# Patent

## Title
Human checkpoint gene and gene for antisense RNA thereof

## Abstract

This is a request for filing a Continuation-In-Part application of pending application, Ser. No. 07/658,398 filed on Feb. 19, 1991, now abandoned.

## Background
1. Technical Field

This invention relates to methods and compositions to enhance the in vivo and in vitro production of fermentable or known and new secondary metabolites, particularly .beta.-lactams and their biosynthetic intermediates using recombinant DNA techniques.

2. Background

.beta.-Lactam antibiotics are the largest family of secondary metabolites produced in nature by microorganisms. The most important classes of the .beta.-lactam antibiotics both clinically and economically are the penicillins (penam) and cephalosporins (cephem). Their biosynthesis occurs via a complex pathway of enzymatic steps; the unravelling of this pathway has been the subject of many studies during the last few decades. The first two steps are the key steps in the biosynthetic pathways of the penam and cephem classes of .beta.-lactam antibiotics. After these two steps the biosynthetic pathways to the penicillins and cephalosporins diverge.

The first step in the biosynthesis of the penicillin, cephalosporin and cephamycin antibiotics is the condensation of the L-isomers of three amino acids, L-.alpha.-amino adipic acid (A), L-cysteine (C) and L-valine (V) into a tripeptide, .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine or ACV. This step is catalyzed by 67 -(L-.alpha.-aminoadipyl)L-cysteinyl-D-valine synthetase or ACVS. In the second step, the tripeptide ACV is oxidatively cyclised by the action of the Isopenicillin N synthase (hereinafter referred to as IPNS) or cyclase. The product of this reaction is Isopenicillin N; this compound contains the typical .beta.-lactam and thiazolidine ring structures and possesses antibacterial activity. From Isopenicillin N the penicillins G or V are formed by exchange of the hydrophilic A side chain by a hydrophobic side chain. The side chains commonly used in industrial processes are either phenylacetic acid (PA), yielding penicillin G, or phenoxyacetic acid (POA), yielding penicillin V; this exchange reaction is catalyzed by the enzyme acyltransferase (hereinafter referred to as AT).

From Isopenicillin N the route to cephalosporin and the cephamycins proceeds via racemization of the A side chain, forming penicillin N. This reaction is catalyzed by an enzyme named epimerase or racemase. The five-membered ring in penicillin N is expanded into a six-membered ring by the action of the enzyme deacetoxy-cephalosporin C synthase or expandase. The fungal enzyme has been shown also to catalyze the next reaction in the pathway, the hydroxylation of the methyl group at the 3'-position of the six-membered ring, forming deacetylcephalosporin C. In Streptomycetes this latter enzyme activity is encoded by a separate gene. From deacetylcephalosporin C, Cephalosporin C is formed by acetylation of the 3'-position. The cephamycins are formed from the same compound by several enzymatic steps.

In vivo synthesis of .beta.-lactams and their precursors can be increased by increasing the activity of enzymes involved in .beta.-lactam biosynthetic pathways. This can be achieved by either increasing the amount of enzyme present or by improving the specific activity of the enzyme. However, obtaining enzymes having the desired activity has typically been limited by the availability of spontaneous mutations in enzymes which are active at points in the pathway.

Currently, the cost effectiveness of in vitro synthesis of .beta.-lactam precursors in cell free extracts is poor in comparison to traditional fermentation processes. These in vitro processes are hampered by the limited amounts of enzyme present within the cell, and hence within the cell free extract, and by the presence of inhibitory factors such as proteases and enzyme inhibitors. In addition, the use of fermentable or known .beta.-lactam antibiotics (i.e. can be produced by fermentation of (.beta.-lactam producing) non-rec-DNA microorganisms) is complicated by a) the development of resistance or tolerance to fermentable or known .beta.-lactam antibiotics by bacterial species, and b) the limitations in therapeutic use, such as, an allergy to penicillin. There is therefore, substantial interest in the development of systems which allow for the efficient and cost-effective production of .beta.-lactam antibiotics (i.e. cannot be produced by fermentation of (.beta.-lactam producing) non-rec-DNA microorganisms) and their precursors, both in vivo and in vitro.

Relevant Literature

Van Liempt et al., (J. Biol. Chem. 1989, 264:3680-3684) have shown in Aspergillus nidulans that the ACV condensation is carried out by a large multi-functional enzyme, ACV synthetase. Similar results have been obtained for the Acremonium chrysogenum ACV synthetase by Banko et al., (J. Amer. Chem. Soc. (1987), 109:2858). The gene encoding ACV synthetase (pcbAB) has been located on the genome of A. nidulans (MacCabe et al., EMBO J. (1990), 9:279-287) and Penicillium chrysogenum (EP-A-320272, published Jun. 14, 1989; U.S. Ser. No. 392,119; D. Smith et al., Bio/Technology (1990), 8:39-41). pcbAB is located just upstream of the gene encoding IPNS.

In vitro synthesis of the tripeptide ACV in cell free extracts (Adlington et al., Biochem. J. (1983), 213:573; G. Banko et al., J. Am. Chem. Soc. (1987), 109:2858; Jensen and Westlake, Developments in Industrial Microbiology (1989), 30:113-119; EP-A-280051) has been used to study parameters of the ACV synthetase-reaction and also to study the feasibility of commercial application of in vitro synthesis of .beta.-lactam antibiotics such as compared to traditional fermentation processes these processes are not commercially attractive. (Jensen, supra.). Several inhibitory compounds for the ACV synthetase reaction have been disclosed (Adlington and Banko, supra). It has also been established that the ACV synthetase has a rather narrow substrate specificity. Only a few amino acids can be substituted for the native .alpha.-amino adipic acid, cysteine and valine.

Amplification of antibiotic biosynthetic genes by increased copy number resulting in an increase in the production of an antibiotic has been described by Skatrud et al., Bio/technology (1989), 7:477-485 and U.S. Ser. No. 392,119, supra). Increased cephalosporin production, using the cefEF gene (Skatrud et al., supra) or penicillin, using the pcbC-penDE gene cluster (U.S. Ser. No. 392,119) has been reported. Expression of .beta.-lactam biosynthetic genes, other than the ACV synthetase gene, has been described in Streptomyces lividans. (Chen et al., Bio/technology, (1988) 6:1222-1224). Publications relating to enzymes included in .beta.-lactam biosynthesis and the cloning of genes encoding these enzymes are as follows. The IPNS has been purified and the gene encoding this enzyme, pcbC, has been cloned from various organisms (reviewed in Miller and Ingolia, Molecular Microbiology 1989, 3:689-695; Martin and Liras, Advances in Biochemical Engineering/Biotechnology (1989), 39:153-187).

The enzyme acyltransferase has been purified (Alvarez et al., Antimicrob. Agents Chemother. 1987, 31:1675-1682; EP-A-336446) and the gene encoding this enzyme (penDE) has been cloned (EP-A-336446; U.S. Pat. No. 5,108,918; Veenstra et al., in: C. L. Hershberger, S. W. Queener and G. Hegeman, eds: Genetics and Molecular Biology of Industrial Microorganisms, (1989), pp 262-269; Barredo et al., Gene 1989, 83:291-300). The pcbC and penDE genes are clustered in the genome of Penicillium chrysogenum (B. Diez et al., Mol. Gen. Genet. (1989), 218:572576; Veenstra, supra).

The epimerase has been purified from Streptomyces clavuligerus (Usui and C-A Yu, Biochem. Biophys. Acta (1989), 999:78-85); the presence of this gene on a large DNA fragment was suggested in EP-A-233715. The enzyme expandase has been isolated both from Acremonium chrysogenum (Kupta et al., FEMS Microbiol. Letters (1987), 169:1-6; Dotzlaf and Yeh, J. Bacteriol. (1986), 16:1611-1618) and from Streptomyces clavuligerus (Rollins et al., Can. J. Microbiol. (1988), 34:1196-1202) and Streptomyces lactamdurans (Cortes et al., J. Gen. Microbiol. (1987), 133:3165-3174). The expandase genes have been cloned from both A. chrysogenum (cefEF, Samson et al., Bio/technology (1987), 5:1207-1214) and from Streptomyces clavuligerus (cefE, Kovacevic et al., J. Bacteriol. (1989), 171:754-760).

Methods, and compositions for use therein, are provided for enhanced expression of .beta.-lactam antibiotic biosynthetic genes, leading to increased production of .beta.-lactam antibiotics and precursors thereto. The methods include the steps of stably transforming a host cell with an expression cassette containing at least one DNA sequence encoding an ACV synthetase (ACVS) or a biologically active mutant or ACV synthetase (ACV') and isolating transformants which produce an enhanced amount of ACV synthetase. The expression cassette includes transcriptional and translational initiation and termination regulatory regions, hereinafter defined as promoter, and transcriptional and translational termination regulatory regions, hereinafter defined as terminator, appropriate for the host cell. The promoter may also be heterologous to the open reading frame. The host cell may be a eukaryote or a prokaryote. Also included is the pcbAB gene from P. chrysogenum and A. chrysogenum, constructs and vectors comprising the pcbAB gene or a mutant thereof, and transformed cells comprising the pcbAB. The subject invention finds use particularly in improved production both in vivo and in vitro of fermentable or known and new .beta.-lactam antibiotics and their precursors, particularly antibiotics of the penam and cephem classes.

FIG. 1 shows a schematic of the distribution of .beta.-lactam producing microorganisms.

FIG. 2 shows a schematic representation of the biosynthetic pathways of the penicillins, cephalosporins and cephamycins.

FIG. 3 shows a restriction site and functional map of the chromosomal region containing the ACV synthetase gene in P. chrysogenum. Probes that have been used for Northern hybridizations are indicated. The region containing the pcbAB gene is shaded. S=SalI.

FIGS. 4A-4D show a detailed physical map of the region encoding the ACV synthetase gene in P. chrysogenum, including the sequencing strategy.

FIG. 5 shows a schematic representation of the cluster of penicillin biosynthetic genes present in the genome of P. chrysogenum.

FIG. 6 shows a restriction site and functional map of construct pPCV01.

FIG. 7 shows a restriction site and functional map of construct pPCV02.

FIG. 8 shows a restriction site and functional map of construct pPCV03.

FIG. 9 shows a restriction site and functional map of the E. coli vector pMAtrp.

FIG. 10 shows a restriction site and functional map of pMA-ACV synthetase.

FIG. 11 shows a restriction site and functional map of pSLACV-01.

FIG. 12A shows a restriction site and functional map of pSLACV-03A.

FIG. 12B shows a restriction site and functional map of pSLACV-03B.

FIGS. 13A-13C show a scheme that shows the sequence homology between domains I, II, and III (SEQ ID NO: 5, 6, and 7) found within the ACVS protein and Gramicidin and Tyrocidin Synthetases (SEQ ID NO: 8 and 9).

FIG. 14 shows a scheme that shows the sequence homology between the ACVS protein (SEQ ID NO: 10) and the thioesterase domain of rat fatty acid synthetase (SEQ ID NO: 11).

FIG. 15 shows a scheme listing the domains and subdomains within the ACVS protein.

FIG. 16 is a restriction site and functional map of the chromosomal region encoding the ACVS gene in A. chrysogenum. Arrows indicate the positions of the IPNS-(pcbC) and ACVS-(pcbAB) genes. The position of phages which have been isolated from a gene library and which contain part of the region are indicated.

FIGS. 17A-17B is a restriction site and functional map of the chromosomal region encoding the ACVS gene in A. chrysogenum. Probes that have been used in Northern Blot hybridizations, and the results obtained, are indicated.

FIGS. 18A-18H show the similarity between the deduced amino acid sequence from the ACVS genes from P. chrysogenum (SEQ ID NO: 2) and A. chrysogenum (SEQ ID NO: 4).

In accordance with the subject invention, methods and compositions are provided which allow for increased, cost-effective production of fermentable or known and new .beta.-lactam antibiotics and their precursors both in vivo and in vitro. The method includes the steps of transforming a host cell using an expression cassette which includes in the 5'-3' direction of transcription, a promoter, an open reading frame encoding an ACVS or ACVS', optionally having a signal sequence for secretion recognized by the host cell; and a terminator. The promoter and terminator are functional in the host cell and provide for efficient expression of ACVS or ACVS' without undesirable effects on the viability and proliferation of the host cell. Transcription and translation of the ACV synthetase DNA sequence will augment levels of ACV synthetase already present in the cell. Transcription and translation of the ACVS' DNA sequence will provide for expression of ACVS' in the host cell, which may have novel or enhanced properties as compared to the native enzyme.

Optionally, the expression cassette may include a transcription regulating sequence which is not subject to repression by substances present in the growth medium. The expression systems may be used to prepare .beta.-lactam antibiotics directly or they may be used to prepare cell free extracts containing large quantities of ACVS or ACVS' for in vitro preparation of said antibiotics. Alternatively, the expression hosts may be used as a source of large quantities of enzyme which can be purified and used in in vitro systems.

In currently used systems, the first step in the in vitro synthesis of new .beta.-lactams or their precursors has been the chemical synthesis of the desired new tripeptide; these modified tripeptides are subsequently cyclised by the action of the IPNS enzyme. The availability of ACVS' offers the advantage that the laborious chemical synthesis of new tripeptides can be avoided; the substantially more efficient and cost effective enzymatic synthesis of the desired tripeptides can be used instead. Additionally, by avoiding the use of harmful chemicals, solvents and the like, the subject invention causes less environmental problems when carried out at an industrial scale than do traditional methods of synthesis. Recognition of some of altered tripeptides as a substrate by IPNS, however, may in turn require the design and use of a modified IPNS enzyme.

Enhanced production of ACV synthetase is achieved by the introduction of extra copies of the gene encoding ACV synthetase (pcbAB gene) into a host cell by transformation: protoplasts are mixed with DNA constructs that contain at least one copy of the gene to be amplified linked to a selectable marker. By choosing the appropriate conditions, some protoplasts will take up the DNA construct which is thereafter stably maintained because the construct has become integrated into the host cell genome. Transformed cells can be selected from the background of so-called "non-transformed" cells by screening for expression of the selectable marker. Amplification of the pcbAB gene, which may be used to produce cephalosporin, penicillin, and cephamycin thus can be expected to result in an increase in intracellular enzyme activity, which in turn will be accompanied by an increase in production of the desired antibiotics. Since ACV synthetase forms part of the biosynthetic pathway of both the penam and the cephem classes of .beta.-lactam anti-biotics, increased production of this enzyme has several applications. Production of ACVS' is achieved by the introduction of at least one copy of a mutant gene encoding ACV synthetase (pcbAB' gene) into a host cell by transformation, as described hereinabove.

Surprisingly, the data presented in the instant invention indicate that the coding region P. chrysogenum pcbAB gene is 11,337 nucleotides long and encodes a protein of 413 kDa. Based on the results obtained for A. nidulans (250 kDa enzyme: Van Liempt et al.) and P. chrysogenum (gene present on 8.times.10.sup.3 nucleotide DNA fragment: EP-A-320272) a gene with a size of at most 8.times.10.sup.3 nucleotides would be predicted. Moreover, these data obtained still allowed for the ACV synthetase activity to be encoded in more than one gene. Besides that, a significant amount of ACV synthetase can now be achieved by using the manipulated pcbAB genes of the present invention.

Only now it can be envisaged that all catalytic activities required for tripeptide formation (i.e. activation of three amino acids, racemization of valine, formation of dipeptide AC and tripeptide ACV, release of ACV) can indeed be present in one single polypeptide chain. ACVS this is a multifunctional enzyme. Multifunctional enzymes are defined herein to be enzymes that consist of one single polypeptide chain and that carry within their structure the ability to perform more than one catalytic reaction. In contrast, in the case of the biosynthesis of Gramicidin S, a peptide antibiotic consisting of two identical units of five amino acids, at least two, and probably three polypeptide chains are involved (e.g. von Dohren, 1982, In: Peptide Antibiotics, W. de Gruyter & Co., Berlin. pp 169-182; Kratzschmar et al., Jour. of Bacteriol. (1989) 171, 5422-5429).

In vitro synthesis of the ACV tripeptide has been described previously (Adlington and Banko, (supra). However, the only available systems up to now have been preparations comprising cell-free extracts of various organisms that possess ACV synthetase activity, followed by an in vitro reaction. The availability of an efficient expression system and the accompanying constructs, designed for high expression of the gene in suitable hosts is highly advantageous. It allows for the design of in vitro systems which do not have the disadvantages of a limited amount of enzyme present within the cell and hence within the cell free extract, or the presence of an excess of negative factors such as proteases or inhibitors or other similar effects. Increased productivity thus is obtained as a result of the enzyme being present in large quantities in the cell-free extracts prepared from the transformed host organisms as compared to the organisms used by for example Adlington and Banko, supra. Alternatively, large quantities of purified enzyme can be obtained and subsequently incubated in systems devoid of negative components.

For preparation of ACV and secondary metabolites, or for preparation of ACV synthetase by recombinant methods, genes encoding ACV synthetase (the pcbAB gene) may be obtained from a variety of sources including Penicillium chrysogenum, Acremonium chrysogenum, Aspergillus nidulans, Flavobacterium or Streptomycetes. The structural genes may be isolated by various techniques. These include isolating mRNA from a host organism which codes for the polypeptide of interest, the mRNA reverse transcribed, the resulting single stranded (ss) DNA used as a template to prepare double stranded (ds) DNA and the dsDNA gene isolated.

Another technique is to isolate the chromosomal DNA from the source organism of interest and, using a probe, appropriately degenerate, comprising a region of the most conserved sequences in the gene of interest, identify sequences encoding ACV synthetase in the genome. The probe can be considerably shorter than the entire sequence, but should be at least 10, preferably at least 14, more preferably at least 20 nucleotides in length. Longer nucleotides are also useful, up to about 100 nucleotides of the gene of interest. Both DNA and RNA probes can be used.

In use, the probe is typically labeled in a detectable manner (for example with .sup.32 P or biotinylated nucleotides) and are incubated with ss DNA or RNA from the organism in which the gene is being sought after separation and/or immobilization of the ss or ds DNA, typically using nitrocellulose paper or nylon membranes. Hybridization is detected by means of autoradiography. Hybridization techniques suitable for use with oligonucleotides are well known to those skilled in the art. Although probes are normally used with a detectable label that allows for easy identification, unlabeled oligonucleotides are also useful, both as precursors of labeled probes and for use in methods that provide for direct detection of DNA or DNA/RNA. Accordingly, the term "oligonucleotide" refers to both labeled and unlabeled forms.

The gene encoding the ACVS can also be isolated from other organisms. For the gene encoding the IPNS, it has been shown (See for example, Ingolia and Queener, Medicinal Research Reviews (1989) 9:245-264) that genes isolated from different organisms show a high degree of homology, ranging from about 70% on the DNA level if two fungal or two Streptomyces genes are compared to 60% or more if a fungal and a Streptomycete gene are compared. Homologies on the protein level are 75% and 54%, respectively. Despite the differences on the DNA and protein level, all IPNS proteins catalyse the same reaction in a similar fashion. Therefore, ACVS sequences and enzymes can be identified that share a minimal homology of about 60% on the DNA level or 50% on the protein level.

Sequences that are at least substantially identical to the sequence given in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ. ID. NO. 4 are of particular interest. SEQ ID NO: 1 and SEQ ID NO: 2 show a nucleotide sequence and deduced amino acid sequence respectively of the P. chrysogenum ACV synthetase gene. SEQ ID NO: 3 AND SEQ ID NO: 4 show the nucleotide sequence and deduced amino acid sequence of the A. chrysogenum ACV synthetase gene respectively. By "substantially identical" is intended sequences which can include conservative mutations, where the sequence encodes the same amino acid sequence, but may have as many as 30% different nucleic acid bases, more usually not more than 10% different bases, or mutations which are non-conservative, where fewer than about 10%, more usually fewer than about 5%, and preferably not more than 1% of the encoded amino acids are substituted or deleted, and there are fewer than 5% of inserted amino acids, where the percentage is based on the number of naturally occurring amino acids in the native enzyme. The degree of change which is acceptable can be determined by assessing the enzymatic activity of the expression product of the isolated gene, where the expression product should retain the ability to catalyze the formation of ACV from its constituting amino acids.

ACV synthetase genes can be isolated by using, for example, the sequence as given in SEQ ID NO: 1, or parts thereof as a probe in heterologous hybridization experiments. These probes can be restriction fragments derived from the ACVS encoding DNA isolated from P. chrysogenum; such restriction fragments can easily be selected and isolated using the restriction map as given in FIG. 4. Alternatively, synthetic oligonucleotide probes can be made based on the data given in SEQ ID NO: 1. In still another variation, oligonucleotides can be designed, based on the data in SEQ ID NO: 1, and used in a PCR reaction to generate a larger probe fragment. In this way, for example, the genes of Acremonium chrysogenum and Aspergillus nidulans can be readily isolated; also the genes from Streptomycetes can be isolated using less stringent hybridization conditions. The genes that are isolated in this fashion are also of interest. This procedure is exemplified by the isolation of the pcbAB gene from A. chrysogenum. The data obtained for this gene in their turn can be used for the gene-isolation procedure as described above. For example, using the data of the present invention, regions with a high homology can be identified, such as the domains of FIGS. 15 and 18 (SEQ ID NO: 12 and 13), and selected for use as a highly specific probe in the isolation of pcbAB genes from more distantly related organisms.

Alternatively, the DNA sequences encoding the ACV synthetase can be synthesized using conventional techniques such as PCR (Polymerase Chain Reactions) or by synthesis of overlapping single strands which may be ligated together to define the desired coding sequences. The termini can be designed to provide restriction sites or one or both termini may be blunt-ended for ligation to complementary ends of an expression vector. For expression of the sequence an initial methionine is provided. Expression vectors are generally available and are amply described in the literature.

For preparation of ACVS' and modified secondary metabolites, or for preparation of ACVS' by recombinant methods, genes encoding ACVS' may be obtained from spontaneous pcbAB' mutant from a variety of sources including Penicillium chrysogenum, Acremonium chrysogenum, Aspergillus nidulans, or from Flavobacterium or the Streptomycetes. Also, sequences that encode biologically active mutant ACV synthetase can be derived from sequences that are at least substantially identical to the sequence of a fermentable or known ACV synthetase or from spontaneous mutant pcbAB alleles. Mutant sequences can be "derived" by a variety of genetic and recombinant DNA techniques, such as in vitro mutagenesis and homologous recombination. The gene of interest encodes biologically active mutant ACV synthetase or a biologically active portion of ACV synthetase or a mutant thereof. A spontaneous mutant gene or a wild type gene (from which a mutant structural gene subsequently can be derived) can be isolated by various techniques using host organisms which are ACV synthetase mutants or wild type. These techniques have been described hereinabove.

Once the ACV synthetase DNA is obtained, mutations can be introduced by a number of in vitro mutagenesis techniques, either random or site-directed. Precise changes to the amino acid sequence are obtained by site-directed mutagenesis techniques which use synthetic oligonucleotides complementary to the region to be modified, except for the desired nucleotide(s) change. Regions are precisely deleted by "loop-out" mutagenesis techniques using synthetic oligonucleotides. Precise insertions are obtained using synthetic oligonucleotides to generate appropriate restriction sites. A series of mutations localized to a region of the ACV synthetase-encoding DNA sequence on a plasmid are generated by in vitro mutagenesis techniques and subsequently identified by cloning and sequencing the isolated mutagenized plasmids.

Once specific mutations have been generated and isolated to individual plasmids, "cassette" mutagenesis is applied to generate a series of new mutants by combining mutations into the same plasmid using appropriate restriction sites. Alternatively, mutagenesis using two or more oligonucleotides directed to different regions of the gene yields mutants with the desired multiple mutations.

Mutant proteins are also generated by the insertion, addition, or substitution of coding sequences from other proteins to ACV synthetase coding sequences. The source proteins may be ACV synthetases from other strains or species or may be unrelated proteins. Such amino acid sequences introduced into ACV synthetase will impart desirable properties or characteristics which originally belonged to the source protein.

Desirable properties are useful properties for activities and functions which include and are not limited to protein stability, secretion, isolation, purification, increased enzymatic activity, resistance to inhibitors, proteases and denaturants, solubility, and modified substrate specificity. Source proteins include those proteins involved in amino acid activation, amino acid racemization, peptide formation, thioesterase activity and the like. Preferred proteins include proteins involved in the biosynthesis of other antibiotic peptides, such as tyrocidin synthetase, gramicidin synthetase or proteins having enzymatic activities similar to those of ACVS, such as long chain fatty acid synthetases.

Although any region of the protein may be mutated, regions of the ACV synthetase protein which serve as candidates for mutagenesis are defined in order to minimize extensive screening of randomly generated mutants. The nucleotide and deduced amino acid sequences of ACV synthetase provided are a powerful tool with which to delineate such regions. Sequence homology comparisons, at both the DNA and amino acid level, identify protein regions with known function or structure.

Hydrophobicity profiles or related biophysical profiles, based on the amino acid sequence, with subsequent comparisons to profiles of other proteins may be used to identify additional protein regions of known structure and function. The finding of sequence or profile homologies indicates that the protein regions share a similar function, activity or enzymatic mechanism. Hydrophobicity or secondary structural profiles can indicate domain "linking" regions, "hinge" regions or "loops" which are candidates for restriction site insertions to generate domain "cassettes."

Regions for mutagenesis or replacement are also defined by correlation of a genetic map of ACV synthetase mutants alleles with a physical map, either at the restriction site or sequence level. Preferred regions for mutagenesis, either site-directed or via substitution include the functional domains and sub-domains of ACV synthetase as provided in FIGS. 13 (SEQ ID NO: 5, 6, and 7), 14 (SEQ ID NO: 10), and 15.

Mutant proteins also include functional proteins formed by various combinations or quarternery assemblies of discrete polypeptides. The polypeptides contain one or more enzymatic activities. Preferably the polypeptides are from the domains of ACV synthetase as defined in FIGS. 13 (SEQ ID NO: 5, 6, and 7), 14 (SEQ ID NO: 10), and 15. Polypeptides from regions of other proteins, as defined in the preceding sections, may also be combined with one or more ACV synthetase polypeptides in the same discrete fashion.

Once the desired DNA sequence has been obtained, it may be manipulated in a variety of ways to provide for expression. It is highly desirable that modifications of the nucleotide sequence, other than the modifications which result in the desired mutation(s), retain the three dimensional structure of the expression product, particularly that portion of the structure which may be responsible for the enzymatic activity of the resulting enzyme. Convenient restriction sites may be designed into the DNA sequence of interest; when possible the restriction site(s) leaves the amino acid sequence of the expression product unaltered. However, in some cases, incorporation of new restriction sites may yield an altered amino acid sequence.

Where the gene encoding ACVS or ACVS' is to be expressed in a host which recognizes the wild type promoter and terminator of the gene of interest, the entire gene with its wild type 5' and 3'-regulatory regions may be introduced into an appropriate expression vector. Where said gene is to be expressed in a host cell which does not recognize the naturally occurring wild type promoter and terminator, further manipulation may be required. Conveniently, a variety of 3'-transcriptional regulatory regions are known and may be inserted downstream from the stop codons. The non-coding 5'-region upstream from a structural gene may be removed by endonuclease restriction, Bal31 restriction or the like. Alternatively, where a convenient restriction site is present near the 5'-terminus of the structural gene, the structural gene may be restricted and an adaptor employed for linking the structural gene to the promoter region, where the adapter provides for the lost nucleotides of the structural gene.

The biosynthesis of .beta.-lactam antibiotics in general, and of penicillin in particular, is subject to glucose repression (Martin and Liras, TIBS (1985), 3:39-44). This repression by glucose has been unequivocally established for the formation of the tripeptide by the ACV synthetase and for the activity of IPNS (Revilla et al., J. Bacteriol. (1986), 168:947-952). It is not known at which stage of expression repression by glucose is exerted; this can, for example, be at the transcriptional or at the translational level. If the former applies, constitutive expression of the pcbAB gene will result in an increase in enzyme activity followed by an increase in the production of ACV, and subsequently of the .beta.-lactam antibiotic derived from it.

Increased expression of the gene in .beta.-lactam producing bacterial or fungal hosts therefore can be obtained by changing the regulation of gene expression. Thus, the transcriptional regulatory region is preferably one which is not subject to repression by, for example, presence or absence of nutrients such as glucose, or expression products in the growth medium. The transcriptional regulatory region may additionally include regulatory sequences which terminate transcription and which provide sequences or structures which inhibit degradation of the mRNA.

Exemplary of changing the regulation of expression is modification of the pcbAB gene. The native sequence generally is replaced by a region which is functional in either the native or heterologous host and wherein expression is either inducible or constitutive. For example, the regulatory sequences can be changed by replacing the pcbAB promoter, which is strongly repressed by glucose, with a promoter which is insensitive to glucose or even is stimulated by it. In the latter situation, antibiotic will be produced during the early stages of the fermentation, when biomass is formed in high-glucose conditions. This modification may further increase the yield of the antibiotic during the fermentation. Expression of the gene may also be brought under control of other promoters, either promoters for which expression can be regulated in a different fashion or promoters that are expressed constitutively.

Illustrative promoters which find use in the subject invention, include, for prokaryotic cells, the lac, trp (Sommerville, Biotechnology and Genetic Engineering Reviews (1988), 6:1-41) or tac promoters of E. coli, or aph or tyrosine synthetase promoters of S. lividans. For filamentous fungi, illustrative promoters include the glyceraldehyde phosphate dehydrogenase (gapdh) promoter, the phosphoglycerate kinase (pgk) promoter, the nitrate reductase promoter and the like. A preferred embodiment of the present invention which is exemplified herein is the use of the pgk promoter of P. chrysogenum, which has been described in U.S. Pat. No. 5,108,918.

In eukaryotic cells, a terminator provides for proper maturation of the mRNA transcript and are necessary for efficient expression. In general, it is preferable to use the native polyadenylation signal associated with the gene of interest. In both eukaryotic and prokaryotic systems, termination regions can also contain sequences or structures which increase the stability of the mRNA species and allow for higher expression. Several examples of prokaryotic sequences are known, for example the trp terminator, the gene 32 (T4) terminator, or synthetic terminators which are similar in sequence to gene 32. For eukaryotes, terminators can be used that are isolated from cloned genes. For yeast, the terminator of the CYC1 gene or the actin gene can be used for example. For filamentous fungi, the terminators isolated from for example the trpC gene, the pgk gene or the penDE gene are useful.

Where it is desired to isolate the ACVS, secretion of the enzyme into the media or into the periplasmic space of the transformed microbial host can improve the efficiency of the isolation procedure. Secretion can be accomplished by using DNA expression cassettes as described herein, which further comprise a signal sequence (secretory leader) that is functional in the host cell. The signal sequence will be heterologous to the ACV synthetase gene and may be homologous or heterologous to the host cell, or may be a synthetic signal sequence. The signal sequence provides a peptide sequence that is in-frame with the enzyme sequence, and may be located 5' or 3' to the ACV synthetase sequence. The signal sequence can also be provided by joining, in-frame, an open reading frame of a protein that is secreted by the host cell and the open reading frame of the ACV synthetase. Illustrative secretory leaders include the secretory leaders of penicillinase, .alpha.-factor, immunoglobulin, T-cell receptors, outer membrane proteins, glucoamylase, fungal amylase and the like. By fusion in proper reading frame, the mature polypeptide may be secreted into the medium.

The promoter and terminator may be homologous (derived from the original host), or heterologous (derived from a foreign source or synthetic DNA sequences). The expression cassette thus may be wholly or partially derived from fermentable or known sources, and either wholly or partially derived from sources homologous to the host cell, or heterologous to the host cell. The various DNA constructs (DNA sequences, vectors, plasmids, expression cassettes) of the invention are isolated and/or purified, or synthesized and thus are not "naturally occurring."

The expression cassette may be included within a replication system for episomal maintenance in an appropriate cellular host or may be provided without a replication system, where it may become integrated into the host genome. Integration may be stimulated in yeast and bacteria by the inclusion of (parts of) ribosomal RNA genes or other yeast genes and subsequin thesearization in these genes.

The DNA may be introduced into the host cell in accordance with known techniques, such as transformation DNA, transfection by contacting the cells with a virus, microinjection of the DNA into cells, biolistic transformation and the like. Both prokaryotic and eukaryotic hosts may be employed, which may include bacteria and fungi, particularly filamentous fungi. Prokaryotic cells include Escherichia coli, Flavobacterium and Streptomyces spp. Eukaryotic cells include filamentous fungi such as Penicillium chrysogenum, Acremonium chrysogenum, Aspergillus nidulans, niger and oryzae; and yeasts such as Saccharomyces cerevisiae, Kluyveromyces lactis. Preferred host cells include P. chrysogenum, A. chrysogenum, A. nidulans. Replacement of the native ACVS gene by the mutant gene may result in in vivo synthesis of .beta.-lactam derivatives. The presence of a wild type gene in these organisms indicates that they allow for efficient expression of the wild type ACVS gene and hence they are inferred to also express the mutant gene without too many difficulties.

Other preferred hosts include the Streptomycetes. Several Streptomycetes also synthesize .beta.-lactams (see FIG. 1). They can be used for the same reasons as the above-mentioned fungi. On the other hand, a Streptomycete such as S. lividans is very amenable to genetic manipulation (Hopwood et al., (1985) Genetic Manipulation of Streptomyces: a Laboratory Manual, The John Innes Foundation, Norwich, U.K.). Moreover, it has been disclosed that .beta.-lactam biosynthetic genes are actively expressed in S. lividans (Chen et al., supra). Therefore, S. lividans is a preferred host for expression of the gene, for isolation of the mutant protein, or to use for preparation of cell-free extracts. Expression of foreign genes in E. coli is very well known in the art. One disadvantage of this organism may be that the ACVS could be too large for production of active enzyme; inclusion bodies may be formed or (over) expression may be harmful to the cell. Yeasts, like S. cerevisiae or K. lactis are examples of frequently used hosts for expression of heterologous proteins.

Transformed host cells subsequently are grown under conditions that are suitable for the antibiotic production. These conditions have been amply described in the literature (Luengo et al., J. Gen. Microbiol. (1979), 115:207-211; Barredo et al., Antimicrob. Agents Chemother. (1988), 32:1061-1067; Queener and Schwartz, In: Rose AH (ed) Secondary Products of Metabolism, Academic Press, London (1979): 35-122; Queener et al., In: Biotechnology of Industrial Antibiotics, E. J. Candamme (ed) Marcel Dekker Inc., New York, Basel (1984): 141-170). Generally media for antibiotic production contain either a slow fermentable carbon source, like lactose, or are limited in the carbon source, e.g. glucose, in a so called fed-batch fermentation procedure. For the production of penicillin G or V the appropriate side chain precursor, as has been described hereinbefore, is added to the medium; for the production of cephalosporin the medium may be supplemented with DL methionine. Generally, Corn Steep Liquor or related compounds are supplied as a nitrogen source.

For prokaryotic hosts, the culture conditions are known in the art (e.g. Maniatis et al., Molecular Cloning, a Laboratory Manual, Cold Spring Harbor Laboratory (First edition, 1982 or second edition, 1989) and Hopwood (supra)); in this case it is advisable to maintain selective pressure by addition to the culture medium of the antibiotic that is used as a selective agent. The secondary metabolite is subsequently isolated from the cultured cells.

ACVS or ACVS' can be purified from the host cells that have been grown under these conditions or, alternatively, using the conditions that are most suited for the expression of the promoter used; preferably, cells are harvested early in the fermentation (2-4 days) for this purpose. For the isolation of ACVS or ACVS'. the procedures as described in Van Liempt et al. (supra) or Banko et al. (supra) can be used. For isolation of ACVS or ACVS' from transformed E. coli, the cells are grown overnight in e.g. TY or LB medium (Maniatis et al., supra) and can be lysed by treatment with lysozyme. Protease inhibitors, such as PMSF or .alpha.-2 macroglobulin can be included in the buffers used, in order to avoid degradation of the ACVS or ACVS' to be purified.

Cell-free extracts can be prepared from the various cultures using the procedures as they are described in Adlington et al. (supra), Banko et al. (supra), Jensen et al. (supra), Zhang an Demain (Biochem. Biophys. Res. Comm. (1990) 196:1145-1152); Jhang et al. (FEMS Microbiol. Lett. (1989) 57:145-150). In general, cells are harvested, washed in suitable buffer and disrupted in a French press, by grinding in liquid nitrogen or by sonication. The presence of glycerol (40-50%) as a stabilizer is crucial, both for isolation of large quantities of the enzyme and for isolation of an active cell-free extract.

The pcbAB genes of the present invention, and more particularly the DNA constructs derived thereof, can be used to transform suitable host cells, in order to increase the fermentable or known ACV synthetase activity present in the host cells. Cells with an increased level of ACV synthetase find their use in the production of increased amounts of .beta.-lactam antibiotics. This increased production can be the result of the increased ACV synthetase activity by itself, or in combination with an increased activity of other enzymes, known in the art. For example, host cells that have been transformed with the pcbAB gene can be retransformed with a construct containing other .beta.-lactam-biosynthetic genes, such as the construct pGJ02A that has been described before (U.S. Ser. No. 392,119). In this way the entire pathway leading to penicillin G or V formation can be amplified. Combined use of these two constructs can also confer the ability to synthesize penicillin to host organisms that by nature lack this ability.

Cells with increased ACV synthetase activity moreover find their use in the isolation of increased quantities of the ACV synthetase enzyme; the isolated enzyme can be used, for example, in in vitro reactions or for the further unraveling of the reaction mechanism.

Cells with increased ACV synthetase activity also find their use in the preparation of cell-free extracts with increased ACV synthetase activity, leading to improved yields--and hence an improved economy--of in vitro synthesis of .beta.-lactam antibiotics and their precursors.

Amplification of the mutant pcbAB gene, particularly one with a phenotype of increased enzyme activity, will result in a further enhancement in intracellular enzyme activity, which in turn may be accompanied by an increase in productivity of the antibiotics of both the cephalosporin and penicillin pathways.

Expression of the mutant pcbAB gene, particularly the one with a phenotype of altered substrate specificity, will result in the synthesis of non-natural .beta.-lactam antibiotics and their precursors.

Cells with increased ACVS' activity also find their use in the isolation of ACVS' enzyme or in the preparation of cell-free extracts with ACVS' activity.

The following examples are offered by way of illustration and not by way of limitation.

General Methods

In all examples described herein, the experimental techniques mentioned are known in the art: these have been described e.g. in T. Maniatis et al., supra.

Deposits

The following organisms have been deposited with Centraal Bureau voor Schimmelcultures (CBS), Oosterstraat 1, 3742 SK Baarn, Netherlands:

E. coli WK6 containing plasmid pPCV01, Accession No. CBS 142.90, was deposited Feb. 28, 1990;

Cosmid HM193, Accession No. CBS 179.89, was deposited on Apr. 3, 1989 as a DNA sample (cosmid clone in E. coli unstable);

P. chrysogenum strain Wisconsin 54-1255 npe5 an ACV synthetase gene mutation, Accession No. CBS 178.89, was deposited on Apr. 3, 1989.

A. Isolation of the pcbAB gene

Chromosomal DNA of P. chrysogenum was isolated and treated as described in U.S. Pat. No. 5,108,918. After partial digestion of the DNA, partials of 20-35 kb in size were isolated and ligated into the BamHI digested cosmid vector pPS07 (see EP-A-0260762) using standard protocols (e.g. Maniatis et al., supra). The ligation mixture was packaed in vitro and the phage lysate was transduced into E. coli HB101 (ATCC 33694), again using methods known in the art. Fresh transductant colonies were grown in 10 ml of L-broth (per litre 10 g of NaCl, 10 g of Bacto-tryptone and 5 g of Bacto-Yeast Extract) under ampicillin selection. Cosmid DNA was isolated and the presence of insert DNA was checked by Eco RI digestion. Insertion containing cosmids were stored in microtiterplates at -20.degree. C.

To isolate cosmid clones containing the IPNS gene and a large amount of flanking regions, the cosmid library was screened for clones containing the IPNS gene. A cosmid library was used, as opposed to a phage lambda library, because cosmid vectors are known in the art to contain larger inserts (20-40 kb) than lambda vectors (9-23 kb). As probes were used two oligonucleotides based on the N-terminal amino acid sequence of the P. chrysogenum IPNS gene: 5'-TCC GGC GAT AAC ATG GAG-3' (SEQ ID NO: 22) and 5'-TCC GGC GAT AAT ATG GAG-3' (SEQ ID NO: 23). The probes were labelled using standard techniques known in the art (e.g. Maniatis et al., supra).

Cosmids hybridizing to the probes were isolated, and the presence of the IPNS gene was confirmed by subcloning, sequence analysis and comparison of the data to the sequence of the IPNS gene described in L. Carr et al., Gene, (1986) 48:57-266).

Cosmid HM193 contains one DNA fragment so identified. This cosmid clone contains about 23 kb of DNA upstream of the IPNS gene. Using parts of cosmid clone HM193 as a probe, cosmid clones containing similar or overlapping inserts have been isolated, using techniques known in the art. The presence of the pcbAB gene on the DNA fragments has been demonstrated in various ways. The DNA fragments were able to complement a mutation in the gene encoding ACV synthetase, which is present in the strain Wisconsin 54-1255 npe5, deposited as CBS 178.89. This is a mutant ACV synthetase-negative P. chrysogenum strain derived from Wis54-1255. Restoration of penicillin production by complementation was accompanied by the reappearance of in vitro ACV synthetase activity in cell free extracts. Moreover, restoration of penicillin production was also accompanied by reappearance of a large protein on SDS-PAGE gels.

B. Localization of the pcbAB gene

Northern hybridizations were performed using mRNA that was isolated from penicillin-producing cultures as described in U.S. Pat. No. 5,108,918. The subcloned SalI fragments indicated in FIG. 3 were used as probes. Using probes I, II, III and IV a large mRNA (.gtoreq.10.times.10.sup.3 nucleotides) segment was detected in the Northern blot hybridizations. Probe V detected the mRNAs of the pcbC and penDE genes (about 1.5.times.103 nucleotides). Using smaller probes (A-D and E-H in FIG. 4), the positions of the putative 5'- and 3'-ends of the gene were located. The gene encoding the ACV synthetase is present on the chromosome of P. chrysogenum as indicated by the shaded region in the schematic of FIG. 3.

C. Polarity of the gene

The direction of transcription was determined by Northern hybridization of mRNA of P. chrysogenum using as a probe the following synthetic oligonucleotides that have been designed based on the nucleotide sequence surrounding the two HindIII sites located within the ACVS coding region (FIG. 4).

Only probes AB1549 and AB1550 hybridized to the ACV synthetase mRNA and the deduced direction of transcription is indicated in FIG. 5. The direction of transcription of the ACV synthetase gene is in the opposite direction to the genes encoding IPNS and AT.

D. Determination of the nucleotide sequence

The nucleotide sequence of a DNA fragment contained in cosmid HM193 containing the ACV synthetase gene was determined by the dideoxy method (Sanger et al., Proc. Natl. Acad. Sci. U.S.A. (1977) 74:5463-5467) using the Sequenase system 2.0 (U.S. Biochemicals, Cleveland, Ohio). Double sequencing reactions with dGTP and dITP were used in some clones to avoid errors (Barnes et al., (1983) Methods in Enzymology 101, 98-122). The sequencing strategy is given in FIGS. 4A-4D. The nucleotide sequence of the 12,364 nucleotide DNA fragment is given in sequence 1 (SEQ ID NO: 1). In this sequence a long open reading frame (ORF) of 11,337 nucleotides was found from which a protein sequence (SEQ ID NO: 2) of 3778 amino acids was deduced.

E. Determination of partial protein sequence of ACV Synthetase

To further confirm that the gene cloned is indeed the gene encoding the P. chrysogenum ACV Synthetase, amino acid sequences have been obtained from ACV synthetase that has been purified from Aspergillus nidulans. The similarity between protein and nucleotide sequence data confirm the identity of the cloned gene.

ACV Synthetase was purified from A. nidulans, strain G-69, as has been described in Van Liempt et al., (supra).

The enzyme containing fractions from the DEAE column were applied to a Mono Q column on a FPLC apparatus (Pharmacia). ACV synthetase was eluted using a 0-300 mM NaCl gradient in Tris/HCl buffer (pH 7.5). The peak fraction, having a protein concentration of 0.5 mg/ml was shown to contain almost pure (over 90%) ACV synthetase; this was demonstrated by SDS-PAGE.

For digestion with protease, 1.25 ml (0.625 .mu.g) of ACV synthetase from the Mono Q fraction was incubated with 62.5 .mu.l (6.3 .mu.g) of Subtilisin (Sigma) for 60 min. at room temperature. The reaction was terminated by the addition of trichloroacetic acid (10% final concentration). The precipitated protein was recovered by centrifugation, dissolved in approximately 200 .mu.l of Laemmli sample buffer, and the mixture was neutralized by the addition of 4M Tris. The protein was dissolved and incubated for 5 min. at 95.degree. C.

A slab gel of 140.times.170.times.1.5 mm of polyacrylamide (separating gel 5% T), with a 3% stacking gel (Laemmli) was allowed to polymerize overnight at 4.degree. C. The digested protein was applied in several slots, and electrophoresis was carried out with 0.02% thioglycolic acid in the upper buffer compartment. After the Bromophenol Blue marker had migrated up to 70% of the gel length, the electrophoresis was terminated and the proteins were transferred electrophoretically onto a PVDF-membrane (Immobilon) in a semidry blotting apparatus (Sartorius). The transfer buffer was 25 mM Tris/HCl (pH 8.5), 0.5 mM dithioerythritol.

After transfer (approximately 2 hrs.) the membrane was washed with water, stained in 0.5% Coomassie R 250, 50% Methanol for 5 min., destained in 50% Methanol, 10% Acetic Acid, washed with water and air dried.

From the complex pattern of protein bands present on the membrane, the bands that were the most pronounced and least contaminated with other nearby bands were excised. The amino acid sequence of the peptides in the excised bands was determined using a gas-phase sequenator (Applied Biosystems model 470a). The following sequence was determined (in this notation amino acids separated by a slash indicates ambiguity of interpretation at this position while an amino acid in parentheses indicates uncertainty in the interpretation; Xxx indicates the presence of an unidentified amino acid): Phe Val Tyr Gln Phe Leu Lys Asn Met Gly Asp/Arg Ser Gly/Trp Ala Asp/Tyr Asp/Val Met Gln Xxx Val (Thr) (Asp/Arg) Tyr Leu Asn (Ala Thr) Ala Xxx (Glu) (Leu/Ser Asp/Gly Lys Ala) Leu Pro Ile Gln (Thr/Gln His/Gln Phe)

F. Comparison of protein and nucleotide sequences

The amino acid sequences from Example 1E (A. nidulans) (SEQ ID NO: 18, 19, and 20) were compared with the deduced amino acid sequence from Example 1D (P. chrysogenum), which is shown in SEQ ID NO: 2. For this comparison the MicroGenie.TM. 6.0 program (Beckman) was used. ##STR1##

The degree of homology found between A. nidulans and P. chrysogenum varies between 50 and 61%. This is very similar to the degree of homology between the IPNS proteins derived from both organisms (e.g. G. Cohen et al., 1990, Trends in Biotechnology 8:105-111); hence the protein data confirm the conclusion that the gene cloned is indeed the P. chrysogenum ACV synthetase gene.

G. Identification of distinct domains in the ACVS enzyme which are used to obtain ACVS' enzyme

From the nucleotide sequence of the pcbAB gene an amino acid sequence has been deduced, as indicated in SEQ ID NO: 2. Upon matrix comparison of this protein sequence with itself, three distinct regions of homology are found: these regions are defined herein as domains. These domains are located between amino acid 301 and 1068 (domain I), 1392 and 2154 (domain II) and between amino acids 2474 and 3295 (Domain III; FIGS. 13A-13C). Similar domains were found in the pcbAB gene of A. chrysogenum. Within these domains, several even more conserved elements can be distinguished. A summary is given in FIG. 15. Since the ACVS enzyme synthesizes a tripeptide, which most probably requires the activation of three amino acids, a role of these three domains in the amino acid activation reactions seems likely. Therefore, the said domains are candidate regions for in vitro mutagenesis.

Comparison of the deduced amino acid sequence with the protein sequences known for other multifunctional enzymes reveals a significant homology with the Bacillus brevis tyrocidin synthetase I (SEQ ID NO: 8) (hereinafter referred to a TYI; Weckerman et al., Nucleic Acids Research (1988), 16:11841) and gramicidin synthetase I (SEQ ID NO: 9) (hereinafter referred to as GSI; Kratzschmar et al., supra; compare FIG. 13). Since both TYI and GSI are involved in activation and racemization of the amino acid phenylalanine, this homology supports the notion that these conserved sequences may represent centers involved in ATP-mediated activation of amino acids. If the mechanism of peptide synthesis by ACVS or Gramicidin Synthetase is comparable, the expected order of the domains in the enzyme is in the same order as that of the amino acids in the tripeptide (Kratzschmar, supra).

Upon comparison of the ACVS protein sequence with other known protein sequences of large enzymes, a significant homology is found with the Fatty Acid Synthetase (long chain) from rat and chicken (FIG. 14; M. Schweizer et al., Nucleic Acids Research (1989) 17:567-586; Z. Yuan et al., PNAS (1988), 85:6328-6331). The homology is found between the COOH-terminal part of the ACVS protein (SEQ ID NO: 10) (domain IV in FIG. 15) and the thioesterase domain (SEQ ID NO: 11) of the long chain Fatty Acid Synthetase proteins. Even the active site of the thioesterase, viz. G.X.S.X.G. (e.g. Kratzschmar, supra), is present in the ACVS protein sequence. A similar homology has been described for a subunit of gramicidin Synthetase; in this case the homology is found between the grsT subunit and the type II fatty acid synthetases. The demonstration of the said homology suggests that ACVS most probably also contains within its structure the ability to release the tripeptide, once it has been formed and bound to the enzyme by thioester bond formation, by the action of its thioesterase domain. This activity may form another target for in vitro mutagenesis, e.g. by increasing the efficiency of the release of the tripeptide, in case this part of the reaction is the rate determining step. However, in experiments designed to change substrate specificity, this domain preferably remains unchanged.

The functional domains of the ACVS protein being identified, it now is possible to construct modified peptide synthetases by the exchange of functional domains. This can be achieved e.g. by interchanging the three domains that have been identified within the ACVS protein. An alternative way is the exchange of ACVS specific domains with domains from other proteins known to have a similar function. Selected domains can be isolated by restriction enzyme digestion of clones containing the genes encoding the said proteins or domains thereof. However, suitable restriction sites at useful positions are seldom encountered. Therefore, the Polymerase Chain Reaction offers a good alternative for the isolation of suitable DNA fragments. In general, DNA fragments containing functional domains are prepared as follows: for each domain two oligonucleotides are designed, one starting at the N-terminal end of the selected domain, in the direction of the C-terminal end. The other oligonucleotide is derived from the C-terminal end of the domain and is designed in the opposite direction; consequently this oligonucleotide is derived from the other DNA strand. At the 5'-end of each oligonucleotide a suitable restriction site can be included in the oligonucleotide, in order to facilitate ligation of the domains after amplification. The DNA fragments between the two oligonucleotides are amplified using the polymerase chain reaction, thereby following the protocols known in the art (described e.g. in `PCR-Technology`, supra). Preferably, Taq DNA polymerase is used for the amplification reaction.

