PHIRE.RTM. Plant Direct PCR Kit (Thermo Fisher Scientific, Waltham, Mass., USA) and the primers shown below.

TABLE-US-00002 Forward Primer (1202690): (SEQ ID NO: 15) 5'-TGCCCCACGATATCTCTCCTTCTCC-3' Reverse Primer (067947): (SEQ ID NO: 16) 5'-CTACATCGAAGCTGAAAGCACGAGA-3'

[0177] Spores from several transformants were collected using a 1 .mu.l loop and transferred to 15 .mu.l of dilution buffer provided by the Kit. The spore samples were incubated at room temperature for 3 minutes and centrifuged at 2000.times.g for one minute. One microliter of each spore sample was used as template. The reaction was composed of 1 .mu.l of a spore suspension, 10 .mu.l of 2.times. PHIRE.RTM. Plant PCR Buffer (Thermo Scientific, Waltham, Mass., USA), 0.5 .mu.M primer 1202690, 0.5 .mu.M primer 067947, 0.4 .mu.l of PHIRE.RTM. Hot Start DNA Polymerase (Thermo Scientific, Waltham, Mass., USA), and 8.2 .mu.l of water. The reaction was performed in an EPPENDORF.RTM. MASTERCYCLER.RTM. (Eppendorf AG, Hamburg, Germany) programmed for 1 cycle at 95.degree. C. for 10 minutes; 35 cycles each at 95.degree. C. for 30 seconds, 55.degree. C. for 30 seconds, and 72.degree. C. for 5 minutes 45 seconds; 1 cycle at 72.degree. C. for 15 minutes; and a 4.degree. C. hold. Since primer 1202690 is located upstream of the 5' flanking region and primer 067947 is located in the hpt marker, only transformants with the deletion cassette in the correct locus would yield a PCR product. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 3.7 kb fragment was observed indicating the deletion cassette was in the correct locus.

[0178] The transformants were then analyzed by Southern analysis according to the following procedure. Genomic DNA from each of the transformants was extracted using a MASTERPURE.TM. Yeast DNA Purification Kit (Epicentre, Madison, Wis., USA). Each transformant was cultivated in 25 ml of YP medium supplemented with 2% glucose in shake flasks for 72 hours with agitation at 200 rpm. The mycelia were collected from the cultures by filtration using Whatman 1 filter paper (Fisher Scientific, Pittsburgh, Pa., USA). The filter paper was inserted in a ceramic funnel placed into a sidearm flask. Under vacuum, the culture broth was filtered and rinsed with water and filtered again. The mycelia were transferred to 2 ml tubes and then dried overnight using a SPEEDVAC.RTM. concentrator (Thermo Fisher Scientific, Waltham, Mass., USA). The dried mycelia were crushed with a metal tool in each tube and approximately 50 .mu.l of the dried mycelia were transferred to new tubes. Three hundred microliters of Yeast Cell Lysis Solution (Epicentre, Madison, Wis., USA) were added to each tube and vortexed. The samples were incubated at 65.degree. C. for 20 minutes and then placed on ice for 5 minutes. One hundred fifty microliters of MPC Protein Precipitation Reagent (Epicentre, Madison, Wis., USA) were added to each tube and then the reactions were vortexed. The tubes were centrifuged for 10 minutes at 9300.times.g. The supernatants were transferred to microcentrifuge tubes followed by 0.5 ml of isopropanol, and then the tubes were centrifuged at 9300.times.g for 10 minutes. The supernatants were discarded and each of the pellets was washed with 0.5 ml of 70% ethanol. The ethanol was removed and discarded and the pellets were briefly dried using a SPEEDVAC.RTM. concentrator. Then the pellets were resuspended in 60 .mu.l of TE buffer. The samples were incubated at 65.degree. C. for about an hour to dissolve the pellet and then 0.3 .mu.l of 100 mg/ml RNAse A (QIAGEN Inc., Valencia, Calif., USA) was added and the samples were incubated at 37.degree. C. for an hour.

[0179] Approximately two micrograms of each genomic DNA sample were digested with 30 units of Bcl I and 10 units of Swa I for 16 hours. The digestions were subjected to 0.8% agarose gel electrophoresis using TAE buffer and blotted onto NYTRAN.RTM. SuperCharge blotting membrane (Schleicher & Schuell BioScience, Keene, N.H., USA) using a TURBOBLOTTER.RTM. (Schleicher & Schuell BioScience, Keene, N.H., USA) for approximately 12-16 hours following the manufacturer's recommendations. A PCR probe, hybridizing to the 5' flanking sequence of the peptaibol synthetase gene, was synthesized by incorporation of digoxigenin-11-dUTP by PCR using a PCR DIG Probe Synthesis Kit (Roche Molecular Biochemicals, Indianapolis, Ind., USA) according to the manufacturer's protocol and the following forward and reverse primers:

TABLE-US-00003 Forward primer (1201259): (SEQ ID NO: 17) 5'-TAGCTAGCTGTCTTGGATGAATCGAGGTTG-3' Reverse primer (1202008): (SEQ ID NO: 18) 5'-TCGTCTTCATGAGCATGTTGTTGGG-3'

[0180] The amplification reaction (50 .mu.l) was composed of 200 .mu.m dNTP's, 0.5 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2, and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase in a final volume of 50 .mu.l. The amplification reaction was performed in a ROBOCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 3 minutes; 35 cycles each at 98.degree. C. for 10 seconds, 55.degree. C. for 15 seconds, and 72.degree. C. for 1.5 minutes; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 0.5 kb fragment was excised from the gel and agarose was extracted using a MINELUTE.RTM. Gel Extraction Kit according to the manufacturer's protocol. The purified fragment was used as template for labelling with digoxygenin using a PCR DIG Probe Synthesis Kit. The reaction consisted of 5 .mu.l of PCR buffer with MgCl.sub.2 (Roche, Indianapolis, Ind., USA), 5 .mu.l of PCR DIG probe synthesis mix which includes 200 .mu.M dNTP (Roche Molecular Biochemicals, Indianapolis, Ind., USA), 1 .mu.M forward primer 1201259, 1 .mu.M reverse primer 1202008, 2.6 units of Enzyme mix, EXPAND.RTM. High Fidelity (Roche, Indianapolis, Ind., USA), and 100 .mu.g of template DNA up to a volume of 50 .mu.l. The amplification reaction was performed in a ROBOCYCLER.RTM. programmed for 1 cycle at 95.degree. C. for 2 minutes; 30 cycles each at 95.degree. C. for 30 seconds, 60.degree. C. for 30 seconds, and 72.degree. C. for 40 seconds; and 1 cycle at 72.degree. C. for 10 minutes.

[0181] The incorporation of digoxygenin was confirmed by a molecular weight shift of the labelled probe which ran at approximately 0.5 kb. Hybridization was performed in DIG Easy Hyb buffer (Roche Molecular Biochemicals, Indianapolis, Ind., USA) at 42.degree. C. for 15-17 hours. The membrane was then washed in 2.times.SSC plus 0.1% SDS for 5 minutes at room temperature followed by two washes in 0.5.times.SSC plus 0.1% SDS for 15 minutes each at 65.degree. C. The probe-target hybrids were detected by a chemiluminescent assay (Roche Molecular Biochemicals, Indianapolis, Ind., USA) following the manufacturer's instructions

[0182] Southern analysis indicated that several of the transformants harbored the deletion cassette in a single copy. One transformant containing the peptaibol synthase gene deletion was designated Trichoderma reesei JyHi002-26A.

Example 5: Construction of a Paracelsin Synthetase Gene Deletion Vector

[0183] The 5' flanking sequence of the Trichoderma reesei strain 981-O-8 paracelsin synthetase gene (Trirre2:23171; SEQ ID NO: 3 for the genomic DNA sequence and SEQ ID NO: 4 for the deduced amino acid sequence) was amplified from genomic DNA of T. reesei strain 981-O-8 using the gene-specific forward and reverse primers shown below.

TABLE-US-00004 Forward primer (1201177): (SEQ ID NO: 19) 5'-tcacatggtttaaacggcgcgccTACTACCTAGTACAGTGCTTATT TA-3' Reverse primer (1201178): (SEQ ID NO: 20) 5'-agccttgttttgtcGTTTTTTCTCCAAATTTGTACAGAATTATC T-3'

[0184] The underlined portion is an Asc I site introduced for cloning and the region in italics represents an introduced extension corresponding to a homologous region of the site of vector insertion necessary for cloning.

[0185] The amplification reaction was composed of 137 ng of T. reesei 981-O-8 genomic DNA, 200 .mu.m dNTP's, 0.4 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2, and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase in a final volume of 50 .mu.l. The amplification reaction was performed in an ROBOCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 3 minutes; 35 cycles each at 98.degree. C. for 10 seconds, 55.degree. C. for 30 seconds, and 72.degree. C. for 1 minute; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 2.0 kb PCR product was observed. The 2.0 kb PCR product was excised from the gel and purified using a MINELUTE.RTM. Gel Extraction Kit according to the manufacturer's protocol.

[0186] The 2.0 kb PCR product was inserted into Asc 1-digested pJfyS1579-41-11 (WO 2011/075677) using an IN-FUSION.RTM. HD ADVANTAGE.RTM. PCR Cloning Kit according to the manufacturer's protocol. The reaction was composed of 200 ng of pJfyS1579-41-11, 100 ng of the PCR product, and 2 .mu.l of IN-FUSION.RTM. HD Enzyme Premix in a 10 .mu.l reaction volume. The reaction was incubated for 15 minutes at 50.degree. C. Two and a half .mu.l were used to transform SOLOPACK.RTM. Gold Supercompetent cells. The DNA was added to the cells and incubated for 30 minutes on ice followed by a heat-shock at 42.degree. C. for 30 seconds. Then SOC medium (250 .mu.l) was added and incubated at 37.degree. C. for 1 hour. The reaction was spread onto 2XYT plus ampicillin plates and incubated overnight at 37.degree. C. Plasmid DNA was purified from several transformants using a BIOROBOT.RTM. 9600 and analyzed by DNA sequencing using a 3130XL Genetic Analyzer to identify a plasmid containing the desired insert. One clone containing the insert was identified and designated plasmid pJyHi001A. Plasmid pJyHi001A was used to insert the 3' flank of the paracelsin synthetase gene.

[0187] The 3' paracelsin synthetase gene flanking sequence was amplified from T. reesei 981-O-8 genomic DNA using PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase and the gene-specific forward and reverse primers shown below.

TABLE-US-00005 Forward Primer (1201179): (SEQ ID NO: 21) 5'-cctagttggagtattcctgcaggAGGAATTGTGCCTGGCTGTTGAGT T-3' Reverse primer (1201523): (SEQ ID NO: 22) 5'-tggccatatttaaatcctgcagggtttaaacGCTTATCGATCCGGCA TATCGCTCT-3'

[0188] The underlined portion is a Sbf I site introduced for cloning, the region in italics represents an introduced extension corresponding to a homologous region of the site of vector insertion necessary for cloning, and the bold portion is an introduced Pme I site for later removal of the bacterial propagation portion of the plasmid.

[0189] The amplification reaction was composed of 137 ng of T. reesei 981-O-8 genomic DNA, 200 .mu.m dNTP's, 0.4 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2, and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase in a final volume of 50 .mu.l. The amplification reaction was performed in an ROBOCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 3 minutes; 35 cycles each at 98.degree. C. for 10 seconds, 55.degree. C. for 30 seconds, and 72.degree. C. for 1 minute; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 2.0 kb fragment was excised from the gel and agarose was extracted using a NUCLEOSPIN.RTM. Extract 11 Kit according to the manufacturer's protocol.

[0190] The 2.0 kb PCR product was inserted into Sbf I-digested pJyHi001A using an IN-FUSION.RTM. HD ADVANTAGE.RTM. PCR Cloning Kit according to the manufacturer's protocol. The reaction was composed of 200 ng of pJyHi001A, 50 ng of the 2.0 kb PCR product, and 2 .mu.l of IN-FUSION.RTM. Enzyme in a 10 .mu.l reaction volume. The reaction was incubated for 15 minutes at 50.degree. C. Forty .mu.l of TE buffer were added to the reaction and 2.5 .mu.l were used to transform SOLOPACK.RTM. Gold Supercompetent cells. The DNA was added to the cells and incubated for 30 minutes on ice followed by a heat-shock at 42.degree. C. for 30 seconds. Then SOC medium (250 .mu.l) was added and incubated at 37.degree. C. for 1 hour. The reaction was spread onto 2XYT plus ampicillin plates and incubated overnight at 37.degree. C. Plasmid DNA was purified from several transformants using a BIOROBOT.RTM. 9600 and analyzed by DNA sequencing using a 3130XL Genetic Analyzer to identify a plasmid containing the desired insert. One clone containing the insert was identified and designated plasmid pJyHi001 (FIG. 2). Plasmid pJyHi001 was used to delete the paracelsin synthetase gene.

Example 6: Generation of Paracelsin Synthetase Gene Deleted Trichoderma reesei Strain

[0191] Trichoderma reesei strain AgJg115-104-7B1 was transformed as described in Example 2 with plasmid pJyHi001. Transformants were transferred from PDA plates supplemented with 1 M sucrose with sterile inoculation loops to new PDA plates and grown at 28.degree. C. for 7 days.

[0192] Transformants of Trichoderma reesei strain AgJg115-104-7B1 containing the pJyHi001 deletion vector in the paracelsin synthetase locus, thereby deleting the paracelsin synthetase gene, were screened by fungal spore PCR using a PHIRE.RTM. Plant Direct PCR Kit and the primers shown below.

TABLE-US-00006 Forward Primer (1202687): (SEQ ID NO: 23) 5'-TACCTTACAGGCCCTCCGCGAGCTA-3' Reverse Primer (067947): (SEQ ID NO: 24) 5'-CTACATCGAAGCTGAAAGCACGAGA-3'

[0193] Spores from several transformants were collected using a 1 .mu.l loop and transferred to 15 .mu.l of dilution buffer provided by the Kit. The spore samples were incubated at room temperature for 3 minutes and centrifuged at 2000.times.g for one minute. One microliter of each spore sample was used as template. The reaction was composed of 1 .mu.l of a spore suspension, 10 .mu.l of 2.times.PHIRE.RTM. Plant PCR Buffer, 0.5 .mu.M primer 1202687, 0.5 .mu.M primer 067947, 0.4 .mu.l of PHIRE.RTM. Hot Start DNA Polymerase, and 8.2 .mu.l of water. The reaction was performed in an EPPENDORF.RTM. MASTERCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 5 minutes; 40 cycles each at 98.degree. C. for 5 seconds and 72.degree. C. for 1 minute 30 seconds; 1 cycle at 72.degree. C. for 1 minute; and a 4.degree. C. hold. Since primer 1202687 is located upstream of the 5' flanking region and primer 067947 is located in the hpt marker, only transformants with the deletion cassette in the correct locus would yield a PCR product. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 3.2 kb fragment was observed indicating the deletion cassette was in the correct locus.

[0194] The transformants were then analyzed by Southern analysis according to the following procedure. Genomic DNA from each of the transformants was extracted using a MASTERPURE.TM. Yeast DNA Purification Kit. Each transformant was cultivated in 25 ml of YP medium supplemented with 2% glucose in shake flasks for 72 hours with agitation at 200 rpm. The mycelia were collected from the cultures by filtration using Whatman 1 filter paper. The filter paper was inserted in a ceramic funnel placed into a sidearm flask. Under vacuum, the culture broth was filtered and rinsed with water and filtered again. The mycelia were transferred to 2 ml tubes and then dried overnight using a SPEEDVAC.RTM. concentrator. The dried mycelia were crushed with a metal tool in each tube and approximately 50 .mu.l of the dried mycelia was transferred to new tubes. Three hundred microliters of Yeast Cell Lysis Solution were added to each tube and vortexed. The samples were incubated at 65.degree. C. for 20 minutes and then placed on ice for 5 minutes. One hundred fifty microliters of MPC Protein Precipitation Reagent were added to each tube and then the reactions were vortexed. The tubes were centrifuged for 10 minutes at 9300.times.g. The supernatants were transferred to microcentrifuge tubes followed by 0.5 ml of isopropanol, and then the tubes were centrifuged at 9300.times.g for 10 minutes. The supernatants were discarded and each of the pellets was washed with 0.5 ml of 70% ethanol. The ethanol was removed and discarded and the pellets were briefly dried using a SPEEDVAC.RTM. concentrator. Then the pellets were resuspended in 60 .mu.l of TE buffer. The samples were incubated at 65.degree. C. for about an hour to dissolve the pellet and then 0.3 .mu.l of 100 mg/ml RNAse A was added and the samples were incubated at 37.degree. C. for an hour.

[0195] Approximately two micrograms of each genomic DNA sample were digested with 20 units of BsiW I for 6 hours. The digestions were subjected to 0.8% agarose gel electrophoresis using TAE buffer and blotted onto NYTRAN.RTM. SuperCharge blotting membrane using a TURBOBLOTTER.RTM. for approximately 12-16 hours following the manufacturer's recommendations. A PCR probe, hybridizing to the 5' flanking sequence of the paracelsin synthetase gene, was synthesized by incorporation of digoxigenin-11-dUTP by PCR using a PCR DIG Probe Synthesis Kit according to the manufacturer's protocol and the following forward and reverse primers:

TABLE-US-00007 Forward primer (1201253): (SEQ ID NO: 25) 5'-ATGTTGGAGCCTTGCCTCCAGAGTCCTCAC-3' Reverse primer (1202005): (SEQ ID NO: 26) 5'-GGGTTCAGTCCAGAAGCAGAACCAGGATCA-3'

[0196] The amplification reaction (50 .mu.l) was composed of 200 .mu.m dNTP's, 0.5 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2, and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase in a final volume of 50 .mu.l. The amplification reaction was performed in a ROBOCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 1 minute; 35 cycles each at 98.degree. C. for 10 seconds, 55.degree. C. for 30 seconds, and 72.degree. C. for 15 seconds; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 0.5 kb fragment was excised from the gel and agarose was extracted using a MINELUTE.RTM. Gel Extraction Kit. The purified fragment was used as template for labelling with digoxygenin using a PCR DIG Probe Synthesis Kit. The reaction consisted of 5 .mu.l of PCR buffer with MgCl.sub.2, 5 .mu.l of PCR DIG probe synthesis mix which includes 200 .mu.M dNTP, 1 .mu.M forward primer 1201253, 1 .mu.M reverse primer 1202005, 2.6 units of Enzyme mix, EXPAND.RTM. High Fidelity, and 100 .mu.g of template DNA up to a volume of 50 .mu.l. The amplification reaction was performed in a ROBOCYCLER.RTM. programmed for 1 cycle at 95.degree. C. for 2 minutes; 30 cycles each at 95.degree. C. for 30 seconds, 60.degree. C. for 30 seconds, and 72.degree. C. for 40 seconds; and 1 cycle at 72.degree. C. for 10 minutes.

[0197] The incorporation of digoxygenin was confirmed by a molecular weight shift of the labelled probe which ran at approximately 0.5 kb. Hybridization was performed in DIG Easy Hyb buffer at 42.degree. C. for 15-17 hours. The membrane was then washed in 2.times.SSC plus 0.1% SDS for 5 minutes at room temperature followed by two washes in 0.5.times.SSC plus 0.1% SDS for 15 minutes each at 65.degree. C. The probe-target hybrids were detected by a chemiluminescent assay (Roche Molecular Biochemicals, Indianapolis, Ind., USA) following the manufacturer's instructions.

[0198] The transformants were also analyzed by PCR using PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase and the primers shown below.

TABLE-US-00008 Forward Primer (1202689): (SEQ ID NO: 27) 5'-CAGATGAGCCCTACATGACGCCAGC-3' Reverse Primer (1200592): (SEQ ID NO: 28) 5'-GGCTCCATACCGACGATATGC-3'

[0199] The amplification reaction was composed of 150 ng of genomic DNA, 200 .mu.m dNTP's, 0.4 .mu.M primers, 3% DMSO, 5.times. PHUSION.RTM. HF Buffer with 1.5 mM MgCl.sub.2, and 2 units of PHUSION.RTM. Hot Start High-Fidelity DNA Polymerase in a final volume of 50 .mu.l. The amplification reaction was performed in an ROBOCYCLER.RTM. programmed for 1 cycle at 98.degree. C. for 30 seconds; 35 cycles each at 98.degree. C. for 10 seconds, 70.degree. C. for 30 seconds, and 72.degree. C. for 2 minutes 18 seconds; and 1 cycle at 72.degree. C. for 10 minutes. PCR products were separated by 0.8% agarose gel electrophoresis using TBE buffer where a 4.6 kb PCR product was expected if the paracelsin synthetase deletion cassette was integrated.

[0200] Both Southern and PCR analysis indicated that several of the transformants harbored the deletion cassette in a single copy. One transformant containing the paracelsin synthetase gene deletion was designated Trichoderma reesei JyHi001-4B.

[0201] The present invention is further described by the following numbered paragraphs:

[0202] [1] A mutant of a parent Trichoderma strain, comprising a polynucleotide encoding a heterologous polypeptide and one or more genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0203] [2] The mutant of paragraph 1, which comprises a modification of the peptaibol synthetase gene.

[0204] [3] The mutant of paragraph 1 or 2, which comprises a modification of the paracelsin synthetase gene.

[0205] [4] The mutant of any of paragraphs 1-3, which comprises a modification of the first terpene cyclase gene.

[0206] [5] The mutant of any of paragraphs 1-4, which comprises a modification of the second terpene cyclase gene.

[0207] [6] The mutant of any of paragraphs 1-5, which comprises a modification of the third terpene cyclase gene.

[0208] [7] The mutant of paragraph 1-6, which comprises a modification of the peptaibol synthetase gene, the paracelsin synthetase gene, the first terpene cyclase gene, the second terpene cyclase gene, and the third terpene cyclase gene.

[0209] [8] The mutant of any of paragraphs 1-7, wherein the Trichoderma strain is selected from the group consisting of Trichoderma harzianum, Trichoderma koningii, Trichoderma longibrachiatum, Trichoderma reesei, and Trichoderma viride.

[0210] [9] The mutant of any of paragraphs 1-8, wherein the Trichoderma strain is Trichoderma reesei.

[0211] [10] The mutant of any of paragraphs 1-9, which produces at least 25% less of one or more of the enzymes selected from the group consisting of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, and the third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0212] [11] The mutant of any of paragraphs 1-10, which is completely deficient in one or more of the enzymes selected from the group consisting of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, and the third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0213] [12] The mutant of any of paragraphs 1-11, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 1 or the cDNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1 or the cDNA sequence thereof.

[0214] [13] The mutant of any of paragraphs 1-12, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity comprising or consisting of SEQ ID NO: 2.

[0215] [14] The mutant of any of paragraphs 1-13, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity selected from the group consisting of: (a) polypeptide comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 4; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 3 or the cDNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 3 or the cDNA sequence thereof.

[0216] [15] The mutant of any of paragraphs 1-14, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity comprising or consisting of SEQ ID NO: 4.

[0217] [16] The mutant of any of paragraphs 1-15, wherein the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 5 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 5 or the genomic DNA sequence thereof.

[0218] [17] The mutant of any of paragraphs 1-16, wherein the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 6.

[0219] [18] The mutant of any of paragraphs 1-17, wherein the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 7 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 7 or the genomic DNA sequence thereof.

[0220] [19] The mutant of any of paragraphs 1-18, wherein the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 8.

[0221] [20] The mutant of any of paragraphs 1-19, wherein the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 10; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 9 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9 or the genomic DNA sequence thereof.

[0222] [21] The mutant of any of paragraphs 1-20, wherein the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 10.

[0223] [22] A method of producing a heterologous polypeptide, comprising: cultivating a mutant of a parent Trichoderma strain in a medium for the production of the heterologous polypeptide, wherein the mutant strain comprises a polynucleotide encoding the heterologous polypeptide and one or more genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene, wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0224] [23] The method of paragraph 22, further comprising recovering the heterologous polypeptide from the cultivation medium.

[0225] [24] The method of paragraph 22 or 23, wherein the mutant comprises a modification of the peptaibol synthetase gene.

[0226] [25] The method of any of paragraphs 22-24, wherein the mutant comprises a modification of the paracelsin synthetase gene.

[0227] [26] The method of any of paragraphs 22-25, wherein the mutant comprises a modification of the first terpene cyclase gene.

[0228] [27] The method of any of paragraphs 22-26, wherein the mutant comprises a modification of the second terpene cyclase gene.

[0229] [28] The method of any of paragraphs 22-27, wherein the mutant comprises a modification of the third terpene cyclase gene.

[0230] [29] The method of any of paragraphs 22-28, wherein the mutant comprises a modification of the peptaibol synthetase gene, the paracelsin synthetase gene, the first terpene cyclase gene, the second terpene cyclase gene, and the third terpene cyclase gene.

[0231] [30] The method of any of paragraphs 22-29, wherein the Trichoderma strain is selected from the group consisting of Trichoderma harzianum, Trichoderma koningii, Trichoderma longibrachiatum, Trichoderma reesei, and Trichoderma viride.

[0232] [31] The method of any of paragraphs 22-30, wherein the Trichoderma strain is Trichoderma reesei.

[0233] [32] The method of any of paragraphs 22-31, wherein the mutant strain produces at least 25% less of one or more of the enzymes selected from the group consisting of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, and the third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0234] [33] The method of any of paragraphs 22-32, wherein the mutant strain is completely deficient in one or more of the enzymes selected from the group consisting of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, and the third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0235] [34] The method of any of paragraphs 22-33, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 1 or the cDNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1 or the cDNA sequence thereof.

[0236] [35] The method of any of paragraphs 22-34, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity comprising or consisting of SEQ ID NO: 2.

[0237] [36] The method of any of paragraphs 22-35, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity selected from the group consisting of: (a) a polypeptide comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 4; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 3 or the cDNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 3 or the cDNA sequence thereof.

[0238] [37] The method of any of paragraphs 22-36, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity comprising or consisting of SEQ ID NO: 4.

[0239] [38] The method of any of paragraphs 22-37, wherein the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 5 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 5 or the genomic DNA sequence thereof.

[0240] [39] The method of any of paragraphs 22-38, wherein the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 6.

[0241] [40] The method of any of paragraphs 22-39, wherein the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 7 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 7 or the genomic DNA sequence thereof.

[0242] [41] The method of any of paragraphs 22-40, wherein the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 8.

[0243] [42] The method of any of paragraphs 22-41, wherein the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 10; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 9 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9 or the genomic DNA sequence thereof.

[0244] [43] The method of any of paragraphs 22-42, wherein the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 10.

[0245] [44] A method for obtaining a mutant of a parent Trichoderma strain, comprising: modifying one or more genes selected from the group consisting of a peptaibol synthetase gene, a paracelsin synthetase gene, a first terpene cyclase gene, a second terpene cyclase gene, and a third terpene cyclase gene; and identifying a mutant strain from step (a) wherein one or more of the genes are modified rendering the mutant strain deficient in the production of one or more of the enzymes selected from the group consisting of a peptaibol synthetase, a paracelsin synthetase, a first terpene cyclase, a second terpene cyclase, and a third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0246] [45] The method of paragraph 44, wherein the mutant comprises a modification of the peptaibol synthetase gene.

[0247] [46] The method of paragraph 44 or 45, wherein the mutant comprises a modification of the paracelsin synthetase gene.

[0248] [47] The method of any of paragraphs 44-46, wherein the mutant comprises a modification of the first terpene cyclase gene.

[0249] [48] The method of any of paragraphs 44-47, wherein the mutant comprises a modification of the second terpene cyclase gene.

[0250] [49] The method of any of paragraphs 44-48, wherein the mutant comprises a modification of the third terpene cyclase gene.

[0251] [50] The method of any of paragraphs 44-49, wherein the mutant comprises a modification of the peptaibol synthetase gene, the paracelsin synthetase gene, the first terpene cyclase gene, the second terpene cyclase gene, and the third terpene cyclase gene.

[0252] [51] The method of any of paragraphs 44-50, wherein the Trichoderma strain is selected from the group consisting of Trichoderma harzianum, Trichoderma koningii, Trichoderma longibrachiatum, Trichoderma reesei, and Trichoderma viride.

[0253] [52] The method of any of paragraphs 44-51, wherein the Trichoderma strain is Trichoderma reesei.

[0254] [53] The method of any of paragraphs 44-52, wherein the mutant strain produces at least 25% less of one or more of the enzymes selected from the group consisting of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, and the third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0255] [54] The method of any of paragraphs 44-53, wherein the mutant strain is completely deficient in one or more of the enzymes selected from the group consisting of the peptaibol synthetase, the paracelsin synthetase, the first terpene cyclase, the second terpene cyclase, and the third terpene cyclase compared to the parent Trichoderma strain when cultivated under identical conditions.

[0256] [55] The method of any of paragraphs 44-54, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 1 or the cDNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1 or the cDNA sequence thereof.

[0257] [56] The method of any of paragraphs 44-55, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity comprising or consisting of SEQ ID NO: 2.

[0258] [57] The method of any of paragraphs 44-56, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity selected from the group consisting of: (a) a polypeptide comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 4; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 3 or the cDNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 3 or the cDNA sequence thereof.

[0259] [58] The method of any of paragraphs 44-57, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity comprising or consisting of SEQ ID NO: 4.

[0260] [59] The method of any of paragraphs 44-58, wherein the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, high stringency conditions, or very high stringency conditions with SEQ ID NO: 5 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 5 or the genomic DNA sequence thereof.

[0261] [60] The method of any of paragraphs 44-59, wherein the first terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 6.

[0262] [61] The method of any of paragraphs 44-60, wherein the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising or consisting of an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 7 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 7 or the genomic DNA sequence thereof.

[0263] [62] The method of any of paragraphs 44-61, wherein the second terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 8.

[0264] [63] The method of any of paragraphs 44-62, wherein the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 10; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions, at least medium stringency conditions, at least medium-high stringency conditions, at least high stringency conditions, or at least very high stringency conditions with SEQ ID NO: 9 or the genomic DNA sequence thereof; or the full-length complement thereof; and (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60%, e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9 or the genomic DNA sequence thereof.

[0265] [64] The method of any of paragraphs 44-63, wherein the third terpene cyclase gene encodes a polypeptide having terpene cyclase activity comprising or consisting of SEQ ID NO: 10.

[0266] The invention described and claimed herein is not to be limited in scope by the specific aspects herein disclosed, since these aspects are intended as illustrations of several aspects of the invention. Any equivalent aspects are intended to be within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. In the case of conflict, the present disclosure including definitions will control. Various references are cited herein, the disclosures of which are incorporated by reference in their entireties.

Sequence CWU 1

1

28150787DNATrichoderma reesei 1cgatggggca acttgtgtct tatcaatcta atctagttgc tgcccatgag actctaaact 60aactaggaac agaataagga aagcaaaaca tgtaagaagc cagtcaaata gactagaatg 120aagaagaaac cgaacagaac aaataatacg agtaaaccga gacaaaggag aaaaagcacg 180agaaaaaaag aaaagagtat caaaagtccc cgttcatcct gcaagcgtat gcacgcgtcg 240aatcgtgcca tcccgctgta cattgccaaa tccttcctcc gaagactgga taaagccaat 300cttcttcata taacgcacgt tgctgtggac agccttctgg gactgctcgc acacatgcgt 360tcccgcattg gccagcgttg caaagtctcg cggcagaccg agctgaccga ggaagtgctg 420caccggccac aggggatgcg tgttgccaac cgtattcatc gaggccaggg cgcgttcagt 480ccattcttgc caggtaaccg gcttgcacgg ggcgtccagc tcggcattga cacggtccca 540gaagtcggac attgtcattc ctcttgccag taggttgaat ggcttgatgg aatcggcaaa 600gagtggaccg aggacgttcg atgcgactac gcccacgtct tgcatgacca tccagtgatc 660agatgcttcc tcggggtagg cctggatcga tgccgccgta gagacgacac gccagacaaa 720gtcgtcgacg ttggaaacgc cattctcggc ccttccgatg atacgaccgg gcttgactgt 780cgacacgcgg ttctgtgtgc tggggaggct gttggccatc ttcgtgataa cagcttcaca 840gacaaacttg gactgagagt agccattgga accactgaga agcgctgcgg aaacggctgg 900gttctctgct ggatccgtaa aggcaccgcc cgacacaaag acaaacttgg gctggcacgg 960cgatgtggcc gttgccatga gcaggtcgac agttgagttg acgttgggag cgctcagcgt 1020ctcatagttg gcgttccagt tgacagatgc tccgttgtga atgatggcat cgatgttggc 1080ttctgattct gacactccag agaggcgctg ccattgtgct tctgtaagac cgagacgcgt 1140cttggagagg tcgccgagcc agatttccag cttcgcttca tcttcatcac gccaccagcc 1200tgcaatcttg gccgtctctc tgattcgatc catcccctgt gctagtgttt tcgagcggac 1260atggacagct atcgacctga ttgctggatt ttcaaccaac cgtctgagaa tctcggtgcc 1320gaggaaacca gtagctccgg tcaggaagac cgtggcttgg tcaggcagtg tagttgtggg 1380attctcaagg agggctcgcg ggtgctgcat ccagggcgag ttggcaatct cgttaacctt 1440ggccatgagg tcgacttgcg catctgggtg atctgcctct gcagccccgt tctccgcgct 1500ctgggagatg aatttggcca tgttgctgat tgtcgtgtgc ttgctgttca acagggtgct 1560cccgagggac actccaaact tgtcaaggac aagcctcgag acgttgacga tgcgaatgga 1620gtcgccgccc agctggtaaa agttgtcgtc cacgctgatg ctttctctgg gtagttcgag 1680gacatctgcc cactctgctc ggagccagtg ttcgaggtct gttgagacgt cgcggaaagg 1740tagacgctgg ccggccaaat gaactgccag gtcttccgaa gagagacctg ccgccgtctg 1800caggagtgct tttctgtcaa gctttccgga ggtgttgagc ggcatggact cgacggcaat 1860gaaatactgg ggaaccatat gactcggcaa gacagtagag aggtctgaag ccagctggga 1920gaagagctcc tgcagcttgc tgctatgatt caatacccgt atgtttgacg catcgctggg 1980gctcgtgtcg ctggagaagc taacaaaggc gacgagggac tcatgggtgt catgacggat 2040cttgtcgaca accgcatgtt cgacatcatg tgattggagc ttaatttgat actcaatctc 2100acccaactca atacgttggc ctcgaatctt gacctgcgta tccttgcggc cgaggtaatg 2160aaggcttcca tccgggttat atcggactag atcgccagtc ttgtagaacc gtcgtcttcc 2220aacgtcaacg gtatcaggaa gccacttgac gttacttatg aatgcgttgt ttgtcttttc 2280ttcatcgtta atgtagccac gagacaaggc atctccttgt accagaagct cgccaacgca 2340cccaatggga gtaagttcat cgtggttctc tgggttgaca acccaacaat gatgagcaaa 2400cccacgacca atggtagtgg ctgatgtggc atcgtcagtg tatcgttgga ggcaggacgc 2460gacgcaggtc tcagtaggtc cgtatgcgtt ccaaaggctg acgttctgac gccacgagtc 2520cacaatgtcc ctggatggag cttcaccacc aagtatcagt gtcttcagcg agggtaccgt 2580ctgtggatca agtgtcttcg cgaatgtcgg agtcagaagg gcagtgttga cgtgggcttg 2640ccccatgaag cttgccgcat gctggatgcg ctccgcgtcg gtgggaacgc acacagtgcc 2700tcctgatatc aaggtggcga agatttcgag gattgacgca tcaaacacat agctagagaa 2760ttggaaggtc ctcgaatccc tagtaacatg gataactttg cacagcctga cgaggaagct 2820ggatatggcc ctgtgttcga taatgacacc cttgggtttt ccggtcgaac cagaggtaaa 2880caggatgtac atggctttgc tgggactgga cctggcagcc ttgagtttcc gtgaggcgga 2940ggcccgacca tttggtcttg agaaaaaggc cgacgaaagc tcaatgttgt ttctggtcat 3000gcccgcacac tctttggctg tactagggga tacgatcatg tactgggcac ttgtttcgtc 3060gatcaaggct tgtcgtcgac tgagcggatg gctcgggtct agcggtagga agacaccgcc 3120agccttgatg atgcccatca tgacaatgat ggaccacacg gatttctcat agcaaaaggg 3180tacgatggct tccgatttga cgcccagttg gatgagatgc aaagctagct cgtccgataa 3240ctgatcgact tctgcatatg tcatgctgcc ggccgttgaa tacagagcct ctttatgcgg 3300tatctttgca acctgcctgg agaacaagtc atggacgcag gcttctatcg gtgcaatgtc 3360gaagctgttc cacttggttg cctgctcagt atcccagggg ctcgcagggg agagttctga 3420cagtgtcttg tcaccattct tctggagctg ctccagaacg taggagaact gctcggccag 3480cgcgttcact tgagaatggt tgacgagatc agtttggtag atgatactca gctggacatc 3540gttttcgagc agctgacact gcacgacaag cggatagctg aagtagtctc caaggagctc 3600accttcagcg aagccttccg cagccacggg ataaaatacg gtggattcag tcccgctgtc 3660agttggagtg aactgctgag ccggctgaac gatgaggagg ttggtaaagt tgcacgcctc 3720cttggcgtca gtgctgattc ttgagatgtt cgccagcccg tactgctcgt gggcgaccat 3780ctcaaaggct tgatcttgca ttgactgaag aagggcggaa atcttttgcc gcttgtcaag 3840ctgaacgcgt ataggaaccg tagcaagagc gagaccaggc atttcgtcaa tgccctgcac 3900ggcagcttgt cgcccagaca cggtcgtgcc gaagcaaatg tcatcgtcat gttcgtactg 3960cgccagcaag atcgcccaag cagtgcgaat gatagtagct ctggtaatgg aggagcccga 4020cggccgctgc aggtggactg tcttgtctag catgccggca atcttttgtg tggtagatga 4080cggcttgttt tgtgtagcca ccacagggaa cgtgccgcgt ttgacgccac gaagttgggt 4140agaccagtag tcgcgggaat tctcctggtc gagctccatg atgtacttga cgaagctggt 4200atacgggaga atcgatggcg gctctgtctg ggagtacatg gcgagcaacg ttcgtagcac 4260aatggacaac gtccatccat cgaagatggt gtgatggatg ttgactgcaa agtattgatc 4320gctgccctgc ttgatgattg caaatcgaca cagcggcgac ccgtaagtca tggtgcagtt 4380ctctttggat aggaggaatg aacgcagatc ggtgtaagtg gaaggccagt gaactggctc 4440ttgaatcaca gcctggactg cagtgcttcc cgagaggacg atccgtgtgc gaaggttgct 4500gcagtatcga atagtttgct cccaggccag tttgaagcgg tcaatatcca catgtggtgc 4560aagacgatag acgtgttttg cgatatagga tcctggctgg ctgatggtca aggccatcaa 4620tcctgtctga aggtctgtgc aagggtagat atcttctatc tcggccaagt ctgaaagttt 4680acactgcgtc tgcacagccc tcagagcgct ctgtttatca ctggtcggta tgaggccgaa 4740ccgttcgact tcgtgagccg tggatgacgg agaagcgtcg agctggatgg cctctgccat 4800cgccgagaga cgcgggtagt tgaatatcat tgccaccgtg aggccaatgt tctgtcgctg 4860ggcgaaggag accagctcaa tggcactgat tgaatctccg ccgagatgga ggaagctgtc 4920gtgcttgcca atggctgata catcgctgat tttgagaact tgggcccaaa ggctctgcag 4980ctctagctcc atgggagttg taggcgatac gtagtcactg gcgctcggtg taaagcgtag 5040gcggtcttga acagagacac ttcgaccaag ctccacgaat gagcggcgat tcaccttgcc 5100tgaggttgtc tgttctggtt tgccttcgaa gatcaagtat gaagaaggaa tcatgtacga 5160aggtaaactt tcttccaagg ccaaatcaag acgagagatg acgctttgag cctgttctga 5220aactgtgtgc atcaactgaa gagcctctga ccgagacgtc atctcgtcgt cggtatacca 5280caggaatgcc agaaggatgt cgtgggcatt ctcatcatct gccttgagga tgtcgacgat 5340gacggccatg ttgtcaggca gtagctcatg gatgcgcgac tcaatctcac cgagctcgac 5400acgctggccg tgtagcttga cttgagtatc cttgcggccc atgtagtcga acgtgccgtc 5460ggcgttgcgg cggaccaaat cgcctgtgcg atacactctc tttcttcctc ctggaagcca 5520atccacgtct tccatccaac tggcggcaac ttcagggctt acgttcaagt agccgcgggc 5580aagcatagga ccctcgataa gaagctcgcc aacacacccc acaggcacaa gctgccgaag 5640attgcctggt tcaacgaccc agaaggcact ggaaataggc cttccaaggt tagtcgatcg 5700acccaatttg ccaacggtgg gattccacgc gcagatggat gcctccgccg gtccatacag 5760accatgtagg tcgacgtgat gcacccagcg atccgcgcac ttcttgctaa tggcctcacc 5820accaaggcac accactttca tatcagggat atcagtagga gataagaggt cggcaactgt 5880aggagtcagg aagacccagt tggcctttga agaccgcatg gcacccgcta ggtcgttcat 5940cctgtcgtgg tcagatggga tgcagagaca ggctccgcgc atcaaagaca cgagacagtc 6000gaggatgccg acatcgaagg tgtaggccga aaattggaag actcgtgtac ccggtccaat 6060gccaaggaga ttgccgtatg cgtcgctgga cgagaccagg tttctgtgtt cgatgaccat 6120gccctttggt ttgcctgtcg agccagaggt aaacaggatc acgctcgcat tatcgggtcg 6180tacattggaa atcactggtt tcgttgggct agggagcccc gaaagcatct cctcatcaac 6240aaagaagaca tcgacgccaa ggccctcgag cactttgcca ctagtcgggc tagacatagc 6300gagagtggca tgcgtgtctt caatgatgcc cttcagtctg gctgccggag cggcagggtc 6360aagagggaca aaagcgccgc cggccatttc gatggccacc atggcaataa cggcccaagc 6420tgacttgggg aagcacagaa gaaccagggt ttcaggacca actccgcgtt cctgtaactc 6480gattgccaag cgcgaagcaa atgttcctac ctgggagtag gtgagttctg catcccacga 6540cgcaatggca acatcatctg gtcgagactg gatgttttct tgaatggccc agtgggtaca 6600agtgttgcta gaaggctcca aacggctgga ctcgactgct tgttggaggt cccaggggct 6660gagaagtgag actgagctca gaggcgcatt cactgcttcc ttcgccacga gttgttgaat 6720gacgtggttc aaatgcgatg acagagcaat gacccgagct tccgacagca ctgtagaatc 6780gtagaaaaag ttcagtctga actcttcagg atagagactg ctgatgatca cgaggggata 6840gttgaagtag ccgtccatgg agtccatcgt gagatcgctt gcggacgcgt caacaacgaa 6900gatactctcg ccatgatcgt ctccagctcc atgtgcaggg ggctggacaa ctaagagact 6960cgagaaatcg caaacctccc tcgcttcagc gctgaccttg gcaatattct gcaagccata 7020ttgctcgtac gggatcatgg atgtgctcag gctctgaatg tcttggacaa atcttgatat 7080aggcgcctga ttgtctagcc gggctctgat ggggacggtg gcaatcattg ggccagatat 7140catctcagct cctggaatcg gggcttgacg gcctgaaacc gtcgctccga acactgcctc 7200gctactgtcg cagtatcggg caaggacaat agcccacgcg gctcgaagaa tcgacgcttg 7260cgtgatagaa gtcttcatgg atctggagaa tggaattgtt gagctgaacc gcttgctttc 7320catgatgcct ggggcagttc ggcgagatgg gaacgaagcg cgctttgcac cagccagttc 7380ttgtgtccag tacgatgcga ccttgtcatt atcgagctct ttcacggatt tgatgaaaga 7440ggagaaaggt cggacttcgg gtgcgtacat gccctggtaa gctgagaaca gcgctgtgaa 7500catgactttc atggtccaac catcgtaaat ggagtggtgg gctgaccaca caaaatagtt 7560ttcacccttc tcagacacga tagagtacca gcagagagga gttccgtaac ccatcttcag 7620attgcgcgac gatccagtca ttgactcgag ggtttcattg tcggcaggca cccattgact 7680gtcacgatca aggactatct gcgtcatgac gccatccaag acgacaatcc gggttcgaag 7740attgtcacaa atatcaacca ccgagtccca cgcagccctg aacatgggta tgtccacaaa 7800gctggagaga tgatgggcat aggtagcaac ataggaccct ggctgcttgg cggtaagggc 7860tatgaggcct tcttgcagag aactgcatgg atacgcatcc gtgatggttc ggtccttcgc 7920caggccgcac aattttcggg cgtcctcccc gagtacaagg cgcttctgtg cttcaggcaa 7980cagactgaat ggctctggag gagagtctgc tggctccata ccatcttgac tcagaacagc 8040ctttgcggct acagccagta gtctgggatc atcaaacaca tcctgtacag tcagagtaat 8100gccctcttcc tttgctgttg agacaaggta tatagccatt atcgaatcgc ctcccagctg 8160gaagaaggtg tcatctctgc cgatggactc cattggcaag ttcatgatct cagcccagat 8220caactgcagg cgctgctcca tttcggtctc tggctgccgt ttttcgctgt gtaacaacga 8280atacatcgct agctgatccc tatcgagagt cgagaggtgc gtctgcagaa gctttctatc 8340cagcttggtc gaagcaatga acggcatgaa ggcacatggg atgaacaagg tcgggatcat 8400gtatcgggga agggcaatac ccaattcccc aacaagggca atcagctggt tctgtaagct 8460ctcgtcggtg gataagaata gagtctccga agcatcggtc ttgacgccgg ctgtcttcgt 8520ttcgtctgtg aagcaaatgt aggcaacaag actggagccg ttgtcgcccc tgacgacgtc 8580aacagccact tgacgcacac cgatcagtga ttgttggata ttgtattcga tttcactcaa 8640ttcaacacgc aatcctcgaa tcttgatctg cgtatccttg cgcgttgaaa actcgattgt 8700tccgtcggca ttataccgac atagatcgcc tgacttgtag aatctgttcc agtgtgattc 8760gtctggacgg ggagcccact cggcagcggg cagaatgctg gtattggtgc gttccgggtc 8820tgcgagatat tcctgcaaca gagtcgggcc ttgaataacg acttccccaa ccgtgccaat 8880aggggcaaga aacccagaat cgggatcgac aatccagcaa aagccgccga cagggcgtcc 8940cacagtgaga ggcgactcgt caactgactt ccactcatgt agagtactga agacacaagt 9000ctcagcaggt ccccagccgt tgatgagacg acgaaccttt ccgaaccagg ctgtcaacac 9060atcgcgagga actgcctcgc ctgcaagcag taggacttcc agcccaggga catcgtccgg 9120gtttagggtc cgcacaaacg aaggcgtcaa gaaagcccag ttgacgttca tgtcctgcat 9180aaacttggac aaatcattca tcctagcatg ctcggatgga atgcatagac aggcgcctgt 9240gataagggga gccacaattt ctccaatcga caagtcgaaa acgaaggctg caaactgtag 9300catacgcact tccggtccaa gtctgagcct cttggcaatc gccttctggc ttgtacacac 9360ggacccatgt tgcattacga ggccctttgg cgtgccggta ctgccagagg taaagaggac 9420gtaggcaata tcgcctgaag aggctctctc tgtagggccc tgtcggctgt tgacctgttt 9480ctgaagctgc ttgtcgaatt caggcgtaat ctggatcgcg gactcgacga gggtggagca 9540aagatcgcta ttgtctggcg agcagagtgc aaacttagcc cgcgtttgac tgacgacttg 9600ttgaagacgc tgtagggggt gtgatgggtc caagggaacc caggccgcgc cagttttgtt 9660gatagccagg atagatacaa aatgccagac tgacttctca aagcatacgt gtatcaagtc 9720gtttgtcttg atctcgtgtg tttgtaccag gtaatttgca agtcggttag ccgcctggtt 9780cagctgggca taactgaagt caccgtccca agagcggatg gccatggcat caggacgttg 9840agcagcctga tcttcaacaa gggtgtggaa acaggaatca acgatctcgg gggtgtccac 9900attgaacttg cgtgattgtt cgatatccca ctgggagacg agagagacat cacgtagcat 9960ctggctgggc tttgactcag ccaactgggc aatcacatgc ttcagctgct cggacaatgc 10020gacgatttgc tgctccgcaa tgcagtgagg gttgtagatc aggacgattc tcatgaagtc 10080gtcgctcaga tgggcttgga ggacaagcgg atatgagaaa tagttctgca ttccatctgc 10140gctgtcatct gtgtcctcga caccaaccag aagagcatct tcgccagtgt tttccagatg 10200tgaaagcatc tttagaggtt gaataaccaa taggctggta aagtcacaag cttcgtcggc 10260gtctggattg agcttgcgaa tactctgcag gccaaattgt tcgaaaggaa tcgcgtcgct 10320tgctcgtgtt tggacttcct ccaggaactt tgtcgtcggt tgatcatggt caagatggat 10380ccggacgggt atagttgcaa tcactggccc aggcatttgt gtcaagcctg ggagcgatgc 10440ttggcgccct gaaaccgtcg cgccaaagca aacgtcggtg ctatcgcaat agcgagcaag 10500gactagtgcc caagcggcac gcacaattgt agctgttgtg atggtggtgt tgctcttgga 10560aagttcaagt tccgctgtca ttgtacgcga agcttcgggc ttgcttgtag acgtaattgg 10620aacggagggg aatgtcgcct ttcgagcgtt ctcaagctgc cttgcccaga aatcgccggc 10680ggcctcgtga tcgagttcca ttgtgtactt gatgaagtgt gagtaaggaa ccgtggtggc 10740aggctcgaga cccttgtagg ctcggtggaa ttcctccaag atgatagaca atgtccagcc 10800atcatagacg gcgtgatgaa ggttgaaaga gaaatagact tcgtcaccgt ccttgaagat 10860ggcagatcgg cagagccgtg agccgtaacc catttccatg gttcgggtct gctgcaaata 10920gctccgaagg gtcattcgtt ctgtggaatc ccagacagta tctcccttca caacgacctg 10980gagggagata gcacccagtc ggatgattct ggtacgcagg ttagggaaac tattgacaat 11040ctgttcccat gctgccttca gaaggctaac atccacatga gacgggatgc gatagttgta 11100cttggcaatg tatgatccag gctgcttaac agccaatgcc atcaaacctt cttgcatctt 11160ggaacacgga tagcaatctt caaccgccat gtctcgagaa agttcgaggc cgaactcttc 11220agcgctttcg gtgatcatat cgcgctgtgg ttcatcaaga agagcaaatg gttcgatggg 11280ggtaaaagct tgagagcttc catcactgat gaaagaagct ttcgatgcaa tagacaacag 11340tcgaccgtct tcgaaaatct gactgactgt gagcgcgact ccttggtcac gagcagcagc 11400aacgagccgg atagccgcaa tggaatcacc gccaatactc aggaagctgt cgtcacgacc 11460aatcgtttcc ataggaatac ccaagacatc agcccagatg gcctgtagct tgccctccat 11520aggggtttgc ggcatggtct ttttgctatt caccagtgaa taggcggcca gctggtcctt 11580cgtaaggctt gatgtaagtc ctcgcaacgt ctttcgatcc agcttgccag acgtggcagt 11640tggcatatgc ttgcattgaa tgaagagggc gggaaccatg tattctggaa gcagaacctt 11700gagttcgcca accatggttg cgagacgctg ctgtgtttct tctcccaaga ccatgaagat 11760atcatcgaga gaattactcg agacgtcgac agtggcatcg ccgaagcaaa agtaagcaac 11820caggtttgag actgagccag acttgaagac atcaaccacg acttgatggg cttcggggaa 11880ggtctccttg atgcgatatt caacttcacc caactccaca cgaaggccgc gaattttaac 11940ttgcgtatcc tttcgcgagt agaacctgat agtgccgtca gggttgtaag aacaaagatc 12000cccggacttg taaaagcgag tccagtgctg cgtatcagga tacattgccc agtcaggtcg 12060accttccagg attgcagcct tgctcttctc ggcgtcgccc agatactcgc gcaacaacgt 12120gggaccctgc acaataagct caccaacagt tccagtcggc gcaagtttcc atggatcttc 12180tggatcaaca atccagcaga acccacccac tggctttcca atcgtcaaag ctgactcttc 12240tgaagatctc cattcgtgca ttgcgctcat gacgcatgtc tccgacgggc cccaagcatt 12300gaagaatctc acttttccaa tccattcttc aaatagggcg cgtgggacag cctcgccacc 12360aagggctacc aattctacac ttggcacatc ctcaggcctc aaggtctgta ggaaggacgg 12420ggtaaggaat aaccaattga tgccggtgtc gttaacgtac tccttcagtc tgttcatacg 12480gtcttcttcg gacggaatgc acacacaggc accgtacatc atggctgcga gcatctcgct 12540gatcgaatag tcaaacacat aggcagcgaa ttgcaggatc ttgacacttg gcgtgaaccc 12600gaagcgtttg ccagcagcca tctgactcgt acagagggca ccgtgttcca tgattaggcc 12660tttgggtaca cctgtgcttc cagaagtgaa caagacatag gcggcgtgct tcggagtgac 12720taaaacgtcc ggaccttgag agctactgaa gcccttctta cagagatcag aatccaggga 12780agaagagacg acaacaacag atgtaactaa ttgggagcat ctttccacat tgtcctgaga 12840cgccagtgca actcgcgcct ttgtctgggc tgttacctgt tgatggcgtt gcagagggtg 12900tgagggatcg atagggaccc aagcggcgcc gactttgttg attgccaaga tggctacagc 12960ataccaggcc gatttggtaa agcacacttg gaccaggtcg tgagctttga ctccgatgtc 13020catgactaga tgatgagcca gcctgttggc tgctttgttc aactcgtcat aggtaagcac 13080cttatcccag cccagtatgg caacagcgtc tggacgtatc tctgcctggc actcaatgag 13140atcgtgcaag caagagtcaa tgatttccgg tggatcttcc ctgttggcct tttctgcgaa 13200tttgacatcc cagtcgcaag tcagagacag atctccaagc agtgactgcg gcttggcaat 13260tagctgcctc atgatgtgtt ccatctgatg agatatggcc agaacctgag actctggcaa 13320gacgttcgag tcatagatga acatcaactt gatgtcttcg cccatgacgt gcccctggat 13380gacgagaggg tacgtgaagt aattctgcaa agagctttcc tcttgtgact caacctcgac 13440gggctgaagc agtgcatgct caccattgat caagtgctgc atcggttgaa caaccaacaa 13500gctcgagaag ttgcacacct cttgagccct aggactgatt ttctggattt cctggaggcc 13560aaactgctcg tagggaatca tcttcagggc ctggctttgt atggtgtcaa gatagtccga 13620aacgctccgg tgcttgtcta atcggacacg gataggcacg gtagcaacag caggcccagg 13680catatcgggc aatcctggaa caggggcttg gcggccagag acagtagcac cgaagcagac 13740atcatccgtc tcacagtatc ttgcgaggag cattgcccat gcagcccgaa tgaccgtagc 13800tttggtggcc gacaagtcgg tcatattggg caactgcata cctcgctcca ggcttttgct 13860agagttcgag ctggtctttg agagcggagg atacgcggcc cggcttgcac cgtcaagctg 13920tgccccccaa tagtttcttg tctcttcgtg attgaggttg ccgacgtatg caacgaacct 13980gttgtacgat tgtagagacg gcggggaccg gccatcatac attgaatgaa ggacgtccat 14040catgagacgc attgtccaac cgtcaaagat ggagtggtgc aaagcccaca caaagtagac 14100ctcgtcccca tccatgacaa tcgcacctcg actcaatcgc gagccataag ccatgtttga 14160cgaacctaga gcgtgcatgt acgactgcag ctcctgtcct tgtacttcat cccatgcgaa 14220atcattctca aggacgagtt ggacggtttg gctcccgacc ataacaactc ttgtgcgcaa 14280gttgtcgcag agttttacca tatcttcaaa tgcagatcgg aacctcaaaa cgtcgacagt 14340acgaccgagg cggtagacga attttgcaac atagcttcca ggctgtttct ctgtaagagc 14400cagaagacct tcctgcatct tggtcgaagg gtaagcatct cgaaggacaa catcatcagc 14460caagtggtaa ttttgtcgca aatcttggct agaaagtaat tgctgggttt gttcatcgat 14520gaggccaaat tgggggattt ctgcagcttg accgcttctc gtgaggctga tcgccttcgc 14580ggcaacggct aatagcctgg ggtcatcaaa gatatccgcc accgaaagcc caatgttgga 14640gttctgagca gcagtgacga agtgaatggc gatgattgaa tcgccaccaa tctgcaggaa 14700gctgtcatcc cgaccaatgg atgtagcagg gacgttcagt agctcggccc aaatgagctg 14760tatccgtttt tccatctccg tctccggacc ctgcttctcc aggtcggaga gcgtatactt 14820ggatagatcc tcaaggctta gagaagacgc catagccttc agcttcttgc gatctagctt 14880gtcagaggtt gtggatggaa ggtacttgca agggacgaat attgacggga ccatataggg 14940gggtagagta gccttcagac gtccttccaa ggctctgaaa gccttctgca tgcgagaggt 15000cggttgtagg aacacttcac cgctcgatcc actactctca

atgtctggct gctcgattcc 15060agacttgaag ctgacaaaag ctatgagact tgcgccagta gtgctcttca agacttcaac 15120agcagcctcg cagacatcat ccagcttgtc gcggatatga tgctcaatat ctccaatctc 15180gacccggaag ccgcgtatct tgacttgcgt atccctgcgg ccaccgaaga caaggttgcc 15240atcagagttg tagaagcata gatcaccagt tcggtagagt cggttccagt gttgggcatc 15300tggttgaggc gcccagctgg gtctgggtat aagggcagcc tttgttcgtt cgggctcatc 15360cagatattca cgtagtagtg ttgggccctg gatagccacc tctcccattg tgccgaatgg 15420cgcaagggac tgaggcatct caggatcgac aatccagcag aagccgccca ccggacggcc 15480gataaccagc gacgaagtct cagcagacgt ccactcatgc acagcactga tgacacaggc 15540ctctgcaggg ccccaggcgt tgatcagtcg cacttttcca aaccatgtga ggcacaagtc 15600ctgggggaca gcttcaccac ctagtaaaag gagttctaga ctagggacgt ctgcgggctg 15660gattgtgcgg gcgaatacgg gtgtgaggaa agcccaatta atttgacgct ttcgaatgaa 15720agtcgcaata ttctccatgc gttctcggtc cgagggaatg caaacacaag ctccggagat 15780cagtggtcca atagattctc cgagagacat gtcgaaaacg taggaagcaa attgcatgat 15840tcgcacactc gaggtcatct tgagtctggt agcaagagcc gtttggctgg tgctgagtga 15900ttggtgctct ataacaaaac cctttggcgt tccagtactg ccagaggtaa acagaatgta 15960ggcaggactg cgaggcgata ttgcgagcgg tttgaatggt tctgacacag aacggcccag 16020ttgttgatcc agctcagccg tgacttcgac cacgtctgtg acgagtttgg cacagagttc 16080ggcattactg ggtgatacca acgccaggcg agccttggtc tggagaacaa tctggcgcaa 16140acgcgcttcg ggctgggatg gctccaaggg aacccaagca gctccagcct tgttgatcgc 16200gaatattgac acgaaatgcc aagcagactt cccaaagcag acactgacaa aatcaccagg 16260cttgacacca tgactgtgga tgagatggta tgctagtctg tccgaagcgg cagccaagtc 16320gctgtacgtg agttccgcat cgcatgccaa gattgctggt gcttgtgggg agatctgagc 16380ttgtttgtca atcaactcat gcacgcatga actgataatc tccggcacct cgctattgac 16440agctaaagcc aattcaaggt cgtgagatga agcgatcaag atagactcga gggaagtgcc 16500agcgcccgaa gcgagctggt gaatgacatg gccaagctgt tcggataagg cttgaacctg 16560gcgctctgtc aaaacatttc gatcgtatgc cactgcaatt tttaccttat caccatacaa 16620gtggccttgt acaatcaggg gatagttgaa gaagttgttc agggagtcag agagaccttc 16680ggtcacctct gcagcagaaa gcagttcctt gctctcctcg ctgttggcaa tgtggcgtat 16740gggctggacg accagcaaac ttgagaactg gcacgcttca taggcgtctc tgctgagttt 16800cgtgatgttc tgtagaccga attgttcgta cggaatcatt cctactgcgc cctgttggac 16860gctctgtaag aaatctgata cgggctgttg acgatccagt ctgactcgta caggaaccgt 16920cgcaatcacc ggccctacca tgtcaacgat tccaggaacg ggagcctgac ggcctgaggt 16980ggcgatgccg aagcatacat cgtcagtgtc acaatatctc gcaaggacaa tggcccaggc 17040ggatcgaatg acggttgcta acgtcacatt gagtttgctg gcatcgacaa agccaattgg 17100tgtttccaaa acacaagtag caactacttt gtcgtgggtg ttatgcagcg aaggcaattg 17160tgctggcttg gcatcatgta gagcatctct ccaataagca gaggcagcct cctcatctat 17220ctgcaaaaga tactggataa aacgagagta aggagtcaag acaggagttt caaggccgaa 17280gtacgctttg tgcaagatgc ccaggataac ttgtgtggac aggccgtcga aaactgtatg 17340atgcatggcc cagaaaaaga acacactccg ctgctcgtct tcaacaaacg caaattgaca 17400caatgctgaa ccgtatgtca ttttgatcgt ctgagcatat cgtagtacag cttgtagatc 17460gtgatacggt agcggctctg aactcgactc gggattcagt acgatttgga atgtcgactt 17520ggccgatgtg ttgatgattc tgctgcgcaa actggcacaa atatgcatag tctgcttcca 17580agctgacttg aaacgagcca catcgacgtg gtcaggaagg cggtagagat atttggcgac 17640gtaactgcca ggttgcttga cggataacgc cattaagccc tcttgaagct tggtacaagg 17700gtaagagtct tcgatgatag cactgtcagg cagcgagcac tgatctcggg cttcagccag 17760gatggtactg gactcccctg ccggaagcat atcgaacggc cggatctcac tgtatacagt 17820caactcatcc tcgacgatgg cgctggccat ttgctcgaga cgaggagatt gaaaaatcgt 17880cgcgactgtc agatcgagac cttgcagttg ggctttcgac accagctgaa tagcagatat 17940cgaatcgcca ccgaggcgta agaagctgtc gttcttgcaa atatcatcag gttcaatacg 18000gagaatctgt gcccatagct cgcgtaactt gaattccatg ggtgtagttg ggagcacgcg 18060gaagctggta tcaggagcaa agcgcagacg ctcttgagca gtgatatgct gggcttggcc 18120agtcaaagac cggcgattga tcttgcccgt tgtggtttgc tccggcttcc cactgaagag 18180gaggtaagag gacggaatca tgtatgaggg caaaattgtg ttcagagacg tatccaagtg 18240caaaaccatg gctcgcgctt catccgatac ggtgtccacg agacgggctg gcgaggcaga 18300gcttccatca gagttccaga tgaaagccaa caaggtagcc ggggcgtcat tgtctttaac 18360aacgtccaca atcgcagcca tgttttgcgg caagaactcc tgaattcggg tctcaatctc 18420tcccagctcg acacgctgac cgtgaagctt aacctgggta tctttgcggc cgatgtagtc 18480gaacgtacca tccgcattcc gcctgacgag atcaccggtt cgataagctc tcctaggtcg 18540gttgtcacca ggaagccagt caacgccttc aagccagttg gcggcgacct cggccgtcac 18600attcagatac ccccgagcaa gcattggacc ctcgataaga agttcaccaa tacagccgat 18660tggcaccagt gatttcgggt cattgacatt aacaacccaa aacgcactgg atatggggtg 18720tccgagattc gtggggcgcc ctgatctccc tactaccgag ttccatgcac agatagacgc 18780ttcggctggg ccatagaggc catgcaggct cacatggcca acccacctgt cagcacactt 18840cttggtaatg gcttcgccac ccagacagac agtcttcaaa gtagggactt ccaccgggtt 18900gaggaggtct gcaacagttg gcgtgaggaa tacccaatcg gctttagacg cagtaatggc 18960ggccgcaagg ttgttcagac ggtcatgatc ggatggaatg cagatgcagg cacctctcat 19020cagcgtcaca agacaatcca ggacaccaac gtcgaacgtg tatgcggaga attggaacac 19080ccgggtgccg gcttcaatct tcaaatcggc accgtaggca tcgctcgagg aacagatact 19140tctgtgctca ataatcatgc cctttggctt gccagtgcta ccagatgtaa agaggatgac 19200gctggcgttg gtaggcctag cctctgaccg caggtcgaac tcggctggca gctcggagat 19260actttgatcg tccactgtaa cagctttcat gccaagtgac tgaagtaatc cttgacactc 19320tgagctggtt atagccagcg tagctcccgt atcctggaga attccttgta atctggctgg 19380cgaggcacca ggatcgaggg gaataaaggc acctccggcc atttgaacag ccaccatagc 19440gaccacagcc cacttcgatt tgtggaagca gagagggacc aatgactcag gtccaacatc 19500aagctcttgc aatcttgcag ctaagcgcgc gacatgtttt ccaagctgag cataggtcag 19560gtctccatcc catgaggaga tagcgatctg gtcaggctgt aatctgactt ggtcttggat 19620caaccagtgt gtgcatgatt ccgttgcagg gcgaagacga gacgcatcga cggccttttg 19680cagttcccac gagccgatca gggaaatatc cttctgcatg ccgctgttat tgagaagctg 19740gtgtgtgaca tgctctatgt gatgagacaa cgcttctatc tggtccttgc caaggacatc 19800ggagttgtaa aagagccgct gctcaatagc cttctcgcca atgccactga tgatgacgag 19860agggtagttg aaatagcctt gcatagcctt ttccgtctcg tcctgttccg tctcgctgtg 19920tgagagaatt gcctttgagt catccccgcc ggcaggatca tgagctggtg gttgaatgac 19980aaggagactg gaaaattcac aagcctcctt cgcatcagaa ctaagcttgg caatattctg 20040caatccgagc tgctcatagg gaatcatgga ggatgcttgt gattgaacat cactcaaaaa 20100ctgagaaaca gggccgttct tatcgagtcg gacacgaact ggaacagttg cgatcatcgg 20160cccgacgatt gattcaacac cctggacagg ggcctgtctg ccggagacgg ttgtaccaaa 20220agtgacatcg tcggtatcgc aataccgggc aaggacgact gcccaagcag cccgaacaac 20280tgtggccttt gttacaggga tattcaaggt ctctggtagc acaatggtcg aatggtacac 20340atccgtcctg gccgcggaga tggagcgttg gctggtcggg aattctgccc gctttgaccc 20400agctagctcc ttggtccaga attctgcggc ctttccggtg tcaatattcc tgtagtagtt 20460gatgaaggag gaataaggcc gaacaggaga cagggaatcg ccatagtagg ctgaatacag 20520ggtgctgaat aggatccgca tcgtccagcc atcgtagatg gagtgatggg ctgaccagac 20580gaaataatcg ctgtcaccat catgaacgat agcacaggaa gagagagccg ttccatatgt 20640catcttcaag ttctcggatg aatcaagaac tgaggacaaa gtctgattct ccgtagatcg 20700ccactggttt ccacctcgaa cgacgatttg aacagactcc ccatccaagt gaatgatgcg 20760agtgcggagg ttggagcaga tatcggacat ctggttccag gcagcaacaa atcgcgagat 20820atcgacatgc ctaggtaacc ggaacacata gttcgccacg taagatccag gctgtttagc 20880agtgagagcc atcagaccct cttgtagtga agtacaaggg tagcagtctt caatcacctg 20940ctcttcggat aagcagcatt gtttgcgaac atcatcacta aagactgcat ccctcagtct 21000gtcggttacc atgctaagtg gcgcgacatg agtttccaac tggtcagttg tcttcgtagc 21060cttcaatgac agagccacca atctggggtc atcaaacaca tccttcacct gaaaggaaat 21120tcccatttct cgggcgcgag aggccaactg aatggccaag atggagtctc cgccaacctg 21180caagaaactg tcgtctcggc caatggaagc agcagggatg cccaaaacat ctgcccaaag 21240agcttgaagt tgaatttcca tctctgtttc gggctcgcgt ttctggctgt tgaggagagc 21300gtaagcattc cgctgctcgt cattcagcga gtccatcagg tggcgcagag tctttctgtc 21360aagcttggtg gacgtaatgg aaggcataaa tctgcaaggg atgaagagag aaggaatcat 21420gtaagtaggc aacgcgatcc ggagctcgcc aagcatgatg gcaatccttt ggcgaaggtc 21480agtcgtgatg gctgcaaata agccatctgc agtgaatagt tcatccgcag atggattctt 21540catctcgtca ctgaagcaaa tgtaagcgac gagattcgac cgaccctcct tttggtacac 21600gtcgacaacg acttgtcgca cgccgtccag aatctcgcga acataatgct caacttcccc 21660gagttcgacc cttaggccac ggatcttgat ctgcgtgtcc ttgcgactgc tgaaaacaat 21720tgtgccgtcg ggaccatagt acccaaggtc accagactta tagaacttat tccaattctt 21780ggagtccggc cgcggcgccc atgttggcag agagtataca gttgagtcct ttgtgcgttc 21840gacatcggca aggtactcgc gtaggatcgt gggaccctgt atgacaatct ctccaagtgt 21900tcctgtcgga gtgagacgct ggggatcttc cgggttgacg atccagcaga accctccaac 21960ggggcggcca acgacaagtg gtgattcatc tacagaagac cattcatgaa gtgtgctgaa 22020gcaacatgtc tcagcaggac cccagccatt gacaagacgg actttgccaa accaagtggt 22080cagcacgtcc cgaggcactg cttcaccggc taagagcaaa agctgcagag caggcatgtc 22140ttccggaacc agggtcctca caaaggccgg cgttagatac gcccaggtaa ccttcgtgtc 22200gttgacaaat tccttcaatc cgttcattcg agtgtcctct gatggaacac agatgcatgc 22260accggaaatc agaggcccga tgatttcacc aatagagaga tcgaacacga aagccgcaaa 22320ctgtagcatc cggacctcag acgtcaggtt gagcctcttg gctatggccg tctggcttgt 22380gcaaacagca ccatgttcca tcactaggcc cttcggtttg cctgtgcttc cagacgtaaa 22440gagcacgtac accgcgtgat tcggcgtaac ggcaacagct ggaccttcgt cgccattttc 22500cgtgacggcc aatctctggt cgagcttatc atcaagtcga acgacgttct caagaagggt 22560tgagcacagc ttttcattgc gtgccgacga caacacaagg gtcgcccgcg tctggtcgac 22620cacttgccgt agcctttgct ctggatacga gggatccaat ggaacccacg ccgcacccgc 22680cttattgatg gcaacaattg caacaaagtg ccaaagagac ttttcaaagc acacatgaac 22740aaggtcgtca ggccgaatgt catagttctt cacaagatga cgcgccagtc gatttgcaga 22800tttgttgagt tggctatagg ttaagtcgcc gtcccaggca gacactgcca aggcgtttgg 22860cgcccggtgg gcctgggctt caatgagctt gtggacgcag gagtcgatta tctctggcac 22920ttcagagttg aactcaacag actgcttaac atcccactca gacgtgatag agaggtcttt 22980cagcaatagg tcgggatgtg aagccagctg agaaacaaca tgctggaact gatgcgagag 23040cgtaataagc tgctgttcag agagagagaa cttgttgtag atgaagacaa gcttgtcccc 23100atcatcatga aggtgagctt ggatgacgag agggtaagtg aaatagcttt ctagtgcttc 23160gtccgccgac tcatcggacc gcgcaacaag gagggcatcg ccagctccat tgatgtgcga 23220cagaatctgc cttggttgaa tcacaagcaa gcttgaaaag tcacaggcgt ctttagcatc 23280gtcgctcaac ttggcaatgt tgtgcagacc gaactgctca tatgcaacca tttccattgc 23340ctgtgactga atgtcctcta ggaagtcgga gatcggtttg ccaccatctt caagatggat 23400tcgaacggga atcgtcgcaa tgactggacc aggcatttcg gccaagccag gaactggcgc 23460ttgccggccc gacaccgttg taccaaaaca aatatcgttg gcatcacagt agcgagccag 23520tacgattgcc caggcagcgc gcaaaatggt tgcctttgta gtaccagcgg aaatcttggg 23580aatttgcatc tccgactcga ggtatcccgt gctgttcgcg ttggctggct gctcgcctgg 23640agtgagacgg ttgggatagc ttgccttctt tgcgttgcga agttggctaa gccaatactc 23700gcttgccgat gcttgatccg aatcgagagt atactggatg aaccgggaat atggactgag 23760ttcggcaacc gcatcgccgt gatatgcgct atccagcgtc tcgagcacca gacgcattgt 23820ccagccgtca aagaccgcgt gatgcatagt caagatgaag cgagtgctcc catcttgggt 23880aatcagagca taacgacaca gtcgggaacc atattccatc ctaatatcgc gtgaagcctc 23940aaggaagcca tccaaagagc cctcttgcgt ggactcccac tcgaaatcgt tctggagcac 24000aacctggata gaggctccgt cgatattcag gattcgagtc cgcaggttgg gacacatctc 24060aaccgttctt tgccacgcag ccttgaagct gtcaatgtca gccgatttag aaaggcggta 24120gtggaatgtg ccaatgtaag agcccggctt ttgcacagct agggccatta gaccttcttg 24180aagcttcgag caagggaatg catcttcgat actcatacta tggctcaagc caaggcaaga 24240tttggcttcg tctgtttgaa ggaagtccaa ctcagcttct tccagcatac caaacggttc 24300aacgtcgccg aagtcatcgt catcatcagc gatgacttcg gctttcgcgg ccacactgag 24360aaggcgagca tcttggaaca cgtccctggc gctgatactg atgccgctct cacgagctgc 24420agagacgagc aagatgactg acatcgaatc gcctccaatc tggaggaagt tatcatccct 24480tccaatcgat tcggctggga tatgcaaaat gtcagcccag acttgctgca atcttgcctc 24540cattgtcgtt tcgagagcac gtttagtact tccgacgagg gagtactgtt cgaactgctc 24600tctagacagc gacgtggcca tctgcacaag gagcttccgg tctagcttgg ttgacgttcc 24660aatcggcata tgttgacagg ggatgaaagt tgtgggaatc atataaggcg gtagaacacc 24720tttgagaaga gagatcaaat catggatttg aggcgcagca ttgttatcca agggtgcgaa 24780tatcgccttt ccgtcagggc ctgttccaag atgggaagaa agagtctcgt tgctgaagct 24840gtaaaaagct actagttgag acgcttcgtc ccgcttcata acgtcgaccg cgacttggcg 24900agcaccagaa aggttcgtga tgatctgttg ctcaatctcg tgcaactcga tacgaagtcc 24960acggatcttg acctgggtat ctttacgacc agcaaactcg attgtaccat ctggattgta 25020atgtcccagg tctccagttc tatagaagcg atcccagcct ctcaattcac gattgggtac 25080ccaatacgga agagaagaca caatgacctc gtcggtcttg gctggattag ccaggtattc 25140cctgaagaga gttgggccct ggtagacaat ttcgccaaca catccggtgg gaacaagttt 25200cctgggatcg tttggatcta cgatccacca attacccaag atagaccgcc caatggtcct 25260gggagagtcg tttggaccag tccatggatg gagggaagcg atgacacatg tctctgttgg 25320accccaggca ttgtatagcc gtagctttcc gaaccacgtt gatacaatat ctgacgcggc 25380agcctcgcct cccacaagaa gtacttgaag gcaaggtatg tcttccggct tcaagctacg 25440cgcaacagtt ggggtagcga atgcggcgtt tacagaagct ttgaccatgt agcctgtcag 25500gttgttcatc tgttcgtccc aagatggcat acatatgcag ccaccgacaa gcagcgttgc 25560gataatttcg aagatgcacg cgtcgaagac aaaggaagca aactggagcg ttctggattg 25620atctgtgagg ccaacgttga gagctaaggc cgtctgcgat gtacacaagg acccgtgttc 25680gatgacgacg cccttgggca tgcctgttgt tccggatgtg aagatgatgt aggcagcatc 25740tgatggagag acgtcgacat tgggtcggtg cttaagcacg tcctttgtag acaaggcctg 25800gtccaaccta gatgacacct cgagaacgaa aggcgtcaga ttggtacact ttgatgtgtt 25860tgtcggagaa gccaagatca gctccgcgcc agtctgcgag atgatctgct ggtaccgctg 25920aacaggatga gtgggatcaa gtggcgacca ggtcgcgcca gctttgttga tggccaagat 25980ggcgacgata taccaagctg acttgtcaaa acagacgtgt acaacatcgc ccttcttgac 26040gtggaagttg ttgatcaggt gatgcgataa cctattggcg caaatatcca gctgttggta 26100cgtgaaacgg gcgtcgcaag catctacggc gagtgtggcc ggatgcttga gcgtctcgtc 26160ttcaatcaga gagtggacgc atcgctcgat agtcgtgggt gggactccgt tggctgaggc 26220ggcaaagtcg acttcccaag gcacctcagc gagcatttgc gacagtgact gattgggaga 26280aacaagaagc tgttcaaaca catgcttgaa ggcgtgagag agaccttgca cctgatgttc 26340aggcacgact gatggatcgt aatacagatc gaggtcgacg ctatcgtcag ccagcatgca 26400ttgagcaacc aggggatagc tcagataacc ctggagcatt tccactttgc tgcttccctc 26460aaggtctgtt gcgaagctga gcaggttgct ctcgtgagtc agtttttgca ccggctgcac 26520aacgaccaat gacttgaagt cacaagcggc cttggctgca tcgttgaggt tcgagatgtt 26580cttcagcccg aattgctcat gtggaatcat gtcaaaggct tggttctgga cacttcgtaa 26640gaatgtcgat acagactgct ggtcgtctat ctggacacga atcggcacag tagcgacaac 26700gaggccaggg atggactcca ggccagggac tgcagcttga cggccagaaa cacttgagcc 26760aaagcacaca tcattgacac cgctatatct ggccagcaca atagcccaag cagctcgtat 26820aatcgcagct tttgtgatgg agctgttgga cgattgtcgg attccgacgg tgattgactg 26880aagcctcgtt tgtttcgact cgattttgcc gccctcgctc accgttggaa agctcatggg 26940cttggcaccc tccaactgag aagtccaaaa ttcggctgag atatcagaat caatacccat 27000gatatacttg acgaatcgag agtacgggta aagcggagag acatccaatg cagtgtaata 27060gctctgcaaa gtgctgagca tcagcggaac tgaccagcca tcgtaaattg aatggtgtag 27120ccggaggcag aagtaattgg cgccatcatg ctcaatcaga gagtagtcac acagcggcaa 27180gccataatca acttcaaggt cttgctggcc atggcttggc aacatcgtct tctcctcgtc 27240attccagcga cagccgtttc tgacaacgac ttggatggtg ctgttattta tgacgatgat 27300acgggttcgc aagtttgcac acgcttccac ggttcggttc catgcggcga taaagcgtga 27360aacgtcggta ccctctccaa ggcggtagcg gaacctggct atatacgcgc ctggttgctt 27420caaagttgta ttcaagaggc cctcttggag cggagtgcaa gggtaggcat cttcaatagc 27480ttggccctcc gtcagtttgc attgaagttc tgcatcgccc cctgatatag ccttgtggat 27540agactggggt accaagctga atggcggaac ttcatcagat gatatgacgt ggccgtcagc 27600cagagccatt ttggtggcaa cagcatgtag ccttgggtcg tcggagatgt ccgtgacaga 27660gatggggaag ccaatctttc gagctatcga aaccagttgg attgcaacaa ctgaatcacc 27720gccgatctgg aagaagttgt catgacgacc gatggattcg gcaggaatac ttagcacttc 27780tgcccataga gactgaagca gcaattccat ctcggttgat gggggttcct tggcagcgtc 27840ggttaacgag taaccggtaa gttggtctcg atcaagcata gctgtgaact gtcggagcga 27900ctttctgtcc agcttgacgg aggtgatgga cggcatgaac ttgcaggtaa tgaacagcgt 27960cggtatcatg taaagtggca ggcttgtcct cagctgtgcc actgcctcgg atatcaatcg 28020ttgcgtgtca tctgtgagcg gcgcaaagac ttcgtcagct gtcgcggtgg aagaaatctt 28080tctgagttcc gaagtgaagc agatgtacgc gaccagagta tggccattgt cagtgttgac 28140gacttccact gcaacttgat ggatggacaa agcttgtgaa atgcgatgct caatctcccc 28200agcctcaatt ctctgacctc ggatcttgat ttgcgtgtcc ctgcgagaac agtactggat 28260ggtgccgtcc gggttataat agcaaaggtc acccgtctta tacagtcggt tccagccaac 28320aagcccttga cgaggaaccc agcttggcat atctgtaacg actgcctcct tggttttgtc 28380gggagctgca aggtactcac ggaggagcgt tggaccctgg acaacaagtt cccccacaac 28440accgatggcg gctagctggc tggtatgctt cgaatcaaca atccaacagc agctgcccac 28500cggcttacca attttgagat acgactcttc tgcagactgc cactcatgtg tactgctgat 28560cacgcaggtt tctgtcggtc cccagccgtt gataaggcgc accttgccaa tccacgtgtt 28620gaagatgtcc agagtgggag cttctccggt aacgacgagt gcttctaagc tctgtgcatc 28680ctcaggactt agtgtccgta ggaaagaagg tgtaagcaaa gtccaattga cggagttctg 28740gttaatgaag gtagcgaggt cgttcatcct tgtccagtcc gacggaatac agacacaggc 28800gcctaacatc agcgtcgcaa agatctctgt gactgagggg tcaaaggtaa acgctgtgaa 28860ttggagcatt cggtcattgc ttttcaggcc gaatctcttt gacaacgcgg tctgactggt 28920gcacacagcg gcatgctcta ggacgatgcc ctttggagta cctgtcgaac cagacgtgaa 28980caggacatat gcggcgttgc gaggagttac cggaatactc gggttatctg aactgatacc 29040cttgctaacc agctgatcat cactcgcgct gttcacttcg agcacacgct cgacgacctt 29100tccacataaa gccgcattgc ctgacgaggc caacgcaagc ttcgcacctg tctggctgac 29160aatttgtcga agccgctgtt cgggatgtga gggatcgaag ggaacccaag ctgcaccagc 29220tttgttgatg gctaagaccg atatcacatg ccagatggac ttctcaaagc acacgtggac 29280gagatcctct atttggagag agtacctgtc tatcagatga tgggataagc ggttggcggc 29340actgttgagt tggctgtagg taagctctcc atcccaagca gaaacagcaa ttgcgtcagg 29400acgttgttca gcttgagcct cgataagtgt gtggatgcat gagtcgatga agtcaggtat 29460ctcttggttg aagctgatgg ccttttccag gtcccaggag gaggcaagtg ttaccgctct 29520taggggtgcg aagcgcagcg acgtaagctg acagacaaca tggctcaatt ggtgagcaag 29580tgcttcagcc tgagcctcaa caagcgcgtt agacttgtag atgatggata gtctgacgga 29640gtcatcgcca agatgtgctt gaacaacgag tggaaagctg tagaacttgt gaaccatgtc 29700ggctggactt tcaacttcga cgtctgcggt cacaaggacg ttgtcaccct cctcgttctc 29760tgtctccgtt ggctggataa gcaggagact cgagaactgg caagcttgtt tggcatcagg 29820accaagcttc gcaatattct gcaagccgta ttgctcaaat gagatcattt ccagtgcctg 29880atcttgtaca gcctcaagga agcaagacac agattgatca aagtccaagc gaactcgaac 29940tggaacagtg gcaagggtag gcccaaccat gtcgataacg tcggggaccg gcgcttggcg 30000acccgataga gacattccaa agcagacatc gtcagtactg caatatcgag atagtaccag 30060agcccaagca gctcggatca atgttgcagt cgttatgttt