Synthesis of pPCV01

This vector was derived from pBluescript II KS M13(+) (Stratagene, La Jolla, Calif.) and contains the phleomycin resistance gene under control of the P. chrysogenum pgk promoter. It moreover contains a synthetic multiple cloning site, including unique SpeI site. The P. chrysogenum pgk gene has been isolated from a genomic cosmid library. To construct the cosmid library, chromosomal DNA of P. chrysogenum was isolated by forming protoplasts from the mycelium as described in EP-A-260762. The protoplasts were analyzed by diluting the isotonic (0.7M KCL) suspension with four volumes of TES buffer (0.05MTris-Hcl pH 8.0, 0.1M EDTA, 0.15M NaCl). To the lysate, 1% sodium lauryl sulfate was added and the mixture was incubated at 55.degree. C. for 30 minutes. After one extraction with phenol and two extractions with chloroform, the DNA was precipitated with ethanol, dried, and dissolved in TE buffer (10M Tris, 1M EDTA pH 8.0). The DNA solution was then treated with 100 .mu.g/ml RNase at 37.degree. C. for one hour and subsequently with 200 .mu.g/ml proteinase K at 42.degree. C. for one hour. The solution was extracted once with phenol and twice with chloroform. An equal volume of isopropanol was laid on top of the aqueous phase and the DNA was collected at the interface by spooling around a glass rod. After drying, the DNA was dissolved in TE buffer. The molecular weight of the DNA preparation obtained was about 10.sup.8. After partial digestion of the DNA with Sau 3A, particles of 20-35 kb in size were isolated and ligated into the BamHI digested cosmid vector PS07 (see EPA 0260762; cf. FIG. 4) using standard protocols (e.g., Maniatis et al. supra). The ligation mixture was packaged in vitro and the phage lysate was transduced into E. coli HB101 (ATCC 33694), again using methods known in the art. Fresh transductant colonies were grown in 10 ml of L-broth (per liter 10 g of NaCl, 10 g of Bacto-tryptone and 5 g of Bacto-yeast extract) on the ampicillin selection. Cosmid DNA was isolated and the presence of insert DNA was checked by EcoRI digestion. Insertion-containing cosmids were stored in microtiter plates at -20.degree. C. The pgk gene was isolated using the corresponding gene of Saccharomyces cerevisiae (Dobson et al., Nucleic Acid Research (1982) 10:2625-2637) as a probe (Van Solingen et al., Nucleic Acid Research (1988) 16:11823). The sequence of part of the promoter is disclosed in U.S. Pat. No. 5,108,918. The promoter and a small part of the coding region can be isolated as a 1.5 kb HindIII fragment.

Synthesis of PCV02

The pcbAB gene is isolated from cosmid clone HM193 as a 1.2.times.10.sup.4 nucleotide SpeI fragment and was subcloned into the vector pPCV0l, using the unique SpeI site. Conditions used were as disclosed in Maniatis et al. (supra) The resulting construct is named pPCV02 (FIG. 8). The orientation of the gene in the vector has been determined by digestion with restriction enzymes.

Transformation

The plasmid pPCV02 is transformed into P. chrysogenum Wis54-1255 npe5 (CBS 178.89) using the procedure described in copending application U.S. Ser. No. 097,455 filed Sep. 16, 1987. Strain npe5 is a non-producing mutant of Wis 45-1255; the npe phenotype is caused by the absence of ACV synthetase activity. Transformants are selected for resistance against 30 .mu.g/ml of phleomycin. Isolated transformants have been tested in a bioassay, as described in U.S. Pat. No. 5,108,918, for a restoration of penicillin production. In a representative experiment penicillin production has been restored in 80% (8 out of 10) of the pPCV02-transformants analyzed; in transformants having received the vector pPCV01, without the ACV synthetase insert, a restoration of the penicillin production has not been demonstrated (0 out of 26).

The construct pPCV02 is also transformed into wild type P. chrysogenum. Selected transformants are assayed for an increased ACV synthetase activity, using cell-free extracts as described in U.S. Pat. No. 5,108,918, or for an increased penicillin productivity, using shake flask experiments, also described in U.S. Pat. No. 5,108,918. chrysogenum pgk promoter

Transcription of the pcbAB gene is subject to glucose repression

mRNA preparations, isolated from Penicillium cultures grown on either glucose- or lactose-containing media (U.S. Pat. No. 5,108,918, are transferred to GeneScreen-plus.RTM. (NEN/DuPont) and hybridized with the 1.5.times.10.sup.3 nucleotide HindIII fragment, which is internal to the pcbAB gene (FIG. 4). In glucose-grown cultures, no pcbAB mRNA is detected, while in the lactose grown cultures, a large mRNA (.gtoreq.10.times.10.sup.3 nucleotides) is detected.

Construction of pPCV03

The region surrounding the ATG start codon of the pcbAB gene is isolated as a 1.7.times.10.sup.3 nucleotide SalI-DraI fragment. The vector pTZ18R (U.S. Biochemical Corporation, Cleveland, Ohio) is digested with SalI and SmaI restriction enzymes. The digested vector and the 1.7.times.10.sup.3 fragment are ligated. A construct containing the pTZ18R vector bearing the 1.7.times.10.sup.3 fragment insert is isolated. Into this construct, the P. chrysogenum pgk promoter is ligated as a 1.5.times.10.sup.3 nucleotides HindIII fragment (U.S. Pat. No. 5,108,918). A construct containing the pgk promoter in the desired orientation (same polarity as the pcbAB fragment) is isolated. From this construct single stranded DNA is isolated by superinfection with the helper phage M13K07, (U.S. Biochemical Corporation, Cleveland, Ohio) using techniques known in the art or as prescribed by the supplier of the pTZ cloning vector. By in vitro mutagenesis using a synthetic oligonucleotide having the following sequence (SEQ. ID. NO. 21): 5'-TGG CTT CAG TTG AGT CAT ATG GGT AGT TAA TGG TAT-3', a DNA fragment containing the mature pgk region and the region upstream of the pcbAB ATG is looped out. This mutagenesis introduces an NdeI site at the position of the ATG (underlined in the oligonucleotide sequence). The construct is named pTZpgk::acvsl. This construct is digested with HindIII and XbaI and the promoter-gene fusion is isolated on a DNA fragment of 2.9.times.10.sup.3 nucleotides as described by Maniatis et al., (supra). This fragment is ligated with the 16.3 kb DNA fragment containing the pcbAB gene, isolated after partial XbaI digestion of pPCV02, the remaining HindIII-XbaI sticky ends are filled in with T4 DNA polymerase and the construct is circularized by the addition of ligase.

The resulting construct, pPCV03 (FIG. 8), is isolated as follows. The ligation mixture is transformed into HB101 (ATCC 33694) using standard techniques. Plasmid DNA is isolated from several transformants and analyzed by restriction enzyme-digestion and agarose gel electrophoresis. Transformants containing the correct DNA constructs are grown on large scale (500 ml) and plasmid DNA is isolated using methods as disclosed in Maniatis et al., (supra) and transformed into P. chrysogenum. Expression of the pcbAB gene, enzyme activity and penicillin production of transformants is analyzed after growth in shaker flasks on both glucose- and lactose containing media; the data obtained are compared with those obtained for transformants containing pPCV02. In contrast to transformants containing pPCV02, transformants containing pPCV03 express the pcbAB gene in glucose-containing media: both an ACV synthetase-specific mRNA and ACV synthetase enzyme activity are detected.

For efficient production of ACV synthetase enzyme in E. coli it is necessary to place the pcbAB gene under control of a promoter which allows efficient gene expression in E. coli. Examples of such efficient promoters are the trp promoter, the lac promoter and the tac promoter. In this example the trp promoter is described, but it will be obvious to those skilled in the art that the experiments can be easily repeated with the lac and tac promoters, leading to similar results. If desired, a runaway replicon can be included in the construct; this will allow for controlled amplification of the plasmid copy number after a temperature shift.

Synthesis of PMA-ACVS

pMAtrp (FIG. 9), having the trp promoter region between -113 and the ATG transcription start flanked by an NdeI site at the position of the ATG (Sommerville, supra), is digested with SmaI and NdeI. From pPCV03 a 1.5.times.10.sup.3 nucleotide NdeI-DraI fragment, containing the 5'-part of the pcbAB gene, is isolated and ligated into the SmaI, NdeI digested pMAtrp. Into the XbaI sites of the resulting construct, the 3'-part of the pcbAB gene was inserted as a 1.0.times.10.sup.4 nucleotide XbaI fragment isolated from HM193 or pPCV02. Constructs are selected for the correct orientation of the inserted XbaI fragment; the construct containing the fragment in the correct orientation is named pMA-ACV synthetase (FIG. 10). Orientation is determined by digestion with various restriction enzymes.

pMA-ACV synthetase is isolated and used to transform a suitable E. coli host, such as, for example E. coli HB101, E. coli C600 or E. coli JM101. Transformants are analyzed by determination of ACV synthetase activity in cell free extracts, by electrophoresis of cell free extracts in 5% polyacrylamide gels (SDS-PAGE) and by immunoblotting, using a polyclonal antiserum which had been raised against purified ACV synthetase.

For expression in a Streptomyces host, several options are available. S. lividans is a preferred host because of the ease of transformation of this host, as compared to several other Streptomycetes.

Expression of the P. chrysogenum ACV synthetase gene under control of the aph promoter

The P. chrysogenum ACV synthetase gene is isolated as the 1.2.times.10.sup.4 nucleotide SpeI fragment described in Example 2. The sticky ends of this fragment are made blunt by treatment with T4 DNA polymerase using the procedures known in the art. The vector pIJ61 has been described by C. J. Thompson et al., (1982) Gene 20, 51-62); reviewed in: D. A. Hopwood et al., supra; the vector can be obtained from D. A. Hopwood. The vector pIJ61 was digested with BamHI, and the ends were made blunt using T4 DNA polymerase. Subsequently, the blunt-ended 1.2.times.10.sup.4 nucleotide SpeI fragment is inserted into the blunt-ended BamHI site via ligation, and the mixture is used to transform S. lividans 66, by the method of Hopwood et al. (D. A. Hopwood et al., 1985, supra). Transformants are selected for resistance to thiostreptone (50 .mu.g/ml) and are subsequently analyzed for the orientation of the pcbAB gene in the same orientation as the aph gene is named pSLACV-01 (FIG. 11).

Selected transformants containing the plasmid pSLACV-01 were cultured as described in Chen et al., (supra). Cell free extracts are prepared and analyzed by SDS-PAGE or immunoblotting for the presence of a large (>250 kDa) protein; the ACV synthetase activity in the extracts is also determined using the procedure as described by Van Liempt (supra).

Expression of the P. chrysogenum pcbAB gene in S.lividans under control of the tyrosinase promoter

The vector pIJ702 is digested with either BglII or SstI. pIJ702 is described by E. Katz et al., Journ. Gen. Microbiol. (1983) 129:2703-2714; reviewed in: D. A. Hopwood et al., supra; obtainable from D. A. Hopwood. BglII digested pIJ702 was made blunt-ended by treatment with T4 DNA polymerase; SstI digested pIJ702 is treated with Mung bean nuclease in order to obtain blunt ends. The blunt-ended SpeI fragment containing the P. chrysogenum pcbAB gene as described hereinabove is inserted into both blunt-ended vectors via ligation. Thiostreptone resistant transformants are screened for a melanin-negative phenotype by application of a soft agar overlay containing tyrosine (0.1 mM) as described in Hopwood et al. (supra). Melanin-negative transformants contained an interrupted tyrosinase gene (by insertion of the ACV synthetase gene) and their colonies remained colorless upon addition of tyrosine, while wild-type colonies turn brown. Analysis by restriction enzyme digestion and agarose gel electrophoresis for the correct orientation of the inserts yielded plasmids pSLACV-03A (SstI site; FIG. 12A) and pSLACV-03B (BglII site; FIG. 12B).

Analysis of transformants is as described hereinabove. Induction of the tyrosinase promoter is established by the addition of methionine (10 mM) to the culture medium. Isolation of the A. chrysogenum pcbAB gene

A gene library of A. chrysogenum C10 (deposited with American Type Culture Collection, Rockville, Md., as ATCC 48272) has been constructed in the lambda cloning vector EMBL3. To this end, A. chrysogenum DNA has been partially digested with Sau3A and fragments ranging in size from 13 to 17.times.10.sup.3 nucleotides have been isolated by sucrose gradient ultracentrifugation. The vector EMBL3 has been digested with BamHI and arms have been separated and purified by sucrose gradient centrifugation. About 0.4 .mu.g of vector arms have been ligated with 0.5 .mu.g of partially digested, purified A. chrysogenum DNA; the ligation mixture has been packaged in vitro using the lambda phage packaging system of Amersham (Buckinghamshire, UK), following the procedure provided by the supplier. The packaged mixture has been used to infect E. coli Q-359 (ATCC 47019); about 70,000 plaques have been obtained.

In order to isolate phages containing the A. chrysogenum pcbAB gene, the gene library first was screened using as a probe the isolated pcbc gene from P. chrysogenum, namely a 1.times.10.sup.3 nucleotide NcoI fragment, carrying the promoterless gene (Barredo et al., (1989)b, Mol. Gen. Genet. 216, 91-98); conditions have been described in Barredo et al., 1989b (supra). Five phages, showing a positive hybridization signal have been purified and a restriction map has been constructed. The position of these phages (F1, F3, F4, F5 and F6) relative to a restriction map of the genomic region is given in FIG. 16.

To identify the presence of another gene on the phages, the isolated DNA has also been hybridized with a 6.0.times.10.sup.3 nucleotide SalI fragment (III in FIG. 3) derived from the P. chrysogenum pcbAB gene as it is present in, for example, HM193. All five phages showed a strong hybridization signal with this latter probe. This finding indicates that in A. chrysogenum the pcbC and pcbAB genes are linked, as they are in P. chrysogenum and as indicated in FIG. 16. To isolate phages with an insert containing more upstream sequences, as compared to the isolated phages (which extend a maximal 11.5.times.10.sup.3 nucleotides upstream from the 5'-end of the pcbC gene) the library has been rescreened using as a probe a 0.9.times.10.sup.3 nucleotide XhoI fragment (probe P6 in FIG. 17) isolated from, for example, phages F1, F3, F5 or F6. This rescreening has yielded another seventeen phages. Eight of these phages have been further purified and characterized; the position of the phages F12, F17, F18, F20, F21, F23, F24 and F25 relative to a restriction map of the genomic region is given in FIG. 14.

Localization of the pcbAB gene of A. chrysogenum

Northern blot hybridizations have been performed using mRNA that has been isolated from A. chrysogenum following the procedure described in Barredo et al., 1989b (supra). As probes, the fragments P1-P8 as indicated in FIG. 17 have been used. Probes P3 and P4 hybridize to a transcript of about 1.15.times.10.sup.3 nucleotides; this transcript is derived from the pcbC gene and encodes the IPNS enzyme. Probes P1, P2, P5, P6 and P7 hybridize to a large mRNA, size >11.times.10.sup.3 nucleotides; this indicates the presence of a large gene in the region covered by these probes. Moreover, the ends of the large transcript have been more accurately mapped by the results using the small probes P5-P8: absence of hybridization using probe P8 indicates that the distal end of the putative pcbAB gene is located within the 0.5.times.10.sup.3 nucleotide AccI fragment preceding P8 (namely in region P7 in FIG. 17) while the hybridization patterns of probes P4 and P5 indicate that the proximal end of the putative pcbAB gene has to be present outside region P4, most probably within region P5. The orientation of the gene has been established by homology with the P. chrysogenum gene; it is transcribed in the opposite direction to the pcbC gene (FIG. 16), which also occurs in P. chrysogenum.

Determination of the nucleotide sequence of the pcbAB gene from A. chrysogenum

The nucleotide sequence of the region encoding the putative pcbAB gene of A. chrysogenum has been determined. Five subclones have been constructed in pBluescript KS(+) (Stratagene, LaJolla, U.S.A.), starting from phage F12 (FIG. 16). The subclones contain the following fragments: A (3.6.times.10.sup.3 nucleotide BamHI), B (1.7.times.10.sup.3 nucleotide SalI-KpnI), C (3.2.times.10.sup.3 nucleotide SalI), D (2.4.times.10.sup.3 nucleotide SalI-PstI) and E (2.0.times.10.sup.3 nucleotide PstI-KpnI). Fragment A has been cloned in both orientations in pBluescript KS(+) which had been digested with BamHI; subsequently the fragment has been subcloned into 23 smaller, overlapping fragments, which have been sequenced using the dideoxy chain termination method (Sanger et al., Proc. Natl. Acad. Sci. (U.S.A.) (1977) 74:5463-5467), using either Sequenase (U.S. Biochemicals, Cleveland, Ohio) or Taq polymerase (Promega, Madison, Wis.). The sticky ends of fragment B have been made blunt, using standard techniques, and the blunt end fragment has been cloned into EcoRV digested pBluescript KS(+). Subsequently, the fragment has been subcloned into fourteen overlapping smaller fragments. These fragments have been sequenced using the dideoxy chain termination method.

Fragments C, D and E have been sequenced by generating sets of ordered deletion mutants using the "Erase-A-Base" system (Promega, Madison, Wis.). To this end, fragment C has been subcloned into SalI-digested pBluescript KS(+) in both orientations; the clones have been opened by digestion with BstXI and XbaI to obtain appropriate ends to generate the deletions. Fragment D has been subcloned in both orientations into EcoRV-digested pBluescript KS(+), after filling in the sticky ends of the fragment. For the generation of sets of deletion mutants, the clones have been opened by digestion with PstI and EcoRI. Fragment E (after filling in the sticky ends) has been subcloned into EcoRV digested pBluescript KS(+) in both orientations; clones have been opened for generation of sets of deletion mutants by digestion with EcoRI and PstI.

The digested clones of the fragments C, D and E have been treated with exonuclease III, followed by deletion of the remaining sticky ends with exonuclease S1. The gaps that have been introduced by both enzymes have been repaired with Klenow DNA polymerase, followed by ligation of the linear molecules and transformation into E. coli. For all treatments, the conditions recommended by the supplier of the "Erase-A-Base" system have been used. The resulting fragments have been sequenced using the dideoxy chain termination method. Clones overlapping the junctions of the five fragments have also been sequenced; the entire region has been sequenced in both strands. The nucleotide sequence of a 11.8.times.10.sup.3 nucleotide DNA fragment is shown in FIG. 16 (SEQ ID NO:3). In this sequence a long open reading frame (ORF) of 11,139 bp has been demonstrated. From this ORF a protein sequence of 3712 amino acids has been deduced (SEQ ID NO:4).

Similarity with the P. chrysogenum pcbAB sequence

The nucleotide sequence of the A. chrysogenum pcbAB gene has been compared with the nucleotide sequence that has been determined for the P. chrysogenum pcbAB gene (Example 1; FIG. 6). A 62.9% homology has been determined at the nucleotide level. At the protein level the similarity is 54.9% (based on the deduced amino acid sequences); a comparison between the deduced amino acid sequences for the P. chrysoqenum (SEQ ID NO:2) and A. chrysogenum (SEQ ID NO:4) ACVS is given in FIGS. 18A-18H.

The ACV synthetase enzyme activities reside on a single gene in P. chrysogenum and A. chrysogenum. Elevated activity of this enzymes can be obtained in host cells using the recombinant compositions of the instant invention. Heterologous expression of ACV synthetase can provide a means of using more efficient and robust hosts for the commercial production of ACV synthetase and its secondary metabolites. Finally, the availability of large amounts of the ACV synthetase-enzyme, for example, by expression of the gene in a suitable host, will allow for better prospects for commercial application of in vitro synthesis of .beta.-lactam antibiotics and their precursors.