gacttgggca tcttgggtag 30120gtcaacaact ttctcgagaa tgcttgtggt agtctcagag ttcgggatac cattcgtggc 30180tgggaagttg gagtgctcgc agttctcgag ctgcgcgttc caataccgtc cagcattgtc 30240aacatccaga gatttgacat attggataaa gcgagcatac gagggaagag gcgacacttc 30300aaggccagag taaaccttct gcagcacggt gaaaatgttt cggttggaca agccatcaaa 30360tacagcgtga tgaaccgacc aaaagaagaa gcatcgccca tcattttgtt taacaatggt 30420accaagtgag agcctcaatg cgtagcccat ctcaacagag cggtgcaact gaatagcttc 30480ttcgacatct cgtccatcaa cagcgggttc gtcgttaaga accacttgga tgggcgtctc 30540attgacgtaa acaatccgtg tgcgcaggct ggtgcagatt tcaacagttt tcgcccacgc 30600tgttttgaag gaatcgacgt tgacatgatc gggaaggcga tagacaaact tcgcaatgta 30660tgagcgaggc tgcttgacgg ccagggccat gaggccttcc tgtaggctcg tacatggata 30720ggcatcgaca gcgtgcgaca atgagccttg gtcacgcaca gcctggatga tcgcctcttt 30780aggaatacta gagaccaact tgaatggctg tatgtcatcg acgagagagt tggcggtcac 30840agagacagcg tgggccattt gttccagctg tggtttgtgg aagatggtag ccacactcag 30900agcaagacca tgcttctgag cgagcgtgac aagccggatt gcactgatgg aatcgccacc 30960aatgcgcatg aaactgtccc gtttgctgat atcttcagcg ttcacgtgga gaacctctgc 31020ccagagatcg cggagtttga actccatggg ctctgtcggc gtttccttct cttcattacc 31080aggaccaaaa cgtgaccgat catcgtagga gatattctga gccagctcaa ggagagaacg 31140tctgtcgact tttccagatg tggtttgatt cggtttgccg tggaaaatga gatagcatga 31200gggaatcata tgtgatggca gagtagtgga caaagacatg tctacatcgg aaatcaagat 31260acgctgctcg tcggataggc taccgatgag ttccaagggc gaggggctgt tggatgtcgc 31320gctgtcggtg taccataaga aagccatgag gctgtcttgc cgttgctcat cgacagattt 31380gacaacatca ataatggcag acatcccagc tggaagaact tgatgaagct ggtgttcgat 31440ctcgccgagt tccacgcgct ggccatggag cttgacctgc gtatctttac gaccgatata 31500gtcgaaagtc ccatcagcgt ttcggcgcac caagtcgcca gttcgatagg ctctgttcgg 31560aaagtcatga ggcagccagc ctgctgtgaa gtattcgatc caattggcag cttgcttttc 31620atcgacattg aggtagcccc gggcaagcaa tgaaccctgg attagcaact ctccgatgca 31680tccaacaggg gcgagcctgt gaatatcggt aggctcaaca acccagaaag cacttgcaag 31740cggcttccct agattagttg acttgccgga ccggcccacg gtagggttcc aggcacatat 31800agaggcctca gcagggccgt agaggccgtg tagctcaacg tggtctttcc atctggcagc 31860agtcttctgg ttgatcgcct ctccgcccag acacactaca cgaagtgtcg gtacgtcggc 31920aggattgagg aggtcagcaa ccgtaggcgt caggaatacc caatttgctt gagtcttgtt 31980gatggcacca gataggtcgt tgagtcgatc ctcttctgaa gggatacaga ggcaaccgcc 32040acgcatgagt gtaacgagag tatctagaat accgacgtcg aacgtgtagg ctgaaaactg 32100aaaaacgcgg ctaccaggtc caatcagcag gtcagaacca tatgcatttg ccgaagagca 32160gagggtatca tgctgaatga ccatgccctt cggtcgacct gtactgccag atgtgaaaag 32220aacaacggct gcatcagacg ggcagtcagt ttgctgtact ggagtagcag cctcaggcaa 32280ggtggcaaca aaagaatcat cgataacgac aacaggaatg tcaaggcctg acataaccga 32340tgcgcagcac gggcttgtca gagcaattgt cgccttaatg tcgtcgagca cactgctgat 32400tcgtgtccgt ggtgccttcg ggtcaagcgg aacgaaagca ccacccgcca gttccacagc 32460gaccatcgtc acgacggccc agacggactt ggggaaacat ataggcacaa aggtctcgcg 32520ccctatgcca agctgtcgta gcttagctgc caggcgggtg accaagcttc caagctcact 32580ataggtaagc tcgccgtccc atgagactac agctggagag gtgggatagg tgcggatcgc 32640atcttgaata agccagtgag tgcaagactg gacgggaagc ttcagtgtct ggcaatccct 32700agcatgcttc acgtcccagt cgctcactag agagatatct ccgagacaaa catcgttggc 32760aagctgctga acaacatgct cgatctggta agagagggct tcaacttgct tttcggccag 32820cactcctgga ttgaagaaca agcgctgctc aacgttgtcg ccggctatcc cgtagatgag 32880aacaagagga tagttaaagt atgagtccat cgtgtcttcg gtcagggcac tttcagcttc 32940cccagcaaga agtatggcct cctcggagtc cgcttgagat gaagcgggag gctggataac 33000gagcaagcta gaaaaactgc atgcttccct tgcatcagag ctgacattgg cgatattctg 33060tattccatat tgttcatagg gaatcacgtc tgtcgtctga ttctgaacgc caagaaggaa 33120ttcggaagtt ttcatctggc tatcaagatg aacacggacc gggatagtgg caattgctag 33180tccaggcatt gcttctaagc ccggaactgg cgcttggcga ccagacacgg tcgtgccaaa 33240ggtgagatca tcactgtcgc agtaacgtgc aagaacaatc gcccaggccg cacgcaagat 33300agatgcttta gtgatggatg acctttccct tacagggaga gcaatggttc tccggtgtac 33360ctgggtaggc tggccatcag ttcccatgtt ggtaccgttg agaggaggga atgaggcccg 33420ctttgagccc tgaagttcgt tagcccagaa gttcgtggca gcatcatgat cgagagacaa 33480tgtgtatttg acgaaggcgt tgtatgcctg cagcggtgat ggctctacgt ttctgtagat 33540gctctccagg gtactcagaa tgagacgaat ggtccaacca tcgtaaatgg catgatgagc 33600tgaccagaca aagtagctgg tgtctgcttc ctgcactgtt gcgtaccaac agagaggcgt 33660accatagctc atttgaaggc ctcggtccga gcggacaagg gaagagagtg tctccttgtc 33720ggttgcctcc caggaggctg ggtcctttag aaggacctgg atcgatgaat catcaaagag 33780aatgattctt gtgcgtaaag cgccgcaaag ctcgacagtc ttcatccacg cggctttgaa 33840gcgacctata tcgacttggc tggccagcct gtatacatat ttagcaacat atgacccccg 33900ctgcttcaca gagagtgcca tgagaccctc ttggattgaa gtagcaggat aggcgtcatc 33960aatggcactc tgtgcaatgc cacattgctc agctgcttgc atgacgattg cgtctcgagt 34020cggcggcggc agaagactga atggcgcaat ttggttgtcc ctcccctcag ctttaccact 34080gaagaccgcc ttcgcagcta ttgcgagtaa cctggaatcg tcaaagacgt ctttcacact 34140gatgaccagg ccctcagccc gcgctgtaga caccaggtgt atagcagaga tcgaatctcc 34200gccaatctgc aagaagctgt catcgcgacc gattgaatca gccggtatgc tcagaataga 34260tgcccagagt gattggaact ttcgctccat gtccgtctca gggggtctct tgttatcatc 34320agaaagcgaa tacatagaga tttgatcctg ggtcaggaga gaggcaactt gacgaagcgc 34380cgtcctgtcg agttttgtcg atgtgatgga aggcatatac ctgcaaacga tgaaaagggt 34440cggaatcatg tagtttggaa tggacaccct caatttgccg accatagcag ctagtaaggg 34500tcgaacttcg actgttatag gcatgagaat gtcgtccatg ctattctctg agctcgtcga 34560ggagcgagtc tcttcagtga agcaaaggta cgagaccaag cgggagccac catcggatgt 34620cgagatgtca acggctacct ggcaaatgcc ttccaggctc tcgcgaatcc ggtattcaac 34680ttcgctaagt tcgacacgta agccgcggat cttgacttga gtatctctgc gactacaaaa 34740ctcgattgtc ccgtccggat tgtacatggc caaatctcct gatttataga agcgtgtcca 34800ctgcgatgcc ttttgcagcg cccaatcggg caaacacgtt accgttgagg atgctgttcg 34860ttcagcgtca tccaggtatt cgcgaaggag cgttgggcct tgcagcatga tttcacccac 34920ggttccaatc ggggccagct ggtcagaacg ctcagggtcc acgatccagc agaaagcccc 34980aactggccta cccaccgtca atggagaatc ctgaggctgc cattcatgca gcgtactgaa 35040cacgcatgtt tcagctggac cccagccgct gatgaatcgc aacttgccaa cccaaacgtc 35100aaagacatct cgaggagtga cctctccaca cagcagcagt agctccagtc ctgggacatc 35160ttccggcttg agaacgcgaa caaatgaagg cgttaggtat gcccagttga cactagcatc 35220cctgatgaag ccagcaacgt cgttcatgcg ggcctgctct gaaggaacac aaacacaggc 35280accagagata agtggtgcaa ctatttctcc gatagagaga tcgaacacga acgccgcaaa 35340ttgaagcatc cggaccttgg aatggaggcc cagcctgcga acaatggctc tctgactgct 35400gcagacggat cgatgttcca taacgagacc tttcgggacg ccggtgctac ccgatgtaaa 35460caggacataa gctgcgttag caggcgaaac cttggtggtc ggcgggttct gactgaaagc 35520agcaccattg cgtgatagtt gttgatctag agaagcagaa acctcaatga caattggtat 35580cagatccttg caaagagagg cgtgagattc agatatcaac accatctgag ccttcgtttg 35640cttgacaatc tgaccgagcc gttccagtgg atgagagggg tcaagaggaa cccatgcggc 35700gccggccttg ttgatagcca aaatggacac gaaataccaa gccgacttct cgaaacacac 35760atggatgagt tcgtccggct taatcgcgtg ctgagatata agatgatatg ctaagcgatt 35820cgctgcagtg tccagctcgg cgtatgtgaa gctaccgtcc catgcgcaga tcgccatggc 35880gtcaggtgtc tgacgggctt gacgctcaaa gagctgatga aagcagccat cgacggcttc 35940tggcacctcg gaattgaact tcatcgcctg ttgaaggtcc catgaggatg tcgttgcgat 36000ggagccaaca tttgactgca acttgaggac aagctccctt gcaacatggt ggaattggtg 36060cgataacgcg acaatttgct cttcgggcag gatggcagag ttgtagatga gaacgagttc 36120cgtcgattca tcgtacagat gcccctgaac aacgagggga taactgaagt agttttgaag 36180agcatactct cctgtctcaa ccttcccatc agctgcaatg aggatagcgt cttggtcacc 36240agcagggtcc aaggcttcct tcggctgaac aactagcaag ctagagaagt cgcaggcctc 36300cttagcacaa gcatgcagtt tgctgatgtt ctgcagacca aactgttcaa attcgaccat 36360cgccagggct tgttcttgga cctcctgcag gaaggcggcg accgatttct gttgaggcac 36420tcggattcgt aatggaactg tcgcaatggc tgggcctggc atgtctatta tgccactcac 36480cggggcttgt cgaccggaaa ttgttgttcc aaagcagata tcgtctgtct cgcaataacg 36540ggtaagaagt aaggcccatg tagcacgaag aattgtagcc cttgtgaagc cagttgcgct 36600cagatctgga agtttgatat tcgtcaccat tgaccgatag ccgtttgaat actcaggaag 36660cttcccgctc gtattggggg ggaacgaggc cttcttggca tcccaaagct gttccaccca 36720gtagtcagca gcagattggg ggttgatagc caaggtgtat tcaatgaaac gagaataggg 36780cgtcaaagct gtggtcttca ttcccttata cacgttatcg agcgtggcga ggacaactcg 36840tatagaccag ccatcgaaga tagcgtggtg catggtccag atgaagtgcg tctggttgtt 36900ctcgtcctta atcaacgcat atcggcaaag gcgagatcca tactcaactt ccagatgctc 36960aattgactga aggtaagact tcaaagtcat acccttcgta tcgtcccaag tgtagtcgct 37020tatgactacc tgaaccgacg agcccttgag gtgaacaact cttgttcgca ggatgccgca 37080tagccgtaca gtcttgtccc aggcggcttt gaaggcggag ggatccacgt tctctgctaa 37140gcggtagtga aagctcgtga tatacgatcc aggctgtttc actgccagga ccataagacc 37200ttcttgcagg tttgtgcacg gatagccgtc ctcaatcttc atcgagcgag tcaatttcag 37260ctcctttctc aatcgcggcg ccaagagggc gtctcgaatg tgcggctcca ataacgcaaa 37320cggctttgca gaaatggcgg aattggcgga gctagagtca acttcgatag gcgctgcgtt 37380caaagcgaca gaggaaagtc gagaatcctt gaagatatcg ttcgctcgaa gctcgatacc 37440atgctcgcgg gccagggcaa tgaggcgaat aatggctatg gaatcgccac cgattgccaa 37500gaaactgtca tgccttccaa tcgattcagc agggactttg agaacatcgg cccaaagctg 37560ctgcaaactg tgctccattg gggtctctgg actggacttg gcctcggtca ccgcatacag 37620ggagtattgc tcaaaggcct gcctatccaa tgccgcagca agacgacgca agagtttcct 37680gtccatcttg gaggatgtca cgagtggcat cttcttgcaa ggaatgaaga aggtaggtac 37740catgtagctt ggaagagcag aagccaagaa accgtgcatc gcctctaaat cgctcctcag 37800atctgccgtc gacggaagga agatatcttc cgttgccaca tcaccagtca tgctagccgg 37860aatggtatcc gtattctgac agataaaggc aactagatga gtaccagctt cgaacttgag 37920cgcttcaaca gcgacttggc atggaccttc caagttgttc cgaatgtggt gttcgatctc 37980acccaattcg acacggagac cgcggatctt gatctgacca tctttgcgac tattgtatct 38040aatggtgccg tctgcgttat aggtagccag atctccagac ttgtagaatc gaccaaacac 38100ctcgcggttg ggaacccagt gaggaagcga ggtaacagtg gcggcagccg ttttctccgg 38160gttctccaaa tattcgagaa gcaggttggg cccttggacc acgatttcac caacggtgcc 38220tactgggctt agctgatgag ggtcattagg gttgacgatc cagcagtttc cacaaattgg 38280gcgtccaatg gtcagatgag agagttcagt agctgtgtat tcatgtacca tggcgatgac 38340cgttgtttcc gttgggcccc agacgttgaa cagccgcacc ttaccgagcc aactgttgac 38400gacttctttg cttggagcct caccaccaag agtcacaagc tctaagcaag gcacgtcttc 38460cggtctgata atgctggcca ctgacggtgt caggaatgcc caggtaacgt tcctttcgcg 38520tatgaaagct ggcaatgaat tcatctgtgt atcccatgaa gggatgcaaa cacaggcgcc 38580tgaaataagg ggactgtaga tctcaaaaag tgaggcatcg aacacgaaag aggagaattg 38640aagcatcctg acaccgtcat gcatctcgag tctctgactc aaagcgactt ggctgctgca 38700gatagcgcgg tgctgaatca cgacaccttt gggaacccct gtggatccag aggtgaagat 38760gatgtatgcg acatcatcgg ggctgacctt cacactgggc ttaaccgcat cattgagtgg 38820tagcctggac atgaactctc cgttgacctc gaggacactg gtggtcacgc ccatgagctt 38880gggcacgttt gcaagggaac aaagagccaa agttgccttg gtctgaccaa cgatattctg 38940atgacgatcc gttggatgtg ctggatcaag aggcacccaa gcggcaccaa tcttgttgat 39000tgctaggatc gccacaataa accaggcgga tttgtcgaag cagactatga ctaggtcacc 39060agccttcact ttgagcgtgc tcaggagata cgtcgccagc ttgtcggcat tttcatcaag 39120ttcggaataa gtgaaatcag cgtcccaaga agagaccgca ggagactcag ggttcagttt 39180tgttcgctgt tcaatcagcg tgtgaatgca tgactcaaca acgagaggtt tgtcggggtt 39240ggaggcgtga gcaaagtcaa taccccattg actagtcatt gacaaatttc cgagcggctc 39300cttataccga aggttcagct cctgcaagac atgctcgaac tggttgcata gaccctgaag 39360ctgaagatcg gagagtacat cagcatcgta gtacagcgtc atgacagcct ggtcctgcat 39420caaatcacat tctaccgtca aaggatagtt gaagaagtcc tctatccaat tctcaatgct 39480tgtttcatca ttggaatcag tggtgaagag ctctccctgg gactttccga tctcatgttg 39540tctcgactgg acaacaaaca agctggtgaa gtcggttgcg tgtttggcac tatcactgag 39600cttcgatatg ttctgaaggc caaactgttc ataagccacc atctcggagg cctgcgtctg 39660gatattctgc agatattcgg aaacatgttg tgaacgatct agacgaactc tcacagggac 39720tgttgcaatc gttgggccag cgatgttgac gaggtcctga acaggcgcct gtcgacctga 39780cgtagttgcg ccgaagcaaa tatcttcgcc ttcacagtac atgctgagga caagcgccca 39840agcgcctcga agtacagagg cttttgtgac agaggagttg ggttgagttg gtaccgctag 39900ctttctcttc atgatctgag tcttctgagc cgttgacgtc ttgttgccag ttgtgacttt 39960ggcgggtggg aatgaagccc tctgagcacc ttctagctcc ataagccagt agtccttagc 40020cgcctttgga tcaagctgtg acaggtattg cacaaaattg gcgaatgggc gaatgggcgg 40080aagaggctcc tgtgcataca gccgttggag aacgtcaagt ttgatctgca ttgtccagcc 40140atcgaagata gcatgatggg caacccaaat aaagtacgtc gacccgtttg aacaactcag 40200gattgcatgc cgcgaaagtc gcgagccata gcccatattg aggctggtca accccttcat 40260gtaggactgg agggtttgac catcagtctc ttcccataag ccatcatgcg agaccacagc 40320ctgtagtgat acatctccgt gctgaacgat cctcgtcctc aaactactac aggccttgat 40380ggtacgttcc caggagtcct tgaaacgatc aagatcaacg ccgtccgcca gtttatatgc 40440ccgtctggca atgtaggagc ctggacgcgt cgcagtcaaa gccatgagac cctcttgcag 40500cggcgtacaa gggattatgt cttcaagttc ttgttcgttc gcaagtccac actgccgccg 40560aatcgaggcg tgtaaagact ccacctctgt cgcttcaatc atgctgaacg gttgagcgtc 40620agtatgctgt gactgcctga tggtcatgca ggcagccatt gaagccagtt gaggctcttt 40680gaagatgttt gcaatgggaa gcaggatgtc ctctcgtgca gcaaggttcg aaagatggat 40740tgcggagatg gaatcacccc caacctcgaa aaagttgtcg aatttggaga tatcttctgt 40800atcgatcttg agcacttgag cccagagact ctgaatcttg agctccattt ccgtcgtggg 40860tgggactttg tcttggcgtg caatggaaaa gctagatatt ctttcgcgag gcatgctggt 40920tgcgagttca cgcagagttc ttctgtcgat cttgtttgac gatgtatgag gcacatctct 40980cattgggaag atgatgctgg gaatcatgta gcctggtagg acacgtcgaa gctcctggat 41040gagggcctgg aaggaagaga cgtatatctc attgctgata aattcggcat aaggatcctc 41100agcatccgtc ggggtattat cgcacaagta gttgtggaat gtgacaaagg caatgatcat 41160cttgcctgct tcacgctcaa tgagatccac cacaacatgc tgtacatctg caaggtttgc 41220tttgatgtgg tattcaatct caccgagctc cagtcgctga ccacgtaact tgacttgcgt 41280gtcttgtcgt ccgaagaact ccaccgttcc gtcggggttg aatctcgcga gatcaccagt 41340cttgtaggct attggtctat cactctctgt ttgagtaggc agccagtcaa gggaatcgac 41400aaaggaggct ttggtcttct cctcgttgtt gatatagcca cgcgcaattg catggccctc 41460aacaagtagt tcaccaacac atcccactgg cgtaaggcga tcatggttgt ccggctccac 41520gatgaacagc cggtgagtaa atggacgtcc aatagtcatg ggtgagtcgt cctgagactt 41580gaaggggtgg ccagcacaat tgacacaagc ttccgcaggt ccataggcat ttatcagctc 41640aactctcccg tgccatgttt tgaggatatc cttcgtggta gcctctccgc cgatagcgac 41700tgtctgtaga gtggggagag tatcgggatc gagagttctg atgaatgatg gcgtcaagca 41760cgccaaggtg actcgtgctt tagtcataaa gcgccatgct ctgtccatcc tctcggtttc 41820tgtaggaata cagagcgtag ctccaaggat gagagtcagg aagatatcca acacgctaac 41880gtcaaagacg tagctcgcga attggaagac tcgtgaagac ttcttgaaat tgaacatatc 41940agaatgcttc aacagcgaag tgcaagccgc cgagtgcgtg acgagcaagc cttttggctt 42000tcccgtagag ccagaagtgt acagaacata cgcagcgtta tgaggctccg gtttcttgta 42060gttactcagc gaatgatagt ccacaggcgt ctcgggagca agtgctaaca atgaggaaga 42120cacctggatg gtgtgcggcg ccatgctttc acaagatgcc gccatcgatg gcgaggagac 42180tatcacttta gcattcacct cctgaaccaa ggcttgcctt cgtgattctg gatgtgtagg 42240atcaagaggc atgtatgcac cacccgcctt caagatacca atcattccaa ccacagccca 42300gatggacttt tgcatgcaga tgggcacaat tgtctcaggc tggacgttgt attgcaaaag 42360ctgacttgca acatgatcag acaggcgatc caaggcagcg tacgtgagcg atccttcggt 42420agagaacaag gcctcatcat cggggcataa tttagcccgc tgagagatta ggtcatgcat 42480acagtgtttt tggaccacaa tctcgtgaga gttccagtcc aagctctgct gaagatccca 42540cgggcttgct ctggatacat ctcgaagaag cgttctcttg tccagagatg caagttgttg 42600aatgatatgg tcgagctggt tggataacgc aagcacttgg aactcggaaa taacgtctgc 42660atcatataca aactcaagct cgacgctgtc atcccccagg tggcattgga ggataagagg 42720ataattgtag tagtcttcca tcgactgcca tgccaaacgc tgttcctccc tggtggagat 42780aaggatcgct tcgtttccgt tggaaccggt tgtcaggtcc tttggctgaa caaccatgag 42840actggtaaaa ttgcatgcgt cctttgcatc agagccaatt ctggctatgt tctgtagccc 42900gaattgctca tgtgccacca tatcattcga ttgcttctga acatcacgaa gaaagtcgga 42960cagtgactga tcggggttca gccgaactcg gactgggagc gtcgaaacaa ccaggccaag 43020aacgctctcc acaccgacaa gaggagcgtt gcgaccagaa acggaggcac caaagcaaat 43080gtcatctgtg ctgcagtatc ttgcaaggag catagcccac gcagctcgta gataggtcgc 43140tctcgtaata gtcccgtttg tcgtctgtgg tatcttaacc tctttcgctg agatttgaac 43200gtttctcttg cttttggcaa ctgctatatc gtctcttggt aaaggaaaca cagcacgtct 43260cgctccatcc atttgtgcct tccagtacgt cttcgaagtc tcaaagtcga gttgcagcgt 43320gtaccgcacg aacgccgagt agggggccag tctcggcact tcactgtctc tgtagatcgc 43380gtgcaacgcc tggaccatga gagccagagt ccacccatca aagattaaat ggtgcatgat 43440tgcaacgaaa tagcaatcgc tattgtcacc atggacgagt gcaaagcggg cgagccgtga 43500tccgtaggac atgcggatac tattcgcttg tctcaaaaag acgtctatgc cttgattgtc 43560tgtgacttcc cattgcgcag gttctttgac gatgacctgg atagagtcca ggctgctgag 43620ctggacgatc ctggtgcgca aattgctgca aacggcaact gttcgctccc aagacgcctt 43680gaagtgaccg atgtcgacat gcctcggaac cttaaacacc atcttcgaaa cgtatgctcc 43740cggttgtttc gtggtcagcg ccatcagtcc ttcctgtagt ttagtacaag ggaacgcatc 43800gtcgactgca tcccaactgg gcaagccgca cagcttaagc agttcatctt gcatcactga 43860gtcgatctgg ccgggctcaa gaaggccaaa tggcgctaca attggagccg aatgggagtc 43920tccgtcggca gaagttgcga tggcagccac tcgccacagt cgtggatcgt cgaagacatc 43980ctggacagag agagatatcc cagcctggcg ggcatcggcc acaaaatgga tcacagcaat 44040tgaatcaccg ccaatctgca agaagctatc gtctcttcca atggcttcca gtggcatttt 44100cagccgtttc gcccaaagcg cttgcaactt gctctccatt gccgtttctg gtgggttctt 44160gacagtatca acaagcgagt aggtggacag gccgtcggga cccagcaatt cgatctggtt 44220cttcaacgta cgcctgtcca gcttggtcga cgtaatcgat ggcatgtatt tgcatggcac 44280gaagaatgac ggtatcatgt atcttggaag attcacggat aggtgaccaa tcatgctgac 44340gatctggctc ttcaactggc tggtgacagg gaggaacatt gcggcgcctt catcggccgc 44400ggcgttaact gtcgtcacca ttcttgtttc attgctgaag caaaagaagg caatcaagct 44460tgaaccacca tcggtggtga ccatgtccac cccaacctgg cagactcctt caagggatgc 44520cttgatctgg tgctctacct ctcccaactc gactcgaaga cctcggatct tgatttgggt 44580gtcttttcgt gtgacaaaga cgagagttcc atccggattg tatttacaca aatcgccaga 44640cttgtagaat cgattccaat ccgctagatt acggtagggc gcccagtccg gcagtgacct 44700gaccgtcgcc gcttcagtct tttcaggatc cgccagatat tctttgagca acgttggccc 44760ctggatgaca acttcaccca cggttccaat aggtgctaga acgtgtgggt tttcggggtc 44820gacaagccaa cagaagccac ccacaggtct gccgatggtc aaagaggatt cgtcaagcga 44880tgtccattcg tgcagtgtac tgaacacgca cgtctcggct ggtccccatc cattaacaag 44940acggaccttg ccaaaccatg tctctagcac atcacgtcct acagcctcgc ctgcaagcag 45000catcagatcg agaccaggga gggtgtccgg gttaagcgtg cgggagaatg aaggagtaag 45060gtaaacccag ttgatcttca tgtcgcgtat gtactcaacg agcccattca ttcgaacctc 45120ttcagacggc acacatatgg tagctccggc aacccatgga

ccgacaatct cgccaattga 45180catgtcaaag acgtatgatg caaattgaag cattctgata tccgacgtca tgcctagcct 45240tctgacagcg gacgtttggc tcgtgcaaac agcctgatgc tgcatgacaa agcctttggg 45300ggtcccagtg cttccagagg taaaaagcac ataagcggca gcgctcgggg acactcgagg 45360cagtcccttg ctacctcgtc tctccgcaat cagcatgtcg tcaagatcag cagagacctc 45420aatgatatgc tcaaccagtt cagagcaaag agcagcattg ctggacgaag tcaacgcaag 45480ttttgcatta gttcgcgcga cgatttgctt ttggcgttgg accgggtgag acgggtcgag 45540aggggcccaa gcagctccag ctttgttaat cgccaggatg gagatcatga accatgctga 45600cttttcaaag caaacgtgaa cgagatcgcc cagttgcacc tgagccgcag agttgctgat 45660cagatagtga gcaagtctat cagcggcaag gttcagctgt tcatatgtca atgtcatgtc 45720ccatgcacag acggcagtag catctggtcg cttgagggca tggcgttcaa tgatctcgtg 45780aaggcatgag gaaacaattt caggctcttc actgttccat tccctgacac gttgcaaatc 45840ccattggctg gatgaagtga cagacttcag aggtatatca tctggctgaa gaagctgctg 45900gataacgtgt tcgaaatgat ggaataacgc tcccagctgg tcctcattca agatgtcatc 45960ataataggtg aactcgagat caatggcatc atttccaagt cgggtttgca gaaccaatgg 46020ataattgaaa tagttgcgca tggcttcctc cgaaatcgtc ttctccaccg ggccttgctg 46080gaggatcgag ttcaaggaag agcaggccac tgaagagaga tgctgggttg gttgaattac 46140caataaattg gcaaaatcac acacttcctt tgcattcggg ccaagtttgg agatgttctg 46200taacccgtac tgttcgtgag caaccatgtg agacgcgtgc gactgaatgt gctgcaggaa 46260ctcagagatg agcatgtcgc gcttcacatg aatgcgcaca ggtaccgtgg cgatcatcgg 46320accaggaatc tcgttcaagc cgggaacggg ggcttgtcgg ccagagagcg tcataccaaa 46380gcaaacatcg tcagagccgc agtactgagc aagaacaagt gcccaggcag cgcggataat 46440ggtagcggtt gtgatcgatg ctttggagtt gcggaacggc atggacttcg tgaagacgcg 46500atcccgagat gttggagata tagaagcaac agggaactgg gaccgttgtg caccatccag 46560ttctttcctc cagtactcgc gggaacggtt agagtcgagc gatccaatgt accgaatgaa 46620gttcgaatat ggcggcgggg gttcaattga gtgcatgctg tgataggcat tctgaaggga 46680atcgagaaca atcttcatgc tcagaccgtc aaaaaccgcg tggtgaacga tccagacaaa 46740gtagatatcg ccgttctctt gatgcaagag tgtactccga ctaaggcaat ctccgtagct 46800catagtaaaa ctgcgagact ccttcagata ttcgttcacg tcgacattgt acactggagc 46860atcccatgca gtgtcagtgg caaccacaaa ttgccaggct tgcgagttga ccagaacaat 46920cctcgaccga agactgccac agtgtttgac gactgtgtcc caggagaccc tgaaccgatc 46980aaggtcaaca tgcggcatga ctttataaac ttgtcgatga atgtacgatc caggttgcct 47040gagtcccagt gccatgaatc cctcttgcag tgtggtgcaa gggtatatat cctccagtgc 47100ttcagcagcg agacggcatt gtctctggat gttcaattcg acatcgtccc tatcctcgct 47160agaaatcaag ctgaacggtt tagcgttgtt gatttcctca gcatcgtcga tcaccgcaac 47220agcagccatg cgtacaagct cgggattctc cgtcacatcc gtcggtgaca gacggattcc 47280atgtcgatag gcagccgttg caagctcagt tgtggtaagg gaatcgccac cgagaagaaa 47340gaagttgtgg tgcttgccaa tatcctcaac gcggatttgg atgacgttgc gaagtacatc 47400tgcccaaatg gcccgcaaga tgagctccaa gtccgtctct ggtgtctcgt cggccgagag 47460gttgcaaggc gttcttgacg cggatctctt gaggatctgt gctcgcctat cctttgcaga 47520caagtgcatc ttgttcgcat ccgcaaggtc gctgtcattg tcatcgccgt agttccatgg 47580gtaacggggc aggccagaga gtgcttgtcc cgtaaacaag gtgtccaggc tcaaagccac 47640agagttctgc cagaggcggc caatcgccga gagaaggctc gccaagcagt ccgtctctct 47700ggactgagat gagatgtagt tgcaagacag actggcagca gagcagattt gggatagcgg 47760accagacaga gtggagtgag gtccaatctc aaggaaaaga ccatgtgtag gagtggtgtc 47820gagaatggac atgactgcag aagagaagcg gacgggagaa accaggttat tgacaaagta 47880atgggggcca aagtccttgg cagaggtcag gattgtgttg ctgacactcg acatgaagac 47940ggcattccgc gttgtttgct gcgtcgaagt gattccttcg ctttgtagaa ggcgcagaaa 48000ttcggcagag actgtttcca tgtggtggga atggaaagct gtgtcgacac gcaacttccg 48060cgtggtaact tgtggtctgg acagctggat cgaagccatg atatcctcca cgacgccgcg 48120gtcgccagag attgtcgtgc tcgtcgggct gttttcgcag gccactacgg ctccatcccg 48180caggaactct cttgtctctt cagcgctgag gccggccacc gccatagccc cgtcgcatac 48240gctcatcgca gcggcatagc catagtaata ggccacgacg gttgcctcct tcaggttcag 48300gtagcctgcc gcgtaggctg cggcaatctc accactggag tggccaacga cagcttccgc 48360cttgagtccg agtcgctcgt actgatgaaa gagtgcgacc tgtagagcgg tcgagaccac 48420acaagccgtt tcaacagagt tgatccgaca aagagggtcg ctggctgatc gctggatctc 48480ctcctcgatc gtccaggagg gtggcgtttt cagttgacgc aagatgctat ccatactctt 48540gatgtcattt ctgaacgcat cgatccgaag aagctctttt cccatgcctg cccattgcgc 48600tccttgacca ctgaacacca tcgtgataga cgggggagca actgggcatt tggcggggct 48660cgctgtgctg aggcatacgc catcgtttcc aatgatagaa aatgctcggt gatcaagagc 48720ttctcggcga atagctcgag tgtaggcaat gtcagagacg agatgcgggt tcgatctggc 48780gaagtcgtgg tgaagctgca tctgctggtt gagagacgtc acgttgtttg cagagaacaa 48840caccagctgt ggcccagcag catcgttgct tgccggggat tcatgctgcc gatgcggctc 48900aatgacgaag tgagattcat gcccggattt tccagcgaag ttgatgcgga ttctttgagc 48960tcgaccagag ggaaggtcga ggtgcttctg gcttggtgtt tcatctgctg gcttaggtaa 49020gcgctggacg ttgacaacaa caacagctgg cggcaaacaa aaacactgtt gactcaaatt 49080cttacccttt gatagagtgg tggctgaata caggacgtcc tgatgctcca aagaggccat 49140ggctttgatc agactgacga ggccagatgc actcttcaga tcgccctggt caggctgaga 49200ggagctccca gcgataagga catcggaaca ctgcatgacc actgttagtt tcacagactc 49260ttcttccgtg ttcaaatctt acaatccatc tggatgggga aaggagactc acttcaacga 49320cttcagcatc actcgaatcc gaactggcag cgcggatgac ggcctgaata ggatttccat 49380cgcggactgc atcgctcagc ggcttgatga acactgcaac aaccgcttct ccctcgagat 49440catccgcagt cgccccggtg gcgatgaggt tgatgcccgc aacgagagcg gcttgggcgc 49500tgccgtttct gacagccttg caggcttcat caagtgtcac cagcgaggca gagtcttcag 49560catcctcaat agttaggctg aagagtatgg atggttagcc tccgcgtgtt gcttcaacta 49620gagcccattt aagactactc acctcggtcc gcggaattca aactgcttgg acacaagctc 49680aaccgtcgag gcatttccct tctccctggc ctctacgtcc tttcggccag gcatcgccac 49740gtagcaagcc acggaagcct tttcgccgcg atagttgacc tcacacgcgt cctcgagaca 49800ctcgtggacg acctcaaaca gcttctgaga atacggatca ctgtcgattc gcccatcagc 49860tgccattgtg aagaaccgcg cgtcaaacgc gctcaagctt ctgttcagtt ggccgctctt 49920ctgagcattt gacgcagacc cttcggcaac cagaccaccg accaatgctt gccagaactc 49980ttcgatgctg tgaataccac cagcaaggcg gagtccaacg ccgcaaatcg cgacgtcaat 50040ctgctttgca gtattgccgc attgatgctt ggagctttcg atagagccat tggtactacc 50100tctagctcct ggctcttcag ccggagactt gattccagtc atattaaaag attgtagaaa 50160gtacttttgt acaagaccga ataataaaat aactaaactt ttcaacagga attgagcatg 50220taccgacgaa gttgccttgg ccgtgcagct gtgtgggagg caggccgtta taagagaatg 50280tctctcctca aggatcggca atgcacactc cggctcctac taatacttat gacagtatta 50340cctacacaca gtggcacaat atgtagccaa tgattgcagc atggctgtta agtcaatgtc 50400tcacagagtt ttcaacactt acgtgtagta tgcagcttta cccgagttca cggggagggc 50460cccctgtcga cttaccgcca ttgtcccacc tatcaaaaca ccattctctc aacttcggcc 50520agggatccag gctattatca gctacgtatc attaaaggta atggtatggc atatacagag 50580tcggggcaga cgttgcctca tcgttgagga tggacatcat catcagccgc cgacgccacc 50640agctcaaggc cacatgtagt tctggctgtg acttgatgtt tcagtgcgga tgcataggta 50700tacagagtat tgatccgtcg atcttacata ctacgagcaa atagtagctg ctggcgtttg 50760ttgtttggac gcctgtagaa cagccat 50787216534PRTTrichoderma reesei 2Met Ala Val Leu Gln Ala Ser Lys Gln Gln Thr Pro Ala Ala Thr Ile 1 5 10 15 Cys Ser Tyr Leu Asp Pro Trp Pro Lys Leu Arg Glu Trp Cys Phe Asp 20 25 30 Arg Trp Asp Asn Gly Ala Met Leu Gln Ser Leu Ala Thr Tyr Cys Ala 35 40 45 Thr Ser Pro Ala Glu Glu Pro Gly Ala Arg Gly Ser Thr Asn Gly Ser 50 55 60 Ile Glu Ser Ser Lys His Gln Cys Gly Asn Thr Ala Lys Gln Ile Asp 65 70 75 80 Val Ala Ile Cys Gly Val Gly Leu Arg Leu Ala Gly Gly Ile His Ser 85 90 95 Ile Glu Glu Phe Trp Gln Ala Leu Val Gly Gly Leu Val Ala Glu Gly 100 105 110 Ser Ala Ser Asn Ala Gln Lys Ser Gly Gln Leu Asn Arg Ser Leu Ser 115 120 125 Ala Phe Asp Ala Arg Phe Phe Thr Met Ala Ala Asp Gly Arg Ile Asp 130 135 140 Ser Asp Pro Tyr Ser Gln Lys Leu Phe Glu Val Val His Glu Cys Leu 145 150 155 160 Glu Asp Ala Cys Glu Val Asn Tyr Arg Gly Glu Lys Ala Ser Val Ala 165 170 175 Cys Tyr Val Ala Met Pro Gly Arg Lys Asp Val Glu Ala Arg Glu Lys 180 185 190 Gly Asn Ala Ser Thr Val Glu Leu Val Ser Lys Gln Phe Glu Phe Arg 195 200 205 Gly Pro Ser Leu Thr Ile Glu Asp Ala Glu Asp Ser Ala Ser Leu Val 210 215 220 Thr Leu Asp Glu Ala Cys Lys Ala Val Arg Asn Gly Ser Ala Gln Ala 225 230 235 240 Ala Leu Val Ala Gly Ile Asn Leu Ile Ala Thr Gly Ala Thr Ala Asp 245 250 255 Asp Leu Glu Gly Glu Ala Val Val Ala Val Phe Ile Lys Pro Leu Ser 260 265 270 Asp Ala Val Arg Asp Gly Asn Pro Ile Gln Ala Val Ile Arg Ala Ala 275 280 285 Ser Ser Asp Ser Ser Asp Ala Glu Val Val Glu Cys Ser Asp Val Leu 290 295 300 Ile Ala Gly Ser Ser Ser Gln Pro Asp Gln Gly Asp Leu Lys Ser Ala 305 310 315 320 Ser Gly Leu Val Ser Leu Ile Lys Ala Met Ala Ser Leu Glu His Gln 325 330 335 Asp Val Leu Tyr Ser Ala Thr Thr Leu Ser Lys Ala Val Val Val Val 340 345 350 Asn Val Gln Arg Leu Pro Lys Pro Ala Asp Glu Thr Pro Ser Gln Lys 355 360 365 His Leu Asp Leu Pro Ser Gly Arg Ala Gln Arg Ile Arg Ile Asn Phe 370 375 380 Ala Gly Lys Ser Gly His Glu Ser His Phe Val Ile Glu Pro His Arg 385 390 395 400 Gln His Glu Ser Pro Ala Ser Asn Asp Ala Ala Gly Pro Gln Leu Val 405 410 415 Leu Phe Ser Ala Asn Asn Val Thr Ser Leu Asn Gln Gln Met Gln Leu 420 425 430 His His Asp Phe Ala Arg Ser Asn Pro His Leu Val Ser Asp Ile Ala 435 440 445 Tyr Thr Arg Ala Ile Arg Arg Glu Ala Leu Asp His Arg Ala Phe Ser 450 455 460 Ile Ile Gly Asn Asp Gly Val Cys Leu Ser Thr Ala Ser Pro Ala Lys 465 470 475 480 Cys Pro Val Ala Pro Pro Ser Ile Thr Met Val Phe Ser Gly Gln Gly 485 490 495 Ala Gln Trp Ala Gly Met Gly Lys Glu Leu Leu Arg Ile Asp Ala Phe 500 505 510 Arg Asn Asp Ile Lys Ser Met Asp Ser Ile Leu Arg Gln Leu Lys Thr 515 520 525 Pro Pro Ser Trp Thr Ile Glu Glu Glu Ile Gln Arg Ser Ala Ser Asp 530 535 540 Pro Leu Cys Arg Ile Asn Ser Val Glu Thr Ala Cys Val Val Ser Thr 545 550 555 560 Ala Leu Gln Val Ala Leu Phe His Gln Tyr Glu Arg Leu Gly Leu Lys 565 570 575 Ala Glu Ala Val Val Gly His Ser Ser Gly Glu Ile Ala Ala Ala Tyr 580 585 590 Ala Ala Gly Tyr Leu Asn Leu Lys Glu Ala Thr Val Val Ala Tyr Tyr 595 600 605 Tyr Gly Tyr Ala Ala Ala Met Ser Val Cys Asp Gly Ala Met Ala Val 610 615 620 Ala Gly Leu Ser Ala Glu Glu Thr Arg Glu Phe Leu Arg Asp Gly Ala 625 630 635 640 Val Val Ala Cys Glu Asn Ser Pro Thr Ser Thr Thr Ile Ser Gly Asp 645 650 655 Arg Gly Val Val Glu Asp Ile Met Ala Ser Ile Gln Leu Ser Arg Pro 660 665 670 Gln Val Thr Thr Arg Lys Leu Arg Val Asp Thr Ala Phe His Ser His 675 680 685 His Met Glu Thr Val Ser Ala Glu Phe Leu Arg Leu Leu Gln Ser Glu 690 695 700 Gly Ile Thr Ser Thr Gln Gln Thr Thr Arg Asn Ala Val Phe Met Ser 705 710 715 720 Ser Val Ser Asn Thr Ile Leu Thr Ser Ala Lys Asp Phe Gly Pro His 725 730 735 Tyr Phe Val Asn Asn Leu Val Ser Pro Val Arg Phe Ser Ser Ala Val 740 745 750 Met Ser Ile Leu Asp Thr Thr Pro Thr His Gly Leu Phe Leu Glu Ile 755 760 765 Gly Pro His Ser Thr Leu Ser Gly Pro Leu Ser Gln Ile Cys Ser Ala 770 775 780 Ala Ser Leu Ser Cys Asn Tyr Ile Ser Ser Gln Ser Arg Glu Thr Asp 785 790 795 800 Cys Leu Ala Ser Leu Leu Ser Ala Ile Gly Arg Leu Trp Gln Asn Ser 805 810 815 Val Ala Leu Ser Leu Asp Thr Leu Phe Thr Gly Gln Ala Leu Ser Gly 820 825 830 Leu Pro Arg Tyr Pro Trp Asn Tyr Gly Asp Asp Asn Asp Ser Asp Leu 835 840 845 Ala Asp Ala Asn Lys Met His Leu Ser Ala Lys Asp Arg Arg Ala Gln 850 855 860 Ile Leu Lys Arg Ser Ala Ser Arg Thr Pro Cys Asn Leu Ser Ala Asp 865 870 875 880 Glu Thr Pro Glu Thr Asp Leu Glu Leu Ile Leu Arg Ala Ile Trp Ala 885 890 895 Asp Val Leu Arg Asn Val Ile Gln Ile Arg Val Glu Asp Ile Gly Lys 900 905 910 His His Asn Phe Phe Leu Leu Gly Gly Asp Ser Leu Thr Thr Thr Glu 915 920 925 Leu Ala Thr Ala Ala Tyr Arg His Gly Ile Arg Leu Ser Pro Thr Asp 930 935 940 Val Thr Glu Asn Pro Glu Leu Val Arg Met Ala Ala Val Ala Val Ile 945 950 955 960 Asp Asp Ala Glu Glu Ile Asn Asn Ala Lys Pro Phe Ser Leu Ile Ser 965 970 975 Ser Glu Asp Arg Asp Asp Val Glu Leu Asn Ile Gln Arg Gln Cys Arg 980 985 990 Leu Ala Ala Glu Ala Leu Glu Asp Ile Tyr Pro Cys Thr Thr Leu Gln 995 1000 1005 Glu Gly Phe Met Ala Leu Gly Leu Arg Gln Pro Gly Ser Tyr Ile 1010 1015 1020 His Arg Gln Val Tyr Lys Val Met Pro His Val Asp Leu Asp Arg 1025 1030 1035 Phe Arg Val Ser Trp Asp Thr Val Val Lys His Cys Gly Ser Leu 1040 1045 1050 Arg Ser Arg Ile Val Leu Val Asn Ser Gln Ala Trp Gln Phe Val 1055 1060 1065 Val Ala Thr Asp Thr Ala Trp Asp Ala Pro Val Tyr Asn Val Asp 1070 1075 1080 Val Asn Glu Tyr Leu Lys Glu Ser Arg Ser Phe Thr Met Ser Tyr 1085 1090 1095 Gly Asp Cys Leu Ser Arg Ser Thr Leu Leu His Gln Glu Asn Gly 1100 1105 1110 Asp Ile Tyr Phe Val Trp Ile Val His His Ala Val Phe Asp Gly 1115 1120 1125 Leu Ser Met Lys Ile Val Leu Asp Ser Leu Gln Asn Ala Tyr His 1130 1135 1140 Ser Met His Ser Ile Glu Pro Pro Pro Pro Tyr Ser Asn Phe Ile 1145 1150 1155 Arg Tyr Ile Gly Ser Leu Asp Ser Asn Arg Ser Arg Glu Tyr Trp 1160 1165 1170 Arg Lys Glu Leu Asp Gly Ala Gln Arg Ser Gln Phe Pro Val Ala 1175 1180 1185 Ser Ile Ser Pro Thr Ser Arg Asp Arg Val Phe Thr Lys Ser Met 1190 1195 1200 Pro Phe Arg Asn Ser Lys Ala Ser Ile Thr Thr Ala Thr Ile Ile 1205 1210 1215 Arg Ala Ala Trp Ala Leu Val Leu Ala Gln Tyr Cys Gly Ser Asp 1220 1225 1230 Asp Val Cys Phe Gly Met Thr Leu Ser Gly Arg Gln Ala Pro Val 1235 1240 1245 Pro Gly Leu Asn Glu Ile Pro Gly Pro Met Ile Ala Thr Val Pro 1250 1255 1260 Val Arg Ile His Val Lys Arg Asp Met Leu Ile Ser Glu Phe Leu 1265 1270 1275 Gln His Ile Gln Ser His Ala Ser His Met Val Ala His Glu Gln 1280 1285 1290 Tyr Gly Leu Gln Asn Ile Ser Lys Leu Gly Pro Asn Ala Lys Glu 1295 1300 1305 His Leu Ser Ser Val Ala Cys Ser Ser Leu Asn Ser Ile Leu Gln 1310 1315 1320 Gln Gly Pro Val Glu Lys Thr Ile Ser Glu Glu Ala Met Arg Asn 1325 1330 1335 Tyr Phe Asn Tyr Pro Leu Val Leu Gln Thr Arg Leu Gly Asn Asp 1340 1345 1350 Ala Ile Asp Leu Glu Phe Thr Tyr Tyr Asp Asp Ile Leu Asn Glu 1355 1360 1365 Asp Gln Leu Gly Ala Leu Phe His His Phe Glu His Val Ile Gln 1370 1375 1380 Gln Leu Leu Gln Pro Asp Asp Ile Pro Leu Lys Ser Val Thr Ser 1385 1390 1395 Ser Ser Gln Trp Asp Leu Gln Arg Val Arg Glu Trp Asn Ser Glu 1400 1405 1410 Glu Pro Glu Ile Val

Ser Ser Cys Leu His Glu Ile Ile Glu Arg 1415 1420 1425 His Ala Leu Lys Arg Pro Asp Ala Thr Ala Val Cys Ala Trp Asp 1430 1435 1440 Met Thr Leu Thr Tyr Glu Gln Leu Asn Leu Ala Ala Asp Arg Leu 1445 1450 1455 Ala His Tyr Leu Ile Ser Asn Ser Ala Ala Gln Val Gln Leu Gly 1460 1465 1470 Asp Leu Val His Val Cys Phe Glu Lys Ser Ala Trp Phe Met Ile 1475 1480 1485 Ser Ile Leu Ala Ile Asn Lys Ala Gly Ala Ala Trp Ala Pro Leu 1490 1495 1500 Asp Pro Ser His Pro Val Gln Arg Gln Lys Gln Ile Val Ala Arg 1505 1510 1515 Thr Asn Ala Lys Leu Ala Leu Thr Ser Ser Ser Asn Ala Ala Leu 1520 1525 1530 Cys Ser Glu Leu Val Glu His Ile Ile Glu Val Ser Ala Asp Leu 1535 1540 1545 Asp Asp Met Leu Ile Ala Glu Arg Arg Gly Ser Lys Gly Leu Pro 1550 1555 1560 Arg Val Ser Pro Ser Ala Ala Ala Tyr Val Leu Phe Thr Ser Gly 1565 1570 1575 Ser Thr Gly Thr Pro Lys Gly Phe Val Met Gln His Gln Ala Val 1580 1585 1590 Cys Thr Ser Gln Thr Ser Ala Val Arg Arg Leu Gly Met Thr Ser 1595 1600 1605 Asp Ile Arg Met Leu Gln Phe Ala Ser Tyr Val Phe Asp Met Ser 1610 1615 1620 Ile Gly Glu Ile Val Gly Pro Trp Val Ala Gly Ala Thr Ile Cys 1625 1630 1635 Val Pro Ser Glu Glu Val Arg Met Asn Gly Leu Val Glu Tyr Ile 1640 1645 1650 Arg Asp Met Lys Ile Asn Trp Val Tyr Leu Thr Pro Ser Phe Ser 1655 1660 1665 Arg Thr Leu Asn Pro Asp Thr Leu Pro Gly Leu Asp Leu Met Leu 1670 1675 1680 Leu Ala Gly Glu Ala Val Gly Arg Asp Val Leu Glu Thr Trp Phe 1685 1690 1695 Gly Lys Val Arg Leu Val Asn Gly Trp Gly Pro Ala Glu Thr Cys 1700 1705 1710 Val Phe Ser Thr Leu His Glu Trp Thr Ser Leu Asp Glu Ser Ser 1715 1720 1725 Leu Thr Ile Gly Arg Pro Val Gly Gly Phe Cys Trp Leu Val Asp 1730 1735 1740 Pro Glu Asn Pro His Val Leu Ala Pro Ile Gly Thr Val Gly Glu 1745 1750 1755 Val Val Ile Gln Gly Pro Thr Leu Leu Lys Glu Tyr Leu Ala Asp 1760 1765 1770 Pro Glu Lys Thr Glu Ala Ala Thr Val Arg Ser Leu Pro Asp Trp 1775 1780 1785 Ala Pro Tyr Arg Asn Leu Ala Asp Trp Asn Arg Phe Tyr Lys Ser 1790 1795 1800 Gly Asp Leu Cys Lys Tyr Asn Pro Asp Gly Thr Leu Val Phe Val 1805 1810 1815 Thr Arg Lys Asp Thr Gln Ile Lys Ile Arg Gly Leu Arg Val Glu 1820 1825 1830 Leu Gly Glu Val Glu His Gln Ile Lys Ala Ser Leu Glu Gly Val 1835 1840 1845 Cys Gln Val Gly Val Asp Met Val Thr Thr Asp Gly Gly Ser Ser 1850 1855 1860 Leu Ile Ala Phe Phe Cys Phe Ser Asn Glu Thr Arg Met Val Thr 1865 1870 1875 Thr Val Asn Ala Ala Ala Asp Glu Gly Ala Ala Met Phe Leu Pro 1880 1885 1890 Val Thr Ser Gln Leu Lys Ser Gln Ile Val Ser Met Ile Gly His 1895 1900 1905 Leu Ser Val Asn Leu Pro Arg Tyr Met Ile Pro Ser Phe Phe Val 1910 1915 1920 Pro Cys Lys Tyr Met Pro Ser Ile Thr Ser Thr Lys Leu Asp Arg 1925 1930 1935 Arg Thr Leu Lys Asn Gln Ile Glu Leu Leu Gly Pro Asp Gly Leu 1940 1945 1950 Ser Thr Tyr Ser Leu Val Asp Thr Val Lys Asn Pro Pro Glu Thr 1955 1960 1965 Ala Met Glu Ser Lys Leu Gln Ala Leu Trp Ala Lys Arg Leu Lys 1970 1975 1980 Met Pro Leu Glu Ala Ile Gly Arg Asp Asp Ser Phe Leu Gln Ile 1985 1990 1995 Gly Gly Asp Ser Ile Ala Val Ile His Phe Val Ala Asp Ala Arg 2000 2005 2010 Gln Ala Gly Ile Ser Leu Ser Val Gln Asp Val Phe Asp Asp Pro 2015 2020 2025 Arg Leu Trp Arg Val Ala Ala Ile Ala Thr Ser Ala Asp Gly Asp 2030 2035 2040 Ser His Ser Ala Pro Ile Val Ala Pro Phe Gly Leu Leu Glu Pro 2045 2050 2055 Gly Gln Ile Asp Ser Val Met Gln Asp Glu Leu Leu Lys Leu Cys 2060 2065 2070 Gly Leu Pro Ser Trp Asp Ala Val Asp Asp Ala Phe Pro Cys Thr 2075 2080 2085 Lys Leu Gln Glu Gly Leu Met Ala Leu Thr Thr Lys Gln Pro Gly 2090 2095 2100 Ala Tyr Val Ser Lys Met Val Phe Lys Val Pro Arg His Val Asp 2105 2110 2115 Ile Gly His Phe Lys Ala Ser Trp Glu Arg Thr Val Ala Val Cys 2120 2125 2130 Ser Asn Leu Arg Thr Arg Ile Val Gln Leu Ser Ser Leu Asp Ser 2135 2140 2145 Ile Gln Val Ile Val Lys Glu Pro Ala Gln Trp Glu Val Thr Asp 2150 2155 2160 Asn Gln Gly Ile Asp Val Phe Leu Arg Gln Ala Asn Ser Ile Arg 2165 2170 2175 Met Ser Tyr Gly Ser Arg Leu Ala Arg Phe Ala Leu Val His Gly 2180 2185 2190 Asp Asn Ser Asp Cys Tyr Phe Val Ala Ile Met His His Leu Ile 2195 2200 2205 Phe Asp Gly Trp Thr Leu Ala Leu Met Val Gln Ala Leu His Ala 2210 2215 2220 Ile Tyr Arg Asp Ser Glu Val Pro Arg Leu Ala Pro Tyr Ser Ala 2225 2230 2235 Phe Val Arg Tyr Thr Leu Gln Leu Asp Phe Glu Thr Ser Lys Thr 2240 2245 2250 Tyr Trp Lys Ala Gln Met Asp Gly Ala Arg Arg Ala Val Phe Pro 2255 2260 2265 Leu Pro Arg Asp Asp Ile Ala Val Ala Lys Ser Lys Arg Asn Val 2270 2275 2280 Gln Ile Ser Ala Lys Glu Val Lys Ile Pro Gln Thr Thr Asn Gly 2285 2290 2295 Thr Ile Thr Arg Ala Thr Tyr Leu Arg Ala Ala Trp Ala Met Leu 2300 2305 2310 Leu Ala Arg Tyr Cys Ser Thr Asp Asp Ile Cys Phe Gly Ala Ser 2315 2320 2325 Val Ser Gly Arg Asn Ala Pro Leu Val Gly Val Glu Ser Val Leu 2330 2335 2340 Gly Leu Val Val Ser Thr Leu Pro Val Arg Val Arg Leu Asn Pro 2345 2350 2355 Asp Gln Ser Leu Ser Asp Phe Leu Arg Asp Val Gln Lys Gln Ser 2360 2365 2370 Asn Asp Met Val Ala His Glu Gln Phe Gly Leu Gln Asn Ile Ala 2375 2380 2385 Arg Ile Gly Ser Asp Ala Lys Asp Ala Cys Asn Phe Thr Ser Leu 2390 2395 2400 Met Val Val Gln Pro Lys Asp Leu Thr Thr Gly Ser Asn Gly Asn 2405 2410 2415 Glu Ala Ile Leu Ile Ser Thr Arg Glu Glu Gln Arg Leu Ala Trp 2420 2425 2430 Gln Ser Met Glu Asp Tyr Tyr Asn Tyr Pro Leu Ile Leu Gln Cys 2435 2440 2445 His Leu Gly Asp Asp Ser Val Glu Leu Glu Phe Val Tyr Asp Ala 2450 2455 2460 Asp Val Ile Ser Glu Phe Gln Val Leu Ala Leu Ser Asn Gln Leu 2465 2470 2475 Asp His Ile Ile Gln Gln Leu Ala Ser Leu Asp Lys Arg Thr Leu 2480 2485 2490 Leu Arg Asp Val Ser Arg Ala Ser Pro Trp Asp Leu Gln Gln Ser 2495 2500 2505 Leu Asp Trp Asn Ser His Glu Ile Val Val Gln Lys His Cys Met 2510 2515 2520 His Asp Leu Ile Ser Gln Arg Ala Lys Leu Cys Pro Asp Asp Glu 2525 2530 2535 Ala Leu Phe Ser Thr Glu Gly Ser Leu Thr Tyr Ala Ala Leu Asp 2540 2545 2550 Arg Leu Ser Asp His Val Ala Ser Gln Leu Leu Gln Tyr Asn Val 2555 2560 2565 Gln Pro Glu Thr Ile Val Pro Ile Cys Met Gln Lys Ser Ile Trp 2570 2575 2580 Ala Val Val Gly Met Ile Gly Ile Leu Lys Ala Gly Gly Ala Tyr 2585 2590 2595 Met Pro Leu Asp Pro Thr His Pro Glu Ser Arg Arg Gln Ala Leu 2600 2605 2610 Val Gln Glu Val Asn Ala Lys Val Ile Val Ser Ser Pro Ser Met 2615 2620 2625 Ala Ala Ser Cys Glu Ser Met Ala Pro His Thr Ile Gln Val Ser 2630 2635 2640 Ser Ser Leu Leu Ala Leu Ala Pro Glu Thr Pro Val Asp Tyr His 2645 2650 2655 Ser Leu Ser Asn Tyr Lys Lys Pro Glu Pro His Asn Ala Ala Tyr 2660 2665 2670 Val Leu Tyr Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Leu Leu 2675 2680 2685 Val Thr His Ser Ala Ala Cys Thr Ser Leu Leu Lys His Ser Asp 2690 2695 2700 Met Phe Asn Phe Lys Lys Ser Ser Arg Val Phe Gln Phe Ala Ser 2705 2710 2715 Tyr Val Phe Asp Val Ser Val Leu Asp Ile Phe Leu Thr Leu Ile 2720 2725 2730 Leu Gly Ala Thr Leu Cys Ile Pro Thr Glu Thr Glu Arg Met Asp 2735 2740 2745 Arg Ala Trp Arg Phe Met Thr Lys Ala Arg Val Thr Leu Ala Cys 2750 2755 2760 Leu Thr Pro Ser Phe Ile Arg Thr Leu Asp Pro Asp Thr Leu Pro 2765 2770 2775 Thr Leu Gln Thr Val Ala Ile Gly Gly Glu Ala Thr Thr Lys Asp 2780 2785 2790 Ile Leu Lys Thr Trp His Gly Arg Val Glu Leu Ile Asn Ala Tyr 2795 2800 2805 Gly Pro Ala Glu Ala Cys Val Asn Cys Ala Gly His Pro Phe Lys 2810 2815 2820 Ser Gln Asp Asp Ser Pro Met Thr Ile Gly Arg Pro Phe Thr His 2825 2830 2835 Arg Leu Phe Ile Val Glu Pro Asp Asn His Asp Arg Leu Thr Pro 2840 2845 2850 Val Gly Cys Val Gly Glu Leu Leu Val Glu Gly His Ala Ile Ala 2855 2860 2865 Arg Gly Tyr Ile Asn Asn Glu Glu Lys Thr Lys Ala Ser Phe Val 2870 2875 2880 Asp Ser Leu Asp Trp Leu Pro Thr Gln Thr Glu Ser Asp Arg Pro 2885 2890 2895 Ile Ala Tyr Lys Thr Gly Asp Leu Ala Arg Phe Asn Pro Asp Gly 2900 2905 2910 Thr Val Glu Phe Phe Gly Arg Gln Asp Thr Gln Val Lys Leu Arg 2915 2920 2925 Gly Gln Arg Leu Glu Leu Gly Glu Ile Glu Tyr His Ile Lys Ala 2930 2935 2940 Asn Leu Ala Asp Val Gln His Val Val Val Asp Leu Ile Glu Arg 2945 2950 2955 Glu Ala Gly Lys Met Ile Ile Ala Phe Val Thr Phe His Asn Tyr 2960 2965 2970 Leu Cys Asp Asn Thr Pro Thr Asp Ala Glu Asp Pro Tyr Ala Glu 2975 2980 2985 Phe Ile Ser Asn Glu Ile Tyr Val Ser Ser Phe Gln Ala Leu Ile 2990 2995 3000 Gln Glu Leu Arg Arg Val Leu Pro Gly Tyr Met Ile Pro Ser Ile 3005 3010 3015 Ile Phe Pro Met Arg Asp Val Pro His Thr Ser Ser Asn Lys Ile 3020 3025 3030 Asp Arg Arg Thr Leu Arg Glu Leu Ala Thr Ser Met Pro Arg Glu 3035 3040 3045 Arg Ile Ser Ser Phe Ser Ile Ala Arg Gln Asp Lys Val Pro Pro 3050 3055 3060 Thr Thr Glu Met Glu Leu Lys Ile Gln Ser Leu Trp Ala Gln Val 3065 3070 3075 Leu Lys Ile Asp Thr Glu Asp Ile Ser Lys Phe Asp Asn Phe Phe 3080 3085 3090 Glu Val Gly Gly Asp Ser Ile Ser Ala Ile His Leu Ser Asn Leu 3095 3100 3105 Ala Ala Arg Glu Asp Ile Leu Leu Pro Ile Ala Asn Ile Phe Lys 3110 3115 3120 Glu Pro Gln Leu Ala Ser Met Ala Ala Cys Met Thr Ile Arg Gln 3125 3130 3135 Ser Gln His Thr Asp Ala Gln Pro Phe Ser Met Ile Glu Ala Thr 3140 3145 3150 Glu Val Glu Ser Leu His Ala Ser Ile Arg Arg Gln Cys Gly Leu 3155 3160 3165 Ala Asn Glu Gln Glu Leu Glu Asp Ile Ile Pro Cys Thr Pro Leu 3170 3175 3180 Gln Glu Gly Leu Met Ala Leu Thr Ala Thr Arg Pro Gly Ser Tyr 3185 3190 3195 Ile Ala Arg Arg Ala Tyr Lys Leu Ala Asp Gly Val Asp Leu Asp 3200 3205 3210 Arg Phe Lys Asp Ser Trp Glu Arg Thr Ile Lys Ala Cys Ser Ser 3215 3220 3225 Leu Arg Thr Arg Ile Val Gln His Gly Asp Val Ser Leu Gln Ala 3230 3235 3240 Val Val Ser His Asp Gly Leu Trp Glu Glu Thr Asp Gly Gln Thr 3245 3250 3255 Leu Gln Ser Tyr Met Lys Gly Leu Thr Ser Leu Asn Met Gly Tyr 3260 3265 3270 Gly Ser Arg Leu Ser Arg His Ala Ile Leu Ser Cys Ser Asn Gly 3275 3280 3285 Ser Thr Tyr Phe Ile Trp Val Ala His His Ala Ile Phe Asp Gly 3290 3295 3300 Trp Thr Met Gln Ile Lys Leu Asp Val Leu Gln Arg Leu Tyr Ala 3305 3310 3315 Gln Glu Pro Leu Pro Pro Ile Arg Pro Phe Ala Asn Phe Val Gln 3320 3325 3330 Tyr Leu Ser Gln Leu Asp Pro Lys Ala Ala Lys Asp Tyr Trp Leu 3335 3340 3345 Met Glu Leu Glu Gly Ala Gln Arg Ala Ser Phe Pro Pro Ala Lys 3350 3355 3360 Val Thr Thr Gly Asn Lys Thr Ser Thr Ala Gln Lys Thr Gln Ile 3365 3370 3375 Met Lys Arg Lys Leu Ala Asn Ile Gln Thr Gln Ala Ser Glu Met 3380 3385 3390 Val Ala Tyr Glu Gln Phe Gly Leu Gln Asn Ile Ser Lys Leu Ser 3395 3400 3405 Asp Ser Ala Lys His Ala Thr Asp Phe Thr Ser Leu Phe Val Val 3410 3415 3420 Gln Ser Arg Gln His Glu Ile Gly Lys Ser Gln Gly Glu Leu Phe 3425 3430 3435 Thr Thr Asp Ser Asn Asp Glu Thr Ser Ile Glu Asn Trp Ile Glu 3440 3445 3450 Asp Phe Phe Asn Tyr Pro Leu Thr Val Glu Cys Asp Leu Met Gln 3455 3460 3465 Asp Gln Ala Val Met Thr Leu Tyr Tyr Asp Ala Asp Val Leu Ser 3470 3475 3480 Asp Leu Gln Leu Gln Gly Leu Cys Asn Gln Phe Glu His Val Leu 3485 3490 3495 Gln Glu Leu Asn Leu Arg Tyr Lys Glu Pro Leu Gly Asn Leu Ser 3500 3505 3510 Met Thr Ser Gln Trp Gly Ile Asp Phe Ala His Ala Ser Asn Pro 3515 3520 3525 Asp Lys Pro Leu Val Val Glu Ser Cys Ile His Thr Leu Ile Glu 3530 3535 3540 Gln Arg Thr Lys Leu Asn Pro Glu Ser Pro Ala Val Ser Ser Trp 3545 3550 3555 Asp Ala Asp Phe Thr Tyr Ser Glu Leu Asp Glu Asn Ala Asp Lys 3560 3565 3570 Leu Ala Thr Tyr Leu Leu Ser Thr Leu Lys Val Lys Ala Gly Asp 3575 3580 3585 Leu Val Ile Val Cys Phe Asp Lys Ser Ala Trp Phe Ile Val Ala 3590 3595 3600 Ile Leu Ala Ile Asn Lys Ile Gly Ala Ala Trp Val Pro Leu Asp 3605