All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

The invention now being fully described, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the appended claims. SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 27 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12364 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: (A) ORGANISM: Penicillium chrysogenum (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 264..11600 (D) OTHER INFORMATION: /function="enzyme" /product= "ACV Synthetase" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: GTCGACAGTTGACAGAGCCAATGGCATCGGATCTGCCCTAGACCGTGCTAGACGAAAGTC60 TCCATCTTGTCTGCGGGCAGTTCTTCAGTCGCCCAGATTCTCGATGGAGATTGGCCAGGT120 CAGCCATATATACCCTGCAATGGCAGACCAATGCAGCAGGCCCAGTATAAGGAATTCCCC180 TCGAGCTTGTCTGTGATTGCGTTTTTTCTAACACTTGTTGTTGCATCCGATCCGTCGCTA240 CCAATTATTGGTCATTGACAGACATGACTCAACTGAAGCCACCGAACGGA290 MetThrGlnLeuLysProProAsnGly 15 ACCACGCCGATAGGCTTCTCGGCCACTACATCCCTGAACGCCAGTGGG338 ThrThrProIleGlyPheSerAlaThrThrSerLeuAsnAlaSerGly 10152025 AGCTCGAGTGTGAAAAATGGGACCATCAAACCCAGCAATGGCATCTTC386 SerSerSerValLysAsnGlyThrIleLysProSerAsnGlyIlePhe 303540 AAGCCCAGCACTAGGGACACCATGGACCCTTGCAGTGGGAATGCGGCC434 LysProSerThrArgAspThrMetAspProCysSerGlyAsnAlaAla 455055 GATGGCAGTATCCGCGTCCGTTTCCGTGGAGGAATCGAACGGTGGAAG482 AspGlySerIleArgValArgPheArgGlyGlyIleGluArgTrpLys 606570 GAGTGCGTCAACCAGGTCCCCGAGCGCTGCGACCTGAGTGGTCTGACA530 GluCysValAsnGlnValProGluArgCysAspLeuSerGlyLeuThr 758085 ACCGACTCCACGCGATATCAGCTCGCATCGACTGGGTTCGGTGACGCG578 ThrAspSerThrArgTyrGlnLeuAlaSerThrGlyPheGlyAspAla 9095100105 AGCGCTGCGTACCAGGAGCGCTTGATGACGGTCCCTGTTGACGTACAT626 SerAlaAlaTyrGlnGluArgLeuMetThrValProValAspValHis 110115120 GCCGCGCTCCAAGAGCTGTGCCTAGAACGCCGTGTGAGCGTGGGATCC674 AlaAlaLeuGlnGluLeuCysLeuGluArgArgValSerValGlySer 125130135 GTCATTAATTTCTCCGTGCACCAGATGCTGAAAGGGTTTGGAAATGGC722 ValIleAsnPheSerValHisGlnMetLeuLysGlyPheGlyAsnGly 140145150 ACACACACTATCACCGCCTCTCTGCACCGTGAGCAGAATTTGCAGAAT770 ThrHisThrIleThrAlaSerLeuHisArgGluGlnAsnLeuGlnAsn 155160165 TCTTCGCCATCCTGGGTAGTCTCCCCCACAATCGTCACCCATGAGAAC818 SerSerProSerTrpValValSerProThrIleValThrHisGluAsn 170175180185 AGAGACGGATGGTCCGTCGCGCAGGCGGTCGAGAGTATCGAAGCGGCG866 ArgAspGlyTrpSerValAlaGlnAlaValGluSerIleGluAlaAla 190195200 CGCGGTTCCGAGAAGGAGTCAGTGACTGCGATTGACTCCGCGTCAAGT914 ArgGlySerGluLysGluSerValThrAlaIleAspSerAlaSerSer 205210215 CTCGTGAAAATGGGGTTATTTGACTTACTCGTCAGCTTTGTCGATGCA962 LeuValLysMetGlyLeuPheAspLeuLeuValSerPheValAspAla 220225230 GACGATGCTCGTATTCCATGTTTCGACTTTCCCCTCGCAGTGATAGTG1010 AspAspAlaArgIleProCysPheAspPheProLeuAlaValIleVal 235240245 CGTGAGTGTGATGCCAACCTCTCGCTGACTCTGCGTTTCTCCGACTGT1058 ArgGluCysAspAlaAsnLeuSerLeuThrLeuArgPheSerAspCys 250255260265 CTCTTCAACGAGGAGACGATATGCAATTTTACCGATGCCCTAAACATC1106 LeuPheAsnGluGluThrIleCysAsnPheThrAspAlaLeuAsnIle 270275280 TTGCTCGCCGAAGCAGTGATAGGAAGAGTGACCCCGGTTGCCGATATC1154 LeuLeuAlaGluAlaValIleGlyArgValThrProValAlaAspIle 285290295 GAACTACTATCCGCGGAGCAGAAGCAGCAGCTGGAAGAGTGGAACAAC1202 GluLeuLeuSerAlaGluGlnLysGlnGlnLeuGluGluTrpAsnAsn 300305310 ACGGATGGCGAGTACCCTTCATCAAAGCGACTGCACCATCTCATTGAA1250 ThrAspGlyGluTyrProSerSerLysArgLeuHisHisLeuIleGlu 315320325 GAGGTGGTTGAACGGCATGAAGACAAAATAGCCGTTGTCTGCGACGAG1298 GluValValGluArgHisGluAspLysIleAlaValValCysAspGlu 330335340345 CGAGAGCTCACTTACGGCGAGCTCAATGCCCAAGGCAACAGCCTCGCA1346 ArgGluLeuThrTyrGlyGluLeuAsnAlaGlnGlyAsnSerLeuAla 350355360 CGCTATCTCCGTTCCATTGGTATCCTGCCCGAGCAGCTAGTCGCATTG1394 ArgTyrLeuArgSerIleGlyIleLeuProGluGlnLeuValAlaLeu 365370375 TTTCTAGATAAGAGCGAGAAGCTCATTGTTACCATCCTCGGCGTGTGG1442 PheLeuAspLysSerGluLysLeuIleValThrIleLeuGlyValTrp 380385390 AAATCCGGCGCCGCCTACGTGCCCATCGACCCGACTTATCCGGATGAG1490 LysSerGlyAlaAlaTyrValProIleAspProThrTyrProAspGlu 395400405 CGAGTGCGCTTCGTGCTGGATGACACCAAGGCACGGGCCATCATCGCC1538 ArgValArgPheValLeuAspAspThrLysAlaArgAlaIleIleAla 410415420425 AGTAATCAACATGTGGAGAGGCTCCAGCGAGAGGTCATCGGCGATAGA1586 SerAsnGlnHisValGluArgLeuGlnArgGluValIleGlyAspArg 430435440 AACCTATGCATTATCCGTCTGGAGCCCTTGTTGGCCTCCCTTGCTCAG1634 AsnLeuCysIleIleArgLeuGluProLeuLeuAlaSerLeuAlaGln 445450455 GATTCCTCAAAATTCCCCGCGCATAACTTGGACGACCTACCCCTCACA1682 AspSerSerLysPheProAlaHisAsnLeuAspAspLeuProLeuThr 460465470 AGCCAGCAGCTCGCCTATGTGACTTACACCTCTGGGACCACTGGTTTC1730 SerGlnGlnLeuAlaTyrValThrTyrThrSerGlyThrThrGlyPhe 475480485 CCAAAGGGCATATTTAAACAACACACCAATGTGGTGAACAGTATTACC1778 ProLysGlyIlePheLysGlnHisThrAsnValValAsnSerIleThr 490495500505 GACCTGTCTGCAAGGTACGGGGTGGCCGGGCAGCACCACGAAGCCATT1826 AspLeuSerAlaArgTyrGlyValAlaGlyGlnHisHisGluAlaIle 510515520 CTGCTTTTCTCGGCCTGCGTGTTCGAGCCGTTCGTTCGACAGACGCTC1874 LeuLeuPheSerAlaCysValPheGluProPheValArgGlnThrLeu 525530535 ATGGCACTCGTGAATGGCCATCTCCTCGCAGTTATCAATGACGTGGAA1922 MetAlaLeuValAsnGlyHisLeuLeuAlaValIleAsnAspValGlu 540545550 AAATATGATGCCGATACGCTCCTGCCGTTCATACGCAGACACAGCATC1970 LysTyrAspAlaAspThrLeuLeuProPheIleArgArgHisSerIle 555560565 ACCTACCTCAATGGTACTGCCTCTGTCTTGCAAGAGTACGACTTTTCC2018 ThrTyrLeuAsnGlyThrAlaSerValLeuGlnGluTyrAspPheSer 570575580585 GACTGCCCATCACTGAATCGGATAATCCTGGTGGGTGAGAACCTGACA2066 AspCysProSerLeuAsnArgIleIleLeuValGlyGluAsnLeuThr 590595600 GAAGCCCGGTATCTGGCGCTGCGCCAGCGGTTCAAGAATCGCATCCTC2114 GluAlaArgTyrLeuAlaLeuArgGlnArgPheLysAsnArgIleLeu 605610615 AACGAGTATGGTTTTACCGAGTCAGCCTTTGTAACGGCCCTCAAGATT2162 AsnGluTyrGlyPheThrGluSerAlaPheValThrAlaLeuLysIle 620625630 TTCGACCCGGAGTCGACCCGTAAGGACACGAGTCTGGGGAGACCGGTG2210 PheAspProGluSerThrArgLysAspThrSerLeuGlyArgProVal 635640645 CGCAACGTCAAGTGCTACATCCTCAATCCATCCCTTAAACGTGTCCCG2258 ArgAsnValLysCysTyrIleLeuAsnProSerLeuLysArgValPro 650655660665 ATTGGAGCTACGGGTGAGTTGCATATCGGAGGGTTGGGCATTTCCAAG2306 IleGlyAlaThrGlyGluLeuHisIleGlyGlyLeuGlyIleSerLys 670675680 GGATACCTCAACCGCCCCGAACTCACGCCGCACCGCTTCATTCCCAAC2354 GlyTyrLeuAsnArgProGluLeuThrProHisArgPheIleProAsn 685690695 CCCTTCCAAACGGATTGCGAGAAGCAGCTCGGGATCAACAGCTTGATG2402 ProPheGlnThrAspCysGluLysGlnLeuGlyIleAsnSerLeuMet 700705710 TACAAGACCGGTGACCTGGCCCGCTGGCTTCCGAACGGCGAGGTTGAG2450 TyrLysThrGlyAspLeuAlaArgTrpLeuProAsnGlyGluValGlu 715720725 TATCTCGGACGCGCAGATTTCCAGATCAAACTGCGAGGTATTCGAATT2498 TyrLeuGlyArgAlaAspPheGlnIleLysLeuArgGlyIleArgIle 730735740745 GAACCTGGTGAAATTGAGACGATGCTGGCTATGTACCCTAGGGTCCGG2546 GluProGlyGluIleGluThrMetLeuAlaMetTyrProArgValArg 750755760 ACCAGTTTAGTGGTGTCCAAAAAGCTCCGCAACGGTCCAGAGGAAACT2594 ThrSerLeuValValSerLysLysLeuArgAsnGlyProGluGluThr 765770775 ACCAACGAGCACCTCGTGGGTTATTATGTTTGTGATAGCGCCTCAGTG2642 ThrAsnGluHisLeuValGlyTyrTyrValCysAspSerAlaSerVal 780785790 TCCGAGGCAGACCTGCTGTCATTTTTAGAGAAGAAACTGCCTCGATAC2690 SerGluAlaAspLeuLeuSerPheLeuGluLysLysLeuProArgTyr 795800805 ATGATTCCCACGCGGTTGGTACAGCTGTCGCAGATCCCAGTGAATGTG2738 MetIleProThrArgLeuValGlnLeuSerGlnIleProValAsnVal 810815820825 AACGGGAAGGCGGACCTACGCGCCTTGCCGGCCGTCGATATCTCCAAT2786 AsnGlyLysAlaAspLeuArgAlaLeuProAlaValAspIleSerAsn 830835840 TCCACGGAGGTGCGTTCCGACCTTCGAGGCGATACGGAAATCGCCCTC2834 SerThrGluValArgSerAspLeuArgGlyAspThrGluIleAlaLeu 845850855 GGGGAAATCTGGGCCGACGTGTTGGGAGCCCGCCAGAGATCCGTCTCT2882 GlyGluIleTrpAlaAspValLeuGlyAlaArgGlnArgSerValSer 860865870 CGCAACGACAACTTCTTCCGCCTAGGAGGGCACAGCATCACCTGCATC2930 ArgAsnAspAsnPhePheArgLeuGlyGlyHisSerIleThrCysIle 875880885 CAACTGATCGCTCGCATCCGACAACGACAACGACTCTCGGTCAGCATC2978 GlnLeuIleAlaArgIleArgGlnArgGlnArgLeuSerValSerIle 890895900905 TCCGTCGAAGATGTTTTTGCAACAAGGACACTTGAGCGCATGGCAGAC3026 SerValGluAspValPheAlaThrArgThrLeuGluArgMetAlaAsp 910915920 CTTCTACAGAACAAGCAGCAGGAGAAATGCGACAAACCCCATGAGGCG3074 LeuLeuGlnAsnLysGlnGlnGluLysCysAspLysProHisGluAla 925930935 CCGACAGAGCTGCTTGAGGAGAATGCAGCAACGGACAATATCTATCTG3122 ProThrGluLeuLeuGluGluAsnAlaAlaThrAspAsnIleTyrLeu 940945950 GCAAACAGTCTTCAGCAGGGCTTCGTCTACCATTACCTCAAGAGCATG3170 AlaAsnSerLeuGlnGlnGlyPheValTyrHisTyrLeuLysSerMet 955960965 GAACAATCCGACGCCTATGTAATGCAGTCCGTTCTTCGGTACAACACC3218 GluGlnSerAspAlaTyrValMetGlnSerValLeuArgTyrAsnThr 970975980985 ACATTGTCTCCAGATCTGTTTCAGAGAGCCTGGAAGCATGCACAGCAG3266 ThrLeuSerProAspLeuPheGlnArgAlaTrpLysHisAlaGlnGln 9909951000 TCCTTTCCAGCGCTGCGGCTGCGGTTCTCATGGGAAAAGGAGGTTTTC3314 SerPheProAlaLeuArgLeuArgPheSerTrpGluLysGluValPhe 100510101015 CAACTGCTCGATCAGGATCCACCATTGGACTGGCGTTTCCTCTACTTC3362 GlnLeuLeuAspGlnAspProProLeuAspTrpArgPheLeuTyrPhe 102010251030 ACCGACGTTGCCGCGGGTGCTGTCGAGGACCGGAAATTGGAAGACTTG3410 ThrAspValAlaAlaGlyAlaValGluAspArgLysLeuGluAspLeu 103510401045 CGGCGCCAAGACCTTACGGAGAGATTCAAGCTGGATGTTGGCAGACTG3458 ArgArgGlnAspLeuThrGluArgPheLysLeuAspValGlyArgLeu 1050105510601065 TTCCGCGTCTATCTGATTAAACACAGCGAGAATCGCTTCACGTGTCTT3506 PheArgValTyrLeuIleLysHisSerGluAsnArgPheThrCysLeu 107010751080 TTCAGCTGCCATCATGCAATCCTCGATGGTTGGAGTCTGCCACTCTTG3554 PheSerCysHisHisAlaIleLeuAspGlyTrpSerLeuProLeuLeu 108510901095 TTCGAAAAGGTTCACGAGACCTACCTGCAACTGCTGCATGGGGACAAT3602 PheGluLysValHisGluThrTyrLeuGlnLeuLeuHisGlyAspAsn 110011051110 CTCACTTCGTCCATGGATGACCCTTACACTCGCACCCAGCGGTATCTC3650 LeuThrSerSerMetAspAspProTyrThrArgThrGlnArgTyrLeu 111511201125 CACGCTCACCGTGAGGATCACCTCGACTTTTGGGCCGGTGTGGTTCAA3698 HisAlaHisArgGluAspHisLeuAspPheTrpAlaGlyValValGln 1130113511401145 AAGATCAACGAACGGTGTGATATGAACGCCTTGTTGAACGAGCGCAGT3746 LysIleAsnGluArgCysAspMetAsnAlaLeuLeuAsnGluArgSer 115011551160 CGTTACAAAGTCCAGCTGGCAGACTATGACCAGGTGCAGGAGCAGCGA3794 ArgTyrLysValGlnLeuAlaAspTyrAspGlnValGlnGluGlnArg 116511701175 CACGTGACAATTGCTCTCTCTGGAGACGCATGGCTAGCAGACCTTCGT3842 HisValThrIleAlaLeuSerGlyAspAlaTrpLeuAlaAspLeuArg 118011851190 CAGACCTGCTCCGCCCAGGGTATTACCTTACATTCGATTCTCCAATTT3890 GlnThrCysSerAlaGlnGlyIleThrLeuHisSerIleLeuGlnPhe 119512001205 GTTTGGCACGCCGTGCTGCACGCTTATGGCGGTGGCACCCACACCATA3938 ValTrpHisAlaValLeuHisAlaTyrGlyGlyGlyThrHisThrIle 1210121512201225 ACCGGCACGACCATTTCTGGAAGGAACCTGCCCATCTTGGGAATTGAA3986 ThrGlyThrThrIleSerGlyArgAsnLeuProIleLeuGlyIleGlu 123012351240 CGAGCAGTTGGTCCGTATATCAACACTCTACCGCTGGTACTCGATCAT4034 ArgAlaValGlyProTyrIleAsnThrLeuProLeuValLeuAspHis 124512501255 TCGACGTTCAAGGATAAGACAATCATGGAGGCCATCGAGGATGTGCAG4082 SerThrPheLysAspLysThrIleMetGluAlaIleGluAspValGln 126012651270 GCCAAGGTAAACGTCATGAACAGCCGGGGCAATGTGGAACTGGGCCGT4130 AlaLysValAsnValMetAsnSerArgGlyAsnValGluLeuGlyArg 127512801285 TTGCACAAAACCGACTTAAAGCACGGATTATTCGATTCTTTATTCGTG4178 LeuHisLysThrAspLeuLysHisGlyLeuPheAspSerLeuPheVal 1290129513001305 CTTGAAAACTACCCGAATTTGGACAAATCGCGAACACTTGAGCACCAG4226 LeuGluAsnTyrProAsnLeuAspLysSerArgThrLeuGluHisGln 131013151320 ACTGAACTGGGGTATTCGATTGAAGGCGGCACTGAGAAGCTGAATTAT4274 ThrGluLeuGlyTyrSerIleGluGlyGlyThrGluLysLeuAsnTyr 132513301335 CCACTGGCTGTCATCGCGCGCGAAGTCGAGACGACTGGCGGATTCACA4322 ProLeuAlaValIleAlaArgGluValGluThrThrGlyGlyPheThr 134013451350 GTATCCATCTGCTACGCCAGTGAGCTATTTGAGGAGGTTATGATCTCC4370 ValSerIleCysTyrAlaSerGluLeuPheGluGluValMetIleSer 135513601365 GAGCTTCTTCATATGGTCCAGGACACACTGATGCAGGTTGCCCGAGGT4418 GluLeuLeuHisMetValGlnAspThrLeuMetGlnValAlaArgGly 1370137513801385 TTGAATGAACCCGTCGGCAGCCTGGAGTATCTCTCATCTATCCAATTG4466 LeuAsnGluProValGlySerLeuGluTyrLeuSerSerIleGlnLeu 139013951400 GAGCAACTCGCCGCGTGGAATGCCACGGAAGCTGAGTTTCCCGATACC4514 GluGlnLeuAlaAlaTrpAsnAlaThrGluAlaGluPheProAspThr 140514101415 ACGCTTCATGAGATGTTTGAAAACGAAGCGAGCCAGAAGCCGGACAAG4562 ThrLeuHisGluMetPheGluAsnGluAlaSerGlnLysProAspLys 142014251430 ATAGCAGTGGTCTATGAGGAGACGTCCTTGACTTACCGCGAGTTGAAT4610 IleAlaValValTyrGluGluThrSerLeuThrTyrArgGluLeuAsn 143514401445 GAGCGGGCGAACCGTATGGCACATCAGCTAAGGTCCGACGTCAGCCCC4658 GluArgAlaAsnArgMetAlaHisGlnLeuArgSerAspValSerPro 1450145514601465 AACCCCAACGAGGTCATTGCGCTGGTGATGGACAAGAGCGAGCATATG4706 AsnProAsnGluValIleAlaLeuValMetAspLysSerGluHisMet 147014751480 ATCGTCAACATTCTGGCCGTATGGAAGAGCGGCGGTGCCTATGTCCCC4754 IleValAsnIleLeuAlaValTrpLysSerGlyGlyAlaTyrValPro 148514901495 ATTGACCCTGGATATCCTAACGACCGCATTCAATATATCCTAGAGGAC4802 IleAspProGlyTyrProAsnAspArgIleGlnTyrIleLeuGluAsp 150015051510 ACACAAGCCCTCGCAGTCATCGCGGACTCCTGCTATCTGCCTCGCATC4850 ThrGlnAlaLeuAlaValIleAlaAspSerCysTyrLeuProArgIle 151515201525 AAGGGAATGGCTGCCTCCGGCACGCTTCTTTATCCCTCTGTCTTGCCT4898 LysGlyMetAlaAlaSerGlyThrLeuLeuTyrProSerValLeuPro 1530153515401545 GCCAATCCGGATTCCAAGTGGAGCGTATCGAACCCTTCACCGTTGAGT4946 AlaAsnProAspSerLysTrpSerValSerAsnProSerProLeuSer 155015551560 CGGAGCACGGACTTAGCTTATATCATCTATACCTCTGGAACGACAGGT4994 ArgSerThrAspLeuAlaTyrIleIleTyrThrSerGlyThrThrGly 156515701575 CGGCCCAAGGGCGTCACGGTAGAGCATCATGGAGTGGTCAACCTGCAG5042 ArgProLysGlyValThrValGluHisHisGlyValValAsnLeuGln 158015851590 GTGTCGCTATCCAAAGTATTCGGACTACGGGATACGGACGACGAGGTA5090 ValSerLeuSerLysValPheGlyLeuArgAspThrAspAspGluVal 159516001605 ATTCTCTCCTTTTCCAACTATGTGTTCGACCATTTCGTGGAGCAGATG5138 IleLeuSerPheSerAsnTyrValPheAspHisPheValGluGlnMet 1610161516201625 ACCGACGCCATTCTCAATGGCCAAACCCTCCTGGTCCTCAACGATGGA5186 ThrAspAlaIleLeuAsnGlyGlnThrLeuLeuValLeuAsnAspGly 163016351640 ATGCGCGGGGACAAAGAGCGACTCTACAGATACATTGAGAAGAACCGA5234 MetArgGlyAspLysGluArgLeuTyrArgTyrIleGluLysAsnArg 164516501655 GTGACCTACTTGTCTGGCACCCCATCCGTGGTCTCCATGTACGAATTT5282 ValThrTyrLeuSerGlyThrProSerValValSerMetTyrGluPhe 166016651670 AGCCGGTTCAAGGACCATCTACGCCGTGTGGACTGCGTGGGGGAGGCG5330 SerArgPheLysAspHisLeuArgArgValAspCysValGlyGluAla 167516801685 TTCAGCGAACCGGTCTTCGACAAGATCCGCGAAACGTTCCATGGCCTC5378 PheSerGluProValPheAspLysIleArgGluThrPheHisGlyLeu 1690169517001705 GTTATCAACGGCTACGGCCCAACTGAAGTTTCCATCACCACCCACAAG5426 ValIleAsnGlyTyrGlyProThrGluValSerIleThrThrHisLys 171017151720 CGGCTCTATCCATTCCCAGAGCGGCGAATGGACAAAAGTATTGGCCAA5474 ArgLeuTyrProPheProGluArgArgMetAspLysSerIleGlyGln 172517301735 CAGGTCCACAATAGCACGAGCTATGTGCTGAACGAGGACATGAAGCGC5522 GlnValHisAsnSerThrSerTyrValLeuAsnGluAspMetLysArg 174017451750 ACCCCCATAGGGGCTGTCGGCGAGCTCTACCTGGGTGGTGAAGGAGTG5570 ThrProIleGlyAlaValGlyGluLeuTyrLeuGlyGlyGluGlyVal 175517601765 GTACGGGGATATCACAATCGCGCAGATGTGACCGCGGAGCGTTTTATT5618 ValArgGlyTyrHisAsnArgAlaAspValThrAlaGluArgPheIle 1770177517801785 CCTAATCCATTCCAGTCGGAAGAAGATAAGCGAGAAGGTCGTAACTCC5666 ProAsnProPheGlnSerGluGluAspLysArgGluGlyArgAsnSer 179017951800 CGTTTGTACAAGACCGGTGACCTGGTACGCTGGATTCCTGGAAGCAGC5714 ArgLeuTyrLysThrGlyAspLeuValArgTrpIleProGlySerSer 180518101815 GGGGAGGTCGAGTATCTAGGTCGTAATGACTTCCAGGTCAAGATTCGC5762 GlyGluValGluTyrLeuGlyArgAsnAspPheGlnValLysIleArg 182018251830 GGACTGCGCATCGAAGTAGGCGAGATTGAGGCCATCCTATCGTCTTAT5810 GlyLeuArgIleGluValGlyGluIleGluAlaIleLeuSerSerTyr 183518401845 CACGGAATCAAACAGTCTGTGGTGATTGCCAAGGATTGCAGAGAAGGG5858 HisGlyIleLysGlnSerValValIleAlaLysAspCysArgGluGly 1850185518601865 GCCCAGAAATTCCTGGTTGGTTACTATGTCGCCGATGCAGCGCTGCCG5906 AlaGlnLysPheLeuValGlyTyrTyrValAlaAspAlaAlaLeuPro 187018751880 TCCGCTGCCATTCGGCGCTTCATGCAGTCTCGGCTCCCTGGCTACATG5954 SerAlaAlaIleArgArgPheMetGlnSerArgLeuProGlyTyrMet 188518901895 GTGCCCTCTCGTCTCATTCTCGTCAGCAAGTTCCCCGTCACTCCTAGT6002 ValProSerArgLeuIleLeuValSerLysPheProValThrProSer 190019051910 GGAAAATTAGACACCAAGGCTTTGCCCCCAGCCGAGGAAGAGAGCGAG6050 GlyLysLeuAspThrLysAlaLeuProProAlaGluGluGluSerGlu 191519201925 ATTGACGTGGTGCCGCCGCGTAGTGAAATCGAACGCTCCTTGTGTGAC6098 IleAspValValProProArgSerGluIleGluArgSerLeuCysAsp 1930193519401945 ATCTGGGCGGAACTACTCGAGATGCACCCAGAGGAGATCGGCATTTAC6146 IleTrpAlaGluLeuLeuGluMetHisProGluGluIleGlyIleTyr 195019551960 AGCGATTTCTTCAGCCTGGGAGGTGACAGCCTAAAGAGCACAAAGCTT6194 SerAspPhePheSerLeuGlyGlyAspSerLeuLysSerThrLysLeu 196519701975 TCCTTCATGATTCACGAGTCCTTTAACCGCGCCGTCTCAGTCAGCGCC6242 SerPheMetIleHisGluSerPheAsnArgAlaValSerValSerAla 198019851990 CTTTTCTGTCACCGGACAGTTGAAGCCCAGACGCACTTGATCCTGAAC6290 LeuPheCysHisArgThrValGluAlaGlnThrHisLeuIleLeuAsn 199520002005 GATGCTGCAGATGTGCACGAAATTACTCCCATAGATTGCAATGATACG6338 AspAlaAlaAspValHisGluIleThrProIleAspCysAsnAspThr 2010201520202025 CAGATGATTCCCGTGTCCCGTGCCCAGGAGCGACTCCTCTTCATCCAC6386 GlnMetIleProValSerArgAlaGlnGluArgLeuLeuPheIleHis 203020352040 GAATTTGAGAATGGCAGCAATGCATACAATATCGACGCTGCATTTGAA6434 GluPheGluAsnGlySerAsnAlaTyrAsnIleAspAlaAlaPheGlu 204520502055 CTGCCTGGCTCGGTTGACGCGTCGCTTCTCGAGCAGGCGCTGCGTGGA6482 LeuProGlySerValAspAlaSerLeuLeuGluGlnAlaLeuArgGly 206020652070 AACCTTGCTCGACATGAGGCGTTGAGAACTTTACTGGTCAAGGATCAC6530 AsnLeuAlaArgHisGluAlaLeuArgThrLeuLeuValLysAspHis 207520802085 GCAACCGGCATCTATCTTCAGAAGGTATTGAGTCCCGATGAAGCCCAG6578 AlaThrGlyIleTyrLeuGlnLysValLeuSerProAspGluAlaGln 2090209521002105 GGCATGTTCTCCGTCAACGTGGACACAGCCAAGCAGGTGGAGCGGCTG6626 GlyMetPheSerValAsnValAspThrAlaLysGlnValGluArgLeu 211021152120 GACCAGGAGATAGCCAGTCTATCCCAGCATGTTTTCCGCCTCGATGAT6674 AspGlnGluIleAlaSerLeuSerGlnHisValPheArgLeuAspAsp 212521302135 GAACTGCCTTGGGAGGCCCGCATCCTTAAACTCGAATCCGGCGGCCTG6722 GluLeuProTrpGluAlaArgIleLeuLysLeuGluSerGlyGlyLeu 214021452150 TATCTCATTCTGGCGTTCCACCATACCTGCTTCGATGCATGGTCATTG6770 TyrLeuIleLeuAlaPheHisHisThrCysPheAspAlaTrpSerLeu 215521602165 AAAGTCTTCGAGCAAGAGCTTCGGGCCTTGTACGCAGCGCTCCAGAAA6818 LysValPheGluGlnGluLeuArgAlaLeuTyrAlaAlaLeuGlnLys 2170217521802185 ACCAAAAGTGCAGCGAACTTACCAGCCCTCAAAGCGCAGTACAAGGAA6866 ThrLysSerAlaAlaAsnLeuProAlaLeuLysAlaGlnTyrLysGlu 219021952200 TACGCGCTCTACCATCGCCGGCAGCTGTCTGGCGATCGCATGCGCAAC6914 TyrAlaLeuTyrHisArgArgGlnLeuSerGlyAspArgMetArgAsn 220522102215 CTGTCAGACTTTTGGCTGCGGAAACTCATTGGCTTGGAACCATTGCAG6962 LeuSerAspPheTrpLeuArgLysLeuIleGlyLeuGluProLeuGln 222022252230 CTGATCACGGACCGCCCACGTCCTGTGCAATTCAAATACGACGGTGAC7010 LeuIleThrAspArgProArgProValGlnPheLysTyrAspGlyAsp 223522402245 GACCTCAGTATCGAACTGAGCAAGAAGGAAACGGAGAACCTGAGGGGG7058 AspLeuSerIleGluLeuSerLysLysGluThrGluAsnLeuArgGly 2250225522602265 GTGGCCAAACGTTGCAAGTCGAGTCTGTACGTCGTGTTGGTTTCCGTT7106 ValAlaLysArgCysLysSerSerLeuTyrValValLeuValSerVal 227022752280 TATTGCGTTATGCTAGCCTCGTACGCGAACCAGTCCGATGTTTCCGTG7154 TyrCysValMetLeuAlaSerTyrAlaAsnGlnSerAspValSerVal 228522902295 GGTATCCCAGTCAGCCACCGAACGCATCCTCAGTTCCAATCGGTCATT7202 GlyIleProValSerHisArgThrHisProGlnPheGlnSerValIle 230023052310 GGATTCTTCGTCAACCTTGTGGTGCTAAGGGTGGATATTTCTCAGTCA7250 GlyPhePheValAsnLeuValValLeuArgValAspIleSerGlnSer 231523202325 GCCATTTGCGGGCTCATCAGAAGGGTAATGAAAGAGCTCGTGGACGCC7298 AlaIleCysGlyLeuIleArgArgValMetLysGluLeuValAspAla 2330233523402345 CAACTGCACCAAGACATGCCGTTCCAGGAAGTGACGAAGCTGCTGCAG7346 GlnLeuHisGlnAspMetProPheGlnGluValThrLysLeuLeuGln 235023552360 GTGGATAATGACCCCAGCCGGCATCCGCTGGTACAGAACGTGTTCAAC7394 ValAspAsnAspProSerArgHisProLeuValGlnAsnValPheAsn 236523702375 TTCGAATCCCGTGCGAACGGAGAACACGATGCCAGGTCGGAGGATGAA7442 PheGluSerArgAlaAsnGlyGluHisAspAlaArgSerGluAspGlu 238023852390 GGATCGCTTGCATTCAATCAATACCGGCCGGTTCAGCCCGTGGATTCC7490 GlySerLeuAlaPheAsnGlnTyrArgProValGlnProValAspSer 239524002405 GTTGCGAAGTTCGATCTGAACGCAACGGTCACGGAATTGGAGTCGGGA7538 ValAlaLysPheAspLeuAsnAlaThrValThrGluLeuGluSerGly 2410241524202425 TTGAGAGTCAACTTCAACTATGCGACCAGCCTATTCAACAAAAGCACG7586 LeuArgValAsnPheAsnTyrAlaThrSerLeuPheAsnLysSerThr 243024352440 ATCCAGGGTTTTTTGCATACCTATGAGTATCTCCTGCGCCAGCTGTCC7634 IleGlnGlyPheLeuHisThrTyrGluTyrLeuLeuArgGlnLeuSer 244524502455 GAACTGAGTGCAGAAGGGATCAATGAGGATACGCAGCTGTCGTTAGTT7682 GluLeuSerAlaGluGlyIleAsnGluAspThrGlnLeuSerLeuVal 246024652470 CGCCCGACAGAGAATGGCGATCTGCACTTGCCATTGGCACAGTCCCCG7730 ArgProThrGluAsnGlyAspLeuHisLeuProLeuAlaGlnSerPro 247524802485 CTTGCGACGACTGCTGAGGAGCAGAAAGTAGCGTCGTTGAACCAGGCC7778 LeuAlaThrThrAlaGluGluGlnLysValAlaSerLeuAsnGlnAla 2490249525002505 TTTGAGCGCGAAGCTTTCCTTGCCGCAGAGAAGATTGCCGTCGTGCAG7826 PheGluArgGluAlaPheLeuAlaAlaGluLysIleAlaValValGln 251025152520 GGAGATAGAGCACTTAGTTATGCTGATCTTAACGGGCAGGCTAACCAG7874 GlyAspArgAlaLeuSerTyrAlaAspLeuAsnGlyGlnAlaAsnGln 252525302535 CTCGCCCGGTACATACAGTCCGTGTCCTGTATTGGGGCAGACGACGGA7922 LeuAlaArgTyrIleGlnSerValSerCysIleGlyAlaAspAspGly 254025452550 ATAGCTTTGATGCTGGAAAAGAGTATCGACACGATTATTTGCATTCTC7970 IleAlaLeuMetLeuGluLysSerIleAspThrIleIleCysIleLeu 255525602565 GCGATTTGGAAGGCTGGTGCAGCATACGTGCCCTTGGATCCGACTTAC8018 AlaIleTrpLysAlaGlyAlaAlaTyrValProLeuAspProThrTyr 2570257525802585 CCACCCGGACGCGTCCAGCTGATTCTGGAGGAGATTAAAGCGAAGGCT8066 ProProGlyArgValGlnLeuIleLeuGluGluIleLysAlaLysAla 259025952600 GTCCTTGTGCACTCCAGTCATGCTTCGAAATGTGAACGCCATGGCGCG8114 ValLeuValHisSerSerHisAlaSerLysCysGluArgHisGlyAla 260526102615 AAGGTGATTGCAGTCGACTCGCCCGCCATCGAGACGGCGGTCAGCCAA8162 LysValIleAlaValAspSerProAlaIleGluThrAlaValSerGln 262026252630 CAGTCAGCTGCTGACCTGCCCACAATTGCTAGCCTCGGCAATCTAGCG8210 GlnSerAlaAlaAspLeuProThrIleAlaSerLeuGlyAsnLeuAla 263526402645 TATATAATCTTTACTTCAGGCACTTCCGGTAAGCCAAAGGGAGTCCTA8258 TyrIleIlePheThrSerGlyThrSerGlyLysProLysGlyValLeu 2650265526602665 GTTGAGCAAAAGGCAGTTCTTCTTCTACGCGATGCCCTCCGGGAGCGG8306 ValGluGlnLysAlaValLeuLeuLeuArgAspAlaLeuArgGluArg 267026752680 TATTTCGGTCGAGACTGTACCAAGCATCATGGCGTCCTGTTCCTGTCC8354 TyrPheGlyArgAspCysThrLysHisHisGlyValLeuPheLeuSer 268526902695 AACTACGTCTTCGACTTCTCCGTCGAACAACTTGTGTTGTCGGTGCTC8402 AsnTyrValPheAspPheSerValGluGlnLeuValLeuSerValLeu 270027052710 AGCGGACACAAGCTGATCGTTCCCCCAGCTGAGTTCGTCGCAGATGAT8450 SerGlyHisLysLeuIleValProProAlaGluPheValAlaAspAsp 271527202725 GAATTTTACAGAATGGCCAGCACGCACGGTCTCTCCTATCTCAGCGGC8498 GluPheTyrArgMetAlaSerThrHisGlyLeuSerTyrLeuSerGly 2730273527402745 ACACCATCCTTACTGCAGAAGATCGATCTGGCACGACTGGACCATCTG8546 ThrProSerLeuLeuGlnLysIleAspLeuAlaArgLeuAspHisLeu 275027552760 CAGGTTGTTACCGCCGCGGGCGAAGAGCTTCACGCCACCCAGTACGAG8594 GlnValValThrAlaAlaGlyGluGluLeuHisAlaThrGlnTyrGlu 276527702775 AAGATGCGCCGCCGATTCAACGGTCCCATCTACAATGCCTATGGTGTC8642 LysMetArgArgArgPheAsnGlyProIleTyrAsnAlaTyrGlyVal 278027852790 ACCGAGACCACGGTGTACAACATTATCGCGGAATTCACAACGAATTCG8690 ThrGluThrThrValTyrAsnIleIleAlaGluPheThrThrAsnSer 279528002805 ATATTTGAGAATGCTCTTCGGGAAGTGCTCCCTGGTACCCGAGCGTAT8738 IlePheGluAsnAlaLeuArgGluValLeuProGlyThrArgAlaTyr 2810281528202825 GTGCTGACCGCGGCACTTCAGCCCGTCCCCTTCGATGCTGTCGGAGAA8786 ValLeuThrAlaAlaLeuGlnProValProPheAspAlaValGlyGlu 283028352840 CTCTATCTTGCCGGCGACACGGTTACGCGTGGTTATCTCAACCAACCT8834 LeuTyrLeuAlaGlyAspThrValThrArgGlyTyrLeuAsnGlnPro 284528502855 CTTCTAACGGATCAGCGATTCATTCCCAACCCTTTCTGCAAAGAGGAG8882 LeuLeuThrAspGlnArgPheIleProAsnProPheCysLysGluGlu 286028652870 GACATCGCTATGGGGCGCTTCGCGCGGCTCTACAAGACCGGCGACCTG8930 AspIleAlaMetGlyArgPheAlaArgLeuTyrLysThrGlyAspLeu 287528802885 GTTCGATCGCGTTTCAACCGTCAGCAGCAGCCGCAGCTGGAATACCTA8978 ValArgSerArgPheAsnArgGlnGlnGlnProGlnLeuGluTyrLeu 2890289529002905 GGAAGAGGCGATCTGCAGATCAAGATGAGGGGATACCGGATCGAGATT9026 GlyArgGlyAspLeuGlnIleLysMetArgGlyTyrArgIleGluIle 291029152920 TCTGAAGTTCAGAACGTGCTCACTTCAAGTCCCGGTGTCCGGGAGGGT9074 SerGluValGlnAsnValLeuThrSerSerProGlyValArgGluGly 292529302935 GCAGTCGTTGCCAAGTATGAGAACAACGATACCTATTCCCGGACCGCT9122 AlaValValAlaLysTyrGluAsnAsnAspThrTyrSerArgThrAla 294029452950 CACTCTCTGGTCGGTTACTATACCACGGACAATGAAACAGTATCGGAA9170 HisSerLeuValGlyTyrTyrThrThrAspAsnGluThrValSerGlu 295529602965 GCCGATATTCTCACTTTCATGAAAGCAAGGCTTCCAACGTACATGGTG9218 AlaAspIleLeuThrPheMetLysAlaArgLeuProThrTyrMetVal 2970297529802985 CCAAGCCACCTCTGCTGTCTGGAAGGCGCACTGCCTGTGACGATTAAC9266 ProSerHisLeuCysCysLeuGluGlyAlaLeuProValThrIleAsn 299029953000 GGAAAGCTCGACGTCCGGAGATTGCCGGAGATTATCAACGACTCCGCG9314 GlyLysLeuAspValArgArgLeuProGluIleIleAsnAspSerAla 300530103015 CAGTCCTCGTACAGCCCACCAAGGAACATAATCGAGGCCAAGATGTGC9362 GlnSerSerTyrSerProProArgAsnIleIleGluAlaLysMetCys 302030253030 AGACTGTGGGAATCCGCCTTGGGAATGGAGCGATGCGGTATCGACGAC9410 ArgLeuTrpGluSerAlaLeuGlyMetGluArgCysGlyIleAspAsp 303530403045 GACCTGTTCAAACTGGGTGGCGACAGCATCACATCTTTGCATCTCGTG9458 AspLeuPheLysLeuGlyGlyAspSerIleThrSerLeuHisLeuVal 3050305530603065 GCCCAGATTCACAACCAGGTGGGCTGCAAGATCACCGTTCGGGATATA9506 AlaGlnIleHisAsnGlnValGlyCysLysIleThrValArgAspIle 307030753080 TTTGAACATCGTACCGCCCGAGCCCTCCATGATCACGTCTTCATGAAG9554 PheGluHisArgThrAlaArgAlaLeuHisAspHisValPheMetLys 308530903095 GACTCCGACCGGAGTAATGTGACTCAGTTCCGAACCGAACAAGGGCCG9602 AspSerAspArgSerAsnValThrGlnPheArgThrGluGlnGlyPro 310031053110 GTCATCGGCGAGGCGCCCCTACTGCCGATTCAAGACTGGTTTTTGTCA9650 ValIleGlyGluAlaProLeuLeuProIleGlnAspTrpPheLeuSer 311531203125 AAGGCTCTGCAGCATCCGATGTATTGGAATCACACTTTCTACGTCCGA9698 LysAlaLeuGlnHisProMetTyrTrpAsnHisThrPheTyrValArg 3130313531403145 ACGCCAGAGCTGGATGTTGATTCCTTAAGCGCTGCTGTCAGGGACTTG9746 ThrProGluLeuAspValAspSerLeuSerAlaAlaValArgAspLeu 315031553160 CAACAGTATCACGATGTTTTCCGCATGCGACTCAAGCGCGAGGAAGTC9794 GlnGlnTyrHisAspValPheArgMetArgLeuLysArgGluGluVal 316531703175 GGATTCGTGCAGTCCTTTGCTGAGGACTTCTCTCCTGCCCAGCTTCGG9842 GlyPheValGlnSerPheAlaGluAspPheSerProAlaGlnLeuArg 318031853190 GTGCTGAACGTAAAAGATGTTGACGGGTCCGCGGCCGTCAACGAGATA9890 ValLeuAsnValLysAspValAspGlySerAlaAlaValAsnGluIle 319532003205 TTGGATGGGTGGCAGTCTGGCTTCAACCTTGAGAACGGACCCATTGGT9938 LeuAspGlyTrpGlnSerGlyPheAsnLeuGluAsnGlyProIleGly 3210321532203225 TCCATTGGCTACCTACATGGGTATGAAGACCGATCCGCGCGAGTCTGG9986 SerIleGlyTyrLeuHisGlyTyrGluAspArgSerAlaArgValTrp 323032353240 TTCTCCGTTCACCATATGGCCATTGACACCGTCAGCTGGCAGATCCTT10034 PheSerValHisHisMetAlaIleAspThrValSerTrpGlnIleLeu 324532503255 GTCCGTGACCTGCAGACGCTGTACCGAAATGGAAGCCTCGGAAGCAAG10082 ValArgAspLeuGlnThrLeuTyrArgAsnGlySerLeuGlySerLys 326032653270 GGCAGCAGTTTCCGGCAGTGGGCTGAAGCCATCCAAAATTACAAGGCG10130 GlySerSerPheArgGlnTrpAlaGluAlaIleGlnAsnTyrLysAla 327532803285 TCAGACTCTGAGAGGAACCATTGGAATAAGCTCGTCATGGAAACAGCT10178 SerAspSerGluArgAsnHisTrpAsnLysLeuValMetGluThrAla 3290329533003305 TCCAGCATATCCGCATTGCCTACGTCAACCGGTTCGCGCGTGCGCCTG10226 SerSerIleSerAlaLeuProThrSerThrGlySerArgValArgLeu 331033153320 AGCAGAAGTTTGAGCCCTGAGAAGACAGCCTCACTGATCCAAGGAGGA10274 SerArgSerLeuSerProGluLysThrAlaSerLeuIleGlnGlyGly 332533303335 ATCGATCGACAGGATGTCTCCGTGTACGACTCCCTCCTGACTTCAGTT10322 IleAspArgGlnAspValSerValTyrAspSerLeuLeuThrSerVal 334033453350 GGATTGGCGCTCCAACATATCGCTCCAACCGGCCCAAGTATGGTTACG10370 GlyLeuAlaLeuGlnHisIleAlaProThrGlyProSerMetValThr 335533603365 ATCGAGGGACATGGCCGTGAAGAAGTGGATCAGACACTGGATGTGAGC10418 IleGluGlyHisGlyArgGluGluValAspGlnThrLeuAspValSer 3370337533803385 CGCACCATGGGTTGGTTCACCACCATGTATCCATTTGAAATTCCCCGT10466 ArgThrMetGlyTrpPheThrThrMetTyrProPheGluIleProArg 339033953400 CTCAGCACCGAGAACATTGTTCAAGGAGTCGTCGCTGTGAGCGAACGG10514 LeuSerThrGluAsnIleValGlnGlyValValAlaValSerGluArg 340534103415 TTCAGACAGGTGCCTGCCCGTGGCGTCGGGTATGGAACCTTGTACGGC10562 PheArgGlnValProAlaArgGlyValGlyTyrGlyThrLeuTyrGly 342034253430 TATACTCAACACCCGCTGCCCCAGGTGACCGTCAACTACCTGGGCCAG10610 TyrThrGlnHisProLeuProGlnValThrValAsnTyrLeuGlyGln 343534403445 CTCGCCCGCAAGCAATCGAAGCCAAAGGAATGGGTCCTCGCGGTGGGC10658 LeuAlaArgLysGlnSerLysProLysGluTrpValLeuAlaValGly 3450345534603465 GACAACGAATTTGAATACGGACTCATGACTAGCCCAGAGGACAAAGAC10706 AspAsnGluPheGluTyrGlyLeuMetThrSerProGluAspLysAsp 347034753480 CGGAGCTCTTCTGCCGTCGACGTCACGGCCGTGTGTATTGACGGCACT10754 ArgSerSerSerAlaValAspValThrAlaValCysIleAspGlyThr 348534903495 ATGATCATCGATGTGGACAGTGCTTGGAGCCTTGAGGAGAGCGAGCAA10802 MetIleIleAspValAspSerAlaTrpSerLeuGluGluSerGluGln 350035053510 TTCATCTCGAGCATCGAGGAAGGACTGAACAAGATCCTCGACGGCAGG10850 PheIleSerSerIleGluGluGlyLeuAsnLysIleLeuAspGlyArg 351535203525 GCAAGTCAGCAAACCTCGCGATTCCCGGATGTTCCTCAACCGGCGGAG10898 AlaSerGlnGlnThrSerArgPheProAspValProGlnProAlaGlu 3530353535403545 ACATATACGCCGTATTTCGAGTATCTGGAACCTCCACGACAGGGACCG10946 ThrTyrThrProTyrPheGluTyrLeuGluProProArgGlnGlyPro 355035553560 ACGCTGTTCCTGCTGCCGCCGGGCGAAGGAGGCGCCGAGAGTTACTTC10994 ThrLeuPheLeuLeuProProGlyGluGlyGlyAlaGluSerTyrPhe 356535703575 AACAACATCGTCAAGCGCCTGCGTCAGACAAATATGGTGGTCTTCAAC11042 AsnAsnIleValLysArgLeuArgGlnThrAsnMetValValPheAsn 358035853590 AACTACTACTTGCACAGCAAACGCCTGCGCACGTTCGAGGAGCTGGCG11090 AsnTyrTyrLeuHisSerLysArgLeuArgThrPheGluGluLeuAla 359536003605 GAAATGTATCTCGACCAAGTACGCGGCATCCAACCACACGGACCGTAC11138 GluMetTyrLeuAspGlnValArgGlyIleGlnProHisGlyProTyr 3610361536203625 CACTTCATCGGATGGAGCTTCGGAGGAATTCTCGCAATGGAAATGTCG11186 HisPheIleGlyTrpSerPheGlyGlyIleLeuAlaMetGluMetSer 363036353640 CGGCGACTGGTAGCCTCGGACGAGAAGATTGGCTTCCTCGGTATTATC11234 ArgArgLeuValAlaSerAspGluLysIleGlyPheLeuGlyIleIle 364536503655 GACACCTATTTCAACGTGCGGGGAGCGACACGCACCATTGGCTTGGGG11282 AspThrTyrPheAsnValArgGlyAlaThrArgThrIleGlyLeuGly 366036653670 GACACTGAGATTCTGGACCCGATCCATCACATCTACAATCCCGATCCG11330 AspThrGluIleLeuAspProIleHisHisIleTyrAsnProAspPro 367536803685 GCCAACTTCCAACGCCTGCCCTCTGCAACAGATCGCATTGTGCTGTTC11378 AlaAsnPheGlnArgLeuProSerAlaThrAspArgIleValLeuPhe 3690369537003705 AAGGCCATGAGGCCGAACAACAAGTACGAATCCGAGAACCAGCGTCGC11426 LysAlaMetArgProAsnAsnLysTyrGluSerGluAsnGlnArgArg 371037153720 CTGTACGAGTACTATGACCGCACTCGACTCAACGGACTGGACAGCTTG11474 LeuTyrGluTyrTyrAspArgThrArgLeuAsnGlyLeuAspSerLeu 372537303735 TTACCAAGCGATTCCGACGTCCAGCTGGTCCCGCTTACGGACGATACA11522 LeuProSerAspSerAspValGlnLeuValProLeuThrAspAspThr 374037453750 CACTTTTCCTGGGTCGGAAATCCACAACAGGTGGAGCAGATGTGTGCG11570 HisPheSerTrpValGlyAsnProGlnGlnValGluGlnMetCysAla 375537603765 ACTATCAAGGAACACCTCGCTCGCTATTGATCCGTCACTAGCAGCAC11617 ThrIleLysGluHisLeuAlaArgTyr 37703775 AGTATATCGGACGATGGAAGTGATGGAGTGGGGGGGATAGGATACGATCAAACCAGAGTG11677 CGGTTCTTTTTCGGGGGAACTAGTCTCTGGTTGAGGAAAGCGAGGTAGCAAATAAACTAC11737 CAAGGTCTAGACCCACATAGTCTGTCATTGTTTTCGATCCTAAATTGATATATAATAGGC11797 GACACCTTTAGTTAGCCAAATTTTCTATATAGAAACACCACGGTTTTTAGGAGTTAGGAC11857 CACGTCAGACCGTGGCCCTTTCACTAACGCTTCCGTTTACATCCATACCGGATGTCGTTG11917 TAGCACATTTATATGATATCATTTAAGACTATATACGCCTATTCCCCCCTATCGAATAGG11977 CCCCTACGTATTTCTTTTGTTTTTTTCTTTTTCTTTTTTTTTTTTTTCTTTTCGCTCTCT12037 CCCCTTTTATACCCAATATCGGATCGAGTTGATAATATCAATATCTAAAACTCCCAATTA12097 AACCTACAAAGCCTATCTTAGTGTAAGTGAATTTGGGCTCTGGACCAAATTCTCCGCCAA12157 GGATAATCTTTCCGATAAACGGTGGTTATCCGGTCATCATAAAAAAGGAAAAGGTACTCC12217 GTCCTCGATAATAAAACGTAACATAAGCATGTCGTTCACCATAGACAAGAGGAACCAACA12277 TCATTAAGCAGGGGATAGGTTCATCCGGTCTAGGGCGTCGAGTGCCACCGCCCGTAGGTT12337 GTCAATCTTGAGCTGGATTTGGAGATC12364 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3778 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: MetThrGlnLeuLysProProAsnGlyThrThrProIleGlyPheSer 151015 AlaThrThrSerLeuAsnAlaSerGlySerSerSerValLysAsnGly 202530 ThrIleLysProSerAsnGlyIlePheLysProSerThrArgAspThr 354045 MetAspProCysSerGlyAsnAlaAlaAspGlySerIleArgValArg 505560 PheArgGlyGlyIleGluArgTrpLysGluCysValAsnGlnValPro 65707580 GluArgCysAspLeuSerGlyLeuThrThrAspSerThrArgTyrGln 859095 LeuAlaSerThrGlyPheGlyAspAlaSerAlaAlaTyrGlnGluArg 100105110 LeuMetThrValProValAspValHisAlaAlaLeuGlnGluLeuCys 115120125 LeuGluArgArgValSerValGlySerValIleAsnPheSerValHis 130135140 GlnMetLeuLysGlyPheGlyAsnGlyThrHisThrIleThrAlaSer 145150155160 LeuHisArgGluGlnAsnLeuGlnAsnSerSerProSerTrpValVal 165170175 SerProThrIleValThrHisGluAsnArgAspGlyTrpSerValAla 180185190 GlnAlaValGluSerIleGluAlaAlaArgGlySerGluLysGluSer 195200205 ValThrAlaIleAspSerAlaSerSerLeuValLysMetGlyLeuPhe 210215220 AspLeuLeuValSerPheValAspAlaAspAspAlaArgIleProCys 225230235240 PheAspPheProLeuAlaValIleValArgGluCysAspAlaAsnLeu 245250255 SerLeuThrLeuArgPheSerAspCysLeuPheAsnGluGluThrIle 260265270 CysAsnPheThrAspAlaLeuAsnIleLeuLeuAlaGluAlaValIle 275280285 GlyArgValThrProValAlaAspIleGluLeuLeuSerAlaGluGln 290295300 LysGlnGlnLeuGluGluTrpAsnAsnThrAspGlyGluTyrProSer 305310315320 SerLysArgLeuHisHisLeuIleGluGluValValGluArgHisGlu 325330335 AspLysIleAlaValValCysAspGluArgGluLeuThrTyrGlyGlu 340345350 LeuAsnAlaGlnGlyAsnSerLeuAlaArgTyrLeuArgSerIleGly 355360365 IleLeuProGluGlnLeuValAlaLeuPheLeuAspLysSerGluLys 370375380 LeuIleValThrIleLeuGlyValTrpLysSerGlyAlaAlaTyrVal 385390395400 ProIleAspProThrTyrProAspGluArgValArgPheValLeuAsp 405410415 AspThrLysAlaArgAlaIleIleAlaSerAsnGlnHisValGluArg 420425430 LeuGlnArgGluValIleGlyAspArgAsnLeuCysIleIleArgLeu 435440445 GluProLeuLeuAlaSerLeuAlaGlnAspSerSerLysPheProAla 450455460 HisAsnLeuAspAspLeuProLeuThrSerGlnGlnLeuAlaTyrVal 465470475480 ThrTyrThrSerGlyThrThrGlyPheProLysGlyIlePheLysGln 485490495 HisThrAsnValValAsnSerIleThrAspLeuSerAlaArgTyrGly 500505510 ValAlaGlyGlnHisHisGluAlaIleLeuLeuPheSerAlaCysVal 515520525 PheGluProPheValArgGlnThrLeuMetAlaLeuValAsnGlyHis 530535540 LeuLeuAlaValIleAsnAspValGluLysTyrAspAlaAspThrLeu 545550555560 LeuProPheIleArgArgHisSerIleThrTyrLeuAsnGlyThrAla 565570575 SerValLeuGlnGluTyrAspPheSerAspCysProSerLeuAsnArg 580585590 IleIleLeuValGlyGluAsnLeuThrGluAlaArgTyrLeuAlaLeu 595600605 ArgGlnArgPheLysAsnArgIleLeuAsnGluTyrGlyPheThrGlu 610615620 SerAlaPheValThrAlaLeuLysIlePheAspProGluSerThrArg 625630635640 LysAspThrSerLeuGlyArgProValArgAsnValLysCysTyrIle 645650655 LeuAsnProSerLeuLysArgValProIleGlyAlaThrGlyGluLeu 660665670 HisIleGlyGlyLeuGlyIleSerLysGlyTyrLeuAsnArgProGlu 675680685 LeuThrProHisArgPheIleProAsnProPheGlnThrAspCysGlu 690695700 LysGlnLeuGlyIleAsnSerLeuMetTyrLysThrGlyAspLeuAla 705710715720 ArgTrpLeuProAsnGlyGluValGluTyrLeuGlyArgAlaAspPhe 725730735 GlnIleLysLeuArgGlyIleArgIleGluProGlyGluIleGluThr 740745750 MetLeuAlaMetTyrProArgValArgThrSerLeuValValSerLys 755760765 LysLeuArgAsnGlyProGluGluThrThrAsnGluHisLeuValGly 770775780 TyrTyrValCysAspSerAlaSerValSerGluAlaAspLeuLeuSer 785790795800 PheLeuGluLysLysLeuProArgTyrMetIleProThrArgLeuVal 805810815 GlnLeuSerGlnIleProValAsnValAsnGlyLysAlaAspLeuArg 820825830 AlaLeuProAlaValAspIleSerAsnSerThrGluValArgSerAsp 835840845 LeuArgGlyAspThrGluIleAlaLeuGlyGluIleTrpAlaAspVal 850855860 LeuGlyAlaArgGlnArgSerValSerArgAsnAspAsnPhePheArg 865870875880 LeuGlyGlyHisSerIleThrCysIleGlnLeuIleAlaArgIleArg 885890895 GlnArgGlnArgLeuSerValSerIleSerValGluAspValPheAla 900905910 ThrArgThrLeuGluArgMetAlaAspLeuLeuGlnAsnLysGlnGln 915920925 GluLysCysAspLysProHisGluAlaProThrGluLeuLeuGluGlu 930935940 AsnAlaAlaThrAspAsnIleTyrLeuAlaAsnSerLeuGlnGlnGly 945950955960 PheValTyrHisTyrLeuLysSerMetGluGlnSerAspAlaTyrVal 965970975 MetGlnSerValLeuArgTyrAsnThrThrLeuSerProAspLeuPhe 980985990 GlnArgAlaTrpLysHisAlaGlnGlnSerPheProAlaLeuArgLeu 99510001005 ArgPheSerTrpGluLysGluValPheGlnLeuLeuAspGlnAspPro 101010151020 ProLeuAspTrpArgPheLeuTyrPheThrAspValAlaAlaGlyAla 1025103010351040 ValGluAspArgLysLeuGluAspLeuArgArgGlnAspLeuThrGlu 104510501055 ArgPheLysLeuAspValGlyArgLeuPheArgValTyrLeuIleLys 106010651070 HisSerGluAsnArgPheThrCysLeuPheSerCysHisHisAlaIle 107510801085 LeuAspGlyTrpSerLeuProLeuLeuPheGluLysValHisGluThr 109010951100 TyrLeuGlnLeuLeuHisGlyAspAsnLeuThrSerSerMetAspAsp 1105111011151120 ProTyrThrArgThrGlnArgTyrLeuHisAlaHisArgGluAspHis 112511301135 LeuAspPheTrpAlaGlyValValGlnLysIleAsnGluArgCysAsp 114011451150 MetAsnAlaLeuLeuAsnGluArgSerArgTyrLysValGlnLeuAla 115511601165 AspTyrAspGlnValGlnGluGlnArgHisValThrIleAlaLeuSer 117011751180 GlyAspAlaTrpLeuAlaAspLeuArgGlnThrCysSerAlaGlnGly 1185119011951200 IleThrLeuHisSerIleLeuGlnPheValTrpHisAlaValLeuHis 120512101215 AlaTyrGlyGlyGlyThrHisThrIleThrGlyThrThrIleSerGly 122012251230 ArgAsnLeuProIleLeuGlyIleGluArgAlaValGlyProTyrIle 123512401245 AsnThrLeuProLeuValLeuAspHisSerThrPheLysAspLysThr 125012551260 IleMetGluAlaIleGluAspValGlnAlaLysValAsnValMetAsn 1265127012751280 SerArgGlyAsnValGluLeuGlyArgLeuHisLysThrAspLeuLys 128512901295 HisGlyLeuPheAspSerLeuPheValLeuGluAsnTyrProAsnLeu 130013051310 AspLysSerArgThrLeuGluHisGlnThrGluLeuGlyTyrSerIle 131513201325 GluGlyGlyThrGluLysLeuAsnTyrProLeuAlaValIleAlaArg 133013351340 GluValGluThrThrGlyGlyPheThrValSerIleCysTyrAlaSer 1345135013551360 GluLeuPheGluGluValMetIleSerGluLeuLeuHisMetValGln 136513701375 AspThrLeuMetGlnValAlaArgGlyLeuAsnGluProValGlySer 138013851390 LeuGluTyrLeuSerSerIleGlnLeuGluGlnLeuAlaAlaTrpAsn 139514001405 AlaThrGluAlaGluPheProAspThrThrLeuHisGluMetPheGlu 141014151420 AsnGluAlaSerGlnLysProAspLysIleAlaValValTyrGluGlu 1425143014351440 ThrSerLeuThrTyrArgGluLeuAsnGluArgAlaAsnArgMetAla 144514501455 HisGlnLeuArgSerAspValSerProAsnProAsnGluValIleAla 146014651470 LeuValMetAspLysSerGluHisMetIleValAsnIleLeuAlaVal 147514801485 TrpLysSerGlyGlyAlaTyrValProIleAspProGlyTyrProAsn 149014951500 AspArgIleGlnTyrIleLeuGluAspThrGlnAlaLeuAlaValIle 1505151015151520 AlaAspSerCysTyrLeuProArgIleLysGlyMetAlaAlaSerGly 152515301535 ThrLeuLeuTyrProSerValLeuProAlaAsnProAspSerLysTrp 154015451550 SerValSerAsnProSerProLeuSerArgSerThrAspLeuAlaTyr 155515601565 IleIleTyrThrSerGlyThrThrGlyArgProLysGlyValThrVal 157015751580 GluHisHisGlyValValAsnLeuGlnValSerLeuSerLysValPhe 1585159015951600 GlyLeuArgAspThrAspAspGluValIleLeuSerPheSerAsnTyr 160516101615 ValPheAspHisPheValGluGlnMetThrAspAlaIleLeuAsnGly 162016251630 GlnThrLeuLeuValLeuAsnAspGlyMetArgGlyAspLysGluArg 163516401645 LeuTyrArgTyrIleGluLysAsnArgValThrTyrLeuSerGlyThr 165016551660 ProSerValValSerMetTyrGluPheSerArgPheLysAspHisLeu 1665167016751680 ArgArgValAspCysValGlyGluAlaPheSerGluProValPheAsp 168516901695 LysIleArgGluThrPheHisGlyLeuValIleAsnGlyTyrGlyPro 170017051710 ThrGluValSerIleThrThrHisLysArgLeuTyrProPheProGlu 171517201725 ArgArgMetAspLysSerIleGlyGlnGlnValHisAsnSerThrSer 173017351740 TyrValLeuAsnGluAspMetLysArgThrProIleGlyAlaValGly 1745175017551760 GluLeuTyrLeuGlyGlyGluGlyValValArgGlyTyrHisAsnArg 176517701775 AlaAspValThrAlaGluArgPheIleProAsnProPheGlnSerGlu 178017851790 GluAspLysArgGluGlyArgAsnSerArgLeuTyrLysThrGlyAsp 179518001805 LeuValArgTrpIleProGlySerSerGlyGluValGluTyrLeuGly 181018151820 ArgAsnAspPheGlnValLysIleArgGlyLeuArgIleGluValGly 1825183018351840 GluIleGluAlaIleLeuSerSerTyrHisGlyIleLysGlnSerVal 184518501855 ValIleAlaLysAspCysArgGluGlyAlaGlnLysPheLeuValGly 186018651870 TyrTyrValAlaAspAlaAlaLeuProSerAlaAlaIleArgArgPhe 187518801885 MetGlnSerArgLeuProGlyTyrMetValProSerArgLeuIleLeu 189018951900 ValSerLysPheProValThrProSerGlyLysLeuAspThrLysAla 1905191019151920 LeuProProAlaGluGluGluSerGluIleAspValValProProArg 192519301935 SerGluIleGluArgSerLeuCysAspIleTrpAlaGluLeuLeuGlu 194019451950 MetHisProGluGluIleGlyIleTyrSerAspPhePheSerLeuGly 195519601965 GlyAspSerLeuLysSerThrLysLeuSerPheMetIleHisGluSer 197019751980 PheAsnArgAlaValSerValSerAlaLeuPheCysHisArgThrVal 1985199019952000 GluAlaGlnThrHisLeuIleLeuAsnAspAlaAlaAspValHisGlu 200520102015 IleThrProIleAspCysAsnAspThrGlnMetIleProValSerArg 202020252030 AlaGlnGluArgLeuLeuPheIleHisGluPheGluAsnGlySerAsn 203520402045 AlaTyrAsnIleAspAlaAlaPheGluLeuProGlySerValAspAla 205020552060 SerLeuLeuGluGlnAlaLeuArgGlyAsnLeuAlaArgHisGluAla 2065207020752080 LeuArgThrLeuLeuValLysAspHisAlaThrGlyIleTyrLeuGln 208520902095 LysValLeuSerProAspGluAlaGlnGlyMetPheSerValAsnVal 210021052110 AspThrAlaLysGlnValGluArgLeuAspGlnGluIleAlaSerLeu 211521202125 SerGlnHisValPheArgLeuAspAspGluLeuProTrpGluAlaArg 213021352140 IleLeuLysLeuGluSerGlyGlyLeuTyrLeuIleLeuAlaPheHis 2145215021552160 HisThrCysPheAspAlaTrpSerLeuLysValPheGluGlnGluLeu 216521702175 ArgAlaLeuTyrAlaAlaLeuGlnLysThrLysSerAlaAlaAsnLeu 218021852190 ProAlaLeuLysAlaGlnTyrLysGluTyrAlaLeuTyrHisArgArg 219522002205 GlnLeuSerGlyAspArgMetArgAsnLeuSerAspPheTrpLeuArg 221022152220 LysLeuIleGlyLeuGluProLeuGlnLeuIleThrAspArgProArg 2225223022352240 ProValGlnPheLysTyrAspGlyAspAspLeuSerIleGluLeuSer 224522502255 LysLysGluThrGluAsnLeuArgGlyValAlaLysArgCysLysSer 226022652270 SerLeuTyrValValLeuValSerValTyrCysValMetLeuAlaSer 227522802285 TyrAlaAsnGlnSerAspValSerValGlyIleProValSerHisArg 229022952300 ThrHisProGlnPheGlnSerValIleGlyPhePheValAsnLeuVal 2305231023152320 ValLeuArgValAspIleSerGlnSerAlaIleCysGlyLeuIleArg 232523302335 ArgValMetLysGluLeuValAspAlaGlnLeuHisGlnAspMetPro 234023452350 PheGlnGluValThrLysLeuLeuGlnValAspAsnAspProSerArg 235523602365 HisProLeuValGlnAsnValPheAsnPheGluSerArgAlaAsnGly 237023752380 GluHisAspAlaArgSerGluAspGluGlySerLeuAlaPheAsnGln 2385239023952400 TyrArgProValGlnProValAspSerValAlaLysPheAspLeuAsn 240524102415 AlaThrValThrGluLeuGluSerGlyLeuArgValAsnPheAsnTyr 242024252430 AlaThrSerLeuPheAsnLysSerThrIleGlnGlyPheLeuHisThr 243524402445 TyrGluTyrLeuLeuArgGlnLeuSerGluLeuSerAlaGluGlyIle 245024552460 AsnGluAspThrGlnLeuSerLeuValArgProThrGluAsnGlyAsp 2465247024752480 LeuHisLeuProLeuAlaGlnSerProLeuAlaThrThrAlaGluGlu 248524902495 GlnLysValAlaSerLeuAsnGlnAlaPheGluArgGluAlaPheLeu 250025052510 AlaAlaGluLysIleAlaValValGlnGlyAspArgAlaLeuSerTyr 251525202525 AlaAspLeuAsnGlyGlnAlaAsnGlnLeuAlaArgTyrIleGlnSer 253025352540 ValSerCysIleGlyAlaAspAspGlyIleAlaLeuMetLeuGluLys 2545255025552560 SerIleAspThrIleIleCysIleLeuAlaIleTrpLysAlaGlyAla 256525702575 AlaTyrValProLeuAspProThrTyrProProGlyArgValGlnLeu 258025852590 IleLeuGluGluIleLysAlaLysAlaValLeuValHisSerSerHis 259526002605 AlaSerLysCysGluArgHisGlyAlaLysValIleAlaValAspSer 261026152620 ProAlaIleGluThrAlaValSerGlnGlnSerAlaAlaAspLeuPro 2625263026352640 ThrIleAlaSerLeuGlyAsnLeuAlaTyrIleIlePheThrSerGly 264526502655 ThrSerGlyLysProLysGlyValLeuValGluGlnLysAlaValLeu 266026652670 LeuLeuArgAspAlaLeuArgGluArgTyrPheGlyArgAspCysThr 267526802685 LysHisHisGlyValLeuPheLeuSerAsnTyrValPheAspPheSer 269026952700 ValGluGlnLeuValLeuSerValLeuSerGlyHisLysLeuIleVal 2705271027152720 ProProAlaGluPheValAlaAspAspGluPheTyrArgMetAlaSer 272527302735 ThrHisGlyLeuSerTyrLeuSerGlyThrProSerLeuLeuGlnLys 274027452750 IleAspLeuAlaArgLeuAspHisLeuGlnValValThrAlaAlaGly 275527602765 GluGluLeuHisAlaThrGlnTyrGluLysMetArgArgArgPheAsn 277027752780 GlyProIleTyrAsnAlaTyrGlyValThrGluThrThrValTyrAsn 2785279027952800 IleIleAlaGluPheThrThrAsnSerIlePheGluAsnAlaLeuArg 280528102815 GluValLeuProGlyThrArgAlaTyrValLeuThrAlaAlaLeuGln 282028252830 ProValProPheAspAlaValGlyGluLeuTyrLeuAlaGlyAspThr 283528402845 ValThrArgGlyTyrLeuAsnGlnProLeuLeuThrAspGlnArgPhe 285028552860 IleProAsnProPheCysLysGluGluAspIleAlaMetGlyArgPhe 2865287028752880 AlaArgLeuTyrLysThrGlyAspLeuValArgSerArgPheAsnArg 288528902895 GlnGlnGlnProGlnLeuGluTyrLeuGlyArgGlyAspLeuGlnIle 290029052910 LysMetArgGlyTyrArgIleGluIleSerGluValGlnAsnValLeu 291529202925 ThrSerSerProGlyValArgGluGlyAlaValValAlaLysTyrGlu 293029352940 AsnAsnAspThrTyrSerArgThrAlaHisSerLeuValGlyTyrTyr 2945295029552960 ThrThrAspAsnGluThrValSerGluAlaAspIleLeuThrPheMet 296529702975 LysAlaArgLeuProThrTyrMetValProSerHisLeuCysCysLeu 298029852990 GluGlyAlaLeuProValThrIleAsnGlyLysLeuAspValArgArg 299530003005 LeuProGluIleIleAsnAspSerAlaGlnSerSerTyrSerProPro 301030153020 ArgAsnIleIleGluAlaLysMetCysArgLeuTrpGluSerAlaLeu 3025303030353040 GlyMetGluArgCysGlyIleAspAspAspLeuPheLysLeuGlyGly 304530503055 AspSerIleThrSerLeuHisLeuValAlaGlnIleHisAsnGlnVal 306030653070 GlyCysLysIleThrValArgAspIlePheGluHisArgThrAlaArg 307530803085 AlaLeuHisAspHisValPheMetLysAspSerAspArgSerAsnVal 309030953100 ThrGlnPheArgThrGluGlnGlyProValIleGlyGluAlaProLeu 3105311031153120 LeuProIleGlnAspTrpPheLeuSerLysAlaLeuGlnHisProMet 312531303135 TyrTrpAsnHisThrPheTyrValArgThrProGluLeuAspValAsp 314031453150 SerLeuSerAlaAlaValArgAspLeuGlnGlnTyrHisAspValPhe 315531603165 ArgMetArgLeuLysArgGluGluValGlyPheValGlnSerPheAla 317031753180 GluAspPheSerProAlaGlnLeuArgValLeuAsnValLysAspVal 3185319031953200 AspGlySerAlaAlaValAsnGluIleLeuAspGlyTrpGlnSerGly 320532103215 PheAsnLeuGluAsnGlyProIleGlySerIleGlyTyrLeuHisGly 322032253230 TyrGluAspArgSerAlaArgValTrpPheSerValHisHisMetAla 323532403245 IleAspThrValSerTrpGlnIleLeuValArgAspLeuGlnThrLeu 325032553260 TyrArgAsnGlySerLeuGlySerLysGlySerSerPheArgGlnTrp 3265327032753280 AlaGluAlaIleGlnAsnTyrLysAlaSerAspSerGluArgAsnHis 328532903295 TrpAsnLysLeuValMetGluThrAlaSerSerIleSerAlaLeuPro 330033053310 ThrSerThrGlySerArgValArgLeuSerArgSerLeuSerProGlu 331533203325 LysThrAlaSerLeuIleGlnGlyGlyIleAspArgGlnAspValSer 333033353340 ValTyrAspSerLeuLeuThrSerValGlyLeuAlaLeuGlnHisIle 3345335033553360 AlaProThrGlyProSerMetValThrIleGluGlyHisGlyArgGlu 336533703375 GluValAspGlnThrLeuAspValSerArgThrMetGlyTrpPheThr 338033853390 ThrMetTyrProPheGluIleProArgLeuSerThrGluAsnIleVal 339534003405 GlnGlyValValAlaValSerGluArgPheArgGlnValProAlaArg 341034153420 GlyValGlyTyrGlyThrLeuTyrGlyTyrThrGlnHisProLeuPro 3425343034353440 GlnValThrValAsnTyrLeuGlyGlnLeuAlaArgLysGlnSerLys 344534503455 ProLysGluTrpValLeuAlaValGlyAspAsnGluPheGluTyrGly 346034653470 LeuMetThrSerProGluAspLysAspArgSerSerSerAlaValAsp 347534803485 ValThrAlaValCysIleAspGlyThrMetIleIleAspValAspSer 349034953500 AlaTrpSerLeuGluGluSerGluGlnPheIleSerSerIleGluGlu 3505351035153520 GlyLeuAsnLysIleLeuAspGlyArgAlaSerGlnGlnThrSerArg 352535303535 PheProAspValProGlnProAlaGluThrTyrThrProTyrPheGlu 354035453550 TyrLeuGluProProArgGlnGlyProThrLeuPheLeuLeuProPro 355535603565 GlyGluGlyGlyAlaGluSerTyrPheAsnAsnIleValLysArgLeu 357035753580 ArgGlnThrAsnMetValValPheAsnAsnTyrTyrLeuHisSerLys 3585359035953600 ArgLeuArgThrPheGluGluLeuAlaGluMetTyrLeuAspGlnVal 360536103615 ArgGlyIleGlnProHisGlyProTyrHisPheIleGlyTrpSerPhe 362036253630 GlyGlyIleLeuAlaMetGluMetSerArgArgLeuValAlaSerAsp 363536403645 GluLysIleGlyPheLeuGlyIleIleAspThrTyrPheAsnValArg 365036553660 GlyAlaThrArgThrIleGlyLeuGlyAspThrGluIleLeuAspPro 3665367036753680 IleHisHisIleTyrAsnProAspProAlaAsnPheGlnArgLeuPro 368536903695 SerAlaThrAspArgIleValLeuPheLysAlaMetArgProAsnAsn 370037053710 LysTyrGluSerGluAsnGlnArgArgLeuTyrGluTyrTyrAspArg 371537203725 ThrArgLeuAsnGlyLeuAspSerLeuLeuProSerAspSerAspVal 373037353740 GlnLeuValProLeuThrAspAspThrHisPheSerTrpValGlyAsn 3745375037553760 ProGlnGlnValGluGlnMetCysAlaThrIleLysGluHisLeuAla 376537703775 ArgTyr (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11601 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: Acremonium chrysogenum (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 388..11526 (D) OTHER INFORMATION: /function="Enzyme" /product= "ACV Synthetase" (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 8050..8052 (D) OTHER INFORMATION: /note= "NNN=GCC, AGU, AGC, UCU, UCC, UCA, or UCG; Xaa=Ala or Ser " (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: GGATGCATGCATTGGCCTGTATCAAAGGTCCGGGATTCCCCAGGAGTATAAGACGTTCGT60 GCTGGGAGATCTAGCGACGTGTTGGGAAATATCGGCCGTAGAGTGCGAAAAAGAACTGGC120 GGAAATATTTCTCCTTGGACTCGGTCACACTCAGTCAGTAGTGGACTGCCAGTCTATCAT180 ACACCTTTGATATCAACATGACTATCCTTACAGGTGCCGACGACGCCTCGTCATACCACA240 GGTATGTCTTCACAGCCTCTGGAAAGCGCAGTTGGGAGCTATCTCTAACATTACCACATC300 AGGCGCAATGGAAGCTCTGATATCCCAAAAGGTGCCATCCACCGCAACGGCTTCGCAGCC360 GCAGCCCCTGACTGCTGGATCCGGTCCGTGGCCCTGGAACAGTGGAAGACT411 ValAlaLeuGluGlnTrpLysThr 15 ACGGTCCAGTCCGTCTCGGAGCGGTGCGATCTGAGCGGGCTGAGCCAG459 ThrValGlnSerValSerGluArgCysAspLeuSerGlyLeuSerGln 101520 CATCCCACCGACTACCAGCTGGCCTCTACGGGCGTGAAGGGCGCAGGC507 HisProThrAspTyrGlnLeuAlaSerThrGlyValLysGlyAlaGly 25303540 GGTAGCAGCATCGAGGAGCGCAGTGCCATCGTCTCAGACGAGTTGTTC555 GlySerSerIleGluGluArgSerAlaIleValSerAspGluLeuPhe 455055 TCGAGTCTGCGAGACGTGTGCTCACAGAGACAGCTGGACCCTCGGTCA603 SerSerLeuArgAspValCysSerGlnArgGlnLeuAspProArgSer 606570 CTCATGCTGTTTTCCGTGCACCAGATGCTCAAGAGGTTCGGAAACGGA651 LeuMetLeuPheSerValHisGlnMetLeuLysArgPheGlyAsnGly 758085 TCTCACACCGTCGTGGCGTCACTCGTAACTTCATCAGAGGGATGCCCT699 SerHisThrValValAlaSerLeuValThrSerSerGluGlyCysPro 9095100 TCAACTTCGGCCTGGAGGGCCATCCCCTCCGTCATCCATCATATAGAG747 SerThrSerAlaTrpArgAlaIleProSerValIleHisHisIleGlu 105110115120 GGCGGAGACAACAACAACACAGTCGCCTCTGCCGTGGAACAGGCGGCG795 GlyGlyAspAsnAsnAsnThrValAlaSerAlaValGluGlnAlaAla 125130135 AATCTCCTGAACTCAGAAGGATCGGGACAGGACCTTCTGATTCCCATC843 AsnLeuLeuAsnSerGluGlySerGlyGlnAspLeuLeuIleProIle 140145150 GGACTCACTGAGCTCGTCAAGTCGGAGCTGATTGACCTCCTGGTCATC891 GlyLeuThrGluLeuValLysSerGluLeuIleAspLeuLeuValIle 155160165 TTCGACGACGAGACAAATAACATACGACTGCCGCAGGACTTCCCACTT939 PheAspAspGluThrAsnAsnIleArgLeuProGlnAspPheProLeu 170175180 ATCCTGCGGATACATCAGCGGCAAGACCACTGGCAGCTGTCAGTCCGG987 IleLeuArgIleHisGlnArgGlnAspHisTrpGlnLeuSerValArg 185190195200 TATCCCTCGCCCCTTTTCGACACCATGGTCATCGACAGCTTTCTGAGC1035 TyrProSerProLeuPheAspThrMetValIleAspSerPheLeuSer 205210215 GCACTTCACAACCTGTTGTCCGCGGTGACAAAACCCTCCCAGCTCGTG1083 AlaLeuHisAsnLeuLeuSerAlaValThrLysProSerGlnLeuVal 220225230 CGCGACATCGAGCTGCTCCCAGAATACCAGGTCGCTCAGCTGGAGAAG1131 ArgAspIleGluLeuLeuProGluTyrGlnValAlaGlnLeuGluLys 235240245 TGGAACAACACAGACGGCGACTACCCCACCGAGAAGCGGCTACATCAT1179 TrpAsnAsnThrAspGlyAspTyrProThrGluLysArgLeuHisHis 250255260 CTGTTCGAGGAGGCAGCAGTGCGTCGTCCCCAACACGTTGCCCTCATC1227 LeuPheGluGluAlaAlaValArgArgProGlnHisValAlaLeuIle 265270275280 TGCGGCGACAAGCGCATCACCTATGAGGAGTTGAATGCTATGGCGAAT1275 CysGlyAspLysArgIleThrTyrGluGluLeuAsnAlaMetAlaAsn 285290295 CGCCTGGCCCACCATCTGGTATCCTCGGGTATCCAGACTGAGCAGCTC1323 ArgLeuAlaHisHisLeuValSerSerGlyIleGlnThrGluGlnLeu 300305310 GTCGGTCTCTTCCTCGACAAGACCGAGCTCATGATCGCTACTATTCTG1371 ValGlyLeuPheLeuAspLysThrGluLeuMetIleAlaThrIleLeu 315320325 GGCATCTGGAAATCTGGTGCCGCGCATGTACCTATCGACCCTGGGTAC1419 GlyIleTrpLysSerGlyAlaAlaHisValProIleAspProGlyTyr 330335340 CCGGACGAGCGTGTCAAGTTCGTCCTGAATGATACGAAGGCGCAAGTG1467 ProAspGluArgValLysPheValLeuAsnAspThrLysAlaGlnVal 345350355360 GTCATTGCTAGTCAGAGGCACGTCGATCGACTGCGGGCTGAGGCTGTT1515 ValIleAlaSerGlnArgHisValAspArgLeuArgAlaGluAlaVal 365370375 GGCGGCCAGCATCTTCGCATCATCGGTCTCGAATCTCTGTTCGACAAC1563 GlyGlyGlnHisLeuArgIleIleGlyLeuGluSerLeuPheAspAsn 380385390 CTTGCTCAACAGACACAACACTCACCAGAGACGTCGGGCAATTTGACC1611 LeuAlaGlnGlnThrGlnHisSerProGluThrSerGlyAsnLeuThr 395400405 CATCTGCCCCTGAACAGCAAACAGCTTGCGTACGTGACATACACCTCG1659 HisLeuProLeuAsnSerLysGlnLeuAlaTyrValThrTyrThrSer 410415420 GGCACCACGGGCTTCCCGAAAGGCATCTACAAGGAGCACACAAGCGTC1707 GlyThrThrGlyPheProLysGlyIleTyrLysGluHisThrSerVal 425430435440 GTTAACAGCATCACCGATCTGTCTGCTCGGTACGGTGTGGCCGGGGAG1755 ValAsnSerIleThrAspLeuSerAlaArgTyrGlyValAlaGlyGlu 445450455 GACGACGAGGTGATACTCGTCTTCTCCGCCTACGTCTTCGAGCCATTC1803 AspAspGluValIleLeuValPheSerAlaTyrValPheGluProPhe 460465470 GTGCGCCAGATGCTCATGGCCCTGACCACGGGCAACTCTCTCGCCATC1851 ValArgGlnMetLeuMetAlaLeuThrThrGlyAsnSerLeuAlaIle 475480485 ATCAGCGACGAGGACAAGTTCGACCCTGACACCCTTATTCCCTTCATC1899 IleSerAspGluAspLysPheAspProAspThrLeuIleProPheIle 490495500 CAAAAACACAAAGTCACTTACATCCACGCCACCTCGTCAGTGTTGCAG1947 GlnLysHisLysValThrTyrIleHisAlaThrSerSerValLeuGln 505510515520 GAGTACGACTTCGGGTCCTGCCCCTCGTTGAAACGCATGATTCTGGTG1995 GluTyrAspPheGlySerCysProSerLeuLysArgMetIleLeuVal 525530535 GGAGAGAACTTGACAGAGCCGCGCTACGAGGCCCTGAGGCAGCGCTTC2043 GlyGluAsnLeuThrGluProArgTyrGluAlaLeuArgGlnArgPhe 540545550 AAGTCGCGCATCCTGAATGAATATGGCTTCACCGAGTCTGCGTTTGTG2091 LysSerArgIleLeuAsnGluTyrGlyPheThrGluSerAlaPheVal 555560565 ACGGCGCTCAACATATTCGAGCCTACCTCACAGAGGAAGGACATGAGT2139 ThrAlaLeuAsnIlePheGluProThrSerGlnArgLysAspMetSer 570575580 CTGGGAAGGCCGGTGCGCAACGTCAAGTGCTATATCTTGGATGCCAAC2187 LeuGlyArgProValArgAsnValLysCysTyrIleLeuAspAlaAsn 585590595600 CTCAAGAGAGTCCCCATCGGTGTTACAGGGGAGCTGCACATCGGTGGC2235 LeuLysArgValProIleGlyValThrGlyGluLeuHisIleGlyGly 605610615 TTGGGTATATCCCGGGGGTACATGAATAGGGAGGAGCTCACAAGGCAG2283 LeuGlyIleSerArgGlyTyrMetAsnArgGluGluLeuThrArgGln 620625630 AAGTTCCTCCCGAACCCCTACCAGACCGATAAGGAGCGCCAACGGGGT2331 LysPheLeuProAsnProTyrGlnThrAspLysGluArgGlnArgGly 635640645 GTCAACTCAACCATGTACAAGACAGGAGATCTGGCCCGCTGGCTACCC2379 ValAsnSerThrMetTyrLysThrGlyAspLeuAlaArgTrpLeuPro 650655660 AGTGGCGAAGTCGAGTATCTCGGCCGTGCCGACTTCCAGATCAAGCTG2427 SerGlyGluValGluTyrLeuGlyArgAlaAspPheGlnIleLysLeu 665670675680 CGCGGCATTCGAATTGAGCCCGGCGAGATCGAGTCCACTCTCGCCATG2475 ArgGlyIleArgIleGluProGlyGluIleGluSerThrLeuAlaMet 685690695 TATCCCGGAATCAGGGCCAGCATCGTCGTGTCAAAGAAGCTTCTCAGT2523 TyrProGlyIleArgAlaSerIleValValSerLysLysLeuLeuSer 700705710 CAGGGGCAGGAGACGATCCAAGACCACCTTGTGGGGTACTATGTTTGC2571 GlnGlyGlnGluThrIleGlnAspHisLeuValGlyTyrTyrValCys 715720725 GATGAGGGCCACATCCCCGAGGGTGACCTGCTGAGCTTCCTGGAGAAG2619 AspGluGlyHisIleProGluGlyAspLeuLeuSerPheLeuGluLys 730735740 AAGCTACCTCGGTACATGGTCCCGACGCGCCTTGTCCAACTGGCTCAG2667 LysLeuProArgTyrMetValProThrArgLeuValGlnLeuAlaGln 745750755760 ATTCCAACCAATATCAACGGCAAGGCGGATCTGCGTGCTCTTCCTGCC2715 IleProThrAsnIleAsnGlyLysAlaAspLeuArgAlaLeuProAla 765770775 GTCGAAGTCGCCGTAGCTCCCACCCACAAGCAGGATGGCGAGCGAGGA2763 ValGluValAlaValAlaProThrHisLysGlnAspGlyGluArgGly 780785790 AACCAGCTGGAGAGCGACCTGGCTGCCATATGGGGCAACATTTTGAGT2811 AsnGlnLeuGluSerAspLeuAlaAlaIleTrpGlyAsnIleLeuSer 795800805 GTTCCCGCTCAAGACATTGGGTCTGAATCCAACTTCTTCCGCCTGGGT2859 ValProAlaGlnAspIleGlySerGluSerAsnPhePheArgLeuGly 810815820 GGCCACAGTATTGCATGCATCCAGCTCATTGCTCGTGTGCGACAGCAG2907 GlyHisSerIleAlaCysIleGlnLeuIleAlaArgValArgGlnGln 825830835840 CTAGGCCAGGGGATTACCCTCGAGGAGGTCTTCCAGACCAAGACGTTG2955 LeuGlyGlnGlyIleThrLeuGluGluValPheGlnThrLysThrLeu 845850855 CGAGCTATGGCTGCCCTCTTGTCGGAAAAGTACACGAAGGCGTCGAAT3003 ArgAlaMetAlaAlaLeuLeuSerGluLysTyrThrLysAlaSerAsn 860865870 GGGACGAACGGAGTGACCAACGGCACTGCTCACGTCAACGGCCACGCA3051 GlyThrAsnGlyValThrAsnGlyThrAlaHisValAsnGlyHisAla 875880885 GCGAACGGCCATGTCAGCGACAGCTACGTGGCCAGCAGTTTGCAGCAA3099 AlaAsnGlyHisValSerAspSerTyrValAlaSerSerLeuGlnGln 890895900 GGCTTTGTTTACCATTCACTCAAGAACGAACTGTCCGAGGCGTACACC3147 GlyPheValTyrHisSerLeuLysAsnGluLeuSerGluAlaTyrThr 905910915920 ATGCAATCCATGATCCACTATGGTGTGCCCCTGAAACGGGATATTTAC3195 MetGlnSerMetIleHisTyrGlyValProLeuLysArgAspIleTyr 925930935 CAAGCGGCATGGCAGAGGGTACAGGGGGAGCACCCTGCACTGCGGCTT3243 GlnAlaAlaTrpGlnArgValGlnGlyGluHisProAlaLeuArgLeu 940945950 CGGTTCACATGGGAGGCCGAAGTGATGCAGATCGTGGACCCGAAATCT3291 ArgPheThrTrpGluAlaGluValMetGlnIleValAspProLysSer 955960965 GAACTCGACTGGCGTGTTGTTGACTGGACCGATGTTTCGAGCCGGGAG3339 GluLeuAspTrpArgValValAspTrpThrAspValSerSerArgGlu 970975980 AAGCAGCTGGTTGCGCTGGAGCAACTCCAAACGGAGGACCTTGCTAAG3387 LysGlnLeuValAlaLeuGluGlnLeuGlnThrGluAspLeuAlaLys 9859909951000 GTCTACCATCTCGATAAGGGGCCCCTTATGCGACTATACCTCATCCTG3435 ValTyrHisLeuAspLysGlyProLeuMetArgLeuTyrLeuIleLeu 100510101015 CTTCCGGACTCAAAGTACTCCTGTCTGTTCAGCTGCCACCATGCCATT3483 LeuProAspSerLysTyrSerCysLeuPheSerCysHisHisAlaIle 102010251030 CTCGATGGGTGGAGTCTGCCCCTGCTCTTCAACAATGTCCACCAGGCC3531 LeuAspGlyTrpSerLeuProLeuLeuPheAsnAsnValHisGlnAla 103510401045 TACCTCGATCTCGTCGAAGGCACTGCTTCGCCCGTCGAGCAGGACGCT3579 TyrLeuAspLeuValGluGlyThrAlaSerProValGluGlnAspAla 105010551060 ACCTACCTACTCGGCCAGCAGTACCTGCAGAGCCACAGGGACGACCAT3627 ThrTyrLeuLeuGlyGlnGlnTyrLeuGlnSerHisArgAspAspHis 1065107010751080 CTCGACTTCTGGGCCGAGCAGATCGGCAGGATCGAAGAGCGCTGCGAC3675 LeuAspPheTrpAlaGluGlnIleGlyArgIleGluGluArgCysAsp 108510901095 ATGAATGCGCTGCTGAATGAGGCCAGCCGATACAAGGTGCCCCTGGCC3723 MetAsnAlaLeuLeuAsnGluAlaSerArgTyrLysValProLeuAla 110011051110 GACTATGACCAAGTCCGCGAGCAGAGGCAGCAGACCATCAGTCTGCCC3771 AspTyrAspGlnValArgGluGlnArgGlnGlnThrIleSerLeuPro 111511201125 TGGAACAACTCCATGGACGCTGGTGTGCGGGAAGAACTCTCCAGTCGT3819 TrpAsnAsnSerMetAspAlaGlyValArgGluGluLeuSerSerArg 113011351140 GGCATCACCCTTCATTCCATTCTACAGACGGTCTGGCACCTGGTCCTC3867 GlyIleThrLeuHisSerIleLeuGlnThrValTrpHisLeuValLeu 1145115011551160 CACTCTTATGGAGGAGGCACCCACACGATCACCGGCACCACCATCTCC3915 HisSerTyrGlyGlyGlyThrHisThrIleThrGlyThrThrIleSer 116511701175 GGCCGTCACCTGCCCGTCCCCGGAATTGAGCGCTCTGTTGGTCTCTTC3963 GlyArgHisLeuProValProGlyIleGluArgSerValGlyLeuPhe 118011851190 ATCAACACACTCCCTATGATCTTTGATCACACCGTCTGCCAGGATATG4011 IleAsnThrLeuProMetIlePheAspHisThrValCysGlnAspMet 119512001205 ACAGCGCTCGAGGCCATTGAGCATGTCCAAGGCCAAGTCAACGCCATG4059 ThrAlaLeuGluAlaIleGluHisValGlnGlyGlnValAsnAlaMet 121012151220 AACTCCCGGGGCAACGTCGAGCTCGGACGCATGAGCAAGAACGACCTC4107 AsnSerArgGlyAsnValGluLeuGlyArgMetSerLysAsnAspLeu 1225123012351240 AAGCACGGGCTCTTCGACACCCTCTTCGTCCTCGAGAACTACCCAAAC4155 LysHisGlyLeuPheAspThrLeuPheValLeuGluAsnTyrProAsn 124512501255 CTCGACACGGAGCAGCGGGAGAAGCACGAGGAGAAGCTCAAGTTCACC4203 LeuAspThrGluGlnArgGluLysHisGluGluLysLeuLysPheThr 126012651270 ATCAAGGGTGGCACGGAGAAGCTCAGTTACCCGCTGGCCGTGATTGCC4251 IleLysGlyGlyThrGluLysLeuSerTyrProLeuAlaValIleAla 127512801285 CAAGAGGACGGCGACAGCGGATGCTCGTTTACGCTCTGCTATGCGGGC4299 GlnGluAspGlyAspSerGlyCysSerPheThrLeuCysTyrAlaGly 129012951300 GAGCTCTTCACGGATGAGTCCATCCAGGCGCTCCTGGACACTGTCCGG4347 GluLeuPheThrAspGluSerIleGlnAlaLeuLeuAspThrValArg 1305131013151320 GACACCCTGAGTGATATTCTCGGGAACATCCATGCCCCTATCCGCAAC4395 AspThrLeuSerAspIleLeuGlyAsnIleHisAlaProIleArgAsn 132513301335 ATGGAGTACCTCTCCTCGAACCAGACGGCGCAGCTCGACAAGTGGAAT4443 MetGluTyrLeuSerSerAsnGlnThrAlaGlnLeuAspLysTrpAsn 134013451350 GCCACCGCCTTCGAGTACCCCAACACCACACTGCACGCCATGTTCGAG4491 AlaThrAlaPheGluTyrProAsnThrThrLeuHisAlaMetPheGlu 135513601365 TCCGAGGCGCAGCAGAAGCCGGACAAGGTGGCCGTGGTGTACGAGGAT4539 SerGluAlaGlnGlnLysProAspLysValAlaValValTyrGluAsp 137013751380 ATCAGGCTGACCTACCGCGAGCTCAACAGCCGTGCCAATGCCCTGGCG4587 IleArgLeuThrTyrArgGluLeuAsnSerArgAlaAsnAlaLeuAla 1385139013951400 TTCTACCTCCTCTCCCAGGCGGCTATCCAACCGAACAAGCTGGTCGGG4635 PheTyrLeuLeuSerGlnAlaAlaIleGlnProAsnLysLeuValGly 140514101415 CTGATCATGGACAAGAGCGAGCACATGATCACGAGCATCCTCGCGGTC4683 LeuIleMetAspLysSerGluHisMetIleThrSerIleLeuAlaVal 142014251430 TGGAAAACGGGTGGAGCCTACGTCCCGATCGACCCTCGATACCCTGAC4731 TrpLysThrGlyGlyAlaTyrValProIleAspProArgTyrProAsp 143514401445 CAGCGTATCCAGTATATCCTGGAGGATACGGCGGCTCTCGCAGTCATC4779 GlnArgIleGlnTyrIleLeuGluAspThrAlaAlaLeuAlaValIle 145014551460 ACGGACAGTCCTCATATTGACCGTCTGCGCAGCATCACCAACAACCGC4827 ThrAspSerProHisIleAspArgLeuArgSerIleThrAsnAsnArg 1465147014751480 CTTCCTGTTATCCAGTCGGACTTTGCTCTCCAACTCCCGCCCAGCCCA4875 LeuProValIleGlnSerAspPheAlaLeuGlnLeuProProSerPro 148514901495 GTTCATCCCGTCTCAAACTGCAAGCCAAGCGACCTCGCCTACATCATG4923 ValHisProValSerAsnCysLysProSerAspLeuAlaTyrIleMet 150015051510 TACACATCCGGCACCACTGGCAACCCCAAGGGTGTCATGGTGGAGCAC4971 TyrThrSerGlyThrThrGlyAsnProLysGlyValMetValGluHis 151515201525 CACGGTGTAGTGAATCTGTGCGTTTCACTCTGCCGGCTCTTCGGCCTT5019 HisGlyValValAsnLeuCysValSerLeuCysArgLeuPheGlyLeu 153015351540 CGGAACACAGATGACGAGGTCATCCTCTCGTTCTCGAACTACGTCTTC5067 ArgAsnThrAspAspGluValIleLeuSerPheSerAsnTyrValPhe 1545155015551560 GACCACTTTGTCGAGCAGATGACGGATGCCCTTCTCAACGGTCAGACT5115 AspHisPheValGluGlnMetThrAspAlaLeuLeuAsnGlyGlnThr 156515701575 CTTGTGGTCCTCAACGACGAGATGCGTGGCGACAAGGAGAGGCTTTAC5163 LeuValValLeuAsnAspGluMetArgGlyAspLysGluArgLeuTyr 158015851590 AGATACATCGAGACCAACCGCGTCACGTACCTCTCGGGGACACCTTCC5211 ArgTyrIleGluThrAsnArgValThrTyrLeuSerGlyThrProSer 159516001605 GTCATCTCCATGTACGAGTTCGACCGGTTCCGCGACCACCTGCGGCGC5259 ValIleSerMetTyrGluPheAspArgPheArgAspHisLeuArgArg 161016151620 GTGGATTGCGTCGGCGAGGCCTTCAGCGAGCCGGTATTCGACAAGATC5307 ValAspCysValGlyGluAlaPheSerGluProValPheAspLysIle 1625163016351640 CGCGAGACGTTCCCGGGTCTCATCATCAACGGTTATGGCCCGACTGAG5355 ArgGluThrPheProGlyLeuIleIleAsnGlyTyrGlyProThrGlu 164516501655 GTGTCTATCACTACCCACAAGCGGCCCTACCCGTTCCCGGAGCGCCGC5403 ValSerIleThrThrHisLysArgProTyrProPheProGluArgArg 166016651670 ACAGACAAGAGCATCGGTTGCCAGCTGGACAACAGCACGAGCTACGTC5451 ThrAspLysSerIleGlyCysGlnLeuAspAsnSerThrSerTyrVal 167516801685 CTCAACGATGACATGAAGCGCGTGCCCATCGGGGCCGTGGGAGAGCTG5499 LeuAsnAspAspMetLysArgValProIleGlyAlaValGlyGluLeu 169016951700 TACCTTGGTGGCGATGGCGTCGCTCGCGGATACCACAACCGGCCAGAC5547 TyrLeuGlyGlyAspGlyValAlaArgGlyTyrHisAsnArgProAsp 1705171017151720 CTGACGGCTGACCGGTTCCCTGCCAACCCCTTCCAGACGGAGCAGGAG5595 LeuThrAlaAspArgPheProAlaAsnProPheGlnThrGluGlnGlu 172517301735 AGACTTGAGGGCCGAAATGCGCGTCTGTATAAGACTGGTGACTTGGTT5643 ArgLeuGluGlyArgAsnAlaArgLeuTyrLysThrGlyAspLeuVal 174017451750 CGCTGGATCCACAATGCAAACGGCGATGGTGAGATCGAGTACCTCGGC5691 ArgTrpIleHisAsnAlaAsnGlyAspGlyGluIleGluTyrLeuGly 175517601765 CGCAACGACTTCCAGGTCAAGATTCGAGGCCAGAGAATCGAGCTGGGA5739 ArgAsnAspPheGlnValLysIleArgGlyGlnArgIleGluLeuGly 177017751780 GAGATCGAGGCCGTGCTTTCATCCTATCCGGGCATCAAACAATCCGTC5787 GluIleGluAlaValLeuSerSerTyrProGlyIleLysGlnSerVal 1785179017951800 GTCCTGGCCAAGGACCGCAAGAATGACGGGCAGAAGTACCTCGTCGGC5835 ValLeuAlaLysAspArgLysAsnAspGlyGlnLysTyrLeuValGly 180518101815 TACTTCGTCTCCTCAGCAGGGTCCCTGTCCGCCCAGGCCATCCGCCGC5883 TyrPheValSerSerAlaGlySerLeuSerAlaGlnAlaIleArgArg 182018251830 TTCATGCTCACGAGCCTGCCCGATTACATGGTTCCTGCGCAGCTGGTG5931 PheMetLeuThrSerLeuProAspTyrMetValProAlaGlnLeuVal 183518401845 CCCATCGCCAAGTTCCCCGTCACCGTGAGCGGGAAGCTCGATGCCAAG5979 ProIleAlaLysPheProValThrValSerGlyLysLeuAspAlaLys 185018551860 GCCTTGCCCGTGCCAGACGATACAGTCGAGGATGACATTGTGCCACCG6027 AlaLeuProValProAspAspThrValGluAspAspIleValProPro 1865187018751880 CGTACCGAGGTTGAGCGCATCCTAGCTGGGATCTGGTCTGAGCTGTTG6075 ArgThrGluValGluArgIleLeuAlaGlyIleTrpSerGluLeuLeu 188518901895 GAGATACCGGTCGACAGGATCAGCATCTACAGTGACTTCTTCAGTCTG6123 GluIleProValAspArgIleSerIleTyrSerAspPhePheSerLeu 190019051910 GGCGGCGACAGTCTCAAGAGTACCAAGCTGTCCTTTGCTGCCACTCGG6171 GlyGlyAspSerLeuLysSerThrLysLeuSerPheAlaAlaThrArg 191519201925 GCTCTCGGTGTGGCCGTCAGTGTCCGCAACTTGTTCAGCCATCCGACT6219 AlaLeuGlyValAlaValSerValArgAsnLeuPheSerHisProThr 193019351940 ATCGAAGCCTTGTCTCAGTGGATTATCAGGGGTTCGAACGAGGTCAAG6267 IleGluAlaLeuSerGlnTrpIleIleArgGlySerAsnGluValLys 1945195019551960 GATGTGGCTGTGGTGAAGGGCGGTGCCAGTCTTGATATCCCCCTATCC6315 AspValAlaValValLysGlyGlyAlaSerLeuAspIleProLeuSer 196519701975 CCTGCCCAGGAAAGACTCATGTTCATCCACGAGTTCGGCCATAGCGGC6363 ProAlaGlnGluArgLeuMetPheIleHisGluPheGlyHisSerGly 198019851990 GAGGATACTGGTGCTTACAATGTGCCTTTGCAGCTGCAGCTTCACCAT6411 GluAspThrGlyAlaTyrAsnValProLeuGlnLeuGlnLeuHisHis 199520002005 GATGTCTGTCTCGAGTCGCTTGAGAAGGCTCTGCGGGATGTCGTCTCG6459 AspValCysLeuGluSerLeuGluLysAlaLeuArgAspValValSer 201020152020 AGACACGAGGCTCTCCGGACCTTGATCACCAGGACCCAGAAGTCCTCC6507 ArgHisGluAlaLeuArgThrLeuIleThrArgThrGlnLysSerSer 2025203020352040 GTGCACTGCCAGAAGATCCTCGACGCCGAAGAAGCGCAAAAGCTCTTC6555 ValHisCysGlnLysIleLeuAspAlaGluGluAlaGlnLysLeuPhe 204520502055 TCTGTTGATGTTCTGCGCCTGACCTCGGAGACGGAGATGCAGGGCAGG6603 SerValAspValLeuArgLeuThrSerGluThrGluMetGlnGlyArg 206020652070 ATGGCCGAGAGTACCGCCCACGCCTTCAAGCTCGACGAGGAACTCCCG6651 MetAlaGluSerThrAlaHisAlaPheLysLeuAspGluGluLeuPro 207520802085 ATTCATGTACGCCTGTACCAGGTTGTACGTGATGGCCGCACGCTCAGC6699 IleHisValArgLeuTyrGlnValValArgAspGlyArgThrLeuSer 209020952100 TTTGCCAGCATCGTCTGCCACCATCTGGCGTTTGACGCGTGGTCATGG6747 PheAlaSerIleValCysHisHisLeuAlaPheAspAlaTrpSerTrp 2105211021152120 GATGTGTTCCAGAGGGACTTGGACGCCTTCTATGCCGTCCATACGAAG6795 AspValPheGlnArgAspLeuAspAlaPheTyrAlaValHisThrLys 212521302135 CACAAGGCTGCCGCCAACCTGCCAACCCTCCGCGTGCAATATAAGGAG6843 HisLysAlaAlaAlaAsnLeuProThrLeuArgValGlnTyrLysGlu 214021452150 TATGCGATAGAGCACCGCCGGGCTCTCCGCGCTGAGCAACACCGTGTT6891 TyrAlaIleGluHisArgArgAlaLeuArgAlaGluGlnHisArgVal 215521602165 CTCGCGGACTACTGGCTGCGCAAGCTCAGTGACATGGAGGCGTCTTAT6939 LeuAlaAspTyrTrpLeuArgLysLeuSerAspMetGluAlaSerTyr 217021752180 CTGGTCCCCGATCGCCCTCGACCGGCGCAGTTTGACTATACCGGGAAC6987 LeuValProAspArgProArgProAlaGlnPheAspTyrThrGlyAsn 2185219021952200 GATCTCCAGTTCTCAACTACTCCCGAGACCACCGCGCAGTTGAAGGAG7035 AspLeuGlnPheSerThrThrProGluThrThrAlaGlnLeuLysGlu 220522102215 CTGGCCAAGCGCGAGGGTTCAAGCCTCTACACCGTTGTGGCGGCGGCG7083 LeuAlaLysArgGluGlySerSerLeuTyrThrValValAlaAlaAla 222022252230 TACTTTCTGCTTCTCTACGTGTACACCAACCAGCGGGATATCACGATT7131 TyrPheLeuLeuLeuTyrValTyrThrAsnGlnArgAspIleThrIle 223522402245 GGTATTCCCGTTGCGCACCGTAACCATCCGGACTTTGAGTCGGTTGTC7179 GlyIleProValAlaHisArgAsnHisProAspPheGluSerValVal 225022552260 GGCTTCTTTGTCAACTTGCTCCCTCTGCGGGTCAACGTGTCTCAGTCG7227 GlyPhePheValAsnLeuLeuProLeuArgValAsnValSerGlnSer 2265227022752280 GACATTCATGGACTTATCCAGGCAGTGCAGAAAGAGCTTGTCGATGCC7275 AspIleHisGlyLeuIleGlnAlaValGlnLysGluLeuValAspAla 228522902295 CAGATCCATCAGGACTTGCCATTCCAGGAGATCACCAAGCTTCTTCAT7323 GlnIleHisGlnAspLeuProPheGlnGluIleThrLysLeuLeuHis 230023052310 GTGCAGCACGATCCAAGCCGCCATCCCCTTCTCCAGGCCGTGTTCAAC7371 ValGlnHisAspProSerArgHisProLeuLeuGlnAlaValPheAsn 231523202325 TGGGAAAACGTACCCGCCAATGTCCACGAGGAGCAGCTGCTTCAGGAG7419 TrpGluAsnValProAlaAsnValHisGluGluGlnLeuLeuGlnGlu 233023352340 TACAAGCCGCCCTCGCCTCTGCCTTCGGCGGCCAAGTTTGATCTCAAC7467 TyrLysProProSerProLeuProSerAlaAlaLysPheAspLeuAsn 2345235023552360 GTCACGGTGAAAGAGAGCGTCAATTCGCTCAACGTCAACTTCAACTAT7515 ValThrValLysGluSerValAsnSerLeuAsnValAsnPheAsnTyr 236523702375 CCTACCAGCCTCTTCGAGGAGGAGACCGTTCAGGGGTTCATGGAAACC7563 ProThrSerLeuPheGluGluGluThrValGlnGlyPheMetGluThr 238023852390 TTCCATCTCCTTCTTCGACAACTGGCCCACAACAAGGCTAGCACAAGC7611 PheHisLeuLeuLeuArgGlnLeuAlaHisAsnLysAlaSerThrSer 239524002405 CTCTCGAAGCTGTCGGTTGAAGATGGAGTGTTGAATCCAGAGCCGACT7659 LeuSerLysLeuSerValGluAspGlyValLeuAsnProGluProThr 241024152420 AACCTTCAGCCCTCAAGCCGGGACAGCGGAAATTCACTCCATGGGCTC7707 AsnLeuGlnProSerSerArgAspSerGlyAsnSerLeuHisGlyLeu 2425243024352440 TTCGAGGACATCGTGGCCTCGACCCCGGACCGCATCGCAATTGCTGAC7755 PheGluAspIleValAlaSerThrProAspArgIleAlaIleAlaAsp 244524502455 GGCACCAGGAGTCTCTCGTACTCCGAACTCAACGAGCGGGCAAACCAG7803 GlyThrArgSerLeuSerTyrSerGluLeuAsnGluArgAlaAsnGln 246024652470 CTCGTACATTTGATCATCTCTTCTGCCAGTATTGTAGCAGACGACCGC7851 LeuValHisLeuIleIleSerSerAlaSerIleValAlaAspAspArg 247524802485 ATCGCTCTTCTTTTGGACAAGAGCATCGATATGGTGATTGCTCTCCTG7899 IleAlaLeuLeuLeuAspLysSerIleAspMetValIleAlaLeuLeu 249024952500 GCAGTTTGGAAGGCCGGTGCCGCATATGTGCCCCTTGACCCGACATAT7947 AlaValTrpLysAlaGlyAlaAlaTyrValProLeuAspProThrTyr 2505251025152520 CCGTCGCAGAGGACTGAGCTCATCTTGGAGGAATCTAGTGCCAGGACG7995 ProSerGlnArgThrGluLeuIleLeuGluGluSerSerAlaArgThr 252525302535 CTCATCACCACTAGAAAGCACACGCCGAGGGGAGGAACAGTCGCAAAT8043 LeuIleThrThrArgLysHisThrProArgGlyGlyThrValAlaAsn 254025452550 GTTCCANNNGTGGTCCTTGACAGCCCCGAGACCCTAGCCTGCCTCAAC8091 ValProXaaValValLeuAspSerProGluThrLeuAlaCysLeuAsn 255525602565 CAGCAGTCAAAGGAAAACCCGACAACGTCAACGCAGAAACCGTCCGAC8139 GlnGlnSerLysGluAsnProThrThrSerThrGlnLysProSerAsp 257025752580 CTCGCATATGTCATCTTCACCTCGGGAACCACAGGCAAGCCCAAGGGG8187 LeuAlaTyrValIlePheThrSerGlyThrThrGlyLysProLysGly 2585259025952600 GTTCTGGTGGAGCACCAGAGCGTAGTCCAGCTGCGCAATTCCCTCATC8235 ValLeuValGluHisGlnSerValValGlnLeuArgAsnSerLeuIle 260526102615 GAGCGATACTTCGGCGAGACCAACGGGTCTCACGCCGTGCTCTTCCTG8283 GluArgTyrPheGlyGluThrAsnGlySerHisAlaValLeuPheLeu 262026252630 TCCAACTACGTCTTCGACTTCTCTCTTGAACAGCTCTGTCTCTCAGTC8331 SerAsnTyrValPheAspPheSerLeuGluGlnLeuCysLeuSerVal 263526402645 TTGGGTGGAAACAAGCTCATCATTCCACCAGAGGAGGGTCTCACGCAC8379 LeuGlyGlyAsnLysLeuIleIleProProGluGluGlyLeuThrHis 265026552660 GAGGCATTCTACGACATCGGCCGCAGGGAGAAGCTATCCTATCTCAGC8427 GluAlaPheTyrAspIleGlyArgArgGluLysLeuSerTyrLeuSer 2665267026752680 GGGACGCCCTCGGTGCTGCAGCAGATTGAGCTCTCCCGTCTGCCGCAT8475 GlyThrProSerValLeuGlnGlnIleGluLeuSerArgLeuProHis 268526902695 CTTCACATGGTCACCGCTGCGGGCGAGGAGTTCCACGCTAGTCAGTTT8523 LeuHisMetValThrAlaAlaGlyGluGluPheHisAlaSerGlnPhe 270027052710 GAGAAGATGCGCTCCCAGTTCGCGGGCCAGATCAACAACGCCTATGGT8571 GluLysMetArgSerGlnPheAlaGlyGlnIleAsnAsnAlaTyrGly 271527202725 ATCACTGAGACGACCGTGTACAACATCATCACCACGTTCAAGGGCGAT8619 IleThrGluThrThrValTyrAsnIleIleThrThrPheLysGlyAsp 273027352740 GCCCCCTTTACCAAGGCACTCTGCCACGGGATCCCCGGAAGTCACGTC8667 AlaProPheThrLysAlaLeuCysHisGlyIleProGlySerHisVal 2745275027552760 TACGTCCTGAACGACCGACTTCAGCGTGTTCCTTTCAACGCTGTTGGC8715 TyrValLeuAsnAspArgLeuGlnArgValProPheAsnAlaValGly 276527702775 GAGCTCTACTTGGGCGGTGACTGCCTTGCTCGCGGGTACCTCAACCAG8763 GluLeuTyrLeuGlyGlyAspCysLeuAlaArgGlyTyrLeuAsnGln 278027852790 GATGCCCTGACCAACGAGCGATTCATCCCCAACCCTTTCTACGAGCCG8811 AspAlaLeuThrAsnGluArgPheIleProAsnProPheTyrGluPro 279528002805 AAACAGGCAAGTGACAGTCGTCCCCAGAGACTCTACAAGACTGGAGAT8859 LysGlnAlaSerAspSerArgProGlnArgLeuTyrLysThrGlyAsp 281028152820 CTGGTGCGCTTCCGTGGACCCCACCATCTCGAGTATCTCGGCCGCAAG8907 LeuValArgPheArgGlyProHisHisLeuGluTyrLeuGlyArgLys 2825283028352840 GACCAGCAGGTCAAGCTGAGGGGCTTCCGCATCGAGCTCTCCGAGGTG8955 AspGlnGlnValLysLeuArgGlyPheArgIleGluLeuSerGluVal 284528502855 CGGGATGCCGTCCTAGCCATCTCTGCTGTTAAGGAGGCTGCCGTCATC9003 ArgAspAlaValLeuAlaIleSerAlaValLysGluAlaAlaValIle 286028652870 CCCAAGTATGACGAGGATGGCTCCGATTCACGAAGGGTCAGCGCCATC9051 ProLysTyrAspGluAspGlySerAspSerArgArgValSerAlaIle 287528802885 GTCTGCTACTACACGCTCAACGCCGGAACTGTGTGCGAAGCATCGAGT9099 ValCysTyrTyrThrLeuAsnAlaGlyThrValCysGluAlaSerSer 289028952900 ATCCGTGACCACCTGCACGCCAACCTTCCCCCGTACATGGTCCCAAGT9147 IleArgAspHisLeuHisAlaAsnLeuProProTyrMetValProSer 2905291029152920 CAGATCCACCAGTTGGAGGGATCTCTCCCCGTGACCGTCAATGGGAAG9195 GlnIleHisGlnLeuGluGlySerLeuProValThrValAsnGlyLys 292529302935 CTCGACCTGAACAGGCTCTCCACAACTCAAGTCTCGCAGCCAGAGCTT9243 LeuAspLeuAsnArgLeuSerThrThrGlnValSerGlnProGluLeu 294029452950 TACACCGCTCCACGAAATTCGACAGAGGAAACCTTGTGCCAGCTTTGG9291 TyrThrAlaProArgAsnSerThrGluGluThrLeuCysGlnLeuTrp 295529602965 GCATCTCTCCTAGGCGTCGACCACTGCGGCATTGACGACGACCTGTTT9339 AlaSerLeuLeuGlyValAspHisCysGlyIleAspAspAspLeuPhe 297029752980 GCCCGAGGCGGCGACAGCATCTCCTCTCTCCGACTAGTGGGTGACATC9387 AlaArgGlyGlyAspSerIleSerSerLeuArgLeuValGlyAspIle 2985299029953000 TACCGCGCGCTAGGACGCAAGGTCACCGTCAAGGACATCTACCTCCAC9435 TyrArgAlaLeuGlyArgLysValThrValLysAspIleTyrLeuHis 300530103015 CGCAGCGTCCGAGCCCTAAGCGAAAATGTCCTGACCGACCAGAAGGAT9483 ArgSerValArgAlaLeuSerGluAsnValLeuThrAspGlnLysAsp 302030253030 AAGGGTACTCTGCCAGCGTCTCCTCCCCTCCAGCGAGCGGAGCAGGGC9531 LysGlyThrLeuProAlaSerProProLeuGlnArgAlaGluGlnGly 303530403045 CAGGTTGAGGGCGACGCACCGCTTCTCCCCATCCAGGACTGGTTCCTT9579 GlnValGluGlyAspAlaProLeuLeuProIleGlnAspTrpPheLeu 305030553060 TCCAAGCCCCTGGATAACCCCGCTTACTGGAACCACTGCTTCACCATT9627 SerLysProLeuAspAsnProAlaTyrTrpAsnHisCysPheThrIle 3065307030753080 CGAACCGGGGCACTCTCCGTCGAAGGGCTCCGGGGTGCTCTGAAGCTG9675 ArgThrGlyAlaLeuSerValGluGlyLeuArgGlyAlaLeuLysLeu 308530903095 CTGCAGGAGCGCCACGACGTGCTGCGTCTGAGACTGCAACGCCGGGAC9723 LeuGlnGluArgHisAspValLeuArgLeuArgLeuGlnArgArgAsp 310031053110 GAAGGTCGCCATGTTCAGACCTTTGCGCGTGACTGCGCGCAACCTCGC9771 GluGlyArgHisValGlnThrPheAlaArgAspCysAlaGlnProArg 311531203125 TTGACTGTGCTAGACCGACGAAGCTTCGAGGACGCAGAGGATGTACAG9819 LeuThrValLeuAspArgArgSerPheGluAspAlaGluAspValGln 313031353140 GAGGCTCTCTGCGAGATCCAATCTCATTTCGACCTCGAGAATGGACCC9867 GluAlaLeuCysGluIleGlnSerHisPheAspLeuGluAsnGlyPro 3145315031553160 