3610 3615 Pro Ala His Pro Thr Asp Arg His Gln Asn Ile Val Gly Gln Thr 3620 3625 3630 Lys Ala Thr Leu Ala Leu Cys Ser Leu Ala Asn Val Pro Lys Leu 3635 3640 3645 Met Gly Val Thr Thr Ser Val Leu Glu Val Asn Gly Glu Phe Met 3650 3655 3660 Ser Arg Leu Pro Leu Asn Asp Ala Val Lys Pro Ser Val Lys Val 3665 3670 3675 Ser Pro Asp Asp Val Ala Tyr Ile Ile Phe Thr Ser Gly Ser Thr 3680 3685 3690 Gly Val Pro Lys Gly Val Val Ile Gln His Arg Ala Ile Cys Ser 3695 3700 3705 Ser Gln Val Ala Leu Ser Gln Arg Leu Glu Met His Asp Gly Val 3710 3715 3720 Arg Met Leu Gln Phe Ser Ser Phe Val Phe Asp Ala Ser Leu Phe 3725 3730 3735 Glu Ile Tyr Ser Pro Leu Ile Ser Gly Ala Cys Val Cys Ile Pro 3740 3745 3750 Ser Trp Asp Thr Gln Met Asn Ser Leu Pro Ala Phe Ile Arg Glu 3755 3760 3765 Arg Asn Val Thr Trp Ala Phe Leu Thr Pro Ser Val Ala Ser Ile 3770 3775 3780 Ile Arg Pro Glu Asp Val Pro Cys Leu Glu Leu Val Thr Leu Gly 3785 3790 3795 Gly Glu Ala Pro Ser Lys Glu Val Val Asn Ser Trp Leu Gly Lys 3800 3805 3810 Val Arg Leu Phe Asn Val Trp Gly Pro Thr Glu Thr Thr Val Ile 3815 3820 3825 Ala Met Val His Glu Tyr Thr Ala Thr Glu Leu Ser His Leu Thr 3830 3835 3840 Ile Gly Arg Pro Ile Cys Gly Asn Cys Trp Ile Val Asn Pro Asn 3845 3850 3855 Asp Pro His Gln Leu Ser Pro Val Gly Thr Val Gly Glu Ile Val 3860 3865 3870 Val Gln Gly Pro Asn Leu Leu Leu Glu Tyr Leu Glu Asn Pro Glu 3875 3880 3885 Lys Thr Ala Ala Ala Thr Val Thr Ser Leu Pro His Trp Val Pro 3890 3895 3900 Asn Arg Glu Val Phe Gly Arg Phe Tyr Lys Ser Gly Asp Leu Ala 3905 3910 3915 Thr Tyr Asn Ala Asp Gly Thr Ile Arg Tyr Asn Ser Arg Lys Asp 3920 3925 3930 Gly Gln Ile Lys Ile Arg Gly Leu Arg Val Glu Leu Gly Glu Ile 3935 3940 3945 Glu His His Ile Arg Asn Asn Leu Glu Gly Pro Cys Gln Val Ala 3950 3955 3960 Val Glu Ala Leu Lys Phe Glu Ala Gly Thr His Leu Val Ala Phe 3965 3970 3975 Ile Cys Gln Asn Thr Asp Thr Ile Pro Ala Ser Met Thr Gly Asp 3980 3985 3990 Val Ala Thr Glu Asp Ile Phe Leu Pro Ser Thr Ala Asp Leu Arg 3995 4000 4005 Ser Asp Leu Glu Ala Met His Gly Phe Leu Ala Ser Ala Leu Pro 4010 4015 4020 Ser Tyr Met Val Pro Thr Phe Phe Ile Pro Cys Lys Lys Met Pro 4025 4030 4035 Leu Val Thr Ser Ser Lys Met Asp Arg Lys Leu Leu Arg Arg Leu 4040 4045 4050 Ala Ala Ala Leu Asp Arg Gln Ala Phe Glu Gln Tyr Ser Leu Tyr 4055 4060 4065 Ala Val Thr Glu Ala Lys Ser Ser Pro Glu Thr Pro Met Glu His 4070 4075 4080 Ser Leu Gln Gln Leu Trp Ala Asp Val Leu Lys Val Pro Ala Glu 4085 4090 4095 Ser Ile Gly Arg His Asp Ser Phe Leu Ala Ile Gly Gly Asp Ser 4100 4105 4110 Ile Ala Ile Ile Arg Leu Ile Ala Leu Ala Arg Glu His Gly Ile 4115 4120 4125 Glu Leu Arg Ala Asn Asp Ile Phe Lys Asp Ser Arg Leu Ser Ser 4130 4135 4140 Val Ala Leu Asn Ala Ala Pro Ile Glu Val Asp Ser Ser Ser Ala 4145 4150 4155 Asn Ser Ala Ile Ser Ala Lys Pro Phe Ala Leu Leu Glu Pro His 4160 4165 4170 Ile Arg Asp Ala Leu Leu Ala Pro Arg Leu Arg Lys Glu Leu Lys 4175 4180 4185 Leu Thr Arg Ser Met Lys Ile Glu Asp Gly Tyr Pro Cys Thr Asn 4190 4195 4200 Leu Gln Glu Gly Leu Met Val Leu Ala Val Lys Gln Pro Gly Ser 4205 4210 4215 Tyr Ile Thr Ser Phe His Tyr Arg Leu Ala Glu Asn Val Asp Pro 4220 4225 4230 Ser Ala Phe Lys Ala Ala Trp Asp Lys Thr Val Arg Leu Cys Gly 4235 4240 4245 Ile Leu Arg Thr Arg Val Val His Leu Lys Gly Ser Ser Val Gln 4250 4255 4260 Val Val Ile Ser Asp Tyr Thr Trp Asp Asp Thr Lys Gly Met Thr 4265 4270 4275 Leu Lys Ser Tyr Leu Gln Ser Ile Glu His Leu Glu Val Glu Tyr 4280 4285 4290 Gly Ser Arg Leu Cys Arg Tyr Ala Leu Ile Lys Asp Glu Asn Asn 4295 4300 4305 Gln Thr His Phe Ile Trp Thr Met His His Ala Ile Phe Asp Gly 4310 4315 4320 Trp Ser Ile Arg Val Val Leu Ala Thr Leu Asp Asn Val Tyr Lys 4325 4330 4335 Gly Met Lys Thr Thr Ala Leu Thr Pro Tyr Ser Arg Phe Ile Glu 4340 4345 4350 Tyr Thr Leu Ala Ile Asn Pro Gln Ser Ala Ala Asp Tyr Trp Val 4355 4360 4365 Glu Gln Leu Trp Asp Ala Lys Lys Ala Ser Phe Pro Pro Asn Thr 4370 4375 4380 Ser Gly Lys Leu Pro Glu Tyr Ser Asn Gly Tyr Arg Ser Met Val 4385 4390 4395 Thr Asn Ile Lys Leu Pro Asp Leu Ser Ala Thr Gly Phe Thr Arg 4400 4405 4410 Ala Thr Ile Leu Arg Ala Thr Trp Ala Leu Leu Leu Thr Arg Tyr 4415 4420 4425 Cys Glu Thr Asp Asp Ile Cys Phe Gly Thr Thr Ile Ser Gly Arg 4430 4435 4440 Gln Ala Pro Val Ser Gly Ile Ile Asp Met Pro Gly Pro Ala Ile 4445 4450 4455 Ala Thr Val Pro Leu Arg Ile Arg Val Pro Gln Gln Lys Ser Val 4460 4465 4470 Ala Ala Phe Leu Gln Glu Val Gln Glu Gln Ala Leu Ala Met Val 4475 4480 4485 Glu Phe Glu Gln Phe Gly Leu Gln Asn Ile Ser Lys Leu His Ala 4490 4495 4500 Cys Ala Lys Glu Ala Cys Asp Phe Ser Ser Leu Leu Val Val Gln 4505 4510 4515 Pro Lys Glu Ala Leu Asp Pro Ala Gly Asp Gln Asp Ala Ile Leu 4520 4525 4530 Ile Ala Ala Asp Gly Lys Val Glu Thr Gly Glu Tyr Ala Leu Gln 4535 4540 4545 Asn Tyr Phe Ser Tyr Pro Leu Val Val Gln Gly His Leu Tyr Asp 4550 4555 4560 Glu Ser Thr Glu Leu Val Leu Ile Tyr Asn Ser Ala Ile Leu Pro 4565 4570 4575 Glu Glu Gln Ile Val Ala Leu Ser His Gln Phe His His Val Ala 4580 4585 4590 Arg Glu Leu Val Leu Lys Leu Gln Ser Asn Val Gly Ser Ile Ala 4595 4600 4605 Thr Thr Ser Ser Trp Asp Leu Gln Gln Ala Met Lys Phe Asn Ser 4610 4615 4620 Glu Val Pro Glu Ala Val Asp Gly Cys Phe His Gln Leu Phe Glu 4625 4630 4635 Arg Gln Ala Arg Gln Thr Pro Asp Ala Met Ala Ile Cys Ala Trp 4640 4645 4650 Asp Gly Ser Phe Thr Tyr Ala Glu Leu Asp Thr Ala Ala Asn Arg 4655 4660 4665 Leu Ala Tyr His Leu Ile Ser Gln His Ala Ile Lys Pro Asp Glu 4670 4675 4680 Leu Ile His Val Cys Phe Glu Lys Ser Ala Trp Tyr Phe Val Ser 4685 4690 4695 Ile Leu Ala Ile Asn Lys Ala Gly Ala Ala Trp Val Pro Leu Asp 4700 4705 4710 Pro Ser His Pro Leu Glu Arg Leu Gly Gln Ile Val Lys Gln Thr 4715 4720 4725 Lys Ala Gln Met Val Leu Ile Ser Glu Ser His Ala Ser Leu Cys 4730 4735 4740 Lys Asp Leu Ile Pro Ile Val Ile Glu Val Ser Ala Ser Leu Asp 4745 4750 4755 Gln Gln Leu Ser Arg Asn Gly Ala Ala Phe Ser Gln Asn Pro Pro 4760 4765 4770 Thr Thr Lys Val Ser Pro Ala Asn Ala Ala Tyr Val Leu Phe Thr 4775 4780 4785 Ser Gly Ser Thr Gly Val Pro Lys Gly Leu Val Met Glu His Arg 4790 4795 4800 Ser Val Cys Ser Ser Gln Arg Ala Ile Val Arg Arg Leu Gly Leu 4805 4810 4815 His Ser Lys Val Arg Met Leu Gln Phe Ala Ala Phe Val Phe Asp 4820 4825 4830 Leu Ser Ile Gly Glu Ile Val Ala Pro Leu Ile Ser Gly Ala Cys 4835 4840 4845 Val Cys Val Pro Ser Glu Gln Ala Arg Met Asn Asp Val Ala Gly 4850 4855 4860 Phe Ile Arg Asp Ala Ser Val Asn Trp Ala Tyr Leu Thr Pro Ser 4865 4870 4875 Phe Val Arg Val Leu Lys Pro Glu Asp Val Pro Gly Leu Glu Leu 4880 4885 4890 Leu Leu Leu Cys Gly Glu Val Thr Pro Arg Asp Val Phe Asp Val 4895 4900 4905 Trp Val Gly Lys Leu Arg Phe Ile Ser Gly Trp Gly Pro Ala Glu 4910 4915 4920 Thr Cys Val Phe Ser Thr Leu His Glu Trp Gln Pro Gln Asp Ser 4925 4930 4935 Pro Leu Thr Val Gly Arg Pro Val Gly Ala Phe Cys Trp Ile Val 4940 4945 4950 Asp Pro Glu Arg Ser Asp Gln Leu Ala Pro Ile Gly Thr Val Gly 4955 4960 4965 Glu Ile Met Leu Gln Gly Pro Thr Leu Leu Arg Glu Tyr Leu Asp 4970 4975 4980 Asp Ala Glu Arg Thr Ala Ser Ser Thr Val Thr Cys Leu Pro Asp 4985 4990 4995 Trp Ala Leu Gln Lys Ala Ser Gln Trp Thr Arg Phe Tyr Lys Ser 5000 5005 5010 Gly Asp Leu Ala Met Tyr Asn Pro Asp Gly Thr Ile Glu Phe Cys 5015 5020 5025 Ser Arg Arg Asp Thr Gln Val Lys Ile Arg Gly Leu Arg Val Glu 5030 5035 5040 Leu Ser Glu Val Glu Tyr Arg Ile Arg Glu Ser Leu Glu Gly Ile 5045 5050 5055 Cys Gln Val Ala Val Asp Ile Ser Thr Ser Asp Gly Gly Ser Arg 5060 5065 5070 Leu Val Ser Tyr Leu Cys Phe Thr Glu Glu Thr Arg Ser Ser Thr 5075 5080 5085 Ser Ser Glu Asn Ser Met Asp Asp Ile Leu Met Pro Ile Thr Val 5090 5095 5100 Glu Val Arg Pro Leu Leu Ala Ala Met Val Gly Lys Leu Arg Val 5105 5110 5115 Ser Ile Pro Asn Tyr Met Ile Pro Thr Leu Phe Ile Val Cys Arg 5120 5125 5130 Tyr Met Pro Ser Ile Thr Ser Thr Lys Leu Asp Arg Thr Ala Leu 5135 5140 5145 Arg Gln Val Ala Ser Leu Leu Thr Gln Asp Gln Ile Ser Met Tyr 5150 5155 5160 Ser Leu Ser Asp Asp Asn Lys Arg Pro Pro Glu Thr Asp Met Glu 5165 5170 5175 Arg Lys Phe Gln Ser Leu Trp Ala Ser Ile Leu Ser Ile Pro Ala 5180 5185 5190 Asp Ser Ile Gly Arg Asp Asp Ser Phe Leu Gln Ile Gly Gly Asp 5195 5200 5205 Ser Ile Ser Ala Ile His Leu Val Ser Thr Ala Arg Ala Glu Gly 5210 5215 5220 Leu Val Ile Ser Val Lys Asp Val Phe Asp Asp Ser Arg Leu Leu 5225 5230 5235 Ala Ile Ala Ala Lys Ala Val Phe Ser Gly Lys Ala Glu Gly Arg 5240 5245 5250 Asp Asn Gln Ile Ala Pro Phe Ser Leu Leu Pro Pro Pro Thr Arg 5255 5260 5265 Asp Ala Ile Val Met Gln Ala Ala Glu Gln Cys Gly Ile Ala Gln 5270 5275 5280 Ser Ala Ile Asp Asp Ala Tyr Pro Ala Thr Ser Ile Gln Glu Gly 5285 5290 5295 Leu Met Ala Leu Ser Val Lys Gln Arg Gly Ser Tyr Val Ala Lys 5300 5305 5310 Tyr Val Tyr Arg Leu Ala Ser Gln Val Asp Ile Gly Arg Phe Lys 5315 5320 5325 Ala Ala Trp Met Lys Thr Val Glu Leu Cys Gly Ala Leu Arg Thr 5330 5335 5340 Arg Ile Ile Leu Phe Asp Asp Ser Ser Ile Gln Val Leu Leu Lys 5345 5350 5355 Asp Pro Ala Ser Trp Glu Ala Thr Asp Lys Glu Thr Leu Ser Ser 5360 5365 5370 Leu Val Arg Ser Asp Arg Gly Leu Gln Met Ser Tyr Gly Thr Pro 5375 5380 5385 Leu Cys Trp Tyr Ala Thr Val Gln Glu Ala Asp Thr Ser Tyr Phe 5390 5395 5400 Val Trp Ser Ala His His Ala Ile Tyr Asp Gly Trp Thr Ile Arg 5405 5410 5415 Leu Ile Leu Ser Thr Leu Glu Ser Ile Tyr Arg Asn Val Glu Pro 5420 5425 5430 Ser Pro Leu Gln Ala Tyr Asn Ala Phe Val Lys Tyr Thr Leu Ser 5435 5440 5445 Leu Asp His Asp Ala Ala Thr Asn Phe Trp Ala Asn Glu Leu Gln 5450 5455 5460 Gly Ser Lys Arg Ala Ser Phe Pro Pro Leu Asn Gly Thr Asn Met 5465 5470 5475 Gly Thr Asp Gly Gln Pro Thr Gln Val His Arg Arg Thr Ile Ala 5480 5485 5490 Leu Pro Val Arg Glu Arg Ser Ser Ile Thr Lys Ala Ser Ile Leu 5495 5500 5505 Arg Ala Ala Trp Ala Ile Val Leu Ala Arg Tyr Cys Asp Ser Asp 5510 5515 5520 Asp Leu Thr Phe Gly Thr Thr Val Ser Gly Arg Gln Ala Pro Val 5525 5530 5535 Pro Gly Leu Glu Ala Met Pro Gly Leu Ala Ile Ala Thr Ile Pro 5540 5545 5550 Val Arg Val His Leu Asp Ser Gln Met Lys Thr Ser Glu Phe Leu 5555 5560 5565 Leu Gly Val Gln Asn Gln Thr Thr Asp Val Ile Pro Tyr Glu Gln 5570 5575 5580 Tyr Gly Ile Gln Asn Ile Ala Asn Val Ser Ser Asp Ala Arg Glu 5585 5590 5595 Ala Cys Ser Phe Ser Ser Leu Leu Val Ile Gln Pro Pro Ala Ser 5600 5605 5610 Ser Gln Ala Asp Ser Glu Glu Ala Ile Leu Leu Ala Gly Glu Ala 5615 5620 5625 Glu Ser Ala Leu Thr Glu Asp Thr Met Asp Ser Tyr Phe Asn Tyr 5630 5635 5640 Pro Leu Val Leu Ile Tyr Gly Ile Ala Gly Asp Asn Val Glu Gln 5645 5650 5655 Arg Leu Phe Phe Asn Pro Gly Val Leu Ala Glu Lys Gln Val Glu 5660 5665 5670 Ala Leu Ser Tyr Gln Ile Glu His Val Val Gln Gln Leu Ala Asn 5675 5680 5685 Asp Val Cys Leu Gly Asp Ile Ser Leu Val Ser Asp Trp Asp Val 5690 5695 5700 Lys His Ala Arg Asp Cys Gln Thr Leu Lys Leu Pro Val Gln Ser 5705 5710 5715 Cys Thr His Trp Leu Ile Gln Asp Ala Ile Arg Thr Tyr Pro Thr 5720 5725 5730 Ser Pro Ala Val Val Ser Trp Asp Gly Glu Leu Thr Tyr Ser Glu 5735 5740 5745 Leu Gly Ser Leu Val Thr Arg Leu Ala Ala Lys Leu Arg Gln Leu 5750 5755 5760 Gly Ile Gly Arg Glu Thr Phe Val Pro Ile Cys Phe Pro Lys Ser 5765 5770 5775 Val Trp Ala Val Val Thr Met Val Ala Val Glu Leu Ala Gly Gly 5780 5785 5790 Ala Phe Val Pro Leu Asp Pro Lys Ala Pro Arg Thr Arg Ile Ser 5795 5800 5805

Ser Val Leu Asp Asp Ile Lys Ala Thr Ile Ala Leu Thr Ser Pro 5810 5815 5820 Cys Cys Ala Ser Val Met Ser Gly Leu Asp Ile Pro Val Val Val 5825 5830 5835 Ile Asp Asp Ser Phe Val Ala Thr Leu Pro Glu Ala Ala Thr Pro 5840 5845 5850 Val Gln Gln Thr Asp Cys Pro Ser Asp Ala Ala Val Val Leu Phe 5855 5860 5865 Thr Ser Gly Ser Thr Gly Arg Pro Lys Gly Met Val Ile Gln His 5870 5875 5880 Asp Thr Leu Cys Ser Ser Ala Asn Ala Tyr Gly Ser Asp Leu Leu 5885 5890 5895 Ile Gly Pro Gly Ser Arg Val Phe Gln Phe Ser Ala Tyr Thr Phe 5900 5905 5910 Asp Val Gly Ile Leu Asp Thr Leu Val Thr Leu Met Arg Gly Gly 5915 5920 5925 Cys Leu Cys Ile Pro Ser Glu Glu Asp Arg Leu Asn Asp Leu Ser 5930 5935 5940 Gly Ala Ile Asn Lys Thr Gln Ala Asn Trp Val Phe Leu Thr Pro 5945 5950 5955 Thr Val Ala Asp Leu Leu Asn Pro Ala Asp Val Pro Thr Leu Arg 5960 5965 5970 Val Val Cys Leu Gly Gly Glu Ala Ile Asn Gln Lys Thr Ala Ala 5975 5980 5985 Arg Trp Lys Asp His Val Glu Leu His Gly Leu Tyr Gly Pro Ala 5990 5995 6000 Glu Ala Ser Ile Cys Ala Trp Asn Pro Thr Val Gly Arg Ser Gly 6005 6010 6015 Lys Ser Thr Asn Leu Gly Lys Pro Leu Ala Ser Ala Phe Trp Val 6020 6025 6030 Val Glu Pro Thr Asp Ile His Arg Leu Ala Pro Val Gly Cys Ile 6035 6040 6045 Gly Glu Leu Leu Ile Gln Gly Ser Leu Leu Ala Arg Gly Tyr Leu 6050 6055 6060 Asn Val Asp Glu Lys Gln Ala Ala Asn Trp Ile Glu Tyr Phe Thr 6065 6070 6075 Ala Gly Trp Leu Pro His Asp Phe Pro Asn Arg Ala Tyr Arg Thr 6080 6085 6090 Gly Asp Leu Val Arg Arg Asn Ala Asp Gly Thr Phe Asp Tyr Ile 6095 6100 6105 Gly Arg Lys Asp Thr Gln Val Lys Leu His Gly Gln Arg Val Glu 6110 6115 6120 Leu Gly Glu Ile Glu His Gln Leu His Gln Val Leu Pro Ala Gly 6125 6130 6135 Met Ser Ala Ile Ile Asp Val Val Lys Ser Val Asp Glu Gln Arg 6140 6145 6150 Gln Asp Ser Leu Met Ala Phe Leu Trp Tyr Thr Asp Ser Ala Thr 6155 6160 6165 Ser Asn Ser Pro Ser Pro Leu Glu Leu Ile Gly Ser Leu Ser Asp 6170 6175 6180 Glu Gln Arg Ile Leu Ile Ser Asp Val Asp Met Ser Leu Ser Thr 6185 6190 6195 Thr Leu Pro Ser His Met Ile Pro Ser Cys Tyr Leu Ile Phe His 6200 6205 6210 Gly Lys Pro Asn Gln Thr Thr Ser Gly Lys Val Asp Arg Arg Ser 6215 6220 6225 Leu Leu Glu Leu Ala Gln Asn Ile Ser Tyr Asp Asp Arg Ser Arg 6230 6235 6240 Phe Gly Pro Gly Asn Glu Glu Lys Glu Thr Pro Thr Glu Pro Met 6245 6250 6255 Glu Phe Lys Leu Arg Asp Leu Trp Ala Glu Val Leu His Val Asn 6260 6265 6270 Ala Glu Asp Ile Ser Lys Arg Asp Ser Phe Met Arg Ile Gly Gly 6275 6280 6285 Asp Ser Ile Ser Ala Ile Arg Leu Val Thr Leu Ala Gln Lys His 6290 6295 6300 Gly Leu Ala Leu Ser Val Ala Thr Ile Phe His Lys Pro Gln Leu 6305 6310 6315 Glu Gln Met Ala His Ala Val Ser Val Thr Ala Asn Ser Leu Val 6320 6325 6330 Asp Asp Ile Gln Pro Phe Lys Leu Val Ser Ser Ile Pro Lys Glu 6335 6340 6345 Ala Ile Ile Gln Ala Val Arg Asp Gln Gly Ser Leu Ser His Ala 6350 6355 6360 Val Asp Ala Tyr Pro Cys Thr Ser Leu Gln Glu Gly Leu Met Ala 6365 6370 6375 Leu Ala Val Lys Gln Pro Arg Ser Tyr Ile Ala Lys Phe Val Tyr 6380 6385 6390 Arg Leu Pro Asp His Val Asn Val Asp Ser Phe Lys Thr Ala Trp 6395 6400 6405 Ala Lys Thr Val Glu Ile Cys Thr Ser Leu Arg Thr Arg Ile Val 6410 6415 6420 Tyr Val Asn Glu Thr Pro Ile Gln Val Val Leu Asn Asp Glu Pro 6425 6430 6435 Ala Val Asp Gly Arg Asp Val Glu Glu Ala Ile Gln Leu His Arg 6440 6445 6450 Ser Val Glu Met Gly Tyr Ala Leu Arg Leu Ser Leu Gly Thr Ile 6455 6460 6465 Val Lys Gln Asn Asp Gly Arg Cys Phe Phe Phe Trp Ser Val His 6470 6475 6480 His Ala Val Phe Asp Gly Leu Ser Asn Arg Asn Ile Phe Thr Val 6485 6490 6495 Leu Gln Lys Val Tyr Ser Gly Leu Glu Val Ser Pro Leu Pro Ser 6500 6505 6510 Tyr Ala Arg Phe Ile Gln Tyr Val Lys Ser Leu Asp Val Asp Asn 6515 6520 6525 Ala Gly Arg Tyr Trp Asn Ala Gln Leu Glu Asn Cys Glu His Ser 6530 6535 6540 Asn Phe Pro Ala Thr Asn Gly Ile Pro Asn Ser Glu Thr Thr Thr 6545 6550 6555 Ser Ile Leu Glu Lys Val Val Asp Leu Pro Lys Met Pro Lys Ser 6560 6565 6570 Asn Ile Thr Thr Ala Thr Leu Ile Arg Ala Ala Trp Ala Leu Val 6575 6580 6585 Leu Ser Arg Tyr Cys Ser Thr Asp Asp Val Cys Phe Gly Met Ser 6590 6595 6600 Leu Ser Gly Arg Gln Ala Pro Val Pro Asp Val Ile Asp Met Val 6605 6610 6615 Gly Pro Thr Leu Ala Thr Val Pro Val Arg Val Arg Leu Asp Phe 6620 6625 6630 Asp Gln Ser Val Ser Cys Phe Leu Glu Ala Val Gln Asp Gln Ala 6635 6640 6645 Leu Glu Met Ile Ser Phe Glu Gln Tyr Gly Leu Gln Asn Ile Ala 6650 6655 6660 Lys Leu Gly Pro Asp Ala Lys Gln Ala Cys Gln Phe Ser Ser Leu 6665 6670 6675 Leu Leu Ile Gln Pro Thr Glu Thr Glu Asn Glu Glu Gly Asp Asn 6680 6685 6690 Val Leu Val Thr Ala Asp Val Glu Val Glu Ser Pro Ala Asp Met 6695 6700 6705 Val His Lys Phe Tyr Ser Phe Pro Leu Val Val Gln Ala His Leu 6710 6715 6720 Gly Asp Asp Ser Val Arg Leu Ser Ile Ile Tyr Lys Ser Asn Ala 6725 6730 6735 Leu Val Glu Ala Gln Ala Glu Ala Leu Ala His Gln Leu Ser His 6740 6745 6750 Val Val Cys Gln Leu Thr Ser Leu Arg Phe Ala Pro Leu Arg Ala 6755 6760 6765 Val Thr Leu Ala Ser Ser Trp Asp Leu Glu Lys Ala Ile Ser Phe 6770 6775 6780 Asn Gln Glu Ile Pro Asp Phe Ile Asp Ser Cys Ile His Thr Leu 6785 6790 6795 Ile Glu Ala Gln Ala Glu Gln Arg Pro Asp Ala Ile Ala Val Ser 6800 6805 6810 Ala Trp Asp Gly Glu Leu Thr Tyr Ser Gln Leu Asn Ser Ala Ala 6815 6820 6825 Asn Arg Leu Ser His His Leu Ile Asp Arg Tyr Ser Leu Gln Ile 6830 6835 6840 Glu Asp Leu Val His Val Cys Phe Glu Lys Ser Ile Trp His Val 6845 6850 6855 Ile Ser Val Leu Ala Ile Asn Lys Ala Gly Ala Ala Trp Val Pro 6860 6865 6870 Phe Asp Pro Ser His Pro Glu Gln Arg Leu Arg Gln Ile Val Ser 6875 6880 6885 Gln Thr Gly Ala Lys Leu Ala Leu Ala Ser Ser Gly Asn Ala Ala 6890 6895 6900 Leu Cys Gly Lys Val Val Glu Arg Val Leu Glu Val Asn Ser Ala 6905 6910 6915 Ser Asp Asp Gln Leu Val Ser Lys Gly Ile Ser Ser Asp Asn Pro 6920 6925 6930 Ser Ile Pro Val Thr Pro Arg Asn Ala Ala Tyr Val Leu Phe Thr 6935 6940 6945 Ser Gly Ser Thr Gly Thr Pro Lys Gly Ile Val Leu Glu His Ala 6950 6955 6960 Ala Val Cys Thr Ser Gln Thr Ala Leu Ser Lys Arg Phe Gly Leu 6965 6970 6975 Lys Ser Asn Asp Arg Met Leu Gln Phe Thr Ala Phe Thr Phe Asp 6980 6985 6990 Pro Ser Val Thr Glu Ile Phe Ala Thr Leu Met Leu Gly Ala Cys 6995 7000 7005 Val Cys Ile Pro Ser Asp Trp Thr Arg Met Asn Asp Leu Ala Thr 7010 7015 7020 Phe Ile Asn Gln Asn Ser Val Asn Trp Thr Leu Leu Thr Pro Ser 7025 7030 7035 Phe Leu Arg Thr Leu Ser Pro Glu Asp Ala Gln Ser Leu Glu Ala 7040 7045 7050 Leu Val Val Thr Gly Glu Ala Pro Thr Leu Asp Ile Phe Asn Thr 7055 7060 7065 Trp Ile Gly Lys Val Arg Leu Ile Asn Gly Trp Gly Pro Thr Glu 7070 7075 7080 Thr Cys Val Ile Ser Ser Thr His Glu Trp Gln Ser Ala Glu Glu 7085 7090 7095 Ser Tyr Leu Lys Ile Gly Lys Pro Val Gly Ser Cys Cys Trp Ile 7100 7105 7110 Val Asp Ser Lys His Thr Ser Gln Leu Ala Ala Ile Gly Val Val 7115 7120 7125 Gly Glu Leu Val Val Gln Gly Pro Thr Leu Leu Arg Glu Tyr Leu 7130 7135 7140 Ala Ala Pro Asp Lys Thr Lys Glu Ala Val Val Thr Asp Met Pro 7145 7150 7155 Ser Trp Val Pro Arg Gln Gly Leu Val Gly Trp Asn Arg Leu Tyr 7160 7165 7170 Lys Thr Gly Asp Leu Cys Tyr Tyr Asn Pro Asp Gly Thr Ile Gln 7175 7180 7185 Tyr Cys Ser Arg Arg Asp Thr Gln Ile Lys Ile Arg Gly Gln Arg 7190 7195 7200 Ile Glu Ala Gly Glu Ile Glu His Arg Ile Ser Gln Ala Leu Ser 7205 7210 7215 Ile His Gln Val Ala Val Glu Val Val Asn Thr Asp Asn Gly His 7220 7225 7230 Thr Leu Val Ala Tyr Ile Cys Phe Thr Ser Glu Leu Arg Lys Ile 7235 7240 7245 Ser Ser Thr Ala Thr Ala Asp Glu Val Phe Ala Pro Leu Thr Asp 7250 7255 7260 Asp Thr Gln Arg Leu Ile Ser Glu Ala Val Ala Gln Leu Arg Thr 7265 7270 7275 Ser Leu Pro Leu Tyr Met Ile Pro Thr Leu Phe Ile Thr Cys Lys 7280 7285 7290 Phe Met Pro Ser Ile Thr Ser Val Lys Leu Asp Arg Lys Ser Leu 7295 7300 7305 Arg Gln Phe Thr Ala Met Leu Asp Arg Asp Gln Leu Thr Gly Tyr 7310 7315 7320 Ser Leu Thr Asp Ala Ala Lys Glu Pro Pro Ser Thr Glu Met Glu 7325 7330 7335 Leu Leu Leu Gln Ser Leu Trp Ala Glu Val Leu Ser Ile Pro Ala 7340 7345 7350 Glu Ser Ile Gly Arg His Asp Asn Phe Phe Gln Ile Gly Gly Asp 7355 7360 7365 Ser Val Val Ala Ile Gln Leu Val Ser Ile Ala Arg Lys Ile Gly 7370 7375 7380 Phe Pro Ile Ser Val Thr Asp Ile Ser Asp Asp Pro Arg Leu His 7385 7390 7395 Ala Val Ala Thr Lys Met Ala Leu Ala Asp Gly His Val Ile Ser 7400 7405 7410 Ser Asp Glu Val Pro Pro Phe Ser Leu Val Pro Gln Ser Ile His 7415 7420 7425 Lys Ala Ile Ser Gly Gly Asp Ala Glu Leu Gln Cys Lys Leu Thr 7430 7435 7440 Glu Gly Gln Ala Ile Glu Asp Ala Tyr Pro Cys Thr Pro Leu Gln 7445 7450 7455 Glu Gly Leu Leu Asn Thr Thr Leu Lys Gln Pro Gly Ala Tyr Ile 7460 7465 7470 Ala Arg Phe Arg Tyr Arg Leu Gly Glu Gly Thr Asp Val Ser Arg 7475 7480 7485 Phe Ile Ala Ala Trp Asn Arg Thr Val Glu Ala Cys Ala Asn Leu 7490 7495 7500 Arg Thr Arg Ile Ile Val Ile Asn Asn Ser Thr Ile Gln Val Val 7505 7510 7515 Val Arg Asn Gly Cys Arg Trp Asn Asp Glu Glu Lys Thr Met Leu 7520 7525 7530 Pro Ser His Gly Gln Gln Asp Leu Glu Val Asp Tyr Gly Leu Pro 7535 7540 7545 Leu Cys Asp Tyr Ser Leu Ile Glu His Asp Gly Ala Asn Tyr Phe 7550 7555 7560 Cys Leu Arg Leu His His Ser Ile Tyr Asp Gly Trp Ser Val Pro 7565 7570 7575 Leu Met Leu Ser Thr Leu Gln Ser Tyr Tyr Thr Ala Leu Asp Val 7580 7585 7590 Ser Pro Leu Tyr Pro Tyr Ser Arg Phe Val Lys Tyr Ile Met Gly 7595 7600 7605 Ile Asp Ser Asp Ile Ser Ala Glu Phe Trp Thr Ser Gln Leu Glu 7610 7615 7620 Gly Ala Lys Pro Met Ser Phe Pro Thr Val Ser Glu Gly Gly Lys 7625 7630 7635 Ile Glu Ser Lys Gln Thr Arg Leu Gln Ser Ile Thr Val Gly Ile 7640 7645 7650 Arg Gln Ser Ser Asn Ser Ser Ile Thr Lys Ala Ala Ile Ile Arg 7655 7660 7665 Ala Ala Trp Ala Ile Val Leu Ala Arg Tyr Ser Gly Val Asn Asp 7670 7675 7680 Val Cys Phe Gly Ser Ser Val Ser Gly Arg Gln Ala Ala Val Pro 7685 7690 7695 Gly Leu Glu Ser Ile Pro Gly Leu Val Val Ala Thr Val Pro Ile 7700 7705 7710 Arg Val Gln Ile Asp Asp Gln Gln Ser Val Ser Thr Phe Leu Arg 7715 7720 7725 Ser Val Gln Asn Gln Ala Phe Asp Met Ile Pro His Glu Gln Phe 7730 7735 7740 Gly Leu Lys Asn Ile Ser Asn Leu Asn Asp Ala Ala Lys Ala Ala 7745 7750 7755 Cys Asp Phe Lys Ser Leu Val Val Val Gln Pro Val Gln Lys Leu 7760 7765 7770 Thr His Glu Ser Asn Leu Leu Ser Phe Ala Thr Asp Leu Glu Gly 7775 7780 7785 Ser Ser Lys Val Glu Met Leu Gln Gly Tyr Leu Ser Tyr Pro Leu 7790 7795 7800 Val Ala Gln Cys Met Leu Ala Asp Asp Ser Val Asp Leu Asp Leu 7805 7810 7815 Tyr Tyr Asp Pro Ser Val Val Pro Glu His Gln Val Gln Gly Leu 7820 7825 7830 Ser His Ala Phe Lys His Val Phe Glu Gln Leu Leu Val Ser Pro 7835 7840 7845 Asn Gln Ser Leu Ser Gln Met Leu Ala Glu Val Pro Trp Glu Val 7850 7855 7860 Asp Phe Ala Ala Ser Ala Asn Gly Val Pro Pro Thr Thr Ile Glu 7865 7870 7875 Arg Cys Val His Ser Leu Ile Glu Asp Glu Thr Leu Lys His Pro 7880 7885 7890 Ala Thr Leu Ala Val Asp Ala Cys Asp Ala Arg Phe Thr Tyr Gln 7895 7900 7905 Gln Leu Asp Ile Cys Ala Asn Arg Leu Ser His His Leu Ile Asn 7910 7915 7920 Asn Phe His Val Lys Lys Gly Asp Val Val His Val Cys Phe Asp 7925 7930 7935 Lys Ser Ala Trp Tyr Ile Val Ala Ile Leu Ala Ile Asn Lys Ala 7940 7945 7950 Gly Ala Thr Trp Ser Pro Leu Asp Pro Thr His Pro Val Gln Arg 7955 7960 7965 Tyr Gln Gln Ile Ile Ser Gln Thr Gly Ala Glu Leu Ile Leu Ala 7970 7975 7980 Ser Pro Thr Asn Thr Ser Lys Cys Thr Asn Leu Thr Pro Phe Val 7985 7990 7995 Leu Glu Val Ser Ser Arg Leu Asp Gln Ala Leu Ser

Thr Lys Asp 8000 8005 8010 Val Leu Lys His Arg Pro Asn Val Asp Val Ser Pro Ser Asp Ala 8015 8020 8025 Ala Tyr Ile Ile Phe Thr Ser Gly Thr Thr Gly Met Pro Lys Gly 8030 8035 8040 Val Val Ile Glu His Gly Ser Leu Cys Thr Ser Gln Thr Ala Leu 8045 8050 8055 Ala Leu Asn Val Gly Leu Thr Asp Gln Ser Arg Thr Leu Gln Phe 8060 8065 8070 Ala Ser Phe Val Phe Asp Ala Cys Ile Phe Glu Ile Ile Ala Thr 8075 8080 8085 Leu Leu Val Gly Gly Cys Ile Cys Met Pro Ser Trp Asp Glu Gln 8090 8095 8100 Met Asn Asn Leu Thr Gly Tyr Met Val Lys Ala Ser Val Asn Ala 8105 8110 8115 Ala Phe Ala Thr Pro Thr Val Ala Arg Ser Leu Lys Pro Glu Asp 8120 8125 8130 Ile Pro Cys Leu Gln Val Leu Leu Val Gly Gly Glu Ala Ala Ala 8135 8140 8145 Ser Asp Ile Val Ser Thr Trp Phe Gly Lys Leu Arg Leu Tyr Asn 8150 8155 8160 Ala Trp Gly Pro Thr Glu Thr Cys Val Ile Ala Ser Leu His Pro 8165 8170 8175 Trp Thr Gly Pro Asn Asp Ser Pro Arg Thr Ile Gly Arg Ser Ile 8180 8185 8190 Leu Gly Asn Trp Trp Ile Val Asp Pro Asn Asp Pro Arg Lys Leu 8195 8200 8205 Val Pro Thr Gly Cys Val Gly Glu Ile Val Tyr Gln Gly Pro Thr 8210 8215 8220 Leu Phe Arg Glu Tyr Leu Ala Asn Pro Ala Lys Thr Asp Glu Val 8225 8230 8235 Ile Val Ser Ser Leu Pro Tyr Trp Val Pro Asn Arg Glu Leu Arg 8240 8245 8250 Gly Trp Asp Arg Phe Tyr Arg Thr Gly Asp Leu Gly His Tyr Asn 8255 8260 8265 Pro Asp Gly Thr Ile Glu Phe Ala Gly Arg Lys Asp Thr Gln Val 8270 8275 8280 Lys Ile Arg Gly Leu Arg Ile Glu Leu His Glu Ile Glu Gln Gln 8285 8290 8295 Ile Ile Thr Asn Leu Ser Gly Ala Arg Gln Val Ala Val Asp Val 8300 8305 8310 Met Lys Arg Asp Glu Ala Ser Gln Leu Val Ala Phe Tyr Ser Phe 8315 8320 8325 Ser Asn Glu Thr Leu Ser Ser His Leu Gly Thr Gly Pro Asp Gly 8330 8335 8340 Lys Ala Ile Phe Ala Pro Leu Asp Asn Asn Ala Ala Pro Gln Ile 8345 8350 8355 His Asp Leu Ile Ser Leu Leu Lys Gly Val Leu Pro Pro Tyr Met 8360 8365 8370 Ile Pro Thr Thr Phe Ile Pro Cys Gln His Met Pro Ile Gly Thr 8375 8380 8385 Ser Thr Lys Leu Asp Arg Lys Leu Leu Val Gln Met Ala Thr Ser 8390 8395 8400 Leu Ser Arg Glu Gln Phe Glu Gln Tyr Ser Leu Val Gly Ser Thr 8405 8410 8415 Lys Arg Ala Leu Glu Thr Thr Met Glu Ala Arg Leu Gln Gln Val 8420 8425 8430 Trp Ala Asp Ile Leu His Ile Pro Ala Glu Ser Ile Gly Arg Asp 8435 8440 8445 Asp Asn Phe Leu Gln Ile Gly Gly Asp Ser Met Ser Val Ile Leu 8450 8455 8460 Leu Val Ser Ala Ala Arg Glu Ser Gly Ile Ser Ile Ser Ala Arg 8465 8470 8475 Asp Val Phe Gln Asp Ala Arg Leu Leu Ser Val Ala Ala Lys Ala 8480 8485 8490 Glu Val Ile Ala Asp Asp Asp Asp Asp Phe Gly Asp Val Glu Pro 8495 8500 8505 Phe Gly Met Leu Glu Glu Ala Glu Leu Asp Phe Leu Gln Thr Asp 8510 8515 8520 Glu Ala Lys Ser Cys Leu Gly Leu Ser His Ser Met Ser Ile Glu 8525 8530 8535 Asp Ala Phe Pro Cys Ser Lys Leu Gln Glu Gly Leu Met Ala Leu 8540 8545 8550 Ala Val Gln Lys Pro Gly Ser Tyr Ile Gly Thr Phe His Tyr Arg 8555 8560 8565 Leu Ser Lys Ser Ala Asp Ile Asp Ser Phe Lys Ala Ala Trp Gln 8570 8575 8580 Arg Thr Val Glu Met Cys Pro Asn Leu Arg Thr Arg Ile Leu Asn 8585 8590 8595 Ile Asp Gly Ala Ser Ile Gln Val Val Leu Gln Asn Asp Phe Glu 8600 8605 8610 Trp Glu Ser Thr Gln Glu Gly Ser Leu Asp Gly Phe Leu Glu Ala 8615 8620 8625 Ser Arg Asp Ile Arg Met Glu Tyr Gly Ser Arg Leu Cys Arg Tyr 8630 8635 8640 Ala Leu Ile Thr Gln Asp Gly Ser Thr Arg Phe Ile Leu Thr Met 8645 8650 8655 His His Ala Val Phe Asp Gly Trp Thr Met Arg Leu Val Leu Glu 8660 8665 8670 Thr Leu Asp Ser Ala Tyr His Gly Asp Ala Val Ala Glu Leu Ser 8675 8680 8685 Pro Tyr Ser Arg Phe Ile Gln Tyr Thr Leu Asp Ser Asp Gln Ala 8690 8695 8700 Ser Ala Ser Glu Tyr Trp Leu Ser Gln Leu Arg Asn Ala Lys Lys 8705 8710 8715 Ala Ser Tyr Pro Asn Arg Leu Thr Pro Gly Glu Gln Pro Ala Asn 8720 8725 8730 Ala Asn Ser Thr Gly Tyr Leu Glu Ser Glu Met Gln Ile Pro Lys 8735 8740 8745 Ile Ser Ala Gly Thr Thr Lys Ala Thr Ile Leu Arg Ala Ala Trp 8750 8755 8760 Ala Ile Val Leu Ala Arg Tyr Cys Asp Ala Asn Asp Ile Cys Phe 8765 8770 8775 Gly Thr Thr Val Ser Gly Arg Gln Ala Pro Val Pro Gly Leu Ala 8780 8785 8790 Glu Met Pro Gly Pro Val Ile Ala Thr Ile Pro Val Arg Ile His 8795 8800 8805 Leu Glu Asp Gly Gly Lys Pro Ile Ser Asp Phe Leu Glu Asp Ile 8810 8815 8820 Gln Ser Gln Ala Met Glu Met Val Ala Tyr Glu Gln Phe Gly Leu 8825 8830 8835 His Asn Ile Ala Lys Leu Ser Asp Asp Ala Lys Asp Ala Cys Asp 8840 8845 8850 Phe Ser Ser Leu Leu Val Ile Gln Pro Arg Gln Ile Leu Ser His 8855 8860 8865 Ile Asn Gly Ala Gly Asp Ala Leu Leu Val Ala Arg Ser Asp Glu 8870 8875 8880 Ser Ala Asp Glu Ala Leu Glu Ser Tyr Phe Thr Tyr Pro Leu Val 8885 8890 8895 Ile Gln Ala His Leu His Asp Asp Gly Asp Lys Leu Val Phe Ile 8900 8905 8910 Tyr Asn Lys Phe Ser Leu Ser Glu Gln Gln Leu Ile Thr Leu Ser 8915 8920 8925 His Gln Phe Gln His Val Val Ser Gln Leu Ala Ser His Pro Asp 8930 8935 8940 Leu Leu Leu Lys Asp Leu Ser Ile Thr Ser Glu Trp Asp Val Lys 8945 8950 8955 Gln Ser Val Glu Phe Asn Ser Glu Val Pro Glu Ile Ile Asp Ser 8960 8965 8970 Cys Val His Lys Leu Ile Glu Ala Gln Ala His Arg Ala Pro Asn 8975 8980 8985 Ala Leu Ala Val Ser Ala Trp Asp Gly Asp Leu Thr Tyr Ser Gln 8990 8995 9000 Leu Asn Lys Ser Ala Asn Arg Leu Ala Arg His Leu Val Lys Asn 9005 9010 9015 Tyr Asp Ile Arg Pro Asp Asp Leu Val His Val Cys Phe Glu Lys 9020 9025 9030 Ser Leu Trp His Phe Val Ala Ile Val Ala Ile Asn Lys Ala Gly 9035 9040 9045 Ala Ala Trp Val Pro Leu Asp Pro Ser Tyr Pro Glu Gln Arg Leu 9050 9055 9060 Arg Gln Val Val Asp Gln Thr Arg Ala Thr Leu Val Leu Ser Ser 9065 9070 9075 Ala Arg Asn Glu Lys Leu Cys Ser Thr Leu Leu Glu Asn Val Val 9080 9085 9090 Arg Leu Asp Asp Lys Leu Asp Gln Arg Leu Ala Val Thr Glu Asn 9095 9100 9105 Gly Asp Glu Gly Pro Ala Val Ala Val Thr Pro Asn His Ala Val 9110 9115 9120 Tyr Val Leu Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Leu 9125 9130 9135 Val Met Glu His Gly Ala Val Cys Thr Ser Gln Thr Ala Ile Ala 9140 9145 9150 Lys Arg Leu Asn Leu Thr Ser Glu Val Arg Met Leu Gln Phe Ala 9155 9160 9165 Ala Phe Val Phe Asp Leu Ser Ile Gly Glu Ile Ile Gly Pro Leu 9170 9175 9180 Ile Ser Gly Ala Cys Ile Cys Val Pro Ser Glu Asp Thr Arg Met 9185 9190 9195 Asn Gly Leu Lys Glu Phe Val Asn Asp Thr Lys Val Thr Trp Ala 9200 9205 9210 Tyr Leu Thr Pro Ala Phe Val Arg Thr Leu Val Pro Glu Asp Met 9215 9220 9225 Pro Ala Leu Gln Leu Leu Leu Leu Ala Gly Glu Ala Val Pro Arg 9230 9235 9240 Asp Val Leu Thr Thr Trp Phe Gly Lys Val Arg Leu Val Asn Gly 9245 9250 9255 Trp Gly Pro Ala Glu Thr Cys Cys Phe Ser Thr Leu His Glu Trp 9260 9265 9270 Ser Ser Val Asp Glu Ser Pro Leu Val Val Gly Arg Pro Val Gly 9275 9280 9285 Gly Phe Cys Trp Ile Val Asn Pro Glu Asp Pro Gln Arg Leu Thr 9290 9295 9300 Pro Thr Gly Thr Leu Gly Glu Ile Val Ile Gln Gly Pro Thr Ile 9305 9310 9315 Leu Arg Glu Tyr Leu Ala Asp Val Glu Arg Thr Lys Asp Ser Thr 9320 9325 9330 Val Tyr Ser Leu Pro Thr Trp Ala Pro Arg Pro Asp Ser Lys Asn 9335 9340 9345 Trp Asn Lys Phe Tyr Lys Ser Gly Asp Leu Gly Tyr Tyr Gly Pro 9350 9355 9360 Asp Gly Thr Ile Val Phe Ser Ser Arg Lys Asp Thr Gln Ile Lys 9365 9370 9375 Ile Arg Gly Leu Arg Val Glu Leu Gly Glu Val Glu His Tyr Val 9380 9385 9390 Arg Glu Ile Leu Asp Gly Val Arg Gln Val Val Val Asp Val Tyr 9395 9400 9405 Gln Lys Glu Gly Arg Ser Asn Leu Val Ala Tyr Ile Cys Phe Ser 9410 9415 9420 Asp Glu Met Lys Asn Pro Ser Ala Asp Glu Leu Phe Thr Ala Asp 9425 9430 9435 Gly Leu Phe Ala Ala Ile Thr Thr Asp Leu Arg Gln Arg Ile Ala 9440 9445 9450 Ile Met Leu Gly Glu Leu Arg Ile Ala Leu Pro Thr Tyr Met Ile 9455 9460 9465 Pro Ser Leu Phe Ile Pro Cys Arg Phe Met Pro Ser Ile Thr Ser 9470 9475 9480 Thr Lys Leu Asp Arg Lys Thr Leu Arg His Leu Met Asp Ser Leu 9485 9490 9495 Asn Asp Glu Gln Arg Asn Ala Tyr Ala Leu Leu Asn Ser Gln Lys 9500 9505 9510 Arg Glu Pro Glu Thr Glu Met Glu Ile Gln Leu Gln Ala Leu Trp 9515 9520 9525 Ala Asp Val Leu Gly Ile Pro Ala Ala Ser Ile Gly Arg Asp Asp 9530 9535 9540 Ser Phe Leu Gln Val Gly Gly Asp Ser Ile Leu Ala Ile Gln Leu 9545 9550 9555 Ala Ser Arg Ala Arg Glu Met Gly Ile Ser Phe Gln Val Lys Asp 9560 9565 9570 Val Phe Asp Asp Pro Arg Leu Val Ala Leu Ser Leu Lys Ala Thr 9575 9580 9585 Lys Thr Thr Asp Gln Leu Glu Thr His Val Ala Pro Leu Ser Met 9590 9595 9600 Val Thr Asp Arg Leu Arg Asp Ala Val Phe Ser Asp Asp Val Arg 9605 9610 9615 Lys Gln Cys Cys Leu Ser Glu Glu Gln Val Ile Glu Asp Cys Tyr 9620 9625 9630 Pro Cys Thr Ser Leu Gln Glu Gly Leu Met Ala Leu Thr Ala Lys 9635 9640 9645 Gln Pro Gly Ser Tyr Val Ala Asn Tyr Val Phe Arg Leu Pro Arg 9650 9655 9660 His Val Asp Ile Ser Arg Phe Val Ala Ala Trp Asn Gln Met Ser 9665 9670 9675 Asp Ile Cys Ser Asn Leu Arg Thr Arg Ile Ile His Leu Asp Gly 9680 9685 9690 Glu Ser Val Gln Ile Val Val Arg Gly Gly Asn Gln Trp Arg Ser 9695 9700 9705 Thr Glu Asn Gln Thr Leu Ser Ser Val Leu Asp Ser Ser Glu Asn 9710 9715 9720 Leu Lys Met Thr Tyr Gly Thr Ala Leu Ser Ser Cys Ala Ile Val 9725 9730 9735 His Asp Gly Asp Ser Asp Tyr Phe Val Trp Ser Ala His His Ser 9740 9745 9750 Ile Tyr Asp Gly Trp Thr Met Arg Ile Leu Phe Ser Thr Leu Tyr 9755 9760 9765 Ser Ala Tyr Tyr Gly Asp Ser Leu Ser Pro Val Arg Pro Tyr Ser 9770 9775 9780 Ser Phe Ile Asn Tyr Tyr Arg Asn Ile Asp Thr Gly Lys Ala Ala 9785 9790 9795 Glu Phe Trp Thr Lys Glu Leu Ala Gly Ser Lys Arg Ala Glu Phe 9800 9805 9810 Pro Thr Ser Gln Arg Ser Ile Ser Ala Ala Arg Thr Asp Val Tyr 9815 9820 9825 His Ser Thr Ile Val Leu Pro Glu Thr Leu Asn Ile Pro Val Thr 9830 9835 9840 Lys Ala Thr Val Val Arg Ala Ala Trp Ala Val Val Leu Ala Arg 9845 9850 9855 Tyr Cys Asp Thr Asp Asp Val Thr Phe Gly Thr Thr Val Ser Gly 9860 9865 9870 Arg Gln Ala Pro Val Gln Gly Val Glu Ser Ile Val Gly Pro Met 9875 9880 9885 Ile Ala Thr Val Pro Val Arg Val Arg Leu Asp Lys Asn Gly Pro 9890 9895 9900 Val Ser Gln Phe Leu Ser Asp Val Gln Ser Gln Ala Ser Ser Met 9905 9910 9915 Ile Pro Tyr Glu Gln Leu Gly Leu Gln Asn Ile Ala Lys Leu Ser 9920 9925 9930 Ser Asp Ala Lys Glu Ala Cys Glu Phe Ser Ser Leu Leu Val Ile 9935 9940 9945 Gln Pro Pro Ala His Asp Pro Ala Gly Gly Asp Asp Ser Lys Ala 9950 9955 9960 Ile Leu Ser His Ser Glu Thr Glu Gln Asp Glu Thr Glu Lys Ala 9965 9970 9975 Met Gln Gly Tyr Phe Asn Tyr Pro Leu Val Ile Ile Ser Gly Ile 9980 9985 9990 Gly Glu Lys Ala Ile Glu Gln Arg Leu Phe Tyr Asn Ser Asp Val 9995 10000 10005 Leu Gly Lys Asp Gln Ile Glu Ala Leu Ser His His Ile Glu His 10010 10015 10020 Val Thr His Gln Leu Leu Asn Asn Ser Gly Met Gln Lys Asp Ile 10025 10030 10035 Ser Leu Ile Gly Ser Trp Glu Leu Gln Lys Ala Val Asp Ala Ser 10040 10045 10050 Arg Leu Arg Pro Ala Thr Glu Ser Cys Thr His Trp Leu Ile Gln 10055 10060 10065 Asp Gln Val Arg Leu Gln Pro Asp Gln Ile Ala Ile Ser Ser Trp 10070 10075 10080 Asp Gly Asp Leu Thr Tyr Ala Gln Leu Gly Lys His Val Ala Arg 10085 10090 10095 Leu Ala Ala Arg Leu Gln Glu Leu Asp Val Gly Pro Glu Ser Leu 10100 10105 10110 Val Pro Leu Cys Phe His Lys Ser Lys Trp Ala Val Val Ala Met 10115 10120 10125 Val Ala Val Gln Met Ala Gly Gly Ala Phe Ile Pro Leu Asp Pro 10130 10135 10140 Gly Ala Ser Pro Ala Arg Leu Gln Gly Ile Leu Gln Asp Thr Gly 10145 10150 10155 Ala Thr Leu Ala Ile Thr Ser Ser Glu Cys Gln Gly Leu Leu Gln 10160 10165 10170 Ser Leu Gly Met Lys Ala Val Thr Val Asp Asp Gln Ser Ile Ser 10175 10180 10185 Glu Leu Pro Ala Glu Phe

Asp Leu Arg Ser Glu Ala Arg Pro Thr 10190 10195 10200 Asn Ala Ser Val Ile Leu Phe Thr Ser Gly Ser Thr Gly Lys Pro 10205 10210 10215 Lys Gly Met Ile Ile Glu His Arg Ser Ile Cys Ser Ser Ser Asp 10220 10225 10230 Ala Tyr Gly Ala Asp Leu Lys Ile Glu Ala Gly Thr Arg Val Phe 10235 10240 10245 Gln Phe Ser Ala Tyr Thr Phe Asp Val Gly Val Leu Asp Cys Leu 10250 10255 10260 Val Thr Leu Met Arg Gly Ala Cys Ile Cys Ile Pro Ser Asp His 10265 10270 10275 Asp Arg Leu Asn Asn Leu Ala Ala Ala Ile Thr Ala Ser Lys Ala 10280 10285 10290 Asp Trp Val Phe Leu Thr Pro Thr Val Ala Asp Leu Leu Asn Pro 10295 10300 10305 Val Glu Val Pro Thr Leu Lys Thr Val Cys Leu Gly Gly Glu Ala 10310 10315 10320 Ile Thr Lys Lys Cys Ala Asp Arg Trp Val Gly His Val Ser Leu 10325 10330 10335 His Gly Leu Tyr Gly Pro Ala Glu Ala Ser Ile Cys Ala Trp Asn 10340 10345 10350 Ser Val Val Gly Arg Ser Gly Arg Pro Thr Asn Leu Gly His Pro 10355 10360 10365 Ile Ser Ser Ala Phe Trp Val Val Asn Val Asn Asp Pro Lys Ser 10370 10375 10380 Leu Val Pro Ile Gly Cys Ile Gly Glu Leu Leu Ile Glu Gly Pro 10385 10390 10395 Met Leu Ala Arg Gly Tyr Leu Asn Val Thr Ala Glu Val Ala Ala 10400 10405 10410 Asn Trp Leu Glu Gly Val Asp Trp Leu Pro Gly Asp Asn Arg Pro 10415 10420 10425 Arg Arg Ala Tyr Arg Thr Gly Asp Leu Val Arg Arg Asn Ala Asp 10430 10435 10440 Gly Thr Phe Asp Tyr Ile Gly Arg Lys Asp Thr Gln Val Lys Leu 10445 10450 10455 His Gly Gln Arg Val Glu Leu Gly Glu Ile Glu Thr Arg Ile Gln 10460 10465 10470 Glu Phe Leu Pro Gln Asn Met Ala Ala Ile Val Asp Val Val Lys 10475 10480 10485 Asp Asn Asp Ala Pro Ala Thr Leu Leu Ala Phe Ile Trp Asn Ser 10490 10495 10500 Asp Gly Ser Ser Ala Ser Pro Ala Arg Leu Val Asp Thr Val Ser 10505 10510 10515 Asp Glu Ala Arg Ala Met Val Leu His Leu Asp Thr Ser Leu Asn 10520 10525 10530 Thr Ile Leu Pro Ser Tyr Met Ile Pro Ser Ser Tyr Leu Leu Phe 10535 10540 10545 Ser Gly Lys Pro Glu Gln Thr Thr Thr Gly Lys Ile Asn Arg Arg 10550 10555 10560 Ser Leu Thr Gly Gln Ala Gln His Ile Thr Ala Gln Glu Arg Leu 10565 10570 10575 Arg Phe Ala Pro Asp Thr Ser Phe Arg Val Leu Pro Thr Thr Pro 10580 10585 10590 Met Glu Phe Lys Leu Arg Glu Leu Trp Ala Gln Ile Leu Arg Ile 10595 10600 10605 Glu Pro Asp Asp Ile Cys Lys Asn Asp Ser Phe Leu Arg Leu Gly 10610 10615 10620 Gly Asp Ser Ile Ser Ala Ile Gln Leu Val Ser Lys Ala Gln Leu 10625 10630 10635 Gln Gly Leu Asp Leu Thr Val Ala Thr Ile Phe Gln Ser Pro Arg 10640 10645 10650 Leu Glu Gln Met Ala Ser Ala Ile Val Glu Asp Glu Leu Thr Val 10655 10660 10665 Tyr Ser Glu Ile Arg Pro Phe Asp Met Leu Pro Ala Gly Glu Ser 10670 10675 10680 Ser Thr Ile Leu Ala Glu Ala Arg Asp Gln Cys Ser Leu Pro Asp 10685 10690 10695 Ser Ala Ile Ile Glu Asp Ser Tyr Pro Cys Thr Lys Leu Gln Glu 10700 10705 10710 Gly Leu Met Ala Leu Ser Val Lys Gln Pro Gly Ser Tyr Val Ala 10715 10720 10725 Lys Tyr Leu Tyr Arg Leu Pro Asp His Val Asp Val Ala Arg Phe 10730 10735 10740 Lys Ser Ala Trp Lys Gln Thr Met His Ile Cys Ala Ser Leu Arg 10745 10750 10755 Ser Arg Ile Ile Asn Thr Ser Ala Lys Ser Thr Phe Gln Ile Val 10760 10765 10770 Leu Asn Pro Glu Ser Ser Ser Glu Pro Leu Pro Tyr His Asp Leu 10775 10780 10785 Gln Ala Val Leu Arg Tyr Ala Gln Thr Ile Lys Met Thr Tyr Gly 10790 10795 10800 Ser Ala Leu Cys Gln Phe Ala Phe Val Glu Asp Glu Gln Arg Ser 10805 10810 10815 Val Phe Phe Phe Trp Ala Met His His Thr Val Phe Asp Gly Leu 10820 10825 10830 Ser Thr Gln Val Ile Leu Gly Ile Leu His Lys Ala Tyr Phe Gly 10835 10840 10845 Leu Glu Thr Pro Val Leu Thr Pro Tyr Ser Arg Phe Ile Gln Tyr 10850 10855 10860 Leu Leu Gln Ile Asp Glu Glu Ala Ala Ser Ala Tyr Trp Arg Asp 10865 10870 10875 Ala Leu His Asp Ala Lys Pro Ala Gln Leu Pro Ser Leu His Asn 10880 10885 10890 Thr His Asp Lys Val Val Ala Thr Cys Val Leu Glu Thr Pro Ile 10895 10900 10905 Gly Phe Val Asp Ala Ser Lys Leu Asn Val Thr Leu Ala Thr Val 10910 10915 10920 Ile Arg Ser Ala Trp Ala Ile Val Leu Ala Arg Tyr Cys Asp Thr 10925 10930 10935 Asp Asp Val Cys Phe Gly Ile Ala Thr Ser Gly Arg Gln Ala Pro 10940 10945 10950 Val Pro Gly Ile Val Asp Met Val Gly Pro Val Ile Ala Thr Val 10955 10960 10965 Pro Val Arg Val Arg Leu Asp Arg Gln Gln Pro Val Ser Asp Phe 10970 10975 10980 Leu Gln Ser Val Gln Gln Gly Ala Val Gly Met Ile Pro Tyr Glu 10985 10990 10995 Gln Phe Gly Leu Gln Asn Ile Thr Lys Leu Ser Arg Asp Ala Tyr 11000 11005 11010 Glu Ala Cys Gln Phe Ser Ser Leu Leu Val Val Gln Pro Ile Arg 11015 11020 11025 His Ile Ala Asn Ser Glu Glu Ser Lys Glu Leu Leu Ser Ala Ala 11030 11035 11040 Glu Val Thr Glu Gly Leu Ser Asp Ser Leu Asn Asn Phe Phe Asn 11045 11050 11055 Tyr Pro Leu Ile Val Gln Gly His Leu Tyr Gly Asp Lys Val Lys 11060 11065 11070 Ile Ala Val Ala Tyr Asp Arg Asn Val Leu Thr Glu Arg Gln Val 11075 11080 11085 Gln Ala Leu Ser Glu Gln Leu Gly His Val Ile His Gln Leu Ala 11090 11095 11100 Ser Gly Ala Gly Thr Ser Leu Glu Ser Ile Leu Ile Ala Ser Ser 11105 11110 11115 His Asp Leu Glu Leu Ala Leu Ala Val Asn Ser Glu Val Pro Glu 11120 11125 11130 Ile Ile Ser Ser Cys Val His Glu Leu Ile Asp Lys Gln Ala Gln 11135 11140 11145 Ile Ser Pro Gln Ala Pro Ala Ile Leu Ala Cys Asp Ala Glu Leu 11150 11155 11160 Thr Tyr Ser Asp Leu Ala Ala Ala Ser Asp Arg Leu Ala Tyr His 11165 11170 11175 Leu Ile His Ser His Gly Val Lys Pro Gly Asp Phe Val Ser Val 11180 11185 11190 Cys Phe Gly Lys Ser Ala Trp His Phe Val Ser Ile Phe Ala Ile 11195 11200 11205 Asn Lys Ala Gly Ala Ala Trp Val Pro Leu Glu Pro Ser Gln Pro 11210 11215 11220 Glu Ala Arg Leu Arg Gln Ile Val Leu Gln Thr Lys Ala Arg Leu 11225 11230 11235 Ala Leu Val Ser Pro Ser Asn Ala Glu Leu Cys Ala Lys Leu Val 11240 11245 11250 Thr Asp Val Val Glu Val Thr Ala Glu Leu Asp Gln Gln Leu Gly 11255 11260 11265 Arg Ser Val Ser Glu Pro Phe Lys Pro Leu Ala Ile Ser Pro Arg 11270 11275 11280 Ser Pro Ala Tyr Ile Leu Phe Thr Ser Gly Ser Thr Gly Thr Pro 11285 11290 11295 Lys Gly Phe Val Ile Glu His Gln Ser Leu Ser Thr Ser Gln Thr 11300 11305 11310 Ala Leu Ala Thr Arg Leu Lys Met Thr Ser Ser Val Arg Ile Met 11315 11320 11325 Gln Phe Ala Ser Tyr Val Phe Asp Met Ser Leu Gly Glu Ser Ile 11330 11335 11340 Gly Pro Leu Ile Ser Gly Ala Cys Val Cys Ile Pro Ser Asp Arg 11345 11350 11355 Glu Arg Met Glu Asn Ile Ala Thr Phe Ile Arg Lys Arg Gln Ile 11360 11365 11370 Asn Trp Ala Phe Leu Thr Pro Val Phe Ala Arg Thr Ile Gln Pro 11375 11380 11385 Ala Asp Val Pro Ser Leu Glu Leu Leu Leu Leu Gly Gly Glu Ala 11390 11395 11400 Val Pro Gln Asp Leu Cys Leu Thr Trp Phe Gly Lys Val Arg Leu 11405 11410 11415 Ile Asn Ala Trp Gly Pro Ala Glu Ala Cys Val Ile Ser Ala Val 11420 11425 11430 His Glu Trp Thr Ser Ala Glu Thr Ser Ser Leu Val Ile Gly Arg 11435 11440 11445 Pro Val Gly Gly Phe Cys Trp Ile Val Asp Pro Glu Met Pro Gln 11450 11455 11460 Ser Leu Ala Pro Phe Gly Thr Met Gly Glu Val Ala Ile Gln Gly 11465 11470 11475 Pro Thr Leu Leu Arg Glu Tyr Leu Asp Glu Pro Glu Arg Thr Lys 11480 11485 11490 Ala Ala Leu Ile Pro Arg Pro Ser Trp Ala Pro Gln Pro Asp Ala 11495 11500 11505 Gln His Trp Asn Arg Leu Tyr Arg Thr Gly Asp Leu Cys Phe Tyr 11510 11515 11520 Asn Ser Asp Gly Asn Leu Val Phe Gly Gly Arg Arg Asp Thr Gln 11525 11530 11535 Val Lys Ile Arg Gly Phe Arg Val Glu Ile Gly Asp Ile Glu His 11540 11545 11550 His Ile Arg Asp Lys Leu Asp Asp Val Cys Glu Ala Ala Val Glu 11555 11560 11565 Val Leu Lys Ser Thr Thr Gly Ala Ser Leu Ile Ala Phe Val Ser 11570 11575 11580 Phe Lys Ser Gly Ile Glu Gln Pro Asp Ile Glu Ser Ser Gly Ser 11585 11590 11595 Ser Gly Glu Val Phe Leu Gln Pro Thr Ser Arg Met Gln Lys Ala 11600 11605 11610 Phe Arg Ala Leu Glu Gly Arg Leu Lys Ala Thr Leu Pro Pro Tyr 11615 11620 11625 Met Val Pro Ser Ile Phe Val Pro Cys Lys Tyr Leu Pro Ser Thr 11630 11635 11640 Thr Ser Asp Lys Leu Asp Arg Lys Lys Leu Lys Ala Met Ala Ser 11645 11650 11655 Ser Leu Ser Leu Glu Asp Leu Ser Lys Tyr Thr Leu Ser Asp Leu 11660 11665 11670 Glu Lys Gln Gly Pro Glu Thr Glu Met Glu Lys Arg Ile Gln Leu 11675 11680 11685 Ile Trp Ala Glu Leu Leu Asn Val Pro Ala Thr Ser Ile Gly Arg 11690 11695 11700 Asp Asp Ser Phe Leu Gln Ile Gly Gly Asp Ser Ile Ile Ala Ile 11705 11710 11715 His Phe Val Thr Ala Ala Gln Asn Ser Asn Ile Gly Leu Ser Val 11720 11725 11730 Ala Asp Ile Phe Asp Asp Pro Arg Leu Leu Ala Val Ala Ala Lys 11735 11740 11745 Ala Ile Ser Leu Thr Arg Ser Gly Gln Ala Ala Glu Ile Pro Gln 11750 11755 11760 Phe Gly Leu Ile Asp Glu Gln Thr Gln Gln Leu Leu Ser Ser Gln 11765 11770 11775 Asp Leu Arg Gln Asn Tyr His Leu Ala Asp Asp Val Val Leu Arg 11780 11785 11790 Asp Ala Tyr Pro Ser Thr Lys Met Gln Glu Gly Leu Leu Ala Leu 11795 11800 11805 Thr Glu Lys Gln Pro Gly Ser Tyr Val Ala Lys Phe Val Tyr Arg 11810 11815 11820 Leu Gly Arg Thr Val Asp Val Leu Arg Phe Arg Ser Ala Phe Glu 11825 11830 11835 Asp Met Val Lys Leu Cys Asp Asn Leu Arg Thr Arg Val Val Met 11840 11845 11850 Val Gly Ser Gln Thr Val Gln Leu Val Leu Glu Asn Asp Phe Ala 11855 11860 11865 Trp Asp Glu Val Gln Gly Gln Glu Leu Gln Ser Tyr Met His Ala 11870 11875 11880 Leu Gly Ser Ser Asn Met Ala Tyr Gly Ser Arg Leu Ser Arg Gly 11885 11890 11895 Ala Ile Val Met Asp Gly Asp Glu Val Tyr Phe Val Trp Ala Leu 11900 11905 11910 His His Ser Ile Phe Asp Gly Trp Thr Met Arg Leu Met Met Asp 11915 11920 11925 Val Leu His Ser Met Tyr Asp Gly Arg Ser Pro Pro Ser Leu Gln 11930 11935 11940 Ser Tyr Asn Arg Phe Val Ala Tyr Val Gly Asn Leu Asn His Glu 11945 11950 11955 Glu Thr Arg Asn Tyr Trp Gly Ala Gln Leu Asp Gly Ala Ser Arg 11960 11965 11970 Ala Ala Tyr Pro Pro Leu Ser Lys Thr Ser Ser Asn Ser Ser Lys 11975 11980 11985 Ser Leu Glu Arg Gly Met Gln Leu Pro Asn Met Thr Asp Leu Ser 11990 11995 12000 Ala Thr Lys Ala Thr Val Ile Arg Ala Ala Trp Ala Met Leu Leu 12005 12010 12015 Ala Arg Tyr Cys Glu Thr Asp Asp Val Cys Phe Gly Ala Thr Val 12020 12025 12030 Ser Gly Arg Gln Ala Pro Val Pro Gly Leu Pro Asp Met Pro Gly 12035 12040 12045 Pro Ala Val Ala Thr Val Pro Ile Arg Val Arg Leu Asp Lys His 12050 12055 12060 Arg Ser Val Ser Asp Tyr Leu Asp Thr Ile Gln Ser Gln Ala Leu 12065 12070 12075 Lys Met Ile Pro Tyr Glu Gln Phe Gly Leu Gln Glu Ile Gln Lys 12080 12085 12090 Ile Ser Pro Arg Ala Gln Glu Val Cys Asn Phe Ser Ser Leu Leu 12095 12100 12105 Val Val Gln Pro Met Gln His Leu Ile Asn Gly Glu His Ala Leu 12110 12115 12120 Leu Gln Pro Val Glu Val Glu Ser Gln Glu Glu Ser Ser Leu Gln 12125 12130 12135 Asn Tyr Phe Thr Tyr Pro Leu Val Ile Gln Gly His Val Met Gly 12140 12145 12150 Glu Asp Ile Lys Leu Met Phe Ile Tyr Asp Ser Asn Val Leu Pro 12155 12160 12165 Glu Ser Gln Val Leu Ala Ile Ser His Gln Met Glu His Ile Met 12170 12175 12180 Arg Gln Leu Ile Ala Lys Pro Gln Ser Leu Leu Gly Asp Leu Ser 12185 12190 12195 Leu Thr Cys Asp Trp Asp Val Lys Phe Ala Glu Lys Ala Asn Arg 12200 12205 12210 Glu Asp Pro Pro Glu Ile Ile Asp Ser Cys Leu His Asp Leu Ile 12215 12220 12225 Glu Cys Gln Ala Glu Ile Arg Pro Asp Ala Val Ala Ile Leu Gly 12230 12235 12240 Trp Asp Lys Val Leu Thr Tyr Asp Glu Leu Asn Lys Ala Ala Asn 12245 12250 12255 Arg Leu Ala His His Leu Val Met Asp Ile Gly Val Lys Ala His 12260 12265 12270 Asp Leu Val Gln Val Cys Phe Thr Lys Ser Ala Trp Tyr Ala Val 12275