CTCTACACAGTGGCGTACATCCACGGTTACGAGGACGGCTCCGCCCGA9915 LeuTyrThrValAlaTyrIleHisGlyTyrGluAspGlySerAlaArg 316531703175 GTGTGGTTTGCCTGCCATCACGTCATGGTCGACACTGTGAGCTGGAAC9963 ValTrpPheAlaCysHisHisValMetValAspThrValSerTrpAsn 318031853190 ATTATACTGCAAGACCTGCAGGCTCTCTATCATGGAGACAGCCTTGGT10011 IleIleLeuGlnAspLeuGlnAlaLeuTyrHisGlyAspSerLeuGly 319532003205 CCCAAGAGCAGCAGCGTGCAGCAGTGGTCGCTAGCTGTCAGCGACTAC10059 ProLysSerSerSerValGlnGlnTrpSerLeuAlaValSerAspTyr 321032153220 AAAATGCCACTGTCGGAGAGGGCGCATTGGAATGTGCTCAGGAAGACA10107 LysMetProLeuSerGluArgAlaHisTrpAsnValLeuArgLysThr 3225323032353240 GTCGCCCAGAGCTTCGAGACCCTGCCTATCTGCATGGGCGGCGTGCTC10155 ValAlaGlnSerPheGluThrLeuProIleCysMetGlyGlyValLeu 324532503255 CAGTGCCAGGAGAAGTTCTCGAGGGAAACGACAACAGCTCTGCTCTCC10203 GlnCysGlnGluLysPheSerArgGluThrThrThrAlaLeuLeuSer 326032653270 AAGGCCTGCCCTGCCTTGGACTCCGGTATGCATGAGATCCTTCTCATG10251 LysAlaCysProAlaLeuAspSerGlyMetHisGluIleLeuLeuMet 327532803285 GCCGTGGGCTCCGCGCTGCAGAAGGCGGCAGGGGATGTCCCTCAGGTC10299 AlaValGlySerAlaLeuGlnLysAlaAlaGlyAspValProGlnVal 329032953300 GTCACGATAGAGGGTCACGGGCGCGAAGATACTATCGACGCAACTCTG10347 ValThrIleGluGlyHisGlyArgGluAspThrIleAspAlaThrLeu 3305331033153320 GACGTCAGCCGGACAGTCGGCTGGTTCACGAGCATGTACCCCTTCGAG10395 AspValSerArgThrValGlyTrpPheThrSerMetTyrProPheGlu 332533303335 ATCCCCAAAGTGACCGACCCCGCTCAGGGCGTCGTCGATGTCAAGGAG10443 IleProLysValThrAspProAlaGlnGlyValValAspValLysGlu 334033453350 GCGATGCGTCGCGTGCCGAATAGGGGTGTCGGTTACGGTCCAGCCTAC10491 AlaMetArgArgValProAsnArgGlyValGlyTyrGlyProAlaTyr 335533603365 GGATACGGCGGATCGTGCCTGCCCGCGGTGAGCTTCAACTACCTTGGT10539 GlyTyrGlyGlySerCysLeuProAlaValSerPheAsnTyrLeuGly 337033753380 CGCCTGGACCAGGCTTCCTCGGGGGCTCAAAGGGACTGGACGCTGGTC10587 ArgLeuAspGlnAlaSerSerGlyAlaGlnArgAspTrpThrLeuVal 3385339033953400 ATGGATGAAGACGAGTATCCGGTCGGACTGTGCACCAGCGCTGAGGAC10635 MetAspGluAspGluTyrProValGlyLeuCysThrSerAlaGluAsp 340534103415 TCGGGACGAAGCTCCTCCATGGTGGATTTCACCTTCTCTATCTCTGGC10683 SerGlyArgSerSerSerMetValAspPheThrPheSerIleSerGly 342034253430 GGCCAGCTTGTCATGGATATGAGTAGCAGCTGGGGCCACGGCGCACGA10731 GlyGlnLeuValMetAspMetSerSerSerTrpGlyHisGlyAlaArg 343534403445 AATGAATTCGTTCGCACAGTTCGTAACACACTAGATGACTTGATCAAA10779 AsnGluPheValArgThrValArgAsnThrLeuAspAspLeuIleLys 345034553460 ACAACGAGCAGCAGGGACTTCAGCGCACCTCTGCCTCCGTCGGATCAG10827 ThrThrSerSerArgAspPheSerAlaProLeuProProSerAspGln 3465347034753480 GAGTCCAGCTTCACCCCTTATTTTGTCTTCGAAGAGGGCGAGCGACAC10875 GluSerSerPheThrProTyrPheValPheGluGluGlyGluArgHis 348534903495 GGCGCTCCGCTCTTCCTGCTCCCACCTGGCGAAGGCGGAGCGGAGAGC10923 GlyAlaProLeuPheLeuLeuProProGlyGluGlyGlyAlaGluSer 350035053510 TACTTCCACAACATTGTCAAGGGTCTCCCGAACCGCAATCTTGTCGTG10971 TyrPheHisAsnIleValLysGlyLeuProAsnArgAsnLeuValVal 351535203525 TTCAACAATCATTACCGCGAGGAGAAGACGCTCCGGACCATCGAGGCG11019 PheAsnAsnHisTyrArgGluGluLysThrLeuArgThrIleGluAla 353035353540 CTGGCCGAGTACTACCTGTCGCACATCCGATCCATCCAGCCGGAGGGG11067 LeuAlaGluTyrTyrLeuSerHisIleArgSerIleGlnProGluGly 3545355035553560 CCATACCACATCCTCGGCTGGAGTTTCGGAGGCATCCTCGGTCTCGAG11115 ProTyrHisIleLeuGlyTrpSerPheGlyGlyIleLeuGlyLeuGlu 356535703575 GCGGCAAAGCGATTGACTGGCGAGGGTCACAAGATTGCCACGCTGGCA11163 AlaAlaLysArgLeuThrGlyGluGlyHisLysIleAlaThrLeuAla 358035853590 CTTATCGATCCGTACTTTGACATCCCGTCCGCGTCCAAGGCCATCGGC11211 LeuIleAspProTyrPheAspIleProSerAlaSerLysAlaIleGly 359536003605 CAACCTGACGATGCCTGCGTCTTGGACCCCATATACCACGTCTACCAC11259 GlnProAspAspAlaCysValLeuAspProIleTyrHisValTyrHis 361036153620 CCGTCGCCGGAGAGCTTCAGGACGGTGTCATCTCTCACTAATCACATA11307 ProSerProGluSerPheArgThrValSerSerLeuThrAsnHisIle 3625363036353640 GCCCTGTTCAAGGCTACCGAGACGAATGACCAGCATGGCAATGCCACG11355 AlaLeuPheLysAlaThrGluThrAsnAspGlnHisGlyAsnAlaThr 364536503655 CAGCAGGCCCTGTATGAGTGGTTTGCCACGTGCCCTTTGAACAACCTG11403 GlnGlnAlaLeuTyrGluTrpPheAlaThrCysProLeuAsnAsnLeu 366036653670 GACAAGTTTTTGGCGGCCGACACGATCAAGGTGGTTCCTCTGGAGGGT11451 AspLysPheLeuAlaAlaAspThrIleLysValValProLeuGluGly 367536803685 ACACATTTTACCTGGGTGCACCACCCGGAGCAGGTGCGCTCAATGTGC11499 ThrHisPheThrTrpValHisHisProGluGlnValArgSerMetCys 369036953700 ACTATGCTGGATGAATGGCTTGGGTGAACGAGGCAGTTGCTGTGAGAGAATGAG11553 ThrMetLeuAspGluTrpLeuGly 37053710 AATGAGACACAAAACGCGGGCGGAAGAGAGACTTCCTCGGACGGCGGG11601 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3712 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION: 2555 (D) OTHER INFORMATION: /note= "Xaa=Ala or Ser" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: ValAlaLeuGluGlnTrpLysThrThrValGlnSerValSerGluArg 151015 CysAspLeuSerGlyLeuSerGlnHisProThrAspTyrGlnLeuAla 202530 SerThrGlyValLysGlyAlaGlyGlySerSerIleGluGluArgSer 354045 AlaIleValSerAspGluLeuPheSerSerLeuArgAspValCysSer 505560 GlnArgGlnLeuAspProArgSerLeuMetLeuPheSerValHisGln 65707580 MetLeuLysArgPheGlyAsnGlySerHisThrValValAlaSerLeu 859095 ValThrSerSerGluGlyCysProSerThrSerAlaTrpArgAlaIle 100105110 ProSerValIleHisHisIleGluGlyGlyAspAsnAsnAsnThrVal 115120125 AlaSerAlaValGluGlnAlaAlaAsnLeuLeuAsnSerGluGlySer 130135140 GlyGlnAspLeuLeuIleProIleGlyLeuThrGluLeuValLysSer 145150155160 GluLeuIleAspLeuLeuValIlePheAspAspGluThrAsnAsnIle 165170175 ArgLeuProGlnAspPheProLeuIleLeuArgIleHisGlnArgGln 180185190 AspHisTrpGlnLeuSerValArgTyrProSerProLeuPheAspThr 195200205 MetValIleAspSerPheLeuSerAlaLeuHisAsnLeuLeuSerAla 210215220 ValThrLysProSerGlnLeuValArgAspIleGluLeuLeuProGlu 225230235240 TyrGlnValAlaGlnLeuGluLysTrpAsnAsnThrAspGlyAspTyr 245250255 ProThrGluLysArgLeuHisHisLeuPheGluGluAlaAlaValArg 260265270 ArgProGlnHisValAlaLeuIleCysGlyAspLysArgIleThrTyr 275280285 GluGluLeuAsnAlaMetAlaAsnArgLeuAlaHisHisLeuValSer 290295300 SerGlyIleGlnThrGluGlnLeuValGlyLeuPheLeuAspLysThr 305310315320 GluLeuMetIleAlaThrIleLeuGlyIleTrpLysSerGlyAlaAla 325330335 HisValProIleAspProGlyTyrProAspGluArgValLysPheVal 340345350 LeuAsnAspThrLysAlaGlnValValIleAlaSerGlnArgHisVal 355360365 AspArgLeuArgAlaGluAlaValGlyGlyGlnHisLeuArgIleIle 370375380 GlyLeuGluSerLeuPheAspAsnLeuAlaGlnGlnThrGlnHisSer 385390395400 ProGluThrSerGlyAsnLeuThrHisLeuProLeuAsnSerLysGln 405410415 LeuAlaTyrValThrTyrThrSerGlyThrThrGlyPheProLysGly 420425430 IleTyrLysGluHisThrSerValValAsnSerIleThrAspLeuSer 435440445 AlaArgTyrGlyValAlaGlyGluAspAspGluValIleLeuValPhe 450455460 SerAlaTyrValPheGluProPheValArgGlnMetLeuMetAlaLeu 465470475480 ThrThrGlyAsnSerLeuAlaIleIleSerAspGluAspLysPheAsp 485490495 ProAspThrLeuIleProPheIleGlnLysHisLysValThrTyrIle 500505510 HisAlaThrSerSerValLeuGlnGluTyrAspPheGlySerCysPro 515520525 SerLeuLysArgMetIleLeuValGlyGluAsnLeuThrGluProArg 530535540 TyrGluAlaLeuArgGlnArgPheLysSerArgIleLeuAsnGluTyr 545550555560 GlyPheThrGluSerAlaPheValThrAlaLeuAsnIlePheGluPro 565570575 ThrSerGlnArgLysAspMetSerLeuGlyArgProValArgAsnVal 580585590 LysCysTyrIleLeuAspAlaAsnLeuLysArgValProIleGlyVal 595600605 ThrGlyGluLeuHisIleGlyGlyLeuGlyIleSerArgGlyTyrMet 610615620 AsnArgGluGluLeuThrArgGlnLysPheLeuProAsnProTyrGln 625630635640 ThrAspLysGluArgGlnArgGlyValAsnSerThrMetTyrLysThr 645650655 GlyAspLeuAlaArgTrpLeuProSerGlyGluValGluTyrLeuGly 660665670 ArgAlaAspPheGlnIleLysLeuArgGlyIleArgIleGluProGly 675680685 GluIleGluSerThrLeuAlaMetTyrProGlyIleArgAlaSerIle 690695700 ValValSerLysLysLeuLeuSerGlnGlyGlnGluThrIleGlnAsp 705710715720 HisLeuValGlyTyrTyrValCysAspGluGlyHisIleProGluGly 725730735 AspLeuLeuSerPheLeuGluLysLysLeuProArgTyrMetValPro 740745750 ThrArgLeuValGlnLeuAlaGlnIleProThrAsnIleAsnGlyLys 755760765 AlaAspLeuArgAlaLeuProAlaValGluValAlaValAlaProThr 770775780 HisLysGlnAspGlyGluArgGlyAsnGlnLeuGluSerAspLeuAla 785790795800 AlaIleTrpGlyAsnIleLeuSerValProAlaGlnAspIleGlySer 805810815 GluSerAsnPhePheArgLeuGlyGlyHisSerIleAlaCysIleGln 820825830 LeuIleAlaArgValArgGlnGlnLeuGlyGlnGlyIleThrLeuGlu 835840845 GluValPheGlnThrLysThrLeuArgAlaMetAlaAlaLeuLeuSer 850855860 GluLysTyrThrLysAlaSerAsnGlyThrAsnGlyValThrAsnGly 865870875880 ThrAlaHisValAsnGlyHisAlaAlaAsnGlyHisValSerAspSer 885890895 TyrValAlaSerSerLeuGlnGlnGlyPheValTyrHisSerLeuLys 900905910 AsnGluLeuSerGluAlaTyrThrMetGlnSerMetIleHisTyrGly 915920925 ValProLeuLysArgAspIleTyrGlnAlaAlaTrpGlnArgValGln 930935940 GlyGluHisProAlaLeuArgLeuArgPheThrTrpGluAlaGluVal 945950955960 MetGlnIleValAspProLysSerGluLeuAspTrpArgValValAsp 965970975 TrpThrAspValSerSerArgGluLysGlnLeuValAlaLeuGluGln 980985990 LeuGlnThrGluAspLeuAlaLysValTyrHisLeuAspLysGlyPro 99510001005 LeuMetArgLeuTyrLeuIleLeuLeuProAspSerLysTyrSerCys 101010151020 LeuPheSerCysHisHisAlaIleLeuAspGlyTrpSerLeuProLeu 1025103010351040 LeuPheAsnAsnValHisGlnAlaTyrLeuAspLeuValGluGlyThr 104510501055 AlaSerProValGluGlnAspAlaThrTyrLeuLeuGlyGlnGlnTyr 106010651070 LeuGlnSerHisArgAspAspHisLeuAspPheTrpAlaGluGlnIle 107510801085 GlyArgIleGluGluArgCysAspMetAsnAlaLeuLeuAsnGluAla 109010951100 SerArgTyrLysValProLeuAlaAspTyrAspGlnValArgGluGln 1105111011151120 ArgGlnGlnThrIleSerLeuProTrpAsnAsnSerMetAspAlaGly 112511301135 ValArgGluGluLeuSerSerArgGlyIleThrLeuHisSerIleLeu 114011451150 GlnThrValTrpHisLeuValLeuHisSerTyrGlyGlyGlyThrHis 115511601165 ThrIleThrGlyThrThrIleSerGlyArgHisLeuProValProGly 117011751180 IleGluArgSerValGlyLeuPheIleAsnThrLeuProMetIlePhe 1185119011951200 AspHisThrValCysGlnAspMetThrAlaLeuGluAlaIleGluHis 120512101215 ValGlnGlyGlnValAsnAlaMetAsnSerArgGlyAsnValGluLeu 122012251230 GlyArgMetSerLysAsnAspLeuLysHisGlyLeuPheAspThrLeu 123512401245 PheValLeuGluAsnTyrProAsnLeuAspThrGluGlnArgGluLys 125012551260 HisGluGluLysLeuLysPheThrIleLysGlyGlyThrGluLysLeu 1265127012751280 SerTyrProLeuAlaValIleAlaGlnGluAspGlyAspSerGlyCys 128512901295 SerPheThrLeuCysTyrAlaGlyGluLeuPheThrAspGluSerIle 130013051310 GlnAlaLeuLeuAspThrValArgAspThrLeuSerAspIleLeuGly 131513201325 AsnIleHisAlaProIleArgAsnMetGluTyrLeuSerSerAsnGln 133013351340 ThrAlaGlnLeuAspLysTrpAsnAlaThrAlaPheGluTyrProAsn 1345135013551360 ThrThrLeuHisAlaMetPheGluSerGluAlaGlnGlnLysProAsp 136513701375 LysValAlaValValTyrGluAspIleArgLeuThrTyrArgGluLeu 138013851390 AsnSerArgAlaAsnAlaLeuAlaPheTyrLeuLeuSerGlnAlaAla 139514001405 IleGlnProAsnLysLeuValGlyLeuIleMetAspLysSerGluHis 141014151420 MetIleThrSerIleLeuAlaValTrpLysThrGlyGlyAlaTyrVal 1425143014351440 ProIleAspProArgTyrProAspGlnArgIleGlnTyrIleLeuGlu 144514501455 AspThrAlaAlaLeuAlaValIleThrAspSerProHisIleAspArg 146014651470 LeuArgSerIleThrAsnAsnArgLeuProValIleGlnSerAspPhe 147514801485 AlaLeuGlnLeuProProSerProValHisProValSerAsnCysLys 149014951500 ProSerAspLeuAlaTyrIleMetTyrThrSerGlyThrThrGlyAsn 1505151015151520 ProLysGlyValMetValGluHisHisGlyValValAsnLeuCysVal 152515301535 SerLeuCysArgLeuPheGlyLeuArgAsnThrAspAspGluValIle 154015451550 LeuSerPheSerAsnTyrValPheAspHisPheValGluGlnMetThr 155515601565 AspAlaLeuLeuAsnGlyGlnThrLeuValValLeuAsnAspGluMet 157015751580 ArgGlyAspLysGluArgLeuTyrArgTyrIleGluThrAsnArgVal 1585159015951600 ThrTyrLeuSerGlyThrProSerValIleSerMetTyrGluPheAsp 160516101615 ArgPheArgAspHisLeuArgArgValAspCysValGlyGluAlaPhe 162016251630 SerGluProValPheAspLysIleArgGluThrPheProGlyLeuIle 163516401645 IleAsnGlyTyrGlyProThrGluValSerIleThrThrHisLysArg 165016551660 ProTyrProPheProGluArgArgThrAspLysSerIleGlyCysGln 1665167016751680 LeuAspAsnSerThrSerTyrValLeuAsnAspAspMetLysArgVal 168516901695 ProIleGlyAlaValGlyGluLeuTyrLeuGlyGlyAspGlyValAla 170017051710 ArgGlyTyrHisAsnArgProAspLeuThrAlaAspArgPheProAla 171517201725 AsnProPheGlnThrGluGlnGluArgLeuGluGlyArgAsnAlaArg 173017351740 LeuTyrLysThrGlyAspLeuValArgTrpIleHisAsnAlaAsnGly 1745175017551760 AspGlyGluIleGluTyrLeuGlyArgAsnAspPheGlnValLysIle 176517701775 ArgGlyGlnArgIleGluLeuGlyGluIleGluAlaValLeuSerSer 178017851790 TyrProGlyIleLysGlnSerValValLeuAlaLysAspArgLysAsn 179518001805 AspGlyGlnLysTyrLeuValGlyTyrPheValSerSerAlaGlySer 181018151820 LeuSerAlaGlnAlaIleArgArgPheMetLeuThrSerLeuProAsp 1825183018351840 TyrMetValProAlaGlnLeuValProIleAlaLysPheProValThr 184518501855 ValSerGlyLysLeuAspAlaLysAlaLeuProValProAspAspThr 186018651870 ValGluAspAspIleValProProArgThrGluValGluArgIleLeu 187518801885 AlaGlyIleTrpSerGluLeuLeuGluIleProValAspArgIleSer 189018951900 IleTyrSerAspPhePheSerLeuGlyGlyAspSerLeuLysSerThr 1905191019151920 LysLeuSerPheAlaAlaThrArgAlaLeuGlyValAlaValSerVal 192519301935 ArgAsnLeuPheSerHisProThrIleGluAlaLeuSerGlnTrpIle 194019451950 IleArgGlySerAsnGluValLysAspValAlaValValLysGlyGly 195519601965 AlaSerLeuAspIleProLeuSerProAlaGlnGluArgLeuMetPhe 197019751980 IleHisGluPheGlyHisSerGlyGluAspThrGlyAlaTyrAsnVal 1985199019952000 ProLeuGlnLeuGlnLeuHisHisAspValCysLeuGluSerLeuGlu 200520102015 LysAlaLeuArgAspValValSerArgHisGluAlaLeuArgThrLeu 202020252030 IleThrArgThrGlnLysSerSerValHisCysGlnLysIleLeuAsp 203520402045 AlaGluGluAlaGlnLysLeuPheSerValAspValLeuArgLeuThr 205020552060 SerGluThrGluMetGlnGlyArgMetAlaGluSerThrAlaHisAla 2065207020752080 PheLysLeuAspGluGluLeuProIleHisValArgLeuTyrGlnVal 208520902095 ValArgAspGlyArgThrLeuSerPheAlaSerIleValCysHisHis 210021052110 LeuAlaPheAspAlaTrpSerTrpAspValPheGlnArgAspLeuAsp 211521202125 AlaPheTyrAlaValHisThrLysHisLysAlaAlaAlaAsnLeuPro 213021352140 ThrLeuArgValGlnTyrLysGluTyrAlaIleGluHisArgArgAla 2145215021552160 LeuArgAlaGluGlnHisArgValLeuAlaAspTyrTrpLeuArgLys 216521702175 LeuSerAspMetGluAlaSerTyrLeuValProAspArgProArgPro 218021852190 AlaGlnPheAspTyrThrGlyAsnAspLeuGlnPheSerThrThrPro 219522002205 GluThrThrAlaGlnLeuLysGluLeuAlaLysArgGluGlySerSer 221022152220 LeuTyrThrValValAlaAlaAlaTyrPheLeuLeuLeuTyrValTyr 2225223022352240 ThrAsnGlnArgAspIleThrIleGlyIleProValAlaHisArgAsn 224522502255 HisProAspPheGluSerValValGlyPhePheValAsnLeuLeuPro 226022652270 LeuArgValAsnValSerGlnSerAspIleHisGlyLeuIleGlnAla 227522802285 ValGlnLysGluLeuValAspAlaGlnIleHisGlnAspLeuProPhe 229022952300 GlnGluIleThrLysLeuLeuHisValGlnHisAspProSerArgHis 2305231023152320 ProLeuLeuGlnAlaValPheAsnTrpGluAsnValProAlaAsnVal 232523302335 HisGluGluGlnLeuLeuGlnGluTyrLysProProSerProLeuPro 234023452350 SerAlaAlaLysPheAspLeuAsnValThrValLysGluSerValAsn 235523602365 SerLeuAsnValAsnPheAsnTyrProThrSerLeuPheGluGluGlu 237023752380 ThrValGlnGlyPheMetGluThrPheHisLeuLeuLeuArgGlnLeu 2385239023952400 AlaHisAsnLysAlaSerThrSerLeuSerLysLeuSerValGluAsp 240524102415 GlyValLeuAsnProGluProThrAsnLeuGlnProSerSerArgAsp 242024252430 SerGlyAsnSerLeuHisGlyLeuPheGluAspIleValAlaSerThr 243524402445 ProAspArgIleAlaIleAlaAspGlyThrArgSerLeuSerTyrSer 245024552460 GluLeuAsnGluArgAlaAsnGlnLeuValHisLeuIleIleSerSer 2465247024752480 AlaSerIleValAlaAspAspArgIleAlaLeuLeuLeuAspLysSer 248524902495 IleAspMetValIleAlaLeuLeuAlaValTrpLysAlaGlyAlaAla 250025052510 TyrValProLeuAspProThrTyrProSerGlnArgThrGluLeuIle 251525202525 LeuGluGluSerSerAlaArgThrLeuIleThrThrArgLysHisThr 253025352540 ProArgGlyGlyThrValAlaAsnValProXaaValValLeuAspSer 2545255025552560 ProGluThrLeuAlaCysLeuAsnGlnGlnSerLysGluAsnProThr 256525702575 ThrSerThrGlnLysProSerAspLeuAlaTyrValIlePheThrSer 258025852590 GlyThrThrGlyLysProLysGlyValLeuValGluHisGlnSerVal 259526002605 ValGlnLeuArgAsnSerLeuIleGluArgTyrPheGlyGluThrAsn 261026152620 GlySerHisAlaValLeuPheLeuSerAsnTyrValPheAspPheSer 2625263026352640 LeuGluGlnLeuCysLeuSerValLeuGlyGlyAsnLysLeuIleIle 264526502655 ProProGluGluGlyLeuThrHisGluAlaPheTyrAspIleGlyArg 266026652670 ArgGluLysLeuSerTyrLeuSerGlyThrProSerValLeuGlnGln 267526802685 IleGluLeuSerArgLeuProHisLeuHisMetValThrAlaAlaGly 269026952700 GluGluPheHisAlaSerGlnPheGluLysMetArgSerGlnPheAla 2705271027152720 GlyGlnIleAsnAsnAlaTyrGlyIleThrGluThrThrValTyrAsn 272527302735 IleIleThrThrPheLysGlyAspAlaProPheThrLysAlaLeuCys 274027452750 HisGlyIleProGlySerHisValTyrValLeuAsnAspArgLeuGln 275527602765 ArgValProPheAsnAlaValGlyGluLeuTyrLeuGlyGlyAspCys 277027752780 LeuAlaArgGlyTyrLeuAsnGlnAspAlaLeuThrAsnGluArgPhe 2785279027952800 IleProAsnProPheTyrGluProLysGlnAlaSerAspSerArgPro 280528102815 GlnArgLeuTyrLysThrGlyAspLeuValArgPheArgGlyProHis 282028252830 HisLeuGluTyrLeuGlyArgLysAspGlnGlnValLysLeuArgGly 283528402845 PheArgIleGluLeuSerGluValArgAspAlaValLeuAlaIleSer 285028552860 AlaValLysGluAlaAlaValIleProLysTyrAspGluAspGlySer 2865287028752880 AspSerArgArgValSerAlaIleValCysTyrTyrThrLeuAsnAla 288528902895 GlyThrValCysGluAlaSerSerIleArgAspHisLeuHisAlaAsn 290029052910 LeuProProTyrMetValProSerGlnIleHisGlnLeuGluGlySer 291529202925 LeuProValThrValAsnGlyLysLeuAspLeuAsnArgLeuSerThr 293029352940 ThrGlnValSerGlnProGluLeuTyrThrAlaProArgAsnSerThr 2945295029552960 GluGluThrLeuCysGlnLeuTrpAlaSerLeuLeuGlyValAspHis 296529702975 CysGlyIleAspAspAspLeuPheAlaArgGlyGlyAspSerIleSer 298029852990 SerLeuArgLeuValGlyAspIleTyrArgAlaLeuGlyArgLysVal 299530003005 ThrValLysAspIleTyrLeuHisArgSerValArgAlaLeuSerGlu 301030153020 AsnValLeuThrAspGlnLysAspLysGlyThrLeuProAlaSerPro 3025303030353040 ProLeuGlnArgAlaGluGlnGlyGlnValGluGlyAspAlaProLeu 304530503055 LeuProIleGlnAspTrpPheLeuSerLysProLeuAspAsnProAla 306030653070 TyrTrpAsnHisCysPheThrIleArgThrGlyAlaLeuSerValGlu 307530803085 GlyLeuArgGlyAlaLeuLysLeuLeuGlnGluArgHisAspValLeu 309030953100 ArgLeuArgLeuGlnArgArgAspGluGlyArgHisValGlnThrPhe 3105311031153120 AlaArgAspCysAlaGlnProArgLeuThrValLeuAspArgArgSer 312531303135 PheGluAspAlaGluAspValGlnGluAlaLeuCysGluIleGlnSer 314031453150 HisPheAspLeuGluAsnGlyProLeuTyrThrValAlaTyrIleHis 315531603165 GlyTyrGluAspGlySerAlaArgValTrpPheAlaCysHisHisVal 317031753180 MetValAspThrValSerTrpAsnIleIleLeuGlnAspLeuGlnAla 3185319031953200 LeuTyrHisGlyAspSerLeuGlyProLysSerSerSerValGlnGln 320532103215 TrpSerLeuAlaValSerAspTyrLysMetProLeuSerGluArgAla 322032253230 HisTrpAsnValLeuArgLysThrValAlaGlnSerPheGluThrLeu 323532403245 ProIleCysMetGlyGlyValLeuGlnCysGlnGluLysPheSerArg 325032553260 GluThrThrThrAlaLeuLeuSerLysAlaCysProAlaLeuAspSer 3265327032753280 GlyMetHisGluIleLeuLeuMetAlaValGlySerAlaLeuGlnLys 328532903295 AlaAlaGlyAspValProGlnValValThrIleGluGlyHisGlyArg 330033053310 GluAspThrIleAspAlaThrLeuAspValSerArgThrValGlyTrp 331533203325 PheThrSerMetTyrProPheGluIleProLysValThrAspProAla 333033353340 GlnGlyValValAspValLysGluAlaMetArgArgValProAsnArg 3345335033553360 GlyValGlyTyrGlyProAlaTyrGlyTyrGlyGlySerCysLeuPro 336533703375 AlaValSerPheAsnTyrLeuGlyArgLeuAspGlnAlaSerSerGly 338033853390 AlaGlnArgAspTrpThrLeuValMetAspGluAspGluTyrProVal 339534003405 GlyLeuCysThrSerAlaGluAspSerGlyArgSerSerSerMetVal 341034153420 AspPheThrPheSerIleSerGlyGlyGlnLeuValMetAspMetSer 3425343034353440 SerSerTrpGlyHisGlyAlaArgAsnGluPheValArgThrValArg 344534503455 AsnThrLeuAspAspLeuIleLysThrThrSerSerArgAspPheSer 346034653470 AlaProLeuProProSerAspGlnGluSerSerPheThrProTyrPhe 347534803485 ValPheGluGluGlyGluArgHisGlyAlaProLeuPheLeuLeuPro 349034953500 ProGlyGluGlyGlyAlaGluSerTyrPheHisAsnIleValLysGly 3505351035153520 LeuProAsnArgAsnLeuValValPheAsnAsnHisTyrArgGluGlu 352535303535 LysThrLeuArgThrIleGluAlaLeuAlaGluTyrTyrLeuSerHis 354035453550 IleArgSerIleGlnProGluGlyProTyrHisIleLeuGlyTrpSer 355535603565 PheGlyGlyIleLeuGlyLeuGluAlaAlaLysArgLeuThrGlyGlu 357035753580 GlyHisLysIleAlaThrLeuAlaLeuIleAspProTyrPheAspIle 3585359035953600 ProSerAlaSerLysAlaIleGlyGlnProAspAspAlaCysValLeu 360536103615 AspProIleTyrHisValTyrHisProSerProGluSerPheArgThr 362036253630 ValSerSerLeuThrAsnHisIleAlaLeuPheLysAlaThrGluThr 363536403645 AsnAspGlnHisGlyAsnAlaThrGlnGlnAlaLeuTyrGluTrpPhe 365036553660 AlaThrCysProLeuAsnAsnLeuAspLysPheLeuAlaAlaAspThr 3665367036753680 IleLysValValProLeuGluGlyThrHisPheThrTrpValHisHis 368536903695 ProGluGlnValArgSerMetCysThrMetLeuAspGluTrpLeuGly 370037053710 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 768 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: Penicillium chrysogenum (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 1..768 (D) OTHER INFORMATION: /label=Domain I /note= "Domain I of ACV Synthetase from Penicillium chrysogenum; aa 301-1068" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: SerAlaGluGlnLysGlnGlnLeuGluGluTrpAsnAsnThrAspGly 151015 GluTyrProSerSerLysArgLeuHisHisLeuIleGluGluValVal 202530 GluArgHisGluAspLysIleAlaValValCysAspGluArgGluLeu 354045 ThrTyrGlyGluLeuAsnAlaGlnGlyAsnSerLeuAlaArgTyrLeu 505560 ArgSerIleGlyIleLeuProGluGlnLeuValAlaLeuPheLeuAsp 65707580 LysSerGluLysLeuIleValThrIleLeuGlyValTrpLysSerGly 859095 AlaAlaTyrValProIleAspProThrTyrProAspGluArgValArg 100105110 PheValLeuAspAspThrLysAlaArgAlaIleIleAlaSerAsnGln 115120125 HisValGluArgLeuGlnArgGluValIleGlyAspArgAsnLeuCys 130135140 IleIleArgLeuGluProLeuLeuAlaSerLeuAlaGlnAspSerSer 145150155160 LysPheProAlaHisAsnLeuAspAspLeuProLeuThrSerGlnGln 165170175 LeuAlaTyrValThrTyrThrSerGlyThrThrGlyPheProLysGly 180185190 IlePheLysGlnHisThrAsnValValAsnSerIleThrAspLeuSer 195200205 AlaArgTyrGlyValAlaGlyGlnHisHisGluAlaIleLeuLeuPhe 210215220 SerAlaCysValPheGluProPheValArgGlnThrLeuMetAlaLeu 225230235240 ValAsnGlyHisLeuLeuAlaValIleAsnAspValGluLysTyrAsp 245250255 AlaAspThrLeuLeuProPheIleArgArgHisSerIleThrTyrLeu 260265270 AsnGlyThrAlaSerValLeuGlnGluTyrAspPheSerAspCysPro 275280285 SerLeuAsnArgIleIleLeuValGlyGluAsnLeuThrGluAlaArg 290295300 TyrLeuAlaLeuArgGlnArgPheLysAsnArgIleLeuAsnGluTyr 305310315320 GlyPheThrGluSerAlaPheValThrAlaLeuLysIlePheAspPro 325330335 GluSerThrArgLysAspThrSerLeuGlyArgProValArgAsnVal 340345350 LysCysTyrIleLeuAsnProSerLeuLysArgValProIleGlyAla 355360365 ThrGlyGluLeuHisIleGlyGlyLeuGlyIleSerLysGlyTyrLeu 370375380 AsnArgProGluLeuThrProHisArgPheIleProAsnProPheGln 385390395400 ThrAspCysGluLysGlnLeuGlyIleAsnSerLeuMetTyrLysThr 405410415 GlyAspLeuAlaArgTrpLeuProAsnGlyGluValGluTyrLeuGly 420425430 ArgAlaAspPheGlnIleLysLeuArgGlyIleArgIleGluProGly 435440445 GluIleGluThrMetLeuAlaMetTyrProArgValArgThrSerLeu 450455460 ValValSerLysLysLeuArgAsnGlyProGluGluThrThrAsnGlu 465470475480 HisLeuValGlyTyrTyrValCysAspSerAlaSerValSerGluAla 485490495 AspLeuLeuSerPheLeuGluLysLysLeuProArgTyrMetIlePro 500505510 ThrArgLeuValGlnLeuSerGlnIleProValAsnValAsnGlyLys 515520525 AlaAspLeuArgAlaLeuProAlaValAspIleSerAsnSerThrGlu 530535540 ValArgSerAspLeuArgGlyAspThrGluIleAlaLeuGlyGluIle 545550555560 TrpAlaAspValLeuGlyAlaArgGlnArgSerValSerArgAsnAsp 565570575 AsnPhePheArgLeuGlyGlyHisSerIleThrCysIleGlnLeuIle 580585590 AlaArgIleArgGlnArgGlnArgLeuSerValSerIleSerValGlu 595600605 AspValPheAlaThrArgThrLeuGluArgMetAlaAspLeuLeuGln 610615620 AsnLysGlnGlnGluLysCysAspLysProHisGluAlaProThrGlu 625630635640 LeuLeuGluGluAsnAlaAlaThrAspAsnIleTyrLeuAlaAsnSer 645650655 LeuGlnGlnGlyPheValTyrHisTyrLeuLysSerMetGluGlnSer 660665670 AspAlaTyrValMetGlnSerValLeuArgTyrAsnThrThrLeuSer 675680685 ProAspLeuPheGlnArgAlaTrpLysHisAlaGlnGlnSerPhePro 690695700 AlaLeuArgLeuArgPheSerTrpGluLysGluValPheGlnLeuLeu 705710715720 AspGlnAspProProLeuAspTrpArgPheLeuTyrPheThrAspVal 725730735 AlaAlaGlyAlaValGluAspArgLysLeuGluAspLeuArgArgGln 740745750 AspLeuThrGluArgPheLysLeuAspValGlyArgLeuPheArgVal 755760765 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 758 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: Penicillium chrysogenum (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 1..758 (D) OTHER INFORMATION: /label=Domain II /note= "Domain II of ACV Synthetase from Penicillium chrysogenum; aa 1397-2154" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: SerSerIleGlnLeuGluGlnLeuAlaAlaTrpAsnAlaThrGluAla 151015 GluPheProAspThrThrLeuHisGluMetPheGluAsnGluAlaSer 202530 GlnLysProAspLysIleAlaValValTyrGluGluThrSerLeuThr 354045 TyrArgGluLeuAsnGluArgAlaAsnArgMetAlaHisGlnLeuArg 505560 SerAspValSerProAsnProAsnGluValIleAlaLeuValMetAsp 65707580 LysSerGluHisMetIleValAsnIleLeuAlaValTrpLysSerGly 859095 GlyAlaTyrValProIleAspProGlyTyrProAsnAspArgIleGln 100105110 TyrIleLeuGluAspThrGlnAlaLeuAlaValIleAlaAspSerCys 115120125 TyrLeuProArgIleLysGlyMetAlaAlaSerGlyThrLeuLeuTyr 130135140 ProSerValLeuProAlaAsnProAspSerLysTrpSerValSerAsn 145150155160 ProSerProLeuSerArgSerThrAspLeuAlaTyrIleIleTyrThr 165170175 SerGlyThrThrGlyArgProLysGlyValThrValGluHisHisGly 180185190 ValValAsnLeuGlnValSerLeuSerLysValPheGlyLeuArgAsp 195200205 ThrAspAspGluValIleLeuSerPheSerAsnTyrValPheAspHis 210215220 PheValGluGlnMetThrAspAlaIleLeuAsnGlyGlnThrLeuLeu 225230235240 ValLeuAsnAspGlyMetArgGlyAspLysGluArgLeuTyrArgTyr 245250255 IleGluLysAsnArgValThrTyrLeuSerGlyThrProSerValVal 260265270 SerMetTyrGluPheSerArgPheLysAspHisLeuArgArgValAsp 275280285 CysValGlyGluAlaPheSerGluProValPheAspLysIleArgGlu 290295300 ThrPheHisGlyLeuValIleAsnGlyTyrGlyProThrGluValSer 305310315320 IleThrThrHisLysArgLeuTyrProPheProGluArgArgMetAsp 325330335 LysSerIleGlyGlnGlnValHisAsnSerThrSerTyrValLeuAsn 340345350 GluAspMetLysArgThrProIleGlyAlaValGlyGluLeuTyrLeu 355360365 GlyGlyGluGlyValValArgGlyTyrHisAsnArgAlaAspValThr 370375380 AlaGluArgPheIleProAsnProPheGlnSerGluGluAspLysArg 385390395400 GluGlyArgAsnSerArgLeuTyrLysThrGlyAspLeuValArgTrp 405410415 IleProGlySerSerGlyGluValGluTyrLeuGlyArgAsnAspPhe 420425430 GlnValLysIleArgGlyLeuArgIleGluLeuGlyGluIleGluAla 435440445 IleLeuSerSerTyrHisGlyIleLysGlnSerValValIleAlaLys 450455460 AspCysArgGluGlyAlaGlnLysPheLeuValGlyTyrTyrValAla 465470475480 AspAlaAlaLeuProSerAlaAlaIleArgArgPheMetGlnSerArg 485490495 LeuProGlyTyrMetValProSerArgLeuIleLeuValSerLysPhe 500505510 ProValThrProSerGlyLysLeuAspThrLysAlaLeuProProAla 515520525 GluGluGluSerGluIleAspValValProProArgSerGluIleGlu 530535540 ArgSerLeuCysAspIleTrpAlaGluLeuLeuGluMetHisProGlu 545550555560 GluIleGlyIleTyrSerAspPhePheSerLeuGlyGlyAspSerLeu 565570575 LysSerThrLysLeuSerPheMetIleHisGluSerPheAsnArgAla 580585590 ValSerValSerAlaLeuPheCysHisArgThrValGluAlaGlnThr 595600605 HisLeuIleLeuAsnAspAlaAlaAspValHisGluIleThrProIle 610615620 AspCysAsnAspThrGlnMetIleProValSerArgAlaGlnGluArg 625630635640 LeuLeuPheIleHisGluPheGluAsnGlySerAsnAlaTyrAsnIle 645650655 AspAlaAlaPheGluLeuProGlySerValAspAlaSerLeuLeuGlu 660665670 GlnAlaLeuArgGlyAsnLeuAlaArgHisGluAlaLeuArgThrLeu 675680685 LeuValLysAspHisAlaThrGlyIleTyrLeuGlnLysValLeuSer 690695700 ProAspGluAlaGlnGlyMetPheSerValAsnValAspThrAlaLys 705710715720 GlnValGluArgLeuAspGlnGluIleAlaSerLeuSerGlnHisVal 725730735 PheArgLeuAspAspGluLeuProTrpGluAlaArgIleLeuLysLeu 740745750 GluSerGlyGlyLeuTyr 755 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 822 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: Penicillium chrysogenum (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 1..822 (D) OTHER INFORMATION: /label=Domain III /note= "Domain III of ACV Synthetase from Penicillium chrysogenum; aa 2474-3295" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: ArgProThrGluAsnGlyAspLeuHisLeuProLeuAlaGlnSerPro 151015 LeuAlaThrThrAlaGluGluGlnLysValAlaSerLeuAsnGlnAla 202530 PheGluArgGluAlaPheLeuAlaAlaGluLysIleAlaValValGln 354045 GlyAspArgAlaLeuSerTyrAlaAspLeuAsnGlyGlnAlaAsnGln 505560 LeuAlaArgTyrIleGlnSerValSerCysIleGlyAlaAspAspGly 65707580 IleAlaLeuMetLeuGluLysSerIleAspThrIleIleCysIleLeu 859095 AlaIleTrpLysAlaGlyAlaAlaTyrValProLeuAspProThrTyr 100105110 ProProGlyArgValGlnLeuIleLeuGluGluIleLysAlaLysAla 115120125 ValLeuValHisSerSerHisAlaSerLysCysGluArgHisGlyAla 130135140 LysValIleAlaValAspSerProAlaIleGluThrAlaValSerGln 145150155160 GlnSerAlaAlaAspLeuProThrIleAlaSerLeuGlyAsnLeuAla 165170175 TyrIleIlePheThrSerGlyThrSerGlyLysProLysGlyValLeu 180185190 ValGluGlnLysAlaValLeuLeuLeuArgAspAlaLeuArgGluArg 195200205 TyrPheGlyArgAspCysThrLysHisHisGlyValLeuPheLeuSer 210215220 AsnTyrValPheAspPheSerValGluGlnLeuValLeuSerValLeu 225230235240 SerGlyHisLysLeuIleValProProAlaGluPheValAlaAspAsp 245250255 GluPheTyrArgMetAlaSerThrHisGlyLeuSerTyrLeuSerGly 260265270 ThrProSerLeuLeuGlnLysIleAspLeuAlaArgLeuAspHisLeu 275280285 GlnValValThrAlaAlaGlyGluGluLeuHisAlaThrGlnTyrGlu 290295300 LysMetArgArgArgPheAsnGlyProIleTyrAsnAlaTyrGlyVal 305310315320 ThrGluThrThrValTyrAsnIleIleAlaGluPheThrThrAsnSer 325330335 IlePheGluAsnAlaLeuArgGluValLeuProGlyThrArgAlaTyr 340345350 ValLeuAsnAlaAlaLeuGlnProValProPheAspAlaValGlyGlu 355360365 LeuTyrLeuAlaGlyAspThrValThrArgGlyTyrLeuAsnGlnPro 370375380 LeuLeuThrAspGlnArgPheIleProAsnProPheCysLysGluGlu 385390395400 AspIleAlaMetGlyArgPheAlaArgLeuTyrLysThrGlyAspLeu 405410415 ValArgSerArgPheAsnArgGlnGlnGlnProGlnLeuGluTyrLeu 420425430 GlyArgGlyAspLeuGlnIleLysMetArgGlyTyrArgIleGluIle 435440445 SerGluValGlnAsnValLeuThrSerSerProGlyValArgGluGly 450455460 AlaValValAlaLysTyrGluAsnAsnAspThrTyrSerArgThrAla 465470475480 HisSerLeuValGlyTyrTyrThrThrAspAsnGluThrValSerGlu 485490495 AlaAspIleLeuThrPheMetLysAlaArgLeuProThrTyrMetVal 500505510 ProSerHisLeuCysCysLeuGluGlyAlaLeuProValThrIleAsn 515520525 GlyLysLeuAspValArgArgLeuProGluIleIleAsnAspSerAla 530535540 GlnSerSerTyrSerProProArgAsnIleIleGluAlaLysMetCys 545550555560 ArgLeuTrpGluSerAlaLeuGlyMetGluArgCysGlyIleAspAsp 565570575 AspLeuPheLysLeuGlyGlyAspSerIleThrSerLeuHisLeuVal 580585590 AlaGlnIleHisAsnGlnValGlyCysLysIleThrValArgAspIle 595600605 PheGluHisArgThrAlaArgAlaLeuHisAspHisValPheMetLys 610615620 AspSerAspArgSerAsnValThrGlnPheArgThrGluGlnGlyPro 625630635640 ValIleGlyGluAlaProLeuLeuProIleGlnAspTrpPheLeuSer 645650655 LysAlaLeuGlnHisProMetTyrTrpAsnHisThrPheTyrValArg 660665670 ThrProGluLeuAspValAspSerLeuSerAlaAlaValArgAspLeu 675680685 GlnGlnTyrHisAspValPheArgMetArgLeuLysArgGluGluVal 690695700 GlyPheValGlnSerPheAlaGluAspPheSerProAlaGlnLeuArg 705710715720 ValLeuAsnValLysAspValAspGlySerAlaAlaValAsnGluIle 725730735 LeuAspGlyTrpGlnSerGlyPheAsnLeuGluAsnGlyProIleGly 740745750 SerIleGlyTyrLeuHisGlyTyrGluAspArgSerAlaArgValTrp 755760765 PheSerValHisHisMetAlaIleAspThrValSerTrpGlnIleLeu 770775780 ValArgAspLeuGlnThrLeuTyrArgAsnGlySerLeuGlySerLys 785790795800 GlySerSerPheArgGlnTrpAlaGluAlaIleGlnAsnTyrLysAla 805810815 SerAspSerGluArgAsn 820 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 798 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: (A) ORGANISM: Bacillus brevis (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: MetLeuAlaAsnGlnAlaAsnLeuIleAspAsnLysArgGluLeuGlu 151015 GlnHisAlaLeuValProTyrAlaGlnGlyLysSerIleHisGlnLeu 202530 PheGluGluGlnAlaGluAlaPheProAspArgValAlaIleValPhe 354045 GluAsnArgArgLeuSerTyrGlnGluLeuAsnArgLysAlaAsnGln 505560 LeuAlaArgAlaLeuLeuGluLysGlyValGlnThrAspSerIleVal 65707580 GlyValMetMetGluLysSerIleGluAsnValIleAlaIleLeuAla 859095 ValLeuLysAlaGlyGlyAlaTyrValProIleAspIleGluTyrPro 100105110 ArgAspArgIleGlnTyrIleLeuGlnAspSerGlnThrLysIleVal 115120125 LeuThrGlnLysSerValSerGlnLeuValHisAspValGlyTyrSer 130135140 GlyGluValValValLeuAspGluGluGlnLeuAspAlaArgGluThr 145150155160 AlaAsnLeuHisGlnProSerLysProThrAspLeuAlaTyrValIle 165170175 TyrThrSerGlyThrThrGlyLysProLysGlyThrMetLeuGluHis 180185190 LysGlyIleAlaIleCysAsnProPheSerLysIleArgLeuAlaSer 195200205 ProSerLysThrGlySerGlyPheLeuProAlaCysArgSerThrHis 210215220 ProPheGlyLysCysSerTrpLeuCysCysLeuAlaProArgValHis 225230235240 ProSerLysGlnThrIleHisAspPheAlaAlaPheGluHisTyrLeu 245250255 SerGluAsnGluLeuThrIleIleThrLeuProProThrTyrLeuThr 260265270 HisLeuThrProGluArgIleThrSerLeuArgIleMetIleThrAla 275280285 GlySerAlaSerSerAlaProLeuValAsnLysTrpLysAspLysLeu 290295300 ArgTyrIleAsnAlaTyrGlyProThrGluThrSerIleCysAlaThr 305310315320 IleTrpGluAlaProSerAsnGlnLeuSerValGlnSerValProIle 325330335 GlyLysProIleGlnAsnThrHisIleTyrIleValAsnGluAspLeu 340345350 GlnLeuLeuProThrAlaAspGluGlyGluLeuCysIleGlyGlyVal 355360365 GlyLeuAlaArgGlyTyrTrpAsnArgProAspLeuThrAlaGluLys 370375380 PheValAspAsnProPheValProGlyGluLysMetTyrArgThrGly 385390395400 AspLeuAlaLysTrpLeuThrAspGlyThrIleGluPheLeuGlyArg 405410415 IleAspHisGlnValLysIleArgGlyHisArgIleGluLeuGlyGlu 420425430 IleGluSerValLeuLeuAlaHisGluHisIleThrGluAlaValVal 435440445 IleAlaArgGluAspGlnHisAlaGlyGlnTyrLeuCysAlaTyrTyr 450455460 IleSerGlnGlnGluAlaThrProAlaGlnLeuArgAspTyrAlaAla 465470475480 GlnLysLeuProAlaTyrMetLeuProSerTyrPheValLysLeuAsp 485490495 LysMetProLeuThrProAsnAspLysIleAspArgLysAlaLeuPro 500505510 GluProAspLeuThrAlaAsnGlnSerGlnAlaAlaTyrHisProPro 515520525 ArgThrGluThrGluSerIleLeuValSerIleTrpGlnAsnValLeu 530535540 GlyIleGluLysIleGlyIleArgAspAsnPheTyrSerLeuGlyGly 545550555560 AspSerIleGlnAlaIleGlnValValAlaArgLeuHisSerTyrGln 565570575 LeuLysLeuGluThrLysAspLeuLeuAsnTyrProThrIleGluGln 580585590 ValAlaLeuPheValLysSerThrThrArgLysSerAspGlnGlyIle 595600605 IleAlaGlyAsnValProLeuThrProIleGlnLysTrpPhePheGly 610615620 LysAsnPheThrAsnThrGlyHisTrpAsnGlnSerSerValLeuTyr 625630635640 ArgProGluGlyPheAspProLysValIleGlnSerValMetAspLys 645650655 IleIleGluHisHisAspAlaValArgMetValTyrGlnHisGluAsn 660665670 GlyAsnValValGlnHisAsnArgGlyLeuGlyGlyGlnLeuTyrAsp 675680685 PhePheSerTyrAsnLeuThrAlaGlnProAspValGlnGlnAlaIle 690695700 GluAlaGluThrGlnArgLeuHisSerSerMetAsnLeuGlnGluGly 705710715720 ProLeuValLysValAlaLeuPheGlnThrLeuHisGlyAspHisPhe 725730735 PheLeuAlaIleHisHisLeuValValAspGlyIleSerTrpArgIle 740745750 LeuPheLysIleTrpGlnProAspThrArgArgHisLeuGlnGlyLys 755760765 ArgSerValCysProLysLysArgIleLeuPheLysAlaGlyHisAsn 770775780 GlyCysLysAsnAsnAlaAsnGluAlaAspLeuLeuSerGlu 785790795 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 797 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: (A) ORGANISM: Bacillus brevis (ix) FEATURE: (A) NAME/KEY: Region (B) LOCATION: 1..797 (D) OTHER INFORMATION: /label=Homology /note= "Homologous region from Gramicidine Synthetase of Bacillus brevis; aa 13-809 " (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: GlnAsnLysAsnGlyThrHisGluGluGluGlnTyrLeuPheAlaVal 151015 AsnAsnThrLysAlaGluTyrProArgAspLysThrIleHisGlnLeu 202530 PheGluGluGlnValSerLysArgProAsnAsnValAlaIleValCys 354045 GluAsnGluGlnLeuThrTyrHisGluLeuAsnValLysAlaAsnGln 505560 LeuAlaArgIlePheIleGluLysGlyIleGlyLysAspThrLeuVal 65707580 GlyIleMetMetGluLysSerIleAspLeuPheIleGlyIleLeuAla 859095 ValLeuLysAlaGlyGlyAlaTyrValProIleAspIleGluTyrPro 100105110 LysGluArgIleGlnTyrIleLeuAspAspSerGlnAlaArgMetLeu 115120125 LeuThrGlnLysHisLeuValHisLeuIleHisAsnIleGlnPheAsn 130135140 GlyGlnValGluIlePheGluGluAspThrIleLysIleArgGluGly 145150155160 ThrAsnLeuHisValProSerLysSerThrAspLeuAlaTyrValIle 165170175 TyrThrSerGlyThrThrGlyAsnProLysGlyThrMetLeuGluHis 180185190 LysGlyIleSerAsnLeuLysValPhePheGluAsnSerLeuAsnVal 195200205 ThrGluLysAspArgIleGlyGlnPheAlaSerIleSerPheAspAla 210215220 SerValTrpGluMetPheMetAlaLeuLeuThrGlyAlaSerLeuTyr 225230235240 IleIleLeuLysAspThrIleAsnAspPheValLysPheGluGlnTyr 245250255 IleAsnGlnLysGluIleThrValIleThrLeuProProThrIleVal 260265270 ValHisLeuAspProGluArgIleLeuSerIleGlnThrLeuIleThr 275280285 AlaGlySerAlaThrSerProSerLeuValAsnLysTrpLysGluLys 290295300 ValThrTyrIleAsnAlaTyrGlyProThrGluThrThrIleCysAla 305310315320 ThrThrTrpValAlaThrLysGluThrIleGlyHisSerValProIle 325330335 GlyAlaProIleGlnAsnThrGlnIleTyrIleValAspGluAsnLeu 340345350 GlnLeuLysSerValGlyGluAlaGlyGluLeuCysIleGlyGlyGlu 355360365 GlyLeuAlaArgGlyTyrTrpLysArgProGluLeuThrSerGlnLys 370375380 PheValAspAsnProPheValProGlyGluLysLeuTyrLysThrGly 385390395400 AspGlnAlaArgTrpLeuSerAspGlyAsnIleGluTyrLeuGlyArg 405410415 IleAspAsnGlnValLysIleArgGlyHisArgValGluLeuGluGlu 420425430 ValGluSerIleLeuLeuLysHisMetTyrIleSerGluThrAlaVal 435440445 SerValHisLysAspHisGlnGluGlnProTyrLeuCysAlaTyrPhe 450455460 ValSerGluLysHisIleProLeuGluGlnLeuArgGlnPheSerSer 465470475480 GluGluLeuProThrTyrMetIleProSerTyrPheIleGlnLeuAsp 485490495 LysMetProLeuThrSerAsnGlyLysIleAspArgLysGlnLeuPro 500505510 GluProAspLeuThrPheGlyMetArgValAspTyrGluAlaProArg 515520525 AsnGluIleGluGluThrLeuValThrIleTrpGlnAspValLeuGly 530535540 IleGluLysIleGlyIleLysAspAsnPheTyrAlaLeuGlyGlyAsp 545550555560 SerIleLysAlaIleGlnValAlaAlaArgLeuHisSerTyrGlnLeu 565570575 LysLeuGluThrLysAspLeuLeuLysTyrProThrIleAspGlnLeu 580585590 ValHisTyrIleLysAspSerLysArgArgSerGluGlnGlyIleVal 595600605 GluGlyGluIleGlyLeuThrProIleGlnHisTrpPhePheGluGln 610615620 GlnPheThrAsnMetHisHisTrpAsnGlnSerTyrMetLeuTyrArg 625630635640 ProAsnGlyPheAspLysGluIleLeuLeuArgValPheAsnLysIle 645650655 ValGluHisHisAspAlaLeuArgMetIleTyrLysHisHisAsnGly 660665670 LysIleValGlnIleAsnArgGlyLeuGluGlyThrLeuPheAspPhe 675680685 TyrThrPheAspLeuThrAlaAsnAspAsnGluGlnGlnValIleCys 690695700 GluGluSerAlaArgLeuGlnAsnSerIleAsnLeuGluValGlyPro 705710715720 LeuValLysIleAlaLeuPheHisThrGlnAsnGlyAspHisLeuPhe 725730735 MetAlaIleHisHisLeuValValAspGlyIleSerTrpArgIleLeu 740745750 PheGluAspLeuAlaThrAlaTyrGluGlnAlaMetHisGlnGlnThr 755760765 IleAlaLeuProGluLysThrAspSerPheLysAspTrpSerIleGlu 770775780 LeuGluLysTyrAlaAsnSerGluLeuPheLeuGluGlu 785790795 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 85 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: Penicillium chrysogenum (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 1..85 (D) OTHER INFORMATION: /label=DomainIV /note= "Domain IV of ACV Synthetase from Penicillium chrysogenum; aa 3563-3647" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: LeuPheLeuLeuProProGlyGluGlyGlyAlaGluSerTyrPheAsn 151015 AsnIleValLysArgLeuArgGlnThrAsnMetValValPheAsnAsn 202530 TyrTyrLeuHisSerLysArgLeuArgThrPheGluGluLeuAlaGlu 354045 MetTyrLeuAspGlnValArgGlyIleGlnProHisGlyProTyrHis 505560 PheIleGlyTrpSerPheGlyGlyIleLeuAlaMetGluMetSerArg 65707580 ArgLeuValAlaSer 85 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 86 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: rat (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 1..86 (D) OTHER INFORMATION: /label=Homology /note= "Homologous region from fatty acid synthetase of rat; aa 2161-2246" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: GluArgProLeuPheLeuValHisProIleGluGlySerIleThrVal 151015 HisPheHisSerLeuAlaAlaLysLeuSerValProThrTyrGlyLeu 202530 GlnCysThrGlnAlaAlaProLeuAspSerIleProAsnLeuAlaAla 354045 TyrTyrIleAspCysIleLysGlnValGlnProGluGlyProTyrArg 505560 ValAlaGlyTyrSerPheGlyAlaCysValAlaPheGluMetCysSer 65707580 GlnLeuGlnAlaGlnGln 85 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3666 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: (A) ORGANISM: Penicillium chrysogenum (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION: 1..3666 (D) OTHER INFORMATION: /label=region /note= "Region of ACV Synthetase; aa 62-3727" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: ArgValArgPheArgGlyGlyIleGluArgTrpLysGluCysValAsn 151015 GlnValProGluArgCysAspLeuSerGlyLeuThrThrAspSerThr 202530 ArgTyrGlnLeuAlaSerThrGlyPheGlyAspAlaSerAlaAlaTyr 354045 GlnGluArgLeuMetThrValProValAspValHisAlaAlaLeuGln 505560 GluLeuCysLeuGluArgArgValSerValGlySerValIleAsnPhe 65707580 SerValHisGlnMetLeuLysGlyPheGlyAsnGlyThrHisThrIle 859095 ThrAlaSerLeuHisArgGluGlnAsnLeuGlnAsnSerSerProSer 100105110 TrpValValSerProThrIleValThrHisGluAsnArgAspGlyTrp 115120125 SerValAlaGlnAlaValGluSerIleGluAlaAlaArgGlySerGlu 130135140 LysGluSerValThrAlaIleAspSerAlaSerSerLeuValLysMet 145150155160 GlyLeuPheAspLeuLeuValSerPheValAspAlaAspAspAlaArg 165170175 IleProCysPheAspPheProLeuAlaValIleValArgGluCysAsp 180185190 AlaAsnLeuSerLeuThrLeuArgPheSerAspCysLeuPheAsnGlu 195200205 GluThrIleCysAsnPheThrAspAlaLeuAsnIleLeuLeuAlaGlu 210215220 AlaValIleGlyArgValThrProValAlaAspIleGluLeuLeuSer 225230235240 AlaGluGlnLysGlnGlnLeuGluGluTrpAsnAsnThrAspGlyGlu 245250255 TyrProSerSerLysArgLeuHisHisLeuIleGluGluValValGlu 260265270 ArgHisGluAspLysIleAlaValValCysAspGluArgGluLeuThr 275280285 TyrGlyGluLeuAsnAlaGlnGlyAsnSerLeuAlaArgTyrLeuArg 290295300 SerIleGlyIleLeuProGluGlnLeuValAlaLeuPheLeuAspLys 305310315320 SerGluLysLeuIleValThrIleLeuGlyValTrpLysSerGlyAla 325330335 AlaTyrValProIleAspProThrTyrProAspGluArgValArgPhe 340345350 ValLeuAspAspThrLysAlaArgAlaIleIleAlaSerAsnGlnHis 355360365 ValGluArgLeuGlnArgGluValIleGlyAspArgAsnLeuCysIle 370375380 IleArgLeuGluProLeuLeuAlaSerLeuAlaGlnAspSerSerLys 385390395400 PheProAlaHisAsnLeuAspAspLeuProLeuThrSerGlnGlnLeu 405410415 AlaTyrValThrTyrThrSerGlyThrThrGlyPheProLysGlyIle 420425430 PheLysGlnHisThrAsnValValAsnSerIleThrAspLeuSerAla 435440445 ArgTyrGlyValAlaGlyGlnHisHisGluAlaIleLeuLeuPheSer 450455460 AlaCysValPheGluProPheValArgGlnThrLeuMetAlaLeuVal 465470475480 AsnGlyHisLeuLeuAlaValIleAsnAspValGluLysTyrAspAla 485490495 AspThrLeuLeuProPheIleArgArgHisSerIleThrTyrLeuAsn 500505510 GlyThrAlaSerValLeuGlnGluTyrAspPheSerAspCysProSer 515520525 LeuAsnArgIleIleLeuValGlyGluAsnLeuThrGluAlaArgTyr 530535540 LeuAlaLeuArgGlnArgPheLysAsnArgIleLeuAsnGluTyrGly 545550555560 PheThrGluSerAlaPheValThrAlaLeuLysIlePheAspProGlu 565570575 SerThrArgLysAspThrSerLeuGlyArgProValArgAsnValLys 580585590 CysTyrIleLeuAsnProSerLeuLysArgValProIleGlyAlaThr 595600605 GlyGluLeuHisIleGlyGlyLeuGlyIleSerLysGlyTyrLeuAsn 610615620 ArgProGluLeuThrProHisArgPheIleProAsnProPheGlnThr 625630635640 AspCysGluLysGlnLeuGlyIleAsnSerLeuMetTyrLysThrGly 645650655 AspLeuAlaArgTrpLeuProAsnGlyGluValGluTyrLeuGlyArg 660665670 AlaAspPheGlnIleLysLeuArgGlyIleArgIleGluProGlyGlu 675680685 IleGluThrMetLeuAlaMetTyrProArgValArgThrSerLeuVal 690695700 ValSerLysLysLeuArgAsnGlyProGluGluThrThrAsnGluHis 705710715720 LeuValGlyTyrTyrValCysAspSerAlaSerValSerGluAlaAsp 725730735 LeuLeuSerPheLeuGluLysLysLeuProArgTyrMetIleProThr 740745750 ArgLeuValGlnLeuSerGlnIleProValAsnValAsnGlyLysAla 755760765 AspLeuArgAlaLeuProAlaValAspIleSerAsnSerThrGluVal 770775780 ArgSerAspLeuArgGlyAspThrGluIleAlaLeuGlyGluIleTrp 785790795800 AlaAspValLeuGlyAlaArgGlnArgSerValSerArgAsnAspAsn 805810815 PhePheArgLeuGlyGlyHisSerIleThrCysIleGlnLeuIleAla 820825830 ArgIleArgGlnArgGlnArgLeuSerValSerIleSerValGluAsp 835840845 ValPheAlaThrArgThrLeuGluArgMetAlaAspLeuLeuGlnAsn 850855860 LysGlnGlnGluLysCysAspLysProHisGluAlaProThrGluLeu 865870875880 LeuGluGluAsnAlaAlaThrAspAsnIleTyrLeuAlaAsnSerLeu 885890895 GlnGlnGlyPheValTyrHisTyrLeuLysSerMetGluGlnSerAsp 900905910 AlaTyrValMetGlnSerValLeuArgTyrAsnThrThrLeuSerPro 915920925 AspLeuPheGlnArgAlaTrpLysHisAlaGlnGlnSerPheProAla 930935940 LeuArgLeuArgPheSerTrpGluLysGluValPheGlnLeuLeuAsp 945950955960 GlnAspProProLeuAspTrpArgPheLeuTyrPheThrAspValAla 965970975 AlaGlyAlaValGluAspArgLysLeuGluAspLeuArgArgGlnAsp 980985990 LeuThrGluArgPheLysLeuAspValGlyArgLeuPheArgValTyr 99510001005 LeuIleLysHisSerGluAsnArgPheThrCysLeuPheSerCysHis 101010151020 HisAlaIleLeuAspGlyTrpSerLeuProLeuLeuPheGluLysVal 1025103010351040 HisGluThrTyrLeuGlnLeuLeuHisGlyAspAsnLeuThrSerSer 104510501055 MetAspAspProTyrThrArgThrGlnArgTyrLeuHisAlaHisArg 106010651070 GluAspHisLeuAspPheTrpAlaGlyValValGlnLysIleAsnGlu 107510801085 ArgCysAspMetAsnAlaLeuLeuAsnGluArgSerArgTyrLysVal 109010951100 GlnLeuAlaAspTyrAspGlnValGlnGluGlnArgHisValThrIle 1105111011151120 AlaLeuSerGlyAspAlaTrpLeuAlaAspLeuArgGlnThrCysSer 112511301135 AlaGlnGlyIleThrLeuHisSerIleLeuGlnPheValTrpHisAla 114011451150 ValLeuHisAlaTyrGlyGlyGlyThrHisThrIleThrGlyThrThr 115511601165 IleSerGlyArgAsnLeuProIleLeuGlyIleGluArgAlaValGly 117011751180 ProTyrIleAsnThrLeuProLeuValLeuAspHisSerThrPheLys 1185119011951200 AspLysThrIleMetGluAlaIleGluAspValGlnAlaLysValAsn 120512101215 ValMetAsnSerArgGlyAsnValGluLeuGlyArgLeuHisLysThr 122012251230 AspLeuLysHisGlyLeuPheAspSerLeuPheValLeuGluAsnTyr 123512401245 ProAsnLeuAspLysSerArgThrLeuGluHisGlnThrGluLeuGly 125012551260 TyrSerIleGluGlyGlyThrGluLysLeuAsnTyrProLeuAlaVal 1265127012751280 IleAlaArgGluValGluThrThrGlyGlyPheThrValSerIleCys 128512901295 TyrAlaSerGluLeuPheGluGluValMetIleSerGluLeuLeuHis 130013051310 MetValGlnAspThrLeuMetGlnValAlaArgGlyLeuAsnGluPro 131513201325 ValGlySerLeuGluTyrLeuSerSerIleGlnLeuGluGlnLeuAla 133013351340 AlaTrpAsnAlaThrGluAlaGluPheProAspThrThrLeuHisGlu 1345135013551360 MetPheGluAsnGluAlaSerGlnLysProAspLysIleAlaValVal 136513701375 TyrGluGluThrSerLeuThrTyrArgGluLeuAsnGluArgAlaAsn 138013851390 ArgMetAlaHisGlnLeuArgSerAspValSerProAsnProAsnGlu 139514001405 ValIleAlaLeuValMetAspLysSerGluHisMetIleValAsnIle 141014151420 LeuAlaValTrpLysSerGlyGlyAlaTyrValProIleAspProGly 1425143014351440 TyrProAsnAspArgIleGlnTyrIleLeuGluAspThrGlnAlaLeu 144514501455 AlaValIleAlaAspSerCysTyrLeuProArgIleLysGlyMetAla 146014651470 AlaSerGlyThrLeuLeuTyrProSerValLeuProAlaAsnProAsp 147514801485 SerLysTrpSerValSerAsnProSerProLeuSerArgSerThrAsp 149014951500 LeuAlaTyrIleIleTyrThrSerGlyThrThrGlyArgProLysGly 1505151015151520 ValThrValGluHisHisGlyValValAsnLeuGlnValSerLeuSer 152515301535 LysValPheGlyLeuArgAspThrAspAspGluValIleLeuSerPhe 154015451550 SerAsnTyrValPheAspHisPheValGluGlnMetThrAspAlaIle 155515601565 LeuAsnGlyGlnThrLeuLeuValLeuAsnAspGlyMetArgGlyAsp 157015751580 LysGluArgLeuTyrArgTyrIleGluLysAsnArgValThrTyrLeu 1585159015951600 SerGlyThrProSerValValSerMetTyrGluPheSerArgPheLys 160516101615 AspHisLeuArgArgValAspCysValGlyGluAlaPheSerGluPro 162016251630 ValPheAspLysIleArgGluThrPheHisGlyLeuValIleAsnGly 163516401645 TyrGlyProThrGluValSerIleThrThrHisLysArgLeuTyrPro 165016551660 PheProGluArgArgMetAspLysSerIleGlyGlnGlnValHisAsn 1665167016751680 SerThrSerTyrValLeuAsnGluAspMetLysArgThrProIleGly 168516901695 AlaValGlyGluLeuTyrLeuGlyGlyGluGlyValValArgGlyTyr 170017051710 HisAsnArgAlaAspValThrAlaGluArgPheIleProAsnProPhe 171517201725 GlnSerGluGluAspLysArgGluGlyArgAsnSerArgLeuTyrLys 173017351740 ThrGlyAspLeuValArgTrpIleProGlySerSerGlyGluValGlu 1745175017551760 TyrLeuGlyArgAsnAspPheGlnValLysIleArgGlyLeuArgIle 176517701775 GluLeuGlyGluIleGluAlaIleLeuSerSerTyrHisGlyIleLys 178017851790 GlnSerValValIleAlaLysAspCysArgGluGlyAlaGlnLysPhe 179518001805 LeuValGlyTyrTyrValAlaAspAlaAlaLeuProSerAlaAlaIle 181018151820 ArgArgPheMetGlnSerArgLeuProGlyTyrMetValProSerArg 1825183018351840 LeuIleLeuValSerLysPheProValThrProSerGlyLysLeuAsp 184518501855 ThrLysAlaLeuProProAlaGluGluGluSerGluIleAspValVal 186018651870 ProProArgSerGluIleGluArgSerLeuCysAspIleTrpAlaGlu 187518801885 LeuLeuGluMetHisProGluGluIleGlyIleTyrSerAspPhePhe 189018951900 SerLeuGlyGlyAspSerLeuLysSerThrLysLeuSerPheMetIle 1905191019151920 HisGluSerPheAsnArgAlaValSerValSerAlaLeuPheCysHis 192519301935 ArgThrValGluAlaGlnThrHisLeuIleLeuAsnAspAlaAlaAsp 194019451950 ValHisGluIleThrProIleAspCysAsnAspThrGlnMetIlePro 195519601965 ValSerArgAlaGlnGluArgLeuLeuPheIleHisGluPheGluAsn 197019751980 GlySerAsnAlaTyrAsnIleAspAlaAlaPheGluLeuProGlySer 1985199019952000 ValAspAlaSerLeuLeuGluGlnAlaLeuArgGlyAsnLeuAlaArg 200520102015 HisGluAlaLeuArgThrLeuLeuValLysAspHisAlaThrGlyIle 202020252030 TyrLeuGlnLysValLeuSerProAspGluAlaGlnGlyMetPheSer 203520402045 ValAsnValAspThrAlaLysGlnValGluArgLeuAspGlnGluIle 205020552060 AlaSerLeuSerGlnHisValPheArgLeuAspAspGluLeuProTrp 2065207020752080 GluAlaArgIleLeuLysLeuGluSerGlyGlyLeuTyrLeuIleLeu 208520902095 AlaPheHisHisThrCysPheAspAlaTrpSerLeuLysValPheGlu 210021052110 GlnGluLeuArgAlaLeuTyrAlaAlaLeuGlnLysThrLysSerAla 211521202125 AlaAsnLeuProAlaLeuLysAlaGlnTyrLysGluTyrAlaLeuTyr 213021352140 HisArgArgGlnLeuSerGlyAspArgMetArgAsnLeuSerAspPhe 2145215021552160 TrpLeuArgLysLeuIleGlyLeuGluProLeuGlnLeuIleThrAsp 216521702175 ArgProArgProValGlnPheLysTyrAspGlyAspAspLeuSerIle 218021852190 GluLeuSerLysLysGluThrGluAsnLeuArgGlyValAlaLysArg 219522002205 CysLysSerSerLeuTyrValValLeuValSerValTyrCysValMet 221022152220 LeuAlaSerTyrAlaAsnGlnSerAspValSerValGlyIleProVal 2225223022352240 SerHisArgThrHisProGlnPheGlnSerValIleGlyPhePheVal 224522502255 AsnLeuValValLeuArgValAspIleSerGlnSerAlaIleCysGly 226022652270 LeuIleArgArgValMetLysGluLeuValAspAlaGlnLeuHisGln 227522802285 AspMetProPheGlnGluValThrLysLeuLeuGlnValAspAsnAsp 229022952300 ProSerArgHisProLeuValGlnAsnValPheAsnPheGluSerArg 2305231023152320 AlaAsnGlyGluHisAspAlaArgSerGluAspGluGlySerLeuAla 232523302335 PheAsnGlnTyrArgProValGlnProValAspSerValAlaLysPhe 234023452350 AspLeuAsnAlaThrValThrGluLeuGluSerGlyLeuArgValAsn 235523602365 PheAsnTyrAlaThrSerLeuPheAsnLysSerThrIleGlnGlyPhe 237023752380 LeuHisThrTyrGluTyrLeuLeuArgGlnLeuSerGluLeuSerAla 2385239023952400 GluGlyIleAsnGluAspThrGlnLeuSerLeuValArgProThrGlu 240524102415 AsnGlyAspLeuHisLeuProLeuAlaGlnSerProLeuAlaThrThr 242024252430 AlaGluGluGlnLysValAlaSerLeuAsnGlnAlaPheGluArgGlu 243524402445 AlaPheLeuAlaAlaGluLysIleAlaValValGlnGlyAspArgAla 245024552460 LeuSerTyrAlaAspLeuAsnGlyGlnAlaAsnGlnLeuAlaArgTyr 2465247024752480 IleGlnSerValSerCysIleGlyAlaAspAspGlyIleAlaLeuMet 248524902495 LeuGluLysSerIleAspThrIleIleCysIleLeuAlaIleTrpLys 250025052510 AlaGlyAlaAlaTyrValProLeuAspProThrTyrProProGlyArg 251525202525 ValGlnLeuIleLeuGluGluIleLysAlaLysAlaValLeuValHis 253025352540 SerSerHisAlaSerLysCysGluArgHisGlyAlaLysValIleAla 2545255025552560 ValAspSerProAlaIleGluThrAlaValSerGlnGlnSerAlaAla 256525702575 AspLeuProThrIleAlaSerLeuGlyAsnLeuAlaTyrIleIlePhe 258025852590 ThrSerGlyThrSerGlyLysProLysGlyValLeuValGluGlnLys 259526002605 AlaValLeuLeuLeuArgAspAlaLeuArgGluArgTyrPheGlyArg 261026152620 AspCysThrLysHisHisGlyValLeuPheLeuSerAsnTyrValPhe 2625263026352640 AspPheSerValGluGlnLeuValLeuSerValLeuSerGlyHisLys 264526502655 LeuIleValProProAlaGluPheValAlaAspAspGluPheTyrArg 266026652670 MetAlaSerThrHisGlyLeuSerTyrLeuSerGlyThrProSerLeu 267526802685 LeuGlnLysIleAspLeuAlaArgLeuAspHisLeuGlnValValThr 269026952700 AlaAlaGlyGluGluLeuHisAlaThrGlnTyrGluLysMetArgArg 2705271027152720 ArgPheAsnGlyProIleTyrAsnAlaTyrGlyValThrGluThrThr 272527302735 ValTyrAsnIleIleAlaGluPheThrThrAsnSerIlePheGluAsn 274027452750 AlaLeuArgGluValLeuProGlyThrArgAlaTyrValLeuAsnAla 275527602765 AlaLeuGlnProValProPheAspAlaValGlyGluLeuTyrLeuAla 277027752780 GlyAspThrValThrArgGlyTyrLeuAsnGlnProLeuLeuThrAsp 2785279027952800 GlnArgPheIleProAsnProPheCysLysGluGluAspIleAlaMet 280528102815 GlyArgPheAlaArgLeuTyrLysThrGlyAspLeuValArgSerArg 282028252830 PheAsnArgGlnGlnGlnProGlnLeuGluTyrLeuGlyArgGlyAsp 283528402845 LeuGlnIleLysMetArgGlyTyrArgIleGluIleSerGluValGln 285028552860 AsnValLeuThrSerSerProGlyValArgGluGlyAlaValValAla 2865287028752880 LysTyrGluAsnAsnAspThrTyrSerArgThrAlaHisSerLeuVal 288528902895 GlyTyrTyrThrThrAspAsnGluThrValSerGluAlaAspIleLeu 290029052910 ThrPheMetLysAlaArgLeuProThrTyrMetValProSerHisLeu 291529202925 CysCysLeuGluGlyAlaLeuProValThrIleAsnGlyLysLeuAsp 293029352940 ValArgArgLeuProGluIleIleAsnAspSerAlaGlnSerSerTyr 2945295029552960 SerProProArgAsnIleIleGluAlaLysMetCysArgLeuTrpGlu 296529702975 SerAlaLeuGlyMetGluArgCysGlyIleAspAspAspLeuPheLys 298029852990 LeuGlyGlyAspSerIleThrSerLeuHisLeuValAlaGlnIleHis 299530003005 AsnGlnValGlyCysLysIleThrValArgAspIlePheGluHisArg 301030153020 ThrAlaArgAlaLeuHisAspHisValPheMetLysAspSerAspArg 3025303030353040 SerAsnValThrGlnPheArgThrGluGlnGlyProValIleGlyGlu 304530503055 AlaProLeuLeuProIleGlnAspTrpPheLeuSerLysAlaLeuGln 306030653070 HisProMetTyrTrpAsnHisThrPheTyrValArgThrProGluLeu 307530803085 AspValAspSerLeuSerAlaAlaValArgAspLeuGlnGlnTyrHis 309030953100 AspValPheArgMetArgLeuLysArgGluGluValGlyPheValGln 3105311031153120 SerPheAlaGluAspPheSerProAlaGlnLeuArgValLeuAsnVal 312531303135 LysAspValAspGlySerAlaAlaValAsnGluIleLeuAspGlyTrp 314031453150 GlnSerGlyPheAsnLeuGluAsnGlyProIleGlySerIleGlyTyr 315531603165 LeuHisGlyTyrGluAspArgSerAlaArgValTrpPheSerValHis 317031753180 HisMetAlaIleAspThrValSerTrpGlnIleLeuValArgAspLeu 3185319031953200 GlnThrLeuTyrArgAsnGlySerLeuGlySerLysGlySerSerPhe 320532103215 ArgGlnTrpAlaGluAlaIleGlnAsnTyrLysAlaSerAspSerGlu 322032253230 ArgAsnHisTrpAsnLysLeuValMetGluThrAlaSerSerIleSer 323532403245 AlaLeuProThrSerThrGlySerArgValArgLeuSerArgSerLeu 325032553260 SerProGluLysThrAlaSerLeuIleGlnGlyGlyIleAspArgGln 3265327032753280 AspValSerValTyrAspSerLeuLeuThrSerValGlyLeuAlaLeu 328532903295 GlnHisIleAlaProThrGlyProSerMetValThrIleGluGlyHis 330033053310 GlyArgGluGluValAspGlnThrLeuAspValSerArgThrMetGly 331533203325 TrpPheThrThrMetTyrProPheGluIleProArgLeuSerThrGlu 333033353340 AsnIleValGlnGlyValValAlaValSerGluArgPheArgGlnVal 3345335033553360 ProAlaArgGlyValGlyTyrGlyThrLeuTyrGlyTyrThrGlnHis 336533703375 ProLeuProGlnValThrValAsnTyrLeuGlyGlnLeuAlaArgLys 338033853390 GlnSerLysProLysGluTrpValLeuAlaValGlyAspAsnGluPhe 339534003405 GluTyrGlyLeuMetThrSerProGluAspLysAspArgSerSerSer 341034153420 AlaValAspValThrAlaValCysIleAspGlyThrMetIleIleAsp 3425343034353440 ValAspSerAlaTrpSerLeuGluGluSerGluGlnPheIleSerSer 344534503455 IleGluGluGlyLeuAsnLysIleLeuAspGlyArgAlaSerGlnGln 346034653470 ThrSerArgPheProAspValProGlnProAlaGluThrTyrThrPro 347534803485 TyrPheGluTyrLeuGluProProArgGlnGlyProThrLeuPheLeu 349034953500 LeuProProGlyGluGlyGlyAlaGluSerTyrPheAsnAsnIleVal 3505351035153520 LysArgLeuArgGlnThrAsnMetValValPheAsnAsnTyrTyrLeu 352535303535 HisSerLysArgLeuArgThrPheGluGluLeuAlaGluMetTyrLeu 354035453550 AspGlnValArgGlyIleGlnProHisGlyProTyrHisPheIleGly 355535603565 TrpSerPheGlyGlyIleLeuAlaMetGluMetSerArgArgLeuVal 357035753580 AlaSerAspGluLysIleGlyPheLeuGlyIleIleAspThrTyrPhe 3585359035953600 AsnValArgGlyAlaThrArgThrIleGlyLeuGlyAspThrGluIle 360536103615 LeuAspProIleHisHisIleTyrAsnProAspProAlaAsnPheGln 362036253630 ArgLeuProSerAlaThrAspArgIleValLeuPheLysAlaMetArg 363536403645 ProAsnAsnLysTyrGluSerGluAsnGlnArgArgLeuTyrGluTyr 365036553660 TyrAsp 3665 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3665 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: (A) ORGANISM: Acremonium chrysogenum (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION: 1..3665 (D) OTHER INFORMATION: /label=ACVS /note= "ACV Synthetase from Acremonium chrysogenum; aa 1-3665" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: ValAlaLeuGluGlnTrpLysThrThrValGlnSerValSerGluArg 151015 CysAspLeuSerGlyLeuSerGlnHisProThrAspTyrGlnLeuAla 202530 SerThrGlyValLysGlyAlaGlyGlySerSerIleGluGluArgSer 354045 AlaIleValSerAspGluLeuPheSerSerLeuArgAspValCysSer 505560 GlnArgGlnLeuAspProArgSerLeuMetLeuPheSerValHisGln 65707580 MetLeuLysArgPheGlyAsnGlySerHisThrValValAlaSerLeu 859095 ValThrSerSerGluGlyCysProSerThrSerAlaTrpArgAlaIle 100105110 ProSerValIleHisHisIleGluGlyGlyAspAsnAsnAsnThrVal 115120125 AlaSerAlaValGluGlnAlaAlaAsnLeuLeuAsnSerGluGlySer 130135140 GlyGlnAspLeuLeuIleProIleGlyLeuThrGluLeuValLysSer 145150155160 GluLeuIleAspLeuLeuValIlePheAspAspGluThrAsnAsnIle 165170175 ArgLeuProGlnAspPheProLeuIleLeuArgIleHisGlnArgGln 180185190 AspHisTrpGlnLeuSerValArgTyrProSerProLeuPheAspThr 195200205 MetValIleAspSerPheLeuSerAlaLeuHisAsnLeuLeuSerAla 210215220 ValThrLysProSerGlnLeuValArgAspIleGluLeuLeuProGlu 225230235240 TyrGlnValAlaGlnLeuGluLysTrpAsnAsnThrAspGlyAspTyr 245250255 ProThrGluLysArgLeuHisHisLeuPheGluGluAlaAlaValArg 260265270 ArgProGlnHisValAlaLeuIleCysGlyAspLysArgIleThrTyr 275280285 GluGluLeuAsnAlaMetAlaAsnArgLeuAlaHisHisLeuValSer 290295300 SerGlyIleGlnThrGluGlnLeuValGlyLeuPheLeuAspLysThr 305310315320 GluLeuMetIleAlaThrIleLeuGlyIleTrpLysSerGlyAlaAla 325330335 HisValProIleAspProGlyTyrProAspGluArgValLysPheVal 340345350 LeuAsnAspThrLysAlaGlnValValIleAlaSerGlnArgHisVal 355360365 AspArgLeuArgAlaGluAlaValGlyGlyGlnHisLeuArgIleIle 370375380 GlyLeuGluSerLeuPheAspAsnLeuAlaGlnGlnThrGlnHisSer 385390395400 ProGluThrSerGlyAsnLeuThrHisLeuProLeuAsnSerLysGln 405410415 LeuAlaTyrValThrTyrThrSerGlyThrThrGlyPheProLysGly 420425430 IleTyrLysGluHisThrSerValValAsnSerIleThrAspLeuSer 435440445 AlaArgTyrGlyValAlaGlyGluAspAspGluValIleLeuValPhe 450455460 SerAlaTyrValPheGluProPheValArgGlnMetLeuMetAlaLeu 465470475480 ThrThrGlyAsnSerLeuAlaIleIleSerAspGluAspLysPheAsp 485490495 ProAspThrLeuIleProPheIleGlnLysHisLysValThrTyrIle 500505510 HisAlaThrSerSerValLeuGlnGluTyrAspPheGlySerCysPro 515520525 SerLeuLysArgMetIleLeuValGlyGluAsnLeuThrGluProArg 530535540 TyrGluAlaLeuArgGlnArgPheLysSerArgIleLeuAsnGluTyr 545550555560 GlyPheThrGluSerAlaPheValThrAlaLeuAsnIlePheGluPro 565570575 ThrSerGlnArgLysAspMetSerLeuGlyArgProValArgAsnVal 580585590 LysCysTyrIleLeuAspAlaAsnLeuLysArgValProIleGlyVal 595600605 ThrGlyGluLeuHisIleGlyGlyLeuGlyIleSerArgGlyTyrMet 610615620 AsnArgGluGluLeuThrArgGlnLysPheLeuProAsnProTyrGln 625630635640 ThrAspLysGluArgGlnArgGlyValAsnSerThrMetTyrLysThr 645650655 GlyAspLeuAlaArgTrpLeuProSerGlyGluValGluTyrLeuGly 660665670 ArgAlaAspPheGlnIleLysLeuArgGlyIleArgIleGluProGly 675680685 GluIleGluSerThrLeuAlaMetTyrProGlyIleArgAlaSerIle 690695700 ValValSerLysLysLeuLeuSerGlnGlyGlnGluThrIleGlnAsp 705710715720 HisLeuValGlyTyrTyrValCysAspGluGlyHisIleProGluGly 725730735 AspLeuLeuSerPheLeuGluLysLysLeuProArgTyrMetValPro 740745750 ThrArgLeuValGlnLeuAlaGlnIleProThrAsnIleAsnGlyLys 755760765 AlaAspLeuArgAlaLeuProAlaValGluValAlaValAlaProThr 770775780 HisLysGlnAspGlyGluArgGlyAsnGlnLeuGluSerAspLeuAla 785790795800 AlaIleTrpGlyAsnIleLeuSerValProAlaGlnAspIleGlySer 805810815 GluSerAsnPhePheArgLeuGlyGlyHisSerIleAlaCysIleGln 820825830 LeuIleAlaArgValArgGlnGlnLeuGlyGlnGlyIleThrLeuGlu 835840845 GluValPheGlnThrLysThrLeuArgAlaMetAlaAlaLeuLeuSer 850855860 GluLysTyrThrLysAlaSerAsnGlyThrAsnGlyValThrAsnGly 865870875880 ThrAlaHisValAsnGlyHisAlaAlaAsnGlyHisValSerAspSer 885890895 TyrValAlaSerSerLeuGlnGlnGlyPheValTyrHisSerLeuLys 900905910 AsnGluLeuSerGluAlaTyrThrMetGlnSerMetIleHisTyrGly 915920925 ValProLeuLysArgAspIleTyrGlnAlaAlaTrpGlnArgValGln 930935940 GlyGluHisProAlaLeuArgLeuArgPheThrTrpGluAlaGluVal 945950955960 MetGlnIleValAspProLysSerGluLeuAspTrpArgValValAsp 965970975 TrpThrAspValSerSerArgGluLysGlnLeuValAlaLeuGluGln 980985990 LeuGlnThrGluAspLeuAlaLysValTyrHisLeuAspLysGlyPro 99510001005 LeuMetArgLeuTyrLeuIleLeuLeuProAspSerLysTyrSerCys 101010151020 LeuPheSerCysHisHisAlaIleLeuAspGlyTrpSerLeuProLeu 1025103010351040 LeuPheAsnAsnValHisGlnAlaTyrLeuAspLeuValGluGlyThr 104510501055 AlaSerProValGluGlnAspAlaThrTyrLeuLeuGlyGlnGlnTyr 106010651070 LeuGlnSerHisArgAspAspHisLeuAspPheTrpAlaGluGlnIle 107510801085 GlyArgIleGluGluArgCysAspMetAsnAlaLeuLeuAsnGluAla 109010951100 SerArgTyrLysValProLeuAlaAspTyrAspGlnValArgGluGln 1105111011151120 ArgGlnGlnThrIleSerLeuProTrpAsnAsnSerMetAspAlaGly 112511301135 ValArgGluGluLeuSerSerArgGlyIleThrLeuHisSerIleLeu 114011451150 GlnThrValTrpHisLeuValLeuHisSerTyrGlyGlyGlyThrHis 115511601165 ThrIleThrGlyThrThrIleSerGlyArgHisLeuProValProGly 117011751180 IleGluArgSerValGlyLeuPheIleAsnThrLeuProMetIlePhe 1185119011951200 AspHisThrValCysGlnAspMetThrAlaLeuGluAlaIleGluHis 120512101215 ValGlnGlyGlnValAsnAlaMetAsnSerArgGlyAsnValGluLeu 122012251230 GlyArgMetSerLysAsnAspLeuLysHisGlyLeuPheAspThrLeu 123512401245 PheValLeuGluAsnTyrProAsnLeuAspThrGluGlnArgGluLys 125012551260 HisGluGluLysLeuLysPheThrIleLysGlyGlyThrGluLysLeu 1265127012751280 SerTyrProLeuAlaValIleAlaGlnGluAspGlyAspSerGlyCys 128512901295 SerPheThrLeuCysTyrAlaGlyGluLeuPheThrAspGluSerIle 130013051310 GlnAlaLeuLeuAspThrValArgAspThrLeuSerAspIleLeuGly 131513201325 AsnIleHisAlaProIleArgAsnMetGluTyrLeuSerSerAsnGln 133013351340 ThrAlaGlnLeuAspLysTrpAsnAlaThrAlaPheGluTyrProAsn 1345135013551360 ThrThrLeuHisAlaMetPheGluSerGluAlaGlnGlnLysProAsp 136513701375 LysValAlaValValTyrGluAspIleArgLeuThrTyrArgGluLeu 138013851390 AsnSerArgAlaAsnAlaLeuAlaPheTyrLeuLeuSerGlnAlaAla 139514001405 IleGlnProAsnLysLeuValGlyLeuIleMetAspLysSerGluHis 141014151420 MetIleThrSerIleLeuAlaValTrpLysThrGlyGlyAlaTyrVal 1425143014351440 ProIleAspProArgTyrProAspGlnArgIleGlnTyrIleLeuGlu 144514501455 AspThrAlaAlaLeuAlaValIleThrAspSerProHisIleAspArg 146014651470 LeuArgSerIleThrAsnAsnArgLeuProValIleGlnSerAspPhe 147514801485 AlaLeuGlnLeuProProSerProValHisProValSerAsnCysLys 149014951500 ProSerAspLeuAlaTyrIleMetTyrThrSerGlyThrThrGlyAsn 1505151015151520 ProLysGlyValMetValGluHisHisGlyValValAsnLeuCysVal 152515301535 SerLeuCysArgLeuPheGlyLeuArgAsnThrAspAspGluValIle 154015451550 LeuSerPheSerAsnTyrValPheAspHisPheValGluGlnMetThr 155515601565 AspAlaLeuLeuAsnGlyGlnThrLeuValValLeuAsnAspGluMet 157015751580 ArgGlyAspLysGluArgLeuTyrArgTyrIleGluThrAsnArgVal 1585159015951600 ThrTyrLeuSerGlyThrProSerValIleSerMetTyrGluPheAsp 160516101615 ArgPheArgAspHisLeuArgArgValAspCysValGlyGluAlaPhe 162016251630 SerGluProValPheAspLysIleArgGluThrPheProGlyLeuIle 163516401645 IleAsnGlyTyrGlyProThrGluValSerIleThrThrHisLysArg 165016551660 ProTyrProPheProGluArgArgThrAspLysSerIleGlyCysGln 1665167016751680 LeuAspAsnSerThrSerTyrValLeuAsnAspAspMetLysArgVal 168516901695 ProIleGlyAlaValGlyGluLeuTyrLeuGlyGlyAspGlyValAla 170017051710 ArgGlyTyrHisAsnArgProAspLeuThrAlaAspArgPheProAla 171517201725 AsnProPheGlnThrGluGlnGluArgLeuGluGlyArgAsnAlaArg 173017351740 LeuTyrLysThrGlyAspLeuValArgTrpIleHisAsnAlaAsnGly 1745175017551760 AspGlyGluIleGluTyrLeuGlyArgAsnAspPheGlnValLysIle 176517701775 ArgGlyGlnArgIleGluLeuGlyGluIleGluAlaValLeuSerSer 178017851790 TyrProGlyIleLysGlnSerValValLeuAlaLysAspArgLysAsn 179518001805 AspGlyGlnLysTyrLeuValGlyTyrPheValSerSerAlaGlySer 181018151820 LeuSerAlaGlnAlaIleArgArgPheMetLeuThrSerLeuProAsp 1825183018351840 TyrMetValProAlaGlnLeuValProIleAlaLysPheProValThr 184518501855 ValSerGlyLysLeuAspAlaLysAlaLeuProValProAspAspThr 186018651870 ValGluAspAspIleValProProArgThrGluValGluArgIleLeu 187518801885 AlaGlyIleTrpSerGluLeuLeuGluIleProValAspArgIleSer 189018951900 IleTyrSerAspPhePheSerLeuGlyGlyAspSerLeuLysSerThr 1905191019151920 LysLeuSerPheAlaAlaThrArgAlaLeuGlyValAlaValSerVal 192519301935 ArgAsnLeuPheSerHisProThrIleGluAlaLeuSerGlnTrpIle 194019451950 IleArgGlySerAsnGluValLysAspValAlaValValLysGlyGly 195519601965 AlaSerLeuAspIleProLeuSerProAlaGlnGluArgLeuMetPhe 197019751980 IleHisGluPheGlyHisSerGlyGluAspThrGlyAlaTyrAsnVal 1985199019952000 ProLeuGlnLeuGlnLeuHisHisAspValCysLeuGluSerLeuGlu 200520102015 LysAlaLeuArgAspValValSerArgHisGluAlaLeuArgThrLeu 202020252030 IleThrArgThrGlnLysSerSerValHisCysGlnLysIleLeuAsp 203520402045 AlaGluGluAlaGlnLysLeuPheSerValAspValLeuArgLeuThr 205020552060 SerGluThrGluMetGlnGlyArgMetAlaGluSerThrAlaHisAla 2065207020752080 PheLysLeuAspGluGluLeuProIleHisValArgLeuTyrGlnVal 208520902095 ValArgAspGlyArgThrLeuSerPheAlaSerIleValCysHisHis 210021052110 LeuAlaPheAspAlaTrpSerTrpAspValPheGlnArgAspLeuAsp 211521202125 AlaPheTyrAlaValHisThrLysHisLysAlaAlaAlaAsnLeuPro 213021352140 ThrLeuArgValGlnTyrLysGluTyrAlaIleGluHisArgArgAla 2145215021552160 LeuArgAlaGluGlnHisArgValLeuAlaAspTyrTrpLeuArgLys 216521702175 LeuSerAspMetGluAlaSerTyrLeuValProAspArgProArgPro 218021852190 AlaGlnPheAspTyrThrGlyAsnAspLeuGlnPheSerThrThrPro 219522002205 GluThrThrAlaGlnLeuLysGluLeuAlaLysArgGluGlySerSer 221022152220 LeuTyrThrValValAlaAlaAlaTyrPheLeuLeuLeuTyrValTyr 2225223022352240 ThrAsnGlnArgAspIleThrIleGlyIleProValAlaHisArgAsn 224522502255 HisProAspPheGluSerValValGlyPhePheValAsnLeuLeuPro 226022652270 LeuArgValAsnValSerGlnSerAspIleHisGlyLeuIleGlnAla 227522802285 ValGlnLysGluLeuValAspAlaGlnIleHisGlnAspLeuProPhe 229022952300 GlnGluIleThrLysLeuLeuHisValGlnHisAspProSerArgHis 2305231023152320 ProLeuLeuGlnAlaValPheAsnTrpGluAsnValProAlaAsnVal 232523302335 HisGluGluGlnLeuLeuGlnGluTyrLysProProSerProLeuPro 234023452350 SerAlaAlaLysPheAspLeuAsnValThrValLysGluSerValAsn 235523602365 SerLeuAsnValAsnPheAsnTyrProThrSerLeuPheGluGluGlu 237023752380 ThrValGlnGlyPheMetGluThrPheHisLeuLeuLeuArgGlnLeu 2385239023952400 AlaHisAsnLysAlaSerThrSerLeuSerLysLeuSerValGluAsp 240524102415 GlyValLeuAsnProGluProThrAsnLeuGlnProSerSerArgAsp 242024252430 SerGlyAsnSerLeuHisGlyLeuPheGluAspIleValAlaSerThr 243524402445 ProAspArgIleAlaIleAlaAspGlyThrArgSerLeuSerTyrSer 245024552460 GluLeuAsnGluArgAlaAsnGlnLeuValHisLeuIleIleSerSer 2465247024752480 AlaSerIleValAlaAspAspArgIleAlaLeuLeuLeuAspLysSer 248524902495 IleAspMetValIleAlaLeuLeuAlaValTrpLysAlaGlyAlaAla 250025052510 TyrValProLeuAspProThrTyrProSerGlnArgThrGluLeuIle 251525202525 LeuGluGluSerSerAlaArgThrLeuIleThrThrArgLysHisThr 253025352540 ProArgGlyGlyThrValAlaAsnValProSerValValLeuAspSer 2545255025552560 ProGluThrLeuAlaCysLeuAsnGlnGlnSerLysGluAsnProThr 256525702575 ThrSerThrGlnLysProSerAspLeuAlaTyrValIlePheThrSer 258025852590 GlyThrThrGlyLysProLysGlyValLeuValGluHisGlnSerVal 259526002605 ValGlnLeuArgAsnSerLeuIleGluArgTyrPheGlyGluThrAsn 261026152620 GlySerHisAlaValLeuPheLeuSerAsnTyrValPheAspPheSer 2625263026352640 LeuGluGlnLeuCysLeuSerValLeuGlyGlyAsnLysLeuIleIle 264526502655 ProProGluGluGlyLeuThrHisGluAlaPheTyrAspIleGlyArg 266026652670 ArgGluLysLeuSerTyrLeuSerGlyThrProSerValLeuGlnGln 267526802685 IleGluLeuSerArgLeuProHisLeuHisMetValThrAlaAlaGly 269026952700 GluGluPheHisAlaSerGlnPheGluLysMetArgSerGlnPheAla 2705271027152720 GlyGlnIleAsnAsnAlaTyrGlyIleThrGluThrThrValTyrAsn 272527302735 IleIleThrThrPheLysGlyAspAlaProPheThrLysAlaLeuCys 274027452750 HisGlyIleProGlySerHisValTyrValLeuAsnAspArgLeuGln 275527602765 ArgValProPheAsnAlaValGlyGluLeuTyrLeuGlyGlyAspCys 277027752780 LeuAlaArgGlyTyrLeuAsnGlnAspAlaLeuThrAsnGluArgPhe 2785279027952800 IleProAsnProPheTyrGluProLysGlnAlaSerAspSerArgPro 280528102815 GlnArgLeuTyrLysThrGlyAspLeuValArgPheArgGlyProHis 282028252830 HisLeuGluTyrLeuGlyArgLysAspGlnGlnValLysLeuArgGly 283528402845 PheArgIleGluLeuSerGluValArgAspAlaValLeuAlaIleSer 285028552860 AlaValLysGluAlaAlaValIleProLysTyrAspGluAspGlySer 2865287028752880 AspSerArgArgValSerAlaIleValCysTyrTyrThrLeuAsnAla 288528902895 GlyThrValCysGluAlaSerSerIleArgAspHisLeuHisAlaAsn 290029052910 LeuProProTyrMetValProSerGlnIleHisGlnLeuGluGlySer 291529202925 LeuProValThrValAsnGlyLysLeuAspLeuAsnArgLeuSerThr 293029352940 ThrGlnValSerGlnProGluLeuTyrThrAlaProArgAsnSerThr 2945295029552960 GluGluThrLeuCysGlnLeuTrpAlaSerLeuLeuGlyValAspHis 296529702975 CysGlyIleAspAspAspLeuPheAlaArgGlyGlyAspSerIleSer 298029852990 SerLeuArgLeuValGlyAspIleTyrArgAlaLeuGlyArgLysVal 299530003005 ThrValLysAspIleTyrLeuHisArgSerValArgAlaLeuSerGlu 301030153020 AsnValLeuThrAspGlnLysAspLysGlyThrLeuProAlaSerPro 3025303030353040 ProLeuGlnArgAlaGluGlnGlyGlnValGluGlyAspAlaProLeu 304530503055 LeuProIleGlnAspTrpPheLeuSerLysProLeuAspAsnProAla 306030653070 TyrTrpAsnHisCysPheThrIleArgThrGlyAlaLeuSerValGlu 307530803085 GlyLeuArgGlyAlaLeuLysLeuLeuGlnGluArgHisAspValLeu 309030953100 ArgLeuArgLeuGlnArgArgAspGluGlyArgHisValGlnThrPhe 3105311031153120 AlaArgAspCysAlaGlnProArgLeuThrValLeuAspArgArgSer 312531303135 PheGluAspAlaGluAspValGlnGluAlaLeuCysGluIleGlnSer 314031453150 HisPheAspLeuGluAsnGlyProLeuTyrThrValAlaTyrIleHis 315531603165 GlyTyrGluAspGlySerAlaArgValTrpPheAlaCysHisHisVal 317031753180 MetValAspThrValSerTrpAsnIleIleLeuGlnAspLeuGlnAla 3185319031953200 LeuTyrHisGlyAspSerLeuGlyProLysSerSerSerValGlnGln 320532103215 TrpSerLeuAlaValSerAspTyrLysMetProLeuSerGluArgAla 322032253230 HisTrpAsnValLeuArgLysThrValAlaGlnSerPheGluThrLeu 323532403245 ProIleCysMetGlyGlyValLeuGlnCysGlnGluLysPheSerArg 325032553260 GluThrThrThrAlaLeuLeuSerLysAlaCysProAlaLeuAspSer 3265327032753280 GlyMetHisGluIleLeuLeuMetAlaValGlySerAlaLeuGlnLys 328532903295 AlaAlaGlyAspValProGlnValValThrIleGluGlyHisGlyArg 330033053310 GluAspThrIleAspAlaThrLeuAspValSerArgThrValGlyTrp 331533203325 PheThrSerMetTyrProPheGluIleProLysValThrAspProAla 333033353340 GlnGlyValValAspValLysGluAlaMetArgArgValProAsnArg 3345335033553360 GlyValGlyTyrGlyProAlaTyrGlyTyrGlyGlySerCysLeuPro 336533703375 AlaValSerPheAsnTyrLeuGlyArgLeuAspGlnAlaSerSerGly 338033853390 AlaGlnArgAspTrpThrLeuValMetAspGluAspGluTyrProVal 339534003405 GlyLeuCysThrSerAlaGluAspSerGlyArgSerSerSerMetVal 341034153420 AspPheThrPheSerIleSerGlyGlyGlnLeuValMetAspMetSer 3425343034353440 SerSerTrpGlyHisGlyAlaArgAsnGluPheValArgThrValArg 344534503455 AsnThrLeuAspAspLeuIleLysThrThrSerSerArgAspPheSer 346034653470 AlaProLeuProProSerAspGlnGluSerSerPheThrProTyrPhe 347534803485 ValPheGluGluGlyGluArgHisGlyAlaProLeuPheLeuLeuPro 349034953500 ProGlyGluGlyGlyAlaGluSerTyrPheHisAsnIleValLysGly 3505351035153520 LeuProAsnArgAsnLeuValValPheAsnAsnHisTyrArgGluGlu 352535303535 LysThrLeuArgThrIleGluAlaLeuAlaGluTyrTyrLeuSerHis 354035453550 IleArgSerIleGlnProGluGlyProTyrHisIleLeuGlyTrpSer 355535603565 PheGlyGlyIleLeuGlyLeuGluAlaAlaLysArgLeuThrGlyGlu 357035753580 GlyHisLysIleAlaThrLeuAlaLeuIleAspProTyrPheAspIle 3585359035953600 ProSerAlaSerLysAlaIleGlyGlnProAspAspAlaCysValLeu 360536103615 AspProIleTyrHisValTyrHisProSerProGluSerPheArgThr 362036253630 ValSerSerLeuThrAsnHisIleAlaLeuPheLysAlaThrGluThr 363536403645 AsnAspGlnHisGlyAsnAlaThrGlnGlnAlaLeuTyrGluTrpPhe 365036553660 Ala 3665 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: CCCAGACGCACTTGATCCTG20 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: GTCCCCGCTTGCGACGACTG20 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: CGGGAATCATCTGCGTATC19 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: CGCGCTCAAAGGCCTGGTTC20 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION: 24..35 (D) OTHER INFORMATION: /label=alternativeaas /note= "aa24=Asp or Arg; aa26=Gly or Trp; aa28=Asp or Tyr; aa29=Asp or Val; aa32=unknown; aa35=Asp or Arg" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: AsnAlaAsnValTyrLeuAlaAsnSerLeuGlnGlnGlyPheValTyr 151015 GlnPheLeuLysAsnMetGlyXaaSerXaaAlaXaaXaaMetGlnXaa 202530 ValThrXaaTyr 35 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION: 5..22 (D) OTHER INFORMATION: /label=alternativeaas /note= "aa5=unknown; aa19=unknown; aa21=Leu or Ser; aa22=Asp or Glu" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: GlnSerValGlnXaaIleLysSerValAlaLysPheAspLeuAsnAla 151015 ThrAlaXaaGluXaaXaaLysAla 20 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION: 1..16 (D) OTHER INFORMATION: /label=alternativeaas /note= "aa1=Gln or Ser or Cys; aa15=Thr or Gln; aa16=His or Gln" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: XaaGlnThrValLeuGlyAspAlaProLeuLeuProIleGlnXaaXaa 151015 Phe (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: TGGCTTCAGTTGAGTCATATGGGTAGTTAATGGTAT36 (2) INFORMATION FOR SEQ ID NO: 22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22: TTCGGCGATAACATGGAG18 (2) INFORMATION FOR SEQ ID NO: 23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Other nucleic acid /synthetic DNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23: TTCGGCGATAATATGGAG18 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11601 