12280 12285 Ala Ile Leu Ala Ile Asn Lys Val Gly Ala Ala Trp Val Pro Ile 12290 12295 12300 Asp Pro Ser His Pro Leu Gln Arg His Gln Gln Val Thr Ala Gln 12305 12310 12315 Thr Lys Ala Arg Val Ala Leu Ala Ser Gln Asp Asn Val Glu Arg 12320 12325 12330 Cys Ser Gln Leu Val Thr Ser Val Val Val Val Ser Ser Ser Leu 12335 12340 12345 Asp Ser Asp Leu Cys Lys Lys Gly Phe Ser Ser Ser Gln Gly Pro 12350 12355 12360 Asp Val Leu Val Thr Pro Lys His Ala Ala Tyr Val Leu Phe Thr 12365 12370 12375 Ser Gly Ser Thr Gly Val Pro Lys Gly Leu Ile Met Glu His Gly 12380 12385 12390 Ala Leu Cys Thr Ser Gln Met Ala Ala Gly Lys Arg Phe Gly Phe 12395 12400 12405 Thr Pro Ser Val Lys Ile Leu Gln Phe Ala Ala Tyr Val Phe Asp 12410 12415 12420 Tyr Ser Ile Ser Glu Met Leu Ala Ala Met Met Tyr Gly Ala Cys 12425 12430 12435 Val Cys Ile Pro Ser Glu Glu Asp Arg Met Asn Arg Leu Lys Glu 12440 12445 12450 Tyr Val Asn Asp Thr Gly Ile Asn Trp Leu Phe Leu Thr Pro Ser 12455 12460 12465 Phe Leu Gln Thr Leu Arg Pro Glu Asp Val Pro Ser Val Glu Leu 12470 12475 12480 Val Ala Leu Gly Gly Glu Ala Val Pro Arg Ala Leu Phe Glu Glu 12485 12490 12495 Trp Ile Gly Lys Val Arg Phe Phe Asn Ala Trp Gly Pro Ser Glu 12500 12505 12510 Thr Cys Val Met Ser Ala Met His Glu Trp Arg Ser Ser Glu Glu 12515 12520 12525 Ser Ala Leu Thr Ile Gly Lys Pro Val Gly Gly Phe Cys Trp Ile 12530 12535 12540 Val Asp Pro Glu Asp Pro Trp Lys Leu Ala Pro Thr Gly Thr Val 12545 12550 12555 Gly Glu Leu Ile Val Gln Gly Pro Thr Leu Leu Arg Glu Tyr Leu 12560 12565 12570 Gly Asp Ala Glu Lys Ser Lys Ala Ala Ile Leu Glu Gly Arg Pro 12575 12580 12585 Asp Trp Ala Met Tyr Pro Asp Thr Gln His Trp Thr Arg Phe Tyr 12590 12595 12600 Lys Ser Gly Asp Leu Cys Ser Tyr Asn Pro Asp Gly Thr Ile Arg 12605 12610 12615 Phe Tyr Ser Arg Lys Asp Thr Gln Val Lys Ile Arg Gly Leu Arg 12620 12625 12630 Val Glu Leu Gly Glu Val Glu Tyr Arg Ile Lys Glu Thr Phe Pro 12635 12640 12645 Glu Ala His Gln Val Val Val Asp Val Phe Lys Ser Gly Ser Val 12650 12655 12660 Ser Asn Leu Val Ala Tyr Phe Cys Phe Gly Asp Ala Thr Val Asp 12665 12670 12675 Val Ser Ser Asn Ser Leu Asp Asp Ile Phe Met Val Leu Gly Glu 12680 12685 12690 Glu Thr Gln Gln Arg Leu Ala Thr Met Val Gly Glu Leu Lys Val 12695 12700 12705 Leu Leu Pro Glu Tyr Met Val Pro Ala Leu Phe Ile Gln Cys Lys 12710 12715 12720 His Met Pro Thr Ala Thr Ser Gly Lys Leu Asp Arg Lys Thr Leu 12725 12730 12735 Arg Gly Leu Thr Ser Ser Leu Thr Lys Asp Gln Leu Ala Ala Tyr 12740 12745 12750 Ser Leu Val Asn Ser Lys Lys Thr Met Pro Gln Thr Pro Met Glu 12755 12760 12765 Gly Lys Leu Gln Ala Ile Trp Ala Asp Val Leu Gly Ile Pro Met 12770 12775 12780 Glu Thr Ile Gly Arg Asp Asp Ser Phe Leu Ser Ile Gly Gly Asp 12785 12790 12795 Ser Ile Ala Ala Ile Arg Leu Val Ala Ala Ala Arg Asp Gln Gly 12800 12805 12810 Val Ala Leu Thr Val Ser Gln Ile Phe Glu Asp Gly Arg Leu Leu 12815 12820 12825 Ser Ile Ala Ser Lys Ala Ser Phe Ile Ser Asp Gly Ser Ser Gln 12830 12835 12840 Ala Phe Thr Pro Ile Glu Pro Phe Ala Leu Leu Asp Glu Pro Gln 12845 12850 12855 Arg Asp Met Ile Thr Glu Ser Ala Glu Glu Phe Gly Leu Glu Leu 12860 12865 12870 Ser Arg Asp Met Ala Val Glu Asp Cys Tyr Pro Cys Ser Lys Met 12875 12880 12885 Gln Glu Gly Leu Met Ala Leu Ala Val Lys Gln Pro Gly Ser Tyr 12890 12895 12900 Ile Ala Lys Tyr Asn Tyr Arg Ile Pro Ser His Val Asp Val Ser 12905 12910 12915 Leu Leu Lys Ala Ala Trp Glu Gln Ile Val Asn Ser Phe Pro Asn 12920 12925 12930 Leu Arg Thr Arg Ile Ile Arg Leu Gly Ala Ile Ser Leu Gln Val 12935 12940 12945 Val Val Lys Gly Asp Thr Val Trp Asp Ser Thr Glu Arg Met Thr 12950 12955 12960 Leu Arg Ser Tyr Leu Gln Gln Thr Arg Thr Met Glu Met Gly Tyr 12965 12970 12975 Gly Ser Arg Leu Cys Arg Ser Ala Ile Phe Lys Asp Gly Asp Glu 12980 12985 12990 Val Tyr Phe Ser Phe Asn Leu His His Ala Val Tyr Asp Gly Trp 12995 13000 13005 Thr Leu Ser Ile Ile Leu Glu Glu Phe His Arg Ala Tyr Lys Gly 13010 13015 13020 Leu Glu Pro Ala Thr Thr Val Pro Tyr Ser His Phe Ile Lys Tyr 13025 13030 13035 Thr Met Glu Leu Asp His Glu Ala Ala Gly Asp Phe Trp Ala Arg 13040 13045 13050 Gln Leu Glu Asn Ala Arg Lys Ala Thr Phe Pro Ser Val Pro Ile 13055 13060 13065 Thr Ser Thr Ser Lys Pro Glu Ala Ser Arg Thr Met Thr Ala Glu 13070 13075 13080 Leu Glu Leu Ser Lys Ser Asn Thr Thr Ile Thr Thr Ala Thr Ile 13085 13090 13095 Val Arg Ala Ala Trp Ala Leu Val Leu Ala Arg Tyr Cys Asp Ser 13100 13105 13110 Thr Asp Val Cys Phe Gly Ala Thr Val Ser Gly Arg Gln Ala Ser 13115 13120 13125 Leu Pro Gly Leu Thr Gln Met Pro Gly Pro Val Ile Ala Thr Ile 13130 13135 13140 Pro Val Arg Ile His Leu Asp His Asp Gln Pro Thr Thr Lys Phe 13145 13150 13155 Leu Glu Glu Val Gln Thr Arg Ala Ser Asp Ala Ile Pro Phe Glu 13160 13165 13170 Gln Phe Gly Leu Gln Ser Ile Arg Lys Leu Asn Pro Asp Ala Asp 13175 13180 13185 Glu Ala Cys Asp Phe Thr Ser Leu Leu Val Ile Gln Pro Leu Lys 13190 13195 13200 Met Leu Ser His Leu Glu Asn Thr Gly Glu Asp Ala Leu Leu Val 13205 13210 13215 Gly Val Glu Asp Thr Asp Asp Ser Ala Asp Gly Met Gln Asn Tyr 13220 13225 13230 Phe Ser Tyr Pro Leu Val Leu Gln Ala His Leu Ser Asp Asp Phe 13235 13240 13245 Met Arg Ile Val Leu Ile Tyr Asn Pro His Cys Ile Ala Glu Gln 13250 13255 13260 Gln Ile Val Ala Leu Ser Glu Gln Leu Lys His Val Ile Ala Gln 13265 13270 13275 Leu Ala Glu Ser Lys Pro Ser Gln Met Leu Arg Asp Val Ser Leu 13280 13285 13290 Val Ser Gln Trp Asp Ile Glu Gln Ser Arg Lys Phe Asn Val Asp 13295 13300 13305 Thr Pro Glu Ile Val Asp Ser Cys Phe His Thr Leu Val Glu Asp 13310 13315 13320 Gln Ala Ala Gln Arg Pro Asp Ala Met Ala Ile Arg Ser Trp Asp 13325 13330 13335 Gly Asp Phe Ser Tyr Ala Gln Leu Asn Gln Ala Ala Asn Arg Leu 13340 13345 13350 Ala Asn Tyr Leu Val Gln Thr His Glu Ile Lys Thr Asn Asp Leu 13355 13360 13365 Ile His Val Cys Phe Glu Lys Ser Val Trp His Phe Val Ser Ile 13370 13375 13380 Leu Ala Ile Asn Lys Thr Gly Ala Ala Trp Val Pro Leu Asp Pro 13385 13390 13395 Ser His Pro Leu Gln Arg Leu Gln Gln Val Val Ser Gln Thr Arg 13400 13405 13410 Ala Lys Phe Ala Leu Cys Ser Pro Asp Asn Ser Asp Leu Cys Ser 13415 13420 13425 Thr Leu Val Glu Ser Ala Ile Gln Ile Thr Pro Glu Phe Asp Lys 13430 13435 13440 Gln Leu Gln Lys Gln Val Asn Ser Arg Gln Gly Pro Thr Glu Arg 13445 13450 13455 Ala Ser Ser Gly Asp Ile Ala Tyr Val Leu Phe Thr Ser Gly Ser 13460 13465 13470 Thr Gly Thr Pro Lys Gly Leu Val Met Gln His Gly Ser Val Cys 13475 13480 13485 Thr Ser Gln Lys Ala Ile Ala Lys Arg Leu Arg Leu Gly Pro Glu 13490 13495 13500 Val Arg Met Leu Gln Phe Ala Ala Phe Val Phe Asp Leu Ser Ile 13505 13510 13515 Gly Glu Ile Val Ala Pro Leu Ile Thr Gly Ala Cys Leu Cys Ile 13520 13525 13530 Pro Ser Glu His Ala Arg Met Asn Asp Leu Ser Lys Phe Met Gln 13535 13540 13545 Asp Met Asn Val Asn Trp Ala Phe Leu Thr Pro Ser Phe Val Arg 13550 13555 13560 Thr Leu Asn Pro Asp Asp Val Pro Gly Leu Glu Val Leu Leu Leu 13565 13570 13575 Ala Gly Glu Ala Val Pro Arg Asp Val Leu Thr Ala Trp Phe Gly 13580 13585 13590 Lys Val Arg Arg Leu Ile Asn Gly Trp Gly Pro Ala Glu Thr Cys 13595 13600 13605 Val Phe Ser Thr Leu His Glu Trp Lys Ser Val Asp Glu Ser Pro 13610 13615 13620 Leu Thr Val Gly Arg Pro Val Gly Gly Phe Cys Trp Ile Val Asp 13625 13630 13635 Pro Asp Ser Gly Phe Leu Ala Pro Ile Gly Thr Val Gly Glu Val 13640 13645 13650 Val Ile Gln Gly Pro Thr Leu Leu Gln Glu Tyr Leu Ala Asp Pro 13655 13660 13665 Glu Arg Thr Asn Thr Ser Ile Leu Pro Ala Ala Glu Trp Ala Pro 13670 13675 13680 Arg Pro Asp Glu Ser His Trp Asn Arg Phe Tyr Lys Ser Gly Asp 13685 13690 13695 Leu Cys Arg Tyr Asn Ala Asp Gly Thr Ile Glu Phe Ser Thr Arg 13700 13705 13710 Lys Asp Thr Gln Ile Lys Ile Arg Gly Leu Arg Val Glu Leu Ser 13715 13720 13725 Glu Ile Glu Tyr Asn Ile Gln Gln Ser Leu Ile Gly Val Arg Gln 13730 13735 13740 Val Ala Val Asp Val Val Arg Gly Asp Asn Gly Ser Ser Leu Val 13745 13750 13755 Ala Tyr Ile Cys Phe Thr Asp Glu Thr Lys Thr Ala Gly Val Lys 13760 13765 13770 Thr Asp Ala Ser Glu Thr Leu Phe Leu Ser Thr Asp Glu Ser Leu 13775 13780 13785 Gln Asn Gln Leu Ile Ala Leu Val Gly Glu Leu Gly Ile Ala Leu 13790 13795 13800 Pro Arg Tyr Met Ile Pro Thr Leu Phe Ile Pro Cys Ala Phe Met 13805 13810 13815 Pro Phe Ile Ala Ser Thr Lys Leu Asp Arg Lys Leu Leu Gln Thr 13820 13825 13830 His Leu Ser Thr Leu Asp Arg Asp Gln Leu Ala Met Tyr Ser Leu 13835 13840 13845 Leu His Ser Glu Lys Arg Gln Pro Glu Thr Glu Met Glu Gln Arg 13850 13855 13860 Leu Gln Leu Ile Trp Ala Glu Ile Met Asn Leu Pro Met Glu Ser 13865 13870 13875 Ile Gly Arg Asp Asp Thr Phe Phe Gln Leu Gly Gly Asp Ser Ile 13880 13885 13890 Met Ala Ile Tyr Leu Val Ser Thr Ala Lys Glu Glu Gly Ile Thr 13895 13900 13905 Leu Thr Val Gln Asp Val Phe Asp Asp Pro Arg Leu Leu Ala Val 13910 13915 13920 Ala Ala Lys Ala Val Leu Ser Gln Asp Gly Met Glu Pro Ala Asp 13925 13930 13935 Ser Pro Pro Glu Pro Phe Ser Leu Leu Pro Glu Ala Gln Lys Arg 13940 13945 13950 Leu Val Leu Gly Glu Asp Ala Arg Lys Leu Cys Gly Leu Ala Lys 13955 13960 13965 Asp Arg Thr Ile Thr Asp Ala Tyr Pro Cys Ser Ser Leu Gln Glu 13970 13975 13980 Gly Leu Ile Ala Leu Thr Ala Lys Gln Pro Gly Ser Tyr Val Ala 13985 13990 13995 Thr Tyr Ala His His Leu Ser Ser Phe Val Asp Ile Pro Met Phe 14000 14005 14010 Arg Ala Ala Trp Asp Ser Val Val Asp Ile Cys Asp Asn Leu Arg 14015 14020 14025 Thr Arg Ile Val Val Leu Asp Gly Val Met Thr Gln Ile Val Leu 14030 14035 14040 Asp Arg Asp Ser Gln Trp Val Pro Ala Asp Asn Glu Thr Leu Glu 14045 14050 14055 Ser Met Thr Gly Ser Ser Arg Asn Leu Lys Met Gly Tyr Gly Thr 14060 14065 14070 Pro Leu Cys Trp Tyr Ser Ile Val Ser Glu Lys Gly Glu Asn Tyr 14075 14080 14085 Phe Val Trp Ser Ala His His Ser Ile Tyr Asp Gly Trp Thr Met 14090 14095 14100 Lys Val Met Phe Thr Ala Leu Phe Ser Ala Tyr Gln Gly Met Tyr 14105 14110 14115 Ala Pro Glu Val Arg Pro Phe Ser Ser Phe Ile Lys Ser Val Lys 14120 14125 14130 Glu Leu Asp Asn Asp Lys Val Ala Ser Tyr Trp Thr Gln Glu Leu 14135 14140 14145 Ala Gly Ala Lys Arg Ala Ser Phe Pro Ser Arg Arg Thr Ala Pro 14150 14155 14160 Gly Ile Met Glu Ser Lys Arg Phe Ser Ser Thr Ile Pro Phe Ser 14165 14170 14175 Arg Ser Met Lys Thr Ser Ile Thr Gln Ala Ser Ile Leu Arg Ala 14180 14185 14190 Ala Trp Ala Ile Val Leu Ala Arg Tyr Cys Asp Ser Ser Glu Ala 14195 14200 14205 Val Phe Gly Ala Thr Val Ser Gly Arg Gln Ala Pro Ile Pro Gly 14210 14215 14220 Ala Glu Met Ile Ser Gly Pro Met Ile Ala Thr Val Pro Ile Arg 14225 14230 14235 Ala Arg Leu Asp Asn Gln Ala Pro Ile Ser Arg Phe Val Gln Asp 14240 14245 14250 Ile Gln Ser Leu Ser Thr Ser Met Ile Pro Tyr Glu Gln Tyr Gly 14255 14260 14265 Leu Gln Asn Ile Ala Lys Val Ser Ala Glu Ala Arg Glu Val Cys 14270 14275 14280 Asp Phe Ser Ser Leu Leu Val Val Gln Pro Pro Ala His Gly Ala 14285 14290 14295 Gly Asp Asp His Gly Glu Ser Ile Phe Val Val Asp Ala Ser Ala 14300 14305 14310 Ser Asp Leu Thr Met Asp Ser Met Asp Gly Tyr Phe Asn Tyr Pro 14315 14320 14325 Leu Val Ile Ile Ser Ser Leu Tyr Pro Glu Glu Phe Arg Leu Asn 14330 14335 14340 Phe Phe Tyr Asp Ser Thr Val Leu Ser Glu Ala Arg Val Ile Ala 14345 14350 14355 Leu Ser Ser His Leu Asn His Val Ile Gln Gln Leu Val Ala Lys 14360 14365 14370 Glu Ala

Val Asn Ala Pro Leu Ser Ser Val Ser Leu Leu Ser Pro 14375 14380 14385 Trp Asp Leu Gln Gln Ala Val Glu Ser Ser Arg Leu Glu Pro Ser 14390 14395 14400 Ser Asn Thr Cys Thr His Trp Ala Ile Gln Glu Asn Ile Gln Ser 14405 14410 14415 Arg Pro Asp Asp Val Ala Ile Ala Ser Trp Asp Ala Glu Leu Thr 14420 14425 14430 Tyr Ser Gln Val Gly Thr Phe Ala Ser Arg Leu Ala Ile Glu Leu 14435 14440 14445 Gln Glu Arg Gly Val Gly Pro Glu Thr Leu Val Leu Leu Cys Phe 14450 14455 14460 Pro Lys Ser Ala Trp Ala Val Ile Ala Met Val Ala Ile Glu Met 14465 14470 14475 Ala Gly Gly Ala Phe Val Pro Leu Asp Pro Ala Ala Pro Ala Ala 14480 14485 14490 Arg Leu Lys Gly Ile Ile Glu Asp Thr His Ala Thr Leu Ala Met 14495 14500 14505 Ser Ser Pro Thr Ser Gly Lys Val Leu Glu Gly Leu Gly Val Asp 14510 14515 14520 Val Phe Phe Val Asp Glu Glu Met Leu Ser Gly Leu Pro Ser Pro 14525 14530 14535 Thr Lys Pro Val Ile Ser Asn Val Arg Pro Asp Asn Ala Ser Val 14540 14545 14550 Ile Leu Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Met Val 14555 14560 14565 Ile Glu His Arg Asn Leu Val Ser Ser Ser Asp Ala Tyr Gly Asn 14570 14575 14580 Leu Leu Gly Ile Gly Pro Gly Thr Arg Val Phe Gln Phe Ser Ala 14585 14590 14595 Tyr Thr Phe Asp Val Gly Ile Leu Asp Cys Leu Val Ser Leu Met 14600 14605 14610 Arg Gly Ala Cys Leu Cys Ile Pro Ser Asp His Asp Arg Met Asn 14615 14620 14625 Asp Leu Ala Gly Ala Met Arg Ser Ser Lys Ala Asn Trp Val Phe 14630 14635 14640 Leu Thr Pro Thr Val Ala Asp Leu Leu Ser Pro Thr Asp Ile Pro 14645 14650 14655 Asp Met Lys Val Val Cys Leu Gly Gly Glu Ala Ile Ser Lys Lys 14660 14665 14670 Cys Ala Asp Arg Trp Val His His Val Asp Leu His Gly Leu Tyr 14675 14680 14685 Gly Pro Ala Glu Ala Ser Ile Cys Ala Trp Asn Pro Thr Val Gly 14690 14695 14700 Lys Leu Gly Arg Ser Thr Asn Leu Gly Arg Pro Ile Ser Ser Ala 14705 14710 14715 Phe Trp Val Val Glu Pro Gly Asn Leu Arg Gln Leu Val Pro Val 14720 14725 14730 Gly Cys Val Gly Glu Leu Leu Ile Glu Gly Pro Met Leu Ala Arg 14735 14740 14745 Gly Tyr Leu Asn Val Ser Pro Glu Val Ala Ala Ser Trp Met Glu 14750 14755 14760 Asp Val Asp Trp Leu Pro Gly Gly Arg Lys Arg Val Tyr Arg Thr 14765 14770 14775 Gly Asp Leu Val Arg Arg Asn Ala Asp Gly Thr Phe Asp Tyr Met 14780 14785 14790 Gly Arg Lys Asp Thr Gln Val Lys Leu His Gly Gln Arg Val Glu 14795 14800 14805 Leu Gly Glu Ile Glu Ser Arg Ile His Glu Leu Leu Pro Asp Asn 14810 14815 14820 Met Ala Val Ile Val Asp Ile Leu Lys Ala Asp Asp Glu Asn Ala 14825 14830 14835 His Asp Ile Leu Leu Ala Phe Leu Trp Tyr Thr Asp Asp Glu Met 14840 14845 14850 Thr Ser Arg Ser Glu Ala Leu Gln Leu Met His Thr Val Ser Glu 14855 14860 14865 Gln Ala Gln Ser Val Ile Ser Arg Leu Asp Leu Ala Leu Glu Glu 14870 14875 14880 Ser Leu Pro Ser Tyr Met Ile Pro Ser Ser Tyr Leu Ile Phe Glu 14885 14890 14895 Gly Lys Pro Glu Gln Thr Thr Ser Gly Lys Val Asn Arg Arg Ser 14900 14905 14910 Phe Val Glu Leu Gly Arg Ser Val Ser Val Gln Asp Arg Leu Arg 14915 14920 14925 Phe Thr Pro Ser Ala Ser Asp Tyr Val Ser Pro Thr Thr Pro Met 14930 14935 14940 Glu Leu Glu Leu Gln Ser Leu Trp Ala Gln Val Leu Lys Ile Ser 14945 14950 14955 Asp Val Ser Ala Ile Gly Lys His Asp Ser Phe Leu His Leu Gly 14960 14965 14970 Gly Asp Ser Ile Ser Ala Ile Glu Leu Val Ser Phe Ala Gln Arg 14975 14980 14985 Gln Asn Ile Gly Leu Thr Val Ala Met Ile Phe Asn Tyr Pro Arg 14990 14995 15000 Leu Ser Ala Met Ala Glu Ala Ile Gln Leu Asp Ala Ser Pro Ser 15005 15010 15015 Ser Thr Ala His Glu Val Glu Arg Phe Gly Leu Ile Pro Thr Ser 15020 15025 15030 Asp Lys Gln Ser Ala Leu Arg Ala Val Gln Thr Gln Cys Lys Leu 15035 15040 15045 Ser Asp Leu Ala Glu Ile Glu Asp Ile Tyr Pro Cys Thr Asp Leu 15050 15055 15060 Gln Thr Gly Leu Met Ala Leu Thr Ile Ser Gln Pro Gly Ser Tyr 15065 15070 15075 Ile Ala Lys His Val Tyr Arg Leu Ala Pro His Val Asp Ile Asp 15080 15085 15090 Arg Phe Lys Leu Ala Trp Glu Gln Thr Ile Arg Tyr Cys Ser Asn 15095 15100 15105 Leu Arg Thr Arg Ile Val Leu Ser Gly Ser Thr Ala Val Gln Ala 15110 15115 15120 Val Ile Gln Glu Pro Val His Trp Pro Ser Thr Tyr Thr Asp Leu 15125 15130 15135 Arg Ser Phe Leu Leu Ser Lys Glu Asn Cys Thr Met Thr Tyr Gly 15140 15145 15150 Ser Pro Leu Cys Arg Phe Ala Ile Ile Lys Gln Gly Ser Asp Gln 15155 15160 15165 Tyr Phe Ala Val Asn Ile His His Thr Ile Phe Asp Gly Trp Thr 15170 15175 15180 Leu Ser Ile Val Leu Arg Thr Leu Leu Ala Met Tyr Ser Gln Thr 15185 15190 15195 Glu Pro Pro Ser Ile Leu Pro Tyr Thr Ser Phe Val Lys Tyr Ile 15200 15205 15210 Met Glu Leu Asp Gln Glu Asn Ser Arg Asp Tyr Trp Ser Thr Gln 15215 15220 15225 Leu Arg Gly Val Lys Arg Gly Thr Phe Pro Val Val Ala Thr Gln 15230 15235 15240 Asn Lys Pro Ser Ser Thr Thr Gln Lys Ile Ala Gly Met Leu Asp 15245 15250 15255 Lys Thr Val His Leu Gln Arg Pro Ser Gly Ser Ser Ile Thr Arg 15260 15265 15270 Ala Thr Ile Ile Arg Thr Ala Trp Ala Ile Leu Leu Ala Gln Tyr 15275 15280 15285 Glu His Asp Asp Asp Ile Cys Phe Gly Thr Thr Val Ser Gly Arg 15290 15295 15300 Gln Ala Ala Val Gln Gly Ile Asp Glu Met Pro Gly Leu Ala Leu 15305 15310 15315 Ala Thr Val Pro Ile Arg Val Gln Leu Asp Lys Arg Gln Lys Ile 15320 15325 15330 Ser Ala Leu Leu Gln Ser Met Gln Asp Gln Ala Phe Glu Met Val 15335 15340 15345 Ala His Glu Gln Tyr Gly Leu Ala Asn Ile Ser Arg Ile Ser Thr 15350 15355 15360 Asp Ala Lys Glu Ala Cys Asn Phe Thr Asn Leu Leu Ile Val Gln 15365 15370 15375 Pro Ala Gln Gln Phe Thr Pro Thr Asp Ser Gly Thr Glu Ser Thr 15380 15385 15390 Val Phe Tyr Pro Val Ala Ala Glu Gly Phe Ala Glu Gly Glu Leu 15395 15400 15405 Leu Gly Asp Tyr Phe Ser Tyr Pro Leu Val Val Gln Cys Gln Leu 15410 15415 15420 Leu Glu Asn Asp Val Gln Leu Ser Ile Ile Tyr Gln Thr Asp Leu 15425 15430 15435 Val Asn His Ser Gln Val Asn Ala Leu Ala Glu Gln Phe Ser Tyr 15440 15445 15450 Val Leu Glu Gln Leu Gln Lys Asn Gly Asp Lys Thr Leu Ser Glu 15455 15460 15465 Leu Ser Pro Ala Ser Pro Trp Asp Thr Glu Gln Ala Thr Lys Trp 15470 15475 15480 Asn Ser Phe Asp Ile Ala Pro Ile Glu Ala Cys Val His Asp Leu 15485 15490 15495 Phe Ser Arg Gln Val Ala Lys Ile Pro His Lys Glu Ala Leu Tyr 15500 15505 15510 Ser Thr Ala Gly Ser Met Thr Tyr Ala Glu Val Asp Gln Leu Ser 15515 15520 15525 Asp Glu Leu Ala Leu His Leu Ile Gln Leu Gly Val Lys Ser Glu 15530 15535 15540 Ala Ile Val Pro Phe Cys Tyr Glu Lys Ser Val Trp Ser Ile Ile 15545 15550 15555 Val Met Met Gly Ile Ile Lys Ala Gly Gly Val Phe Leu Pro Leu 15560 15565 15570 Asp Pro Ser His Pro Leu Ser Arg Arg Gln Ala Leu Ile Asp Glu 15575 15580 15585 Thr Ser Ala Gln Tyr Met Ile Val Ser Pro Ser Thr Ala Lys Glu 15590 15595 15600 Cys Ala Gly Met Thr Arg Asn Asn Ile Glu Leu Ser Ser Ala Phe 15605 15610 15615 Phe Ser Arg Pro Asn Gly Arg Ala Ser Ala Ser Arg Lys Leu Lys 15620 15625 15630 Ala Ala Arg Ser Ser Pro Ser Lys Ala Met Tyr Ile Leu Phe Thr 15635 15640 15645 Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Ile Ile Glu His Arg 15650 15655 15660 Ala Ile Ser Ser Phe Leu Val Arg Leu Cys Lys Val Ile His Val 15665 15670 15675 Thr Arg Asp Ser Arg Thr Phe Gln Phe Ser Ser Tyr Val Phe Asp 15680 15685 15690 Ala Ser Ile Leu Glu Ile Phe Ala Thr Leu Ile Ser Gly Gly Thr 15695 15700 15705 Val Cys Val Pro Thr Asp Ala Glu Arg Ile Gln His Ala Ala Ser 15710 15715 15720 Phe Met Gly Gln Ala His Val Asn Thr Ala Leu Leu Thr Pro Thr 15725 15730 15735 Phe Ala Lys Thr Leu Asp Pro Gln Thr Val Pro Ser Leu Lys Thr 15740 15745 15750 Leu Ile Leu Gly Gly Glu Ala Pro Ser Arg Asp Ile Val Asp Ser 15755 15760 15765 Trp Arg Gln Asn Val Ser Leu Trp Asn Ala Tyr Gly Pro Thr Glu 15770 15775 15780 Thr Cys Val Ala Ser Cys Leu Gln Arg Tyr Thr Asp Asp Ala Thr 15785 15790 15795 Ser Ala Thr Thr Ile Gly Arg Gly Phe Ala His His Cys Trp Val 15800 15805 15810 Val Asn Pro Glu Asn His Asp Glu Leu Thr Pro Ile Gly Cys Val 15815 15820 15825 Gly Glu Leu Leu Val Gln Gly Asp Ala Leu Ser Arg Gly Tyr Ile 15830 15835 15840 Asn Asp Glu Glu Lys Thr Asn Asn Ala Phe Ile Ser Asn Val Lys 15845 15850 15855 Trp Leu Pro Asp Thr Val Asp Val Gly Arg Arg Arg Phe Tyr Lys 15860 15865 15870 Thr Gly Asp Leu Val Arg Tyr Asn Pro Asp Gly Ser Leu His Tyr 15875 15880 15885 Leu Gly Arg Lys Asp Thr Gln Val Lys Ile Arg Gly Gln Arg Ile 15890 15895 15900 Glu Leu Gly Glu Ile Glu Tyr Gln Ile Lys Leu Gln Ser His Asp 15905 15910 15915 Val Glu His Ala Val Val Asp Lys Ile Arg His Asp Thr His Glu 15920 15925 15930 Ser Leu Val Ala Phe Val Ser Phe Ser Ser Asp Thr Ser Pro Ser 15935 15940 15945 Asp Ala Ser Asn Ile Arg Val Leu Asn His Ser Ser Lys Leu Gln 15950 15955 15960 Glu Leu Phe Ser Gln Leu Ala Ser Asp Leu Ser Thr Val Leu Pro 15965 15970 15975 Ser His Met Val Pro Gln Tyr Phe Ile Ala Val Glu Ser Met Pro 15980 15985 15990 Leu Asn Thr Ser Gly Lys Leu Asp Arg Lys Ala Leu Leu Gln Thr 15995 16000 16005 Ala Ala Gly Leu Ser Ser Glu Asp Leu Ala Val His Leu Ala Gly 16010 16015 16020 Gln Arg Leu Pro Phe Arg Asp Val Ser Thr Asp Leu Glu His Trp 16025 16030 16035 Leu Arg Ala Glu Trp Ala Asp Val Leu Glu Leu Pro Arg Glu Ser 16040 16045 16050 Ile Ser Val Asp Asp Asn Phe Tyr Gln Leu Gly Gly Asp Ser Ile 16055 16060 16065 Arg Ile Val Asn Val Ser Arg Leu Val Leu Asp Lys Phe Gly Val 16070 16075 16080 Ser Leu Gly Ser Thr Leu Leu Asn Ser Lys His Thr Thr Ile Ser 16085 16090 16095 Asn Met Ala Lys Phe Ile Ser Gln Ser Ala Glu Asn Gly Ala Ala 16100 16105 16110 Glu Ala Asp His Pro Asp Ala Gln Val Asp Leu Met Ala Lys Val 16115 16120 16125 Asn Glu Ile Ala Asn Ser Pro Trp Met Gln His Pro Arg Ala Leu 16130 16135 16140 Leu Glu Asn Pro Thr Thr Thr Leu Pro Asp Gln Ala Thr Val Phe 16145 16150 16155 Leu Thr Gly Ala Thr Gly Phe Leu Gly Thr Glu Ile Leu Arg Arg 16160 16165 16170 Leu Val Glu Asn Pro Ala Ile Arg Ser Ile Ala Val His Val Arg 16175 16180 16185 Ser Lys Thr Leu Ala Gln Gly Met Asp Arg Ile Arg Glu Thr Ala 16190 16195 16200 Lys Ile Ala Gly Trp Trp Arg Asp Glu Asp Glu Ala Lys Leu Glu 16205 16210 16215 Ile Trp Leu Gly Asp Leu Ser Lys Thr Arg Leu Gly Leu Thr Glu 16220 16225 16230 Ala Gln Trp Gln Arg Leu Ser Gly Val Ser Glu Ser Glu Ala Asn 16235 16240 16245 Ile Asp Ala Ile Ile His Asn Gly Ala Ser Val Asn Trp Asn Ala 16250 16255 16260 Asn Tyr Glu Thr Leu Ser Ala Pro Asn Val Asn Ser Thr Val Asp 16265 16270 16275 Leu Leu Met Ala Thr Ala Thr Ser Pro Cys Gln Pro Lys Phe Val 16280 16285 16290 Phe Val Ser Gly Gly Ala Phe Thr Asp Pro Ala Glu Asn Pro Ala 16295 16300 16305 Val Ser Ala Ala Leu Leu Ser Gly Ser Asn Gly Tyr Ser Gln Ser 16310 16315 16320 Lys Phe Val Cys Glu Ala Val Ile Thr Lys Met Ala Asn Ser Leu 16325 16330 16335 Pro Ser Thr Gln Asn Arg Val Ser Thr Val Lys Pro Gly Arg Ile 16340 16345 16350 Ile Gly Arg Ala Glu Asn Gly Val Ser Asn Val Asp Asp Phe Val 16355 16360 16365 Trp Arg Val Val Ser Thr Ala Ala Ser Ile Gln Ala Tyr Pro Glu 16370 16375 16380 Glu Ala Ser Asp His Trp Met Val Met Gln Asp Val Gly Val Val 16385 16390 16395 Ala Ser Asn Val Leu Gly Pro Leu Phe Ala Asp Ser Ile Lys Pro 16400 16405 16410 Phe Asn Leu Leu Ala Arg Gly Met Thr Met Ser Asp Phe Trp Asp 16415 16420 16425 Arg Val Asn Ala Glu Leu Asp Ala Pro Cys Lys Pro Val Thr Trp 16430 16435 16440 Gln Glu Trp Thr Glu Arg Ala Leu Ala Ser Met Asn Thr Val Gly 16445 16450 16455 Asn Thr His Pro Leu Trp Pro Val Gln His Phe Leu Gly Gln Leu

16460 16465 16470 Gly Leu Pro Arg Asp Phe Ala Thr Leu Ala Asn Ala Gly Thr His 16475 16480 16485 Val Cys Glu Gln Ser Gln Lys Ala Val His Ser Asn Val Arg Tyr 16490 16495 16500 Met Lys Lys Ile Gly Phe Ile Gln Ser Ser Glu Glu Gly Phe Gly 16505 16510 16515 Asn Val Gln Arg Asp Gly Thr Ile Arg Arg Val His Thr Leu Ala 16520 16525 16530 Gly 369518DNATrichoderma reesei 3atggcgccga acactacgta cgaagatggg aacaaatccc tcatcccaat tgccatctgc 60ggcgttggca tccggcttcc tggtggcatt cgcaatgccg agcaactctg ggagtccctc 120gtcaacgacc gtgttcagcc gcgtgtggat ggcaatgaag aggaagaact agacgctgtt 180gatgcttcgt tcttctcctt gaccgaggca gagctcgaga gctgcagccc tctgcagcgg 240aagctcttgg aggtgactcg tgagtgtttt gaggatgcgt gcgagatcga cttccggggc 300gaggatgctc gtgtgggctg ctatgccggt agtattggag aggacgatgt gtcgatggtg 360tcactgaagc atgatttggg aggcccgagg ttcgtttact atccggactg ctgtcctccc 420tccccccttt gagtataatt tctgggttgc taacgagttt tttgggctta gcatggcgat 480tagagagtcg acgtcgtcat ttctcgtggc tctgcatgag gcttgctccg ctgttcgatc 540tggcagtgcc aaatctgcag ttgttctggg agctgcccag aatggcgctg tgggaggcga 600ggccgtgtca gctgtatata tcaagacact gcctgatgcc atgcgcagag gcaacccaat 660tcgcgccatc attcgagctt ctagcattat gacgctcagt ggccgaagtt ctgtggctga 720ggcccatgag gagctcattc gcgaggccta cgatgccgcg ggcctagata tccgatcagc 780ccttgtagtt gaggtgggtg taacaatgac ctgattgaag catcatgaac gagagaatgt 840ctaatatgct aacttgaatg ataactagtg gagcggagat gccgaagctg aagtctctgc 900aattaacagc gcctttggcg agcagggtat ctatttgacc aagggtgcgt cgggcttgac 960gagcttggtc aaggccgtgg taacattgga gaaccggaca atctctccga atattgtatc 1020tggtaagttt catgctgctc aagtccgccg aaaagtcagg cccaagtctc taacgtaaag 1080aaacatcagc atcctctacc cccggagcgc tcgtagctac gcaggccatt ccgttcccgc 1140atgatcgcgc agagagagcc agcatcattg cctctgacgc tgagggacac agcgctcatg 1200ttatcgtcga ctctcacccc cggcctactc cgcgagtatc tgagtcccgg ccgcaacttg 1260ttctgttctc tgcgaacaac ccagcttctt tggctaagca gatcgagctg caccgcctgt 1320atgctgaatc tcacccagac gatgctgccg acatcgccta tactcgcgct ctccgacgcg 1380aggctctgga ctacaaggca ttctccatcc tttcgaactc atccttcgtc aacacttcca 1440actacgccaa gtcttccgcg cgggctccgg ccatcaccat ggtgttcaac ggccagggtg 1500ctcagtgggc gggaatgggc aaggagctca tcttgaccga ctcaagcttc agggaagaca 1560tcaggaagat ggatctggtt ctgaagggac tgaacatacc cgcaacctgg tcgattgaag 1620aggagcttct ccgtgatgct gccgaccccg acaacaggat caacacctca aagttctcct 1680accctctcag cacggcgctt cagattgccc tggtcaactg tttcaaacgc cttggtgtta 1740cgcccaaggc cgtcgttggt cactccagtg gtgagattgc tgctgcctat gctgcgggct 1800ttctctcttt cgaagacgcc atcacagtcg cttactacta cggccatatt actaccaggg 1860accagaagga cggtgccatg ggcgtggtaa gcttaggtgc agaggaaacg gaggggtttc 1920tcgagcaggg cgtggtcatt gcttgtgaga actcacccac tagcaccacc atttccggcg 1980accgtgaggc ggttgagcga gtcttgaagt ttgtcaaggc agcaaagcct gaggtgactg 2040ctcgtctgct gaaggttgat actgcgtatc actctgaaca catgactcag cttgccgatg 2100agctgcttga ccttttgacg gcggagaaga ttgcttcgca tgcaaccagg aagagcgagg 2160ccatctttat ttctaccgtc agcgagaagg ttctgaagga gaagagcgag tttggagcag 2220cgtactgggt ctccaacctg gtgtcacctg tccgcttcag ctcgtccgtc tccaacctcc 2280tcggcatgtc atctgaggaa actctgttcc tggaagttgg acctcattct gccctctccg 2340tgcctctgtc ccagatctgt gccgctgcag atgtccgatg caattatgtc tcgtcccaaa 2400ctcgtggggc tgatagtgca gtgagctttc tctctgctgt tggaaggctg tggcaggagt 2460cggctgtgcc gaatctcgcc cctttgttct cccacggcag ggcaatttct gggttacctc 2520agtatccctg gagttacgga acctctgatg aggactccga tgctactgct ctatctgccc 2580gtgagaagcg ggctcgtgtc tttgcagagg acagctctct ggagagcgag ctcgccgacg 2640aagaggctcc taccactgag gtggagattg ttcttcgagc tgtctgggtt gagatcctcc 2700gggatgtgaa ccgaatccgt aagcaggaca ttggaaagaa gcacaacttc ttcctgcttg 2760gcggcgactc tctcacaacc atcgagcttg ttactgctgc ttatcaatac ggcattcgtc 2820tgagtccggc agccgtatcg gacaacgctg agcttgccca gatggcagct gtggcaacca 2880tcgaacacga cagcgcaatg atggctgaga caaagccctt cagcttgatt agcagtgaaa 2940aggttgatga tatcaagcac cagatccgga aggagtgcaa gcttgcccct accgagacta 3000ttgaggatat ctatccttgc acgactctcc aggaaggttt catggccctg ggtatgaagc 3060agcctggctc ttacatccac agagtcgtgt acaagctgat gccagaaatt gatgttgatc 3120aattcaaggc ttcctgggag gccaccatca gccaatgcgg aagcttgcgt tcgcgagtag 3180cccttctcgg cggtcgagct ctccaagctg tgatgacgga agatattgct tgggagcagc 3240ctgctccagg cctggacatc aacgcttatc tcaaccgaac gcgaagcatc agcatgagct 3300acggcgagcg cctgagcaga catgccctgg tacgagacag caatggcggc gtctactttg 3360tgtggctcat tcaccacgcc gtgtttgacg gtctcaccat gcgaatcgtc ctggacgccc 3420tctacaacgc ttatcatggc aatgacgcca aagccttgcg tccgtactcc aactttatcc 3480gctatgtcga atccattgat tccgccgcgt ctaccgagta ctggcaaaag cagcttgatg 3540gtgctcagcg cgctcacttc ccgcccgcga gactgtctgc cacatctgaa gaccgagtca 3600tgaagaggac tatgcctttc cataacgcga agacctcttc cgtgaccacc gctacgattc 3660ttcgtgcggc ttgggctctc cttcttgcgc gctactgcga ctctgatgat gtgtgctttg 3720gtactacact gtcgggtcgt caggctgcgg tgcccggatt gaacgagatt ccaggaccca 3780tgattgcgac tgtgcctatc cgagtcaaga ttgatcgtgg catgactgtg tcctctttcc 3840tcgagaagat tcagacacaa gcggcagaca tggtggccca tgagcagtac ggtcttcaga 3900acatctcgaa actgtcccag gacgccgagg aggcatgcga cttttccaac ctcatcgtca 3960ttcagccaaa caaccatctg acgtccatgg ctgatactgc ttctgatgcc atcttgcagc 4020agggatcccg cgaaaaggct ctctcggaag aggctatgcg caattacttc aactatcccc 4080tcgttttgca gcctcgcatt ggcgaggaca gcatcgagct ggacttgacg tattacgctg 4140atgccatcac tgagggccag cttgaggctc tgtgtgttca ctacgagcac attgttcagc 4200aattgcttgc tccgacggac atgcccctca gtgacctttc ggtatctggc tcgtgggacc 4260tggaagaggc gatcaaggcc aacgacgaaa caccagagat tgtcgacatg tgtcttcatc 4320agcttattga gagacagtcg aaggcaaacc ccgatgcccc tgctattcat gcctgggata 4380tggagctgtc ttactcgcaa ctcgatcgtg ctgccaaccg cctcgctcat catctcgtca 4440agtcctgtgg cgtcaaggat caggacttcg tccacgtctg ctttgagaaa tcggcctggt 4500ttttcgtgtc tgttattgct gtcaataagg ctggtgctac ctgggttccc ttggatccct 4560cgcacccgct gcagaggcag caacaggttg tctcgcagac aaaggcgacg ctggccttgg 4620cttcccctag caatgtcgag atgtgttctg agttggtcaa taccgtcgtt gaggtgtctt 4680cagccctgga tgagaagcta tctaagaccg aagagagctc ttacggacca gtacgcaatg 4740tgtcaccaga taatgcagcc tatgttctgt ttacttctgg aagtactgga acgccaaagg 4800gtctggtcat gcagcacagg gctgtctgca cctcgcagac cgctattacc aagcgcctgg 4860aaatgacctc tagcgtaagg atgcttcaat ttgcatcctt tgtcttcgat ctctctatcg 4920gtgagattgt tggtccctgg gtggttggcg gctgtctctg cgttccgtct gaggaaacga 4980ggatgaacaa cctggtggac ttcatcaaca cgatgcaagt caactgggcc tatctgacgc 5040cctcgtttac gcgcactttg aaccctgacg acgttccagg cttggatttg ctgttgtttg 5100ctggcgaggc tgttggccga gatgtgtttg aagcttggtt tggcaaggtg cggctgatca 5160atggttgggg ccctgccgaa acttgtgtct tctcaaccct ccacgagtgg aagagcttcg 5220aggaatctcc gttgacggtc ggtaagccgg ttggcggata ctgctggatt gttgatccgc 5280atgatccgca gcgattagcc cctgtcggaa cccttggaga agttgtcatc caggggccga 5340cggttcttcg cgagtatctg gctgatacta ccaagactga ggcctcgctg gtgcgtagcc 5400tccccgagtg ggtgccaaac cgtacagctg cgcactggga tcgattttac aagtcgggtg 5460acctgtgtcg gtacaatgcg gacggcacca ttgagtttgg atctcgtaag gatagccagg 5520ttaagattcg aggccttcgt gtcgagcttg gagaaatcga gcatcatatc cgcgagtctc 5580tggaaggcgt caagcaggtc gctgttgatg tggcaaaggg agatggtggc gcgatcatcg 5640tgtcctactt ctcctttacc gacgaaaccc gcactgctgg caagaactcc gagacgagcg 5700tcagagatgt gttcgtcccg atgactcctg agctccagag tcaactgaca gccttggttg 5760gccagctgag cgttacactt cctcgataca tgatcccgac gctatttatc ccctgccact 5820acatgccctt tatcacttcg acaaagttgg atatgaagct cctgcgactg gcaatgtcca 5880atcttggtaa ggacgacatt gcgaggtatt cccttgtgga tagcaagaag cgtgctccgg 5940aaacggagat ggagactcgt atccaggcga tctgggcgga tctcctgaag ctgtcgcccg 6000agttcatcgg tcgagatgat agctttttga gaatgggcgg tgactctatt gctgccatct 6060attttgtgtc tgcggctcgc gatgccggta tttccatcgc tgtgaaggac gttttcgacg 6120acccccgatt gttccaggtg gcctccaagg ctaccctcct ctccaacgcg ggccgttctt 6180ctcagactga gccctttacc ctgcttccag aatcgttgag caaactcatg caaagcgatg 6240ctattcgatc tcgctacggc ctgggacagc gccagacgat cgaggacgcc tatccttgca 6300cccccctcca ggaaggtctc atggccctga ctgccaagca acgcggctca tacgtctcgc 6360aatggttcta ccgaatgcct agacatatcg ataccgccaa gttcaaggct gcttggaacg 6420aggccgttga gcgaaatgcc actctgagga ctcgtatcat gctggaggaa ggttctgcag 6480tgcaagctgt catttcgaat gacggcgatt gggaagacac tgagggactc aaccttgagt 6540ccttcaaaga cgtaatctct cagctggaca ttggctatgg aactcgtctg accagatttg 6600ctcttgttga ggaccatgat gacacttact ttgtctggat catccaccat gctatcaacg 6660acggctggag catgcgcatc gtcctcgata gcgtttacaa cagctactac ggtcagaagg 6720tcgcctccct gacgccttac tccaacttca tcaactacct gagtaatata gatggcgagg 6780cagcggcaaa cttctggcga tcgaacctgg ctggtgctca acggcctatc tatcctgctg 6840ctggcagcta ctcaactgct gacagctctg gagactcaac ccgtgttgtc gatcgcttgg 6900tgtccttttc cagccatgaa gacgcctcca ttaccatggc cactattatt cgagcggcct 6960gggcaattgt gcttggcaag cattgtgacg ccagcgatgt ctgctatggc gcgacggttt 7020ctggtcgcca ggctgatatg gacggcctct tgtcaactcc cggtgctgtc attgccaccg 7080tcccaatccg agtccctttg gaagctgatc agcctgtgag ccagatgctg caggacttgc 7140agggtcacgg tctggatatg gttccctatg agcagtatgg tctgcccaac atcgccaaac 7200tgagcccgga ggcccgcgag gcttgtgact ttacctccct gctggtaatt cagcccaagg 7260aacaggagag ctccatcttc aactccaaaa atggtctgct gcagtcggat gctgaagaag 7320atcacctgtt gattgagtct atggacaagt acttcaacta tccattggtc atgctcagct 7380acatgacaga agacagcgtg aatcagaggt ttatatataa gcctgacatg ctgtccgagg 7440ctgaagtcga ggccctctct tatcagtttg aatacgtcgt ccagcagctt ctgagtcctg 7500accaaaagct tatcagcgac atctctcttg ttggagagcg tgagattcag catgccgctg 7560acgtatctcg atatcgcccc gccaccgagt cttgcactca ctgggagatt tacaagcaga 7620ttgaagccca gccagatgcc cctgcctttg actcctggga cgccaagctc acataccgtg 7680aagtcggtgt tttggctact cgcttggccg ctaagttgca gagacttggt gttggatcgg 7740acgttatggt gcccatttcg ttccccaaga gcaccccggc catgatcacc atggttgcta 7800tccagatggc tggtggtgct cttgtgccgc ttgaccctgc agctccattg gcccgtctgc 7860aaagtatcgt ttctgatacg caggcgaagc tcatcgtcac ccatccttct ctcgaggaga 7920aacttcaaga gcttggcgtg gacctcctga ttgtggacct gtccatgttg gataagttgc 7980ccgatcccag caccaagttc atctcgtcag atgccacgcc agagagtctt tacgctgtct 8040tgtttacgtc tggctctacc ggcaagccca agggcattcg cattccgcat agcagtctct 8100gctctgtaag cgatgcccat gctgcggaaa ccggcgttgg gcctggcagc agagtgttcc 8160agttttcggc ttacacgttc gatatcggca ttctcgatgt cttggtcact ctcatgcgcg 8220gtggctgcgt ctgtgtgcct tcggaccacg atcgcctcaa caacctcgcg ggcgtcatca 8280gtgctctcca ggccaactgg gttttcttga cgcctactgt cgccgacatg ctcaacccag 8340cagacgtccc ttgtttgaca accatcaacc tgggaggcga agccgtcaac aagaagtcat 8400ccgagaggtg gcagggctac actactctga acggccttta cggtcctgct gaggcctcga 8460tttgcgctcg caacgcggat gtgcacaacg gtgcatctac taacttgggc tttcctctgt 8520ccagtgcttt ctgggctgtc gagccaaacg acccaagccg tcttgtgccc atcggctgta 8580tcggcgagtt gctcatccag agtcctatct tggcttacgg atacctcaat gccgatgcaa 8640agaataatgc aaattggctg gaggatatga catacgactg gcttccagcc aatgggccaa 8700agcgagccta tcgaactggt gatttggttt gccgcaaccc tgatggcacg ttcgagtaca 8760tgggccgaag ggacaaccag gtcaagatcc gtggccagcg tgtcgagctg ggtgagatcg 8820aatatactgt cctgaccaac cttcccggcg cgaagcagat cctggtggat gtcattaaca 8880atgacgaagc cggtctcagc ctcatcacct atttatgctt caacgacgac accaagggca 8940gcgacaagaa cctggaggat atcttcctga ccaccactcc cgagatgaag cagaagttct 9000ctgacatgct tggccaactg cacatcaccc ttcctcacta catgattccg accatcttcg 9060ttccgtgcaa gtacatgcct atcaacactt cagctaagct ggaccgcaag gctctccgcg 9120cttgtgcggc tgtcctgagc aaagacgagc tggcggctta cacgctctct gatgatgagg 9180acaagcaacc acccgagacc ccgatggaag caaggctgca gcagatctgg gcggacactc 9240tcaagatttc gcctggctct attggccgcg gctccaactt tttgcgcttg ggtggtgatt 9300ccattgcagc catttacagc gtgatggctg cgaatgaggc tggaatcatc ttgacagtga 9360aggacatctt tgacgacccg cgattgtcaa aggttgctct caaggctgtt gaggtcagtg 9420gagatgtagc ccagcaaaac gccgtcattg agcctttcag ccttcttgac gcacacagac 9480gcaactgggc catgagcgac gaggttcatg gcttgtgcaa gctgcttccg caccagactg 9540ttgaagatgc tttccctact accagcttcc aagagggcct catggctatg gctgtgaagc 9600agccgggatc ttacattgca aaacacgttt acaagatccc caagcatgtt gatctccagc 9660tcttcaagga ggcttgggag cagactgtga agctgtgcgg cattctgcgt accaggatcg 9720tgctcaacca ggggtcgtct attcaggttg ttatcaaaga cgatgttgcc tgggatgtga 9780cttacggcca ggacgtagtc tcctatatcg actcaacaag gaacattgag atgacctatg 9840gctcacgcct gtgtcgctat gcccttatcg aggagcgcag cggcgacaga tactttgtct 9900ggaccattca ccacactgcc tttgacggtt ggacgatgca aatcattctt gagactctgc 9960aaagtgtcta tcgtcaacag aacccctctc cacctcgggc atactcccac ttcatccggt 10020acacgtccga gattgaccaa gccgaagcca aggacttttg gtcttctcaa ctccaggatg 10080ctcgtcgtgc tgctttccca gctgccggct cgtcttccgc cccgtcgacc actcgcgtca 10140tgaagaagag gatctcaatt cccagcctgg aggagacatc catcacaaag ccatcaattc 10200tgcgcgctgc ttgggctatt gttcttggcc ggtatagcga tgccgatgat atctgcttcg 10260ggacaacaat ttccggtcgt caagctcctc tggcaggcat gactgagatt gccggccctg 10320ccgtagccac ggtgcccgtc agggtccgtc tcgatggttc aaagcctgtg gcccagttcc 10380tccatgacat ccagagccag gcctctgaga tggtagccta cgagcagttt ggtttgcaga 10440atattgccaa ggtcagcgaa agtgctcggg aggcttgtga cttctcaagc ttgcttgtca 10500tccagcccgg ccacttcctg cagtatggcg atgaaagcac tgatgcaatt ctcattggcg 10560acgacaagag cattgaggag gaggtcatgc agaactactt cacgtatccc ctcatcgtgg 10620aaggtgtctt gtacgaagac catgttgagc ttcttgtgat ttacaatgcc aacgtcttgg 10680ccgagtcgca aatcactgcc ttgacgtatc acttcgagca tgtcacccag cagcttgcta 10740gccaggaggg tcttgtgatc ggggatgtct ctgtttccgg ttcttgggat ctggagcaga 10800gtctccaagc aaacaacgag gttcctgaaa ttgtcgactc ttgtatccac gagttggtcg 10860aaaaacaggc cctcgaacgt cccggcgccc ctgctgttgt gggttgggac cgggttttca 10920cctatgctga actcaacgag gccgctaacc ggttggccca tcatctcacg cagacctttg 10980ccatcaaagc cgatgagctg attcatgttt gctttgaaaa gtcggcatgg cattttgtcg 11040cgatcctggc tattaataaa gctggtgccg gatgggttcc ccttgatccg tcacatcctg 11100agcagcggtt gcgccagatt gccagccaga cccgggcaag aatcatacta acatcaccgg 11160ccaatttgga tatttgtgcc cgtcttggct tgtctgtcat tgagatcagc ccgttctttg 11220atcagaagct tatcaagagc ggcatgaata gcagcgctgg gccagacgtc aaggtgacgc 11280ctcgtaacat tgcttacgtc ctctttacct ccggttctac tggtactcct aagggactgg 11340tcatggaaca tggctctgta tgcacgtcac agaccgctat cagccggaga ctcggattga 11400ctgccgatgt tcgtatgctg cagtttgcag cctttgtttt cgatctttct atcggtgaaa 11460tcgttgcgcc actgatttca ggtgcttctt tgcacatccc tgacgaaaac actcgattga 11520atgacctgcc caacttcatc cagaagaaac aaatcaattg ggccttcctt acccccgcgt 11580tcgcccgcac tctgaagcca gaagacgtcc ctgctctaga cctcttattg ctagcaggag 11640aagccgttag tcgcgatgtg tttgaaagct ggttcggaaa ggtcagactt atcaatggct 11700ggggcccagc tgagacgtgc gttttctcga ctcttcatga gtggaggtct atcaacgaga 11760gtcccctaac tgtcggccgg ccggtcggcg gtttctgctg gattgtcgat ccggaacacc 11820ctgacaagct ggctcccacg ggcaccgtcg gcgaggtcgt tatccaaggc ccgaccctgc 11880ttcgggaata ccttgcagac gctgagagga ccaagctgtc gaccgtctat gacttgcccg 11940cttgggcacc ccgccgcgag ttacagcatt ggagccgatt ctacaagtcc ggtgacttgt 12000gttactacaa cccggatggt accatcgaat tctcaactcg taaggatacg cagatcaaga 12060ttcgcggcct tcgtgttgaa ttgggcgaaa tcgagcacca cctgcagctt gcccttgatg 12120acattcgtca ggtcgccgtc gacgtgttta agggtgaaag tggctcaaat ctcgtggcct 12180acttctgctt caacgaggag agcaagacgg ctgatgctcg tgttgcgggt gacgataagg 12240gtcctttcat gcccatcgat gaagaccttc aagcccgcct tattgcagcc tcgggtgaat 12300tgagggttgt tcttccgtcc tacatggtgc caaccttctt cattccctgt agctatatgc 12360caaccagcac atcgaccaag cttgaccgca aggagctgaa gcggtatacc gctgccttat 12420ccgtcgaaga gctatcgaaa tactcccttg tcgatggcaa aaagagggca cccgagactc 12480cgatggaaag ccagttacag cagatatggg ctgaaatttt gaacattcct atggagtcgg 12540ttggacgcga tgacagcttc cttggcctcg gcggtgactc tatcacggcc atccacttgg 12600ttaacgtcat gcgggaagag ggtatctcgt tgaccgtcaa ggacatcttt gatgaccctc 12660gcctgctgtc tgtcgccagc aaggctataa ccaccgagga ggtacttgaa ctcgatgaga 12720ttgagccatt cagcctcctg gaaaaggaga tccgtgatgc tgttctatca gaggatcttc 12780gacaagaact caagctcgcc aagtgccagc ttgtcgagga tgcttatcca tgcagcaagc 12840tccaggaagg ccttatggtc ctttctgtga agcagcccgg atcatacgtc gccaagtaca 12900cctatcgtct tcctgcccat gtcgaccttc aacgcttcaa ggaggcgtgg gagtacacct 12960cgtctgctgt tgaagcactc cgaactcgtc ttgtcatgat tgacggttct tgtgtccagg 13020tcgtcatcaa cgaggagatc ccctgggaga ctacaaagac ggatgatatt cgatcggcca 13080tagcatcggc tcagtctctc cgcatgacat acggctcatc tctgtcgcgc tacacaatcc 13140tcgaggacca agacggcagc aactatttca tgtgggctgt ccaccactct gtccatgatg 13200gttggtcgat gaggatagtc ctggagacgt tgcggcgaga gtatgagggc cgggcatcgg 13260ccccggttat gccctacaac ggattcattc gctataccct tggtctcgac ctggaggccg 13320ctgctgagta ttggagcagc cagctggata acgccaagcg ggccagtttc cctgctgctg 13380ccactacctc tagcgaaacg aagcacatca cgcgaatgat gacaaagtct attccattcc 13440ctgcttccat gaacccagcc atcacaaagg ccacagtttt gcgagctgct tgggccgtca 13500tcctagctcg ttactgcgat acagacgatg tcacgtttgg gtctaccatt tctggtaggc 13560aggcggcagt tccaggcctg accgagatgg ctggtccagc tgttgccact gttcccgtcc 13620gtatccgtct cgataagcag cagcgcgtgt ccaaattcct tcaaggtgta cagagtcaag 13680cctctgagat gatccccttc gaacaatttg gcctgcagag catctccagg cttggtgctg 13740atgcgaggga tgcgtgcgac tttacttccc tgatgctagt tcaacccatg cagcatcttg 13800ctggcgagga tctcgacagt gtcatggtgc ctgctcttga acaagagaca caagaggatc 13860aattgcagaa ttacttctca taccctcttg ttctgcaggg ccatatccat gacgatcgag 13920ttgagctcgt cttgatctac gactctgtcg ttcttccaga accacagctt gttgccttgt 13980cacatcagtt caatggcgtt gtccagcagc ttctcagcgg caaggattgc aagcttggcg 14040aaatctcagt ggcgagcccc tgggatctcg accttgcaca ggcttccaac ggcgatggcc 14100ctgaaatcgt tgatgattgt gctcatctca taatcgagcg gcaaacgaag cagactcccc 14160atgcccatgc tgtacatgct tgggatggct cactcaccta cagtgagctt gatcttgctg 14220ccaacaggct cgccaatctc ttgatccaac gtcacggggt caaggtcggc gatgtcgttc 14280atgtgtgctt tgaaaagtct ctttggtatg tggtttcggt cctggccatc aacaaggctg 14340gagctgcttg ggtgccaatg gacccggcac acccattcca acggcttcaa caggttgcca 14400gtcaaactgg tgcaaagctc gcgctctcat ctgctatcca cagccccctg tgctccaagc 14460ttctggacac ggttgttgaa gtgtcctcaa acctggatga gcagttgaag agtgacgaga 14520ccatcagtca tgtcaagcca accactaagg