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: Acremonium chrysogenum (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 388..11526 (D) OTHER INFORMATION: /function="Enzyme" /product= "ACV Synthetase" (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 8050..8052 (D) OTHER INFORMATION: /note= "NNN=AGU, AGC, UCU, UCC, UCA, or UCG" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: GGATGCATGCATTGGCCTGTATCAAAGGTCCGGGATTCCCCAGGAGTATAAGACGTTCGT60 GCTGGGAGATCTAGCGACGTGTTGGGAAATATCGGCCGTAGAGTGCGAAAAAGAACTGGC120 GGAAATATTTCTCCTTGGACTCGGTCACACTCAGTCAGTAGTGGACTGCCAGTCTATCAT180 ACACCTTTGATATCAACATGACTATCCTTACAGGTGCCGACGACGCCTCGTCATACCACA240 GGTATGTCTTCACAGCCTCTGGAAAGCGCAGTTGGGAGCTATCTCTAACATTACCACATC300 AGGCGCAATGGAAGCTCTGATATCCCAAAAGGTGCCATCCACCGCAACGGCTTCGCAGCC360 GCAGCCCCTGACTGCTGGATCCGGTCCGTGGCCCTGGAACAGTGGAAGACT411 ValAlaLeuGluGlnTrpLysThr 15 ACGGTCCAGTCCGTCTCGGAGCGGTGCGATCTGAGCGGGCTGAGCCAG459 ThrValGlnSerValSerGluArgCysAspLeuSerGlyLeuSerGln 101520 CATCCCACCGACTACCAGCTGGCCTCTACGGGCGTGAAGGGCGCAGGC507 HisProThrAspTyrGlnLeuAlaSerThrGlyValLysGlyAlaGly 25303540 GGTAGCAGCATCGAGGAGCGCAGTGCCATCGTCTCAGACGAGTTGTTC555 GlySerSerIleGluGluArgSerAlaIleValSerAspGluLeuPhe 455055 TCGAGTCTGCGAGACGTGTGCTCACAGAGACAGCTGGACCCTCGGTCA603 SerSerLeuArgAspValCysSerGlnArgGlnLeuAspProArgSer 606570 CTCATGCTGTTTTCCGTGCACCAGATGCTCAAGAGGTTCGGAAACGGA651 LeuMetLeuPheSerValHisGlnMetLeuLysArgPheGlyAsnGly 758085 TCTCACACCGTCGTGGCGTCACTCGTAACTTCATCAGAGGGATGCCCT699 SerHisThrValValAlaSerLeuValThrSerSerGluGlyCysPro 9095100 TCAACTTCGGCCTGGAGGGCCATCCCCTCCGTCATCCATCATATAGAG747 SerThrSerAlaTrpArgAlaIleProSerValIleHisHisIleGlu 105110115120 GGCGGAGACAACAACAACACAGTCGCCTCTGCCGTGGAACAGGCGGCG795 GlyGlyAspAsnAsnAsnThrValAlaSerAlaValGluGlnAlaAla 125130135 AATCTCCTGAACTCAGAAGGATCGGGACAGGACCTTCTGATTCCCATC843 AsnLeuLeuAsnSerGluGlySerGlyGlnAspLeuLeuIleProIle 140145150 GGACTCACTGAGCTCGTCAAGTCGGAGCTGATTGACCTCCTGGTCATC891 GlyLeuThrGluLeuValLysSerGluLeuIleAspLeuLeuValIle 155160165 TTCGACGACGAGACAAATAACATACGACTGCCGCAGGACTTCCCACTT939 PheAspAspGluThrAsnAsnIleArgLeuProGlnAspPheProLeu 170175180 ATCCTGCGGATACATCAGCGGCAAGACCACTGGCAGCTGTCAGTCCGG987 IleLeuArgIleHisGlnArgGlnAspHisTrpGlnLeuSerValArg 185190195200 TATCCCTCGCCCCTTTTCGACACCATGGTCATCGACAGCTTTCTGAGC1035 TyrProSerProLeuPheAspThrMetValIleAspSerPheLeuSer 205210215 GCACTTCACAACCTGTTGTCCGCGGTGACAAAACCCTCCCAGCTCGTG1083 AlaLeuHisAsnLeuLeuSerAlaValThrLysProSerGlnLeuVal 220225230 CGCGACATCGAGCTGCTCCCAGAATACCAGGTCGCTCAGCTGGAGAAG1131 ArgAspIleGluLeuLeuProGluTyrGlnValAlaGlnLeuGluLys 235240245 TGGAACAACACAGACGGCGACTACCCCACCGAGAAGCGGCTACATCAT1179 TrpAsnAsnThrAspGlyAspTyrProThrGluLysArgLeuHisHis 250255260 CTGTTCGAGGAGGCAGCAGTGCGTCGTCCCCAACACGTTGCCCTCATC1227 LeuPheGluGluAlaAlaValArgArgProGlnHisValAlaLeuIle 265270275280 TGCGGCGACAAGCGCATCACCTATGAGGAGTTGAATGCTATGGCGAAT1275 CysGlyAspLysArgIleThrTyrGluGluLeuAsnAlaMetAlaAsn 285290295 CGCCTGGCCCACCATCTGGTATCCTCGGGTATCCAGACTGAGCAGCTC1323 ArgLeuAlaHisHisLeuValSerSerGlyIleGlnThrGluGlnLeu 300305310 GTCGGTCTCTTCCTCGACAAGACCGAGCTCATGATCGCTACTATTCTG1371 ValGlyLeuPheLeuAspLysThrGluLeuMetIleAlaThrIleLeu 315320325 GGCATCTGGAAATCTGGTGCCGCGCATGTACCTATCGACCCTGGGTAC1419 GlyIleTrpLysSerGlyAlaAlaHisValProIleAspProGlyTyr 330335340 CCGGACGAGCGTGTCAAGTTCGTCCTGAATGATACGAAGGCGCAAGTG1467 ProAspGluArgValLysPheValLeuAsnAspThrLysAlaGlnVal 345350355360 GTCATTGCTAGTCAGAGGCACGTCGATCGACTGCGGGCTGAGGCTGTT1515 ValIleAlaSerGlnArgHisValAspArgLeuArgAlaGluAlaVal 365370375 GGCGGCCAGCATCTTCGCATCATCGGTCTCGAATCTCTGTTCGACAAC1563 GlyGlyGlnHisLeuArgIleIleGlyLeuGluSerLeuPheAspAsn 380385390 CTTGCTCAACAGACACAACACTCACCAGAGACGTCGGGCAATTTGACC1611 LeuAlaGlnGlnThrGlnHisSerProGluThrSerGlyAsnLeuThr 395400405 CATCTGCCCCTGAACAGCAAACAGCTTGCGTACGTGACATACACCTCG1659 HisLeuProLeuAsnSerLysGlnLeuAlaTyrValThrTyrThrSer 410415420 GGCACCACGGGCTTCCCGAAAGGCATCTACAAGGAGCACACAAGCGTC1707 GlyThrThrGlyPheProLysGlyIleTyrLysGluHisThrSerVal 425430435440 GTTAACAGCATCACCGATCTGTCTGCTCGGTACGGTGTGGCCGGGGAG1755 ValAsnSerIleThrAspLeuSerAlaArgTyrGlyValAlaGlyGlu 445450455 GACGACGAGGTGATACTCGTCTTCTCCGCCTACGTCTTCGAGCCATTC1803 AspAspGluValIleLeuValPheSerAlaTyrValPheGluProPhe 460465470 GTGCGCCAGATGCTCATGGCCCTGACCACGGGCAACTCTCTCGCCATC1851 ValArgGlnMetLeuMetAlaLeuThrThrGlyAsnSerLeuAlaIle 475480485 ATCAGCGACGAGGACAAGTTCGACCCTGACACCCTTATTCCCTTCATC1899 IleSerAspGluAspLysPheAspProAspThrLeuIleProPheIle 490495500 CAAAAACACAAAGTCACTTACATCCACGCCACCTCGTCAGTGTTGCAG1947 GlnLysHisLysValThrTyrIleHisAlaThrSerSerValLeuGln 505510515520 GAGTACGACTTCGGGTCCTGCCCCTCGTTGAAACGCATGATTCTGGTG1995 GluTyrAspPheGlySerCysProSerLeuLysArgMetIleLeuVal 525530535 GGAGAGAACTTGACAGAGCCGCGCTACGAGGCCCTGAGGCAGCGCTTC2043 GlyGluAsnLeuThrGluProArgTyrGluAlaLeuArgGlnArgPhe 540545550 AAGTCGCGCATCCTGAATGAATATGGCTTCACCGAGTCTGCGTTTGTG2091 LysSerArgIleLeuAsnGluTyrGlyPheThrGluSerAlaPheVal 555560565 ACGGCGCTCAACATATTCGAGCCTACCTCACAGAGGAAGGACATGAGT2139 ThrAlaLeuAsnIlePheGluProThrSerGlnArgLysAspMetSer 570575580 CTGGGAAGGCCGGTGCGCAACGTCAAGTGCTATATCTTGGATGCCAAC2187 LeuGlyArgProValArgAsnValLysCysTyrIleLeuAspAlaAsn 585590595600 CTCAAGAGAGTCCCCATCGGTGTTACAGGGGAGCTGCACATCGGTGGC2235 LeuLysArgValProIleGlyValThrGlyGluLeuHisIleGlyGly 605610615 TTGGGTATATCCCGGGGGTACATGAATAGGGAGGAGCTCACAAGGCAG2283 LeuGlyIleSerArgGlyTyrMetAsnArgGluGluLeuThrArgGln 620625630 AAGTTCCTCCCGAACCCCTACCAGACCGATAAGGAGCGCCAACGGGGT2331 LysPheLeuProAsnProTyrGlnThrAspLysGluArgGlnArgGly 635640645 GTCAACTCAACCATGTACAAGACAGGAGATCTGGCCCGCTGGCTACCC2379 ValAsnSerThrMetTyrLysThrGlyAspLeuAlaArgTrpLeuPro 650655660 AGTGGCGAAGTCGAGTATCTCGGCCGTGCCGACTTCCAGATCAAGCTG2427 SerGlyGluValGluTyrLeuGlyArgAlaAspPheGlnIleLysLeu 665670675680 CGCGGCATTCGAATTGAGCCCGGCGAGATCGAGTCCACTCTCGCCATG2475 ArgGlyIleArgIleGluProGlyGluIleGluSerThrLeuAlaMet 685690695 TATCCCGGAATCAGGGCCAGCATCGTCGTGTCAAAGAAGCTTCTCAGT2523 TyrProGlyIleArgAlaSerIleValValSerLysLysLeuLeuSer 700705710 CAGGGGCAGGAGACGATCCAAGACCACCTTGTGGGGTACTATGTTTGC2571 GlnGlyGlnGluThrIleGlnAspHisLeuValGlyTyrTyrValCys 715720725 GATGAGGGCCACATCCCCGAGGGTGACCTGCTGAGCTTCCTGGAGAAG2619 AspGluGlyHisIleProGluGlyAspLeuLeuSerPheLeuGluLys 730735740 AAGCTACCTCGGTACATGGTCCCGACGCGCCTTGTCCAACTGGCTCAG2667 LysLeuProArgTyrMetValProThrArgLeuValGlnLeuAlaGln 745750755760 ATTCCAACCAATATCAACGGCAAGGCGGATCTGCGTGCTCTTCCTGCC2715 IleProThrAsnIleAsnGlyLysAlaAspLeuArgAlaLeuProAla 765770775 GTCGAAGTCGCCGTAGCTCCCACCCACAAGCAGGATGGCGAGCGAGGA2763 ValGluValAlaValAlaProThrHisLysGlnAspGlyGluArgGly 780785790 AACCAGCTGGAGAGCGACCTGGCTGCCATATGGGGCAACATTTTGAGT2811 AsnGlnLeuGluSerAspLeuAlaAlaIleTrpGlyAsnIleLeuSer 795800805 GTTCCCGCTCAAGACATTGGGTCTGAATCCAACTTCTTCCGCCTGGGT2859 ValProAlaGlnAspIleGlySerGluSerAsnPhePheArgLeuGly 810815820 GGCCACAGTATTGCATGCATCCAGCTCATTGCTCGTGTGCGACAGCAG2907 GlyHisSerIleAlaCysIleGlnLeuIleAlaArgValArgGlnGln 825830835840 CTAGGCCAGGGGATTACCCTCGAGGAGGTCTTCCAGACCAAGACGTTG2955 LeuGlyGlnGlyIleThrLeuGluGluValPheGlnThrLysThrLeu 845850855 CGAGCTATGGCTGCCCTCTTGTCGGAAAAGTACACGAAGGCGTCGAAT3003 ArgAlaMetAlaAlaLeuLeuSerGluLysTyrThrLysAlaSerAsn 860865870 GGGACGAACGGAGTGACCAACGGCACTGCTCACGTCAACGGCCACGCA3051 GlyThrAsnGlyValThrAsnGlyThrAlaHisValAsnGlyHisAla 875880885 GCGAACGGCCATGTCAGCGACAGCTACGTGGCCAGCAGTTTGCAGCAA3099 AlaAsnGlyHisValSerAspSerTyrValAlaSerSerLeuGlnGln 890895900 GGCTTTGTTTACCATTCACTCAAGAACGAACTGTCCGAGGCGTACACC3147 GlyPheValTyrHisSerLeuLysAsnGluLeuSerGluAlaTyrThr 905910915920 ATGCAATCCATGATCCACTATGGTGTGCCCCTGAAACGGGATATTTAC3195 MetGlnSerMetIleHisTyrGlyValProLeuLysArgAspIleTyr 925930935 CAAGCGGCATGGCAGAGGGTACAGGGGGAGCACCCTGCACTGCGGCTT3243 GlnAlaAlaTrpGlnArgValGlnGlyGluHisProAlaLeuArgLeu 940945950 CGGTTCACATGGGAGGCCGAAGTGATGCAGATCGTGGACCCGAAATCT3291 ArgPheThrTrpGluAlaGluValMetGlnIleValAspProLysSer 955960965 GAACTCGACTGGCGTGTTGTTGACTGGACCGATGTTTCGAGCCGGGAG3339 GluLeuAspTrpArgValValAspTrpThrAspValSerSerArgGlu 970975980 AAGCAGCTGGTTGCGCTGGAGCAACTCCAAACGGAGGACCTTGCTAAG3387 LysGlnLeuValAlaLeuGluGlnLeuGlnThrGluAspLeuAlaLys 9859909951000 GTCTACCATCTCGATAAGGGGCCCCTTATGCGACTATACCTCATCCTG3435 ValTyrHisLeuAspLysGlyProLeuMetArgLeuTyrLeuIleLeu 100510101015 CTTCCGGACTCAAAGTACTCCTGTCTGTTCAGCTGCCACCATGCCATT3483 LeuProAspSerLysTyrSerCysLeuPheSerCysHisHisAlaIle 102010251030 CTCGATGGGTGGAGTCTGCCCCTGCTCTTCAACAATGTCCACCAGGCC3531 LeuAspGlyTrpSerLeuProLeuLeuPheAsnAsnValHisGlnAla 103510401045 TACCTCGATCTCGTCGAAGGCACTGCTTCGCCCGTCGAGCAGGACGCT3579 TyrLeuAspLeuValGluGlyThrAlaSerProValGluGlnAspAla 105010551060 ACCTACCTACTCGGCCAGCAGTACCTGCAGAGCCACAGGGACGACCAT3627 ThrTyrLeuLeuGlyGlnGlnTyrLeuGlnSerHisArgAspAspHis 1065107010751080 CTCGACTTCTGGGCCGAGCAGATCGGCAGGATCGAAGAGCGCTGCGAC3675 LeuAspPheTrpAlaGluGlnIleGlyArgIleGluGluArgCysAsp 108510901095 ATGAATGCGCTGCTGAATGAGGCCAGCCGATACAAGGTGCCCCTGGCC3723 MetAsnAlaLeuLeuAsnGluAlaSerArgTyrLysValProLeuAla 110011051110 GACTATGACCAAGTCCGCGAGCAGAGGCAGCAGACCATCAGTCTGCCC3771 AspTyrAspGlnValArgGluGlnArgGlnGlnThrIleSerLeuPro 111511201125 TGGAACAACTCCATGGACGCTGGTGTGCGGGAAGAACTCTCCAGTCGT3819 TrpAsnAsnSerMetAspAlaGlyValArgGluGluLeuSerSerArg 113011351140 GGCATCACCCTTCATTCCATTCTACAGACGGTCTGGCACCTGGTCCTC3867 GlyIleThrLeuHisSerIleLeuGlnThrValTrpHisLeuValLeu 1145115011551160 CACTCTTATGGAGGAGGCACCCACACGATCACCGGCACCACCATCTCC3915 HisSerTyrGlyGlyGlyThrHisThrIleThrGlyThrThrIleSer 116511701175 GGCCGTCACCTGCCCGTCCCCGGAATTGAGCGCTCTGTTGGTCTCTTC3963 GlyArgHisLeuProValProGlyIleGluArgSerValGlyLeuPhe 118011851190 ATCAACACACTCCCTATGATCTTTGATCACACCGTCTGCCAGGATATG4011 IleAsnThrLeuProMetIlePheAspHisThrValCysGlnAspMet 119512001205 ACAGCGCTCGAGGCCATTGAGCATGTCCAAGGCCAAGTCAACGCCATG4059 ThrAlaLeuGluAlaIleGluHisValGlnGlyGlnValAsnAlaMet 121012151220 AACTCCCGGGGCAACGTCGAGCTCGGACGCATGAGCAAGAACGACCTC4107 AsnSerArgGlyAsnValGluLeuGlyArgMetSerLysAsnAspLeu 1225123012351240 AAGCACGGGCTCTTCGACACCCTCTTCGTCCTCGAGAACTACCCAAAC4155 LysHisGlyLeuPheAspThrLeuPheValLeuGluAsnTyrProAsn 124512501255 CTCGACACGGAGCAGCGGGAGAAGCACGAGGAGAAGCTCAAGTTCACC4203 LeuAspThrGluGlnArgGluLysHisGluGluLysLeuLysPheThr 126012651270 ATCAAGGGTGGCACGGAGAAGCTCAGTTACCCGCTGGCCGTGATTGCC4251 IleLysGlyGlyThrGluLysLeuSerTyrProLeuAlaValIleAla 127512801285 CAAGAGGACGGCGACAGCGGATGCTCGTTTACGCTCTGCTATGCGGGC4299 GlnGluAspGlyAspSerGlyCysSerPheThrLeuCysTyrAlaGly 129012951300 GAGCTCTTCACGGATGAGTCCATCCAGGCGCTCCTGGACACTGTCCGG4347 GluLeuPheThrAspGluSerIleGlnAlaLeuLeuAspThrValArg 1305131013151320 GACACCCTGAGTGATATTCTCGGGAACATCCATGCCCCTATCCGCAAC4395 AspThrLeuSerAspIleLeuGlyAsnIleHisAlaProIleArgAsn 132513301335 ATGGAGTACCTCTCCTCGAACCAGACGGCGCAGCTCGACAAGTGGAAT4443 MetGluTyrLeuSerSerAsnGlnThrAlaGlnLeuAspLysTrpAsn 134013451350 GCCACCGCCTTCGAGTACCCCAACACCACACTGCACGCCATGTTCGAG4491 AlaThrAlaPheGluTyrProAsnThrThrLeuHisAlaMetPheGlu 135513601365 TCCGAGGCGCAGCAGAAGCCGGACAAGGTGGCCGTGGTGTACGAGGAT4539 SerGluAlaGlnGlnLysProAspLysValAlaValValTyrGluAsp 137013751380 ATCAGGCTGACCTACCGCGAGCTCAACAGCCGTGCCAATGCCCTGGCG4587 IleArgLeuThrTyrArgGluLeuAsnSerArgAlaAsnAlaLeuAla 1385139013951400 TTCTACCTCCTCTCCCAGGCGGCTATCCAACCGAACAAGCTGGTCGGG4635 PheTyrLeuLeuSerGlnAlaAlaIleGlnProAsnLysLeuValGly 140514101415 CTGATCATGGACAAGAGCGAGCACATGATCACGAGCATCCTCGCGGTC4683 LeuIleMetAspLysSerGluHisMetIleThrSerIleLeuAlaVal 142014251430 TGGAAAACGGGTGGAGCCTACGTCCCGATCGACCCTCGATACCCTGAC4731 TrpLysThrGlyGlyAlaTyrValProIleAspProArgTyrProAsp 143514401445 CAGCGTATCCAGTATATCCTGGAGGATACGGCGGCTCTCGCAGTCATC4779 GlnArgIleGlnTyrIleLeuGluAspThrAlaAlaLeuAlaValIle 145014551460 ACGGACAGTCCTCATATTGACCGTCTGCGCAGCATCACCAACAACCGC4827 ThrAspSerProHisIleAspArgLeuArgSerIleThrAsnAsnArg 1465147014751480 CTTCCTGTTATCCAGTCGGACTTTGCTCTCCAACTCCCGCCCAGCCCA4875 LeuProValIleGlnSerAspPheAlaLeuGlnLeuProProSerPro 148514901495 GTTCATCCCGTCTCAAACTGCAAGCCAAGCGACCTCGCCTACATCATG4923 ValHisProValSerAsnCysLysProSerAspLeuAlaTyrIleMet 150015051510 TACACATCCGGCACCACTGGCAACCCCAAGGGTGTCATGGTGGAGCAC4971 TyrThrSerGlyThrThrGlyAsnProLysGlyValMetValGluHis 151515201525 CACGGTGTAGTGAATCTGTGCGTTTCACTCTGCCGGCTCTTCGGCCTT5019 HisGlyValValAsnLeuCysValSerLeuCysArgLeuPheGlyLeu 153015351540 CGGAACACAGATGACGAGGTCATCCTCTCGTTCTCGAACTACGTCTTC5067 ArgAsnThrAspAspGluValIleLeuSerPheSerAsnTyrValPhe 1545155015551560 GACCACTTTGTCGAGCAGATGACGGATGCCCTTCTCAACGGTCAGACT5115 AspHisPheValGluGlnMetThrAspAlaLeuLeuAsnGlyGlnThr 156515701575 CTTGTGGTCCTCAACGACGAGATGCGTGGCGACAAGGAGAGGCTTTAC5163 LeuValValLeuAsnAspGluMetArgGlyAspLysGluArgLeuTyr 158015851590 AGATACATCGAGACCAACCGCGTCACGTACCTCTCGGGGACACCTTCC5211 ArgTyrIleGluThrAsnArgValThrTyrLeuSerGlyThrProSer 159516001605 GTCATCTCCATGTACGAGTTCGACCGGTTCCGCGACCACCTGCGGCGC5259 ValIleSerMetTyrGluPheAspArgPheArgAspHisLeuArgArg 161016151620 GTGGATTGCGTCGGCGAGGCCTTCAGCGAGCCGGTATTCGACAAGATC5307 ValAspCysValGlyGluAlaPheSerGluProValPheAspLysIle 1625163016351640 CGCGAGACGTTCCCGGGTCTCATCATCAACGGTTATGGCCCGACTGAG5355 ArgGluThrPheProGlyLeuIleIleAsnGlyTyrGlyProThrGlu 164516501655 GTGTCTATCACTACCCACAAGCGGCCCTACCCGTTCCCGGAGCGCCGC5403 ValSerIleThrThrHisLysArgProTyrProPheProGluArgArg 166016651670 ACAGACAAGAGCATCGGTTGCCAGCTGGACAACAGCACGAGCTACGTC5451 ThrAspLysSerIleGlyCysGlnLeuAspAsnSerThrSerTyrVal 167516801685 CTCAACGATGACATGAAGCGCGTGCCCATCGGGGCCGTGGGAGAGCTG5499 LeuAsnAspAspMetLysArgValProIleGlyAlaValGlyGluLeu 169016951700 TACCTTGGTGGCGATGGCGTCGCTCGCGGATACCACAACCGGCCAGAC5547 TyrLeuGlyGlyAspGlyValAlaArgGlyTyrHisAsnArgProAsp 1705171017151720 CTGACGGCTGACCGGTTCCCTGCCAACCCCTTCCAGACGGAGCAGGAG5595 LeuThrAlaAspArgPheProAlaAsnProPheGlnThrGluGlnGlu 172517301735 AGACTTGAGGGCCGAAATGCGCGTCTGTATAAGACTGGTGACTTGGTT5643 ArgLeuGluGlyArgAsnAlaArgLeuTyrLysThrGlyAspLeuVal 174017451750 CGCTGGATCCACAATGCAAACGGCGATGGTGAGATCGAGTACCTCGGC5691 ArgTrpIleHisAsnAlaAsnGlyAspGlyGluIleGluTyrLeuGly 175517601765 CGCAACGACTTCCAGGTCAAGATTCGAGGCCAGAGAATCGAGCTGGGA5739 ArgAsnAspPheGlnValLysIleArgGlyGlnArgIleGluLeuGly 177017751780 GAGATCGAGGCCGTGCTTTCATCCTATCCGGGCATCAAACAATCCGTC5787 GluIleGluAlaValLeuSerSerTyrProGlyIleLysGlnSerVal 1785179017951800 GTCCTGGCCAAGGACCGCAAGAATGACGGGCAGAAGTACCTCGTCGGC5835 ValLeuAlaLysAspArgLysAsnAspGlyGlnLysTyrLeuValGly 180518101815 TACTTCGTCTCCTCAGCAGGGTCCCTGTCCGCCCAGGCCATCCGCCGC5883 TyrPheValSerSerAlaGlySerLeuSerAlaGlnAlaIleArgArg 182018251830 TTCATGCTCACGAGCCTGCCCGATTACATGGTTCCTGCGCAGCTGGTG5931 PheMetLeuThrSerLeuProAspTyrMetValProAlaGlnLeuVal 183518401845 CCCATCGCCAAGTTCCCCGTCACCGTGAGCGGGAAGCTCGATGCCAAG5979 ProIleAlaLysPheProValThrValSerGlyLysLeuAspAlaLys 185018551860 GCCTTGCCCGTGCCAGACGATACAGTCGAGGATGACATTGTGCCACCG6027 AlaLeuProValProAspAspThrValGluAspAspIleValProPro 1865187018751880 CGTACCGAGGTTGAGCGCATCCTAGCTGGGATCTGGTCTGAGCTGTTG6075 ArgThrGluValGluArgIleLeuAlaGlyIleTrpSerGluLeuLeu 188518901895 GAGATACCGGTCGACAGGATCAGCATCTACAGTGACTTCTTCAGTCTG6123 GluIleProValAspArgIleSerIleTyrSerAspPhePheSerLeu 190019051910 GGCGGCGACAGTCTCAAGAGTACCAAGCTGTCCTTTGCTGCCACTCGG6171 GlyGlyAspSerLeuLysSerThrLysLeuSerPheAlaAlaThrArg 191519201925 GCTCTCGGTGTGGCCGTCAGTGTCCGCAACTTGTTCAGCCATCCGACT6219 AlaLeuGlyValAlaValSerValArgAsnLeuPheSerHisProThr 193019351940 ATCGAAGCCTTGTCTCAGTGGATTATCAGGGGTTCGAACGAGGTCAAG6267 IleGluAlaLeuSerGlnTrpIleIleArgGlySerAsnGluValLys 1945195019551960 GATGTGGCTGTGGTGAAGGGCGGTGCCAGTCTTGATATCCCCCTATCC6315 AspValAlaValValLysGlyGlyAlaSerLeuAspIleProLeuSer 196519701975 CCTGCCCAGGAAAGACTCATGTTCATCCACGAGTTCGGCCATAGCGGC6363 ProAlaGlnGluArgLeuMetPheIleHisGluPheGlyHisSerGly 198019851990 GAGGATACTGGTGCTTACAATGTGCCTTTGCAGCTGCAGCTTCACCAT6411 GluAspThrGlyAlaTyrAsnValProLeuGlnLeuGlnLeuHisHis 199520002005 GATGTCTGTCTCGAGTCGCTTGAGAAGGCTCTGCGGGATGTCGTCTCG6459 AspValCysLeuGluSerLeuGluLysAlaLeuArgAspValValSer 201020152020 AGACACGAGGCTCTCCGGACCTTGATCACCAGGACCCAGAAGTCCTCC6507 ArgHisGluAlaLeuArgThrLeuIleThrArgThrGlnLysSerSer 2025203020352040 GTGCACTGCCAGAAGATCCTCGACGCCGAAGAAGCGCAAAAGCTCTTC6555 ValHisCysGlnLysIleLeuAspAlaGluGluAlaGlnLysLeuPhe 204520502055 TCTGTTGATGTTCTGCGCCTGACCTCGGAGACGGAGATGCAGGGCAGG6603 SerValAspValLeuArgLeuThrSerGluThrGluMetGlnGlyArg 206020652070 ATGGCCGAGAGTACCGCCCACGCCTTCAAGCTCGACGAGGAACTCCCG6651 MetAlaGluSerThrAlaHisAlaPheLysLeuAspGluGluLeuPro 207520802085 ATTCATGTACGCCTGTACCAGGTTGTACGTGATGGCCGCACGCTCAGC6699 IleHisValArgLeuTyrGlnValValArgAspGlyArgThrLeuSer 209020952100 TTTGCCAGCATCGTCTGCCACCATCTGGCGTTTGACGCGTGGTCATGG6747 PheAlaSerIleValCysHisHisLeuAlaPheAspAlaTrpSerTrp 2105211021152120 GATGTGTTCCAGAGGGACTTGGACGCCTTCTATGCCGTCCATACGAAG6795 AspValPheGlnArgAspLeuAspAlaPheTyrAlaValHisThrLys 212521302135 CACAAGGCTGCCGCCAACCTGCCAACCCTCCGCGTGCAATATAAGGAG6843 HisLysAlaAlaAlaAsnLeuProThrLeuArgValGlnTyrLysGlu 214021452150 TATGCGATAGAGCACCGCCGGGCTCTCCGCGCTGAGCAACACCGTGTT6891 TyrAlaIleGluHisArgArgAlaLeuArgAlaGluGlnHisArgVal 215521602165 CTCGCGGACTACTGGCTGCGCAAGCTCAGTGACATGGAGGCGTCTTAT6939 LeuAlaAspTyrTrpLeuArgLysLeuSerAspMetGluAlaSerTyr 217021752180 CTGGTCCCCGATCGCCCTCGACCGGCGCAGTTTGACTATACCGGGAAC6987 LeuValProAspArgProArgProAlaGlnPheAspTyrThrGlyAsn 2185219021952200 GATCTCCAGTTCTCAACTACTCCCGAGACCACCGCGCAGTTGAAGGAG7035 AspLeuGlnPheSerThrThrProGluThrThrAlaGlnLeuLysGlu 220522102215 CTGGCCAAGCGCGAGGGTTCAAGCCTCTACACCGTTGTGGCGGCGGCG7083 LeuAlaLysArgGluGlySerSerLeuTyrThrValValAlaAlaAla 222022252230 TACTTTCTGCTTCTCTACGTGTACACCAACCAGCGGGATATCACGATT7131 TyrPheLeuLeuLeuTyrValTyrThrAsnGlnArgAspIleThrIle 223522402245 GGTATTCCCGTTGCGCACCGTAACCATCCGGACTTTGAGTCGGTTGTC7179 GlyIleProValAlaHisArgAsnHisProAspPheGluSerValVal 225022552260 GGCTTCTTTGTCAACTTGCTCCCTCTGCGGGTCAACGTGTCTCAGTCG7227 GlyPhePheValAsnLeuLeuProLeuArgValAsnValSerGlnSer 2265227022752280 GACATTCATGGACTTATCCAGGCAGTGCAGAAAGAGCTTGTCGATGCC7275 AspIleHisGlyLeuIleGlnAlaValGlnLysGluLeuValAspAla 228522902295 CAGATCCATCAGGACTTGCCATTCCAGGAGATCACCAAGCTTCTTCAT7323 GlnIleHisGlnAspLeuProPheGlnGluIleThrLysLeuLeuHis 230023052310 GTGCAGCACGATCCAAGCCGCCATCCCCTTCTCCAGGCCGTGTTCAAC7371 ValGlnHisAspProSerArgHisProLeuLeuGlnAlaValPheAsn 231523202325 TGGGAAAACGTACCCGCCAATGTCCACGAGGAGCAGCTGCTTCAGGAG7419 TrpGluAsnValProAlaAsnValHisGluGluGlnLeuLeuGlnGlu 233023352340 TACAAGCCGCCCTCGCCTCTGCCTTCGGCGGCCAAGTTTGATCTCAAC7467 TyrLysProProSerProLeuProSerAlaAlaLysPheAspLeuAsn 2345235023552360 GTCACGGTGAAAGAGAGCGTCAATTCGCTCAACGTCAACTTCAACTAT7515 ValThrValLysGluSerValAsnSerLeuAsnValAsnPheAsnTyr 236523702375 CCTACCAGCCTCTTCGAGGAGGAGACCGTTCAGGGGTTCATGGAAACC7563 ProThrSerLeuPheGluGluGluThrValGlnGlyPheMetGluThr 238023852390 TTCCATCTCCTTCTTCGACAACTGGCCCACAACAAGGCTAGCACAAGC7611 PheHisLeuLeuLeuArgGlnLeuAlaHisAsnLysAlaSerThrSer 239524002405 CTCTCGAAGCTGTCGGTTGAAGATGGAGTGTTGAATCCAGAGCCGACT7659 LeuSerLysLeuSerValGluAspGlyValLeuAsnProGluProThr 241024152420 AACCTTCAGCCCTCAAGCCGGGACAGCGGAAATTCACTCCATGGGCTC7707 AsnLeuGlnProSerSerArgAspSerGlyAsnSerLeuHisGlyLeu 2425243024352440 TTCGAGGACATCGTGGCCTCGACCCCGGACCGCATCGCAATTGCTGAC7755 PheGluAspIleValAlaSerThrProAspArgIleAlaIleAlaAsp 244524502455 GGCACCAGGAGTCTCTCGTACTCCGAACTCAACGAGCGGGCAAACCAG7803 GlyThrArgSerLeuSerTyrSerGluLeuAsnGluArgAlaAsnGln 246024652470 CTCGTACATTTGATCATCTCTTCTGCCAGTATTGTAGCAGACGACCGC7851 LeuValHisLeuIleIleSerSerAlaSerIleValAlaAspAspArg 247524802485 ATCGCTCTTCTTTTGGACAAGAGCATCGATATGGTGATTGCTCTCCTG7899 IleAlaLeuLeuLeuAspLysSerIleAspMetValIleAlaLeuLeu 249024952500 GCAGTTTGGAAGGCCGGTGCCGCATATGTGCCCCTTGACCCGACATAT7947 AlaValTrpLysAlaGlyAlaAlaTyrValProLeuAspProThrTyr 2505251025152520 CCGTCGCAGAGGACTGAGCTCATCTTGGAGGAATCTAGTGCCAGGACG7995 ProSerGlnArgThrGluLeuIleLeuGluGluSerSerAlaArgThr 252525302535 CTCATCACCACTAGAAAGCACACGCCGAGGGGAGGAACAGTCGCAAAT8043 LeuIleThrThrArgLysHisThrProArgGlyGlyThrValAlaAsn 254025452550 GTTCCANNNGTGGTCCTTGACAGCCCCGAGACCCTAGCCTGCCTCAAC8091 ValProSerValValLeuAspSerProGluThrLeuAlaCysLeuAsn 255525602565 CAGCAGTCAAAGGAAAACCCGACAACGTCAACGCAGAAACCGTCCGAC8139 GlnGlnSerLysGluAsnProThrThrSerThrGlnLysProSerAsp 257025752580 CTCGCATATGTCATCTTCACCTCGGGAACCACAGGCAAGCCCAAGGGG8187 LeuAlaTyrValIlePheThrSerGlyThrThrGlyLysProLysGly 2585259025952600 GTTCTGGTGGAGCACCAGAGCGTAGTCCAGCTGCGCAATTCCCTCATC8235 ValLeuValGluHisGlnSerValValGlnLeuArgAsnSerLeuIle 260526102615 GAGCGATACTTCGGCGAGACCAACGGGTCTCACGCCGTGCTCTTCCTG8283 GluArgTyrPheGlyGluThrAsnGlySerHisAlaValLeuPheLeu 262026252630 TCCAACTACGTCTTCGACTTCTCTCTTGAACAGCTCTGTCTCTCAGTC8331 SerAsnTyrValPheAspPheSerLeuGluGlnLeuCysLeuSerVal 263526402645 TTGGGTGGAAACAAGCTCATCATTCCACCAGAGGAGGGTCTCACGCAC8379 LeuGlyGlyAsnLysLeuIleIleProProGluGluGlyLeuThrHis 265026552660 GAGGCATTCTACGACATCGGCCGCAGGGAGAAGCTATCCTATCTCAGC8427 GluAlaPheTyrAspIleGlyArgArgGluLysLeuSerTyrLeuSer 2665267026752680 GGGACGCCCTCGGTGCTGCAGCAGATTGAGCTCTCCCGTCTGCCGCAT8475 GlyThrProSerValLeuGlnGlnIleGluLeuSerArgLeuProHis 268526902695 CTTCACATGGTCACCGCTGCGGGCGAGGAGTTCCACGCTAGTCAGTTT8523 LeuHisMetValThrAlaAlaGlyGluGluPheHisAlaSerGlnPhe 270027052710 GAGAAGATGCGCTCCCAGTTCGCGGGCCAGATCAACAACGCCTATGGT8571 GluLysMetArgSerGlnPheAlaGlyGlnIleAsnAsnAlaTyrGly 271527202725 ATCACTGAGACGACCGTGTACAACATCATCACCACGTTCAAGGGCGAT8619 IleThrGluThrThrValTyrAsnIleIleThrThrPheLysGlyAsp 273027352740 GCCCCCTTTACCAAGGCACTCTGCCACGGGATCCCCGGAAGTCACGTC8667 AlaProPheThrLysAlaLeuCysHisGlyIleProGlySerHisVal 2745275027552760 TACGTCCTGAACGACCGACTTCAGCGTGTTCCTTTCAACGCTGTTGGC8715 TyrValLeuAsnAspArgLeuGlnArgValProPheAsnAlaValGly 276527702775 GAGCTCTACTTGGGCGGTGACTGCCTTGCTCGCGGGTACCTCAACCAG8763 GluLeuTyrLeuGlyGlyAspCysLeuAlaArgGlyTyrLeuAsnGln 278027852790 GATGCCCTGACCAACGAGCGATTCATCCCCAACCCTTTCTACGAGCCG8811 AspAlaLeuThrAsnGluArgPheIleProAsnProPheTyrGluPro 279528002805 AAACAGGCAAGTGACAGTCGTCCCCAGAGACTCTACAAGACTGGAGAT8859 LysGlnAlaSerAspSerArgProGlnArgLeuTyrLysThrGlyAsp 281028152820 CTGGTGCGCTTCCGTGGACCCCACCATCTCGAGTATCTCGGCCGCAAG8907 LeuValArgPheArgGlyProHisHisLeuGluTyrLeuGlyArgLys 2825283028352840 GACCAGCAGGTCAAGCTGAGGGGCTTCCGCATCGAGCTCTCCGAGGTG8955 AspGlnGlnValLysLeuArgGlyPheArgIleGluLeuSerGluVal 284528502855 CGGGATGCCGTCCTAGCCATCTCTGCTGTTAAGGAGGCTGCCGTCATC9003 ArgAspAlaValLeuAlaIleSerAlaValLysGluAlaAlaValIle 286028652870 CCCAAGTATGACGAGGATGGCTCCGATTCACGAAGGGTCAGCGCCATC9051 ProLysTyrAspGluAspGlySerAspSerArgArgValSerAlaIle 287528802885 GTCTGCTACTACACGCTCAACGCCGGAACTGTGTGCGAAGCATCGAGT9099 ValCysTyrTyrThrLeuAsnAlaGlyThrValCysGluAlaSerSer 289028952900 ATCCGTGACCACCTGCACGCCAACCTTCCCCCGTACATGGTCCCAAGT9147 IleArgAspHisLeuHisAlaAsnLeuProProTyrMetValProSer 2905291029152920 CAGATCCACCAGTTGGAGGGATCTCTCCCCGTGACCGTCAATGGGAAG9195 GlnIleHisGlnLeuGluGlySerLeuProValThrValAsnGlyLys 292529302935 CTCGACCTGAACAGGCTCTCCACAACTCAAGTCTCGCAGCCAGAGCTT9243 LeuAspLeuAsnArgLeuSerThrThrGlnValSerGlnProGluLeu 294029452950 TACACCGCTCCACGAAATTCGACAGAGGAAACCTTGTGCCAGCTTTGG9291 TyrThrAlaProArgAsnSerThrGluGluThrLeuCysGlnLeuTrp 295529602965 GCATCTCTCCTAGGCGTCGACCACTGCGGCATTGACGACGACCTGTTT9339 AlaSerLeuLeuGlyValAspHisCysGlyIleAspAspAspLeuPhe 297029752980 GCCCGAGGCGGCGACAGCATCTCCTCTCTCCGACTAGTGGGTGACATC9387 AlaArgGlyGlyAspSerIleSerSerLeuArgLeuValGlyAspIle 2985299029953000 TACCGCGCGCTAGGACGCAAGGTCACCGTCAAGGACATCTACCTCCAC9435 TyrArgAlaLeuGlyArgLysValThrValLysAspIleTyrLeuHis 300530103015 CGCAGCGTCCGAGCCCTAAGCGAAAATGTCCTGACCGACCAGAAGGAT9483 ArgSerValArgAlaLeuSerGluAsnValLeuThrAspGlnLysAsp 302030253030 AAGGGTACTCTGCCAGCGTCTCCTCCCCTCCAGCGAGCGGAGCAGGGC9531 LysGlyThrLeuProAlaSerProProLeuGlnArgAlaGluGlnGly 303530403045 CAGGTTGAGGGCGACGCACCGCTTCTCCCCATCCAGGACTGGTTCCTT9579 GlnValGluGlyAspAlaProLeuLeuProIleGlnAspTrpPheLeu 305030553060 TCCAAGCCCCTGGATAACCCCGCTTACTGGAACCACTGCTTCACCATT9627 SerLysProLeuAspAsnProAlaTyrTrpAsnHisCysPheThrIle 3065307030753080 CGAACCGGGGCACTCTCCGTCGAAGGGCTCCGGGGTGCTCTGAAGCTG9675 ArgThrGlyAlaLeuSerValGluGlyLeuArgGlyAlaLeuLysLeu 308530903095 CTGCAGGAGCGCCACGACGTGCTGCGTCTGAGACTGCAACGCCGGGAC9723 LeuGlnGluArgHisAspValLeuArgLeuArgLeuGlnArgArgAsp 310031053110 GAAGGTCGCCATGTTCAGACCTTTGCGCGTGACTGCGCGCAACCTCGC9771 GluGlyArgHisValGlnThrPheAlaArgAspCysAlaGlnProArg 311531203125 TTGACTGTGCTAGACCGACGAAGCTTCGAGGACGCAGAGGATGTACAG9819 LeuThrValLeuAspArgArgSerPheGluAspAlaGluAspValGln 313031353140 GAGGCTCTCTGCGAGATCCAATCTCATTTCGACCTCGAGAATGGACCC9867 GluAlaLeuCysGluIleGlnSerHisPheAspLeuGluAsnGlyPro 3145315031553160 CTCTACACAGTGGCGTACATCCACGGTTACGAGGACGGCTCCGCCCGA9915 LeuTyrThrValAlaTyrIleHisGlyTyrGluAspGlySerAlaArg 316531703175 GTGTGGTTTGCCTGCCATCACGTCATGGTCGACACTGTGAGCTGGAAC9963 ValTrpPheAlaCysHisHisValMetValAspThrValSerTrpAsn 318031853190 ATTATACTGCAAGACCTGCAGGCTCTCTATCATGGAGACAGCCTTGGT10011 IleIleLeuGlnAspLeuGlnAlaLeuTyrHisGlyAspSerLeuGly 319532003205 CCCAAGAGCAGCAGCGTGCAGCAGTGGTCGCTAGCTGTCAGCGACTAC10059 ProLysSerSerSerValGlnGlnTrpSerLeuAlaValSerAspTyr 321032153220 AAAATGCCACTGTCGGAGAGGGCGCATTGGAATGTGCTCAGGAAGACA10107 LysMetProLeuSerGluArgAlaHisTrpAsnValLeuArgLysThr 3225323032353240 GTCGCCCAGAGCTTCGAGACCCTGCCTATCTGCATGGGCGGCGTGCTC10155 ValAlaGlnSerPheGluThrLeuProIleCysMetGlyGlyValLeu 324532503255 CAGTGCCAGGAGAAGTTCTCGAGGGAAACGACAACAGCTCTGCTCTCC10203 GlnCysGlnGluLysPheSerArgGluThrThrThrAlaLeuLeuSer 326032653270 AAGGCCTGCCCTGCCTTGGACTCCGGTATGCATGAGATCCTTCTCATG10251 LysAlaCysProAlaLeuAspSerGlyMetHisGluIleLeuLeuMet 327532803285 GCCGTGGGCTCCGCGCTGCAGAAGGCGGCAGGGGATGTCCCTCAGGTC10299 AlaValGlySerAlaLeuGlnLysAlaAlaGlyAspValProGlnVal 329032953300 GTCACGATAGAGGGTCACGGGCGCGAAGATACTATCGACGCAACTCTG10347 ValThrIleGluGlyHisGlyArgGluAspThrIleAspAlaThrLeu 3305331033153320 GACGTCAGCCGGACAGTCGGCTGGTTCACGAGCATGTACCCCTTCGAG10395 AspValSerArgThrValGlyTrpPheThrSerMetTyrProPheGlu 332533303335 ATCCCCAAAGTGACCGACCCCGCTCAGGGCGTCGTCGATGTCAAGGAG10443 IleProLysValThrAspProAlaGlnGlyValValAspValLysGlu 334033453350 GCGATGCGTCGCGTGCCGAATAGGGGTGTCGGTTACGGTCCAGCCTAC10491 AlaMetArgArgValProAsnArgGlyValGlyTyrGlyProAlaTyr 335533603365 GGATACGGCGGATCGTGCCTGCCCGCGGTGAGCTTCAACTACCTTGGT10539 GlyTyrGlyGlySerCysLeuProAlaValSerPheAsnTyrLeuGly 337033753380 CGCCTGGACCAGGCTTCCTCGGGGGCTCAAAGGGACTGGACGCTGGTC10587 ArgLeuAspGlnAlaSerSerGlyAlaGlnArgAspTrpThrLeuVal 3385339033953400 ATGGATGAAGACGAGTATCCGGTCGGACTGTGCACCAGCGCTGAGGAC10635 MetAspGluAspGluTyrProValGlyLeuCysThrSerAlaGluAsp 340534103415 TCGGGACGAAGCTCCTCCATGGTGGATTTCACCTTCTCTATCTCTGGC10683 SerGlyArgSerSerSerMetValAspPheThrPheSerIleSerGly 342034253430 GGCCAGCTTGTCATGGATATGAGTAGCAGCTGGGGCCACGGCGCACGA10731 GlyGlnLeuValMetAspMetSerSerSerTrpGlyHisGlyAlaArg 343534403445 AATGAATTCGTTCGCACAGTTCGTAACACACTAGATGACTTGATCAAA10779 AsnGluPheValArgThrValArgAsnThrLeuAspAspLeuIleLys 345034553460 ACAACGAGCAGCAGGGACTTCAGCGCACCTCTGCCTCCGTCGGATCAG10827 ThrThrSerSerArgAspPheSerAlaProLeuProProSerAspGln 3465347034753480 GAGTCCAGCTTCACCCCTTATTTTGTCTTCGAAGAGGGCGAGCGACAC10875 GluSerSerPheThrProTyrPheValPheGluGluGlyGluArgHis 348534903495 GGCGCTCCGCTCTTCCTGCTCCCACCTGGCGAAGGCGGAGCGGAGAGC10923 GlyAlaProLeuPheLeuLeuProProGlyGluGlyGlyAlaGluSer 350035053510 TACTTCCACAACATTGTCAAGGGTCTCCCGAACCGCAATCTTGTCGTG10971 TyrPheHisAsnIleValLysGlyLeuProAsnArgAsnLeuValVal 351535203525 TTCAACAATCATTACCGCGAGGAGAAGACGCTCCGGACCATCGAGGCG11019 PheAsnAsnHisTyrArgGluGluLysThrLeuArgThrIleGluAla 353035353540 CTGGCCGAGTACTACCTGTCGCACATCCGATCCATCCAGCCGGAGGGG11067 LeuAlaGluTyrTyrLeuSerHisIleArgSerIleGlnProGluGly 3545355035553560 CCATACCACATCCTCGGCTGGAGTTTCGGAGGCATCCTCGGTCTCGAG11115 ProTyrHisIleLeuGlyTrpSerPheGlyGlyIleLeuGlyLeuGlu 356535703575 GCGGCAAAGCGATTGACTGGCGAGGGTCACAAGATTGCCACGCTGGCA11163 AlaAlaLysArgLeuThrGlyGluGlyHisLysIleAlaThrLeuAla 358035853590 CTTATCGATCCGTACTTTGACATCCCGTCCGCGTCCAAGGCCATCGGC11211 LeuIleAspProTyrPheAspIleProSerAlaSerLysAlaIleGly 359536003605 CAACCTGACGATGCCTGCGTCTTGGACCCCATATACCACGTCTACCAC11259 GlnProAspAspAlaCysValLeuAspProIleTyrHisValTyrHis 361036153620 CCGTCGCCGGAGAGCTTCAGGACGGTGTCATCTCTCACTAATCACATA11307 ProSerProGluSerPheArgThrValSerSerLeuThrAsnHisIle 3625363036353640 GCCCTGTTCAAGGCTACCGAGACGAATGACCAGCATGGCAATGCCACG11355 AlaLeuPheLysAlaThrGluThrAsnAspGlnHisGlyAsnAlaThr 364536503655 CAGCAGGCCCTGTATGAGTGGTTTGCCACGTGCCCTTTGAACAACCTG11403 GlnGlnAlaLeuTyrGluTrpPheAlaThrCysProLeuAsnAsnLeu 366036653670 GACAAGTTTTTGGCGGCCGACACGATCAAGGTGGTTCCTCTGGAGGGT11451 AspLysPheLeuAlaAlaAspThrIleLysValValProLeuGluGly 367536803685 ACACATTTTACCTGGGTGCACCACCCGGAGCAGGTGCGCTCAATGTGC11499 ThrHisPheThrTrpValHisHisProGluGlnValArgSerMetCys 369036953700 ACTATGCTGGATGAATGGCTTGGGTGAACGAGGCAGTTGCTGTGAGAGAATGAG11553 ThrMetLeuAspGluTrpLeuGly 37053710 AATGAGACACAAAACGCGGGCGGAAGAGAGACTTCCTCGGACGGCGGG11601 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3712 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: ValAlaLeuGluGlnTrpLysThrThrValGlnSerValSerGluArg 151015 CysAspLeuSerGlyLeuSerGlnHisProThrAspTyrGlnLeuAla 202530 SerThrGlyValLysGlyAlaGlyGlySerSerIleGluGluArgSer 354045 AlaIleValSerAspGluLeuPheSerSerLeuArgAspValCysSer 505560 GlnArgGlnLeuAspProArgSerLeuMetLeuPheSerValHisGln 65707580 MetLeuLysArgPheGlyAsnGlySerHisThrValValAlaSerLeu 859095 ValThrSerSerGluGlyCysProSerThrSerAlaTrpArgAlaIle 100105110 ProSerValIleHisHisIleGluGlyGlyAspAsnAsnAsnThrVal 115120125 AlaSerAlaValGluGlnAlaAlaAsnLeuLeuAsnSerGluGlySer 130135140 GlyGlnAspLeuLeuIleProIleGlyLeuThrGluLeuValLysSer 145150155160 GluLeuIleAspLeuLeuValIlePheAspAspGluThrAsnAsnIle 165170175 ArgLeuProGlnAspPheProLeuIleLeuArgIleHisGlnArgGln 180185190 AspHisTrpGlnLeuSerValArgTyrProSerProLeuPheAspThr 195200205 MetValIleAspSerPheLeuSerAlaLeuHisAsnLeuLeuSerAla 210215220 ValThrLysProSerGlnLeuValArgAspIleGluLeuLeuProGlu 225230235240 TyrGlnValAlaGlnLeuGluLysTrpAsnAsnThrAspGlyAspTyr 245250255 ProThrGluLysArgLeuHisHisLeuPheGluGluAlaAlaValArg 260265270 ArgProGlnHisValAlaLeuIleCysGlyAspLysArgIleThrTyr 275280285 GluGluLeuAsnAlaMetAlaAsnArgLeuAlaHisHisLeuValSer 290295300 SerGlyIleGlnThrGluGlnLeuValGlyLeuPheLeuAspLysThr 305310315320 GluLeuMetIleAlaThrIleLeuGlyIleTrpLysSerGlyAlaAla 325330335 HisValProIleAspProGlyTyrProAspGluArgValLysPheVal 340345350 LeuAsnAspThrLysAlaGlnValValIleAlaSerGlnArgHisVal 355360365 AspArgLeuArgAlaGluAlaValGlyGlyGlnHisLeuArgIleIle 370375380 GlyLeuGluSerLeuPheAspAsnLeuAlaGlnGlnThrGlnHisSer 385390395400 ProGluThrSerGlyAsnLeuThrHisLeuProLeuAsnSerLysGln 405410415 LeuAlaTyrValThrTyrThrSerGlyThrThrGlyPheProLysGly 420425430 IleTyrLysGluHisThrSerValValAsnSerIleThrAspLeuSer 435440445 AlaArgTyrGlyValAlaGlyGluAspAspGluValIleLeuValPhe 450455460 SerAlaTyrValPheGluProPheValArgGlnMetLeuMetAlaLeu 465470475480 ThrThrGlyAsnSerLeuAlaIleIleSerAspGluAspLysPheAsp 485490495 ProAspThrLeuIleProPheIleGlnLysHisLysValThrTyrIle 500505510 HisAlaThrSerSerValLeuGlnGluTyrAspPheGlySerCysPro 515520525 SerLeuLysArgMetIleLeuValGlyGluAsnLeuThrGluProArg 530535540 TyrGluAlaLeuArgGlnArgPheLysSerArgIleLeuAsnGluTyr 545550555560 GlyPheThrGluSerAlaPheValThrAlaLeuAsnIlePheGluPro 565570575 ThrSerGlnArgLysAspMetSerLeuGlyArgProValArgAsnVal 580585590 LysCysTyrIleLeuAspAlaAsnLeuLysArgValProIleGlyVal 595600605 ThrGlyGluLeuHisIleGlyGlyLeuGlyIleSerArgGlyTyrMet 610615620 AsnArgGluGluLeuThrArgGlnLysPheLeuProAsnProTyrGln 625630635640 ThrAspLysGluArgGlnArgGlyValAsnSerThrMetTyrLysThr 645650655 GlyAspLeuAlaArgTrpLeuProSerGlyGluValGluTyrLeuGly 660665670 ArgAlaAspPheGlnIleLysLeuArgGlyIleArgIleGluProGly 675680685 GluIleGluSerThrLeuAlaMetTyrProGlyIleArgAlaSerIle 690695700 ValValSerLysLysLeuLeuSerGlnGlyGlnGluThrIleGlnAsp 705710715720 HisLeuValGlyTyrTyrValCysAspGluGlyHisIleProGluGly 725730735 AspLeuLeuSerPheLeuGluLysLysLeuProArgTyrMetValPro 740745750 ThrArgLeuValGlnLeuAlaGlnIleProThrAsnIleAsnGlyLys 755760765 AlaAspLeuArgAlaLeuProAlaValGluValAlaValAlaProThr 770775780 HisLysGlnAspGlyGluArgGlyAsnGlnLeuGluSerAspLeuAla 785790795800 AlaIleTrpGlyAsnIleLeuSerValProAlaGlnAspIleGlySer 805810815 GluSerAsnPhePheArgLeuGlyGlyHisSerIleAlaCysIleGln 820825830 LeuIleAlaArgValArgGlnGlnLeuGlyGlnGlyIleThrLeuGlu 835840845 GluValPheGlnThrLysThrLeuArgAlaMetAlaAlaLeuLeuSer 850855860 GluLysTyrThrLysAlaSerAsnGlyThrAsnGlyValThrAsnGly 865870875880 ThrAlaHisValAsnGlyHisAlaAlaAsnGlyHisValSerAspSer 885890895 TyrValAlaSerSerLeuGlnGlnGlyPheValTyrHisSerLeuLys 900905910 AsnGluLeuSerGluAlaTyrThrMetGlnSerMetIleHisTyrGly 915920925 ValProLeuLysArgAspIleTyrGlnAlaAlaTrpGlnArgValGln 930935940 GlyGluHisProAlaLeuArgLeuArgPheThrTrpGluAlaGluVal 945950955960 MetGlnIleValAspProLysSerGluLeuAspTrpArgValValAsp 965970975 TrpThrAspValSerSerArgGluLysGlnLeuValAlaLeuGluGln 980985990 LeuGlnThrGluAspLeuAlaLysValTyrHisLeuAspLysGlyPro 99510001005 LeuMetArgLeuTyrLeuIleLeuLeuProAspSerLysTyrSerCys 101010151020 LeuPheSerCysHisHisAlaIleLeuAspGlyTrpSerLeuProLeu 1025103010351040 LeuPheAsnAsnValHisGlnAlaTyrLeuAspLeuValGluGlyThr 104510501055 AlaSerProValGluGlnAspAlaThrTyrLeuLeuGlyGlnGlnTyr 106010651070 LeuGlnSerHisArgAspAspHisLeuAspPheTrpAlaGluGlnIle 107510801085 GlyArgIleGluGluArgCysAspMetAsnAlaLeuLeuAsnGluAla 109010951100 SerArgTyrLysValProLeuAlaAspTyrAspGlnValArgGluGln 1105111011151120 ArgGlnGlnThrIleSerLeuProTrpAsnAsnSerMetAspAlaGly 112511301135 ValArgGluGluLeuSerSerArgGlyIleThrLeuHisSerIleLeu 114011451150 GlnThrValTrpHisLeuValLeuHisSerTyrGlyGlyGlyThrHis 115511601165 ThrIleThrGlyThrThrIleSerGlyArgHisLeuProValProGly 117011751180 IleGluArgSerValGlyLeuPheIleAsnThrLeuProMetIlePhe 1185119011951200 AspHisThrValCysGlnAspMetThrAlaLeuGluAlaIleGluHis 120512101215 ValGlnGlyGlnValAsnAlaMetAsnSerArgGlyAsnValGluLeu 122012251230 GlyArgMetSerLysAsnAspLeuLysHisGlyLeuPheAspThrLeu 123512401245 PheValLeuGluAsnTyrProAsnLeuAspThrGluGlnArgGluLys 125012551260 HisGluGluLysLeuLysPheThrIleLysGlyGlyThrGluLysLeu 1265127012751280 SerTyrProLeuAlaValIleAlaGlnGluAspGlyAspSerGlyCys 128512901295 SerPheThrLeuCysTyrAlaGlyGluLeuPheThrAspGluSerIle 130013051310 GlnAlaLeuLeuAspThrValArgAspThrLeuSerAspIleLeuGly 131513201325 AsnIleHisAlaProIleArgAsnMetGluTyrLeuSerSerAsnGln 133013351340 ThrAlaGlnLeuAspLysTrpAsnAlaThrAlaPheGluTyrProAsn 1345135013551360 ThrThrLeuHisAlaMetPheGluSerGluAlaGlnGlnLysProAsp 136513701375 LysValAlaValValTyrGluAspIleArgLeuThrTyrArgGluLeu 138013851390 AsnSerArgAlaAsnAlaLeuAlaPheTyrLeuLeuSerGlnAlaAla 139514001405 IleGlnProAsnLysLeuValGlyLeuIleMetAspLysSerGluHis 141014151420 MetIleThrSerIleLeuAlaValTrpLysThrGlyGlyAlaTyrVal 1425143014351440 ProIleAspProArgTyrProAspGlnArgIleGlnTyrIleLeuGlu 144514501455 AspThrAlaAlaLeuAlaValIleThrAspSerProHisIleAspArg 146014651470 LeuArgSerIleThrAsnAsnArgLeuProValIleGlnSerAspPhe 147514801485 AlaLeuGlnLeuProProSerProValHisProValSerAsnCysLys 149014951500 ProSerAspLeuAlaTyrIleMetTyrThrSerGlyThrThrGlyAsn 1505151015151520 ProLysGlyValMetValGluHisHisGlyValValAsnLeuCysVal 152515301535 SerLeuCysArgLeuPheGlyLeuArgAsnThrAspAspGluValIle 154015451550 