tgacccccaa cgacgctgtc tacctgctct 14580ttacttccgg tagtactggc gttcctaagg gtatcattat ggaacatgcc tctctttgca 14640ccagccagcg tgatatcgca aagagactcg gcctgactag cagcgtcaga atgcttcaat 14700tctcgtcctt tgtctttgac gtttccgtgg gagaaatcat gctttccctt atgcatggtg 14760gttgcatttg cataccatct gaccacgatc gtctcaacaa cttggatgga ttcatccgag 14820acgccgaggt gacctgggca ttcctgacac catcgtttgc acgcacactc cgccctcaag 14880acgttccatc ccttgagctc attgtccttg ccggagagcc cgtcagccag gacgtctttg 14940acctctggtt cggtaaggca aggcttgtca atggttgggg acctgctgag acttgcgttc 15000tgagtgctat ccacgaatgg aaatccgcag acgaatcgcc gttgaccatc ggacgttcgg 15060ttggaagctt tgcctggatt gtcgacgcag agaattcgaa ccgtctagcc ccggttggat 15120gtatcggaga aatcgtcatg caggggccta ctctcctccg tgagtacttg gctgacccgg 15180ccaagacggc ctcatcgacc atgacctctt tgccgaactg ggcaccccgc gccaatgaca 15240agaaatgggg tcgtttctat aagactggcg atctgggttt ctacaaccct gatggaacga 15300tccactactc tggccgcaag gatacacagg tcaagatccg tggtcttcgc gttgagcttg 15360gtgaagttga gcatcacatt cggaatgcac ttgaatccat ccgacaggtt gccgttgatg 15420tgttccgaac agaaaccgga acgaacctcg tctcatacat ctgctttagc agcgagacga 15480aaactcccgg accaaacacc gaccccaatg gtgatgacgt tttcctctac atgactcgga 15540acgtccagag cgatttgaac atcgccatca acaagctcaa cgccctgctg cctagctaca 15600tgatcccaac ttactggatt ccttgtgact acatgccgct gatttcctcc ggcaagttgg 15660acagggtcaa gctccgcaag cagatggctg cgttgactca ggaggagctg gaggcctatt 15720cactgactga tgccgacaag cgcgctccgg acacagccat ggaagtgcga ctgcaaagca 15780tgtgggctga gatcttgaac attcccgctc agaccattgg caaggacgac aacttcctcc 15840gtattggtgg tgactcaatc gctgctatca gattggtctc gatggctcgc gagcgcggca 15900tcaccctcac ggtcaatggc atttttgaag atccgcgcct gtcatctatg gctgccactg 15960ccggggcggc tgatggggat gatgagcttc tgactcctat tcctgctttc tccctcctgg 16020atgacagcac tcgagacccg atccaggctc ccagcatcta ccaagacttg ggcctgaatg 16080tcacacagcg gatcgaggac gcatatccaa ccaccaagct ccaagaaggc ctcatggccc 16140tctccgccaa gcagcccgga tcgtacattg ccaagttcct ctatcgtatt cccaagcaca 16200ttgaagtcgc tcgcttcaag gatgcctgga gacgcacggt tgatgcttgt cccaaccttc 16260gcacccggat cctcctcacc gaaggaggcc acagcacgca gcttgtgatt agccacgatt 16320tcgagtggga tctcgtcgag aatgaagacc ttcactccta tctccagctg actcaggact 16380ttgagatggg ttacggttcg cagctttctc ggtacgcgct gatcaagcac acggatggcg 16440agacgtactt catgtggagc gtgcatcacg ctgttttcga tggtctgtct actcagaacg 16500tattgaacat tcttgagaag gcctatcaag gcaaagacgt cctagaaacg cctccgtatg 16560cccgcttcat caagtatacc cttggactgg atgcagaggc tgcagcaaca tactggagag 16620aacaattaca gagctctcgc aaggccactt tccctgcgtc aagtgaagta tccaacaagc 16680ctggcgccac tcgtgtcctt gaacgatcca tcgagctgcc caagatggcc tcatcgggca 16740ttactctcgc caccgttgtt cggtctgctt gggccatggt cctcgcacgc tacagcgatt 16800cggaagatgt cacctttggt acaagcatct caggccgtca ggccccagta cccgagttga 16860tggacatggt tggacccatc atcgcaaccg tccctgtgag ggtccgcgta gaccaagcgc 16920agctggctac tgacttcctt caagctgtcc agaggcagac actcgaaatg gttccctacg 16980agcagttcgg tctacagagt atagccaagg tcagcgaaga cgccaaggag gcttgtgact 17040ttacttcgct cttggtgatt cagcctatgc aacacgtgtc cgactctgaa tccgccgatt 17100ctgtccttgt acacgcagat ggagcgctaa aggaggaggc cgaatcgatg gagaactatt 17160tctcgtaccc cctcattgtc caggctcatc tgtatgagga ccgcatcaac attgttctca 17220tctacgactc gactatcctg gccaagacac agctagaagc cctctctcaa cagcttggac 17280atgttatgtg ccagcttgcg gcagccactg acgagaaatc gttgggatcg gtatccatta 17340cttctgactg ggatctggag cgcgctgttt catttaacag tgacgttcct gaaatcgttg 17400atgcttgtgt gcatgacctt gttgcacgtc aggctgagct tcgaccagat tctgtcgcta 17460tatctgcgtg ggatgccgag ctcacatata gccagcttaa cctcgctgcc aatagactgg 17520cgaaccacat catcacagcc tatgggatca agcctaatga cttcattcac gtgtgttttg 17580agaagtcagc ttggcacttt gttgccattt tggctatcaa taaggctgga gccgcttggg 17640tgcctcttga ctcttctcat ccagagcagc gtcttcgtca agtggttagc cagacgaatg 17700ccaggctggt tttgacgtct cctagcaact ccacgctttg ttccggacta cttgcagacg 17760tccttgaagt cacaccagca ttggaccaaa agctagctgc aacagttggc tcccaggctc 17820ccaaggtcgc tgtgacgcct gaacatgctg tgtatgctct gttcacctcc ggatctaccg 17880gtacccctaa gggcctcgtt atgcagcacc gagctgtttg cacctcgcag acggccattg 17940ccaaacggtt aggtctgtca tcggacattc gacaacttca attcgctgcg ttcgttttcg 18000atctatccat tggtgagatt atcgcgccat taatcagcgg agcttgcgtt tgtgttcctt 18060ctgaagacgt ccggatgaac agcattaccg agtacattcg tgaccagcgc atcaactggg 18120cattcttgac cccttcgtac gttcgtacct tacggccaaa ggatgtacct ggcctggaac 18180tacttcttct tgccggtgaa gctgtaccta aggagatcct taacacatgg ttcgggaaat 18240tgcgccttgt caacggctgg gggccagccg agacctgtgt cttcagtacc ctgcacgaat 18300ggaagtcagt cgacgaaagt cctcttaccg ttggcaagcc agttggaggc ttctgctggg 18360ttgtcgaccc ggagaacccc cataagctag cccctgttgg cactttgggc gaggttgtca 18420tccaaggtcc gaccttactt cgcgagtatc tggctgatcc agaacgtacc gcggcttcct 18480cagccacagc ccctgactgg gcaccgcagc ctgactccaa gcattggggg cgcctttaca 18540aatctggtga tctctgctcc tacaaccctg atggaactct tgagttctcg tccagaaagg 18600acacacagat caagattcga ggccttcgtg tggagttggg tgaggtggaa caccacatcc 18660aaacggcgat gcgcggcctg cgccagattg ctgttgacgt ttacaagggc gagagcggaa 18720cgaatcttgt ggcttatctg tgctttaccg acgagacccg agcctcttct gctgaccaca 18780gcccattcat gtccgtcgac aagaagcttc agaaccaact gaatgctttg gtcggcgaat 18840tgggagttac gctgccgcgg tatatgatcc ccacgcttta cataccctgt agcttcatgc 18900cgtcaatcac gtcgaccaag ctggaccgca atgaattgcg ccgtcgtacc gccagcctca 18960cccgcgatga actgtctcaa tattccctgc tgggaggcaa caagagggct ccggaaaccg 19020acgtggagcg cgcgcttcaa cggatctggt ccggcatctt gggcctctcg ccggacgcaa 19080ttggccgaga cgacagcttc ctcggtctgg gaggtgactc gattactgcg atacagcttg 19140ttggggtttg tcgtgatcaa ggcatttctc tgtcggtcaa ggatatcttc aacgaccctc 19200ggcttatcgc tgtggccaag gctgctcagt cgctgagctc tgttgacgat gtcgctattg 19260agcctttcgg cctgttggat gatgaactgc gtcgtctcgc tacgagtgaa accgccaggg 19320ctcagtgcca tcttgcaaca gaagccgtca tcgaggacgc ctatccttgc acaaagttcc 19380aagaaggcct tatggctctc tccatcaagt ctcctggatc atatgttgcc aagtatgcct 19440atcggctggc ggatgatgtt gacattgagc agttcaagtc aagctggaag aagaccgttt 19500ctctctgccc taccctgcgc acacgcatcg tgcttcttgg tgaccgctgc gtgcagttgg 19560ttgtcaagga ggatgcagag tttgtatcat ctaccgcttc aagcttcgag tcagccatgc 19620ttgaagctcg taatgtgcaa atgacatacg gcacgccgct gtcacagtat actctgttcc 19680aaggagaaga tggcttctac ttcatctggg ttgttcatca tacggttcac gacggatgga 19740ccatgcgtct tgtgcttgaa acgctgcaga acctccacca gggctcgacc accagctcgc 19800tgaagccgta ttcaaacttc atcaagtatg cgatggatgt tgtgcaagac ccggctgtcg 19860agaaatactg gtcgcagcag ctggatggag cagtccaggc gtcctatccc cctcgcccaa 19920ggtctgacaa gcagcacaag gcagttaccc gcatgatgac caagactatc caagtgccaa 19980acaacactca gtcttcagtt accatggcga ctctcctgcg tgccacctgg gctatcatcc 20040ttgctcgtta ctccaacact gacgatatct gctttgccac gacggtgtct ggccgtcaag 20100cctctgtttc ggacatcttg cagatacccg ggcctatcgt tgcgactatc ccagtgcgcg 20160tacgactcaa tggccagcag actgtgctgg aatatttgga gagtgtgcag catcaagcta 20220cacagatgat tccccacgag caatacgggt tgcaaaacat ttccaggatc tcagaaaaca 20280tcagcgatgc cattgacttc tcaagtctac tggtcatcca gcctcgatcg cacctggact 20340ctggcaatgg tgacggaagc aatgagaaca ttcttattcc taccgttgag gacgatgaag 20400ctgtagcaga ccttctgcaa gattacttca cgtatcctct ggttattcag ggcaacctgt 20460tagatgacca tatcgacctg ctcctgacct acgatagcac tgtcctgtcc gaggtcgagc 20520tcagccgatt ggctgtgcaa ttcgaacacg ttgctcagca gctcctggat tccgatcatg 20580tcaagctggg agatctctcg ttggtgcccc cgcaagacgt tcaacaggcc attgcgtgga 20640acacagaaga ccccgagatc gttgaagatt gcatccacaa attggtcgaa cgacaagcca 20700tttctactcc ggatgccatc gccatcgact cttgggatgg gaagctgacg tacgcccagt 20760tagacgaggc tgcgacacgt ttatctcatc acctcatcaa gacatatgat gtcgcccctg 20820atgatcttgt ccttctcttg ttcgggaaat cgttgtggta catcatctcg acaattgccg 20880tcaacaaggc tggagcagcc tgggttcccc ttgacccagc tcaccccatg cagcgtctgc 20940agcaagttac cagacagacg aaagctcagg tgattctcgc gtcatctctg caatgcgagc 21000tggctcaaga actgctgaac actgttgttg aagtcagcca agccctggac gatgccctca 21060ccacggcagg ctccacgctc cgcactccag atgccatggt ttcctccaga gacaaggcct 21120atgtcctgtt cacttccggc agcaccggag tgccaaaagg tatcgtgatc agccacggat 21180ctgtctgcac gagtcaaact gctatttcta gccgtctggg cctgcacagc ggtgttcgga 21240tgctccagtt ctctgccttc gtcttcgatg tctctgttgg cgagatatat ggctcgttaa 21300tccgcggcgc ttgcgttgtt ataccatccg acgagattcg catgaatgac ctgaccagat 21360tcatgcggga gaaagaggtc acttgggcat gtttcacccc ttcattcatc gagactcttc 21420atccagctga tctggaaaat ctggagctgg tcatcctaga gggtgaacct tctaagagac 21480atatactaga ggaatggttc ggcaaggtca agctgatcaa tggctggggc cctgcggaaa 21540cctgtgtatt cagcagtatg cacgagtgga agtcagccac cgaaagccct gttactatcg 21600gcaagcctgt gggctgcttt gcgtggattg ctgatcccga caatcatcat cgccttgctc 21660caatcggtac tgttggcgag attgtgctcc agggtccgac actgttgtgc gaatacctcg 21720atgaccctat gcagacgcag gccagtatcc tcaagtcaat cccaagctgg gctccacgcc 21780gcgaatcgca gcactggaac cggttctact taaccggcga tctaggctgc tataaccctg 21840acggaaccct cgcgtatcac ggccggaagg atactcaagt caagattcga ggccttcgcg 21900tggaattgga tgaggtcgag caccatatcc gcagcctgct aagtgatgtt gttcatgtca 21960ctgtggacgt tcacaagtcc gaggcaggtt cgagtctggt tgcctatctt gcttacactg 22020aggagagtgt ggacgacgag gatgcactgt tcctgccctt gacgaacgag ctgcaaaagg 22080atctggatgc catgtccagt cagcttagtg tcttgttgcc tcggtatatg gtaccaactc 22140tctatatccc gtgctcgcac atgcctttcc tgtcatctgg gaagacggat agggctcagt 22200tacgcagact tacttccgaa ctaagccaag agcagctcga ggcctatgcg ctggacgata 22260ccaagaagga ggctgccgaa acagaggctg agttgcgtct tcgagatgtc tgggccaaga 22320ttctgggcct ttctgctcaa tcaattggtc gtcacgatag cttcttgcgt attggaggcg 22380attcaattgc agccatccag ctggtcaccg ctgccagaga ggccggcatc atcttctcag 22440tgaaggatgt ctttgatgac tcccgacttt ggaagctggc tgaatttgcc tcatccaaga 22500cggaatcgga aaaggttgtg gaggccattg caccattcag cctgcttcgc acttccctca 22560acgagacagc tgtaactgct attctgcagc agcaatatgg tttgaccgac agtgtcgtcg 22620ttgaggatgc ctatccctct acgaagcttc aggagggtct tatggccatc tctgctaagc 22680agcctggaac atatgttgca aagcaggtct acggcctgcc tgagcacgtt gaccttgata 22740ccttcaaggc agcctgggag cgaacagttg agctttgtgt caatttgagg acgcgtctcg 22800tcatcgccgg tgatgcaagt gtgcaggtgg ttattcggaa cgaagaaatc gagtgggaga 22860cttgcaatac aaccgtgcaa gcctacctct cccagcagtt caacatggga tacggttccc 22920gactgttccg taacggaatc gttcatgagc cctcggggca gaacttcttt gtcctgagca 22980ttcaccatgc catctttgat ggttggacgc tcccgatgct tatggagaca ctggactctg 23040cgtatcgcgg cgtcgaagct tccgccctcc gcccatacgc tgagtttgtc aagtatatcc 23100tggacattga tgaggcagct gctggtgact actggcgagg ccaactccaa gatgccaagc 23160gtgcctcgtt cccgccgtcg gccccggttc aatcatctca gacgattacc aggatccttg 23220agaagcccct caacttctct cactcaatca aatccggcat caccaaggca tcagtcctca 23280gggctgcctg ggccctggtg ttatccaggt attctgatag cgatgatgtg acatttggtg 23340tcaacgtttc cggacgtaat gccgcagttg caggcattga atcgatgccc ggccttgttg 23400tcgccacggt cccggtccgc gtgagactgg accccgaaca aacggtttcc caatttgtgg 23460aaagcattca gtctcaatcg actgatatga tcccttacga gcagttcggt ctacaagaca 23520tctccaagct tagccccgag gcgaaggacg cttgcgattt ctcatccctc atggtcatcc 23580agcccatgtc tagcatcgcc aacaacaagt ctgttcttga gcctccccca gaggacaagg 23640ctgctgctga agagagcttg cagaactact tcacttaccc tctggttatc caagctcacc 23700tgcatgatga tggtgcggtc aatctgctgc tgatttacga tgcgaatgtg ctctccgagg 23760atcaacttca agcactatcc atccagtttg atcatgtggt gcaacaatta cttggccaag 23820attccggggc taagctaagg gatgtcacca ttgccggacc atgggatttg cagcaggcta 23880tgagttacaa cgtcaaggag cccgggatcg tcaacgcctg tgtacacgag cttattgctc 23940aacaagcggc ccgagatccc catcacgagg ctatctactc aagcgaaggc acagttacat 24000atgccacctt ggatcgtctc tccagcctct tggcccacca cctacatgct catggagtac 24060ggcctgagtc ggtggttcca ttctgcttcg acaagtctgc gtgggccatc atcgcgatgc 24120tcgctattct gaaggctggt ggtgttttcc tcccccttga cccctcacac ccgcgcaacc 24180gtcgtgaggc tctgatcgag gaagtcggag cagaggtcat gattgtctct ccctcgtcgt 24240ctgtcacctg cgagggtcta actcccacca tggtagagct gacgactccg ctacttgagc 24300agctttcatc gacctatgat gccttccagc agattcatcc caagccaaag cctagcaatg 24360cagcctacgt cctttttaca tcaggctcta ccggcaagcc gaaaggtgtc ttgatggagc 24420actcgggctt tgccaccagc accctgggac acggccgggt gtataacctt ggcccgactt 24480ctcgtgtctt ccagttttcc aactatgtct ttgatggaag cttgggtgag atcttcacca 24540cgctctcgtt tggcggcact gtttgtgtgc cctctgagac tgaaagactc caagaagcgc 24600ctacctttat gcgcaagtcc cgtgttaata ctgccatgtt gacgccttct tttgttcgga 24660cctttacgcc cgaccaagtc ccgtcgctcc aattgcttgt cctcggtggt gaagcctcgt 24720caaaagatct catcgagact tggtgcgacc gcctgcgtct tgtcaacggc tatggaccag 24780ctgaagcttg caattacgcg acaacgcatg acttcaagcc gactgactct cctcgcacga 24840ttggccgcgg cttcaacagc gcatgttgga ttgttgagcc aaccgactac aataggctga 24900cccctattgg atgtgtcgga gagttgatta tccaaggaaa tgctcttgct cgcggctaca 24960tcaacgaccc caagcgcact gcagactcgt ttgtcactgc tgtcgactgt ctgcccagag 25020acatgatttc cggccctcac aggttctacc tgaccggcga tcttgttcgg tacaactcca 25080ccggcgaaat ggagtatctt ggtaggaagg atacccaggt caagctccgc ggccaacgtc 25140ttgagcttgg cgaaatcgag taccaagtca agcagtcatt gcctgagatt gagcacgttg 25200ctgtcgatgt ggttcatcgc gagaccggcg atgcccttat tgcgttcgtc tcgttcaagg 25260acacggcttc ttctgcttca agtgacatac tctcccttga tgacgagatg cactctacct 25320tggccacagt catggagcac ctgaagagct ctcttcctgg ctacatggtg cccagcacta 25380tccttccctt gaagaagatg ccattcatta cctcgatgaa agttgatcgg aagaggctta 25440ttgctgttgc agctgaatta tcgttggaag aacttacctc attctccctt gtcaagcgtg 25500actttgctcc gcccaccaca gccatggaga agaagttggc cgacctctgg gctcaagtcc 25560ttaagattga tgtcggcagc attggcaaga atgatagttt ccttcagatt ggtggtgatt 25620ccatcacctc gatccatctg gtcacgcttg cgcaaaagtc tggcatcaat ctgacggtag 25680ccggcatctt tgacgactct aagttatcat caatggcaca ctcagctggc gaaggcgata 25740ttgagccagt ttacgaggtg gtgccattcg atatggttgc cacacacaat ctgagctctc 25800tgatggaaga agtgcgcacc aagtgtgggc tgcccggttc tgcggtgatc gaggatatct 25860accctgcaac aagcttccag gaaggcctca tggcactggc cgtgaagcag cctggctcct 25920acattgccaa gcaggtctat cagctgccaa ggggtgttga cgttgctcgc ttcaaggccg 25980cctgggagac aactgcgcgc atgtgcagca acctccgtac tcggatcgtt cttgctggtg 26040atgcctctgt ccaggtcatc ttgaaggata ttggctcttg ggaagtcact tcaaacatga 26100cactcaagtc gtatcttcag gcgactcaga agattaacat ggactatggc tctgcgctga 26160gccgccacgc gctcattgag caggctgatg gcaagaacta ctttgtatgg tcaatccacc 26220acactgtatt tgatggctgg acgactcgcc tggtactcaa caccttgctc tctgcataca 26280tgggtgaaca gattgtcccg cttgagccgt atgcccgctt catcaactac gccatcaatc 26340tcaatatcga tgccgccaag tcctactgga ccgagcagct gttggatgcc aagcgggcat 26400tattccctgc tgtctccaac gaggtttccc gcaacaagac gtcaaacact cgtgtgctcg 26460agaaggcctt ggatctgccg caagtgaagc agacctcgat aaccatggcc tcgatcttgc 26520gcgccacatg gtccatcgtc cttgcccaat actgcgatac agacgacgtg acgttcggca 26580caacggtatc cggacgacaa gcccctgtat cgggtatcac tgaaatggcc gggccagttg 26640ttgctactgt ccctgtacgc gttcgactcg acagaaacgc ttcggttcca gagtttctca 26700agggcatcca gactcaggct tcccagatga ttccatttga acagtttggt ctgcagaata 26760ttgccaagtt gaatgttgag gccaaggaag cttgcgactt cagatcactc ttggtcatcc 26820aaccaatgaa gaagctgctt gacactggcg atcgcgaagc catcatggag cctgtttcag 26880cgactacccg ggatgaggaa gactttatgc aaaactactt ctcttatccc ctcgtcatcc 26940aaggccatgt gtatgaggaa tcggtcaatc tggtcctgat ctatgatgcg gacattctgc 27000ctgagcaaca gctgcttgct ttggctcatc aattcgagca tgtcgcacag caacttgttg 27060ctaaaggcaa ccgtactacc aagcttggag acgtatctgt gtctggtgct tgggacctgg 27120atttcgctct gcgtcagaac agcgaggtgc ccgagctcat cgactcttgc ttccacaccc 27180ttgttgaaca gcaagctgtc gtacggcctg aggctcctgc aatcaacgga tgggatgcca 27240agttcacgta tgcccagctc aacgaggctg ctaacagatt ggcgaaccac cttgttgcag 27300agtacgagat caacaacgac gagcttatcc acgtctgctt tgaaaaatct gcttggttct 27360tcgttgcaat tctagccatc aacaaggccg gcgcagcttg ggttccccta gacccctccc 27420acccatctca acgccatcaa caggttgtca accagacaaa ggcccgcctt gccctcgttt 27480cgacctccca catttcgact tgtgtcgacc ttgtggacga cattctagaa gtatcatcca 27540caaccgatga gcttcttcgc aagtcgcagt cttctcgcca tggtcctact cgcaaggtct 27600cgccgtccaa cgctgcgtat gtactcttta cctcgggctc aaccggcaca ccaaagggcc 27660ttgtcatgga gcacggaagc gtttgcacat cacaaacagc cattgtgaag cgcctgaaca 27720tgacgcccag tgtcaggatt ctgcaattcg ctgcctttgt gttcgatctg tcgataggcg 27780aaattgtcgc accactgatt accggtgcat gcatctgcgt gccttcagag cacgccagga 27840tgaatgcgct gcctgaattc gttcggcaga acaacgtcaa ctgggcctat ctcacgccat 27900catacattca aacccttagc ccgaaggacg tgcccggcct tgaattggtg ttgcttgccg 27960gcgaagctgt gagcagggac atcttggatg cttggtttgg caaggttcgt ctggttaatg 28020gctggggtcc agctgagacg tgtgtgtttt ccactcttca tgagtggcgg tccaaggatg 28080aagagtctcc tctcacgatt ggccgccccg tgggaggctt cacttggatt gtcgatcccg 28140aaaaccccca gaagctcgca cccatcggag ttccaggtga agttgtaatc cagggaccaa 28200caatcctcag ggagtatctg gatgatcctg tccgcacctc agacagcacc gtttacagtc 28260tccctccttg ggctcctaat cgaggaacca agtggaacag gttctacaag tctggtgatc 28320tttgctcgta caatgccgac ggaacgatcg agttcatcag tcgcaaagac actcaaatca 28380agatccgagg ccttcgagtc gaactaggcg aagtcgaaca ccacgtcaag tctgctttgg 28440acgtccgaca tgttgctgtc gatgtgcttc gatccagcaa tggttcgaac ctggtggcct 28500acttctgctt cagtgatcag acgagaatga atggtactcg tggaacttct gatggaagcg 28560gattgtttgc tgagatggac gacgaactgc aaactcgtct tactgccgtg atcggccagt 28620tgaatatttc gttgccgcgg tatatggtgc cgactttctt catcccttgc cagtacatgc 28680ctaccattac ctccacgaag ctggatagga actacctgaa acggcaaacc gcggcgctca 28740gccaggaaga gcttaccatg tattctcttc tacaaggagg gaagaagcgt gcaccagaaa 28800aagacatgga gaagcaactc cagtctatct ggtctcagat actttccatt ccatctgaga 28860gcattggcct tgacgatagc ttccttggcc taggcggcga ctcaatcagc gctatccgcc 28920tcgtggcttt atgccgtgag gaggccgtct cgcttacagc gcaggatatc ttcgacgacc 28980cacgcctgtt tgctgttgcg gcacgcgccc agaagatgaa cgtagttgtg gaagaatctc 29040ttgacatcgc tcccttctct ctcctcagcg agaagtccca ggaactggtc aaggccgatg 29100atgtgcgcgc tcagtgcaac ctgtcctggg aaaccgttgt cgatgcgtac ccctgcactc 29160ctctgcaaga aggtctcatg gccctctctg tcaagcagcc gggatcgtat atggcaagat 29220acgtctatcg catgcctcga accgtgaaca ttgcgcggtt caagtggtcc tgggagcgaa 29280ccgtttctct ctgcgacaat cttcgcaccc gcatagttct cgtcggcggc agagctacgc 29340agattgtggt cgatgggcct attgattggg atgtcagcca cgacttggag gcgcatctct 29400cggccatgaa gtccatcaag atgacctacg gctctgccct ttcgcagatc gccctggtca 29460aacaggacaa tggcgacatg ttcttcacat gggccgtcca tcactctgtc ttcgacggct 29520ggacagttcc catcctgttc aataccctgc aagctgtcta ccagggcgtc aagcccatcc 29580cacccgctcc atacgctcga ttcatcaaat

tcaccatggg tatcgacaac gacaacactg 29640tccagtactg gaaggatcag ttgcacaatg caaagaaagc cacattccct ccagctgcag 29700cccagtcggg ctcagtacaa gtgctggaaa catcgatcaa ctacacacag gcgcctggct 29760cgtctatcac cagagccacc atcttgcgtg cggcatgggc cctcgtccta gcccggtact 29820ctgagagcaa cgacatcacc ttcggcacca cgatctctgg tcgacaggcg cctgtggatg 29880agatcaccaa catggctggc ccagctgtgg ccacggtccc tgtgcgagtt cgtcttgaga 29940aacagcagac tgtatctgcc ttcttacagg gagttcaaag ccaggccatg aagatgattt 30000cctatgagca gtacggtctg caaaacatct caaaggttag cctggatgcc aaggaggttt 30060gtgactttac gtccttgttg gtcatccaac ccgttgagga cttggcgtac cttgatgatg 30120atgctctcct agtcaatgcc ggaccggaac tcactggcga gacagagatg atgcagaact 30180atttctcgta ccccctcatt atccaaggcc atctatatga gaatagcatc aagctgatgc 30240ttgtgtatga cactcaagtc atttcgacgg gcaagatgga cgcattgtcc caccacttca 30300acgctgccgt tcaacagctc actcgcaatg gcaacgccct cctagacaat gtatcacttg 30360cgagtgagtg ggatatggag aaggcaatcg ccttgaatag tggctcacct gatgctattg 30420aacgctgttt ccacgacatg gttgatgaag tcgctttagt acgaggtgac gctccggccc 30480tttctggctg ggataaatcc tttacgtaca aggaaatgac tgaggcgacg aaccgtcttg 30540ctcactatct cgtcaatgat tatggcgtca aagtgggaga tatcattcat gtgtgcttcg 30600agaagtcggc ttggttcatt atcgcgactc tggccatcaa caaagccggt gcagcctggt 30660caactctcga cacgtctcac cccatcgagc ggtaccagaa gattgtcagt cagacaggat 30720caaagctggc gctggcttcc gctgccaact cgtatcgatg tgttggcgtg ttgcctcacg 30780ttatcgagct tactcctgag cttgatgcta ggcttgccaa gaacacttct tggagcgctt 30840gcggaccagc tgttgcagtt attcccagcg atatggctta tatcctgttc acctctggat 30900ctactggtgt gcccaagggt gtggtcattg agcacgccac gctttgcacc agtcaaacgt 30960ctctgtcaca gactcttggt ttccacgagg aatacaaggt tcttcaattc tcgtcttatt 31020cgttcgatgc cgcggtgttt gagattgatt caactctcct gactggcgct tgcctgtacg 31080tgccctcgtg ggacgaacag atgaatgagt tggtgggcta tatccgaaag cacacaatta 31140cctgcacgct cctgactcca actctggctc gaaccctccg ccccgaggat gttccgtctc 31200tgaatatgtt gatattgggt ggtgaagctc ccactcgaga tatcctcgat atctggtttg 31260gcaaattgaa gctcgtcaac ggctggggtc cgaccgaggc atgtgttatc gcgtgcctcc 31320attcgtggac ttcggtagac gagtctccca gcgtcatcgg tcgaccaatt ggtggctcta 31380tatgggttgt tgatccggat gatgccactc gcatggcccc cgtgggaacg gtcggagaga 31440ttgcagttca aggccggaac ttgttccgtg gatatctctc tgatcccgtc aaaacggctg 31500ctgctacagt gacaggcctt ccggagtggg ttccaaagcg tgattcctct gctcactggg 31560atcgcttcta tctcaccggt gatttgggct tcatcaacga agccggtaac gtcgagtact 31620gcactcgcaa agacacccag gtcaagattc gaggacagcg actcgagctt ggggagattg 31680agcatcatat ccaagccaac ctcgaaggtg ttcgacaggt cgccgtggac gtcatcaagt 31740ccgatgctgg ttctacgctc gttgcttttg ttagcttctc tgatgccacg gaaccaatag 31800actctgacac atcggctttc ctgccacttt ccggagatct ccaagcaaca atcaccagcc 31860tggtgggaac tctgggcact ctgatgcctc gatacatggt gccaagtgcc tttatcccat 31920gcgcttacat gcccctcgca acgtccacca agttggaccg caagaaattg aaagagcttg 31980ctgcctccct gagccaggat gaactgtcta tctactcgct cgccaatgaa caaaaggccg 32040ctcctcagac tgctatggag agccgtatcc aggcgatatg gtcccaggtc ttaaacgtca 32100gcatcgattc tatcggacgc gacgattcgt tcctccagat tggtggtgat tctatcctcg 32160ctattcagct cgtttccgtt gctcgggatg ccaacgttaa gattaccgtt ggcgacgtgt 32220ttgatgatcc ccggttgctc gctgttgccg caaaggccac tgaacttgac gataacggcg 32280aggtcattgc taacatcgag ccttttggcc ttttggatga acccttgaag gacctggttc 32340tgagccagcg catccaagag cagtacagcc ttccaactga tcgcgagatt gaagatgcct 32400atccgtgcac gaagctccag gagggtctca tggctctcgc cgtcaaacag cccggttctt 32460acattgccaa gttcctctac cgcctctcca gcaacgttga cgtctcgcat ttcaaggctt 32520cttgggaaga gaccgttcgt ctcctaccca atttgcgcac caggatcttc actgccggca 32580acatgtctat tcaggccatc ctcaaggacg acatctcctg gcaaccaaca gaaggcgact 32640ctctgcgatc atacatgggc tcagctcaga actttgagat gacctatggt tcgccgctgg 32700ctcgatatgc cctcatcgag gacaatggag atacttattt cgtcctgtcg atgcaccacg 32760ctgtctttga cggttggggc atcagggtgt tgatgagcgt tttccattct gtgttccgca 32820agcaagcccc cgttatcgag ccgtatgtac gtttcgtgca gtacaccatg gatgtcaaca 32880acgatgaagc ttcagactac tggcggtctc agttccaggg tgcgagacaa accatcttcc 32940cgcccaatgc atctgcatca gagagcagga agaacagcac tcagacggtc gaaaagatga 33000ttgagctgcc tagcatgaac aagtcgtcta tcacaaaggc caccatgctc cgagctgcct 33060gggctattgt cctttccagg tattgcgaca gtgacgatgt tactttcggc atcaccatct 33120cgggccggca ggcgcctgta catggcctaa tcaacatgac gggtcctgct atcgcaactg 33180ttcccgtgcg tgttgctatg gatcgcaaga cggttgtcaa ggattacctg caggccatcc 33240agagccaggc aaatggcatg gttccctttg aacaattcgg cctgcaaaat atctctcgcc 33300ttagtgctga ggctaaggat gcctgcgact ttggcagtct ccttgtcatc caacccatcc 33360aatcactggc ctacgtcgat gagagtgcag acactgtctt tatcccgctt gacgtggata 33420aggaggttac cgataccgtc cagaattact tcagctaccc cttggtcatc caaggccaca 33480tgcatgaaga cttcatcaac cttgtgctca tctatgacac aggtgtgtta gcagagagcc 33540agatggttgc cttgtctcac caattcgaga atgtcctgaa gcaactcgcg tccaagcccg 33600atctggagct gggctctgta tcaatggctg gtgactggga tcttgaattc tccaagagac 33660agaacagcga ggttcccgag atccttgatg tttgtgttca tcagcttatt gagaagcaag 33720ccgctgccca gccagatgcc cctgccgtcc tgagctggga ccatagcttt acgtacaagc 33780agctcaacga agcatccaac aggctggcac atctccttgt caacaaatac cacgtcaagc 33840ccaacgacct ggttcacgtt tgctttgaca agtgtgcttg gcatttcgtc gcaataactg 33900ccatcaacaa ggttggcgca gcttgggtgc cacttgatcc ctcgcatcct gaaatgcgac 33960ttcgtcaaat cgtttcccag actcgggcca ctctgactct tgtgtcttca tctaatgcat 34020ctctatgctc ttctcttact gagagggtca tagaagtcaa tgcaagcctt gataacgagc 34080ttctggcagt ggaaagcggt gaatatggcc cttctgtgga cgtctcctcg cacagcgccg 34140cctacgtgtt gttcacgtcc ggtagcacgg gcgttccaaa gggtttcgtt atggagcacg 34200gctctgtatg tacgtcgcag attgctatcg ccaggagact tggactagga ccaaacgttc 34260ggatgctgca gttcgctgca tttgtctttg acttgtccat cggcgagatc gttggtccgc 34320tcatctcagg tgcctgcatc tgtgttcctt cagaagacac tcgtataaat ggcatcgttg 34380ccttcattaa cgagacgaag gttacttggg cctacataac accatccttt gcccgtacaa 34440tcaagccgtc cgaagtgcct cacctagagc tcctgctact ggctggtgaa gctgtccccc 34500gggatgtttt cgcaacttgg tttggcagca ctgtccgcct tatcaatggc tgggggccag 34560ccgagacctg cgtgttctct actctccacg aatggaagtc tgctgatgaa agtcctctga 34620cagtcggtcg tccggtgggt ggattctgct ggatcgctga ccccgaggat cctagtcgac 34680ttgcagcaac cggtacccta ggtgaaatcc ttatccaagg acctacaatc cttcgggaat 34740acctctcaga cgtcgccaga acggaggcta cggtcatcaa gtcccttccg gagtgggctc 34800ccttccgcaa cgaacctggc tgggatcgga tgtataagtc aggagatctt ggcttctaca 34860accctgatgg aaccattgaa ttctccagtc gcaaggatac ccaagtcaag atccgtggtc 34920tgagggtcga gttaggtgaa gttgaacatc acgttcaggt cgctttaccc ggcgttaaac 34980aaatcgctgt agacgtcttc cagggcgaaa acggtaccaa cctcgtggcc ttcttctcct 35040tcaatgatga aacccgccaa atccatgaag cagattcgtc cggacctttt gagccgctcg 35100acgacaactt gcaggatcgc cttactgctg tcgtcggtga gcttagtgta tctctgcccc 35160gatacatgat tcctaccctc ttcatccctt gcaagtatat gccgtctatc acgtccacca 35220agcttgaccg gaacgaactc aagcgtcgca gcacagcact tagccagtct gaactcgctg 35280tgtattcgtt gcagggcgga aagaagaggg ctcctgagac accaatggag agcctcatcc 35340aagccctttg gtcagacatc ttgcacgttc cggccgattc tattggccgt gacgacagct 35400ttttgggcct aggtggcgat tcaattactg caatccacct ggtcagcatt gctcgtgaga 35460agggcattca acttgttgtg aaggacatct ttgacgatcc tcgtctcttg gccgtgtcca 35520gtaaagccaa ggagatggac atcgaggctc gacaagagct gcttgaggta tcgccgttca 35580gtcttctgaa tgctgaaact catgatctcg ctatcggtcc aagtgtcaga cagcaactca 35640atttgctcga aggccagacg attgacgatg cgtacccctg taccaagctt caggaaggtc 35700tcatggcctt gtcagttact caaccgggat cctacatcgc gagatatgtc taccgtctat 35760ccagacaagt cgatgttgct cgcttcaagt ccgcctggga aaccactgtt gctctgcgtg 35820atatcctacg aacgcggatc gtcatgatta acggcacatg cattcaactg gttgtcaagg 35880gtggtgtcgt ctgggatctt atcgattccg agagtctgga ggaagctgcc cacaagacgc 35940actctcacac catgacctat ggctcgcaac tatccagaac ctccatctat gagaccaaga 36000ctggcgacaa gtacttcctg tggactgttc atcacgccat ccacgacggc tggtctgtgc 36060ctgtcatctt cagcactctc tatcaagctt atgaaggtct ggaactgggg actcccaagt 36120cttactccgg cttcatccga tacactttgg agcttgatca ggaggctgct agcaattact 36180ggagagaaca gctgcaagac gccaagcggg ccagtttccc caaaaccgga ctcacgacaa 36240aatccgccga caatgagcag aagattcagg tcatgtcgac ttctctcagc ttcccttcat 36300catccaacga agctgtcact aaggctagcg tcatgagggc tgcctgggcg gttgtccttg 36360caagatactg cgacagtgat gacgtctgct ttggtgccac catctctgga agacaggcac 36420ctgtgcatgg tgtactcgag atggccggcc cggcagttgc aactgtgcct gtgcgtgtga 36480agctggacaa gggccagagc atccctcagt tccttcaagt catccagaac caagcccatg 36540agatggttcc atatgagcaa tatggtctac aaagtattgc gaagctggga gcagatgcaa 36600gagatgcttg cgattttacg tctctcttgc tgatccagcc tgttcagcgc ctttcttcgg 36660gcgttgcaga tgaggagggc ctcttggttc ctgctcagtc agagatcaag gacatggttc 36720agaactacta cagctatcct ctcgttatcc agggtcacgt atacgatgac cgagctgatc 36780tcgttttgat ctacgactca acggttgttc cagagcccca gatgactgct ctttctcacc 36840actttgacaa tgtggtgcag cagctgttgg ctgtggatgg caagttgggc gacatttctg 36900ttgctggttc atgggatctt gagcttgcac aaaagtccaa tggcgacgga cccgagatca 36960ttgaggactg catccactcc atcattgaga gacaggtcca acagaggcca aactcacctg 37020ccgtcgatgc ttgggacgga cgtctgacct acagccagct ggatcacgcc gccaataggc 37080tcgctcacct gcttgttgat gactatgcgg ttcaagttgg cgacattgtg cacgtctgct 37140ttgaaaagtc gatgtggtac attgtggcta ttctcgcgat caacaaggcc ggtgccgcct 37200gggcacccct cgattctgcg catcctttcc agagactcca ggctgttgct aagcaaaccg 37260gtgccaaact ggcccttgct tcgactgcaa acgccggact ctgcaagcag cttgtggatc 37320gtgtgattga agtgtcggca gctctcgacg aaaagctctc gtccaacgcc gtcagcagcg 37380gaaagggacc tcaagtcaat gtatcccctc tagatgctgc gtatatcctg ttcacatctg 37440gttccactgg tacaccaaag ggtatcgtga tgcaacatgg agcactctgc acaagtcaaa 37500cggacatcag tcgatggctg ggccttgacc acaccgtcag gatgctgcaa ttctcatcgt 37560ttgtgttcga tgtgtctgtc ggtgagatca tggagccgtt gatgaacggt gcctgtgtct 37620gtgttccttc ggaccacatg cgtctcaaca gcctcgatgt ctttgtccgc gatttcaacg 37680tgacttgggc gtatctgacc ccgtcattta cgcgcacctt gaagccggaa gacttccctg 37740gactcgagct tctgttgctt atcggagaag ccgtcactca ggatgtcctc gatacgtggt 37800ttggtcttcc taacacccgc ttcgtcaacg cttggggtcc tgcagagacg tgcgttttca 37860gcacactgta tgactggcag tccaatactg agtctccctt gacgattgga cgagctgttg 37920gtgcgtatgt gtgggttgtg gatgctgaga atccccagcg gctcgctcct acaggctgct 37980taggcgaaat cgtcgttcaa ggccctccac tcctcaggga atatcttgct gatccttcga 38040aaacggcggc tgctactgtg acggagctcc ctgagtgggc tccccgacga gaattgacca 38100aatggaaccg cttctaccgg actggtgacc tgggcttcta cagtcatgat ggtctgcttc 38160actatgccag ccgcaaggac actcaagtca agattcgtgg attgcgtgtt gagttgggcg 38220aagttgaaca ccatatccga agctcgttgg atggtgttcg ccaggttgct gtcgacgtct 38280tcaagactga gacgggagcc aacttggtga cctacttctg ctttaccgat gacaccaaga 38340ctcctggccc tgacaccgat cctgagggca aagatgtgtt catgtctatt gacgctgccc 38400tacaggagaa gctgggcaac atgttgagca aattgaactc atcactgcct gggtacatga 38460ttccaacact ctttatccct tgcgactaca tgcctctcat ctcgtctgcc aagttggacc 38520gtgtcaagct tcgtcgcatc acagccgagc tcagtcaaga tcaactggaa tcctattcgt 38580tgcttgacac cgataaacgg gcgcccgaga cggaaatgga gattcgtctc cagaagctct 38640gggctgagat cctcaactta ccggaatcct cgattggccg agacgacaac ttcctacgaa 38700ttggtggtga ctcgattgct gctattcgtc ttgtttcaat ggcccgcgac gtcggaatca 38760gcctgacagt tgacgacatc ttcaatgacg ctcgtctgat ttcaattgct gccaaagctg 38820ttgatggcga tgtatatagc tccatcatgg cgccgattga tgcattcagc ctcttgtcac 38880ccggaactgg agacttggtt ctgccctcag ctctccccga agggcaggtt atcgaagatg 38940cttacccttg cagcaagctt caagaaggtc tcatggctct cgctgtgaag caaccgggct 39000catacatcgc caagtatgtc tacaagctcc cagagcatgt ggacgttgtc aagttcaaag 39060cggcttggga gcgcacagtg gagttgtcca gcatcttgcg cactcgcatc atccagatca 39120acggccgttc gatccaggtt gtcatcaatg gtgatgtaac ctgggatgag actgatggca 39180gcttgcagcc gtgccttgct cgtgctcaat ctctcgagat gggctacggt gatcgtcttt 39240gccagtacgc tctcattcga gatggcaaca gcacatattt catgtggaat gtgcaccatg 39300ctgtcattga tggtctgtca actcaaaaca ttctggccac gcttttcagg ctctacagcg 39360gcatcgacgt gttgtcagtt cccccatttg cgcgcttcat caagtacatt ctcggtctcg 39420atgaagaggt cacagccaac tattggaaga cgcagctgtc caacgcccgc aaggccattt 39480tcccgccctc aaaggatgcc tccaatgaca agccagaggc tactcgaacg ttggagacgt 39540ctattgatct tccttccagc atcaagaact caaccatcac aatggccaca gttgtccgat 39600ctgcctgggc catcgtgctt gcgaggtact gtgagactga cgatgtgaca tttggtacta 39660caatctcagg tcggcaggct cctatccccg aggtcatgga aatggtcggt cctattattg 39720ccaccgtgcc agtccgcgtc cgtattgatc gccgtcagct cgtctcggag ttcctcgaag 39780gcgtgcagaa gcaagctgtg gagatgacgg cctttgaaca gtacggcctt caaaatatcg 39840ccaggctgag tgaggacgcg cgtgatgctt gtgactttgg cagtcttctc gtggtccagc 39900ctatgcagca tcttggtggc gccggcaacg acgatgccat cttggtcgat gctgcaattc 39960cggacaatag ttctgctgag tctctccgga actatttctc ttatcccctt gtcatccagg 40020ctcacttgta cgatgatcat gtcaaccttg tgctggtcta cgactcgaac gtcatcccag 40080aggctcgact ggtggcatta tcgcatcacc tcagtcatgt tatgacacag ttgaccacca 40140ctgagccagc tgccttggac actgtgtcag tctcttcgcc atatgacgtc cagaaggcat 40200tgtcattcaa tactgaagtc ccagaggtca ttgacgcctg cattcatgaa ttgttcgaac 40260aacaggccag tttgcgtccg caagcgccag ctattgccgc ttgggacggc aacttaacct 40320acgacgagct taacaaagca gctaacaagt tggctcacca cctcgtcaac gtctatggtg 40380tcaagcctaa cgatttcgta cacgtttgct tcgagaaatc agcttggtac atcgtctcga 40440tccttgcaat caacaaagct ggcgccactt gggtcccctt ggatccctcc caccctgagc 40500aacgatggca gtctatcatc agccaaacaa aggccactct tgctctggtc tcgccgggta 40560gtgttggccc cctatcacgc ttgatcgaca atgttgtcgc ggttgattcg aacctcgata 40620gcttgcttcc tgaacatgac gcggcacgag gcctcagtgt gtcaatctcc cctagtacag 40680ctgcatacgt gctgtttact tcgggttcaa ccggcactcc caagggattc atcatcgagc 40740acaggtcgat atgcacaagc cagaaggcgt tcaacaagag gctacgctac catgaaaacg 40800tgcgcgtctt acactttgcg gctactgttt tcgatctctc gattggtgaa atcatcatgt 40860cgcttctaaa aggagcgtgt ctatgtgttc cttctgagca cactcgattg aatggcatcg 40920tcgactttat ccgcgacatg aagatcaatt ggctctatct cacgccctct ttcttgcgaa 40980cgatagatcc aagccaggtt cccaatgtcg aattgattct cctggcaggc gaagctgtgc 41040cgcgcgaggt tttcgagacc tggtacggac gcgttcgtct gttgaacggc tggggtccag 41100cggaaacatg tgtcacgagc gccatccatg agtttgaatc tgctgacgac tcaccgttga 41160ccgtcggtcg ccctgtgggt ggcttctgct ggattgttga tccagagaac ccacagcttc 41220ttgcgccgac agggaccgtg ggcgaggtcg tcatccaagg accaacattg cttcgcgagt 41280atttggataa ccccgaaaag acgcaagaga caacagtcta tgagctacct gactgggcac 41340cccgtcccga tgagaagaac tggagtaggt tctacaagac gggcgatttg tgcttctaca 41400acccggatgg cactattgag ttttcctctc gtaaggacac acaggtcaag attcgcggtc 41460tccgtgtcga gcttggcgaa atcgagtacc atgttcaagc atcgctggaa ggaatccgtc 41520aaattgctgt ggacgtcgtc aaaaccgaca acggctctca cttggtcgct tatctgtgct 41580tcaacgatca gatgcgtcaa cctgacgaag ctgaggtcaa cgggccattt acccctatcg 41640atgctgagct tcaagacaag ctcattggcg cagtcagcat gttgaatgtg acgctcccga 41700ggtatatgat tccgacattc tatatcccgt gcagctacat gccctacaac acatctggta 41760agctggatcg aagggagctc aagacgcaaa ctgctgctct aggccagtcc ggactgagca 41820atttctcact acacggcgtt gataagcgtg cccccgagac gccgatggag attgagctac 41880agaaggtctg gtcaacggtc ctgtctctcc cgaccgactc gattggccgt gatgatagct 41940tccttggctt gggcggtgat tcaatcatgg ctatccatct tgtcagcgcg tgccgcgaag 42000ctggcatctc ccttaccgtc aaggacgttt ttgatgatcc tcgcctgtcc gcggttgctt 42060ctaaggcttc ccgccttgac tctacggatc aagagacctc cgtcgcgcct ttcagtttgt 42120tgcccgaccg tatccgcgag atggcgctca gcaacgatgt ccgatcacaa gtttcattgt 42180ccgccagcga ctcagtggaa gatgcctacc cttgctcaaa actccaggat ggtctgatgg 42240ccttgtccgt caagcagcga ggctcctatg tcgcacagta tgtgtacaag ctgtcgacca 42300gtgtcgacct cgagagattc aaggctgctt gggagaagac actccagctt tgtgcaaacc 42360ttcgcacccg tatcgtcatg cttgatggca tttgcgttca actactgatc gatggcccgg 42420cggaatggga cgaccaatct ccaacggact tgaaggccac tgttgatgcg actcgcactg 42480acatgaccta cggctctcgt cttaaccgtt ttgctcttgt ccaggatccc gagtttggca 42540accactttgt ctggtcatca caccacgccg ttcatgacgg ttggaccctt agaattgtca 42600tgaatactct gtacggagtc tatctaaacc aaacggcacc tcgtcttctc ccgtattccg 42660cctttatccg ctacacagtc aacatcaacg cggacgatgc caatgccttt tggagcgagc 42720agctgaggaa cgcgaagcgt gccacgtttc caccaatgcc ccgtatcgag tcccatgcta 42780gcatcactcg catgatgaac aagacgattt ccttccctcc ctccgtcaag acaacgacta 42840cgaaggctac tattctccgt gctgcttggg ccattctcct agcccgttac tgtgattctg 42900acgatatcac gtttggaacc acaatttctg gccgtcaagc tcctgtgccg ggcctcacgg 42960aaatgccagg cccagtcgtt gcaacagtcc cgattcgcgt tcgcattgat gccagccagc 43020cagtgtctcg cttcctgagc aagatacagt cacaagcaac tgacatgatt gcctatgaac 43080agttcggtct gcagaacatc atcaagctgg gtgctgacgc taaggatgcc tgcgagttct 43140cttctcttct cgtcatccag cctcgaactc acttggatgc aattgagagc aaggaagctt 43200ctgatcccct gatgacgact tcggtggcgg caaagggcgc tgagcaactc atgcaaggct 43260attttacgta cccccttgtg atccaaggcc acgtttttga cgactctatt gagctccttt 43320tgacgtatga ctcgaccatc ctgtcggaag tcgccatgga agctctttgc catcaatttg 43380acgttgtctc taaccagctg gtcaaggaat ccaatgaccc tcttggttcc gtcgccgtct 43440ctggtgaatg ggatctcgag caagcaaaga agtggaacgt tgagaatccc gacatcctcg 43500acacatgcat ccacaacctc atcgaagagc aagcacgcat cagaccagac gcaccggcca 43560tttgcgcttg gaatggtgag atgagctaca gccagctcaa cttcgctgct aacaagcttg 43620cccatcacct tctcaacgcc ggcgtcaagt ccgaggactt ggtacacgtt tgttttgaga 43680agtcgctgtg gttctttatc tccattgtcg caattaacaa ggtgggcgca gcttgggtgc 43740cgcttgattc atctcaccct gagcagcgtc tgcgccaagt cgtgagccag actcgtgccc 43800aatttgcgtt gtcttctcct accaatgccg ctctttgtgg aagcctcgtc gacaaggtca 43860tcgaagtgtc acaaggcctc atcgacagtt tcccgtacga tggtgccaat ggaccggcca 43920tcaaggtacc atcaagcaac gctgcatatg tcctcttcac ttcgggcagc acaggaacgc 43980caaagggtct tgttatgcag caccaagccg tctgtaccag tcaagccgcc atcgctaaaa 44040ggcttcgcct gacgcctgat gtgagaattc tccaattcgc cgcatacgtc ttcgatttat 44100cgattggaga gatcgttgct cccttaatcc atggagcttg tgtatgtgtg ccatcggagg 44160agatgagaat gaatgggctg aaggaattca tccgggacgc atccatcaac tgggtatttt 44220tgacgccttc ctttgttcga acgctgcggc ctgaagacgt acccaatctt gatctactgc 44280tccttgccgg tgaagccgtg ggaagagata tcctcgacac atggttcggt aaggtacgct 44340tggtcaatgg ctggggtcct gctgaaacgt gtgtcttctc cacgctacac gagtgggctt 44400ccattgacga gtctccattg actgttggaa cacctgtcgg aggtcactgt tggatcgtgg 44460acgccgagga ctccagcaag ctggcgccaa tcggctgctt gggtgaagtc gttcttcagg 44520gcccaacgct acttcgtgag tatcttgctg atcctcagag gagcaaggag gccatcatca 44580cctcgttgcc gtcatgggcg ccaaagcaag acagtcagcc ttggagccgc ttttacaagt 44640ccggcgactt gtgctactac aaccctgacg

gcacgctcga attctatagc cgcaaggata 44700cccaggtcaa gattcgtggc ctccgtgtgg aactgggcga ggttgaacac cacattcgtg 44760aatcgcttga aggtgtccga caggtggctg tagatgtgtt gaagtcagaa acaggtacta 44820acctggtctc atacctctgc ttcaacgacg actctcagcc cgtctcgtca gagcttcaag 44880caagcgatgt ctatctcccc cttgatgccg acatccagac tcgcatcacg gccatggttg 44940gcgagcttag tgtgaccctt ccacggtata tgattcccac gctgttcatt ccttgcaaat 45000tcatgcctgt cattacctcc accaagttgg acaggaaaac actcaaggca atgacggcgt 45060ccctagacag ggatcagcta gcacactact cgctgattga tagcaagaag agagctcccg 45120agaccgagat ggaaacccgc ctccaggtca tctgggccga catcctcggt cttcctgtcg 45180actcgattgg ccgtgacgat agcttcctcc agattggagg tgattctatt actgcaatct 45240acttggtgtc taaggcccgt gaagccggca tctcgcttgt tgtcaaggat gtctttgaag 45300actcgcgtct gcttgccgtt gcttccaagg ccgtcttctc ggaatacgcc caagaggatc 45360aggagcccgt cgtacccttc agcctcttga acgaacagac ccgtgccctc gtgcttggcg 45420gcgaggttcg caaactgtgc ggccttgctg aagatcagat catcgaagat gcttatcctt 45480gcacgtcact gcaggaaggt ctgatggcct tgaccgtgaa gcaaccgggc tcgtacgttg 45540ccaagtatgt ttacaagctt gcgcccttcg tcgacgtcga tcgcctcaag gctgcgtgga 45600gccgcactgt tgagctctgc ggcaacatga gaacgcgaat cgttctgcta aatggctcgc 45660ctgtccaact gctccttaag gaggacagcc agtggcagtc actggaggcc gagacacttg 45720cctcagttgc cacgtcttct cgcgacttga tgatgggcta tggatcacct ctttgctggt 45780acggaattct cgaagagaac gatgctcgat atctggtgtg gtcggcccat cattccatct 45840acgatggctg ggtgatgcgt atcctggtga ctaccctata cacggtatat cacggcgcgg 45900aagtcacgcc tttgcagccc tattccggct tcatcaagta caatatggag ctggatagtg 45960cttcttccgc tgagttttgg cgagagcaat tgtcaggctc caagagggcg gcattcccag 46020cccgacagcc cgctgccaca tcatcgtcct caacgcagat attcaaatcc agcatcagca 46080ttggacaagc caaacagagc agcatcacaa aggcctctat tttaagggct gcctgggcta 46140tcgttcttgc gagatactgc gataccaacg atgttagctt tggtgcgact gtgtcgggtc 46200gccacgctcc tgtggctggt ctcgagacca tgcccggtcc tatgattgcg actgtcccag 46260ttcgcgttca cttggatcgt gcttccacca agtcccagtt ccttgcaagc atccaaagcc 46320aggcccacga gatggttcct tatgaacagt ttggtcttca aaacatctca aaggtaagcc 46380aggatgctag ggatacttgc gatttctcaa gcttgctcgt catccaaccc cctgcgacca 46440ccatctcaga agaggactcc aagaccaaca tcctcgtcta tggtgacgcg gaacagagcc 46500gcacggatga cgctatgcaa aactacttca actatcctct cgtcattatc atgaacacct 46560ttgaggatca cattctgcag cgcttcttct acaacccaga cgtcctggac gaggctcgag 46620tgtctgcttt gtcgcagcac attggccatg ttgttgagca gcttctggca tcaagcgatg 46680aagccctcga cagcattgac ctcgtcagcg actgggacgt gcagcacgct gtggaatcca 46740cacggctgaa gccgtcaacc gagtcatgta cgcattggct catccgagat cgcattgaga 46800agcagcccag cgatcccgct attgcttctt gggatggcga tctcacatat gaagagttgg 46860gcgtcttagc atcccgtctt gcgtggaaac ttcaaggcct cggcgttgga cccgagtccc 46920tcattccatt gtgcttcccc aagtctacct gggcagttgt tgcaatggtt gctattgaga 46980tggctggtgg tgccttcgtt ccccttgacc ctaaggcgcc tgttgctcgt cttcgtggta 47040tcattgaaga caccaagtca accctggcag ttgccagccc gtcatgccag gatgctcttc 47100atgagattgg catcgatgtg ttggccgtcg acgaggctct cctgctggag ttatccgacc 47160ccgtggaggg cattcagtca aaggcagggc caaaggacgc aagtgttgtg ttgttcacct 47220caggatcaac cggaaagccc aagggaatgg ttatccagca caacagctta tgctcatctg 47280gaaatgcgta cggccaggac ctcaacatcg gacctggaac gcgtgtcttc caattctctg 47340cctatacctt cgacgttggt gtacttgact gcctcgtttc tctcatgcgg ggtgcgacga 47400tatgcattcc ttcagaccat gctcgcctca atgaccttgc tggagctatg actgcaacca 47460aggccaattg ggtgttcctt acacctacgg ttgcggatct tctttcacca gcagatgttc 47520catatctcaa ggtcctctgc ttgggtggtg aagccattag caagaagtgt gcagaccgat 47580ggatcaacta cactgagctc catggcttat acggccctgc tgaggcttcc atctgtgcct 47640ggaacccaag tgttggcaag tctgggcggt caaccaacct cggaagaccg atatcatcag 47700ccttctgggt agtcgagccc aataaccata agcaacttgt ccccgttggt tgtattggtg 47760agctcttgat cgaagggcca atgctcgctc gaggatatct caacgtcagt gccgacgttg 47820cttccaactg gatggataac gtcgactggc tcccgggaag cgacaagaag agagtctaca 47880ggacaggtga cttggttcgc cgcaacgctg acggaacgtt tgagtttatg ggccgtaaag 47940atacacaagt gaagctccac ggtcaacgtg ttgagcttgg cgaaatcgag gcccgtatcc 48000acgaattcct ccccagtgac atggctgcta tcgtcgccgt tgtcaaggac gaacacggcc 48060atgacagctt gcttgctttc atgtggtaca ccgaaggggt cgttgcctct cgatcgaccg 48120cccatctcat ggaggttgtc tcagacgagg cgcgtgccac catctctcat gttgactctt 48180ccctcgaaat ggtgctgcct tcatacatga ttccatcgtc ttatctggta ttcgagggca 48240agcctgaaca aaccgtcaat ggcaaagttg accgaaaagc actgctggct cacgctcaga 48300acttatcaac acaagatcgt ctgcgattcg cgcctgttgt tggcaagagt gagccaccga 48360gcacccccat ggagttcagg ctcagagacc tctgggctca ggtgttgcag attgacgctg 48420agtctattag caagaatgat agcttcctgc gtattggagg tgactctatc agcgcaatcc 48480agctcgtctc tttggcccag cagaataaca ttggcctcac ggtagctgcc atctttaacg 48540atcctcgctt atcccacatg gctgaggctg ccaacgttga cgacatcatg cccgtctatg 48600agactaagcc atttagtatc atcccggctt cggctatgga tgaggttctc gcccaagtac 48660gctctcagtg cgacaatctc tcagagacag ccatcatcga agatgcttat ccctgcactc 48720gattacaaga agggttgatg atcctggctg tgaagcaacc tgggtcatac gtcgccaagc 48780atgtgtatcg cctttctgat aacatcaacg tcgcgcgatt caagcgcgcg tgggatcaga 48840ccgttgaagc ctgtgcagcg ctgcggacgc gaatcgtcct tgttgacggc tcagcttacc 48900aagccgtcat caaagactct gtgaaatggc agacagcatc cgacattcgt tcattctcca 48960tgtctccgga caacactcaa atgggctacg gctcccctct atgccggtac gcgcttattg 49020agcagaatgg tgagaggtac ttcgtttgga atactcatca cacggtatat gacgggtgga 49080ctttgcccct gatcatgggc acgcttcacg ctttctacag cggcactgat gcccctccac 49140tcctccccta ttctggcttc gtcaagtatg tgacggaaat ggactctgcg gctgctagtg 49200agtattggac tcaacagctt gagggtgcta ggaagactac tttccctcct ggagctgaag 49260ccgtcaagac caagaaatcg cagatgtcaa ccagggtcat gcgcaacacg gtccaattcc 49320cacggtcgac taatacgtca atcacgaagg cttctgtcct tcgagccgcc tgggcgattg 49380tgctcgcacg gtataacgat actgacgatg tctgcttcgg atctacagtc tccggccgcc 49440atgctcctgt accaggaatc gagcgaatgc ctggccttgc ggtcgcgact gtccctgtcc 49500gcgtcaagct ggatcagaag cagtccctgg atgccttcat ggagggtatt cagtcgcagg 49560cctctgagat ggtcgcatat gagcaattcg gcattcagaa catatccaaa ttgaacgcca 49620aggctaagga ggcttgcgat ttcaccagct tgttggttgt acaaccgacc cagcacatca 49680cttcgactgg aaacgccagc gaagaagccc tccttactgc cgcagcaacg gacgacattg 49740ctgctgacga gatgctggac aactatttca actacccctt ggtcctgcag tgttacgtgc 49800ttgataacca agtcgagctt gtcctcgtct atgactgcga tgtcattgct gagcatcaac 49860tcgttggctt gtcccaccag ttccagcatg tagttaccca actgcttagc caggatggtc 49920ctctatctgc tgtttctgta gcaagtgaat gggaccttga gtttgctcag gcgtccaatc 49980acgatgagcc tgctgttgtt gacgactgca tccacaacat gatcgagcaa cgagccctga 50040tgaaccccaa cgctgaggcc gtcagtgcct gggacgcccg ctttacctac gctgagttgg 50100accggtctgc taatatactg gcaaaccatc tgatccaatc aaggggcgtt caagtaggcg 50160acttggtcca cgtgtgcttc gagaagtcgg cttggtatgt cgtatcaatc ttggccatca 50220acaaagcggg tgcagcttgg attccactgg atccgtcaca tcctgccgaa cgccaccaac 50280aagtggttgg gcaaactcgc tccagattgg ccctcacgtc gcccgcaaat gctgccaagt 50340gtgccaacct tgtagccaac gttttggagg tgacgagagg gctcctcgat gacctggaaa 50400cgcaagtcaa ccatgcaagg ccagtcacaa gtgtcggtcc tcaagatgtg gcctatatac 50460tgttcacgtc cggatcgact ggtgttccca agggcgttgt tatggaacac ggagctctct 50520gcagtagcca gacgtccatc agcaagcgac ttggctatgc acctggtgtg cggatgcttc 50580aattcgcctc gtttgtcttc gacgcctgta ttggcgagat aatcgctcca ctgatctcgg 50640gctcctgcgt ctgtatcccg tcatgggaga cacagatgaa ctcactgacc agctacatcc 50700gcgaggaaaa tgttacttgg gccatgctca ccccgtcgtt tgcccgtacc atggatccta 50760gcgaggtacc ttgcttggag ctcctgatcc tgatcggcga ggctgtcagc cgcgacgtat 50820tcgagctgtg gttcggcaag ctccgtctac tcaacggttg gggtcctacg gaaacgtgtg 50880tctttggtgc tctgcacgag tggcagtcca tcgacgaatc tcagatgacc atcggtcaac 50940cagtcggtgg ttactgctgg atagtcgacc ctgaagatcc gcagagatta gcccctacag 51000gcacctttgg tgaggttgtt attcaagggc ctaatctgct tcgcgagtat cttgccgatg 51060aggtcaagac ggcttcatca actgttcctg tcctcccaga atgggctccc aacaggcatt 51120tgcgtcattg gaaccggttc tataagacag gcgatctggc gatgtacaac ccagatggaa 51180ccattcagta ctacagccgc aaggacacgc aggtcaagat ccgaggtttg agagtggaat 51240tgggcgaagt cgaacaccac gtacgacaga atctcgacgc cgtccaacaa gttgctgtgg 51300acgtgttcaa gacggattct ggcgtcaacc tcgtttcgtt tgtgtgcttc aacaacgaca 51360ccctcccggc cagcatgact ggcgatatca ccagcaagga catcatcacg cccttgacgg 51420gcgagctcaa ggagagcatc aacagccttc tgggtcgtct aaacgtcctc ttaccgggat 51480acatgattcc tacgttgttc atcccattca aggccatgcc actcgtcaca tctggcaagc 51540ttgataggaa gcttctgttg aagcttactg cttcgcttga gaaggagcag ctagaggaat 51600atgccctcac tggcggtgac aagagagagc ccgagactga gttggaatac cgcttacagg 51660agctatgggc tactctgctg aatatgccag cttccgccat tggccgcgat gacagcttcc 51720tgcggattgg cggtgactca attgccgcca tccgccttgt ctccaaggcc cgtgagagcg 51780gcatatctct cagtgttgat gacatcttca gtgatccccg cctcctagct gtcgcagcta 51840aagctaccga ctcagcagct gaaatcgagg atattgtccc aattgagccg ttcagcctca 51900ttaatgaggc tcaacactcc atggtcctta gcagttcctc ggacttgcac ctgtcagccg 51960acatggaaat cgaagatgcc tacccctgct caaagctcca ggagggtctg atggctttgg 52020ctgtgaagca acctggctcg tacattgcca agtaccatta ccgcctgcct tcccacatcg 52080acgtggcccg gttcaagcgt gcctgggaga tgactgttga gacgtgtgcc aacatgcgga 52140ctcgcatcat caccgttggt gggatgacga ttcagacggt catcaagaac gacattgctt 52200gggaggatac tactggtatg actctcatgt cgtatgtacg tgccacccag aagaccgaga 52260tgggctacgg ttctcgtctc tgccgttacg ccttggtcga agaggagggc caggatgtcc 52320agtttgtctg gagcattcac cacgccgtct tcgacggttg gacaacgccc atcatcatga 52380gcgctttaca cagcgcatac agaggtctgg agatgcccaa gattgagaac tacgccaggt 52440tcatcaagta tacgatggac atcaactacc aagacgccag tgagtattgg atgagggagc 52500ttcacgacgt gaagaaggct actttcccgt cgtctgtttc cgttgaagca tcggacaagg 52560gcgatgtcac aaagttcatg gagaccagaa tcgacctgcc ccgaaacgac gtcggtgtca 52620caaaggccac tattcttcgt gctgcttggg ctgtggtcct tgcacgctac tgcgataccg 52680atgatgtttg cttcggcaca acaatttcag gtcgacaagc ccctattgcc gggctcatgg 52740agatgcctgg tccagtcatc gcgactgtgc caatccgcgt tcgattggac cgacagaaga 52800ccgttgacga cttccttcaa ggcgtgcaag accaagctac caagatggtc gcctacgagc 52860aattcggcct tcaaagcatc ggcaaactga gcgctgacgc aaaggacgcg tgtgactttt 52920catcgctcct ggttatccag cctctccaga ctctgatcta caacgacgat gacgagcagg 52980ctctactggc tgcttcagca gctgcggctg acaccaagga ccaggtgatg cagaattact 53040tctcatatcc attggtcata caagcgcact tgcatgacga tcacatcagc ctggtcttga 53100tctacaactc tatggccctt ccggaagccc aactgtttgc cctgtcgcag cagttcaagc 53160acgtcgtgga gcagctagta ttggaacctc agcttagtct cggttctctg tctattgcct 53220ccggctggga cgttgcacaa tctctcaaat ttaatgccga aatcccagag attgtcgact 53280cttgtgtcca tcagctcatc gaaaggcaag ctgagatccg ccctgacgca atggcaataa 53340gggcctggga cgccgaattg acgtatcgag aattcaaccg tgctgcaaat cgtcttgcca 53400actatctaac ggcatcctac gacatcaagc cggatgagct gatccatgtc tgcttcgaga 53460agtccgcttg gttctttgtg tctatcctgg ccatcaacaa gtcgggtgcc gcatgggtgc 53520ccctcgaccc atctcaccca gagcagcgac ttcgacaagt tgtgtctcaa acgcgagcca 53580ggatagcact tacttcacct tcgaaccgtg acctggttac cggcttggtt gactctgttg 53640ttactgtgga ctctcagctc gatgtgcaac tgtcaaaggt tgacgagcac agccaaaagg 53700gcccggaaac agccgtgtcg tcagacaacg ccgtttatgt tctcttcaca tctggatcaa 53760ctggtacacc caagggcctt gttatgcagc acggctcggt gtgtacgtct cagacggcta 53820ttgtcaagcg gctaggccta acccctgacg tccgcatgtt gcaatttgct gcctttgtat 53880ttgacctttc tatcggagag atcattgcac cccttatcac aggcgcctgt ctgtgtatac 53940cgtcggacca tacgaggatg aatggcctta cacagtatat cagggatacg ggcatcaatt 54000gggcgttcct tacaccctca ttcatccgga caatcaaccc tgccgaggtt cccggcctgg 54060aactcgtctt actagctggc gaggccgtcc cgcgggacgt cttgactacc tggtttggca 54120aggtccgttt ggtcaatggc tgggggcctg ccgagacgtg tgtgttttca acactccacg 54180agtggcaatc agttaacgag tcacccctta cggttggtag gcctgtcggt ggtttctgct 54240gggttgttga tcccgaagat cctcatcgcc tagctccgac cggaacgctt ggagaagtcg 54300tcatacaggg tccgacgttg ctacgagagt atctctctga tcctgaacga acacaggcct 54360ctacagtgta tgaccttccc aagtgggcac ctcgccccga ctccagacac tggaacaagt 54420tctacaagtc cggtgatttg tgctattaca accaggacgg cacaatcgaa ttttcgactc 54480gtaaagacac tcaaatcaaa atccgtggct tacgggtaga gcttggagag gtccagcacc 54540atatccaaca ggcactgcct tcggccaggc aggtcgccgt ggacgtgtac aggggcgaaa 54600acggtacgaa cctggtcgcc tatctgtgct tcagcgatga cacccgcacg gctggcatca 54660gcggcggtgc atctgacggc ccattcttgc cgctcagcga agatttgcag tcgacgttgg 54720cggccgttgt tgggcagctc agcatctcgt tgccccggta tatgattccg accatgttca 54780tcccctgcag ctacatgccc ttcatcacct caacaaagct tgaccgtaat gagctgaaga 54840agctcacaag ctcactggac aaggcccaga tcgcccagta ctcactcctt ggcggcaaga 54900aacgctcgcc agaaacgcca atggaagtgt tcctgcagaa gctttggtcc gagctacttg 54960gtgtgccggt tgagtccatc ggtcgtgatg atagcttcct ggggcttggt ggtgattcca 55020ttactgccat ccacatggtc agcgctgcca gagaatccgg cgtctcgctt gcagtcaagg 55080aaatctttga cgatccgcgc ttatcggccg ttgcaagcaa ggctcgcgag attgagcaag 55140atgagcagac ttcactcgtc gacgctactc ccttctatct ggtagacgaa tctatccgcc 55200agctggccat tggcgatgaa gttcgacaac tctgtgacct gacaaacaac gaagaagtcg 55260aagatgccta tccggtaacc atgttccagg agggcctcat ggctctgtca gcgaagcagc 55320cgggctccta cattgccaag tatgcctata gattgtctga gcacgttgat gttgctcgct 55380tcaaggccgc ttgggagact actgtttcat tgtgcccgac tctgcgcacc cgactcgtcc 55440ttctgaatgg caaatgcacg caggtagtcg tcaaggggga aaccgggtgg cagtctcagg 55500aacacacgga tgttcacgct gctattcaag acgctcagac ggctgaaatg acctacggct 55560ctcatctttc tcaagctatc atggtcaacg atgcaagcaa cggaaacaac tacttcatct 55620ggacagttca ccatgcggtt cacgatggct ggacggtccg tctcatcatg accactttgc 55680agaatgccta taacaacctc gaggtacctg atctgaaacc gtattccggc ttcattcagt 55740acctgggatc tatcaaggct gatgacacca tcaacttctg gactcagcag ctacaaggtg 55800ccagcaaggc gtcttatccg ccatccaagc cagcatccgc acctgagtcg gtcactcgac 55860tcatcaccaa gacaatccaa gccagctcct cggccaatgc tgccatcaca aaggccacca 55920tcatgcgggc gacctgggct atactgttag cccgctactg cgataccgac gatgtcactt 55980taggtacgtc catctctggc cgacaggctc cagtgtctgg cctcatggac atgcccggcc 56040ctgtggttgc gactgttccc gtacgagtcc gtctggaccg aagtcagaca atcagcaagt 56100acctccaggc catccagagt caggcccacg agatggtgcc atacgagcag tatggcttga 56160caaacattgg caagatcaac tctgacttca gagatgtctg tgactttacg agcttgctgg 56220ttgttcagcc tcgaacgcac ttggattctc gaagcaaggg cacgtctact gagtctgacg 56280cttcgtcggc cgctctgctt ctgcctgcca atgtcgaagg cggttcggtc gaggacttga 56340tgcaaggtta cttttcgtat ccccttgtta tacaaggcca cctgatgagt gactccattg 56400agctggtcat tacctatgac tcttccgtcc tctccgaggc atccatggaa gccatgtgtc 56460atcagtttga gcatgtggct tcgcaactct ttgcggacga gggacgtaca ttgggcgact 56520tgacggttgc ttcctcctgg gatctcgaac gcgcgagagc ctttaactct gaagccccaa 56580tggtcatgga tacttgcatc catcacctca ttgaagctca agtcagaaaa actcctgatc 56640tgccagcggt ctgggcctgg gatgggcagt tgacctaccg ccagcttaac gaagcggcca 56700accggttagc ccactatctc atcaacgagc acaatgtcca ggttgaagat cttgtccacg 56760tctgcttcga aaaatctgtt tggcactggg tctctgtgct tgccatcaac aaggctgggg 56820ccgtatgggt tcctctggac ccatcacacc ctgagcagcg ccttcgccag gttgcctctc 56880agactcagtc cacgctggct ctgacatcgg atactacgaa gagcctcctg tctcatatta 56940ttgatcgggt ggtcgaagtc tctcctgcat tgttcgagca gattgatgtc cgactcggtg 57000aaaaggagcc tcaggtctcg gtctcagcca gcaatgctgc gtacattctc ttcacctctg 57060gatccacggg tacgcccaag ggtctggtca tgacacacgg tgctttgaca accagtcaga 57120ccgccatcaa gaagcgaatg ggcaccggca ctcataccag agccctccag tttgcttcgt 57180acgtgtttga catgtctgtc ggcgaaggct tcgtacagct tatttctggc gcctgcattt 57240tcattccatc ggagcacacc agaatgaatg gcctgaagca gttcatcacc gaacacagaa 57300tcaactctct gtggctgacc ccgtccttta tccggactct cagtccagag caagtgccaa 57360cggttgactt tgtgttcttg gctggtgaag ctattccacg cgacgtgttc accacttggt 57420gtaccaaggt ccgcttgtgg aacggttggg gccctgctga gacttgcgtc gtcagctcct 57480tgcacgagtt tacaagcctt gatgagtcgc cattgacaat tggtcgtcct attggagggt 57540actgctggat tgttgaccct acggaccata cgaagcttgc ccctatcggc acaatgggcg 57600aggtcgtcat ccaaagtccc acgattctga gggaatacct tgccgacgtc gagcgcacca 57660aggcctctac ggtatatgag ctacctgagt gggcgccata ccgagaccag gctccttggt 57720cacgattctt caagtccggc gatctggcgt catataaccc tgacggtaca ctcgaattcg 57780ctagccgaaa ggatacccaa gtcaagattc gcggtctgcg tgttgagctt ggagaaatcg 57840agcatcacgt ccgcagcagc ctcacagacg ctcgtcaagt tgctgttgat gttttcagga 57900ccgatgccgg cacaagactc attgcgtact tctgctactc tgatgtgacg cgcactgccg 57960gcaattctca gccggataac gatgacatct tcctgcctgt gacggaagac cttcagagac 58020agctcaccag catggtcagc cagctgcatg tcacgctgcc tcggtacatg gtgccctcgc 58080tcttcattcc atgccgttac atgcctttca ttacgtccac caagcttgac aggaaccggt 58140tgaagaagct tgtttccgag ctcagccaag aagaccatgc ggcgtactcg ttaagcaacg 58200gcgtcaagcg catgcctgac actgagatgg aggcccgtat gcaggagctt tggtccgtcg 58260tgttgcacat gcccaaggaa gagattggct gcgatgaaag cttcctgcaa atcggtggtg 58320attctattac tgccatccag ctcgttacca acgctcgtga ggctggtatc tcaattgctg 58380tcaaggatat ctttgacgac cctcgccttt cgaagcttgc cctggtggct gcagccaact 58440ctgatcagag caatgcgtcc acgatagtcg aacccttcag cctcctggga gactccctta 58500ctaaggaact ggtcacagaa gctgccaagg agcaatgcaa cctcgccggg gatgacctgc 58560ttgatgatgc ctatccttgc acaaagctac aggaaggtct catggccctt gcaatcaagc 58620aacccggatc ttacattgcc aagtatgtgt atcaaattcc cgaccacgtc gatgtttcca 58680gattccgcaa ggcctgggag cgtaccgtcc agagctgtgc caaccttcgc acacgcatgg 58740tgcttgtcaa cggcattacc gtccaagttc tgctgaagga cgacattgag tgggataaca 58800ccgacgatac ttcgctcgag acttatgctc gctcaacgct ccacatagag atgggttttg 58860cccagcgtct gtgtcgctat gccctcattg aagaagagac tggtaactac tttgctttca 58920gcatccatca taccatcttt gatggttggt ctcttccgct ggtgatgggt accttgtctg 58980cggcctacta cgatcttgag cttccttctc tgcagtcata tgcagcattc gtcaagtaca 59040ccatggaact cgatcacggc gtcgcttccg actactggga gaagcagctc aagggtgcca 59100aacgcgcaag tttcccggcg ccgagcgata agtcagggtc ttctcagacg cgtgtggcga 59160acaagaccat tggcttcccc aagtcaaaga cgtccatcac aaaggcctct attctgcgcg 59220ccgcttgggc catcgtattg gcccgctact ctgacagtga tgatgtctgc ttcggcacca 59280cagtctctgg tcgcaatgcc aatgtggctg gtcttgaggc tatgcctggt cttgtggtcg 59340ccaccgttcc tgttcgtatt catgttgaca agcagaagcc tctttctgga ttcctgcaag 59400atgttcagaa gcaggccaat gacatggttg atttcgaaca atttggtatc cagaatatct 59460ccagacttgg ctccgacgca aaggacgctt gcgacttcac ctctctcctg gctatccaac 59520ctgtccagca tatgagtgca gacagcggca atcctgctga ccagggtgct attgtcattc 59580ccgctgcctc gccccatgtt aatgctgagg acatgctgca gaactatttc tcttacccct 59640tggttattca gtgccacctc atggatgacc atgtgaatct ggtcctcgtc tacgacactg 59700atgtccttga agagacacag ctgaacgcgc

tcatgcagca gttcgaccat gttgtccagc 59760aactgagtgc ccagggtaat gagccattgg gcgacgtcag tatctcaggg ccttgggatc 59820ttgaacaagc tctgcagctg aatagcagga aacccgactt tgtccacact tgtcttcacg 59880acatcttctc aaagcatgcg ctgagttctc ctcaccacga ggctatttac tcgtccgaag 59940gcagccttac ctatggtgaa cttgaccacc tgaccgatat cctcgccacg catctgagct 60000ctctaggtgc cggccccgag acagtggtgc ccttctgctt cgagaaatcg atgtgggcgg 60060tggttgccat cctagcaatt cttaaggctg gcgccgcgtt tgtgcccctt gatccttcgc 60120atccaaccag ccgtcgcgag gctttggtca aggaagtcag tgctcgcgtg cttgtggctt 60180cttctagcgc tatcgcctca tgcaaaggaa tgtttgagca cgttgttgag ctgtcaccca 60240gtgttatggc taagctggcc gcttctgtaa cgcctaggat cctgccaaag gttggaccga 60300ggaacacggc atatgtcctg ttcacctccg gttcgacggg caagcccaag ggcgttgtta 60360tgcagcatgg ctcattcagc tctactacta ttggatatgg caaggtgtat aacctgtcac 60420cgttgtcgag agtgttccag ttctccaact atatctttga tggtagcttg ggcgagatct 60480ttggtccgtt ggcctttggt ggaacaatct gcatccccag tgaggacgaa cgcctcggta 60540gtgcccctgc cttcatgagc acgtcaaagg tcaacacagc catgttgacc ccgtcctttg 60600tgcgaacctt tacgcctgac caggtgccgc atctgacgac ccttgttctt ggcggcgaag 60660ctgcttccaa gagcaccttg gagatgtggg ttaaccgcgt cactttgtac aacggatacg 60720gaccagctga agcttgcaac tacgcgacta cacacgtctt caagtcaagt tccgagtctc 60780ctcgtatcat cggatccgga ttcaacggtg cttgttgggt cgttgaacct gataaccaca 60840acatccttgc ccctataggt tgcacaggag agctggttct gcaaggccac gctctggctc 60900gcggctatct caatgacaag gcgaagacag agcaatcgtt tgttagcgac attagttctc 60960ttccatcatc ttcgctgcat gagcctaagc gattctacct cacaggagac ttggtccgct 61020acaattcaaa cggtaagctc gaatacctgg gacgaaagga ctctcaggtc aaattgcgtg 61080gtcagcgtct agaactgggt gaaatcgaat acaacatcac tcagtcactc aagagcgtgc 61140gagacgtcgc tgttgatgtc attcacaaag acaccggtga cttgctagtc gcgttcattt 61200cgttctctgg caacgcggac gctcagtggg attcggataa cctgcttctg aacctccttg 61260ctgctgatga gtccatgaga tccctgcttg atggtttgag agagggcttg aaggcctctc 61320taccaggcta catggtacca agcatcattc tccctcttcg atgcatgcct ttcatcacat 61380caatgaagct cgacaagaag ccgcttcttt cgcttgccca cagcctctct atcgagtaca 61440ttgctgccta ctcggcatcc aagagagaaa aggtcgagcc cgcgtctgac ctcgagttca 61500agctccgtga tctgtgggcg caagtcctca agctagagcc tggcgaaata ggacgcaacg 61560atgccttcct ggaaattggc ggtgactcga tctctgctat ccacctggtg actgctgcac 61620agcaagccgg aattagcatt accgttgcaa acatctttgc cgattctcga ctttcatctc 61680tagcagcttc ggcaaaggtc ggatacgtcg ccaagagctt cgacgtgaag cccttcagca 61740tgctacccgg tatcagcatc gaagaactga ccagtctggc ccaagctaaa tgcaatttgc 61800caaactacct tgcccttgag gatgcttacc cttgcacaag tcttcaggag ggtttgatgg 61860caattgcaat caagcaacct ggatcctaca tcgccaagca cgtctatcag ttgccccctc 61920atgtcgatgt tggtcgcttc aagacctcct gggagcgtac tgtcgaggct tgcagcaacc 61980tgcgtacccg gatcattctt gttgacaaga aacatgttca agtcgttgtc aaggatgaca 62040tctcctggga ctctggcctg ggccacggcc tggagtctta catccgcgct tctcaaagcc 62100ttgatatgaa gtatggatcg cgactttgcc gatatgctct gatccaagat gaggagaccg 62160gcgacaactt cttctccctc agcgtgcacc acacaatctt tgatggttgg agcttgcctc 62220ttatcctcgg tacactgaat gctttctacc gcgatactga ggtcccagcc ctgcagcctt 62280actctggctt tgtcaagtac acccttgacc ttgacgagac ggctgctgtc aactattgga 62340ccacgcagct gtctggagct aagaaggctg ccttcccgcc cactacggac gtcatcggcc 62400ccgactctgt caagcctgct tctcagttcc tgaacaaggt cattgagttc ccgcgaacga 62460cgaactcatc catcaccaag gcgaccatcc ttcgaacggc atgggccatt gtccttgccc 62520gctactccga ttcagacgac atctgcttcg gcacaactgt gtctggccgt cacgcgtccg 62580tccctggtct tgaggctact acaggcttgg tcgttgctac tgtgcctgtc cgcgtccgcc 62640ttgacacaca gcaatcggta gccaaactcc tccgcgatgt gcagattcaa gcctcggaaa 62700tggtcgagta cgaacaatat ggcctccaga atatctccaa gattggtgcc gagttcaagg 62760acgccgttga tttcagcagc ttgctggctg ttcagcctat ccagcacatt ggatcaacgg 62820gtgaaagctc cgaggaggcc ctcctggtcg ctgctgattc cgaacttctt cgtgccgaag 62880aggcgctgca gaattacttc aactaccctc tggtcgtcca gtgtcacgta tacgatgaca 62940tggtcaacct gatgttcatc tatgacccca gcgtcttgtc tgagcaccaa ctccaggcca 63000tctcacagca ctacgatcac gttgtgcagc agctgctgac gcagagcgaa gaaactctca 63060gtagcctgtc ccttgcaggc ccttgggacc ttcagcaagt cctcgggtgg aatgccagtg 63120ctccggaact tatcgaggcc tgtgtccacg acttgatttc cgacaatgcc cagcgcgatc 63180ccaaccatga agcgatcttt tcgtctgagg gtagcatgac ctatgctgct cttgaccggt 63240taaccgacgt cctagcaagc catctttgcc agctgggcgt tggtccagag acgattgttc 63300ccttctgctt cgaaaagtcc atgtgggctg tcgtcgctat tgtcggtatc ctcaaggcgg 63360gaggtgtctt cgttcccctg gacccttcgc atccgatcaa ccgccgtgaa gccctcgtca 63420aggaagttgg cgcccaaatc atcattgcat ccgagtcggc cgctgcctcg tgtgctggca 63480tggctcctcg cattgtccag ctttcgtccg acttcatggc tcgcttatct gccccaagcc 63540aaaccctcgt cgagcccaga cgccccagcc catcaaatgc agcctatgtg ctgttcactt 63600ctggctcaac gggcaagcct aaaggtgtgg tcatggaaca ctctgctctg acaacaagca 63660caatcggtta cggccgcgtc tacgagctca gccctgcatc ccgcgtgttc caattctcca 63720actacatctt tgacggcagc ttgggtgaga ttctcgcaac actgaccttt ggcggtactg 63780tctgtattcc agacgaagtc gaacgtctgc aggatgctcc aggctttgta cgcaaggccc 63840agatcaacac tgccatgttg acgccctcgt ttgtccgcac gtttacgcct gaccaggttc 63900ccagcctcaa gacattggta cttggtggtg agcctgctgg tagggacatt cttgatgctt 63960ggtgcgattg tgtgaagctc atcaatggtt acggacctgc cgaggcttgc aactacgcaa 64020cgtggcatcc attttcatcg agcagagact cgccgcgtgt catcggaaag gcattcaaca 64080gttcttgctg ggttgtcgaa ccgaacaacc atcacgcact cactcccgtc ggttgtgttg 64140gtgaactcgc catccagggc catgtgcttg cccgtgggta catcaatgat ttagagagaa 64200ccagaagctc ctttgtcacc gagattgctt ccttgtcgtc agtcatcgct ggtcctcagc 64260gcttctacct gactggtgat ttggtgagat actgcagcga cggctctctc gagtatcttg 64320gccgtaagga cactcaagtc aagcttcgtg gccaacgtat cgagctcggc gaagttgaat 64380atcatgtcca gcgagctctt ccagatatcg agcatgcggc tgtggacatc atcactagag 64440aagctggaca agcccttgtt gcctttgtgt cgtttgcggg cacttacgac gacaatgaga 64500ctaccagctt ctctgataac ctgatcaagc caagtgacag tcttcgtgct gccatcgtct 64560cccttctcga caacctcaag gctgtgctcc ccgctttcat gatgcccagt cttgtcttgc 64620cggtccgaaa catgcccttc atcacatcga tgaagctcga caggaaacaa ctgcgaactc 64680tcgcaagctc tctgtctcct gaggagctcg ccacttttgc tcccagcaag gcagacaagg 64740ttgagccgac cactgacatg gaactcaagc tgcgcgacct ttgggcccag atccttggga 64800tcccggcgga agagattggc aagaacgata gcttcctaca aatcggaggt gactccatct 64860cagccatcca cttggtgact ctggctcaag aaacgggcat ctcactcacc gtggccacca 64920tctttgccga cccgagactg tcctcagttg ctgcatcggc ccatctcggc ggtatcagtg 64980atgcctacga ggctgagccc ttcagtctga tccagcattc tgagagcgat gccatcactc 65040gtgagattga gcagcagtgc aaactctctg ctggccagtc gatcgaggat gcttacccaa 65100caaccaagct gcaggaaggt ctcatggcct tgtccgtcaa gcagcccggc tcttacacag 65160ctcgctacgt gtaccgcctt cctgatcacg tcgatgttga gcgattcaag gcggcttggg 65220acaagacagt tgaggtttgc cacaaccttc gaacatccat tgttcttgtt ggctacaccg 65280ctatccaagc cgtcatcaag gacacttcaa ggtcgctgtg ggagcctgcc acgggcgttt 65340cgctgcagtc ctacatgaag aaggcgattg gatccttcaa catgggctat ggctctcgtc 65400tctgccgcta tgctctgatt gaagatggcg gcagcactta tttcgcctgg cacattcacc 65460actcggtgta tgacggttgg acgcacccgc tcatcatggg ctcgctctac gccgcttact 65520ttggcaccga aatgcctcct ctacggcctt tcgcccgctt cgtaaaatac acgacgagca 65580tcgaccaaca cgaggccgca gagtactgga gacgccaact tcacgacgcc aggccggctt 65640cgttccctgc cgttgaccag cagttgactg cttcgaagag caaggctgat gtgacccgaa 65700tcttgagaaa ggctgtcgac ttccctcgcc tgaccaactc atccatcacc aaggccacaa 65760tcatgagggc agcttggtct attgtcttgg ctcaatactg cggtgttgac gacgtgtgct 65820tcgggactac actctcgggc cgtcacgcac cagttccagg attggattct atgcctggtc 65880ctatgcttgc taccgttcct gtccgaatcc gtttggctca agatcagcca gcatcgcggt 65940tcctgcaaga cgtccagatt caggccgcag agatggttgc ctatgagcag tttggcctcc 66000agaatatcgc agctctaagc cctgacgcca aacaagcatg cgacttttcg agcttgctgg 66060tcatccaacc tgcccaacag cagatttccg acgacaaggc cgtgtctgaa acggacatga 66120tcctattgcc cggcgactct gaaaactctg ctgaagaatc gatgcagaac tttgccaatt 66180atcccttggt ccttcaaatt gccatcatgg acagccatgt cgagctgctg ctgatttacg 66240acaccaatgc tctgaccgaa ttccaggcta cagccatttc tgagcagttt ggcaacgttg 66300caagacaact cgttgcccaa gatgagactt tgattggtga tgtcaaggta gctggttcat 66360gggacctgca gaagcagctg gaatggaacc acgaaatcta tggtccttca gaaaccactc 66420tgcacgatct cttctcgaag caagttgctc gcagacctgc tcaccaagct ttgtacagca 66480gcgaaggaag catgacatac agcaagctgg atcgactgac aactcagctt gcagtctacc 66540tcagcagtct tggtgttcga cccgaaacca tcgtgccttt ctgcttcgac aagtccatct 66600gggccattgt cgcgatgatt ggtattctca aggccggtgg tgttttcatg cccttggacc 66660cgtcctaccc agcaagccgc cgccaggcct tgatagacga ggtcaacgcc cagttcatga 66720ttgtgtcacc cacaaccgcc cctgactctc aaggcatggt tcaaaacatg attgagctct 66780cgccatctct gattgccttc ttctctacaa tcgacaccgg cgaccaatcg tttatcaagt 66840caggtcccaa caatgccgcc tatgtcttgt ttacatcagg ttcaactggc aagccaaagg 66900gcgtcgtcat tgaccacaag gccatttccg cagccctcct ccgacaacgc gaggcctttt 66960cattcaacga cgacacaagg acgctgcaat tcgccaactt cgtcttcgac gcttgtatcg 67020ccgagatctt ctccgcgctg gtggccggtg ctaccgtttg cgtgcccaca gagcacgaac 67080gtgttcacaa cactgcagct ttcatccgtg aggctcgcat caaccacgcc ttcctgactc 67140cgacctttat caagactctc tctccggagc agattcccgg tatgaagact gtcattctta 67200tgggtgaagc gccctctcaa gaaatcatcg acacctgggc cgacgagatc gaccttcaca 67260acggctatgg cccagcagag ggctgcgttg gttcgaccaa caacacgtat tcgtcgtcga 67320tcaaggtatc agtcaccaac gtgggtcgta gctttaccca cggactctgg attgtcgacc 67380ctgataacca caaccgcctc atgcccatcg gctgcgttgg tgagttgctg ctccagggtt 67440cgtctctggc acgcggctac atcaacgacg aggaaaagtc aagacagtct ttcatcgatc 67500aagtcgagtg gctaccagcg aatgtcaatg ttggtgaacg ccgcttctac aagactggtg 67560acttggttcg ctacactcca gatggatcga tcgagtacgt cagccgaaag gacacgcaag 67620tcaagatccg cggccagcgt atcgagcttg gcgagatcga ataccacgtc aaacgctcca 67680acgcttctat tgagcacgtt gttgtcgaca ttactcgaca ggccggccgc gagtctcttc 67740tcgcctttgt gtgcttcagc tcgcatcaag agacggagag tgcttccaag gagactcgcc 67800tcacggagct caccagcgaa ctccgcgaga cgctgtctga cattgctaca actatcgcat 67860cgacgctccc tagccacatg gtgcccaagt atctcatccc tgtcgaccac atgcctcaca 67920acgctgccgg caagttagac cgaaagatgc ttctcgcatc cattgccaac cttacgccgg 67980atgatctttc gaaatacctc gctggccagc gtctgccctt ccgtgactgc tctaccgacg 68040tcgagttctg gctccgtaac cagtgggcgt ctacgcttga tcttcctgca gagaccatcg 68100gaatggatga caacttctac agtctgggcg gtgattctat ccgcattgtc accatttcca 68160aggctatcct tagccagtat gatgtctcac tcggcatgtc ccttctcaac tcgaagcata 68220ccacgattgc aaacatggcc aagcacatcg acagcgaacg cagtgggcaa gacggcgcag 68280aacttggagt cgtcgatatc aacggcgaga tctcatctct ctcacgctcg atcctggctt 68340ctggtgatct taacgtcgtt tcccactcta agactgagct gcctgagcag gccaccgtct 68400ttttgactgg tgccactggc ttcctcggtc aagaactcct cagacaactt ctctgcaacg 68460actccattgc ctccatcatc gccctggtac gatccaagtc tgccaaccac ggaatggacc 68520gtctccgcga cactgcgaag attgcaggct ggtggcgcga agagtacaca agcaagattg 68580agatttggtg tggtgatctg agcaagaagc gcatgggcct gagcagttcg caatgggctc 68640gcctggccgg ccagtccagc aacaacaacg tcgatgccat catccacaac ggtgccatcg 68700tcaactggaa cgccgactac gacaagatgc gtgccgccaa cgttgattcc acggtggatc 68760tcctcaaggc taccgtcacc tcgcccgctt cccccaagtt cgtcttcgtc tccggcggca 68820tcaagtctga tcccaccacc gaccgcacag ctctgggcca gtatctcaac aactcgactg 68880gctacatcca gaccaagttc gtctccgagg gcatcatcca ggaggtcatc aagaccctcc 68940cggctgacca gaaccgcatt tccactctca agcccggccg catcatcgga tctcctgaaa 69000ctggtgtggc caacgtggac gatgtgctgt ggcgaattgt ttccgccgcc gcttctcttg 69060gagtctatcc tgccgagccc gaggaccatt gggtctacat ctccgacgtt gacactgtgg 69120catcatccgt gctcagccaa ctttacagca agcagggcat cgctccctac gtcagtgcca 69180cgggcggcat gccggcaaca gtcttctggg atctcatcaa caaggagctg gacgtcccct 69240gcgagcctct ttctcaagat gaatggactc accgtgcgtt ggagtcgatg aatcaagtcg 69300gcgacaagca tcctctgtgg cctgtgcagc acttccttgg caaccttggc actcctcgat 69360ctgctcaaga cattgagatc gaaggcagtg agcacaagca gtggcacatg gctgtaaaga 69420tgagcatgcg ctaccttatg aaggtcggct tcattcagac gtccactgat ggctttgctc 69480agcctcgtcg ggcggacact ttccagcgcc atggctga 69518420873PRTTrichoderma reesei 4Met Ala Pro Asn Thr Thr Tyr Glu Asp Gly Asn Lys Ser Leu Ile Pro 1 5 10 15 Ile Ala Ile Cys Gly Val Gly Ile Arg Leu Pro Gly Gly Ile Arg Asn 20 25 30 Ala Glu Gln Leu Trp Glu Ser Leu Val Asn Asp Arg Val Gln Pro Arg 35 40 45 Val Asp Gly Asn Glu Glu Glu Glu Leu Asp Ala Val Asp Ala Ser Phe 50 55 60 Phe Ser Leu Thr Glu Ala Glu Leu Glu Ser Cys Ser Pro Leu Gln Arg 65 70 75 80 Lys Leu Leu Glu Val Thr Arg Glu Cys Phe Glu Asp Ala Cys Glu Ile 85 90 95 Asp Phe Arg Gly Glu Asp Ala Arg Val Gly Cys Tyr Ala Gly Ser Ile 100 105 110 Gly Glu Asp Asp Val Ser Met Val Ser Leu Lys His Asp Leu Gly Gly 115 120 125 Pro Ser Met Ala Ile Arg Glu Ser Thr Ser Ser Phe Leu Val Ala Leu 130 135 140 His Glu Ala Cys Ser Ala Val Arg Ser Gly Ser Ala Lys Ser Ala Val 145 150 155 160 Val Leu Gly Ala Ala Gln Asn Gly Ala Val Gly Gly Glu Ala Val Ser 165 170 175 Ala Val Tyr Ile Lys Thr Leu Pro Asp Ala Met Arg Arg Gly Asn Pro 180 185 190 Ile Arg Ala Ile Ile Arg Ala Ser Ser Ile Met Thr Leu Ser Gly Arg 195 200 205 Ile Glu Gly Ala Ser Gly Leu Thr Ser Leu Val Lys Ala Val Val Thr 210 215 220 Leu Glu Asn Arg Thr Ile Ser Pro Asn Ile Val Ser Gly Lys Phe His 225 230 235 240 Ala Ala Gln Val Arg Arg Lys Val Arg Pro Lys Ser Leu Thr Ala Ser 245 250 255 Ile Ile Ala Ser Asp Ala Glu Gly His Ser Ala His Val Ile Val Asp 260 265 270 Ser His Pro Arg Pro Thr Pro Arg Val Ser Glu Ser Arg Pro Gln Leu 275 280 285 Val Leu Phe Ser Ala Asn Asn Pro Ala Ser Leu Ala Lys Gln Ile Glu 290 295 300 Leu His Arg Leu Tyr Ala Glu Ser His Pro Asp Asp Ala Ala Asp Ile 305 310 315 320 Ala Tyr Thr Arg Ala Leu Arg Arg Glu Ala Leu Asp Tyr Lys Ala Phe 325 330 335 Ser Ile Leu Ser Asn Ser Ser Phe Val Asn Thr Ser Asn Tyr Ala Lys 340 345 350 Ser Ser Ala Arg Ala Pro Ala Ile Thr Met Val Phe Asn Gly Gln Gly 355 360 365 Ala Gln Trp Ala Gly Met Gly Lys Glu Leu Ile Leu Thr Asp Ser Ser 370 375 380 Phe Arg Glu Asp Ile Arg Lys Met Asp Leu Val Leu Lys Gly Leu Asn 385 390 395 400 Ile Pro Ala Thr Trp Ser Ile Glu Glu Glu Leu Leu Arg Asp Ala Ala 405 410 415 Asp Pro Asp Asn Arg Ile Asn Thr Ser Lys Phe Ser Tyr Pro Leu Ser 420 425 430 Thr Ala Leu Gln Ile Ala Leu Val Asn Cys Phe Lys Arg Leu Gly Val 435 440 445 Thr Pro Lys Ala Val Val Gly His Ser Ser Gly Glu Ile Ala Ala Ala 450 455 460 Tyr Ala Ala Gly Phe Leu Ser Phe Glu Asp Ala Ile Thr Val Ala Tyr 465 470 475 480 Tyr Tyr Gly His Ile Thr Thr Arg Asp Gln Lys Asp Gly Ala Met Gly 485 490 495 Val Val Ser Leu Gly Ala Glu Glu Thr Glu Gly Phe Leu Glu Gln Gly 500 505 510 Val Val Ile Ala Cys Glu Asn Ser Pro Thr Ser Thr Thr Ile Ser Gly 515 520 525 Asp Arg Glu Ala Val Glu Arg Val Leu Lys Phe Val Lys Ala Ala Lys 530 535 540 Pro Glu Val Thr Ala Arg Leu Leu Lys Val Asp Thr Ala Tyr His Ser 545 550 555 560 Glu His Met Thr Gln Leu Ala Asp Glu Leu Leu Asp Leu Leu Thr Ala 565 570 575 Glu Lys Ile Ala Ser His Ala Thr Arg Lys Ser Glu Ala Ile Phe Ile 580 585 590 Ser Thr Val Ser Glu Lys Val Leu Lys Glu Lys Ser Glu Phe Gly Ala 595 600 605 Ala Tyr Trp Val Ser Asn Leu Val Ser Pro Val Arg Phe Ser Ser Ser 610 615 620 Val Ser Asn Leu Leu Gly Met Ser Ser Glu Glu Thr Leu Phe Leu Glu 625 630 635 640 Val Gly Pro His Ser Ala Leu Ser Val Pro Leu Ser Gln Ile Cys Ala 645 650 655 Ala Ala Asp Val Arg Cys Asn Tyr Val Ser Ser Gln Thr Arg Gly Ala 660 665 670 Asp Ser Ala Val Ser Phe Leu Ser Ala Val Gly Arg Leu Trp Gln Glu 675 680 685 Ser Ala Val Pro Asn Leu Ala Pro Leu Phe Ser His Gly Arg Ala Ile 690 695 700 Ser Gly Leu Pro Gln Tyr Pro Trp Ser Tyr Gly Thr Ser Asp Glu Asp 705 710 715 720 Ser Asp Ala Thr Ala Leu Ser Ala Arg Glu Lys Arg Ala Arg Val Phe 725 730 735 Ala Glu Asp Ser Ser Leu Glu Ser Glu Leu Ala Asp Glu Glu Ala Pro 740 745 750 Thr Thr Glu Val Glu Ile Val Leu Arg Ala Val Trp Val Glu Ile Leu 755 760 765 Arg Asp Val Asn Arg Ile Arg Lys Gln Asp Ile Gly Lys Lys His Asn 770 775 780 Phe Phe Leu Leu Gly Gly Asp Ser Leu Thr Thr Ile Glu Leu Val Thr 785 790 795

800 Ala Ala Tyr Gln Tyr Gly Ile Arg Leu Ser Pro Ala Ala Val Ser Asp 805 810 815 Asn Ala Glu Leu Ala Gln Met Ala Ala Val Ala Thr Ile Glu His Asp 820 825 830 Ser Ala Met Met Ala Glu Thr Lys Pro Phe Ser Leu Ile Ser Ser Glu 835 840 845 Lys Val Asp Asp Ile Lys His Gln Ile Arg Lys Glu Cys Lys Leu Ala 850 855 860 Pro Thr Glu Thr Ile Glu Asp Ile Tyr Pro Cys Thr Thr Leu Gln Glu 865 870 875 880 Gly Phe Met Ala Leu Gly Met Lys Gln Pro Gly Ser Tyr Ile His Arg 885 890 895 Val Val Tyr Lys Leu Met Pro Glu Ile Asp Val Asp Gln Phe Lys Ala 900 905 910 Ser Trp Glu Ala Thr Ile Ser Gln Cys Gly Ser Leu Arg Ser Arg Val 915 920 925 Ala Leu Leu Gly Gly Arg Ala Leu Gln Ala Val Met Thr Glu Asp Ile 930 935 940 Ala Trp Glu Gln Pro Ala Pro Gly Leu Asp Ile Asn Ala Tyr Leu Asn 945 950 955 960 Arg Thr Arg Ser Ile Ser Met Ser Tyr Gly Glu Arg Leu Ser Arg His 965 970 975 Ala Leu Val Arg Asp Ser Asn Gly Gly Val Tyr Phe Val Trp Leu Ile 980 985 990 His His Ala Val Phe Asp Gly Leu Thr Met Arg Ile Val Leu Asp Ala 995 1000 1005 Leu Tyr Asn Ala Tyr His Gly Asn Asp Ala Lys Ala Leu Arg Pro 1010 1015 1020 Tyr Ser Asn Phe Ile Arg Tyr Val Glu Ser Ile Asp Ser Ala Ala 1025 1030 1035 Ser Thr Glu Tyr Trp Gln Lys Gln Leu Asp Gly Ala Gln Arg Ala 1040 1045 1050 His Phe Pro Pro Ala Arg Leu Ser Ala Thr Ser Glu Asp Arg Val 1055 1060 1065 Met Lys Arg Thr Met Pro Phe His Asn Ala Lys Thr Ser Ser Val 1070 1075 1080 Thr Thr Ala Thr Ile Leu Arg Ala Ala Trp Ala Leu Leu Leu Ala 1085 1090 1095 Arg Tyr Cys Asp Ser Asp Asp Val Cys Phe Gly Thr Thr Leu Ser 1100 1105 1110 Gly Arg Gln Ala Ala Val Pro Gly Leu Asn Glu Ile Pro Gly Pro 1115 1120 1125 Met Ile Ala Thr Val Pro Ile Arg Val Lys Ile Asp Arg Gly Met 1130 1135 1140 Thr Val Ser Ser Phe Leu Glu Lys Ile Gln Thr Gln Ala Ala Asp 1145 1150 1155 Met Val Ala His Glu Gln Tyr Gly Leu Gln Asn Ile Ser Lys Leu 1160 1165 1170 Ser Gln Asp Ala Glu Glu Ala Cys Asp Phe Ser Asn Leu Ile Val 1175 1180 1185 Ile Gln Pro Asn Asn His Leu Thr Ser Met Ala Asp Thr Ala Ser 1190 1195 1200 Asp Ala Ile Leu Gln Gln Gly Ser Arg Glu Lys Ala Leu Ser Glu 1205 1210 1215 Glu Ala Met Arg Asn Tyr Phe Asn Tyr Pro Leu Val Leu Gln Pro 1220 1225 1230 Arg Ile Gly Glu Asp Ser Ile Glu Leu Asp Leu Thr Tyr Tyr Ala 1235 1240 1245 Asp Ala Ile Thr Glu Gly Gln Leu Glu Ala Leu Cys Val His Tyr 1250 1255 1260 Glu His Ile Val Gln Gln Leu Leu Ala Pro Thr Asp Met Pro Leu 1265 1270 1275 Ser Asp Leu Ser Val Ser Gly Ser Trp Asp Leu Glu Glu Ala Ile 1280 1285 1290 Lys Ala Asn Asp Glu Thr Pro Glu Ile Val Asp Met Cys Leu His 1295 1300 1305 Gln Leu Ile Glu Arg Gln Ser Lys Ala Asn Pro Asp Ala Pro Ala 1310 1315 1320 Ile His Ala Trp Asp Met Glu Leu Ser Tyr Ser Gln Leu Asp Arg 1325 1330 1335 Ala Ala Asn Arg Leu Ala His His Leu Val Lys Ser Cys Gly Val 1340 1345 1350 Lys Asp Gln Asp Phe Val His Val Cys Phe Glu Lys Ser Ala Trp 1355 1360 1365 Phe Phe Val Ser Val Ile Ala Val Asn Lys Ala Gly Ala Thr Trp 1370 1375 1380 Val Pro Leu Asp Pro Ser His Pro Leu Gln Arg Gln Gln Gln Val 1385 1390 1395 Val Ser Gln Thr Lys Ala Thr Leu Ala Leu Ala Ser Pro Ser Asn 1400 1405 1410 Val Glu Met Cys Ser Glu Leu Val Asn Thr Val Val Glu Val Ser 1415 1420 1425 Ser Ala Leu Asp Glu Lys Leu Ser Lys Thr Glu Glu Ser Ser Tyr 1430 1435 1440 Gly Pro Val Arg Asn Val Ser Pro Asp Asn Ala Ala Tyr Val Leu 1445 1450 1455 Phe Thr Ser Gly Ser Thr Gly Thr Pro Lys Gly Leu Val Met Gln 1460 1465 1470 His Arg Ala Val Cys Thr Ser Gln Thr Ala Ile Thr Lys Arg Leu 1475 1480 1485 Glu Met Thr Ser Ser Val Arg Met Leu Gln Phe Ala Ser Phe Val 1490 1495 1500 Phe Asp Leu Ser Ile Gly Glu Ile Val Gly Pro Trp Val Val Gly 1505 1510 1515 Gly Cys Leu Cys Val Pro Ser Glu Glu Thr Arg Met Asn Asn Leu 1520 1525 1530 Val Asp Phe Ile Asn Thr Met Gln Val Asn Trp Ala Tyr Leu Thr 1535 1540 1545 Pro Ser Phe Thr Arg Thr Leu Asn Pro Asp Asp Val Pro Gly Leu 1550 1555 1560 Asp Leu Leu Leu Phe Ala Gly Glu Ala Val Gly Arg Asp Val Phe 1565 1570 1575 Glu Ala Trp Phe Gly Lys Val Arg Leu Ile Asn Gly Trp Gly Pro 1580 1585 1590 Ala Glu Thr Cys Val Phe Ser Thr Leu His Glu Trp Lys Ser Phe 1595 1600 1605 Glu Glu Ser Pro Leu Thr Val Gly Lys Pro Val Gly Gly Tyr Cys 1610 1615 1620 Trp Ile Val Asp Pro His Asp Pro Gln Arg Leu Ala Pro Val Gly 1625 1630 1635 Thr Leu Gly Glu Val Val Ile Gln Gly Pro Thr Val Leu Arg Glu 1640 1645 1650 Tyr Leu Ala Asp Thr Thr Lys Thr Glu Ala Ser Leu Val Arg Ser 1655 1660 1665 Leu Pro Glu Trp Val Pro Asn Arg Thr Ala Ala His Trp Asp Arg 1670 1675 1680 Phe Tyr Lys Ser Gly Asp Leu Cys Arg Tyr Asn Ala Asp Gly Thr 1685 1690 1695 Ile Glu Phe Gly Ser Arg Lys Asp Ser Gln Val Lys Ile Arg Gly 1700 1705 1710 Leu Arg Val Glu Leu Gly Glu Ile Glu His His Ile Arg Glu Ser 1715 1720 1725 Leu Glu Gly Val Lys Gln Val Ala Val Asp Val Ala Lys Gly Asp 1730 1735 1740 Gly Gly Ala Ile Ile Val Ser Tyr Phe Ser Phe Thr Asp Glu Thr 1745 1750 1755 Arg Thr Ala Gly Lys Asn Ser Glu Thr Ser Val Arg Asp Val Phe 1760 1765 1770 Val Pro Met Thr Pro Glu Leu Gln Ser Gln Leu Thr Ala Leu Val 1775 1780 1785 Gly Gln Leu Ser Val Thr Leu Pro Arg Tyr Met Ile Pro Thr Leu 1790 1795 1800 Phe Ile Pro Cys His Tyr Met Pro Phe Ile Thr Ser Thr Lys Leu 1805 1810 1815 Asp Met Lys Leu Leu Arg Leu Ala Met Ser Asn Leu Gly Lys Asp 1820 1825 1830 Asp Ile Ala Arg Tyr Ser Leu Val Asp Ser Lys Lys Arg Ala Pro 1835 1840 1845 Glu Thr Glu Met Glu Thr Arg Ile Gln Ala Ile Trp Ala Asp Leu 1850 1855 1860 Leu Lys Leu Ser Pro Glu Phe Ile Gly Arg Asp Asp Ser Phe Leu 1865 1870 1875 Arg Met Gly Gly Asp Ser Ile Ala Ala Ile Tyr Phe Val Ser Ala 1880 1885 1890 Ala Arg Asp Ala Gly Ile Ser Ile Ala Val Lys Asp Val Phe Asp 1895 1900 1905 Asp Pro Arg Leu Phe Gln Val Ala Ser Lys Ala Thr Leu Leu Ser 1910 1915 1920 Asn Ala Gly Arg Ser Ser Gln Thr Glu Pro Phe Thr Leu Leu Pro 1925 1930 1935 Glu Ser Leu Ser Lys Leu Met Gln Ser Asp Ala Ile Arg Ser Arg 1940 1945 1950 Tyr Gly Leu Gly Gln Arg Gln Thr Ile Glu Asp Ala Tyr Pro Cys 1955 1960 1965 Thr Pro Leu Gln Glu Gly Leu Met Ala Leu Thr Ala Lys Gln Arg 1970 1975 1980 Gly Ser Tyr Val Ser Gln Trp Phe Tyr Arg Met Pro Arg His Ile 1985 1990 1995 Asp Thr Ala Lys Phe Lys Ala Ala Trp Asn Glu Ala Val Glu Arg 2000 2005 2010 Asn Ala Thr Leu Arg Thr Arg Ile Met Leu Glu Glu Gly Ser Ala 2015 2020 2025 Val Gln Ala Val Ile Ser Asn Asp Gly Asp Trp Glu Asp Thr Glu 2030 2035 2040 Gly Leu Asn Leu Glu Ser Phe Lys Asp Val Ile Ser Gln Leu Asp 2045 2050 2055 Ile Gly Tyr Gly Thr Arg Leu Thr Arg Phe Ala Leu Val Glu Asp 2060 2065 2070 His Asp Asp Thr Tyr Phe Val Trp Ile Ile His His Ala Ile Asn 2075 2080 2085 Asp Gly Trp Ser Met Arg Ile Val Leu Asp Ser Val Tyr Asn Ser 2090 2095 2100 Tyr Tyr Gly Gln Lys Val Ala Ser Leu Thr Pro Tyr Ser Asn Phe 2105 2110 2115 Ile Asn Tyr Leu Ser Asn Ile Asp Gly Glu Ala Ala Ala Asn Phe 2120 2125 2130 Trp Arg Ser Asn Leu Ala Gly Ala Gln Arg Pro Ile Tyr Pro Ala 2135 2140 2145 Ala Gly Ser Tyr Ser Thr Ala Asp Ser Ser Gly Asp Ser Thr Arg 2150 2155 2160 Val Val Asp Arg Leu Val Ser Phe Ser Ser His Glu Asp Ala Ser 2165 2170 2175 Ile Thr Met Ala Thr Ile Ile Arg Ala Ala Trp Ala Ile Val Leu 2180 2185 2190 Gly Lys His Cys Asp Ala Ser Asp Val Cys Tyr Gly Ala Thr Val 2195 2200 2205 Ser Gly Arg Gln Ala Asp Met Asp Gly Leu Leu Ser Thr Pro Gly 2210 2215 2220 Ala Val Ile Ala Thr Val Pro Ile Arg Val Pro Leu Glu Ala Asp 2225 2230 2235 Gln Pro Val Ser Gln Met Leu Gln Asp Leu Gln Gly His Gly Leu 2240 2245 2250 Asp Met Val Pro Tyr Glu Gln Tyr Gly Leu Pro Asn Ile Ala Lys 2255 2260 2265 Leu Ser Pro Glu Ala Arg Glu Ala Cys Asp Phe Thr Ser Leu Leu 2270 2275 2280 Val Ile Gln Pro Lys Glu Gln Glu Ser Ser Ile Phe Asn Ser Lys 2285 2290 2295 Asn Gly Leu Leu Gln Ser Asp Ala Glu Glu Asp His Leu Leu Ile 2300 2305 2310 Glu Ser Met Asp Lys Tyr Phe Asn Tyr Pro Leu Val Met Leu Ser 2315 2320 2325 Tyr Met Thr Glu Asp Ser Val Asn Gln Arg Phe Ile Tyr Lys Pro 2330 2335 2340 Asp Met Leu Ser Glu Ala Glu Val Glu Ala Leu Ser Tyr Gln Phe 2345 2350 2355 Glu Tyr Val Val Gln Gln Leu Leu Ser Pro Asp Gln Lys Leu Ile 2360 2365 2370 Ser Asp Ile Ser Leu Val Gly Glu Pro Thr Ser Leu Gln Ala Asn 2375 2380 2385 Asn Glu Val Pro Glu Ile Val Asp Ser Cys Ile His Glu Leu Val 2390 2395 2400 Glu Lys Gln Ala Leu Glu Arg Pro Gly Ala Pro Ala Val Val Gly 2405 2410 2415 Trp Asp Arg Val Phe Thr Tyr Ala Glu Leu Asn Glu Ala Ala Asn 2420 2425 2430 Arg Leu Ala His His Leu Thr Gln Thr Phe Ala Ile Lys Ala Asp 2435 2440 2445 Glu Leu Ile His Val Cys Phe Glu Lys Ser Ala Trp His Phe Val 2450 2455 2460 Ala Ile Leu Ala Ile Asn Lys Ala Gly Ala Gly Trp Val Pro Leu 2465 2470 2475 Asp Pro Ser His Pro Glu Gln Arg Leu Arg Gln Ile Ala Ser Gln 2480 2485 2490 Thr Arg Ala Arg Ile Ile Leu Thr Ser Pro Ala Asn Leu Asp Ile 2495 2500 2505 Cys Ala Arg Leu Gly Leu Ser Val Ile Glu Ile Ser Pro Phe Phe 2510 2515 2520 Asp Gln Lys Leu Ile Lys Ser Gly Met Asn Ser Ser Ala Gly Pro 2525 2530 2535 Asp Val Lys Val Thr Pro Arg Asn Ile Ala Tyr Val Leu Phe Thr 2540 2545 2550 Ser Gly Ser Thr Gly Thr Pro Lys Gly Leu Val Met Glu His Gly 2555 2560 2565 Ser Val Cys Thr Ser Gln Thr Ala Ile Ser Arg Arg Leu Gly Leu 2570 2575 2580 Thr Ala Asp Val Arg Met Leu Gln Phe Ala Ala Phe Val Phe Asp 2585 2590 2595 Leu Ser Ile Gly Glu Ile Val Ala Pro Leu Ile Ser Gly Ala Ser 2600 2605 2610 Leu His Ile Pro Asp Glu Asn Thr Arg Leu Asn Asp Leu Pro Asn 2615 2620 2625 Phe Ile Gln Lys Lys Gln Ile Asn Trp Ala Phe Leu Thr Pro Ala 2630 2635 2640 Phe Ala Arg Thr Leu Lys Pro Glu Asp Val Pro Ala Leu Asp Leu 2645 2650 2655 Leu Leu Leu Ala Gly Glu Ala Val Ser Arg Asp Val Phe Glu Ser 2660 2665 2670 Trp Phe Gly Lys Val Arg Leu Ile Asn Gly Trp Gly Pro Ala Glu 2675 2680 2685 Thr Cys Val Phe Ser Thr Leu His Glu Trp Arg Ser Ile Asn Glu 2690 2695 2700 Ser Pro Leu Thr Val Gly Arg Pro Val Gly Gly Phe Cys Trp Ile 2705 2710 2715 Val Asp Pro Glu His Pro Asp Lys Leu Ala Pro Thr Gly Thr Val 2720 2725 2730 Gly Glu Val Val Ile Gln Gly Pro Thr Leu Leu Arg Glu Tyr Leu 2735 2740 2745 Ala Asp Ala Glu Arg Thr Lys Leu Ser Thr Val Tyr Asp Leu Pro 2750 2755 2760 Ala Trp Ala Pro Arg Arg Glu Leu Gln His Trp Ser Arg Phe Tyr 2765 2770 2775 Lys Ser Gly Asp Leu Cys Tyr Tyr Asn Pro Asp Gly Thr Ile Glu 2780 2785 2790 Phe Ser Thr Arg Lys Asp Thr Gln Ile Lys Ile Arg Gly Leu Arg 2795 2800 2805 Val Glu Leu Gly Glu Ile Glu His His Leu Gln Leu Ala Leu Asp 2810 2815 2820 Asp Ile Arg Gln Val Ala Val Asp Val Phe Lys Gly Glu Ser Gly 2825 2830 2835 Ser Asn Leu Val Ala Tyr Phe Cys Phe Asn Glu Glu Ser Lys Thr 2840 2845 2850 Ala Asp Ala Arg Val Ala Gly Asp Asp Lys Gly Pro Phe Met Pro 2855 2860 2865 Ile Asp Glu Asp Leu Gln Ala Arg Leu Ile Ala Ala Ser Gly Glu 2870 2875 2880 Leu Arg Val Val Leu Pro Ser Tyr Met Val Pro Thr Phe Phe Ile 2885 2890 2895 Pro Cys Ser Tyr Met Pro Thr Ser Thr Ser Thr Lys Leu Asp Arg 2900 2905 2910 Lys Glu Leu Lys Arg Tyr Thr Ala Ala Leu Ser Val Glu Glu Leu 2915 2920 2925 Ser Lys Tyr Ser Leu Val Asp Gly Lys Lys Arg Ala Pro Glu Thr 2930 2935 2940 Pro Met Glu Ser Gln Leu Gln Gln Ile Trp Ala Glu Ile Leu Asn 2945 2950 2955 Ile Pro Met Glu Ser Val Gly Arg Asp Asp Ser Phe Leu Gly Leu 2960 2965 2970 Gly Gly Asp Ser Ile Thr Ala Ile His Leu Val Asn Val Met Arg 2975 2980 2985 Glu Glu Gly Ile Ser Leu Thr Val Lys Asp Ile Phe Asp Asp Pro 2990 2995 3000 Arg Leu Leu Ser Val

Ala Ser Lys Ala Ile Thr Thr Glu Glu Val 3005 3010 3015 Leu Glu Leu Asp Glu Ile Glu Pro Phe Ser Leu Leu Glu Lys Glu 3020 3025 3030 Ile Arg Asp Ala Val Leu Ser Glu Asp Leu Arg Gln Glu Leu Lys 3035 3040 3045 Leu Ala Lys Cys Gln Leu Val Glu Asp Ala Tyr Pro Cys Ser Lys 3050 3055 3060 Leu Gln Glu Gly Leu Met Val Leu Ser Val Lys Gln Pro Gly Ser 3065 3070 3075 Tyr Val Ala Lys Tyr Thr Tyr Arg Leu Pro Ala His Val Asp Leu 3080 3085 3090 Gln Arg Phe Lys Glu Ala Trp Glu Tyr Thr Ser Ser Ala Val Glu 3095 3100 3105 Ala Leu Arg Thr Arg Leu Val Met Ile Asp Gly Ser Cys Val Gln 3110 3115 3120 Val Val Ile Asn Glu Glu Ile Pro Trp Glu Thr Thr Lys Thr Asp 3125 3130 3135 Asp Ile Arg Ser Ala Ile Ala Ser Ala Gln Ser Leu Arg Met Thr 3140 3145 3150 Tyr Gly Ser Ser Leu Ser Arg Tyr Thr Ile Leu Glu Asp Gln Asp 3155 3160 3165 Gly Ser Asn Tyr Phe Met Trp Ala Val His His Ser Val His Asp 3170 3175 3180 Gly Trp Ser Met Arg Ile Val Leu Glu Thr Leu Arg Arg Glu Tyr 3185 3190 3195 Glu Gly Arg Ala Ser Ala Pro Val Met Pro Tyr Asn Gly Phe Ile 3200 3205 3210 Arg Tyr Thr Leu Gly Leu Asp Leu Glu Ala Ala Ala Glu Tyr Trp 3215 3220 3225 Ser Ser Gln Leu Asp Asn Ala Lys Arg Ala Ser Phe Pro Ala Ala 3230 3235 3240 Ala Thr Thr Ser Ser Glu Thr Lys His Ile Thr Arg Met Met Thr 3245 3250 3255 Lys Ser Ile Pro Phe Pro Ala Ser Met Asn Pro Ala Ile Thr Lys 3260 3265 3270 Ala Thr Val Leu Arg Ala Ala Trp Ala Val Ile Leu Ala Arg Tyr 3275 3280 3285 Cys Asp Thr Asp Asp Val Thr Phe Gly Ser Thr Ile Ser Gly Arg 3290 3295 3300 Gln Ala Ala Val Pro Gly Leu Thr Glu Met Ala Gly Pro Ala Val 3305 3310 3315 Ala Thr Val Pro Val Arg Ile Arg Leu Asp Lys Gln Gln Arg Val 3320 3325 3330 Ser Lys Phe Leu Gln Gly Val Gln Ser Gln Ala Ser Glu Met Ile 3335 3340 3345 Pro Phe Glu Gln Phe Gly Leu Gln Ser Ile Ser Arg Leu Gly Ala 3350 3355 3360 Asp Ala Arg Asp Ala Cys Asp Phe Thr Ser Leu Met Leu Val Gln 3365 3370 3375 Pro Met Gln His Leu Ala Gly Glu Asp Leu Asp Ser Val Met Val 3380 3385 3390 Pro Ala Leu Glu Gln Glu Thr Gln Glu Asp Gln Leu Gln Asn Tyr 3395 3400 3405 Phe Ser Tyr Pro Leu Val Leu Gln Gly His Ile His Asp Asp Arg 3410 3415 3420 Val Glu Leu Val Leu Ile Tyr Asp Ser Val Val Leu Pro Glu Pro 3425 3430 3435 Gln Leu Val Ala Leu Ser His Gln Phe Asn Gly Val Val Gln Gln 3440 3445 3450 Leu Leu Ser Gly Lys Asp Cys Lys Leu Gly Glu Ile Ser Val Ala 3455 3460 3465 Ser Pro Trp Asp Leu Asp Leu Ala Gln Ala Ser Asn Gly Asp Gly 3470 3475 3480 Pro Glu Ile Val Asp Asp Cys Ala His Leu Ile Ile Glu Arg Gln 3485 3490 3495 Thr Lys Gln Thr Pro His Ala His Ala Val His Ala Trp Asp Gly 3500 3505 3510 Ser Leu Thr Tyr Ser Glu Leu Asp Leu Ala Ala Asn Arg Leu Ala 3515 3520 3525 Asn Leu Leu Ile Gln Arg His Gly Val Lys Val Gly Asp Val Val 3530 3535 3540 His Val Cys Phe Glu Lys Ser Leu Trp Tyr Val Val Ser Val Leu 3545 3550 3555 Ala Ile Asn Lys Ala Gly Ala Ala Trp Val Pro Met Asp Pro Ala 3560 3565 3570 His Pro Phe Gln Arg Leu Gln Gln Val Ala Ser Gln Thr Gly Ala 3575 3580 3585 Lys Leu Ala Leu Ser Ser Ala Ile His Ser Pro Leu Cys Ser Lys 3590 3595 3600 Leu Leu Asp Thr Val Val Glu Val Ser Ser Asn Leu Asp Glu Gln 3605 3610 3615 Leu Lys Ser Asp Glu Thr Ile Ser His Val Lys Pro Thr Thr Lys 3620 3625 3630 Val Thr Pro Asn Asp Ala Val Tyr Leu Leu Phe Thr Ser Gly Ser 3635 3640 3645 Thr Gly Val Pro Lys Gly Ile Ile Met Glu His Ala Ser Leu Cys 3650 3655 3660 Thr Ser Gln Arg Asp Ile Ala Lys Arg Leu Gly Leu Thr Ser Ser 3665 3670 3675 Val Arg Met Leu Gln Phe Ser Ser Phe Val Phe Asp Val Ser Val 3680 3685 3690 Gly Glu Ile Met Leu Ser Leu Met His Gly Gly Cys Ile Cys Ile 3695 3700 3705 Pro Ser Asp His Asp Arg Leu Asn Asn Leu Asp Gly Phe Ile Arg 3710 3715 3720 Asp Ala Glu Val Thr Trp Ala Phe Leu Thr Pro Ser Phe Ala Arg 3725 3730 3735 Thr Leu Arg Pro Gln Asp Val Pro Ser Leu Glu Leu Ile Val Leu 3740 3745 3750 Ala Gly Glu Pro Val Ser Gln Asp Val Phe Asp Leu Trp Phe Gly 3755 3760 3765 Lys Ala Arg Leu Val Asn Gly Trp Gly Pro Ala Glu Thr Cys Val 3770 3775 3780 Leu Ser Ala Ile His Glu Trp Lys Ser Ala Asp Glu Ser Pro Leu 3785 3790 3795 Thr Ile Gly Arg Ser Val Gly Ser Phe Ala Trp Ile Val Asp Ala 3800 3805 3810 Glu Asn Ser Asn Arg Leu Ala Pro Val Gly Cys Ile Gly Glu Ile 3815 3820 3825 Val Met Gln Gly Pro Thr Leu Leu Arg Glu Tyr Leu Ala Asp Pro 3830 3835 3840 Ala Lys Thr Ala Ser Ser Thr Met Thr Ser Leu Pro Asn Trp Ala 3845 3850 3855 Pro Arg Ala Asn Asp Lys Lys Trp Gly Arg Phe Tyr Lys Thr Gly 3860 3865 3870 Asp Leu Gly Phe Tyr Asn Pro Asp Gly Thr Ile His Tyr Ser Gly 3875 3880 3885 Arg Lys Asp Thr Gln Val Lys Ile Arg Gly Leu Arg Val Glu Leu 3890 3895 3900 Gly Glu Val Glu His His Ile Arg Asn Ala Leu Glu Ser Ile Arg 3905 3910 3915 Gln Val Ala Val Asp Val Phe Arg Thr Glu Thr Gly Thr Asn Leu 3920 3925 3930 Val Ser Tyr Ile Cys Phe Ser Ser Glu Thr Lys Thr Pro Gly Pro 3935 3940 3945 Asn Thr Asp Pro Asn Gly Asp Asp Val Phe Leu Tyr Met Thr Arg 3950 3955 3960 Asn Val Gln Ser Asp Leu Asn Ile Ala Ile Asn Lys Leu Asn Ala 3965 3970 3975 Leu Leu Pro Ser Tyr Met Ile Pro Thr Tyr Trp Ile Pro Cys Asp 3980 3985 3990 Tyr Met Pro Leu Ile Ser Ser Gly Lys Leu Asp Arg Val Lys Leu 3995 4000 4005 Arg Lys Gln Met Ala Ala Leu Thr Gln Glu Glu Leu Glu Ala Tyr 4010 4015 4020 Ser Leu Thr Asp Ala Asp Lys Arg Ala Pro Asp Thr Ala Met Glu 4025 4030 4035 Val Arg Leu Gln Ser Met Trp Ala Glu Ile Leu Asn Ile Pro Ala 4040 4045 4050 Gln Thr Ile Gly Lys Asp Asp Asn Phe Leu Arg Ile Gly Gly Asp 4055 4060 4065 Ser Ile Ala Ala Ile Arg Leu Val Ser Met Ala Arg Glu Arg Gly 4070 4075 4080 Ile Thr Leu Thr Val Asn Gly Ile Phe Glu Asp Pro Arg Leu Ser 4085 4090 4095 Ser Met Ala Ala Thr Ala Gly Ala Ala Asp Gly Asp Asp Glu Leu 4100 4105 4110 Leu Thr Pro Ile Pro Ala Phe Ser Leu Leu Asp Asp Ser Thr Arg 4115 4120 4125 Asp Pro Ile Gln Ala Pro Ser Ile Tyr Gln Asp Leu Gly Leu Asn 4130 4135 4140 Val Thr Gln Arg Ile Glu Asp Ala Tyr Pro Thr Thr Lys Leu Gln 4145 4150 4155 Glu Gly Leu Met Ala Leu Ser Ala Lys Gln Pro Gly Ser Tyr Ile 4160 4165 4170 Ala Lys Phe Leu Tyr Arg Ile Pro Lys His Ile Glu Val Ala Arg 4175 4180 4185 Phe Lys Asp Ala Trp Arg Arg Thr Val Asp Ala Cys Pro Asn Leu 4190 4195 4200 Arg Thr Arg Ile Leu Leu Thr Glu Gly Gly His Ser Thr Gln Leu 4205 4210 4215 Val Ile Ser His Asp Phe Glu Trp Asp Leu Val Glu Asn Glu Asp 4220 4225 4230 Leu His Ser Tyr Leu Gln Leu Thr Gln Asp Phe Glu Met Gly Tyr 4235 4240 4245 Gly Ser Gln Leu Ser Arg Tyr Ala Leu Ile Lys His Thr Asp Gly 4250 4255 4260 Glu Thr Tyr Phe Met Trp Ser Val His His Ala Val Phe Asp Gly 4265 4270 4275 Leu Ser Thr Gln Asn Val Leu Asn Ile Leu Glu Lys Ala Tyr Gln 4280 4285 4290 Gly Lys Asp Val Leu Glu Thr Pro Pro Tyr Ala Arg Phe Ile Lys 4295 4300 4305 Tyr Thr Leu Gly Leu Asp Ala Glu Ala Ala Ala Thr Tyr Trp Arg 4310 4315 4320 Glu Gln Leu Gln Ser Ser Arg Lys Ala Thr Phe Pro Ala Ser Ser 4325 4330 4335 Glu Val Ser Asn Lys Pro Gly Ala Thr Arg Val Leu Glu Arg Ser 4340 4345 4350 Ile Glu Leu Pro Lys Met Ala Ser Ser Gly Ile Thr Leu Ala Thr 4355 4360 4365 Val Val Arg Ser Ala Trp Ala Met Val Leu Ala Arg Tyr Ser Asp 4370 4375 4380 Ser Glu Asp Val Thr Phe Gly Thr Ser Ile Ser Gly Arg Gln Ala 4385 4390 4395 Pro Val Pro Glu Leu Met Asp Met Val Gly Pro Ile Ile Ala Thr 4400 4405 4410 Val Pro Val Arg Val Arg Val Asp Gln Ala Gln Leu Ala Thr Asp 4415 4420 4425 Phe Leu Gln Ala Val Gln Arg Gln Thr Leu Glu Met Val Pro Tyr 4430 4435 4440 Glu Gln Phe Gly Leu Gln Ser Ile Ala Lys Val Ser Glu Asp Ala 4445 4450 4455 Lys Glu Ala Cys Asp Phe Thr Ser Leu Leu Val Ile Gln Pro Met 4460 4465 4470 Gln His Val Ser Asp Ser Glu Ser Ala Asp Ser Val Leu Val His 4475 4480 4485 Ala Asp Gly Ala Leu Lys Glu Glu Ala Glu Ser Met Glu Asn Tyr 4490 4495 4500 Phe Ser Tyr Pro Leu Ile Val Gln Ala His Leu Tyr Glu Asp Arg 4505 4510 4515 Ile Asn Ile Val Leu Ile Tyr Asp Ser Thr Ile Leu Ala Lys Thr 4520 4525 4530 Gln Leu Glu Ala Leu Ser Gln Gln Leu Gly His Val Met Cys Gln 4535 4540 4545 Leu Ala Ala Ala Thr Asp Glu Lys Ser Leu Gly Ser Val Ser Ile 4550 4555 4560 Thr Ser Asp Trp Asp Leu Glu Arg Ala Val Ser Phe Asn Ser Asp 4565 4570 4575 Val Pro Glu Ile Val Asp Ala Cys Val His Asp Leu Val Ala Arg 4580 4585 4590 Gln Ala Glu Leu Arg Pro Asp Ser Val Ala Ile Ser Ala Trp Asp 4595 4600 4605 Ala Glu Leu Thr Tyr Ser Gln Leu Asn Leu Ala Ala Asn Arg Leu 4610 4615 4620 Ala Asn His Ile Ile Thr Ala Tyr Gly Ile Lys Pro Asn Asp Phe 4625 4630 4635 Ile His Val Cys Phe Glu Lys Ser Ala Trp His Phe Val Ala Ile 4640 4645 4650 Leu Ala Ile Asn Lys Ala Gly Ala Ala Trp Val Pro Leu Asp Ser 4655 4660 4665 Ser His Pro Glu Gln Arg Leu Arg Gln Val Val Ser Gln Thr Asn 4670 4675 4680 Ala Arg Leu Val Leu Thr Ser Pro Ser Asn Ser Thr Leu Cys Ser 4685 4690 4695 Gly Leu Leu Ala Asp Val Leu Glu Val Thr Pro Ala Leu Asp Gln 4700 4705 4710 Lys Leu Ala Ala Thr Val Gly Ser Gln Ala Pro Lys Val Ala Val 4715 4720 4725 Thr Pro Glu His Ala Val Tyr Ala Leu Phe Thr Ser Gly Ser Thr 4730 4735 4740 Gly Thr Pro Lys Gly Leu Val Met Gln His Arg Ala Val Cys Thr 4745 4750 4755 Ser Gln Thr Ala Ile Ala Lys Arg Leu Gly Leu Ser Ser Asp Ile 4760 4765 4770 Arg Gln Leu Gln Phe Ala Ala Phe Val Phe Asp Leu Ser Ile Gly 4775 4780 4785 Glu Ile Ile Ala Pro Leu Ile Ser Gly Ala Cys Val Cys Val Pro 4790 4795 4800 Ser Glu Asp Val Arg Met Asn Ser Ile Thr Glu Tyr Ile Arg Asp 4805 4810 4815 Gln Arg Ile Asn Trp Ala Phe Leu Thr Pro Ser Tyr Val Arg Thr 4820 4825 4830 Leu Arg Pro Lys Asp Val Pro Gly Leu Glu Leu Leu Leu Leu Ala 4835 4840 4845 Gly Glu Ala Val Pro Lys Glu Ile Leu Asn Thr Trp Phe Gly Lys 4850 4855 4860 Leu Arg Leu Val Asn Gly Trp Gly Pro Ala Glu Thr Cys Val Phe 4865 4870 4875 Ser Thr Leu His Glu Trp Lys Ser Val Asp Glu Ser Pro Leu Thr 4880 4885 4890 Val Gly Lys Pro Val Gly Gly Phe Cys Trp Val Val Asp Pro Glu 4895 4900 4905 Asn Pro His Lys Leu Ala Pro Val Gly Thr Leu Gly Glu Val Val 4910 4915 4920 Ile Gln Gly Pro Thr Leu Leu Arg Glu Tyr Leu Ala Asp Pro Glu 4925 4930 4935 Arg Thr Ala Ala Ser Ser Ala Thr Ala Pro Asp Trp Ala Pro Gln 4940 4945 4950 Pro Asp Ser Lys His Trp Gly Arg Leu Tyr Lys Ser Gly Asp Leu 4955 4960 4965 Cys Ser Tyr Asn Pro Asp Gly Thr Leu Glu Phe Ser Ser Arg Lys 4970 4975 4980 Asp Thr Gln Ile Lys Ile Arg Gly Leu Arg Val Glu Leu Gly Glu 4985 4990 4995 Val Glu His His Ile Gln Thr Ala Met Arg Gly Leu Arg Gln Ile 5000 5005 5010 Ala Val Asp Val Tyr Lys Gly Glu Ser Gly Thr Asn Leu Val Ala 5015 5020 5025 Tyr Leu Cys Phe Thr Asp Glu Thr Arg Ala Ser Ser Ala Asp His 5030 5035 5040 Ser Pro Phe Met Ser Val Asp Lys Lys Leu Gln Asn Gln Leu Asn 5045 5050 5055 Ala Leu Val Gly Glu Leu Gly Val Thr Leu Pro Arg Tyr Met Ile 5060 5065 5070 Pro Thr Leu Tyr Ile Pro Cys Ser Phe Met Pro Ser Ile Thr Ser 5075 5080 5085 Thr Lys Leu Asp Arg Asn Glu Leu Arg Arg Arg Thr Ala Ser Leu 5090 5095 5100 Thr Arg Asp Glu Leu Ser Gln Tyr Ser Leu Leu Gly Gly Asn Lys 5105 5110 5115 Arg Ala Pro Glu Thr Asp Val Glu Arg Ala Leu Gln Arg Ile Trp 5120 5125 5130 Ser Gly Ile Leu Gly Leu Ser Pro Asp Ala Ile Gly Arg Asp Asp 5135 5140 5145 Ser Phe Leu Gly Leu Gly Gly Asp Ser Ile Thr Ala Ile Gln Leu 5150 5155 5160 Val Gly Val Cys Arg Asp Gln Gly Ile Ser Leu Ser Val Lys Asp 5165 5170 5175 Ile Phe Asn Asp Pro Arg Leu Ile Ala Val Ala Lys Ala Ala Gln 5180 5185 5190 Ser Leu Ser Ser Val Asp Asp Val Ala Ile Glu Pro Phe Gly Leu 5195

5200 5205 Leu Asp Asp Glu Leu Arg Arg Leu Ala Thr Ser Glu Thr Ala Arg 5210 5215 5220 Ala Gln Cys His Leu Ala Thr Glu Ala Val Ile Glu Asp Ala Tyr 5225 5230 5235 Pro Cys Thr Lys Phe Gln Glu Gly Leu Met Ala Leu Ser Ile Lys 5240 5245 5250 Ser Pro Gly Ser Tyr Val Ala Lys Tyr Ala Tyr Arg Leu Ala Asp 5255 5260 5265 Asp Val Asp Ile Glu Gln Phe Lys Ser Ser Trp Lys Lys Thr Val 5270 5275 5280 Ser Leu Cys Pro Thr Leu Arg Thr Arg Ile Val Leu Leu Gly Asp 5285 5290 5295 Arg Cys Val Gln Leu Val Val Lys Glu Asp Ala Glu Phe Val Ser 5300 5305 5310 Ser Thr Ala Ser Ser Phe Glu Ser Ala Met Leu Glu Ala Arg Asn 5315 5320 5325 Val Gln Met Thr Tyr Gly Thr Pro Leu Ser Gln Tyr Thr Leu Phe 5330 5335 5340 Gln Gly Glu Asp Gly Phe Tyr Phe Ile Trp Val Val His His Thr 5345 5350 5355 Val His Asp Gly Trp Thr Met Arg Leu Val Leu Glu Thr Leu Gln 5360 5365 5370 Asn Leu His Gln Gly Ser Thr Thr Ser Ser Leu Lys Pro Tyr Ser 5375 5380 5385 Asn Phe Ile Lys Tyr Ala Met Asp Val Val Gln Asp Pro Ala Val 5390 5395 5400 Glu Lys Tyr Trp Ser Gln Gln Leu Asp Gly Ala Val Gln Ala Ser 5405 5410 5415 Tyr Pro Pro Arg Pro Arg Ser Asp Lys Gln His Lys Ala Val Thr 5420 5425 5430 Arg Met Met Thr Lys Thr Ile Gln Val Pro Asn Asn Thr Gln Ser 5435 5440 5445 Ser Val Thr Met Ala Thr Leu Leu Arg Ala Thr Trp Ala Ile Ile 5450 5455 5460 Leu Ala Arg Tyr Ser Asn Thr Asp Asp Ile Cys Phe Ala Thr Thr 5465 5470 5475 Val Ser Gly Arg Gln Ala Ser Val Ser Asp Ile Leu Gln Ile Pro 5480 5485 5490 Gly Pro Ile Val Ala Thr Ile Pro Val Arg Val Arg Leu Asn Gly 5495 5500 5505 Gln Gln Thr Val Leu Glu Tyr Leu Glu Ser Val Gln His Gln Ala 5510 5515 5520 Thr Gln Met Ile Pro His Glu Gln Tyr Gly Leu Gln Asn Ile Ser 5525 5530 5535 Arg Ile Ser Glu Asn Ile Ser Asp Ala Ile Asp Phe Ser Ser Leu 5540 5545 5550 Leu Val Ile Gln Pro Arg Ser His Leu Asp Ser Gly Asn Gly Asp 5555 5560 5565 Gly Ser Asn Glu Asn Ile Leu Ile Pro Thr Val Glu Asp Asp Glu 5570 5575 5580 Ala Val Ala Asp Leu Leu Gln Asp Tyr Phe Thr Tyr Pro Leu Val 5585 5590 5595 Ile Gln Gly Asn Leu Leu Asp Asp His Ile Asp Leu Leu Leu Thr 5600 5605 5610 Tyr Asp Ser Thr Val Leu Ser Glu Val Glu Leu Ser Arg Leu Ala 5615 5620 5625 Val Gln Phe Glu His Val Ala Gln Gln Leu Leu Asp Ser Asp His 5630 5635 5640 Val Lys Leu Gly Asp Leu Ser Leu Val Pro Pro Gln Asp Val Gln 5645 5650 5655 Gln Ala Ile Ala Trp Asn Thr Glu Asp Pro Glu Ile Val Glu Asp 5660 5665 5670 Cys Ile His Lys Leu Val Glu Arg Gln Ala Ile Ser Thr Pro Asp 5675 5680 5685 Ala Ile Ala Ile Asp Ser Trp Asp Gly Lys Leu Thr Tyr Ala Gln 5690 5695 5700 Leu Asp Glu Ala Ala Thr Arg Leu Ser His His Leu Ile Lys Thr 5705 5710 5715 Tyr Asp Val Ala Pro Asp Asp Leu Val Leu Leu Leu Phe Gly Lys 5720 5725 5730 Ser Leu Trp Tyr Ile Ile Ser Thr Ile Ala Val Asn Lys Ala Gly 5735 5740 5745 Ala Ala Trp Val Pro Leu Asp Pro Ala His Pro Met Gln Arg Leu 5750 5755 5760 Gln Gln Val Thr Arg Gln Thr Lys Ala Gln Val Ile Leu Ala Ser 5765 5770 5775 Ser Leu Gln Cys Glu Leu Ala Gln Glu Leu Leu Asn Thr Val Val 5780 5785 5790 Glu Val Ser Gln Ala Leu Asp Asp Ala Leu Thr Thr Ala Gly Ser 5795 5800 5805 Thr Leu Arg Thr Pro Asp Ala Met Val Ser Ser Arg Asp Lys Ala 5810 5815 5820 Tyr Val Leu Phe Thr Ser Gly Ser Thr Gly Val Pro Lys Gly Ile 5825 5830 5835 Val Ile Ser His Gly Ser Val Cys Thr Ser Gln Thr Ala Ile Ser 5840 5845 5850 Ser Arg Leu Gly Leu His Ser Gly Val Arg Met Leu Gln Phe Ser 5855 5860 5865 Ala Phe Val Phe Asp Val Ser Val Gly Glu Ile Tyr Gly Ser Leu 5870 5875 5880 Ile Arg Gly Ala Cys Val Val Ile Pro Ser Asp Glu Ile Arg Met 5885 5890 5895 Asn Asp Leu Thr Arg Phe Met Arg Glu Lys Glu Val Thr Trp Ala 5900 5905 5910 Cys Phe Thr Pro Ser Phe Ile Glu Thr Leu His Pro Ala Asp Leu 5915 5920 5925 Glu Asn Leu Glu Leu Val Ile Leu Glu Gly Glu Pro Ser Lys Arg 5930 5935 5940 His Ile Leu Glu Glu Trp Phe Gly Lys Val Lys Leu Ile Asn Gly 5945 5950 5955 Trp Gly Pro Ala Glu Thr Cys Val Phe Ser Ser Met His Glu Trp 5960 5965 5970 Lys Ser Ala Thr Glu Ser Pro Val Thr Ile Gly Lys Pro Val Gly 5975 5980 5985 Cys Phe Ala Trp Ile Ala Asp Pro Asp Asn His His Arg Leu Ala 5990 5995 6000 Pro Ile Gly Thr Val Gly Glu Ile Val Leu Gln Gly Pro Thr Leu 6005 6010 6015 Leu Cys Glu Tyr Leu Asp Asp Pro Met Gln Thr Gln Ala Ser Ile 6020 6025 6030 Leu Lys Ser Ile Pro Ser Trp Ala Pro Arg Arg Glu Ser Gln His 6035 6040 6045 Trp Asn Arg Phe Tyr Leu Thr Gly Asp Leu Gly Cys Tyr Asn Pro 6050 6055 6060 Asp Gly Thr Leu Ala Tyr His Gly Arg Lys Asp Thr Gln Val Lys 6065 6070 6075 Ile Arg Gly Leu Arg Val Glu Leu Asp Glu Val Glu His His Ile 6080 6085 6090 Arg Ser Leu Leu Ser Asp Val Val His Val Thr Val Asp Val His 6095 6100 6105 Lys Ser Glu Ala Gly Ser Ser Leu Val Ala Tyr Leu Ala Tyr Thr 6110 6115 6120 Glu Glu Ser Val Asp Asp Glu Asp Ala Leu Phe Leu Pro Leu Thr 6125 6130 6135 Asn Glu Leu Gln Lys Asp Leu Asp Ala Met Ser Ser Gln Leu Ser 6140 6145 6150 Val Leu Leu Pro Arg Tyr Met Val Pro Thr Leu Tyr Ile Pro Cys 6155 6160 6165 Ser His Met Pro Phe Leu Ser Ser Gly Lys Thr Asp Arg Ala Gln 6170 6175 6180 Leu Arg Arg Leu Thr Ser Glu Leu Ser Gln Glu Gln Leu Glu Ala 6185 6190 6195 Tyr Ala Leu Asp Asp Thr Lys Lys Glu Ala Ala Glu Thr Glu Ala 6200 6205 6210 Glu Leu Arg Leu Arg Asp Val Trp Ala Lys Ile Leu Gly Leu Ser 6215 6220 6225 Ala Gln Ser Ile Gly Arg His Asp Ser Phe Leu Arg Ile Gly Gly 6230 6235 6240 Asp Ser Ile Ala Ala Ile Gln Leu Val Thr Ala Ala Arg Glu Ala 6245 6250 6255 Gly Ile Ile Phe Ser Val Lys Asp Val Phe Asp Asp Ser Arg Leu 6260 6265 6270 Trp Lys Leu Ala Glu Phe Ala Ser Ser Lys Thr Glu Ser Glu Lys 6275 6280 6285 Val Val Glu Ala Ile Ala Pro Phe Ser Leu Leu Arg Thr Ser Leu 6290 6295 6300 Asn Glu Thr Ala Val Thr Ala Ile Leu Gln Gln Gln Tyr Gly Leu 6305 6310 6315 Thr Asp Ser Val Val Val Glu Asp Ala Tyr Pro Ser Thr Lys Leu 6320 6325 6330 Gln Glu Gly Leu Met Ala Ile Ser Ala Lys Gln Pro Gly Thr Tyr 6335 6340 6345 Val Ala Lys Gln Val Tyr Gly Leu Pro Glu His Val Asp Leu Asp 6350 6355 6360 Thr Phe Lys Ala Ala Trp Glu Arg Thr Val Glu Leu Cys Val Asn 6365 6370 6375 Leu Arg Thr Arg Leu Val Ile Ala Gly Asp Ala Ser Val Gln Val 6380 6385 6390 Val Ile Arg Asn Glu Glu Ile Glu Trp Glu Thr Cys Asn Thr Thr 6395 6400 6405 Val Gln Ala Tyr Leu Ser Gln Gln Phe Asn Met Gly Tyr Gly Ser 6410 6415 6420 Arg Leu Phe Arg Asn Gly Ile Val His Glu Pro Ser Gly Gln Asn 6425 6430 6435 Phe Phe Val Leu Ser Ile His His Ala Ile Phe Asp Gly Trp Thr 6440 6445 6450 Leu Pro Met Leu Met Glu Thr Leu Asp Ser Ala Tyr Arg Gly Val 6455 6460 6465 Glu Ala Ser Ala Leu Arg Pro Tyr Ala Glu Phe Val Lys Tyr Ile 6470 6475 6480 Leu Asp Ile Asp Glu Ala Ala Ala Gly Asp Tyr Trp Arg Gly Gln 6485 6490 6495 Leu Gln Asp Ala Lys Arg Ala Ser Phe Pro Pro Ser Ala Pro Val 6500 6505 6510 Gln Ser Ser Gln Thr Ile Thr Arg Ile Leu Glu Lys Pro Leu Asn 6515 6520 6525 Phe Ser His Ser Ile Lys Ser Gly Ile Thr Lys Ala Ser Val Leu 6530 6535 6540 Arg Ala Ala Trp Ala Leu Val Leu Ser Arg Tyr Ser Asp Ser Asp 6545 6550 6555 Asp Val Thr Phe Gly Val Asn Val Ser Gly Arg Asn Ala Ala Val 6560 6565 6570 Ala Gly Ile Glu Ser Met Pro Gly Leu Val Val Ala Thr Val Pro 6575 6580 6585 Val Arg Val Arg Leu Asp Pro Glu Gln Thr Val Ser Gln Phe Val 6590 6595 6600 Glu Ser Ile Gln Ser Gln Ser Thr Asp Met Ile Pro Tyr Glu Gln 6605 6610 6615 Phe Gly Leu Gln Asp Ile Ser Lys Leu Ser Pro Glu Ala Lys Asp 6620 6625 6630 Ala Cys Asp Phe Ser Ser Leu Met Val Ile Gln Pro Met Ser Ser 6635 6640 6645 Ile Ala Asn Asn Lys Ser Val Leu Glu Pro Pro Pro Glu Asp Lys 6650 6655 6660 Ala Ala Ala Glu Glu Ser Leu Gln Asn Tyr Phe Thr Tyr Pro Leu 6665 6670 6675 Val Ile Gln Ala His Leu His Asp Asp Gly Ala Val Asn Leu Leu 6680 6685 6690 Leu Ile Tyr Asp Ala Asn Val Leu Ser Glu Asp Gln Leu Gln Ala 6695 6700 6705 Leu Ser Ile Gln Phe Asp His Val Val Gln Gln Leu Leu Gly Gln 6710 6715 6720 Asp Ser Gly Ala Lys Leu Arg Asp Val Thr Ile Ala Gly Pro Trp 6725 6730 6735 Asp Leu Gln Gln Ala Met Ser Tyr Asn Val Lys Glu Pro Gly Ile 6740 6745 6750 Val Asn Ala Cys Val His Glu Leu Ile Ala Gln Gln Ala Ala Arg 6755 6760 6765 Asp Pro His His Glu Ala Ile Tyr Ser Ser Glu Gly Thr Val Thr 6770 6775 6780 Tyr Ala Thr Leu Asp Arg Leu Ser Ser Leu Leu Ala His His Leu 6785 6790 6795 His Ala His Gly Val Arg Pro Glu Ser Val Val Pro Phe Cys Phe 6800 6805 6810 Asp Lys Ser Ala Trp Ala Ile Ile Ala Met Leu Ala Ile Leu Lys 6815 6820 6825 Ala Gly Gly Val Phe Leu Pro Leu Asp Pro Ser His Pro Arg Asn 6830 6835 6840 Arg Arg Glu Ala Leu Ile Glu Glu Val Gly Ala Glu Val Met Ile 6845 6850 6855 Val Ser Pro Ser Ser Ser Val Thr Cys Glu Gly Leu Thr Pro Thr 6860 6865 6870 Met Val Glu Leu Thr Thr Pro Leu Leu Glu Gln Leu Ser Ser Thr 6875 6880 6885 Tyr Asp Ala Phe Gln Gln Ile His Pro Lys Pro Lys Pro Ser Asn 6890 6895 6900 Ala Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys 6905 6910 6915 Gly Val Leu Met Glu His Ser Gly Phe Ala Thr Ser Thr Leu Gly 6920 6925 6930 His Gly Arg Val Tyr Asn Leu Gly Pro Thr Ser Arg Val Phe Gln 6935 6940 6945 Phe Ser Asn Tyr Val Phe Asp Gly Ser Leu Gly Glu Ile Phe Thr 6950 6955 6960 Thr Leu Ser Phe Gly Gly Thr Val Cys Val Pro Ser Glu Thr Glu 6965 6970 6975 Arg Leu Gln Glu Ala Pro Thr Phe Met Arg Lys Ser Arg Val Asn 6980 6985 6990 Thr Ala Met Leu Thr Pro Ser Phe Val Arg Thr Phe Thr Pro Asp 6995 7000 7005 Gln Val Pro Ser Leu Gln Leu Leu Val Leu Gly Gly Glu Ala Ser 7010 7015 7020 Ser Lys Asp Leu Ile Glu Thr Trp Cys Asp Arg Leu Arg Leu Val 7025 7030 7035 Asn Gly Tyr Gly Pro Ala Glu Ala Cys Asn Tyr Ala Thr Thr His 7040 7045 7050 Asp Phe Lys Pro Thr Asp Ser Pro Arg Thr Ile Gly Arg Gly Phe 7055 7060 7065 Asn Ser Ala Cys Trp Ile Val Glu Pro Thr Asp Tyr Asn Arg Leu 7070 7075 7080 Thr Pro Ile Gly Cys Val Gly Glu Leu Ile Ile Gln Gly Asn Ala 7085 7090 7095 Leu Ala Arg Gly Tyr Ile Asn Asp Pro Lys Arg Thr Ala Asp Ser 7100 7105 7110 Phe Val Thr Ala Val Asp Cys Leu Pro Arg Asp Met Ile Ser Gly 7115 7120 7125 Pro His Arg Phe Tyr Leu Thr Gly Asp Leu Val Arg Tyr Asn Ser 7130 7135 7140 Thr Gly Glu Met Glu Tyr Leu Gly Arg Lys Asp Thr Gln Val Lys 7145 7150 7155 Leu Arg Gly Gln Arg Leu Glu Leu Gly Glu Ile Glu Tyr Gln Val 7160 7165 7170 Lys Gln Ser Leu Pro Glu Ile Glu His Val Ala Val Asp Val Val 7175 7180 7185 His Arg Glu Thr Gly Asp Ala Leu Ile Ala Phe Val Ser Phe Lys 7190 7195 7200 Asp Thr Ala Ser Ser Ala Ser Ser Asp Ile Leu Ser Leu Asp Asp 7205 7210 7215 Glu Met His Ser Thr Leu Ala Thr Val Met Glu His Leu Lys Ser 7220 7225 7230 Ser Leu Pro Gly Tyr Met Val Pro Ser Thr Ile Leu Pro Leu Lys 7235 7240 7245 Lys Met Pro Phe Ile Thr Ser Met Lys Val Asp Arg Lys Arg Leu 7250 7255 7260 Ile Ala Val Ala Ala Glu Leu Ser Leu Glu Glu Leu Thr Ser Phe 7265 7270 7275 Ser Leu Val Lys Arg Asp Phe Ala Pro Pro Thr Thr Ala Met Glu 7280 7285 7290 Lys Lys Leu Ala Asp Leu Trp Ala Gln Val Leu Lys Ile Asp Val 7295 7300 7305 Gly Ser Ile Gly Lys Asn Asp Ser Phe Leu Gln Ile Gly Gly Asp 7310 7315 7320 Ser Ile Thr Ser Ile His Leu Val Thr Leu Ala Gln Lys Ser Gly 7325 7330 7335 Ile Asn Leu Thr Val Ala Gly Ile Phe Asp Asp Ser Lys Leu Ser 7340 7345 7350 Ser Met Ala His Ser Ala Gly Glu Gly Asp Ile Glu Pro Val Tyr 7355 7360 7365 Glu Val Val Pro Phe Asp Met Val Ala Thr His Asn Leu Ser Ser 7370 7375 7380 Leu Met Glu Glu Val Arg Thr Lys Cys Gly Leu Pro Gly Ser Ala 7385 7390 7395

Val Ile Glu Asp Ile Tyr Pro Ala Thr Ser Phe Gln Glu Gly Leu 7400 7405 7410 Met Ala Leu Ala Val Lys Gln Pro Gly Ser Tyr Ile Ala Lys Gln 7415 7420 7425 Val Tyr Gln Leu Pro Arg Gly Val Asp Val Ala Arg Phe Lys Ala 7430 7435 7440 Ala Trp Glu Thr Thr Ala Arg Met Cys Ser Asn Leu Arg Thr Arg 7445 7450 7455 Ile Val Leu Ala Gly Asp Ala Ser Val Gln Val Ile Leu Lys Asp 7460 7465 7470 Ile Gly Ser Trp Glu Val Thr Ser Asn Met Thr Leu Lys Ser Tyr 7475 7480 7485 Leu Gln Ala Thr Gln Lys Ile Asn Met Asp Tyr Gly Ser Ala Leu 7490 7495 7500 Ser Arg His Ala Leu Ile Glu Gln Ala Asp Gly Lys Asn Tyr Phe 7505 7510 7515 Val Trp Ser Ile His His Thr Val Phe Asp Gly Trp Thr Thr Arg 7520 7525 7530 Leu Val Leu Asn Thr Leu Leu Ser Ala Tyr Met Gly Glu Gln Ile 7535 7540 7545 Val Pro Leu Glu Pro Tyr Ala Arg Phe Ile Asn Tyr Ala Ile Asn 7550 7555 7560 Leu Asn Ile Asp Ala Ala Lys Ser Tyr Trp Thr Glu Gln Leu Leu 7565 7570 7575 Asp Ala Lys Arg Ala Leu Phe Pro Ala Val Ser Asn Glu Val Ser 7580 7585 7590 Arg Asn Lys Thr Ser Asn Thr Arg Val Leu Glu Lys Ala Leu Asp 7595 7600 7605 Leu Pro Gln Val Lys Gln Thr Ser Ile Thr Met Ala Ser Ile Leu 7610 7615 7620 Arg Ala Thr Trp Ser Ile Val Leu Ala Gln Tyr Cys Asp Thr Asp 7625 7630 7635 Asp Val Thr Phe Gly Thr Thr Val Ser Gly Arg Gln Ala Pro Val 7640 7645 7650 Ser Gly Ile Thr Glu Met Ala Gly Pro Val Val Ala Thr Val Pro 7655 7660 7665 Val Arg Val Arg Leu Asp Arg Asn Ala Ser Val Pro Glu Phe Leu 7670 7675 7680 Lys Gly Ile Gln Thr Gln Ala Ser Gln Met Ile Pro Phe Glu Gln 7685 7690 7695 Phe Gly Leu Gln Asn Ile Ala Lys Leu Asn Val Glu Ala Lys Glu 7700 7705 7710 Ala Cys Asp Phe Arg Ser Leu Leu Val Ile Gln Pro Met Lys Lys 7715 7720 7725 Leu Leu Asp Thr Gly Asp Arg Glu Ala Ile Met Glu Pro Val Ser 7730 7735 7740 Ala Thr Thr Arg Asp Glu Glu Asp Phe Met Gln Asn Tyr Phe Ser 7745 7750 7755 Tyr Pro Leu Val Ile Gln Gly His Val Tyr Glu Glu Ser Val Asn 7760 7765 7770 Leu Val Leu Ile Tyr Asp Ala Asp Ile Leu Pro Glu Gln Gln Leu 7775 7780 7785 Leu Ala Leu Ala His Gln Phe Glu His Val Ala Gln Gln Leu Val 7790 7795 7800 Ala Lys Gly Asn Arg Thr Thr Lys Leu Gly Asp Val Ser Val Ser 7805 7810 7815 Gly Ala Trp Asp Leu Asp Phe Ala Leu Arg Gln Asn Ser Glu Val 7820 7825 7830 Pro Glu Leu Ile Asp Ser Cys Phe His Thr Leu Val Glu Gln Gln 7835 7840 7845 Ala Val Val Arg Pro Glu Ala Pro Ala Ile Asn Gly Trp Asp Ala 7850 7855 7860 Lys Phe Thr Tyr Ala Gln Leu Asn Glu Ala Ala Asn Arg Leu Ala 7865 7870 7875 Asn His Leu Val Ala Glu Tyr Glu Ile Asn Asn Asp Glu Leu Ile 7880 7885 7890 His Val Cys Phe Glu Lys Ser Ala Trp Phe Phe Val Ala Ile Leu 7895 7900 7905 Ala Ile Asn Lys Ala Gly Ala Ala Trp Val Pro Leu Asp Pro Ser 7910 7915 7920 His Pro Ser Gln Arg His Gln Gln Val Val Asn Gln Thr Lys Ala 7925 7930 7935 Arg Leu Ala Leu Val Ser Thr Ser His Ile Ser Thr Cys Val Asp 7940 7945 7950 Leu Val Asp Asp Ile Leu Glu Val Ser Ser Thr Thr Asp Glu Leu 7955 7960 7965 Leu Arg Lys Ser Gln Ser Ser Arg His Gly Pro Thr Arg Lys Val 7970 7975 7980 Ser Pro Ser Asn Ala Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr 7985 7990 7995 Gly Thr Pro Lys Gly Leu Val Met Glu His Gly Ser Val Cys Thr 8000 8005 8010 Ser Gln Thr Ala Ile Val Lys Arg Leu Asn Met Thr Pro Ser Val 8015 8020 8025 Arg Ile Leu Gln Phe Ala Ala Phe Val Phe Asp Leu Ser Ile Gly 8030 8035 8040 Glu Ile Val Ala Pro Leu Ile Thr Gly Ala Cys Ile Cys Val Pro 8045 8050 8055 Ser Glu His Ala Arg Met Asn Ala Leu Pro Glu Phe Val Arg Gln 8060 8065 8070 Asn Asn Val Asn Trp Ala Tyr Leu Thr Pro Ser Tyr Ile Gln Thr 8075 8080 8085 Leu Ser Pro Lys Asp Val Pro Gly Leu Glu Leu Val Leu Leu Ala 8090 8095 8100 Gly Glu Ala Val Ser Arg Asp Ile Leu Asp Ala Trp Phe Gly Lys 8105 8110 8115 Val Arg Leu Val Asn Gly Trp Gly Pro Ala Glu Thr Cys Val Phe 8120 8125 8130 Ser Thr Leu His Glu Trp Arg Ser Lys Asp Glu Glu Ser Pro Leu 8135 8140 8145 Thr Ile Gly Arg Pro Val Gly Gly Phe Thr Trp Ile Val Asp Pro 8150 8155 8160 Glu Asn Pro Gln Lys Leu Ala Pro Ile Gly Val Pro Gly Glu Val 8165 8170 8175 Val Ile Gln Gly Pro Thr Ile Leu Arg Glu Tyr Leu Asp Asp Pro 8180 8185 8190 Val Arg Thr Ser Asp Ser Thr Val Tyr Ser Leu Pro Pro Trp Ala 8195 8200 8205 Pro Asn Arg Gly Thr Lys Trp Asn Arg Phe Tyr Lys Ser Gly Asp 8210 8215 8220 Leu Cys Ser Tyr Asn Ala Asp Gly Thr Ile Glu Phe Ile Ser Arg 8225 8230 8235 Lys Asp Thr Gln Ile Lys Ile Arg Gly Leu Arg Val Glu Leu Gly 8240 8245 8250 Glu Val Glu His His Val Lys Ser Ala Leu Asp Val Arg His Val 8255 8260 8265 Ala Val Asp Val Leu Arg Ser Ser Asn Gly Ser Asn Leu Val Ala 8270 8275 8280 Tyr Phe Cys Phe Ser Asp Gln Thr Arg Met Asn Gly Thr Arg Gly 8285 8290 8295 Thr Ser Asp Gly Ser Gly Leu Phe Ala Glu Met Asp Asp Glu Leu 8300 8305 8310 Gln Thr Arg Leu Thr Ala Val Ile Gly Gln Leu Asn Ile Ser Leu 8315 8320 8325 Pro Arg Tyr Met Val Pro Thr Phe Phe Ile Pro Cys Gln Tyr Met 8330 8335 8340 Pro Thr Ile Thr Ser Thr Lys Leu Asp Arg Asn Tyr Leu Lys Arg 8345 8350 8355 Gln Thr Ala Ala Leu Ser Gln Glu Glu Leu Thr Met Tyr Ser Leu 8360 8365 8370 Leu Gln Gly Gly Lys Lys Arg Ala Pro Glu Lys Asp Met Glu Lys 8375 8380 8385 Gln Leu Gln Ser Ile Trp Ser Gln Ile Leu Ser Ile Pro Ser Glu 8390 8395 8400 Ser Ile Gly Leu Asp Asp Ser Phe Leu Gly Leu Gly Gly Asp Ser 8405 8410 8415 Ile Ser Ala Ile Arg Leu Val Ala Leu Cys Arg Glu Glu Ala Val 8420 8425 8430 Ser Leu Thr Ala Gln Asp Ile Phe Asp Asp Pro Arg Leu Phe Ala 8435 8440 8445 Val Ala Ala Arg Ala Gln Lys Met Asn Val Val Val Glu Glu Ser 8450 8455 8460 Leu Asp Ile Ala Pro Phe Ser Leu Leu Ser Glu Lys Ser Gln Glu 8465 8470 8475 Leu Val Lys Ala Asp Asp Val Arg Ala Gln Cys Asn Leu Ser Trp 8480 8485 8490 Glu Thr Val Val Asp Ala Tyr Pro Cys Thr Pro Leu Gln Glu Gly 8495 8500 8505 Leu Met Ala Leu Ser Val Lys Gln Pro Gly Ser Tyr Met Ala Arg 8510 8515 8520 Tyr Val Tyr Arg Met Pro Arg Thr Val Asn Ile Ala Arg Phe Lys 8525 8530 8535 Trp Ser Trp Glu Arg Thr Val Ser Leu Cys Asp Asn Leu Arg Thr 8540 8545 8550 Arg Ile Val Leu Val Gly Gly Arg Ala Thr Gln Ile Val Val Asp 8555 8560 8565 Gly Pro Ile Asp Trp Asp Val Ser His Asp Leu Glu Ala His Leu 8570 8575 8580 Ser Ala Met Lys Ser Ile Lys Met Thr Tyr Gly Ser Ala Leu Ser 8585 8590 8595 Gln Ile Ala Leu Val Lys Gln Asp Asn Gly Asp Met Phe Phe Thr 8600 8605 8610 Trp Ala Val His His Ser Val Phe Asp Gly Trp Thr Val Pro Ile 8615 8620 8625 Leu Phe Asn Thr Leu Gln Ala Val Tyr Gln Gly Val Lys Pro Ile 8630 8635 8640 Pro Pro Ala Pro Tyr Ala Arg Phe Ile Lys Phe Thr Met Gly Ile 8645 8650 8655 Asp Asn Asp Asn Thr Val Gln Tyr Trp Lys Asp Gln Leu His Asn 8660 8665 8670 Ala Lys Lys Ala Thr Phe Pro Pro Ala Ala Ala Gln Ser Gly Ser 8675 8680 8685 Val Gln Val Leu Glu Thr Ser Ile Asn Tyr Thr Gln Ala Pro Gly 8690 8695 8700 Ser Ser Ile Thr Arg Ala Thr Ile Leu Arg Ala Ala Trp Ala Leu 8705 8710 8715 Val Leu Ala Arg Tyr Ser Glu Ser Asn Asp Ile Thr Phe Gly Thr 8720 8725 8730 Thr Ile Ser Gly Arg Gln Ala Pro Val Asp Glu Ile Thr Asn Met 8735 8740 8745 Ala Gly Pro Ala Val Ala Thr Val Pro Val Arg Val Arg Leu Glu 8750 8755 8760 Lys Gln Gln Thr Val Ser Ala Phe Leu Gln Gly Val Gln Ser Gln 8765 8770 8775 Ala Met Lys Met Ile Ser Tyr Glu Gln Tyr Gly Leu Gln Asn Ile 8780 8785 8790 Ser Lys Val Ser Leu Asp Ala Lys Glu Val Cys Asp Phe Thr Ser 8795 8800 8805 Leu Leu Val Ile Gln Pro Val Glu Asp Leu Ala Tyr Leu Asp Asp 8810 8815 8820 Asp Ala Leu Leu Val Asn Ala Gly Pro Glu Leu Thr Gly Glu Thr 8825 8830 8835 Glu Met Met Gln Asn Tyr Phe Ser Tyr Pro Leu Ile Ile Gln Gly 8840 8845 8850 His Leu Tyr Glu Asn Ser Ile Lys Leu Met Leu Val Tyr Asp Thr 8855 8860 8865 Gln Val Ile Ser Thr Gly Lys Met Asp Ala Leu Ser His His Phe 8870 8875 8880 Asn Ala Ala Val Gln Gln Leu Thr Arg Asn Gly Asn Ala Leu Leu 8885 8890 8895 Asp Asn Val Ser Leu Ala Ser Glu Trp Asp Met Glu Lys Ala Ile 8900 8905 8910 Ala Leu Asn Ser Gly Ser Pro Asp Ala Ile Glu Arg Cys Phe His 8915 8920 8925 Asp Met Val Asp Glu Val Ala Leu Val Arg Gly Asp Ala Pro Ala 8930 8935 8940 Leu Ser Gly Trp Asp Lys Ser Phe Thr Tyr Lys Glu Met Thr Glu 8945 8950 8955 Ala Thr Asn Arg Leu Ala His Tyr Leu Val Asn Asp Tyr Gly Val 8960 8965 8970 Lys Val Gly Asp Ile Ile His Val Cys Phe Glu Lys Ser Ala Trp 8975 8980 8985 Phe Ile Ile Ala Thr Leu Ala Ile Asn Lys Ala Gly Ala Ala Trp 8990 8995 9000 Ser Thr Leu Asp Thr Ser His Pro Ile Glu Arg Tyr Gln Lys Ile 9005 9010 9015 Val Ser Gln Thr Gly Ser Lys Leu Ala Leu Ala Ser Ala Ala Asn 9020 9025 9030 Ser Tyr Arg Cys Val Gly Val Leu Pro His Val Ile Glu Leu Thr 9035 9040 9045 Pro Glu Leu Asp Ala Arg Leu Ala Lys Asn Thr Ser Trp Ser Ala 9050 9055 9060 Cys Gly Pro Ala Val Ala Val Ile Pro Ser Asp Met Ala Tyr Ile 9065 9070 9075 Leu Phe Thr Ser Gly Ser Thr Gly Val Pro Lys Gly Val Val Ile 9080 9085 9090 Glu His Ala Thr Leu Cys Thr Ser Gln Thr Ser Leu Ser Gln Thr 9095 9100 9105 Leu Gly Phe His Glu Glu Tyr Lys Val Leu Gln Phe Ser Ser Tyr 9110 9115 9120 Ser Phe Asp Ala Ala Val Phe Glu Ile Asp Ser Thr Leu Leu Thr 9125 9130 9135 Gly Ala Cys Leu Tyr Val Pro Ser Trp Asp Glu Gln Met Asn Glu 9140 9145 9150 Leu Val Gly Tyr Ile Arg Lys His Thr Ile Thr Cys Thr Leu Leu 9155 9160 9165 Thr Pro Thr Leu Ala Arg Thr Leu Arg Pro Glu Asp Val Pro Ser 9170 9175 9180 Leu Asn Met Leu Ile Leu Gly Gly Glu Ala Pro Thr Arg Asp Ile 9185 9190 9195 Leu Asp Ile Trp Phe Gly Lys Leu Lys Leu Val Asn Gly Trp Gly 9200 9205 9210 Pro Thr Glu Ala Cys Val Ile Ala Cys Leu His Ser Trp Thr Ser 9215 9220 9225 Val Asp Glu Ser Pro Ser Val Ile Gly Arg Pro Ile Gly Gly Ser 9230 9235 9240 Ile Trp Val Val Asp Pro Asp Asp Ala Thr Arg Met Ala Pro Val 9245 9250 9255 Gly Thr Val Gly Glu Ile Ala Val Gln Gly Arg Asn Leu Phe Arg 9260 9265 9270 Gly Tyr Leu Ser Asp Pro Val Lys Thr Ala Ala Ala Thr Val Thr 9275 9280 9285 Gly Leu Pro Glu Trp Val Pro Lys Arg Asp Ser Ser Ala His Trp 9290 9295 9300 Asp Arg Phe Tyr Leu Thr Gly Asp Leu Gly Phe Ile Asn Glu Ala 9305 9310 9315 Gly Asn Val Glu Tyr Cys Thr Arg Lys Asp Thr Gln Val Lys Ile 9320 9325 9330 Arg Gly Gln Arg Leu Glu Leu Gly Glu Ile Glu His His Ile Gln 9335 9340 9345 Ala Asn Leu Glu Gly Val Arg Gln Val Ala Val Asp Val Ile Lys 9350 9355 9360 Ser Asp Ala Gly Ser Thr Leu Val Ala Phe Val Ser Phe Ser Asp 9365 9370 9375 Ala Thr Glu Pro Ile Asp Ser Asp Thr Ser Ala Phe Leu Pro Leu 9380 9385 9390 Ser Gly Asp Leu Gln Ala Thr Ile Thr Ser Leu Val Gly Thr Leu 9395 9400 9405 Gly Thr Leu Met Pro Arg Tyr Met Val Pro Ser Ala Phe Ile Pro 9410 9415 9420 Cys Ala Tyr Met Pro Leu Ala Thr Ser Thr Lys Leu Asp Arg Lys 9425 9430 9435 Lys Leu Lys Glu Leu Ala Ala Ser Leu Ser Gln Asp Glu Leu Ser 9440 9445 9450 Ile Tyr Ser Leu Ala Asn Glu Gln Lys Ala Ala Pro Gln Thr Ala 9455 9460 9465 Met Glu Ser Arg Ile Gln Ala Ile Trp Ser Gln Val Leu Asn Val 9470 9475 9480 Ser Ile Asp Ser Ile Gly Arg Asp Asp Ser Phe Leu Gln Ile Gly 9485 9490 9495 Gly Asp Ser Ile Leu Ala Ile Gln Leu Val Ser Val Ala Arg Asp 9500 9505 9510 Ala Asn Val Lys Ile Thr Val Gly Asp Val Phe Asp Asp Pro Arg 9515 9520 9525 Leu Leu Ala Val Ala Ala Lys Ala Thr Glu Leu Asp Asp Asn Gly 9530 9535 9540 Glu Val Ile Ala Asn Ile Glu Pro Phe Gly Leu Leu Asp Glu Pro 9545 9550 9555 Leu Lys Asp Leu Val Leu Ser Gln Arg Ile Gln Glu Gln Tyr Ser 9560 9565 9570 Leu Pro Thr Asp Arg Glu Ile Glu Asp Ala Tyr Pro Cys Thr Lys 9575 9580 9585 Leu Gln Glu Gly Leu Met Ala Leu Ala Val Lys Gln

Pro Gly Ser 9590 9595 9600 Tyr Ile Ala Lys Phe Leu Tyr Arg Leu Ser Ser Asn Val Asp Val 9605 9610 9615 Ser His Phe Lys Ala Ser Trp Glu Glu Thr Val Arg Leu Leu Pro 9620 9625 9630 Asn Leu Arg Thr Arg Ile Phe Thr Ala Gly Asn Met Ser Ile Gln 9635 9640 9645 Ala Ile Leu Lys Asp Asp Ile Ser Trp Gln Pro Thr Glu Gly Asp 9650 9655 9660 Ser Leu Arg Ser Tyr Met Gly Ser Ala Gln Asn Phe Glu Met Thr 9665 9670 9675 Tyr Gly Ser Pro Leu Ala Arg Tyr Ala Leu Ile Glu Asp Asn Gly 9680 9685 9690 Asp Thr Tyr Phe Val Leu Ser Met His His Ala Val Phe Asp Gly 9695 9700 9705 Trp Gly Ile Arg Val Leu Met Ser Val Phe His Ser Val Phe Arg 9710 9715 9720 Lys Gln Ala Pro Val Ile Glu Pro Tyr Val Arg Phe Val Gln Tyr 9725 9730 9735 Thr Met Asp Val Asn Asn Asp Glu Ala Ser Asp Tyr Trp Arg Ser 9740 9745 9750 Gln Phe Gln Gly Ala Arg Gln Thr Ile Phe Pro Pro Asn Ala Ser 9755 9760 9765 Ala Ser Glu Ser Arg Lys Asn Ser Thr Gln Thr Val Glu Lys Met 9770 9775 9780 Ile Glu Leu Pro Ser Met Asn Lys Ser Ser Ile Thr Lys Ala Thr 9785 9790 9795 Met Leu Arg Ala Ala Trp Ala Ile Val Leu Ser Arg Tyr Cys Asp 9800 9805 9810 Ser Asp Asp Val Thr Phe Gly Ile Thr Ile Ser Gly Arg Gln Ala 9815 9820 9825 Pro Val His Gly Leu Ile Asn Met Thr Gly Pro Ala Ile Ala Thr 9830 9835 9840 Val Pro Val Arg Val Ala Met Asp Arg Lys Thr Val Val Lys Asp 9845 9850 9855 Tyr Leu Gln Ala Ile Gln Ser Gln Ala Asn Gly Met Val Pro Phe 9860 9865 9870 Glu Gln Phe Gly Leu Gln Asn Ile Ser Arg Leu Ser Ala Glu Ala 9875 9880 9885 Lys Asp Ala Cys Asp Phe Gly Ser Leu Leu Val Ile Gln Pro Ile 9890 9895 9900 Gln Ser Leu Ala Tyr Val Asp Glu Ser Ala Asp Thr Val Phe Ile 9905 9910 9915 Pro Leu Asp Val Asp Lys Glu Val Thr Asp Thr Val Gln Asn Tyr 9920 9925 9930 Phe Ser Tyr Pro Leu Val Ile Gln Gly His Met His Glu Asp Phe 9935 9940 9945 Ile Asn Leu Val Leu Ile Tyr Asp Thr Gly Val Leu Ala Glu Ser 9950 9955 9960 Gln Met Val Ala Leu Ser His Gln Phe Glu Asn Val Leu Lys Gln 9965 9970 9975 Leu Ala Ser Lys Pro Asp Leu Glu Leu Gly Ser Val Ser Met Ala 9980 9985 9990 Gly Asp Trp Asp Leu Glu Phe Ser Lys Arg Gln Asn Ser Glu Val 9995 10000 10005 Pro Glu Ile Leu Asp Val Cys Val His Gln Leu Ile Glu Lys Gln 10010 10015 10020 Ala Ala Ala Gln Pro Asp Ala Pro Ala Val Leu Ser Trp Asp His 10025 10030 10035 Ser Phe Thr Tyr Lys Gln Leu Asn Glu Ala Ser Asn Arg Leu Ala 10040 10045 10050 His Leu Leu Val Asn Lys Tyr His Val Lys Pro Asn Asp Leu Val 10055 10060 10065 His Val Cys Phe Asp Lys Cys Ala Trp His Phe Val Ala Ile Thr 10070 10075 10080 Ala Ile Asn Lys Val Gly Ala Ala Trp Val Pro Leu Asp Pro Ser 10085 10090 10095 His Pro Glu Met Arg Leu Arg Gln Ile Val Ser Gln Thr Arg Ala 10100 10105 10110 Thr Leu Thr Leu Val Ser Ser Ser Asn Ala Ser Leu Cys Ser Ser 10115 10120 10125 Leu Thr Glu Arg Val Ile Glu Val Asn Ala Ser Leu Asp Asn Glu 10130 10135 10140 Leu Leu Ala Val Glu Ser Gly Glu Tyr Gly Pro Ser Val Asp Val 10145 10150 10155 Ser Ser His Ser Ala Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr 10160 10165 10170 Gly Val Pro Lys Gly Phe Val Met Glu His Gly Ser Val Cys Thr 10175 10180 10185 Ser Gln Ile Ala Ile Ala Arg Arg Leu Gly Leu Gly Pro Asn Val 10190 10195 10200 Arg Met Leu Gln Phe Ala Ala Phe Val Phe Asp Leu Ser Ile Gly 10205 10210 10215 Glu Ile Val Gly Pro Leu Ile Ser Gly Ala Cys Ile Cys Val Pro 10220 10225 10230 Ser Glu Asp Thr Arg Ile Asn Gly Ile Val Ala Phe Ile Asn Glu 10235 10240 10245 Thr Lys Val Thr Trp Ala Tyr Ile Thr Pro Ser Phe Ala Arg Thr 10250 10255 10260 Ile Lys Pro Ser Glu Val Pro His Leu Glu Leu Leu Leu Leu Ala 10265 10270 10275 Gly Glu Ala Val Pro Arg Asp Val Phe Ala Thr Trp Phe Gly Ser 10280 10285 10290 Thr Val Arg Leu Ile Asn Gly Trp Gly Pro Ala Glu Thr Cys Val 10295 10300 10305 Phe Ser Thr Leu His Glu Trp Lys Ser Ala Asp Glu Ser Pro Leu 10310 10315 10320 Thr Val Gly Arg Pro Val Gly Gly Phe Cys Trp Ile Ala Asp Pro 10325 10330 10335 Glu Asp Pro Ser Arg Leu Ala Ala Thr Gly Thr Leu Gly Glu Ile 10340 10345 10350 Leu Ile Gln Gly Pro Thr Ile Leu Arg Glu Tyr Leu Ser Asp Val 10355 10360 10365 Ala Arg Thr Glu Ala Thr Val Ile Lys Ser Leu Pro Glu Trp Ala 10370 10375 10380 Pro Phe Arg Asn Glu Pro Gly Trp Asp Arg Met Tyr Lys Ser Gly 10385 10390 10395 Asp Leu Gly Phe Tyr Asn Pro Asp Gly Thr Ile Glu Phe Ser Ser 10400 10405 10410 Arg Lys Asp Thr Gln Val Lys Ile Arg Gly Leu Arg Val Glu Leu 10415 10420 10425 Gly Glu Val Glu His His Val Gln Val Ala Leu Pro Gly Val Lys 10430 10435 10440 Gln Ile Ala Val Asp Val Phe Gln Gly Glu Asn Gly Thr Asn Leu 10445 10450 10455 Val Ala Phe Phe Ser Phe Asn Asp Glu Thr Arg Gln Ile His Glu 10460 10465 10470 Ala Asp Ser Ser Gly Pro Phe Glu Pro Leu Asp Asp Asn Leu Gln 10475 10480 10485 Asp Arg Leu Thr Ala Val Val Gly Glu Leu Ser Val Ser Leu Pro 10490 10495 10500 Arg Tyr Met Ile Pro Thr Leu Phe Ile Pro Cys Lys Tyr Met Pro 10505 10510 10515 Ser Ile Thr Ser Thr Lys Leu Asp Arg Asn Glu Leu Lys Arg Arg 10520 10525 10530 Ser Thr Ala Leu Ser Gln Ser Glu Leu Ala Val Tyr Ser Leu Gln 10535 10540 10545 Gly Gly Lys Lys Arg Ala Pro Glu Thr Pro Met Glu Ser Leu Ile 10550 10555 10560 Gln Ala Leu Trp Ser Asp Ile Leu His Val Pro Ala Asp Ser Ile 10565 10570 10575 Gly Arg Asp Asp Ser Phe Leu Gly Leu Gly Gly Asp Ser Ile Thr 10580 10585 10590 Ala Ile His Leu Val Ser Ile Ala Arg Glu Lys Gly Ile Gln Leu 10595 10600 10605 Val Val Lys Asp Ile Phe Asp Asp Pro Arg Leu Leu Ala Val Ser 10610 10615 10620 Ser Lys Ala Lys Glu Met Asp Ile Glu Ala Arg Gln Glu Leu Leu 10625 10630 10635 Glu Val Ser Pro Phe Ser Leu Leu Asn Ala Glu Thr His Asp Leu 10640 10645 10650 Ala Ile Gly Pro Ser Val Arg Gln Gln Leu Asn Leu Leu Glu Gly 10655 10660 10665 Gln Thr Ile Asp Asp Ala Tyr Pro Cys Thr Lys Leu Gln Glu Gly 10670 10675 10680 Leu Met Ala Leu Ser Val Thr Gln Pro Gly Ser Tyr Ile Ala Arg 10685 10690 10695 Tyr Val Tyr Arg Leu Ser Arg Gln Val Asp Val Ala Arg Phe Lys 10700 10705 10710 Ser Ala Trp Glu Thr Thr Val Ala Leu Arg Asp Ile Leu Arg Thr 10715 10720 10725 Arg Ile Val Met Ile Asn Gly Thr Cys Ile Gln Leu Val Val Lys 10730 10735 10740 Gly Gly Val Val Trp Asp Leu Ile Asp Ser Glu Ser Leu Glu Glu 10745 10750 10755 Ala Ala His Lys Thr His Ser His Thr Met Thr Tyr Gly Ser Gln 10760 10765 10770 Leu Ser Arg Thr Ser Ile Tyr Glu Thr Lys Thr Gly Asp Lys Tyr 10775 10780 10785 Phe Leu Trp Thr Val His His Ala Ile His Asp Gly Trp Ser Val 10790 10795 10800 Pro Val Ile Phe Ser Thr Leu Tyr Gln Ala Tyr Glu Gly Leu Glu 10805 10810 10815 Leu Gly Thr Pro Lys Ser Tyr Ser Gly Phe Ile Arg Tyr Thr Leu 10820 10825 10830 Glu Leu Asp Gln Glu Ala Ala Ser Asn Tyr Trp Arg Glu Gln Leu 10835 10840 10845 Gln Asp Ala Lys Arg Ala Ser Phe Pro Lys Thr Gly Leu Thr Thr 10850 10855 10860 Lys Ser Ala Asp Asn Glu Gln Lys Ile Gln Val Met Ser Thr Ser 10865 10870 10875 Leu Ser Phe Pro Ser Ser Ser Asn Glu Ala Val Thr Lys Ala Ser 10880 10885 10890 Val Met Arg Ala Ala Trp Ala Val Val Leu Ala Arg Tyr Cys Asp 10895 10900 10905 Ser Asp Asp Val Cys Phe Gly Ala Thr Ile Ser Gly Arg Gln Ala 10910 10915 10920 Pro Val His Gly Val Leu Glu Met Ala Gly Pro Ala Val Ala Thr 10925 10930 10935 Val Pro Val Arg Val Lys Leu Asp Lys Gly Gln Ser Ile Pro Gln 10940 10945 10950 Phe Leu Gln Val Ile Gln Asn Gln Ala His Glu Met Val Pro Tyr 10955 10960 10965 Glu Gln Tyr Gly Leu Gln Ser Ile Ala Lys Leu Gly Ala Asp Ala 10970 10975 10980 Arg Asp Ala Cys Asp Phe Thr Ser Leu Leu Leu Ile Gln Pro Val 10985 10990 10995 Gln Arg Leu Ser Ser Gly Val Ala Asp Glu Glu Gly Leu Leu Val 11000 11005 11010 Pro Ala Gln Ser Glu Ile Lys Asp Met Val Gln Asn Tyr Tyr Ser 11015 11020 11025 Tyr Pro Leu Val Ile Gln Gly His Val Tyr Asp Asp Arg Ala Asp 11030 11035 11040 Leu Val Leu Ile Tyr Asp Ser Thr Val Val Pro Glu Pro Gln Met 11045 11050 11055 Thr Ala Leu Ser His His Phe Asp Asn Val Val Gln Gln Leu Leu 11060 11065 11070 Ala Val Asp Gly Lys Leu Gly Asp Ile Ser Val Ala Gly Ser Trp 11075 11080 11085 Asp Leu Glu Leu Ala Gln Lys Ser Asn Gly Asp Gly Pro Glu Ile 11090 11095 11100 Ile Glu Asp Cys Ile His Ser Ile Ile Glu Arg Gln Val Gln Gln 11105 11110 11115 Arg Pro Asn Ser Pro Ala Val Asp Ala Trp Asp Gly Arg Leu Thr 11120 11125 11130 Tyr Ser Gln Leu Asp His Ala Ala Asn Arg Leu Ala His Leu Leu 11135 11140 11145 Val Asp Asp Tyr Ala Val Gln Val Gly Asp Ile Val His Val Cys 11150 11155 11160 Phe Glu Lys Ser Met Trp Tyr Ile Val Ala Ile Leu Ala Ile Asn 11165 11170 11175 Lys Ala Gly Ala Ala Trp Ala Pro Leu Asp Ser Ala His Pro Phe 11180 11185 11190 Gln Arg Leu Gln Ala Val Ala Lys Gln Thr Gly Ala Lys Leu Ala 11195 11200 11205 Leu Ala Ser Thr Ala Asn Ala Gly Leu Cys Lys Gln Leu Val Asp 11210 11215 11220 Arg Val Ile Glu Val Ser Ala Ala Leu Asp Glu Lys Leu Ser Ser 11225 11230 11235 Asn Ala Val Ser Ser Gly Lys Gly Pro Gln Val Asn Val Ser Pro 11240 11245 11250 Leu Asp Ala Ala Tyr Ile Leu Phe Thr Ser Gly Ser Thr Gly Thr 11255 11260 11265 Pro Lys Gly Ile Val Met Gln His Gly Ala Leu Cys Thr Ser Gln 11270 11275 11280 Thr Asp Ile Ser Arg Trp Leu Gly Leu Asp His Thr Val Arg Met 11285 11290 11295 Leu Gln Phe Ser Ser Phe Val Phe Asp Val Ser Val Gly Glu Ile 11300 11305 11310 Met Glu Pro Leu Met Asn Gly Ala Cys Val Cys Val Pro Ser Asp 11315 11320 11325 His Met Arg Leu Asn Ser Leu Asp Val Phe Val Arg Asp Phe Asn 11330 11335 11340 Val Thr Trp Ala Tyr Leu Thr Pro Ser Phe Thr Arg Thr Leu Lys 11345 11350 11355 Pro Glu Asp Phe Pro Gly Leu Glu Leu Leu Leu Leu Ile Gly Glu 11360 11365 11370 Ala Val Thr Gln Asp Val Leu Asp Thr Trp Phe Gly Leu Pro Asn 11375 11380 11385 Thr Arg Phe Val Asn Ala Trp Gly Pro Ala Glu Thr Cys Val Phe 11390 11395 11400 Ser Thr Leu Tyr Asp Trp Gln Ser Asn Thr Glu Ser Pro Leu Thr 11405 11410 11415 Ile Gly Arg Ala Val Gly Ala Tyr Val Trp Val Val Asp Ala Glu 11420 11425 11430 Asn Pro Gln Arg Leu Ala Pro Thr Gly Cys Leu Gly Glu Ile Val 11435 11440 11445 Val Gln Gly Pro Pro Leu Leu Arg Glu Tyr Leu Ala Asp Pro Ser 11450 11455 11460 Lys Thr Ala Ala Ala Thr Val Thr Glu Leu Pro Glu Trp Ala Pro 11465 11470 11475 Arg Arg Glu Leu Thr Lys Trp Asn Arg Phe Tyr Arg Thr Gly Asp 11480 11485 11490 Leu Gly Phe Tyr Ser His Asp Gly Leu Leu His Tyr Ala Ser Arg 11495 11500 11505 Lys Asp Thr Gln Val Lys Ile Arg Gly Leu Arg Val Glu Leu Gly 11510 11515 11520 Glu Val Glu His His Ile Arg Ser Ser Leu Asp Gly Val Arg Gln 11525 11530 11535 Val Ala Val Asp Val Phe Lys Thr Glu Thr Gly Ala Asn Leu Val 11540 11545 11550 Thr Tyr Phe Cys Phe Thr Asp Asp Thr Lys Thr Pro Gly Pro Asp 11555 11560 11565 Thr Asp Pro Glu Gly Lys Asp Val Phe Met Ser Ile Asp Ala Ala 11570 11575 11580 Leu Gln Glu Lys Leu Gly Asn Met Leu Ser Lys Leu Asn Ser Ser 11585 11590 11595 Leu Pro Gly Tyr Met Ile Pro Thr Leu Phe Ile Pro Cys Asp Tyr 11600 11605 11610 Met Pro Leu Ile Ser Ser Ala Lys Leu Asp Arg Val Lys Leu Arg 11615 11620 11625 Arg Ile Thr Ala Glu Leu Ser Gln Asp Gln Leu Glu Ser Tyr Ser 11630 11635 11640 Leu Leu Asp Thr Asp Lys Arg Ala Pro Glu Thr Glu Met Glu Ile 11645 11650 11655 Arg Leu Gln Lys Leu Trp Ala Glu Ile Leu Asn Leu Pro Glu Ser 11660 11665 11670 Ser Ile Gly Arg Asp Asp Asn Phe Leu Arg Ile Gly Gly Asp Ser 11675 11680 11685 Ile Ala Ala Ile Arg Leu Val Ser Met Ala Arg Asp Val Gly Ile 11690 11695 11700 Ser Leu Thr Val

Asp Asp Ile Phe Asn Asp Ala Arg Leu Ile Ser 11705 11710 11715 Ile Ala Ala Lys Ala Val Asp Gly Asp Val Tyr Ser Ser Ile Met 11720 11725 11730 Ala Pro Ile Asp Ala Phe Ser Leu Leu Ser Pro Gly Thr Gly Asp 11735 11740 11745 Leu Val Leu Pro Ser Ala Leu Pro Glu Gly Gln Val Ile Glu Asp 11750 11755 11760 Ala Tyr Pro Cys Ser Lys Leu Gln Glu Gly Leu Met Ala Leu Ala 11765 11770 11775 Val Lys Gln Pro Gly Ser Tyr Ile Ala Lys Tyr Val Tyr Lys Leu 11780 11785 11790 Pro Glu His Val Asp Val Val Lys Phe Lys Ala Ala Trp Glu Arg 11795 11800 11805 Thr Val Glu Leu Ser Ser Ile Leu Arg Thr Arg Ile Ile Gln Ile 11810 11815 11820 Asn Gly Arg Ser Ile Gln Val Val Ile Asn Gly Asp Val Thr Trp 11825 11830 11835 Asp Glu Thr Asp Gly Ser Leu Gln Pro Cys Leu Ala Arg Ala Gln 11840 11845 11850 Ser Leu Glu Met Gly Tyr Gly Asp Arg Leu Cys Gln Tyr Ala Leu 11855 11860 11865 Ile Arg Asp Gly Asn Ser Thr Tyr Phe Met Trp Asn Val His His 11870 11875 11880 Ala Val Ile Asp Gly Leu Ser Thr Gln Asn Ile Leu Ala Thr Leu 11885 11890 11895 Phe Arg Leu Tyr Ser Gly Ile Asp Val Leu Ser Val Pro Pro Phe 11900 11905 11910 Ala Arg Phe Ile Lys Tyr Ile Leu Gly Leu Asp Glu Glu Val Thr 11915 11920 11925 Ala Asn Tyr Trp Lys Thr Gln Leu Ser Asn Ala Arg Lys Ala Ile 11930 11935 11940 Phe Pro Pro Ser Lys Asp Ala Ser Asn Asp Lys Pro Glu Ala Thr 11945 11950 11955 Arg Thr Leu Glu Thr Ser Ile Asp Leu Pro Ser Ser Ile Lys Asn 11960 11965 11970 Ser Thr Ile Thr Met Ala Thr Val Val Arg Ser Ala Trp Ala Ile 11975 11980 11985 Val Leu Ala Arg Tyr Cys Glu Thr Asp Asp Val Thr Phe Gly Thr 11990 11995 12000 Thr Ile Ser Gly Arg Gln Ala Pro Ile Pro Glu Val Met Glu Met 12005 12010 12015 Val Gly Pro Ile Ile Ala Thr Val Pro Val Arg Val Arg Ile Asp 12020 12025 12030 Arg Arg Gln Leu Val Ser Glu Phe Leu Glu Gly Val Gln Lys Gln 12035 12040 12045 Ala Val Glu Met Thr Ala Phe Glu Gln Tyr Gly Leu Gln Asn Ile 12050 12055 12060 Ala Arg Leu Ser Glu Asp Ala Arg Asp Ala Cys Asp Phe Gly Ser 12065 12070 12075 Leu Leu Val Val Gln Pro Met Gln His Leu Gly Gly Ala Gly Asn 12080 12085 12090 Asp Asp Ala Ile Leu Val Asp Ala Ala Ile Pro Asp Asn Ser Ser 12095 12100 12105 Ala Glu Ser Leu Arg Asn Tyr Phe Ser Tyr Pro Leu Val Ile Gln 12110 12115 12120 Ala His Leu Tyr Asp Asp His Val Asn Leu Val Leu Val Tyr Asp 12125 12130 12135 Ser Asn Val Ile Pro Glu Ala Arg Leu Val Ala Leu Ser His His 12140 12145 12150 Leu Ser His Val Met Thr Gln Leu Thr Thr Thr Glu Pro Ala Ala 12155 12160 12165 Leu Asp Thr Val Ser Val Ser Ser Pro Tyr Asp Val Gln Lys Ala 12170 12175 12180 Leu Ser Phe Asn Thr Glu Val Pro Glu Val Ile Asp Ala Cys Ile 12185 12190 12195 His Glu Leu Phe Glu Gln Gln Ala Ser Leu Arg Pro Gln Ala Pro 12200 12205 12210 Ala Ile Ala Ala Trp Asp Gly Asn Leu Thr Tyr Asp Glu Leu Asn 12215 12220 12225 Lys Ala Ala Asn Lys Leu Ala His His Leu Val Asn Val Tyr Gly 12230 12235 12240 Val Lys Pro Asn Asp Phe Val His Val Cys Phe Glu Lys Ser Ala 12245 12250 12255 Trp Tyr Ile Val Ser Ile Leu Ala Ile Asn Lys Ala Gly Ala Thr 12260 12265 12270 Trp Val Pro Leu Asp Pro Ser His Pro Glu Gln Arg Trp Gln Ser 12275 12280 12285 Ile Ile Ser Gln Thr Lys Ala Thr Leu Ala Leu Val Ser Pro Gly 12290 12295 12300 Ser Val Gly Pro Leu Ser Arg Leu Ile Asp Asn Val Val Ala Val 12305 12310 12315 Asp Ser Asn Leu Asp Ser Leu Leu Pro Glu His Asp Ala Ala Arg 12320 12325 12330 Gly Leu Ser Val Ser Ile Ser Pro Ser Thr Ala Ala Tyr Val Leu 12335 12340 12345 Phe Thr Ser Gly Ser Thr Gly Thr Pro Lys Gly Phe Ile Ile Glu 12350 12355 12360 His Arg Ser Ile Cys Thr Ser Gln Lys Ala Phe Asn Lys Arg Leu 12365 12370 12375 Arg Tyr His Glu Asn Val Arg Val Leu His Phe Ala Ala Thr Val 12380 12385 12390 Phe Asp Leu Ser Ile Gly Glu Ile Ile Met Ser Leu Leu Lys Gly 12395 12400 12405 Ala Cys Leu Cys Val Pro Ser Glu His Thr Arg Leu Asn Gly Ile 12410 12415 12420 Val Asp Phe Ile Arg Asp Met Lys Ile Asn Trp Leu Tyr Leu Thr 12425 12430 12435 Pro Ser Phe Leu Arg Thr Ile Asp Pro Ser Gln Val Pro Asn Val 12440 12445 12450 Glu Leu Ile Leu Leu Ala Gly Glu Ala Val Pro Arg Glu Val Phe 12455 12460 12465 Glu Thr Trp Tyr Gly Arg Val Arg Leu Leu Asn Gly Trp Gly Pro 12470 12475 12480 Ala Glu Thr Cys Val Thr Ser Ala Ile His Glu Phe Glu Ser Ala 12485 12490 12495 Asp Asp Ser Pro Leu Thr Val Gly Arg Pro Val Gly Gly Phe Cys 12500 12505 12510 Trp Ile Val Asp Pro Glu Asn Pro Gln Leu Leu Ala Pro Thr Gly 12515 12520 12525 Thr Val Gly Glu Val Val Ile Gln Gly Pro Thr Leu Leu Arg Glu 12530 12535 12540 Tyr Leu Asp Asn Pro Glu Lys Thr Gln Glu Thr Thr Val Tyr Glu 12545 12550 12555 Leu Pro Asp Trp Ala Pro Arg Pro Asp Glu Lys Asn Trp Ser Arg 12560 12565 12570 Phe Tyr Lys Thr Gly Asp Leu Cys Phe Tyr Asn Pro Asp Gly Thr 12575 12580 12585 Ile Glu Phe Ser Ser Arg Lys Asp Thr Gln Val Lys Ile Arg Gly 12590 12595 12600 Leu Arg Val Glu Leu Gly Glu Ile Glu Tyr His Val Gln Ala Ser 12605 12610 12615 Leu Glu Gly Ile Arg Gln Ile Ala Val Asp Val Val Lys Thr Asp 12620 12625 12630 Asn Gly Ser His Leu Val Ala Tyr Leu Cys Phe Asn Asp Gln Met 12635 12640 12645 Arg Gln Pro Asp Glu Ala Glu Val Asn Gly Pro Phe Thr Pro Ile 12650 12655 12660 Asp Ala Glu Leu Gln Asp Lys Leu Ile Gly Ala Val Ser Met Leu 12665 12670 12675 Asn Val Thr Leu Pro Arg Tyr Met Ile Pro Thr Phe Tyr Ile Pro 12680 12685 12690 Cys Ser Tyr Met Pro Tyr Asn Thr Ser Gly Lys Leu Asp Arg Arg 12695 12700 12705 Glu Leu Lys Thr Gln Thr Ala Ala Leu Gly Gln Ser Gly Leu Ser 12710 12715 12720 Asn Phe Ser Leu His Gly Val Asp Lys Arg Ala Pro Glu Thr Pro 12725 12730 12735 Met Glu Ile Glu Leu Gln Lys Val Trp Ser Thr Val Leu Ser Leu 12740 12745 12750 Pro Thr Asp Ser Ile Gly Arg Asp Asp Ser Phe Leu Gly Leu Gly 12755 12760 12765 Gly Asp Ser Ile Met Ala Ile His Leu Val Ser Ala Cys Arg Glu 12770 12775 12780 Ala Gly Ile Ser Leu Thr Val Lys Asp Val Phe Asp Asp Pro Arg 12785 12790 12795 Leu Ser Ala Val Ala Ser Lys Ala Ser Arg Leu Asp Ser Thr Asp 12800 12805 12810 Gln Glu Thr Ser Val Ala Pro Phe Ser Leu Leu Pro Asp Arg Ile 12815 12820 12825 Arg Glu Met Ala Leu Ser Asn Asp Val Arg Ser Gln Val Ser Leu 12830 12835 12840 Ser Ala Ser Asp Ser Val Glu Asp Ala Tyr Pro Cys Ser Lys Leu 12845 12850 12855 Gln Asp Gly Leu Met Ala Leu Ser Val Lys Gln Arg Gly Ser Tyr 12860 12865 12870 Val Ala Gln Tyr Val Tyr Lys Leu Ser Thr Ser Val Asp Leu Glu 12875 12880 12885 Arg Phe Lys Ala Ala Trp Glu Lys Thr Leu Gln Leu Cys Ala Asn 12890 12895 12900 Leu Arg Thr Arg Ile Val Met Leu Asp Gly Ile Cys Val Gln Leu 12905 12910 12915 Leu Ile Asp Gly Pro Ala Glu Trp Asp Asp Gln Ser Pro Thr Asp 12920 12925 12930 Leu Lys Ala Thr Val Asp Ala Thr Arg Thr Asp Met Thr Tyr Gly 12935 12940 12945 Ser Arg Leu Asn Arg Phe Ala Leu Val Gln Asp Pro Glu Phe Gly 12950 12955 12960 Asn His Phe Val Trp Ser Ser His His Ala Val His Asp Gly Trp 12965 12970 12975 Thr Leu Arg Ile Val Met Asn Thr Leu Tyr Gly Val Tyr Leu Asn 12980 12985 12990 Gln Thr Ala Pro Arg Leu Leu Pro Tyr Ser Ala Phe Ile Arg Tyr 12995 13000 13005 Thr Val Asn Ile Asn Ala Asp Asp Ala Asn Ala Phe Trp Ser Glu 13010 13015 13020 Gln Leu Arg Asn Ala Lys Arg Ala Thr Phe Pro Pro Met Pro Arg 13025 13030 13035 Ile Glu Ser His Ala Ser Ile Thr Arg Met Met Asn Lys Thr Ile 13040 13045 13050 Ser Phe Pro Pro Ser Val Lys Thr Thr Thr Thr Lys Ala Thr Ile 13055 13060 13065 Leu Arg Ala Ala Trp Ala Ile Leu Leu Ala Arg Tyr Cys Asp Ser 13070 13075 13080 Asp Asp Ile Thr Phe Gly Thr Thr Ile Ser Gly Arg Gln Ala Pro 13085 13090 13095 Val Pro Gly Leu Thr Glu Met Pro Gly Pro Val Val Ala Thr Val 13100 13105 13110 Pro Ile Arg Val Arg Ile Asp Ala Ser Gln Pro Val Ser Arg Phe 13115 13120 13125 Leu Ser Lys Ile Gln Ser Gln Ala Thr Asp Met Ile Ala Tyr Glu 13130 13135 13140 Gln Phe Gly Leu Gln Asn Ile Ile Lys Leu Gly Ala Asp Ala Lys 13145 13150 13155 Asp Ala Cys Glu Phe Ser Ser Leu Leu Val Ile Gln Pro Arg Thr 13160 13165 13170 His Leu Asp Ala Ile Glu Ser Lys Glu Ala Ser Asp Pro Leu Met 13175 13180 13185 Thr Thr Ser Val Ala Ala Lys Gly Ala Glu Gln Leu Met Gln Gly 13190 13195 13200 Tyr Phe Thr Tyr Pro Leu Val Ile Gln Gly His Val Phe Asp Asp 13205 13210 13215 Ser Ile Glu Leu Leu Leu Thr Tyr Asp Ser Thr Ile Leu Ser Glu 13220 13225 13230 Val Ala Met Glu Ala Leu Cys His Gln Phe Asp Val Val Ser Asn 13235 13240 13245 Gln Leu Val Lys Glu Ser Asn Asp Pro Leu Gly Ser Val Ala Val 13250 13255 13260 Ser Gly Glu Trp Asp Leu Glu Gln Ala Lys Lys Trp Asn Val Glu 13265 13270 13275 Asn Pro Asp Ile Leu Asp Thr Cys Ile His Asn Leu Ile Glu Glu 13280 13285 13290 Gln Ala Arg Ile Arg Pro Asp Ala Pro Ala Ile Cys Ala Trp Asn 13295 13300 13305 Gly Glu Met Ser Tyr Ser Gln Leu Asn Phe Ala Ala Asn Lys Leu 13310 13315 13320 Ala His His Leu Leu Asn Ala Gly Val Lys Ser Glu Asp Leu Val 13325 13330 13335 His Val Cys Phe Glu Lys Ser Leu Trp Phe Phe Ile Ser Ile Val 13340 13345 13350 Ala Ile Asn Lys Val Gly Ala Ala Trp Val Pro Leu Asp Ser Ser 13355 13360 13365 His Pro Glu Gln Arg Leu Arg Gln Val Val Ser Gln Thr Arg Ala 13370 13375 13380 Gln Phe Ala Leu Ser Ser Pro Thr Asn Ala Ala Leu Cys Gly Ser 13385 13390 13395 Leu Val Asp Lys Val Ile Glu Val Ser Gln Gly Leu Ile Asp Ser 13400 13405 13410 Phe Pro Tyr Asp Gly Ala Asn Gly Pro Ala Ile Lys Val Pro Ser 13415 13420 13425 Ser Asn Ala Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr Gly Thr 13430 13435 13440 Pro Lys Gly Leu Val Met Gln His Gln Ala Val Cys Thr Ser Gln 13445 13450 13455 Ala Ala Ile Ala Lys Arg Leu Arg Leu Thr Pro Asp Val Arg Ile 13460 13465 13470 Leu Gln Phe Ala Ala Tyr Val Phe Asp Leu Ser Ile Gly Glu Ile 13475 13480 13485 Val Ala Pro Leu Ile His Gly Ala Cys Val Cys Val Pro Ser Glu 13490 13495 13500 Glu Met Arg Met Asn Gly Leu Lys Glu Phe Ile Arg Asp Ala Ser 13505 13510 13515 Ile Asn Trp Val Phe Leu Thr Pro Ser Phe Val Arg Thr Leu Arg 13520 13525 13530 Pro Glu Asp Val Pro Asn Leu Asp Leu Leu Leu Leu Ala Gly Glu 13535 13540 13545 Ala Val Gly Arg Asp Ile Leu Asp Thr Trp Phe Gly Lys Val Arg 13550 13555 13560 Leu Val Asn Gly Trp Gly Pro Ala Glu Thr Cys Val Phe Ser Thr 13565 13570 13575 Leu His Glu Trp Ala Ser Ile Asp Glu Ser Pro Leu Thr Val Gly 13580 13585 13590 Thr Pro Val Gly Gly His Cys Trp Ile Val Asp Ala Glu Asp Ser 13595 13600 13605 Ser Lys Leu Ala Pro Ile Gly Cys Leu Gly Glu Val Val Leu Gln 13610 13615 13620 Gly Pro Thr Leu Leu Arg Glu Tyr Leu Ala Asp Pro Gln Arg Ser 13625 13630 13635 Lys Glu Ala Ile Ile Thr Ser Leu Pro Ser Trp Ala Pro Lys Gln 13640 13645 13650 Asp Ser Gln Pro Trp Ser Arg Phe Tyr Lys Ser Gly Asp Leu Cys 13655 13660 13665 Tyr Tyr Asn Pro Asp Gly Thr Leu Glu Phe Tyr Ser Arg Lys Asp 13670 13675 13680 Thr Gln Val Lys Ile Arg Gly Leu Arg Val Glu Leu Gly Glu Val 13685 13690 13695 Glu His His Ile Arg Glu Ser Leu Glu Gly Val Arg Gln Val Ala 13700 13705 13710 Val Asp Val Leu Lys Ser Glu Thr Gly Thr Asn Leu Val Ser Tyr 13715 13720 13725 Leu Cys Phe Asn Asp Asp Ser Gln Pro Val Ser Ser Glu Leu Gln 13730 13735 13740 Ala Ser Asp Val Tyr Leu Pro Leu Asp Ala Asp Ile Gln Thr Arg 13745 13750 13755 Ile Thr Ala Met Val Gly Glu Leu Ser Val Thr Leu Pro Arg Tyr 13760 13765 13770 Met Ile Pro Thr Leu Phe Ile Pro Cys Lys Phe Met Pro Val Ile 13775 13780 13785 Thr Ser Thr Lys Leu Asp Arg Lys Thr Leu Lys Ala Met Thr Ala 13790

13795 13800 Ser Leu Asp Arg Asp Gln Leu Ala His Tyr Ser Leu Ile Asp Ser 13805 13810 13815 Lys Lys Arg Ala Pro Glu Thr Glu Met Glu Thr Arg Leu Gln Val 13820 13825 13830 Ile Trp Ala Asp Ile Leu Gly Leu Pro Val Asp Ser Ile Gly Arg 13835 13840 13845 Asp Asp Ser Phe Leu Gln Ile Gly Gly Asp Ser Ile Thr Ala Ile 13850 13855 13860 Tyr Leu Val Ser Lys Ala Arg Glu Ala Gly Ile Ser Leu Val Val 13865 13870 13875 Lys Asp Val Phe Glu Asp Ser Arg Leu Leu Ala Val Ala Ser Lys 13880 13885 13890 Ala Val Phe Ser Glu Tyr Ala Gln Glu Asp Gln Glu Pro Val Val 13895 13900 13905 Pro Phe Ser Leu Leu Asn Glu Gln Thr Arg Ala Leu Val Leu Gly 13910 13915 13920 Gly Glu Val Arg Lys Leu Cys Gly Leu Ala Glu Asp Gln Ile Ile 13925 13930 13935 Glu Asp Ala Tyr Pro Cys Thr Ser Leu Gln Glu Gly Leu Met Ala 13940 13945 13950 Leu Thr Val Lys Gln Pro Gly Ser Tyr Val Ala Lys Tyr Val Tyr 13955 13960 13965 Lys Leu Ala Pro Phe Val Asp Val Asp Arg Leu Lys Ala Ala Trp 13970 13975 13980 Ser Arg Thr Val Glu Leu Cys Gly Asn Met Arg Thr Arg Ile Val 13985 13990 13995 Leu Leu Asn Gly Ser Pro Val Gln Leu Leu Leu Lys Glu Asp Ser 14000 14005 14010 Gln Trp Gln Ser Leu Glu Ala Glu Thr Leu Ala Ser Val Ala Thr 14015 14020 14025 Ser Ser Arg Asp Leu Met Met Gly Tyr Gly Ser Pro Leu Cys Trp 14030 14035 14040 Tyr Gly Ile Leu Glu Glu Asn Asp Ala Arg Tyr Leu Val Trp Ser 14045 14050 14055 Ala His His Ser Ile Tyr Asp Gly Trp Val Met Arg Ile Leu Val 14060 14065 14070 Thr Thr Leu Tyr Thr Val Tyr His Gly Ala Glu Val Thr Pro Leu 14075 14080 14085 Gln Pro Tyr Ser Gly Phe Ile Lys Tyr Asn Met Glu Leu Asp Ser 14090 14095 14100 Ala Ser Ser Ala Glu Phe Trp Arg Glu Gln Leu Ser Gly Ser Lys 14105 14110 14115 Arg Ala Ala Phe Pro Ala Arg Gln Pro Ala Ala Thr Ser Ser Ser 14120 14125 14130 Ser Thr Gln Ile Phe Lys Ser Ser Ile Ser Ile Gly Gln Ala Lys 14135 14140 14145 Gln Ser Ser Ile Thr Lys Ala Ser Ile Leu Arg Ala Ala Trp Ala 14150 14155 14160 Ile Val Leu Ala Arg Tyr Cys Asp Thr Asn Asp Val Ser Phe Gly 14165 14170 14175 Ala Thr Val Ser Gly Arg His Ala Pro Val Ala Gly Leu Glu Thr 14180 14185 14190 Met Pro Gly Pro Met Ile Ala Thr Val Pro Val Arg Val His Leu 14195 14200 14205 Asp Arg Ala Ser Thr Lys Ser Gln Phe Leu Ala Ser Ile Gln Ser 14210 14215 14220 Gln Ala His Glu Met Val Pro Tyr Glu Gln Phe Gly Leu Gln Asn 14225 14230 14235 Ile Ser Lys Val Ser Gln Asp Ala Arg Asp Thr Cys Asp Phe Ser 14240 14245 14250 Ser Leu Leu Val Ile Gln Pro Pro Ala Thr Thr Ile Ser Glu Glu 14255 14260 14265 Asp Ser Lys Thr Asn Ile Leu Val Tyr Gly Asp Ala Glu Gln Ser 14270 14275 14280 Arg Thr Asp Asp Ala Met Gln Asn Tyr Phe Asn Tyr Pro Leu Val 14285 14290 14295 Ile Ile Met Asn Thr Phe Glu Asp His Ile Leu Gln Arg Phe Phe 14300 14305 14310 Tyr Asn Pro Asp Val Leu Asp Glu Ala Arg Val Ser Ala Leu Ser 14315 14320 14325 Gln His Ile Gly His Val Val Glu Gln Leu Leu Ala Ser Ser Asp 14330 14335 14340 Glu Ala Leu Asp Ser Ile Asp Leu Val Ser Asp Trp Asp Val Gln 14345 14350 14355 His Ala Val Glu Ser Thr Arg Leu Lys Pro Ser Thr Glu Ser Cys 14360 14365 14370 Thr His Trp Leu Ile Arg Asp Arg Ile Glu Lys Gln Pro Ser Asp 14375 14380 14385 Pro Ala Ile Ala Ser Trp Asp Gly Asp Leu Thr Tyr Glu Glu Leu 14390 14395 14400 Gly Val Leu Ala Ser Arg Leu Ala Trp Lys Leu Gln Gly Leu Gly 14405 14410 14415 Val Gly Pro Glu Ser Leu Ile Pro Leu Cys Phe Pro Lys Ser Thr 14420 14425 14430 Trp Ala Val Val Ala Met Val Ala Ile Glu Met Ala Gly Gly Ala 14435 14440 14445 Phe Val Pro Leu Asp Pro Lys Ala Pro Val Ala Arg Leu Arg Gly 14450 14455 14460 Ile Ile Glu Asp Thr Lys Ser Thr Leu Ala Val Ala Ser Pro Ser 14465 14470 14475 Cys Gln Asp Ala Leu His Glu Ile Gly Ile Asp Val Leu Ala Val 14480 14485 14490 Asp Glu Ala Leu Leu Leu Glu Leu Ser Asp Pro Val Glu Gly Ile 14495 14500 14505 Gln Ser Lys Ala Gly Pro Lys Asp Ala Ser Val Val Leu Phe Thr 14510 14515 14520 Ser Gly Ser Thr Gly Lys Pro Lys Gly Met Val Ile Gln His Asn 14525 14530 14535 Ser Leu Cys Ser Ser Gly Asn Ala Tyr Gly Gln Asp Leu Asn Ile 14540 14545 14550 Gly Pro Gly Thr Arg Val Phe Gln Phe Ser Ala Tyr Thr Phe Asp 14555 14560 14565 Val Gly Val Leu Asp Cys Leu Val Ser Leu Met Arg Gly Ala Thr 14570 14575 14580 Ile Cys Ile Pro Ser Asp His Ala Arg Leu Asn Asp Leu Ala Gly 14585 14590 14595 Ala Met Thr Ala Thr Lys Ala Asn Trp Val Phe Leu Thr Pro Thr 14600 14605 14610 Val Ala Asp Leu Leu Ser Pro Ala Asp Val Pro Tyr Leu Lys Val 14615 14620 14625 Leu Cys Leu Gly Gly Glu Ala Ile Ser Lys Lys Cys Ala Asp Arg 14630 14635 14640 Trp Ile Asn Tyr Thr Glu Leu His Gly Leu Tyr Gly Pro Ala Glu 14645 14650 14655 Ala Ser Ile Cys Ala Trp Asn Pro Ser Val Gly Lys Ser Gly Arg 14660 14665 14670 Ser Thr Asn Leu Gly Arg Pro Ile Ser Ser Ala Phe Trp Val Val 14675 14680 14685 Glu Pro Asn Asn His Lys Gln Leu Val Pro Val Gly Cys Ile Gly 14690 14695 14700 Glu Leu Leu Ile Glu Gly Pro Met Leu Ala Arg Gly Tyr Leu Asn 14705 14710 14715 Val Ser Ala Asp Val Ala Ser Asn Trp Met Asp Asn Val Asp Trp 14720 14725 14730 Leu Pro Gly Ser Asp Lys Lys Arg Val Tyr Arg Thr Gly Asp Leu 14735 14740 14745 Val Arg Arg Asn Ala Asp Gly Thr Phe Glu Phe Met Gly Arg Lys 14750 14755 14760 Asp Thr Gln Val Lys Leu His Gly Gln Arg Val Glu Leu Gly Glu 14765 14770 14775 Ile Glu Ala Arg Ile His Glu Phe Leu Pro Ser Asp Met Ala Ala 14780 14785 14790 Ile Val Ala Val Val Lys Asp Glu His Gly His Asp Ser Leu Leu 14795 14800 14805 Ala Phe Met Trp Tyr Thr Glu Gly Val Val Ala Ser Arg Ser Thr 14810 14815 14820 Ala His Leu Met Glu Val Val Ser Asp Glu Ala Arg Ala Thr Ile 14825 14830 14835 Ser His Val Asp Ser Ser Leu Glu Met Val Leu Pro Ser Tyr Met 14840 14845 14850 Ile Pro Ser Ser Tyr Leu Val Phe Glu Gly Lys Pro Glu Gln Thr 14855 14860 14865 Val Asn Gly Lys Val Asp Arg Lys Ala Leu Leu Ala His Ala Gln 14870 14875 14880 Asn Leu Ser Thr Gln Asp Arg Leu Arg Phe Ala Pro Val Val Gly 14885 14890 14895 Lys Ser Glu Pro Pro Ser Thr Pro Met Glu Phe Arg Leu Arg Asp 14900 14905 14910 Leu Trp Ala Gln Val Leu Gln Ile Asp Ala Glu Ser Ile Ser Lys 14915 14920 14925 Asn Asp Ser Phe Leu Arg Ile Gly Gly Asp Ser Ile Ser Ala Ile 14930 14935 14940 Gln Leu Val Ser Leu Ala Gln Gln Asn Asn Ile Gly Leu Thr Val 14945 14950 14955 Ala Ala Ile Phe Asn Asp Pro Arg Leu Ser His Met Ala Glu Ala 14960 14965 14970 Ala Asn Val Asp Asp Ile Met Pro Val Tyr Glu Thr Lys Pro Phe 14975 14980 14985 Ser Ile Ile Pro Ala Ser Ala Met Asp Glu Val Leu Ala Gln Val 14990 14995 15000 Arg Ser Gln Cys Asp Asn Leu Ser Glu Thr Ala Ile Ile Glu Asp 15005 15010 15015 Ala Tyr Pro Cys Thr Arg Leu Gln Glu Gly Leu Met Ile Leu Ala 15020 15025 15030 Val Lys Gln Pro Gly Ser Tyr Val Ala Lys His Val Tyr Arg Leu 15035 15040 15045 Ser Asp Asn Ile Asn Val Ala Arg Phe Lys Arg Ala Trp Asp Gln 15050 15055 15060 Thr Val Glu Ala Cys Ala Ala Leu Arg Thr Arg Ile Val Leu Val 15065 15070 15075 Asp Gly Ser Ala Tyr Gln Ala Val Ile Lys Asp Ser Val Lys Trp 15080 15085 15090 Gln Thr Ala Ser Asp Ile Arg Ser Phe Ser Met Ser Pro Asp Asn 15095 15100 15105 Thr Gln Met Gly Tyr Gly Ser Pro Leu Cys Arg Tyr Ala Leu Ile 15110 15115 15120 Glu Gln Asn Gly Glu Arg Tyr Phe Val Trp Asn Thr His His Thr 15125 15130 15135 Val Tyr Asp Gly Trp Thr Leu Pro Leu Ile Met Gly Thr Leu His 15140 15145 15150 Ala Phe Tyr Ser Gly Thr Asp Ala Pro Pro Leu Leu Pro Tyr Ser 15155 15160 15165 Gly Phe Val Lys Tyr Val Thr Glu Met Asp Ser Ala Ala Ala Ser 15170 15175 15180 Glu Tyr Trp Thr Gln Gln Leu Glu Gly Ala Arg Lys Thr Thr Phe 15185 15190 15195 Pro Pro Gly Ala Glu Ala Val Lys Thr Lys Lys Ser Gln Met Ser 15200 15205 15210 Thr Arg Val Met Arg Asn Thr Val Gln Phe Pro Arg Ser Thr Asn 15215 15220 15225 Thr Ser Ile Thr Lys Ala Ser Val Leu Arg Ala Ala Trp Ala Ile 15230 15235 15240 Val Leu Ala Arg Tyr Asn Asp Thr Asp Asp Val Cys Phe Gly Ser 15245 15250 15255 Thr Val Ser Gly Arg His Ala Pro Val Pro Gly Ile Glu Arg Met 15260 15265 15270 Pro Gly Leu Ala Val Ala Thr Val Pro Val Arg Val Lys Leu Asp 15275 15280 15285 Gln Lys Gln Ser Leu Asp Ala Phe Met Glu Gly Ile Gln Ser Gln 15290 15295 15300 Ala Ser Glu Met Val Ala Tyr Glu Gln Phe Gly Ile Gln Asn Ile 15305 15310 15315 Ser Lys Leu Asn Ala Lys Ala Lys Glu Ala Cys Asp Phe Thr Ser 15320 15325 15330 Leu Leu Val Val Gln Pro Thr Gln His Ile Thr Ser Thr Gly Asn 15335 15340 15345 Ala Ser Glu Glu Ala Leu Leu Thr Ala Ala Ala Thr Asp Asp Ile 15350 15355 15360 Ala Ala Asp Glu Met Leu Asp Asn Tyr Phe Asn Tyr Pro Leu Val 15365 15370 15375 Leu Gln Cys Tyr Val Leu Asp Asn Gln Val Glu Leu Val Leu Val 15380 15385 15390 Tyr Asp Cys Asp Val Ile Ala Glu His Gln Leu Val Gly Leu Ser 15395 15400 15405 His Gln Phe Gln His Val Val Thr Gln Leu Leu Ser Gln Asp Gly 15410 15415 15420 Pro Leu Ser Ala Val Ser Val Ala Ser Glu Trp Asp Leu Glu Phe 15425 15430 15435 Ala Gln Ala Ser Asn His Asp Glu Pro Ala Val Val Asp Asp Cys 15440 15445 15450 Ile His Asn Met Ile Glu Gln Arg Ala Leu Met Asn Pro Asn Ala 15455 15460 15465 Glu Ala Val Ser Ala Trp Asp Ala Arg Phe Thr Tyr Ala Glu Leu 15470 15475 15480 Asp Arg Ser Ala Asn Ile Leu Ala Asn His Leu Ile Gln Ser Arg 15485 15490 15495 Gly Val Gln Val Gly Asp Leu Val His Val Cys Phe Glu Lys Ser 15500 15505 15510 Ala Trp Tyr Val Val Ser Ile Leu Ala Ile Asn Lys Ala Gly Ala 15515 15520 15525 Ala Trp Ile Pro Leu Asp Pro Ser His Pro Ala Glu Arg His Gln 15530 15535 15540 Gln Val Val Gly Gln Thr Arg Ser Arg Leu Ala Leu Thr Ser Pro 15545 15550 15555 Ala Asn Ala Ala Lys Cys Ala Asn Leu Val Ala Asn Val Leu Glu 15560 15565 15570 Val Thr Arg Gly Leu Leu Asp Asp Leu Glu Thr Gln Val Asn His 15575 15580 15585 Ala Arg Pro Val Thr Ser Val Gly Pro Gln Asp Val Ala Tyr Ile 15590 15595 15600 Leu Phe Thr Ser Gly Ser Thr Gly Val Pro Lys Gly Val Val Met 15605 15610 15615 Glu His Gly Ala Leu Cys Ser Ser Gln Thr Ser Ile Ser Lys Arg 15620 15625 15630 Leu Gly Tyr Ala Pro Gly Val Arg Met Leu Gln Phe Ala Ser Phe 15635 15640 15645 Val Phe Asp Ala Cys Ile Gly Glu Ile Ile Ala Pro Leu Ile Ser 15650 15655 15660 Gly Ser Cys Val Cys Ile Pro Ser Trp Glu Thr Gln Met Asn Ser 15665 15670 15675 Leu Thr Ser Tyr Ile Arg Glu Glu Asn Val Thr Trp Ala Met Leu 15680 15685 15690 Thr Pro Ser Phe Ala Arg Thr Met Asp Pro Ser Glu Val Pro Cys 15695 15700 15705 Leu Glu Leu Leu Ile Leu Ile Gly Glu Ala Val Ser Arg Asp Val 15710 15715 15720 Phe Glu Leu Trp Phe Gly Lys Leu Arg Leu Leu Asn Gly Trp Gly 15725 15730 15735 Pro Thr Glu Thr Cys Val Phe Gly Ala Leu His Glu Trp Gln Ser 15740 15745 15750 Ile Asp Glu Ser Gln Met Thr Ile Gly Gln Pro Val Gly Gly Tyr 15755 15760 15765 Cys Trp Ile Val Asp Pro Glu Asp Pro Gln Arg Leu Ala Pro Thr 15770 15775 15780 Gly Thr Phe Gly Glu Val Val Ile Gln Gly Pro Asn Leu Leu Arg 15785 15790 15795 Glu Tyr Leu Ala Asp Glu Val Lys Thr Ala Ser Ser Thr Val Pro 15800 15805 15810 Val Leu Pro Glu Trp Ala Pro Asn Arg His Leu Arg His Trp Asn 15815 15820 15825 Arg Phe Tyr Lys Thr Gly Asp Leu Ala Met Tyr Asn Pro Asp Gly 15830 15835 15840 Thr Ile Gln Tyr Tyr Ser Arg Lys Asp Thr Gln Val Lys Ile Arg 15845 15850 15855 Gly Leu Arg Val Glu Leu Gly Glu Val Glu His His Val Arg Gln 15860 15865 15870 Asn Leu Asp Ala Val Gln Gln Val Ala Val Asp Val Phe Lys Thr 15875 15880 15885 Asp

Ser Gly Val Asn Leu Val Ser Phe Val Cys Phe Asn Asn Asp 15890 15895 15900 Thr Leu Pro Ala Ser Met Thr Gly Asp Ile Thr Ser Lys Asp Ile 15905 15910 15915 Ile Thr Pro Leu Thr Gly Glu Leu Lys Glu Ser Ile Asn Ser Leu 15920 15925 15930 Leu Gly Arg Leu Asn Val Leu Leu Pro Gly Tyr Met Ile Pro Thr 15935 15940 15945 Leu Phe Ile Pro Phe Lys Ala Met Pro Leu Val Thr Ser Gly Lys 15950 15955 15960 Leu Asp Arg Lys Leu Leu Leu Lys Leu Thr Ala Ser Leu Glu Lys 15965 15970 15975 Glu Gln Leu Glu Glu Tyr Ala Leu Thr Gly Gly Asp Lys Arg Glu 15980 15985 15990 Pro Glu Thr Glu Leu Glu Tyr Arg Leu Gln Glu Leu Trp Ala Thr 15995 16000 16005 Leu Leu Asn Met Pro Ala Ser Ala Ile Gly Arg Asp Asp Ser Phe 16010 16015 16020 Leu Arg Ile Gly Gly Asp Ser Ile Ala Ala Ile Arg Leu Val Ser 16025 16030 16035 Lys Ala Arg Glu Ser Gly Ile Ser Leu Ser Val Asp Asp Ile Phe 16040 16045 16050 Ser Asp Pro Arg Leu Leu Ala Val Ala Ala Lys Ala Thr Asp Ser 16055 16060 16065 Ala Ala Glu Ile Glu Asp Ile Val Pro Ile Glu Pro Phe Ser Leu 16070 16075 16080 Ile Asn Glu Ala Gln His Ser Met Val Leu Ser Ser Ser Ser Asp 16085 16090 16095 Leu His Leu Ser Ala Asp Met Glu Ile Glu Asp Ala Tyr Pro Cys 16100 16105 16110 Ser Lys Leu Gln Glu Gly Leu Met Ala Leu Ala Val Lys Gln Pro 16115 16120 16125 Gly Ser Tyr Ile Ala Lys Tyr His Tyr Arg Leu Pro Ser His Ile 16130 16135 16140 Asp Val Ala Arg Phe Lys Arg Ala Trp Glu Met Thr Val Glu Thr 16145 16150 16155 Cys Ala Asn Met Arg Thr Arg Ile Ile Thr Val Gly Gly Met Thr 16160 16165 16170 Ile Gln Thr Val Ile Lys Asn Asp Ile Ala Trp Glu Asp Thr Thr 16175 16180 16185 Gly Met Thr Leu Met Ser Tyr Val Arg Ala Thr Gln Lys Thr Glu 16190 16195 16200 Met Gly Tyr Gly Ser Arg Leu Cys Arg Tyr Ala Leu Val Glu Glu 16205 16210 16215 Glu Gly Gln Asp Val Gln Phe Val Trp Ser Ile His His Ala Val 16220 16225 16230 Phe Asp Gly Trp Thr Thr Pro Ile Ile Met Ser Ala Leu His Ser 16235 16240 16245 Ala Tyr Arg Gly Leu Glu Met Pro Lys Ile Glu Asn Tyr Ala Arg 16250 16255 16260 Phe Ile Lys Tyr Thr Met Asp Ile Asn Tyr Gln Asp Ala Ser Glu 16265 16270 16275 Tyr Trp Met Arg Glu Leu His Asp Val Lys Lys Ala Thr Phe Pro 16280 16285 16290 Ser Ser Val Ser Val Glu Ala Ser Asp Lys Gly Asp Val Thr Lys 16295 16300 16305 Phe Met Glu Thr Arg Ile Asp Leu Pro Arg Asn Asp Val Gly Val 16310 16315 16320 Thr Lys Ala Thr Ile Leu Arg Ala Ala Trp Ala Val Val Leu Ala 16325 16330 16335 Arg Tyr Cys Asp Thr Asp Asp Val Cys Phe Gly Thr Thr Ile Ser 16340 16345 16350 Gly Arg Gln Ala Pro Ile Ala Gly Leu Met Glu Met Pro Gly Pro 16355 16360 16365 Val Ile Ala Thr Val Pro Ile Arg Val Arg Leu Asp Arg Gln Lys 16370 16375 16380 Thr Val Asp Asp Phe Leu Gln Gly Val Gln Asp Gln Ala Thr Lys 16385 16390 16395 Met Val Ala Tyr Glu Gln Phe Gly Leu Gln Ser Ile Gly Lys Leu 16400 16405 16410 Ser Ala Asp Ala Lys Asp Ala Cys Asp Phe Ser Ser Leu Leu Val 16415 16420 16425 Ile Gln Pro Leu Gln Thr Leu Ile Tyr Asn Asp Asp Asp Glu Gln 16430 16435 16440 Ala Leu Leu Ala Ala Ser Ala Ala Ala Ala Asp Thr Lys Asp Gln 16445 16450 16455 Val Met Gln Asn Tyr Phe Ser Tyr Pro Leu Val Ile Gln Ala His 16460 16465 16470 Leu His Asp Asp His Ile Ser Leu Val Leu Ile Tyr Asn Ser Met 16475 16480 16485 Ala Leu Pro Glu Ala Gln Leu Phe Ala Leu Ser Gln Gln Phe Lys 16490 16495 16500 His Val Val Glu Gln Leu Val Leu Glu Pro Gln Leu Ser Leu Gly 16505 16510 16515 Ser Leu Ser Ile Ala Ser Gly Trp Asp Val Ala Gln Ser Leu Lys 16520 16525 16530 Phe Asn Ala Glu Ile Pro Glu Ile Val Asp Ser Cys Val His Gln 16535 16540 16545 Leu Ile Glu Arg Gln Ala Glu Ile Arg Pro Asp Ala Met Ala Ile 16550 16555 16560 Arg Ala Trp Asp Ala Glu Leu Thr Tyr Arg Glu Phe Asn Arg Ala 16565 16570 16575 Ala Asn Arg Leu Ala Asn Tyr Leu Thr Ala Ser Tyr Asp Ile Lys 16580 16585 16590 Pro Asp Glu Leu Ile His Val Cys Phe Glu Lys Ser Ala Trp Phe 16595 16600 16605 Phe Val Ser Ile Leu Ala Ile Asn Lys Ser Gly Ala Ala Trp Val 16610 16615 16620 Pro Leu Asp Pro Ser His Pro Glu Gln Arg Leu Arg Gln Val Val 16625 16630 16635 Ser Gln Thr Arg Ala Arg Ile Ala Leu Thr Ser Pro Ser Asn Arg 16640 16645 16650 Asp Leu Val Thr Gly Leu Val Asp Ser Val Val Thr Val Asp Ser 16655 16660 16665 Gln Leu Asp Val Gln Leu Ser Lys Val Asp Glu His Ser Gln Lys 16670 16675 16680 Gly Pro Glu Thr Ala Val Ser Ser Asp Asn Ala Val Tyr Val Leu 16685 16690 16695 Phe Thr Ser Gly Ser Thr Gly Thr Pro Lys Gly Leu Val Met Gln 16700 16705 16710 His Gly Ser Val Cys Thr Ser Gln Thr Ala Ile Val Lys Arg Leu 16715 16720 16725 Gly Leu Thr Pro Asp Val Arg Met Leu Gln Phe Ala Ala Phe Val 16730 16735 16740 Phe Asp Leu Ser Ile Gly Glu Ile Ile Ala Pro Leu Ile Thr Gly 16745 16750 16755 Ala Cys Leu Cys Ile Pro Ser Asp His Thr Arg Met Asn Gly Leu 16760 16765 16770 Thr Gln Tyr Ile Arg Asp Thr Gly Ile Asn Trp Ala Phe Leu Thr 16775 16780 16785 Pro Ser Phe Ile Arg Thr Ile Asn Pro Ala Glu Val Pro Gly Leu 16790 16795 16800 Glu Leu Val Leu Leu Ala Gly Glu Ala Val Pro Arg Asp Val Leu 16805 16810 16815 Thr Thr Trp Phe Gly Lys Val Arg Leu Val Asn Gly Trp Gly Pro 16820 16825 16830 Ala Glu Thr Cys Val Phe Ser Thr Leu His Glu Trp Gln Ser Val 16835 16840 16845 Asn Glu Ser Pro Leu Thr Val Gly Arg Pro Val Gly Gly Phe Cys 16850 16855 16860 Trp Val Val Asp Pro Glu Asp Pro His Arg Leu Ala Pro Thr Gly 16865 16870 16875 Thr Leu Gly Glu Val Val Ile Gln Gly Pro Thr Leu Leu Arg Glu 16880 16885 16890 Tyr Leu Ser Asp Pro Glu Arg Thr Gln Ala Ser Thr Val Tyr Asp 16895 16900 16905 Leu Pro Lys Trp Ala Pro Arg Pro Asp Ser Arg His Trp Asn Lys 16910 16915 16920 Phe Tyr Lys Ser Gly Asp Leu Cys Tyr Tyr Asn Gln Asp Gly Thr 16925 16930 16935 Ile Glu Phe Ser Thr Arg Lys Asp Thr Gln Ile Lys Ile Arg Gly 16940 16945 16950 Leu Arg Val Glu Leu Gly Glu Val Gln His His Ile Gln Gln Ala 16955 16960 16965 Leu Pro Ser Ala Arg Gln Val Ala Val Asp Val Tyr Arg Gly Glu 16970 16975 16980 Asn Gly Thr Asn Leu Val Ala Tyr Leu Cys Phe Ser Asp Asp Thr 16985 16990 16995 Arg Thr Ala Gly Ile Ser Gly Gly Ala Ser Asp Gly Pro Phe Leu 17000 17005 17010 Pro Leu Ser Glu Asp Leu Gln Ser Thr Leu Ala Ala Val Val Gly 17015 17020 17025 Gln Leu Ser Ile Ser Leu Pro Arg Tyr Met Ile Pro Thr Met Phe 17030 17035 17040 Ile Pro Cys Ser Tyr Met Pro Phe Ile Thr Ser Thr Lys Leu Asp 17045 17050 17055 Arg Asn Glu Leu Lys Lys Leu Thr Ser Ser Leu Asp Lys Ala Gln 17060 17065 17070 Ile Ala Gln Tyr Ser Leu Leu Gly Gly Lys Lys Arg Ser Pro Glu 17075 17080 17085 Thr Pro Met Glu Val Phe Leu Gln Lys Leu Trp Ser Glu Leu Leu 17090 17095 17100 Gly Val Pro Val Glu Ser Ile Gly Arg Asp Asp Ser Phe Leu Gly 17105 17110 17115 Leu Gly Gly Asp Ser Ile Thr Ala Ile His Met Val Ser Ala Ala 17120 17125 17130 Arg Glu Ser Gly Val Ser Leu Ala Val Lys Glu Ile Phe Asp Asp 17135 17140 17145 Pro Arg Leu Ser Ala Val Ala Ser Lys Ala Arg Glu Ile Glu Gln 17150 17155 17160 Asp Glu Gln Thr Ser Leu Val Asp Ala Thr Pro Phe Tyr Leu Val 17165 17170 17175 Asp Glu Ser Ile Arg Gln Leu Ala Ile Gly Asp Glu Val Arg Gln 17180 17185 17190 Leu Cys Asp Leu Thr Asn Asn Glu Glu Val Glu Asp Ala Tyr Pro 17195 17200 17205 Val Thr Met Phe Gln Glu Gly Leu Met Ala Leu Ser Ala Lys Gln 17210 17215 17220 Pro Gly Ser Tyr Ile Ala Lys Tyr Ala Tyr Arg Leu Ser Glu His 17225 17230 17235 Val Asp Val Ala Arg Phe Lys Ala Ala Trp Glu Thr Thr Val Ser 17240 17245 17250 Leu Cys Pro Thr Leu Arg Thr Arg Leu Val Leu Leu Asn Gly Lys 17255 17260 17265 Cys Thr Gln Val Val Val Lys Gly Glu Thr Gly Trp Gln Ser Gln 17270 17275 17280 Glu His Thr Asp Val His Ala Ala Ile Gln Asp Ala Gln Thr Ala 17285 17290 17295 Glu Met Thr Tyr Gly Ser His Leu Ser Gln Ala Ile Met Val Asn 17300 17305 17310 Asp Ala Ser Asn Gly Asn Asn Tyr Phe Ile Trp Thr Val His His 17315 17320 17325 Ala Val His Asp Gly Trp Thr Val Arg Leu Ile Met Thr Thr Leu 17330 17335 17340 Gln Asn Ala Tyr Asn Asn Leu Glu Val Pro Asp Leu Lys Pro Tyr 17345 17350 17355 Ser Gly Phe Ile Gln Tyr Leu Gly Ser Ile Lys Ala Asp Asp Thr 17360 17365 17370 Ile Asn Phe Trp Thr Gln Gln Leu Gln Gly Ala Ser Lys Ala Ser 17375 17380 17385 Tyr Pro Pro Ser Lys Pro Ala Ser Ala Pro Glu Ser Val Thr Arg 17390 17395 17400 Leu Ile Thr Lys Thr Ile Gln Ala Ser Ser Ser Ala Asn Ala Ala 17405 17410 17415 Ile Thr Lys Ala Thr Ile Met Arg Ala Thr Trp Ala Ile Leu Leu 17420 17425 17430 Ala Arg Tyr Cys Asp Thr Asp Asp Val Thr Leu Gly Thr Ser Ile 17435 17440 17445 Ser Gly Arg Gln Ala Pro Val Ser Gly Leu Met Asp Met Pro Gly 17450 17455 17460 Pro Val Val Ala Thr Val Pro Val Arg Val Arg Leu Asp Arg Ser 17465 17470 17475 Gln Thr Ile Ser Lys Tyr Leu Gln Ala Ile Gln Ser Gln Ala His 17480 17485 17490 Glu Met Val Pro Tyr Glu Gln Tyr Gly Leu Thr Asn Ile Gly Lys 17495 17500 17505 Ile Asn Ser Asp Phe Arg Asp Val Cys Asp Phe Thr Ser Leu Leu 17510 17515 17520 Val Val Gln Pro Arg Thr His Leu Asp Ser Arg Ser Lys Gly Thr 17525 17530 17535 Ser Thr Glu Ser Asp Ala Ser Ser Ala Ala Leu Leu Leu Pro Ala 17540 17545 17550 Asn Val Glu Gly Gly Ser Val Glu Asp Leu Met Gln Gly Tyr Phe 17555 17560 17565 Ser Tyr Pro Leu Val Ile Gln Gly His Leu Met Ser Asp Ser Ile 17570 17575 17580 Glu Leu Val Ile Thr Tyr Asp Ser Ser Val Leu Ser Glu Ala Ser 17585 17590 17595 Met Glu Ala Met Cys His Gln Phe Glu His Val Ala Ser Gln Leu 17600 17605 17610 Phe Ala Asp Glu Gly Arg Thr Leu Gly Asp Leu Thr Val Ala Ser 17615 17620 17625 Ser Trp Asp Leu Glu Arg Ala Arg Ala Phe Asn Ser Glu Ala Pro 17630 17635 17640 Met Val Met Asp Thr Cys Ile His His Leu Ile Glu Ala Gln Val 17645 17650 17655 Arg Lys Thr Pro Asp Leu Pro Ala Val Trp Ala Trp Asp Gly Gln 17660 17665 17670 Leu Thr Tyr Arg Gln Leu Asn Glu Ala Ala Asn Arg Leu Ala His 17675 17680 17685 Tyr Leu Ile Asn Glu His Asn Val Gln Val Glu Asp Leu Val His 17690 17695 17700 Val Cys Phe Glu Lys Ser Val Trp His Trp Val Ser Val Leu Ala 17705 17710 17715 Ile Asn Lys Ala Gly Ala Val Trp Val Pro Leu Asp Pro Ser His 17720 17725 17730 Pro Glu Gln Arg Leu Arg Gln Val Ala Ser Gln Thr Gln Ser Thr 17735 17740 17745 Leu Ala Leu Thr Ser Asp Thr Thr Lys Ser Leu Leu Ser His Ile 17750 17755 17760 Ile Asp Arg Val Val Glu Val Ser Pro Ala Leu Phe Glu Gln Ile 17765 17770 17775 Asp Val Arg Leu Gly Glu Lys Glu Pro Gln Val Ser Val Ser Ala 17780 17785 17790 Ser Asn Ala Ala Tyr Ile Leu Phe Thr Ser Gly Ser Thr Gly Thr 17795 17800 17805 Pro Lys Gly Leu Val Met Thr His Gly Ala Leu Thr Thr Ser Gln 17810 17815 17820 Thr Ala Ile Lys Lys Arg Met Gly Thr Gly Thr His Thr Arg Ala 17825 17830 17835 Leu Gln Phe Ala Ser Tyr Val Phe Asp Met Ser Val Gly Glu Gly 17840 17845 17850 Phe Val Gln Leu Ile Ser Gly Ala Cys Ile Phe Ile Pro Ser Glu 17855 17860 17865 His Thr Arg Met Asn Gly Leu Lys Gln Phe Ile Thr Glu His Arg 17870 17875 17880 Ile Asn Ser Leu Trp Leu Thr Pro Ser Phe Ile Arg Thr Leu Ser 17885 17890 17895 Pro Glu Gln Val Pro Thr Val Asp Phe Val Phe Leu Ala Gly Glu 17900 17905 17910 Ala Ile Pro Arg Asp Val Phe Thr Thr Trp Cys Thr Lys Val Arg 17915 17920 17925 Leu Trp Asn Gly Trp Gly Pro Ala Glu Thr Cys Val Val Ser Ser 17930 17935 17940 Leu His Glu Phe Thr Ser Leu Asp Glu Ser Pro Leu Thr Ile Gly 17945 17950 17955 Arg Pro Ile Gly Gly Tyr Cys Trp Ile Val Asp Pro Thr Asp His 17960 17965 17970 Thr Lys Leu Ala Pro Ile Gly Thr Met Gly Glu Val Val Ile

Gln 17975 17980 17985 Ser Pro Thr Ile Leu Arg Glu Tyr Leu Ala Asp Val Glu Arg Thr 17990 17995 18000 Lys Ala Ser Thr Val Tyr Glu Leu Pro Glu Trp Ala Pro Tyr Arg 18005 18010 18015 Asp Gln Ala Pro Trp Ser Arg Phe Phe Lys Ser Gly Asp Leu Ala 18020 18025 18030 Ser Tyr Asn Pro Asp Gly Thr Leu Glu Phe Ala Ser Arg Lys Asp 18035 18040 18045 Thr Gln Val Lys Ile Arg Gly Leu Arg Val Glu Leu Gly Glu Ile 18050 18055 18060 Glu His His Val Arg Ser Ser Leu Thr Asp Ala Arg Gln Val Ala 18065 18070 18075 Val Asp Val Phe Arg Thr Asp Ala Gly Thr Arg Leu Ile Ala Tyr 18080 18085 18090 Phe Cys Tyr Ser Asp Val Thr Arg Thr Ala Gly Asn Ser Gln Pro 18095 18100 18105 Asp Asn Asp Asp Ile Phe Leu Pro Val Thr Glu Asp Leu Gln Arg 18110 18115 18120 Gln Leu Thr Ser Met Val Ser Gln Leu His Val Thr Leu Pro Arg 18125 18130 18135 Tyr Met Val Pro Ser Leu Phe Ile Pro Cys Arg Tyr Met Pro Phe 18140 18145 18150 Ile Thr Ser Thr Lys Leu Asp Arg Asn Arg Leu Lys Lys Leu Val 18155 18160 18165 Ser Glu Leu Ser Gln Glu Asp His Ala Ala Tyr Ser Leu Ser Asn 18170 18175 18180 Gly Val Lys Arg Met Pro Asp Thr Glu Met Glu Ala Arg Met Gln 18185 18190 18195 Glu Leu Trp Ser Val Val Leu His Met Pro Lys Glu Glu Ile Gly 18200 18205 18210 Cys Asp Glu Ser Phe Leu Gln Ile Gly Gly Asp Ser Ile Thr Ala 18215 18220 18225 Ile Gln Leu Val Thr Asn Ala Arg Glu Ala Gly Ile Ser Ile Ala 18230 18235 18240 Val Lys Asp Ile Phe Asp Asp Pro Arg Leu Ser Lys Leu Ala Leu 18245 18250 18255 Val Ala Ala Ala Asn Ser Asp Gln Ser Asn Ala Ser Thr Ile Val 18260 18265 18270 Glu Pro Phe Ser Leu Leu Gly Asp Ser Leu Thr Lys Glu Leu Val 18275 18280 18285 Thr Glu Ala Ala Lys Glu Gln Cys Asn Leu Ala Gly Asp Asp Leu 18290 18295 18300 Leu Asp Asp Ala Tyr Pro Cys Thr Lys Leu Gln Glu Gly Leu Met 18305 18310 18315 Ala Leu Ala Ile Lys Gln Pro Gly Ser Tyr Ile Ala Lys Tyr Val 18320 18325 18330 Tyr Gln Ile Pro Asp His Val Asp Val Ser Arg Phe Arg Lys Ala 18335 18340 18345 Trp Glu Arg Thr Val Gln Ser Cys Ala Asn Leu Arg Thr Arg Met 18350 18355 18360 Val Leu Val Asn Gly Ile Thr Val Gln Val Leu Leu Lys Asp Asp 18365 18370 18375 Ile Glu Trp Asp Asn Thr Asp Asp Thr Ser Leu Glu Thr Tyr Ala 18380 18385 18390 Arg Ser Thr Leu His Ile Glu Met Gly Phe Ala Gln Arg Leu Cys 18395 18400 18405 Arg Tyr Ala Leu Ile Glu Glu Glu Thr Gly Asn Tyr Phe Ala Phe 18410 18415 18420 Ser Ile His His Thr Ile Phe Asp Gly Trp Ser Leu Pro Leu Val 18425 18430 18435 Met Gly Thr Leu Ser Ala Ala Tyr Tyr Asp Leu Glu Leu Pro Ser 18440 18445 18450 Leu Gln Ser Tyr Ala Ala Phe Val Lys Tyr Thr Met Glu Leu Asp 18455 18460 18465 His Gly Val Ala Ser Asp Tyr Trp Glu Lys Gln Leu Lys Gly Ala 18470 18475 18480 Lys Arg Ala Ser Phe Pro Ala Pro Ser Asp Lys Ser Gly Ser Ser 18485 18490 18495 Gln Thr Arg Val Ala Asn Lys Thr Ile Gly Phe Pro Lys Ser Lys 18500 18505 18510 Thr Ser Ile Thr Lys Ala Ser Ile Leu Arg Ala Ala Trp Ala Ile 18515 18520 18525 Val Leu Ala Arg Tyr Ser Asp Ser Asp Asp Val Cys Phe Gly Thr 18530 18535 18540 Thr Val Ser Gly Arg Asn Ala Asn Val Ala Gly Leu Glu Ala Met 18545 18550 18555 Pro Gly Leu Val Val Ala Thr Val Pro Val Arg Ile His Val Asp 18560 18565 18570 Lys Gln Lys Pro Leu Ser Gly Phe Leu Gln Asp Val Gln Lys Gln 18575 18580 18585 Ala Asn Asp Met Val Asp Phe Glu Gln Phe Gly Ile Gln Asn Ile 18590 18595 18600 Ser Arg Leu Gly Ser Asp Ala Lys Asp Ala Cys Asp Phe Thr Ser 18605 18610 18615 Leu Leu Ala Ile Gln Pro Val Gln His Met Ser Ala Asp Ser Gly 18620 18625 18630 Asn Pro Ala Asp Gln Gly Ala Ile Val Ile Pro Ala Ala Ser Pro 18635 18640 18645 His Val Asn Ala Glu Asp Met Leu Gln Asn Tyr Phe Ser Tyr Pro 18650 18655 18660 Leu Val Ile Gln Cys His Leu Met Asp Asp His Val Asn Leu Val 18665 18670 18675 Leu Val Tyr Asp Thr Asp Val Leu Glu Glu Thr Gln Leu Asn Ala 18680 18685 18690 Leu Met Gln Gln Phe Asp His Val Val Gln Gln Leu Ser Ala Gln 18695 18700 18705 Gly Asn Glu Pro Leu Gly Asp Val Ser Ile Ser Gly Pro Trp Asp 18710 18715 18720 Leu Glu Gln Ala Leu Gln Leu Asn Ser Arg Lys Pro Asp Phe Val 18725 18730 18735 His Thr Cys Leu His Asp Ile Phe Ser Lys His Ala Leu Ser Ser 18740 18745 18750 Pro His His Glu Ala Ile Tyr Ser Ser Glu Gly Ser Leu Thr Tyr 18755 18760 18765 Gly Glu Leu Asp His Leu Thr Asp Ile Leu Ala Thr His Leu Ser 18770 18775 18780 Ser Leu Gly Ala Gly Pro Glu Thr Val Val Pro Phe Cys Phe Glu 18785 18790 18795 Lys Ser Met Trp Ala Val Val Ala Ile Leu Ala Ile Leu Lys Ala 18800 18805 18810 Gly Ala Ala Phe Val Pro Leu Asp Pro Ser His Pro Thr Ser Arg 18815 18820 18825 Arg Glu Ala Leu Val Lys Glu Val Ser Ala Arg Val Leu Val Ala 18830 18835 18840 Ser Ser Ser Ala Ile Ala Ser Cys Lys Gly Met Phe Glu His Val 18845 18850 18855 Val Glu Leu Ser Pro Ser Val Met Ala Lys Leu Ala Ala Ser Val 18860 18865 18870 Thr Pro Arg Ile Leu Pro Lys Val Gly Pro Arg Asn Thr Ala Tyr 18875 18880 18885 Val Leu Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Val 18890 18895 18900 Met Gln His Gly Ser Phe Ser Ser Thr Thr Ile Gly Tyr Gly Lys 18905 18910 18915 Val Tyr Asn Leu Ser Pro Leu Ser Arg Val Phe Gln Phe Ser Asn 18920 18925 18930 Tyr Ile Phe Asp Gly Ser Leu Gly Glu Ile Phe Gly Pro Leu Ala 18935 18940 18945 Phe Gly Gly Thr Ile Cys Ile Pro Ser Glu Asp Glu Arg Leu Gly 18950 18955 18960 Ser Ala Pro Ala Phe Met Ser Thr Ser Lys Val Asn Thr Ala Met 18965 18970 18975 Leu Thr Pro Ser Phe Val Arg Thr Phe Thr Pro Asp Gln Val Pro 18980 18985 18990 His Leu Thr Thr Leu Val Leu Gly Gly Glu Ala Ala Ser Lys Ser 18995 19000 19005 Thr Leu Glu Met Trp Val Asn Arg Val Thr Leu Tyr Asn Gly Tyr 19010 19015 19020 Gly Pro Ala Glu Ala Cys Asn Tyr Ala Thr Thr His Val Phe Lys 19025 19030 19035 Ser Ser Ser Glu Ser Pro Arg Ile Ile Gly Ser Gly Phe Asn Gly 19040 19045 19050 Ala Cys Trp Val Val Glu Pro Asp Asn His Asn Ile Leu Ala Pro 19055 19060 19065 Ile Gly Cys Thr Gly Glu Leu Val Leu Gln Gly His Ala Leu Ala 19070 19075 19080 Arg Gly Tyr Leu Asn Asp Lys Ala Lys Thr Glu Gln Ser Phe Val 19085 19090 19095 Ser Asp Ile Ser Ser Leu Pro Ser Ser Ser Leu His Glu Pro Lys 19100 19105 19110 Arg Phe Tyr Leu Thr Gly Asp Leu Val Arg Tyr Asn Ser Asn Gly 19115 19120 19125 Lys Leu Glu Tyr Leu Gly Arg Lys Asp Ser Gln Val Lys Leu Arg 19130 19135 19140 Gly Gln Arg Leu Glu Leu Gly Glu Ile Glu Tyr Asn Ile Thr Gln 19145 19150 19155 Ser Leu Lys Ser Val Arg Asp Val Ala Val Asp Val Ile His Lys 19160 19165 19170 Asp Thr Gly Asp Leu Leu Val Ala Phe Ile Ser Phe Ser Gly Asn 19175 19180 19185 Ala Asp Ala Gln Trp Asp Ser Asp Asn Leu Leu Leu Asn Leu Leu 19190 19195 19200 Ala Ala Asp Glu Ser Met Arg Ser Leu Leu Asp Gly Leu Arg Glu 19205 19210 19215 Gly Leu Lys Ala Ser Leu Pro Gly Tyr Met Ala Val Leu Pro Ala 19220 19225 19230 Phe Met Met Pro Ser Leu Val Leu Pro Val Arg Asn Met Pro Phe 19235 19240 19245 Ile Thr Ser Met Lys Leu Asp Arg Lys Gln Leu Arg Thr Leu Ala 19250 19255 19260 Ser Ser Leu Ser Pro Glu Glu Leu Ala Thr Phe Ala Pro Ser Lys 19265 19270 19275 Ala Asp Lys Val Glu Pro Thr Thr Asp Met Glu Leu Lys Leu Arg 19280 19285 19290 Asp Leu Trp Ala Gln Ile Leu Gly Ile Pro Ala Glu Glu Ile Gly 19295 19300 19305 Lys Asn Asp Ser Phe Leu Gln Ile Gly Gly Asp Ser Ile Ser Ala 19310 19315 19320 Ile His Leu Val Thr Leu Ala Gln Glu Thr Gly Ile Ser Leu Thr 19325 19330 19335 Val Ala Thr Ile Phe Ala Asp Pro Arg Leu Ser Ser Val Ala Ala 19340 19345 19350 Ser Ala His Leu Gly Gly Ile Ser Asp Ala Tyr Glu Ala Glu Pro 19355 19360 19365 Phe Ser Leu Ile Gln His Ser Glu Ser Asp Ala Ile Thr Arg Glu 19370 19375 19380 Ile Glu Gln Gln Cys Lys Leu Ser Ala Gly Gln Ser Ile Glu Asp 19385 19390 19395 Ala Tyr Pro Thr Thr Lys Leu Gln Glu Gly Leu Met Ala Leu Ser 19400 19405 19410 Val Lys Gln Pro Gly Ser Tyr Thr Ala Arg Tyr Val Tyr Arg Leu 19415 19420 19425 Pro Asp His Val Asp Val Glu Arg Phe Lys Ala Ala Trp Asp Lys 19430 19435 19440 Thr Val Glu Val Cys His Asn Leu Arg Thr Ser Ile Val Leu Val 19445 19450 19455 Gly Tyr Thr Ala Ile Gln Ala Val Ile Lys Asp Thr Ser Arg Ser 19460 19465 19470 Leu Trp Glu Pro Ala Thr Gly Val Ser Leu Gln Ser Tyr Met Lys 19475 19480 19485 Lys Ala Ile Gly Ser Phe Asn Met Gly Tyr Gly Ser Arg Leu Cys 19490 19495 19500 Arg Tyr Ala Leu Ile Glu Asp Gly Gly Ser Thr Tyr Phe Ala Trp 19505 19510 19515 His Ile His His Ser Val Tyr Asp Gly Trp Thr His Pro Leu Ile 19520 19525 19530 Met Gly Ser Leu Tyr Ala Ala Tyr Phe Gly Thr Glu Met Pro Pro 19535 19540 19545 Leu Arg Pro Phe Ala Arg Phe Val Lys Tyr Thr Thr Ser Ile Asp 19550 19555 19560 Gln His Glu Ala Ala Glu Tyr Trp Arg Arg Gln Leu His Asp Ala 19565 19570 19575 Arg Pro Ala Ser Phe Pro Ala Val Asp Gln Gln Leu Thr Ala Ser 19580 19585 19590 Lys Ser Lys Ala Asp Val Thr Arg Ile Leu Arg Lys Ala Val Asp 19595 19600 19605 Phe Pro Arg Leu Thr Asn Ser Ser Ile Thr Lys Ala Thr Ile Met 19610 19615 19620 Arg Ala Ala Trp Ser Ile Val Leu Ala Gln Tyr Cys Gly Val Asp 19625 19630 19635 Asp Val Cys Phe Gly Thr Thr Leu Ser Gly Arg His Ala Pro Val 19640 19645 19650 Pro Gly Leu Asp Ser Met Pro Gly Pro Met Leu Ala Thr Val Pro 19655 19660 19665 Val Arg Ile Arg Leu Ala Gln Asp Gln Pro Ala Ser Arg Phe Leu 19670 19675 19680 Gln Asp Val Gln Ile Gln Ala Ala Glu Met Val Ala Tyr Glu Gln 19685 19690 19695 Phe Gly Leu Gln Asn Ile Ala Ala Leu Ser Pro Asp Ala Lys Gln 19700 19705 19710 Ala Cys Asp Phe Ser Ser Leu Leu Val Ile Gln Pro Ala Gln Gln 19715 19720 19725 Gln Ile Ser Asp Asp Lys Ala Val Ser Glu Thr Asp Met Ile Leu 19730 19735 19740 Leu Pro Gly Asp Ser Glu Asn Ser Ala Glu Glu Ser Met Gln Asn 19745 19750 19755 Phe Ala Asn Tyr Pro Leu Val Leu Gln Ile Ala Ile Met Asp Ser 19760 19765 19770 His Val Glu Leu Leu Leu Ile Tyr Asp Thr Asn Ala Leu Thr Glu 19775 19780 19785 Phe Gln Ala Thr Ala Ile Ser Glu Gln Phe Gly Asn Val Ala Arg 19790 19795 19800 Gln Leu Val Ala Gln Asp Glu Thr Leu Ile Gly Asp Val Lys Val 19805 19810 19815 Ala Gly Ser Trp Asp Leu Gln Lys Gln Leu Glu Trp Asn His Glu 19820 19825 19830 Ile Tyr Gly Pro Ser Glu Thr Thr Leu His Asp Leu Phe Ser Lys 19835 19840 19845 Gln Val Ala Arg Arg Pro Ala His Gln Ala Leu Tyr Ser Ser Glu 19850 19855 19860 Gly Ser Met Thr Tyr Ser Lys Leu Asp Arg Leu Thr Thr Gln Leu 19865 19870 19875 Ala Val Tyr Leu Ser Ser Leu Gly Val Arg Pro Glu Thr Ile Val 19880 19885 19890 Pro Phe Cys Phe Asp Lys Ser Ile Trp Ala Ile Val Ala Met Ile 19895 19900 19905 Gly Ile Leu Lys Ala Gly Gly Val Phe Met Pro Leu Asp Pro Ser 19910 19915 19920 Tyr Pro Ala Ser Arg Arg Gln Ala Leu Ile Asp Glu Val Asn Ala 19925 19930 19935 Gln Phe Met Ile Val Ser Pro Thr Thr Ala Pro Asp Ser Gln Gly 19940 19945 19950 Met Val Gln Asn Met Ile Glu Leu Ser Pro Ser Leu Ile Ala Phe 19955 19960 19965 Phe Ser Thr Ile Asp Thr Gly Asp Gln Ser Phe Ile Lys Ser Gly 19970 19975 19980 Pro Asn Asn Ala Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr Gly 19985 19990 19995 Lys Pro Lys Gly Val Val Ile Asp His Lys Ala Ile Ser Ala Ala 20000 20005 20010 Leu Leu Arg Gln Arg Glu Ala Phe Ser Phe Asn Asp Asp Thr Arg 20015 20020 20025 Thr Leu Gln Phe Ala Asn Phe Val Phe Asp Ala Cys Ile Ala Glu 20030 20035 20040 Ile Phe Ser Ala Leu Val Ala Gly Ala Thr Val Cys Val Pro Thr 20045 20050 20055 Glu His Glu Arg Val His Asn Thr Ala Ala Phe Ile Arg Glu Ala 20060 20065 20070

Arg Ile Asn His Ala Phe Leu Thr Pro Thr Phe Ile Lys Thr Leu 20075 20080 20085 Ser Pro Glu Gln Ile Pro Gly Met Lys Thr Val Ile Leu Met Gly 20090 20095 20100 Glu Ala Pro Ser Gln Glu Ile Ile Asp Thr Trp Ala Asp Glu Ile 20105 20110 20115 Asp Leu His Asn Gly Tyr Gly Pro Ala Glu Gly Cys Val Gly Ser 20120 20125 20130 Thr Asn Asn Thr Tyr Ser Ser Ser Ile Lys Val Ser Val Thr Asn 20135 20140 20145 Val Gly Arg Ser Phe Thr His Gly Leu Trp Ile Val Asp Pro Asp 20150 20155 20160 Asn His Asn Arg Leu Met Pro Ile Gly Cys Val Gly Glu Leu Leu 20165 20170 20175 Leu Gln Gly Ser Ser Leu Ala Arg Gly Tyr Ile Asn Asp Glu Glu 20180 20185 20190 Lys Ser Arg Gln Ser Phe Ile Asp Gln Val Glu Trp Leu Pro Ala 20195 20200 20205 Asn Val Asn Val Gly Glu Arg Arg Phe Tyr Lys Thr Gly Asp Leu 20210 20215 20220 Val Arg Tyr Thr Pro Asp Gly Ser Ile Glu Tyr Val Ser Arg Lys 20225 20230 20235 Asp Thr Gln Val Lys Ile Arg Gly Gln Arg Ile Glu Leu Gly Glu 20240 20245 20250 Ile Glu Tyr His Val Lys Arg Ser Asn Ala Ser Ile Glu His Val 20255 20260 20265 Val Val Asp Ile Thr Arg Gln Ala Gly Arg Glu Ser Leu Leu Ala 20270 20275 20280 Phe Val Cys Phe Ser Ser His Gln Glu Thr Glu Ser Ala Ser Lys 20285 20290 20295 Glu Thr Arg Leu Thr Glu Leu Thr Ser Glu Leu Arg Glu Thr Leu 20300 20305 20310 Ser Asp Ile Ala Thr Thr Ile Ala Ser Thr Leu Pro Ser His Met 20315 20320 20325 Val Pro Lys Tyr Leu Ile Pro Val Asp His Met Pro His Asn Ala 20330 20335 20340 Ala Gly Lys Leu Asp Arg Lys Met Leu Leu Ala Ser Ile Ala Asn 20345 20350 20355 Leu Thr Pro Asp Asp Leu Ser Lys Tyr Leu Ala Gly Gln Arg Leu 20360 20365 20370 Pro Phe Arg Asp Cys Ser Thr Asp Val Glu Phe Trp Leu Arg Asn 20375 20380 20385 Gln Trp Ala Ser Thr Leu Asp Leu Pro Ala Glu Thr Ile Gly Met 20390 20395 20400 Asp Asp Asn Phe Tyr Ser Leu Gly Gly Asp Ser Ile Arg Ile Val 20405 20410 20415 Thr Ile Ser Lys Ala Ile Leu Ser Gln Tyr Asp Val Ser Leu Gly 20420 20425 20430 Met Ser Leu Leu Asn Ser Lys His Thr Thr Ile Ala Asn Met Ala 20435 20440 20445 Lys His Ile Asp Ser Glu Arg Ser Gly Gln Asp Gly Ala Glu Leu 20450 20455 20460 Gly Val Val Asp Ile Asn Gly Glu Ile Ser Ser Leu Ser Arg Ser 20465 20470 20475 Ile Leu Ala Ser Gly Asp Leu Asn Val Val Ser His Ser Lys Thr 20480 20485 20490 Glu Leu Pro Glu Gln Ala Thr Val Phe Leu Thr Gly Ala Thr Gly 20495 20500 20505 Phe Leu Gly Gln Glu Leu Leu Arg Gln Leu Leu Cys Asn Asp Ser 20510 20515 20520 Ile Ala Ser Ile Ile Ala Leu Val Arg Ser Lys Ser Ala Asn His 20525 20530 20535 Gly Met Asp Arg Leu Arg Asp Thr Ala Lys Ile Ala Gly Trp Trp 20540 20545 20550 Arg Glu Glu Tyr Thr Ser Lys Ile Glu Ile Trp Cys Gly Asp Leu 20555 20560 20565 Ser Lys Lys Arg Met Gly Leu Ser Ser Ser Gln Trp Ala Arg Leu 20570 20575 20580 Ala Gly Gln Ser Ser Asn Asn Asn Val Asp Ala Ile Ile His Asn 20585 20590 20595 Gly Ala Ile Val Asn Trp Asn Ala Asp Tyr Asp Lys Met Arg Ala 20600 20605 20610 Ala Asn Val Asp Ser Thr Val Asp Leu Leu Lys Ala Thr Val Thr 20615 20620 20625 Ser Pro Ala Ser Pro Lys Phe Val Phe Val Ser Gly Gly Ile Lys 20630 20635 20640 Ser Asp Pro Thr Thr Asp Arg Thr Ala Leu Gly Gln Tyr Leu Asn 20645 20650 20655 Asn Ser Thr Gly Tyr Ile Gln Thr Lys Phe Val Ser Glu Gly Ile 20660 20665 20670 Ile Gln Glu Val Ile Lys Thr Leu Pro Ala Asp Gln Asn Arg Ile 20675 20680 20685 Ser Thr Leu Lys Pro Gly Arg Ile Ile Gly Ser Pro Glu Thr Gly 20690 20695 20700 Val Ala Asn Val Asp Asp Val Leu Trp Arg Ile Val Ser Ala Ala 20705 20710 20715 Ala Ser Leu Gly Val Tyr Pro Ala Glu Pro Glu Asp His Trp Val 20720 20725 20730 Tyr Ile Ser Asp Val Asp Thr Val Ala Ser Ser Val Leu Ser Gln 20735 20740 20745 Leu Tyr Ser Lys Gln Gly Ile Ala Pro Tyr Val Ser Ala Thr Gly 20750 20755 20760 Gly Met Pro Ala Thr Val Phe Trp Asp Leu Ile Asn Lys Glu Leu 20765 20770 20775 Asp Val Pro Cys Glu Pro Leu Ser Gln Asp Glu Trp Thr His Arg 20780 20785 20790 Ala Leu Glu Ser Met Asn Gln Val Gly Asp Lys His Pro Leu Trp 20795 20800 20805 Pro Val Gln His Phe Leu Gly Asn Leu Gly Thr Pro Arg Ser Ala 20810 20815 20820 Gln Asp Ile Glu Ile Glu Gly Ser Glu His Lys Gln Trp His Met 20825 20830 20835 Ala Val Lys Met Ser Met Arg Tyr Leu Met Lys Val Gly Phe Ile 20840 20845 20850 Gln Thr Ser Thr Asp Gly Phe Ala Gln Pro Arg Arg Ala Asp Thr 20855 20860 20865 Phe Gln Arg His Gly 20870 51014DNATrichoderma reesei 5atgtctactc taacagttct ggagcctacc ttgcggctag acgcacctac agtcaagtta 60caatcaccaa agcaagcaga caggcaactc caggtcgtga ttccggattt gttctcctcg 120atcatggctg ttgagcccac catcaatcct cattacaaag atgtcaaggc cgaagcagat 180gcgtggttca aaagtttgtt gcagttgaaa gggaaagcag aggcgacttt caacaagacc 240gactttggat tcgcagctgc tgtatgggcc ccttcagcag acaaggacag gttccgcaca 300gctgtcgact gggcaaattg gatattctat tttgatgatc aattcgatga aggacatcta 360gcaaacgatc cagctgcggc gcaggcagag attgattcca tactcgccat cctggatgac 420aagccaactc ttgctcagac cgacaagcca ctcatatatg cttttcagtc tatttgggac 480agaataaagg cggtatgtag acctctgcta cgcgaacgtt ggaaagatgc ccataagaaa 540tacgtcgagg ggttgatcta tcaaactcag cgaacaaagc ttggttctgc tgcctccgca 600agcgtggatg aatacatgag ttaccgaagg gaaacgatcg gtgttatatt ggctattcga 660ctggttgaat atgcagagaa catcaagctt tcccaagctc agatggatca cccggcactg 720cagttgtgca ctcgaacgat tgtagatctc gtgattctct caaatgacat cttatcatac 780aagaaagaag agctcaatga tgcagggaac aatctagtca caatactcaa ggcacagaac 840ctctccgatc aggaggcaat ggacaaaata ggcagaatgc tcgacgcttg ctatgagagt 900tggtacaacg caatggatga gctaccagtt tggggggcag gaatcgacca agaggtgcgc 960agatatctgg ttgtttgtcg taacgtgggt cttggcaatc ttcactggag gtaa 10146337PRTTrichoderma reesei 6Met Ser Thr Leu Thr Val Leu Glu Pro Thr Leu Arg Leu Asp Ala Pro 1 5 10 15 Thr Val Lys Leu Gln Ser Pro Lys Gln Ala Asp Arg Gln Leu Gln Val 20 25 30 Val Ile Pro Asp Leu Phe Ser Ser Ile Met Ala Val Glu Pro Thr Ile 35 40 45 Asn Pro His Tyr Lys Asp Val Lys Ala Glu Ala Asp Ala Trp Phe Lys 50 55 60 Ser Leu Leu Gln Leu Lys Gly Lys Ala Glu Ala Thr Phe Asn Lys Thr 65 70 75 80 Asp Phe Gly Phe Ala Ala Ala Val Trp Ala Pro Ser Ala Asp Lys Asp 85 90 95 Arg Phe Arg Thr Ala Val Asp Trp Ala Asn Trp Ile Phe Tyr Phe Asp 100 105 110 Asp Gln Phe Asp Glu Gly His Leu Ala Asn Asp Pro Ala Ala Ala Gln 115 120 125 Ala Glu Ile Asp Ser Ile Leu Ala Ile Leu Asp Asp Lys Pro Thr Leu 130 135 140 Ala Gln Thr Asp Lys Pro Leu Ile Tyr Ala Phe Gln Ser Ile Trp Asp 145 150 155 160 Arg Ile Lys Ala Val Cys Arg Pro Leu Leu Arg Glu Arg Trp Lys Asp 165 170 175 Ala His Lys Lys Tyr Val Glu Gly Leu Ile Tyr Gln Thr Gln Arg Thr 180 185 190 Lys Leu Gly Ser Ala Ala Ser Ala Ser Val Asp Glu Tyr Met Ser Tyr 195 200 205 Arg Arg Glu Thr Ile Gly Val Ile Leu Ala Ile Arg Leu Val Glu Tyr 210 215 220 Ala Glu Asn Ile Lys Leu Ser Gln Ala Gln Met Asp His Pro Ala Leu 225 230 235 240 Gln Leu Cys Thr Arg Thr Ile Val Asp Leu Val Ile Leu Ser Asn Asp 245 250 255 Ile Leu Ser Tyr Lys Lys Glu Glu Leu Asn Asp Ala Gly Asn Asn Leu 260 265 270 Val Thr Ile Leu Lys Ala Gln Asn Leu Ser Asp Gln Glu Ala Met Asp 275 280 285 Lys Ile Gly Arg Met Leu Asp Ala Cys Tyr Glu Ser Trp Tyr Asn Ala 290 295 300 Met Asp Glu Leu Pro Val Trp Gly Ala Gly Ile Asp Gln Glu Val Arg 305 310 315 320 Arg Tyr Leu Val Val Cys Arg Asn Val Gly Leu Gly Asn Leu His Trp 325 330 335 Arg 7684DNATrichoderma reesei 7atgcagcgta ttctcgctct cactgctgct gcggcaggcc tctttgtgac agccttgggc 60accaaagttc caagtgtcaa tgtcccatca tgcccgcgca tcggttccgt ttcctacacc 120acgtcggtgc ccgaccggac tccatttccg cgtacgcagg tcgacctgtg ctataccgac 180gatagcctcg agctcacatt tatcgcctat gacgaggtga attacttctt caacgcgtcc 240cagggaacca acgacgacat ctgggagtac gaagtcatgg aggccttcat ctacaagggc 300actgaagacc ctcagacata cgtcgagctc gaggtcaatc ccaacaatgt gacataccaa 360gcatttgttt acaatccttc caagaaccgg acagcgggcg caccgttcga ccacttcttc 420atttcggatc ccgcaaccga cggcttcaag gccaagacga tcctcaacaa gccagcaaag 480acttggagaa gcacccttac cgtccctcta ggtatcttca atgttgatgt cggcaaggca 540aagggtacct cttggaggat gaattttttc aggactgtag ttagcccgga gatttatcca 600aatcagattc tgggcggctg gggtgtcccg gatcaggcga gcttccatat caccaagtat 660tttggcaagg tgaagtttat ctga 6848227PRTTrichoderma reesei 8Met Gln Arg Ile Leu Ala Leu Thr Ala Ala Ala Ala Gly Leu Phe Val 1 5 10 15 Thr Ala Leu Gly Thr Lys Val Pro Ser Val Asn Val Pro Ser Cys Pro 20 25 30 Arg Ile Gly Ser Val Ser Tyr Thr Thr Ser Val Pro Asp Arg Thr Pro 35 40 45 Phe Pro Arg Thr Gln Val Asp Leu Cys Tyr Thr Asp Asp Ser Leu Glu 50 55 60 Leu Thr Phe Ile Ala Tyr Asp Glu Val Asn Tyr Phe Phe Asn Ala Ser 65 70 75 80 Gln Gly Thr Asn Asp Asp Ile Trp Glu Tyr Glu Val Met Glu Ala Phe 85 90 95 Ile Tyr Lys Gly Thr Glu Asp Pro Gln Thr Tyr Val Glu Leu Glu Val 100 105 110 Asn Pro Asn Asn Val Thr Tyr Gln Ala Phe Val Tyr Asn Pro Ser Lys 115 120 125 Asn Arg Thr Ala Gly Ala Pro Phe Asp His Phe Phe Ile Ser Asp Pro 130 135 140 Ala Thr Asp Gly Phe Lys Ala Lys Thr Ile Leu Asn Lys Pro Ala Lys 145 150 155 160 Thr Trp Arg Ser Thr Leu Thr Val Pro Leu Gly Ile Phe Asn Val Asp 165 170 175 Val Gly Lys Ala Lys Gly Thr Ser Trp Arg Met Asn Phe Phe Arg Thr 180 185 190 Val Val Ser Pro Glu Ile Tyr Pro Asn Gln Ile Leu Gly Gly Trp Gly 195 200 205 Val Pro Asp Gln Ala Ser Phe His Ile Thr Lys Tyr Phe Gly Lys Val 210 215 220 Lys Phe Ile 225 9993DNATrichoderma reesei 9atggaaccgg agcagatcac ggtgctcctt cctgacatgt tccagacgtt cctcaagcag 60ccgcctcgca tcaatcctca ctaccaatcg gttaagttgg agtctgaaga agggcttgcg 120aggttctgct ctttcgagcc gagcatgagg aagagagtga acaaatgcga cttttcatac 180ttttgtgcca ttgccgctcc ctttgcctct cgagcgagat ttcgtaccat ctgcgattgg 240gggaactggg tatttccata cgatgacatg tttgataatg ggcatcttcg caacgagccg 300gaagaatctc aacgcgtcat ggagagcctc atgatgccca tgttgggcaa tacggcgaat 360ttgaactctc aagaccggct tcgcatcgtg cagtttcacg acacggtcgt tgagagaatg 420gctctaagaa caccaaaagg cgtgcagaga agatttgccc ttgccatgca gggatactgc 480cgaggcgctc tcacccaaat cgatcatcaa ttctctggaa agatcccgac actggaggaa 540attgccatga ttcgccgaga gtctgctgga tgcaggcctc tatactacct tgttgaatac 600gcacatcgcc tccgagtgcc ggatgaggtg tttgagcatc ccattatcca ggagctggag 660aatcttggcc aggatatggc agagggcgta ccgcacaaca tggtcacagt ctgtcgacgg 720aacggcatgt cggcacaaaa ggcattcaac acagtcggca ggctcctcga gcgccgctat 780gagcgatggg acaaagccga ggcaagcctt ccgagctggg gcagggaggc tgatgttgag 840gtccgaaagt acattgaggg catcaaatgt gttgtcaagg ccaatctcaa ttggagtttc 900aaatcggagc gctacctcgg cgcaaatcct gaagtggttc gagccactcg gaaagttcac 960attctggcag attcgcctcc cattggcgtt tga 99310330PRTTrichoderma reesei 10Met Glu Pro Glu Gln Ile Thr Val Leu Leu Pro Asp Met Phe Gln Thr 1 5 10 15 Phe Leu Lys Gln Pro Pro Arg Ile Asn Pro His Tyr Gln Ser Val Lys 20 25 30 Leu Glu Ser Glu Glu Gly Leu Ala Arg Phe Cys Ser Phe Glu Pro Ser 35 40 45 Met Arg Lys Arg Val Asn Lys Cys Asp Phe Ser Tyr Phe Cys Ala Ile 50 55 60 Ala Ala Pro Phe Ala Ser Arg Ala Arg Phe Arg Thr Ile Cys Asp Trp 65 70 75 80 Gly Asn Trp Val Phe Pro Tyr Asp Asp Met Phe Asp Asn Gly His Leu 85 90 95 Arg Asn Glu Pro Glu Glu Ser Gln Arg Val Met Glu Ser Leu Met Met 100 105 110 Pro Met Leu Gly Asn Thr Ala Asn Leu Asn Ser Gln Asp Arg Leu Arg 115 120 125 Ile Val Gln Phe His Asp Thr Val Val Glu Arg Met Ala Leu Arg Thr 130 135 140 Pro Lys Gly Val Gln Arg Arg Phe Ala Leu Ala Met Gln Gly Tyr Cys 145 150 155 160 Arg Gly Ala Leu Thr Gln Ile Asp His Gln Phe Ser Gly Lys Ile Pro 165 170 175 Thr Leu Glu Glu Ile Ala Met Ile Arg Arg Glu Ser Ala Gly Cys Arg 180 185 190 Pro Leu Tyr Tyr Leu Val Glu Tyr Ala His Arg Leu Arg Val Pro Asp 195 200 205 Glu Val Phe Glu His Pro Ile Ile Gln Glu Leu Glu Asn Leu Gly Gln 210 215 220 Asp Met Ala Glu Gly Val Pro His Asn Met Val Thr Val Cys Arg Arg 225 230 235 240 Asn Gly Met Ser Ala Gln Lys Ala Phe Asn Thr Val Gly Arg Leu Leu 245 250 255 Glu Arg Arg Tyr Glu Arg Trp Asp Lys Ala Glu Ala Ser Leu Pro Ser 260 265 270 Trp Gly Arg Glu Ala Asp Val Glu Val Arg Lys Tyr Ile Glu Gly Ile 275 280 285 Lys Cys Val Val Lys Ala Asn Leu Asn Trp Ser Phe Lys Ser Glu Arg 290 295 300 Tyr Leu Gly Ala Asn Pro Glu Val Val Arg Ala Thr Arg Lys Val His 305 310 315 320 Ile Leu Ala Asp Ser Pro Pro Ile Gly Val 325 330 1148DNAArtificial SequenceArtificial DNA Primer 11tcacatggtt taaacggcgc gccgacccga aagaacgcaa aagtccat 481241DNAArtificial SequenceArtificial DNA Primer 12agccttgttt tgtcgtgtca agaacttgga tctcctagga g 411348DNAArtificial SequenceArtificial DNA Primer 13cctagttgga gtattcctgc aggtcctcat ctgtggctca tattaggt 481455DNAArtificial SequenceArtificial DNA Primer 14tggccatatt taaatcctgc agggtttaaa ccaaggcggg atagtgtcgg ttctt 551525DNAArtificial SequenceArtificial DNA Primer 15tgccccacga tatctctcct tctcc

251625DNAArtificial SequenceArtificial DNA Primer 16ctacatcgaa gctgaaagca cgaga 251730DNAArtificial SequenceArtificial DNA Primer 17tagctagctg tcttggatga atcgaggttg 301825DNAArtificial SequenceArtificial DNA Primer 18tcgtcttcat gagcatgttg ttggg 251948DNAArtificial SequenceArtificial DNA Primer 19tcacatggtt taaacggcgc gcctactacc tagtacagtg cttattta 482045DNAArtificial SequenceArtificial DNA Primer 20agccttgttt tgtcgttttt tctccaaatt tgtacagaat tatct 452148DNAArtificial SequenceArtificial DNA Primer 21cctagttgga gtattcctgc aggaggaatt gtgcctggct gttgagtt 482256DNAArtificial SequenceArtificial DNA Primer 22tggccatatt taaatcctgc agggtttaaa cgcttatcga tccggcatat cgctct 562325DNAArtificial SequenceARTIFICIAL DNA PRIMER 23taccttacag gccctccgcg agcta 252425DNAArtificial SequenceARTIFICIAL DNA PRIMER 24ctacatcgaa gctgaaagca cgaga 252530DNAArtificial SequenceARTIFICIAL DNA PRIMER 25atgttggagc cttgcctcca gagtcctcac 302630DNAArtificial SequenceARTIFICIAL DNA PRIMER 26gggttcagtc cagaagcaga accaggatca 302725DNAArtificial SequenceARTIFICIAL DNA PRIMER 27cagatgagcc ctacatgacg ccagc 252821DNAArtificial SequenceARTIFICIAL DNA PRIMER 28ggctccatac cgacgatatg c 21

Claims

1-19. (canceled)

20. A mutant of a parent Trichoderma strain, comprising a polynucleotide encoding a heterologous polypeptide and a peptaibol synthetase gene and a paracelsin synthetase gene, wherein the peptaibol synthetase gene and the paracelsin synthetase gene are modified rendering the mutant strain deficient in the production of a peptaibol synthetase and a paracelsin synthetase compared to the parent Trichoderma reesei strain when cultivated under identical conditions, wherein the heterologous polypeptide is selected from the group consisting of an acetylmannan esterase, acetylxylan esterase, am inopeptidase, alpha-amylase, arabinanase, arabinofuranosidase, carbohydrase, carboxypeptidase, catalase, cellobiohydrolase, cellulase, cellulose inducing protein, chitinase, coumaric acid esterase, cyclodextrin glycosyltransferase, cutinase, cyclodextrin glycosyltransferase, deoxyribonuclease, endoglucanase, esterase, expansin, feruloyl esterase, AA9 polypeptide, alpha-galactosidase, beta-galactosidase, glucocerebrosidase, glucose oxidase, alpha-glucosidase, beta-glucosidase, glucuronidase, glucuronoyl esterase, haloperoxidase, hemicellulase, invertase, isomerase, laccase, ligase, lipase, mannanase, mannosidase, mutanase, oxidase, pectinolytic enzyme, peroxidase, phospholipase, phytase, phenoloxidase, polyphenoloxidase, proteolytic enzyme, ribonuclease, swollenin, alpha-1,6-transglucosidase, transglutaminase, urokinase, xylanase, and beta-xylosidase.

21. The mutant of claim 20, wherein the peptaibol synthetase gene encodes a polypeptide having peptaibol synthetase activity selected from the group consisting of: (a) a polypeptide comprising an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 2; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions with SEQ ID NO: 1 or the cDNA sequence thereof; or the full-length complement thereof; (c) a polypeptide encoded by a polynucleotide comprising a nucleotide sequence having at least 60% sequence identity to SEQ ID NO: 1 or the cDNA sequence thereof; and (d) a polypeptide comprising or consisting of SEQ ID NO: 2.

22. The mutant of claim 20, wherein the paracelsin synthetase gene encodes a polypeptide having paracelsin synthetase activity selected from the group consisting of: (a) polypeptide comprising or consisting of an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 4; (b) a polypeptide encoded by a polynucleotide that hybridizes under at least low stringency conditions with SEQ ID NO: 3 or the cDNA sequence thereof; or the full-length complement thereof; (c) a polypeptide encoded by a polynucleotide comprising or consisting of a nucleotide sequence having at least 60% sequence identity to SEQ ID NO: 3 or the cDNA sequence thereof; and (d) a polypeptide comprising or consisting of SEQ ID NO: 4.