LeuSerPheSerAsnTyrValPheAspHisPheValGluGlnMetThr 155515601565 AspAlaLeuLeuAsnGlyGlnThrLeuValValLeuAsnAspGluMet 157015751580 ArgGlyAspLysGluArgLeuTyrArgTyrIleGluThrAsnArgVal 1585159015951600 ThrTyrLeuSerGlyThrProSerValIleSerMetTyrGluPheAsp 160516101615 ArgPheArgAspHisLeuArgArgValAspCysValGlyGluAlaPhe 162016251630 SerGluProValPheAspLysIleArgGluThrPheProGlyLeuIle 163516401645 IleAsnGlyTyrGlyProThrGluValSerIleThrThrHisLysArg 165016551660 ProTyrProPheProGluArgArgThrAspLysSerIleGlyCysGln 1665167016751680 LeuAspAsnSerThrSerTyrValLeuAsnAspAspMetLysArgVal 168516901695 ProIleGlyAlaValGlyGluLeuTyrLeuGlyGlyAspGlyValAla 170017051710 ArgGlyTyrHisAsnArgProAspLeuThrAlaAspArgPheProAla 171517201725 AsnProPheGlnThrGluGlnGluArgLeuGluGlyArgAsnAlaArg 173017351740 LeuTyrLysThrGlyAspLeuValArgTrpIleHisAsnAlaAsnGly 1745175017551760 AspGlyGluIleGluTyrLeuGlyArgAsnAspPheGlnValLysIle 176517701775 ArgGlyGlnArgIleGluLeuGlyGluIleGluAlaValLeuSerSer 178017851790 TyrProGlyIleLysGlnSerValValLeuAlaLysAspArgLysAsn 179518001805 AspGlyGlnLysTyrLeuValGlyTyrPheValSerSerAlaGlySer 181018151820 LeuSerAlaGlnAlaIleArgArgPheMetLeuThrSerLeuProAsp 1825183018351840 TyrMetValProAlaGlnLeuValProIleAlaLysPheProValThr 184518501855 ValSerGlyLysLeuAspAlaLysAlaLeuProValProAspAspThr 186018651870 ValGluAspAspIleValProProArgThrGluValGluArgIleLeu 187518801885 AlaGlyIleTrpSerGluLeuLeuGluIleProValAspArgIleSer 189018951900 IleTyrSerAspPhePheSerLeuGlyGlyAspSerLeuLysSerThr 1905191019151920 LysLeuSerPheAlaAlaThrArgAlaLeuGlyValAlaValSerVal 192519301935 ArgAsnLeuPheSerHisProThrIleGluAlaLeuSerGlnTrpIle 194019451950 IleArgGlySerAsnGluValLysAspValAlaValValLysGlyGly 195519601965 AlaSerLeuAspIleProLeuSerProAlaGlnGluArgLeuMetPhe 197019751980 IleHisGluPheGlyHisSerGlyGluAspThrGlyAlaTyrAsnVal 1985199019952000 ProLeuGlnLeuGlnLeuHisHisAspValCysLeuGluSerLeuGlu 200520102015 LysAlaLeuArgAspValValSerArgHisGluAlaLeuArgThrLeu 202020252030 IleThrArgThrGlnLysSerSerValHisCysGlnLysIleLeuAsp 203520402045 AlaGluGluAlaGlnLysLeuPheSerValAspValLeuArgLeuThr 205020552060 SerGluThrGluMetGlnGlyArgMetAlaGluSerThrAlaHisAla 2065207020752080 PheLysLeuAspGluGluLeuProIleHisValArgLeuTyrGlnVal 208520902095 ValArgAspGlyArgThrLeuSerPheAlaSerIleValCysHisHis 210021052110 LeuAlaPheAspAlaTrpSerTrpAspValPheGlnArgAspLeuAsp 211521202125 AlaPheTyrAlaValHisThrLysHisLysAlaAlaAlaAsnLeuPro 213021352140 ThrLeuArgValGlnTyrLysGluTyrAlaIleGluHisArgArgAla 2145215021552160 LeuArgAlaGluGlnHisArgValLeuAlaAspTyrTrpLeuArgLys 216521702175 LeuSerAspMetGluAlaSerTyrLeuValProAspArgProArgPro 218021852190 AlaGlnPheAspTyrThrGlyAsnAspLeuGlnPheSerThrThrPro 219522002205 GluThrThrAlaGlnLeuLysGluLeuAlaLysArgGluGlySerSer 221022152220 LeuTyrThrValValAlaAlaAlaTyrPheLeuLeuLeuTyrValTyr 2225223022352240 ThrAsnGlnArgAspIleThrIleGlyIleProValAlaHisArgAsn 224522502255 HisProAspPheGluSerValValGlyPhePheValAsnLeuLeuPro 226022652270 LeuArgValAsnValSerGlnSerAspIleHisGlyLeuIleGlnAla 227522802285 ValGlnLysGluLeuValAspAlaGlnIleHisGlnAspLeuProPhe 229022952300 GlnGluIleThrLysLeuLeuHisValGlnHisAspProSerArgHis 2305231023152320 ProLeuLeuGlnAlaValPheAsnTrpGluAsnValProAlaAsnVal 232523302335 HisGluGluGlnLeuLeuGlnGluTyrLysProProSerProLeuPro 234023452350 SerAlaAlaLysPheAspLeuAsnValThrValLysGluSerValAsn 235523602365 SerLeuAsnValAsnPheAsnTyrProThrSerLeuPheGluGluGlu 237023752380 ThrValGlnGlyPheMetGluThrPheHisLeuLeuLeuArgGlnLeu 2385239023952400 AlaHisAsnLysAlaSerThrSerLeuSerLysLeuSerValGluAsp 240524102415 GlyValLeuAsnProGluProThrAsnLeuGlnProSerSerArgAsp 242024252430 SerGlyAsnSerLeuHisGlyLeuPheGluAspIleValAlaSerThr 243524402445 ProAspArgIleAlaIleAlaAspGlyThrArgSerLeuSerTyrSer 245024552460 GluLeuAsnGluArgAlaAsnGlnLeuValHisLeuIleIleSerSer 2465247024752480 AlaSerIleValAlaAspAspArgIleAlaLeuLeuLeuAspLysSer 248524902495 IleAspMetValIleAlaLeuLeuAlaValTrpLysAlaGlyAlaAla 250025052510 TyrValProLeuAspProThrTyrProSerGlnArgThrGluLeuIle 251525202525 LeuGluGluSerSerAlaArgThrLeuIleThrThrArgLysHisThr 253025352540 ProArgGlyGlyThrValAlaAsnValProSerValValLeuAspSer 2545255025552560 ProGluThrLeuAlaCysLeuAsnGlnGlnSerLysGluAsnProThr 256525702575 ThrSerThrGlnLysProSerAspLeuAlaTyrValIlePheThrSer 258025852590 GlyThrThrGlyLysProLysGlyValLeuValGluHisGlnSerVal 259526002605 ValGlnLeuArgAsnSerLeuIleGluArgTyrPheGlyGluThrAsn 261026152620 GlySerHisAlaValLeuPheLeuSerAsnTyrValPheAspPheSer 2625263026352640 LeuGluGlnLeuCysLeuSerValLeuGlyGlyAsnLysLeuIleIle 264526502655 ProProGluGluGlyLeuThrHisGluAlaPheTyrAspIleGlyArg 266026652670 ArgGluLysLeuSerTyrLeuSerGlyThrProSerValLeuGlnGln 267526802685 IleGluLeuSerArgLeuProHisLeuHisMetValThrAlaAlaGly 269026952700 GluGluPheHisAlaSerGlnPheGluLysMetArgSerGlnPheAla 2705271027152720 GlyGlnIleAsnAsnAlaTyrGlyIleThrGluThrThrValTyrAsn 272527302735 IleIleThrThrPheLysGlyAspAlaProPheThrLysAlaLeuCys 274027452750 HisGlyIleProGlySerHisValTyrValLeuAsnAspArgLeuGln 275527602765 ArgValProPheAsnAlaValGlyGluLeuTyrLeuGlyGlyAspCys 277027752780 LeuAlaArgGlyTyrLeuAsnGlnAspAlaLeuThrAsnGluArgPhe 2785279027952800 IleProAsnProPheTyrGluProLysGlnAlaSerAspSerArgPro 280528102815 GlnArgLeuTyrLysThrGlyAspLeuValArgPheArgGlyProHis 282028252830 HisLeuGluTyrLeuGlyArgLysAspGlnGlnValLysLeuArgGly 283528402845 PheArgIleGluLeuSerGluValArgAspAlaValLeuAlaIleSer 285028552860 AlaValLysGluAlaAlaValIleProLysTyrAspGluAspGlySer 2865287028752880 AspSerArgArgValSerAlaIleValCysTyrTyrThrLeuAsnAla 288528902895 GlyThrValCysGluAlaSerSerIleArgAspHisLeuHisAlaAsn 290029052910 LeuProProTyrMetValProSerGlnIleHisGlnLeuGluGlySer 291529202925 LeuProValThrValAsnGlyLysLeuAspLeuAsnArgLeuSerThr 293029352940 ThrGlnValSerGlnProGluLeuTyrThrAlaProArgAsnSerThr 2945295029552960 GluGluThrLeuCysGlnLeuTrpAlaSerLeuLeuGlyValAspHis 296529702975 CysGlyIleAspAspAspLeuPheAlaArgGlyGlyAspSerIleSer 298029852990 SerLeuArgLeuValGlyAspIleTyrArgAlaLeuGlyArgLysVal 299530003005 ThrValLysAspIleTyrLeuHisArgSerValArgAlaLeuSerGlu 301030153020 AsnValLeuThrAspGlnLysAspLysGlyThrLeuProAlaSerPro 3025303030353040 ProLeuGlnArgAlaGluGlnGlyGlnValGluGlyAspAlaProLeu 304530503055 LeuProIleGlnAspTrpPheLeuSerLysProLeuAspAsnProAla 306030653070 TyrTrpAsnHisCysPheThrIleArgThrGlyAlaLeuSerValGlu 307530803085 GlyLeuArgGlyAlaLeuLysLeuLeuGlnGluArgHisAspValLeu 309030953100 ArgLeuArgLeuGlnArgArgAspGluGlyArgHisValGlnThrPhe 3105311031153120 AlaArgAspCysAlaGlnProArgLeuThrValLeuAspArgArgSer 312531303135 PheGluAspAlaGluAspValGlnGluAlaLeuCysGluIleGlnSer 314031453150 HisPheAspLeuGluAsnGlyProLeuTyrThrValAlaTyrIleHis 315531603165 GlyTyrGluAspGlySerAlaArgValTrpPheAlaCysHisHisVal 317031753180 MetValAspThrValSerTrpAsnIleIleLeuGlnAspLeuGlnAla 3185319031953200 LeuTyrHisGlyAspSerLeuGlyProLysSerSerSerValGlnGln 320532103215 TrpSerLeuAlaValSerAspTyrLysMetProLeuSerGluArgAla 322032253230 HisTrpAsnValLeuArgLysThrValAlaGlnSerPheGluThrLeu 323532403245 ProIleCysMetGlyGlyValLeuGlnCysGlnGluLysPheSerArg 325032553260 GluThrThrThrAlaLeuLeuSerLysAlaCysProAlaLeuAspSer 3265327032753280 GlyMetHisGluIleLeuLeuMetAlaValGlySerAlaLeuGlnLys 328532903295 AlaAlaGlyAspValProGlnValValThrIleGluGlyHisGlyArg 330033053310 GluAspThrIleAspAlaThrLeuAspValSerArgThrValGlyTrp 331533203325 PheThrSerMetTyrProPheGluIleProLysValThrAspProAla 333033353340 GlnGlyValValAspValLysGluAlaMetArgArgValProAsnArg 3345335033553360 GlyValGlyTyrGlyProAlaTyrGlyTyrGlyGlySerCysLeuPro 336533703375 AlaValSerPheAsnTyrLeuGlyArgLeuAspGlnAlaSerSerGly 338033853390 AlaGlnArgAspTrpThrLeuValMetAspGluAspGluTyrProVal 339534003405 GlyLeuCysThrSerAlaGluAspSerGlyArgSerSerSerMetVal 341034153420 AspPheThrPheSerIleSerGlyGlyGlnLeuValMetAspMetSer 3425343034353440 SerSerTrpGlyHisGlyAlaArgAsnGluPheValArgThrValArg 344534503455 AsnThrLeuAspAspLeuIleLysThrThrSerSerArgAspPheSer 346034653470 AlaProLeuProProSerAspGlnGluSerSerPheThrProTyrPhe 347534803485 ValPheGluGluGlyGluArgHisGlyAlaProLeuPheLeuLeuPro 349034953500 ProGlyGluGlyGlyAlaGluSerTyrPheHisAsnIleValLysGly 3505351035153520 LeuProAsnArgAsnLeuValValPheAsnAsnHisTyrArgGluGlu 352535303535 LysThrLeuArgThrIleGluAlaLeuAlaGluTyrTyrLeuSerHis 354035453550 IleArgSerIleGlnProGluGlyProTyrHisIleLeuGlyTrpSer 355535603565 PheGlyGlyIleLeuGlyLeuGluAlaAlaLysArgLeuThrGlyGlu 357035753580 GlyHisLysIleAlaThrLeuAlaLeuIleAspProTyrPheAspIle 3585359035953600 ProSerAlaSerLysAlaIleGlyGlnProAspAspAlaCysValLeu 360536103615 AspProIleTyrHisValTyrHisProSerProGluSerPheArgThr 362036253630 ValSerSerLeuThrAsnHisIleAlaLeuPheLysAlaThrGluThr 363536403645 AsnAspGlnHisGlyAsnAlaThrGlnGlnAlaLeuTyrGluTrpPhe 365036553660 AlaThrCysProLeuAsnAsnLeuAspLysPheLeuAlaAlaAspThr 3665367036753680 IleLysValValProLeuGluGlyThrHisPheThrTrpValHisHis 368536903695 ProGluGlnValArgSerMetCysThrMetLeuAspGluTrpLeuGly 370037053710 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11444 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: GTCGACAGTTGACAGAGCCAATGGCATCGGATCTGCCCTAGACCGTGCTAGACGAAAGTC60 TCCATCTTGTCTGCGGGCAGTTCTTCAGTCGCCCAGATTCTCGATGGAGATTGGCCAGGT120 CAGCCATATATACCCTGCAATGGCAGACCAATGCAGCAGGCCCAGTATAAGGAATTCCCC180 TCGAGCTTGTCTGTGATTGCGTTTTTTCTAACACTTGTTGTTGCATCCGATCCGTCGCTA240 CCAATTATTGGTCATTGACAGACATGACTCAACTGAAGCCACCGAACGGA290 MetThrGlnLeuLysProProAsnGly 15 ACCACGCCGATAGGCTTCTCGGCCACTACATCCCTGAACGCCAGTGGG338 ThrThrProIleGlyPheSerAlaThrThrSerLeuAsnAlaSerGly 10152025 AGCTCGAGTGTGAAAAATGGGACCATCAAACCCAGCAATGGCATCTTC386 SerSerSerValLysAsnGlyThrIleLysProSerAsnGlyIlePhe 303540 AAGCCCAGCACTAGGGACACCATGGACCCTTGCAGTGGGAATGCGGCC434 LysProSerThrArgAspThrMetAspProCysSerGlyAsnAlaAla 455055 GATGGCAGTATCCGCGTCCGTTTCCGTGGAGGAATCGAACGGTGGAAG482 AspGlySerIleArgValArgPheArgGlyGlyIleGluArgTrpLys 606570 GAGTGCGTCAACCAGGTCCCCGAGCGCTGCGACCTGAGTGGTCTGACA530 GluCysValAsnGlnValProGluArgCysAspLeuSerGlyLeuThr 758085 ACCGACTCCACGCGATATCAGCTCGCATCGACTGGGTTCGGTGACGCG578 ThrAspSerThrArgTyrGlnLeuAlaSerThrGlyPheGlyAspAla 9095100105 AGCGCTGCGTACCAGGAGCGCTTGATGACGGTCCCTGTTGACGTACAT626 SerAlaAlaTyrGlnGluArgLeuMetThrValProValAspValHis 110115120 GCCGCGCTCCAAGAGCTGTGCCTAGAACGCCGTGTGAGCGTGGGATCC674 AlaAlaLeuGlnGluLeuCysLeuGluArgArgValSerValGlySer 125130135 GTCATTAATTTCTCCGTGCACCAGATGCTGAAAGGGTTTGGAAATGGC722 ValIleAsnPheSerValHisGlnMetLeuLysGlyPheGlyAsnGly 140145150 ACACACACTATCACCGCCTCTCTGCACCGTGAGCAGAATTTGCAGAAT770 ThrHisThrIleThrAlaSerLeuHisArgGluGlnAsnLeuGlnAsn 155160165 TCTTCGCCATCCTGGGTAGTCTCCCCCACAATCGTCACCCATGAGAAC818 SerSerProSerTrpValValSerProThrIleValThrHisGluAsn 170175180185 AGAGACGGATGGTCCGTCGCGCAGGCGGTCGAGAGTATCGAAGCGGCG866 ArgAspGlyTrpSerValAlaGlnAlaValGluSerIleGluAlaAla 190195200 CGCGGTTCCGAGAAGGAGTCAGTGACTGCGATTGACTCCGCGTCAAGT914 ArgGlySerGluLysGluSerValThrAlaIleAspSerAlaSerSer 205210215 CTCGTGAAAATGGGGTTATTTGACTTACTCGTCAGCTTTGTCGATGCA962 LeuValLysMetGlyLeuPheAspLeuLeuValSerPheValAspAla 220225230 GACGATGCTCGTATTCCATGTTTCGACTTTCCCCTCGCAGTGATAGTG1010 AspAspAlaArgIleProCysPheAspPheProLeuAlaValIleVal 235240245 CGTGAGTGTGATGCCAACCTCTCGCTGACTCTGCGTTTCTCCGACTGT1058 ArgGluCysAspAlaAsnLeuSerLeuThrLeuArgPheSerAspCys 250255260265 CTCTTCAACGAGGAGACGATATGCAATTTTACCGATGCCCTAAACATC1106 LeuPheAsnGluGluThrIleCysAsnPheThrAspAlaLeuAsnIle 270275280 TTGCTCGCCGAAGCAGTGATAGGAAGAGTGACCCCGGTTGCCGATATC1154 LeuLeuAlaGluAlaValIleGlyArgValThrProValAlaAspIle 285290295 GAACTACTATCCGCGGAGCAGAAGCAGCAGCTGGAAGAGTGGAACAAC1202 GluLeuLeuSerAlaGluGlnLysGlnGlnLeuGluGluTrpAsnAsn 300305310 ACGGATGGCGAGTACCCTTCATCAAAGCGACTGCACCATCTCATTGAA1250 ThrAspGlyGluTyrProSerSerLysArgLeuHisHisLeuIleGlu 315320325 GAGGTGGTTGAACGGCATGAAGACAAAATAGCCGTTGTCTGCGACGAG1298 GluValValGluArgHisGluAspLysIleAlaValValCysAspGlu 330335340345 CGAGAGCTCACTTACGGCGAGCTCAATGCCCAAGGCAACAGCCTCGCA1346 ArgGluLeuThrTyrGlyGluLeuAsnAlaGlnGlyAsnSerLeuAla 350355360 CGCTATCTCCGTTCCATTGGTATCCTGCCCGAGCAGCTAGTCGCATTG1394 ArgTyrLeuArgSerIleGlyIleLeuProGluGlnLeuValAlaLeu 365370375 TTTCTAGATAAGAGCGAGAAGCTCATTGTTACCATCCTCGGCGTGTGG1442 PheLeuAspLysSerGluLysLeuIleValThrIleLeuGlyValTrp 380385390 AAATCCGGCGCCGCCTACGTGCCCATCGACCCGACTTATCCGGATGAG1490 LysSerGlyAlaAlaTyrValProIleAspProThrTyrProAspGlu 395400405 CGAGTGCGCTTCGTGCTGGATGACACCAAGGCACGGGCCATCATCGCC1538 ArgValArgPheValLeuAspAspThrLysAlaArgAlaIleIleAla 410415420425 AGTAATCAACATGTGGAGAGGCTCCAGCGAGAGGTCATCGGCGATAGA1586 SerAsnGlnHisValGluArgLeuGlnArgGluValIleGlyAspArg 430435440 AACCTATGCATTATCCGTCTGGAGCCCTTGTTGGCCTCCCTTGCTCAG1634 AsnLeuCysIleIleArgLeuGluProLeuLeuAlaSerLeuAlaGln 445450455 GATTCCTCAAAATTCCCCGCGCATAACTTGGACGACCTACCCCTCACA1682 AspSerSerLysPheProAlaHisAsnLeuAspAspLeuProLeuThr 460465470 AGCCAGCAGCTCGCCTATGTGACTTACACCTCTGGGACCACTGGTTTC1730 SerGlnGlnLeuAlaTyrValThrTyrThrSerGlyThrThrGlyPhe 475480485 CCAAAGGGCATATTTAAACAACACACCAATGTGGTGAACAGTATTACC1778 ProLysGlyIlePheLysGlnHisThrAsnValValAsnSerIleThr 490495500505 GACCTGTCTGCAAGGTACGGGGTGGCCGGGCAGCACCACGAAGCCATT1826 AspLeuSerAlaArgTyrGlyValAlaGlyGlnHisHisGluAlaIle 510515520 CTGCTTTTCTCGGCCTGCGTGTTCGAGCCGTTCGTTCGACAGACGCTC1874 LeuLeuPheSerAlaCysValPheGluProPheValArgGlnThrLeu 525530535 ATGGCACTCGTGAATGGCCATCTCCTCGCAGTTATCAATGACGTGGAA1922 MetAlaLeuValAsnGlyHisLeuLeuAlaValIleAsnAspValGlu 540545550 AAATATGATGCCGATACGCTCCTGCCGTTCATACGCAGACACAGCATC1970 LysTyrAspAlaAspThrLeuLeuProPheIleArgArgHisSerIle 555560565 ACCTACCTCAATGGTACTGCCTCTGTCTTGCAAGAGTACGACTTTTCC2018 ThrTyrLeuAsnGlyThrAlaSerValLeuGlnGluTyrAspPheSer 570575580585 GACTGCCCATCACTGAATCGGATAATCCTGGTGGGTGAGAACCTGACA2066 AspCysProSerLeuAsnArgIleIleLeuValGlyGluAsnLeuThr 590595600 GAAGCCCGGTATCTGGCGCTGCGCCAGCGGTTCAAGAATCGCATCCTC2114 GluAlaArgTyrLeuAlaLeuArgGlnArgPheLysAsnArgIleLeu 605610615 AACGAGTATGGTTTTACCGAGTCAGCCTTTGTAACGGCCCTCAAGATT2162 AsnGluTyrGlyPheThrGluSerAlaPheValThrAlaLeuLysIle 620625630 TTCGACCCGGAGTCGACCCGTAAGGACACGAGTCTGGGGAGACCGGTG2210 PheAspProGluSerThrArgLysAspThrSerLeuGlyArgProVal 635640645 CGCAACGTCAAGTGCTACATCCTCAATCCATCCCTTAAACGTGTCCCG2258 ArgAsnValLysCysTyrIleLeuAsnProSerLeuLysArgValPro 650655660665 ATTGGAGCTACGGGTGAGTTGCATATCGGAGGGTTGGGCATTTCCAAG2306 IleGlyAlaThrGlyGluLeuHisIleGlyGlyLeuGlyIleSerLys 670675680 GGATACCTCAACCGCCCCGAACTCACGCCGCACCGCTTCATTCCCAAC2354 GlyTyrLeuAsnArgProGluLeuThrProHisArgPheIleProAsn 685690695 CCCTTCCAAACGGATTGCGAGAAGCAGCTCGGGATCAACAGCTTGATG2402 ProPheGlnThrAspCysGluLysGlnLeuGlyIleAsnSerLeuMet 700705710 TACAAGACCGGTGACCTGGCCCGCTGGCTTCCGAACGGCGAGGTTGAG2450 TyrLysThrGlyAspLeuAlaArgTrpLeuProAsnGlyGluValGlu 715720725 TATCTCGGACGCGCAGATTTCCAGATCAAACTGCGAGGTATTCGAATT2498 TyrLeuGlyArgAlaAspPheGlnIleLysLeuArgGlyIleArgIle 730735740745 GAACCTGGTGAAATTGAGACGATGCTGGCTATGTACCCTAGGGTCCGG2546 GluProGlyGluIleGluThrMetLeuAlaMetTyrProArgValArg 750755760 ACCAGTTTAGTGGTGTCCAAAAAGCTCCGCAACGGTCCAGAGGAAACT2594 ThrSerLeuValValSerLysLysLeuArgAsnGlyProGluGluThr 765770775 ACCAACGAGCACCTCGTGGGTTATTATGTTTGTGATAGCGCCTCAGTG2642 ThrAsnGluHisLeuValGlyTyrTyrValCysAspSerAlaSerVal 780785790 TCCGAGGCAGACCTGCTGTCATTTTTAGAGAAGAAACTGCCTCGATAC2690 SerGluAlaAspLeuLeuSerPheLeuGluLysLysLeuProArgTyr 795800805 ATGATTCCCACGCGGTTGGTACAGCTGTCGCAGATCCCAGTGAATGTG2738 MetIleProThrArgLeuValGlnLeuSerGlnIleProValAsnVal 810815820825 AACGGGAAGGCGGACCTACGCGCCTTGCCGGCCGTCGATATCTCCAAT2786 AsnGlyLysAlaAspLeuArgAlaLeuProAlaValAspIleSerAsn 830835840 TCCACGGAGGTGCGTTCCGACCTTCGAGGCGATACGGAAATCGCCCTC2834 SerThrGluValArgSerAspLeuArgGlyAspThrGluIleAlaLeu 845850855 GGGGAAATCTGGGCCGACGTGTTGGGAGCCCGCCAGAGATCCGTCTCT2882 GlyGluIleTrpAlaAspValLeuGlyAlaArgGlnArgSerValSer 860865870 CGCAACGACAACTTCTTCCGCCTAGGAGGGCACAGCATCACCTGCATC2930 ArgAsnAspAsnPhePheArgLeuGlyGlyHisSerIleThrCysIle 875880885 CAACTGATCGCTCGCATCCGACAACGACAACGACTCTCGGTCAGCATC2978 GlnLeuIleAlaArgIleArgGlnArgGlnArgLeuSerValSerIle 890895900905 TCCGTCGAAGATGTTTTTGCAACAAGGACACTTGAGCGCATGGCAGAC3026 SerValGluAspValPheAlaThrArgThrLeuGluArgMetAlaAsp 910915920 CTTCTACAGAACAAGCAGCAGGAGAAATGCGACAAACCCCATGAGGCG3074 LeuLeuGlnAsnLysGlnGlnGluLysCysAspLysProHisGluAla 925930935 CCGACAGAGCTGCTTGAGGAGAATGCAGCAACGGACAATATCTATCTG3122 ProThrGluLeuLeuGluGluAsnAlaAlaThrAspAsnIleTyrLeu 940945950 GCAAACAGTCTTCAGCAGGGCTTCGTCTACCATTACCTCAAGAGCATG3170 AlaAsnSerLeuGlnGlnGlyPheValTyrHisTyrLeuLysSerMet 955960965 GAACAATCCGACGCCTATGTAATGCAGTCCGTTCTTCGGTACAACACC3218 GluGlnSerAspAlaTyrValMetGlnSerValLeuArgTyrAsnThr 970975980985 ACATTGTCTCCAGATCTGTTTCAGAGAGCCTGGAAGCATGCACAGCAG3266 ThrLeuSerProAspLeuPheGlnArgAlaTrpLysHisAlaGlnGln 9909951000 TCCTTTCCAGCGCTGCGGCTGCGGTTCTCATGGGAAAAGGAGGTTTTC3314 SerPheProAlaLeuArgLeuArgPheSerTrpGluLysGluValPhe 100510101015 CAACTGCTCGATCAGGATCCACCATTGGACTGGCGTTTCCTCTACTTC3362 GlnLeuLeuAspGlnAspProProLeuAspTrpArgPheLeuTyrPhe 102010251030 ACCGACGTTGCCGCGGGTGCTGTCGAGGACCGGAAATTGGAAGACTTG3410 ThrAspValAlaAlaGlyAlaValGluAspArgLysLeuGluAspLeu 103510401045 CGGCGCCAAGACCTTACGGAGAGATTCAAGCTGGATGTTGGCAGACTG3458 ArgArgGlnAspLeuThrGluArgPheLysLeuAspValGlyArgLeu 1050105510601065 TTCCGCGTCTATCTGATTAAACACAGCGAGAATCGCTTCACGTGTCTT3506 PheArgValTyrLeuIleLysHisSerGluAsnArgPheThrCysLeu 107010751080 TTCAGCTGCCATCATGCAATCCTCGATGGTTGGAGTCTGCCACTCTTG3554 PheSerCysHisHisAlaIleLeuAspGlyTrpSerLeuProLeuLeu 108510901095 TTCGAAAAGGTTCACGAGACCTACCTGCAACTGCTGCATGGGGACAAT3602 PheGluLysValHisGluThrTyrLeuGlnLeuLeuHisGlyAspAsn 110011051110 CTCACTTCGTCCATGGATGACCCTTACACTCGCACCCAGCGGTATCTC3650 LeuThrSerSerMetAspAspProTyrThrArgThrGlnArgTyrLeu 111511201125 CACGCTCACCGTGAGGATCACCTCGACTTTTGGGCCGGTGTGGTTCAA3698 HisAlaHisArgGluAspHisLeuAspPheTrpAlaGlyValValGln 1130113511401145 AAGATCAACGAACGGTGTGATATGAACGCCTTGTTGAACGAGCGCAGT3746 LysIleAsnGluArgCysAspMetAsnAlaLeuLeuAsnGluArgSer 115011551160 CGTTACAAAGTCCAGCTGGCAGACTATGACCAGGTGCAGGAGCAGCGA3794 ArgTyrLysValGlnLeuAlaAspTyrAspGlnValGlnGluGlnArg 116511701175 CACGTGACAATTGCTCTCTCTGGAGACGCATGGCTAGCAGACCTTCGT3842 HisValThrIleAlaLeuSerGlyAspAlaTrpLeuAlaAspLeuArg 118011851190 CAGACCTGCTCCGCCCAGGGTATTACCTTACATTCGATTCTCCAATTT3890 GlnThrCysSerAlaGlnGlyIleThrLeuHisSerIleLeuGlnPhe 119512001205 GTTTGGCACGCCGTGCTGCACGCTTATGGCGGTGGCACCCACACCATA3938 ValTrpHisAlaValLeuHisAlaTyrGlyGlyGlyThrHisThrIle 1210121512201225 ACCGGCACGACCATTTCTGGAAGGAACCTGCCCATCTTGGGAATTGAA3986 ThrGlyThrThrIleSerGlyArgAsnLeuProIleLeuGlyIleGlu 123012351240 CGAGCAGTTGGTCCGTATATCAACACTCTACCGCTGGTACTCGATCAT4034 ArgAlaValGlyProTyrIleAsnThrLeuProLeuValLeuAspHis 124512501255 TCGACGTTCAAGGATAAGACAATCATGGAGGCCATCGAGGATGTGCAG4082 SerThrPheLysAspLysThrIleMetGluAlaIleGluAspValGln 126012651270 GCCAAGGTAAACGTCATGAACAGCCGGGGCAATGTGGAACTGGGCCGT4130 AlaLysValAsnValMetAsnSerArgGlyAsnValGluLeuGlyArg 127512801285 TTGCACAAAACCGACTTAAAGCACGGATTATTCGATTCTTTATTCGTG4178 LeuHisLysThrAspLeuLysHisGlyLeuPheAspSerLeuPheVal 1290129513001305 CTTGAAAACTACCCGAATTTGGACAAATCGCGAACACTTGAGCACCAG4226 LeuGluAsnTyrProAsnLeuAspLysSerArgThrLeuGluHisGln 131013151320 ACTGAACTGGGGTATTCGATTGAAGGCGGCACTGAGAAGCTGAATTAT4274 ThrGluLeuGlyTyrSerIleGluGlyGlyThrGluLysLeuAsnTyr 132513301335 CCACTGGCTGTCATCGCGCGCGAAGTCGAGACGACTGGCGGATTCACA4322 ProLeuAlaValIleAlaArgGluValGluThrThrGlyGlyPheThr 134013451350 GTATCCATCTGCTACGCCAGTGAGCTATTTGAGGAGGTTATGATCTCC4370 ValSerIleCysTyrAlaSerGluLeuPheGluGluValMetIleSer 135513601365 GAGCTTCTTCATATGGTCCAGGACACACTGATGCAGGTTGCCCGAGGT4418 GluLeuLeuHisMetValGlnAspThrLeuMetGlnValAlaArgGly 1370137513801385 TTGAATGAACCCGTCGGCAGCCTGGAGTATCTCTCATCTATCCAATTG4466 LeuAsnGluProValGlySerLeuGluTyrLeuSerSerIleGlnLeu 139013951400 GAGCAACTCGCCGCGTGGAATGCCACGGAAGCTGAGTTTCCCGATACC4514 GluGlnLeuAlaAlaTrpAsnAlaThrGluAlaGluPheProAspThr 140514101415 ACGCTTCATGAGATGTTTGAAAACGAAGCGAGCCAGAAGCCGGACAAG4562 ThrLeuHisGluMetPheGluAsnGluAlaSerGlnLysProAspLys 142014251430 ATAGCAGTGGTCTATGAGGAGACGTCCTTGACTTACCGCGAGTTGAAT4610 IleAlaValValTyrGluGluThrSerLeuThrTyrArgGluLeuAsn 143514401445 GAGCGGGCGAACCGTATGGCACATCAGCTAAGGTCCGACGTCAGCCCC4658 GluArgAlaAsnArgMetAlaHisGlnLeuArgSerAspValSerPro 1450145514601465 AACCCCAACGAGGTCATTGCGCTGGTGATGGACAAGAGCGAGCATATG4706 AsnProAsnGluValIleAlaLeuValMetAspLysSerGluHisMet 147014751480 ATCGTCAACATTCTGGCCGTATGGAAGAGCGGCGGTGCCTATGTCCCC4754 IleValAsnIleLeuAlaValTrpLysSerGlyGlyAlaTyrValPro 148514901495 ATTGACCCTGGATATCCTAACGACCGCATTCAATATATCCTAGAGGAC4802 IleAspProGlyTyrProAsnAspArgIleGlnTyrIleLeuGluAsp 150015051510 ACACAAGCCCTCGCAGTCATCGCGGACTCCTGCTATCTGCCTCGCATC4850 ThrGlnAlaLeuAlaValIleAlaAspSerCysTyrLeuProArgIle 151515201525 AAGGGAATGGCTGCCTCCGGCACGCTTCTTTATCCCTCTGTCTTGCCT4898 LysGlyMetAlaAlaSerGlyThrLeuLeuTyrProSerValLeuPro 1530153515401545 GCCAATCCGGATTCCAAGTGGAGCGTATCGAACCCTTCACCGTTGAGT4946 AlaAsnProAspSerLysTrpSerValSerAsnProSerProLeuSer 155015551560 CGGAGCACGGACTTAGCTTATATCATCTATACCTCTGGAACGACAGGT4994 ArgSerThrAspLeuAlaTyrIleIleTyrThrSerGlyThrThrGly 156515701575 CGGCCCAAGGGCGTCACGGTAGAGCATCATGGAGTGGTCAACCTGCAG5042 ArgProLysGlyValThrValGluHisHisGlyValValAsnLeuGln 158015851590 GTGTCGCTATCCAAAGTATTCGGACTACGGGATACGGACGACGAGGTA5090 ValSerLeuSerLysValPheGlyLeuArgAspThrAspAspGluVal 159516001605 ATTCTCTCCTTTTCCAACTATGTGTTCGACCATTTCGTGGAGCAGATG5138 IleLeuSerPheSerAsnTyrValPheAspHisPheValGluGlnMet 1610161516201625 ACCGACGCCATTCTCAATGGCCAAACCCTCCTGGTCCTCAACGATGGA5186 ThrAspAlaIleLeuAsnGlyGlnThrLeuLeuValLeuAsnAspGly 163016351640 ATGCGCGGGGACAAAGAGCGACTCTACAGATACATTGAGAAGAACCGA5234 MetArgGlyAspLysGluArgLeuTyrArgTyrIleGluLysAsnArg 164516501655 GTGACCTACTTGTCTGGCACCCCATCCGTGGTCTCCATGTACGAATTT5282 ValThrTyrLeuSerGlyThrProSerValValSerMetTyrGluPhe 166016651670 AGCCGGTTCAAGGACCATCTACGCCGTGTGGACTGCGTGGGGGAGGCG5330 SerArgPheLysAspHisLeuArgArgValAspCysValGlyGluAla 167516801685 TTCAGCGAACCGGTCTTCGACAAGATCCGCGAAACGTTCCATGGCCTC5378 PheSerGluProValPheAspLysIleArgGluThrPheHisGlyLeu 1690169517001705 GTTATCAACGGCTACGGCCCAACTGAAGTTTCCATCACCACCCACAAG5426 ValIleAsnGlyTyrGlyProThrGluValSerIleThrThrHisLys 171017151720 CGGCTCTATCCATTCCCAGAGCGGCGAATGGACAAAAGTATTGGCCAA5474 ArgLeuTyrProPheProGluArgArgMetAspLysSerIleGlyGln 172517301735 CAGGTCCACAATAGCACGAGCTATGTGCTGAACGAGGACATGAAGCGC5522 GlnValHisAsnSerThrSerTyrValLeuAsnGluAspMetLysArg 174017451750 ACCCCCATAGGGGCTGTCGGCGAGCTCTACCTGGGTGGTGAAGGAGTG5570 ThrProIleGlyAlaValGlyGluLeuTyrLeuGlyGlyGluGlyVal 175517601765 GTACGGGGATATCACAATCGCGCAGATGTGACCGCGGAGCGTTTTATT5618 ValArgGlyTyrHisAsnArgAlaAspValThrAlaGluArgPheIle 1770177517801785 CCTAATCCATTCCAGTCGGAAGAAGATAAGCGAGAAGGTCGTAACTCC5666 ProAsnProPheGlnSerGluGluAspLysArgGluGlyArgAsnSer 179017951800 CGTTTGTACAAGACCGGTGACCTGGTACGCTGGATTCCTGGAAGCAGC5714 ArgLeuTyrLysThrGlyAspLeuValArgTrpIleProGlySerSer 180518101815 GGGGAGGTCGAGTATCTAGGTCGTAATGACTTCCAGGTCAAGATTCGC5762 GlyGluValGluTyrLeuGlyArgAsnAspPheGlnValLysIleArg 182018251830 GGACTGCGCATCGAAGTAGGCGAGATTGAGGCCATCCTATCGTCTTAT5810 GlyLeuArgIleGluValGlyGluIleGluAlaIleLeuSerSerTyr 183518401845 CACGGAATCAAACAGTCTGTGGTGATTGCCAAGGATTGCAGAGAAGGG5858 HisGlyIleLysGlnSerValValIleAlaLysAspCysArgGluGly 1850185518601865 GCCCAGAAATTCCTGGTTGGTTACTATGTCGCCGATGCAGCGCTGCCG5906 AlaGlnLysPheLeuValGlyTyrTyrValAlaAspAlaAlaLeuPro 187018751880 TCCGCTGCCATTCGGCGCTTCATGCAGTCTCGGCTCCCTGGCTACATG5954 SerAlaAlaIleArgArgPheMetGlnSerArgLeuProGlyTyrMet 188518901895 GTGCCCTCTCGTCTCATTCTCGTCAGCAAGTTCCCCGTCACTCCTAGT6002 ValProSerArgLeuIleLeuValSerLysPheProValThrProSer 190019051910 GGAAAATTAGACACCAAGGCTTTGCCCCCAGCCGAGGAAGAGAGCGAG6050 GlyLysLeuAspThrLysAlaLeuProProAlaGluGluGluSerGlu 191519201925 ATTGACGTGGTGCCGCCGCGTAGTGAAATCGAACGCTCCTTGTGTGAC6098 IleAspValValProProArgSerGluIleGluArgSerLeuCysAsp 1930193519401945 ATCTGGGCGGAACTACTCGAGATGCACCCAGAGGAGATCGGCATTTAC6146 IleTrpAlaGluLeuLeuGluMetHisProGluGluIleGlyIleTyr 195019551960 AGCGATTTCTTCAGCCTGGGAGGTGACAGCCTAAAGAGCACAAAGCTT6194 SerAspPhePheSerLeuGlyGlyAspSerLeuLysSerThrLysLeu 196519701975 TCCTTCATGATTCACGAGTCCTTTAACCGCGCCGTCTCAGTCAGCGCC6242 SerPheMetIleHisGluSerPheAsnArgAlaValSerValSerAla 198019851990 CTTTTCTGTCACCGGACAGTTGAAGCCCAGACGCACTTGATCCTGAAC6290 LeuPheCysHisArgThrValGluAlaGlnThrHisLeuIleLeuAsn 199520002005 GATGCTGCAGATGTGCACGAAATTACTCCCATAGATTGCAATGATACG6338 AspAlaAlaAspValHisGluIleThrProIleAspCysAsnAspThr 2010201520202025 CAGATGATTCCCGTGTCCCGTGCCCAGGAGCGACTCCTCTTCATCCAC6386 GlnMetIleProValSerArgAlaGlnGluArgLeuLeuPheIleHis 203020352040 GAATTTGAGAATGGCAGCAATGCATACAATATCGACGCTGCATTTGAA6434 GluPheGluAsnGlySerAsnAlaTyrAsnIleAspAlaAlaPheGlu 204520502055 CTGCCTGGCTCGGTTGACGCGTCGCTTCTCGAGCAGGCGCTGCGTGGA6482 LeuProGlySerValAspAlaSerLeuLeuGluGlnAlaLeuArgGly 206020652070 AACCTTGCTCGACATGAGGCGTTGAGAACTTTACTGGTCAAGGATCAC6530 AsnLeuAlaArgHisGluAlaLeuArgThrLeuLeuValLysAspHis 207520802085 GCAACCGGCATCTATCTTCAGAAGGTATTGAGTCCCGATGAAGCCCAG6578 AlaThrGlyIleTyrLeuGlnLysValLeuSerProAspGluAlaGln 2090209521002105 GGCATGTTCTCCGTCAACGTGGACACAGCCAAGCAGGTGGAGCGGCTG6626 GlyMetPheSerValAsnValAspThrAlaLysGlnValGluArgLeu 211021152120 GACCAGGAGATAGCCAGTCTATCCCAGCATGTTTTCCGCCTCGATGAT6674 AspGlnGluIleAlaSerLeuSerGlnHisValPheArgLeuAspAsp 212521302135 GAACTGCCTTGGGAGGCCCGCATCCTTAAACTCGAATCCGGCGGCCTG6722 GluLeuProTrpGluAlaArgIleLeuLysLeuGluSerGlyGlyLeu 214021452150 TATCTCATTCTGGCGTTCCACCATACCTGCTTCGATGCATGGTCATTG6770 TyrLeuIleLeuAlaPheHisHisThrCysPheAspAlaTrpSerLeu 215521602165 AAAGTCTTCGAGCAAGAGCTTCGGGCCTTGTACGCAGCGCTCCAGAAA6818 LysValPheGluGlnGluLeuArgAlaLeuTyrAlaAlaLeuGlnLys 2170217521802185 ACCAAAAGTGCAGCGAACTTACCAGCCCTCAAAGCGCAGTACAAGGAA6866 ThrLysSerAlaAlaAsnLeuProAlaLeuLysAlaGlnTyrLysGlu 219021952200 TACGCGCTCTACCATCGCCGGCAGCTGTCTGGCGATCGCATGCGCAAC6914 TyrAlaLeuTyrHisArgArgGlnLeuSerGlyAspArgMetArgAsn 220522102215 CTGTCAGACTTTTGGCTGCGGAAACTCATTGGCTTGGAACCATTGCAG6962 LeuSerAspPheTrpLeuArgLysLeuIleGlyLeuGluProLeuGln 222022252230 CTGATCACGGACCGCCCACGTCCTGTGCAATTCAAATACGACGGTGAC7010 LeuIleThrAspArgProArgProValGlnPheLysTyrAspGlyAsp 223522402245 GACCTCAGTATCGAACTGAGCAAGAAGGAAACGGAGAACCTGAGGGGG7058 AspLeuSerIleGluLeuSerLysLysGluThrGluAsnLeuArgGly 2250225522602265 GTGGCCAAACGTTGCAAGTCGAGTCTGTACGTCGTGTTGGTTTCCGTT7106 ValAlaLysArgCysLysSerSerLeuTyrValValLeuValSerVal 227022752280 TATTGCGTTATGCTAGCCTCGTACGCGAACCAGTCCGATGTTTCCGTG7154 TyrCysValMetLeuAlaSerTyrAlaAsnGlnSerAspValSerVal 228522902295 GGTATCCCAGTCAGCCACCGAACGCATCCTCAGTTCCAATCGGTCATT7202 GlyIleProValSerHisArgThrHisProGlnPheGlnSerValIle 230023052310 GGATTCTTCGTCAACCTTGTGGTGCTAAGGGTGGATATTTCTCAGTCA7250 GlyPhePheValAsnLeuValValLeuArgValAspIleSerGlnSer 231523202325 GCCATTTGCGGGCTCATCAGAAGGGTAATGAAAGAGCTCGTGGACGCC7298 AlaIleCysGlyLeuIleArgArgValMetLysGluLeuValAspAla 2330233523402345 CAACTGCACCAAGACATGCCGTTCCAGGAAGTGACGAAGCTGCTGCAG7346 GlnLeuHisGlnAspMetProPheGlnGluValThrLysLeuLeuGln 235023552360 GTGGATAATGACCCCAGCCGGCATCCGCTGGTACAGAACGTGTTCAAC7394 ValAspAsnAspProSerArgHisProLeuValGlnAsnValPheAsn 236523702375 TTCGAATCCCGTGCGAACGGAGAACACGATGCCAGGTCGGAGGATGAA7442 PheGluSerArgAlaAsnGlyGluHisAspAlaArgSerGluAspGlu 238023852390 GGATCGCTTGCATTCAATCAATACCGGCCGGTTCAGCCCGTGGATTCC7490 GlySerLeuAlaPheAsnGlnTyrArgProValGlnProValAspSer 239524002405 GTTGCGAAGTTCGATCTGAACGCAACGGTCACGGAATTGGAGTCGGGA7538 ValAlaLysPheAspLeuAsnAlaThrValThrGluLeuGluSerGly 2410241524202425 TTGAGAGTCAACTTCAACTATGCGACCAGCCTATTCAACAAAAGCACG7586 LeuArgValAsnPheAsnTyrAlaThrSerLeuPheAsnLysSerThr 243024352440 ATCCAGGGTTTTTTGCATACCTATGAGTATCTCCTGCGCCAGCTGTCC7634 IleGlnGlyPheLeuHisThrTyrGluTyrLeuLeuArgGlnLeuSer 244524502455 GAACTGAGTGCAGAAGGGATCAATGAGGATACGCAGCTGTCGTTAGTT7682 GluLeuSerAlaGluGlyIleAsnGluAspThrGlnLeuSerLeuVal 246024652470 CGCCCGACAGAGAATGGCGATCTGCACTTGCCATTGGCACAGTCCCCG7730 ArgProThrGluAsnGlyAspLeuHisLeuProLeuAlaGlnSerPro 247524802485 CTTGCGACGACTGCTGAGGAGCAGAAAGTAGCGTCGTTGAACCAGGCC7778 LeuAlaThrThrAlaGluGluGlnLysValAlaSerLeuAsnGlnAla 2490249525002505 TTTGAGCGCGAAGCTTTCCTTGCCGCAGAGAAGATTGCCGTCGTGCAG7826 PheGluArgGluAlaPheLeuAlaAlaGluLysIleAlaValValGln 251025152520 GGAGATAGAGCACTTAGTTATGCTGATCTTAACGGGCAGGCTAACCAG7874 GlyAspArgAlaLeuSerTyrAlaAspLeuAsnGlyGlnAlaAsnGln 252525302535 CTCGCCCGGTACATACAGTCCGTGTCCTGTATTGGGGCAGACGACGGA7922 LeuAlaArgTyrIleGlnSerValSerCysIleGlyAlaAspAspGly 254025452550 ATAGCTTTGATGCTGGAAAAGAGTATCGACACGATTATTTGCATTCTC7970 IleAlaLeuMetLeuGluLysSerIleAspThrIleIleCysIleLeu 255525602565 GCGATTTGGAAGGCTGGTGCAGCATACGTGCCCTTGGATCCGACTTAC8018 AlaIleTrpLysAlaGlyAlaAlaTyrValProLeuAspProThrTyr 2570257525802585 CCACCCGGACGCGTCCAGCTGATTCTGGAGGAGATTAAAGCGAAGGCT8066 ProProGlyArgValGlnLeuIleLeuGluGluIleLysAlaLysAla 259025952600 GTCCTTGTGCACTCCAGTCATGCTTCGAAATGTGAACGCCATGGCGCG8114 ValLeuValHisSerSerHisAlaSerLysCysGluArgHisGlyAla 260526102615 AAGGTGATTGCAGTCGACTCGCCCGCCATCGAGACGGCGGTCAGCCAA8162 LysValIleAlaValAspSerProAlaIleGluThrAlaValSerGln 262026252630 CAGTCAGCTGCTGACCTGCCCACAATTGCTAGCCTCGGCAATCTAGCG8210 GlnSerAlaAlaAspLeuProThrIleAlaSerLeuGlyAsnLeuAla 263526402645 TATATAATCTTTACTTCAGGCACTTCCGGTAAGCCAAAGGGAGTCCTA8258 TyrIleIlePheThrSerGlyThrSerGlyLysProLysGlyValLeu 2650265526602665 GTTGAGCAAAAGGCAGTTCTTCTTCTACGCGATGCCCTCCGGGAGCGG8306 ValGluGlnLysAlaValLeuLeuLeuArgAspAlaLeuArgGluArg 267026752680 TATTTCGGTCGAGACTGTACCAAGCATCATGGCGTCCTGTTCCTGTCC8354 TyrPheGlyArgAspCysThrLysHisHisGlyValLeuPheLeuSer 268526902695 AACTACGTCTTCGACTTCTCCGTCGAACAACTTGTGTTGTCGGTGCTC8402 AsnTyrValPheAspPheSerValGluGlnLeuValLeuSerValLeu 270027052710 AGCGGACACAAGCTGATCGTTCCCCCAGCTGAGTTCGTCGCAGATGAT8450 SerGlyHisLysLeuIleValProProAlaGluPheValAlaAspAsp 271527202725 GAATTTTACAGAATGGCCAGCACGCACGGTCTCTCCTATCTCAGCGGC8498 GluPheTyrArgMetAlaSerThrHisGlyLeuSerTyrLeuSerGly 2730273527402745 ACACCATCCTTACTGCAGAAGATCGATCTGGCACGACTGGACCATCTG8546 ThrProSerLeuLeuGlnLysIleAspLeuAlaArgLeuAspHisLeu 275027552760 CAGGTTGTTACCGCCGCGGGCGAAGAGCTTCACGCCACCCAGTACGAG8594 GlnValValThrAlaAlaGlyGluGluLeuHisAlaThrGlnTyrGlu 276527702775 AAGATGCGCCGCCGATTCAACGGTCCCATCTACAATGCCTATGGTGTC8642 LysMetArgArgArgPheAsnGlyProIleTyrAsnAlaTyrGlyVal 278027852790 ACCGAGACCACGGTGTACAACATTATCGCGGAATTCACAACGAATTCG8690 ThrGluThrThrValTyrAsnIleIleAlaGluPheThrThrAsnSer 279528002805 ATATTTGAGAATGCTCTTCGGGAAGTGCTCCCTGGTACCCGAGCGTAT8738 IlePheGluAsnAlaLeuArgGluValLeuProGlyThrArgAlaTyr 2810281528202825 GTGCTGACCGCGGCACTTCAGCCCGTCCCCTTCGATGCTGTCGGAGAA8786 ValLeuThrAlaAlaLeuGlnProValProPheAspAlaValGlyGlu 283028352840 CTCTATCTTGCCGGCGACACGGTTACGCGTGGTTATCTCAACCAACCT8834 LeuTyrLeuAlaGlyAspThrValThrArgGlyTyrLeuAsnGlnPro 284528502855 CTTCTAACGGATCAGCGATTCATTCCCAACCCTTTCTGCAAAGAGGAG8882 LeuLeuThrAspGlnArgPheIleProAsnProPheCysLysGluGlu 286028652870 GACATCGCTATGGGGCGCTTCGCGCGGCTCTACAAGACCGGCGACCTG8930 AspIleAlaMetGlyArgPheAlaArgLeuTyrLysThrGlyAspLeu 287528802885 GTTCGATCGCGTTTCAACCGTCAGCAGCAGCCGCAGCTGGAATACCTA8978 ValArgSerArgPheAsnArgGlnGlnGlnProGlnLeuGluTyrLeu 2890289529002905 GGAAGAGGCGATCTGCAGATCAAGATGAGGGGATACCGGATCGAGATT9026 GlyArgGlyAspLeuGlnIleLysMetArgGlyTyrArgIleGluIle 291029152920 TCTGAAGTTCAGAACGTGCTCACTTCAAGTCCCGGTGTCCGGGAGGGT9074 SerGluValGlnAsnValLeuThrSerSerProGlyValArgGluGly 292529302935 GCAGTCGTTGCCAAGTATGAGAACAACGATACCTATTCCCGGACCGCT9122 AlaValValAlaLysTyrGluAsnAsnAspThrTyrSerArgThrAla 294029452950 CACTCTCTGGTCGGTTACTATACCACGGACAATGAAACAGTATCGGAA9170 HisSerLeuValGlyTyrTyrThrThrAspAsnGluThrValSerGlu 295529602965 GCCGATATTCTCACTTTCATGAAAGCAAGGCTTCCAACGTACATGGTG9218 AlaAspIleLeuThrPheMetLysAlaArgLeuProThrTyrMetVal 2970297529802985 CCAAGCCACCTCTGCTGTCTGGAAGGCGCACTGCCTGTGACGATTAAC9266 ProSerHisLeuCysCysLeuGluGlyAlaLeuProValThrIleAsn 299029953000 GGAAAGCTCGACGTCCGGAGATTGCCGGAGATTATCAACGACTCCGCG9314 GlyLysLeuAspValArgArgLeuProGluIleIleAsnAspSerAla 300530103015 CAGTCCTCGTACAGCCCACCAAGGAACATAATCGAGGCCAAGATGTGC9362 GlnSerSerTyrSerProProArgAsnIleIleGluAlaLysMetCys 302030253030 AGACTGTGGGAATCCGCCTTGGGAATGGAGCGATGCGGTATCGACGAC9410 ArgLeuTrpGluSerAlaLeuGlyMetGluArgCysGlyIleAspAsp 303530403045 GACCTGTTCAAACTGGGTGGCGACAGCATCACATCTTTGCATCTCGTG9458 AspLeuPheLysLeuGlyGlyAspSerIleThrSerLeuHisLeuVal 3050305530603065 GCCCAGATTCACAACCAGGTGGGCTGCAAGATCACCGTTCGGGATATA9506 AlaGlnIleHisAsnGlnValGlyCysLysIleThrValArgAspIle 307030753080 TTTGAACATCGTACCGCCCGAGCCCTCCATGATCACGTCTTCATGAAG9554 PheGluHisArgThrAlaArgAlaLeuHisAspHisValPheMetLys 308530903095 GACTCCGACCGGAGTAATGTGACTCAGTTCCGAACCGAACAAGGGCCG9602 AspSerAspArgSerAsnValThrGlnPheArgThrGluGlnGlyPro 310031053110 GTCATCGGCGAGGCGCCCCTACTGCCGATTCAAGACTGGTTTTTGTCA9650 ValIleGlyGluAlaProLeuLeuProIleGlnAspTrpPheLeuSer 311531203125 AAGGCTCTGCAGCATCCGATGTATTGGAATCACACTTTCTACGTCCGA9698 LysAlaLeuGlnHisProMetTyrTrpAsnHisThrPheTyrValArg 3130313531403145 ACGCCAGAGCTGGATGTTGATTCCTTAAGCGCTGCTGTCAGGGACTTG9746 ThrProGluLeuAspValAspSerLeuSerAlaAlaValArgAspLeu 315031553160 CAACAGTATCACGATGTTTTCCGCATGCGACTCAAGCGCGAGGAAGTC9794 GlnGlnTyrHisAspValPheArgMetArgLeuLysArgGluGluVal 316531703175 GGATTCGTGCAGTCCTTTGCTGAGGACTTCTCTCCTGCCCAGCTTCGG9842 GlyPheValGlnSerPheAlaGluAspPheSerProAlaGlnLeuArg 318031853190 GTGCTGAACGTAAAAGATGTTGACGGGTCCGCGGCCGTCAACGAGATA9890 ValLeuAsnValLysAspValAspGlySerAlaAlaValAsnGluIle 319532003205 TTGGATGGGTGGCAGTCTGGCTTCAACCTTGAGAACGGACCCATTGGT9938 LeuAspGlyTrpGlnSerGlyPheAsnLeuGluAsnGlyProIleGly 3210321532203225 TCCATTGGCTACCTACATGGGTATGAAGACCGATCCGCGCGAGTCTGG9986 SerIleGlyTyrLeuHisGlyTyrGluAspArgSerAlaArgValTrp 323032353240 TTCTCCGTTCACCATATGGCCATTGACACCGTCAGCTGGCAGATCCTT10034 PheSerValHisHisMetAlaIleAspThrValSerTrpGlnIleLeu 324532503255 GTCCGTGACCTGCAGACGCTGTACCGAAATGGAAGCCTCGGAAGCAAG10082 ValArgAspLeuGlnThrLeuTyrArgAsnGlySerLeuGlySerLys 326032653270 GGCAGCAGTTTCCGGCAGTGGGCTGAAGCCATCCAAAATTACAAGGCG10130 GlySerSerPheArgGlnTrpAlaGluAlaIleGlnAsnTyrLysAla 327532803285 TCAGACTCTGAGAGGAACCATTGGAATAAGCTCGTCATGGAAACAGCT10178 SerAspSerGluArgAsnHisTrpAsnLysLeuValMetGluThrAla 3290329533003305 TCCAGCATATCCGCATTGCCTACGTCAACCGGTTCGCGCGTGCGCCTG10226 SerSerIleSerAlaLeuProThrSerThrGlySerArgValArgLeu 331033153320 AGCAGAAGTTTGAGCCCTGAGAAGACAGCCTCACTGATCCAAGGAGGA10274 SerArgSerLeuSerProGluLysThrAlaSerLeuIleGlnGlyGly 332533303335 ATCGATCGACAGGATGTCTCCGTGTACGACTCCCTCCTGACTTCAGTT10322 IleAspArgGlnAspValSerValTyrAspSerLeuLeuThrSerVal 334033453350 GGATTGGCGCTCCAACATATCGCTCCAACCGGCCCAAGTATGGTTACG10370 GlyLeuAlaLeuGlnHisIleAlaProThrGlyProSerMetValThr 335533603365 ATCGAGGGACATGGCCGTGAAGAAGTGGATCAGACACTGGATGTGAGC10418 IleGluGlyHisGlyArgGluGluValAspGlnThrLeuAspValSer 3370337533803385 CGCACCATGGGTTGGTTCACCACCATGTATCCATTTGAAATTCCCCGT10466 ArgThrMetGlyTrpPheThrThrMetTyrProPheGluIleProArg 339033953400 CTCAGCACCGAGAACATTGTTCAAGGAGTCGTCGCTGTGAGCGAACGG10514 LeuSerThrGluAsnIleValGlnGlyValValAlaValSerGluArg 340534103415 TTCAGACAGGTGCCTGCCCGTGGCGTCGGGTATGGAACCTTGTACGGC10562 PheArgGlnValProAlaArgGlyValGlyTyrGlyThrLeuTyrGly 342034253430 TATACTCAACACCCGCTGCCCCAGGTGACCGTCAACTACCTGGGCCAG10610 TyrThrGlnHisProLeuProGlnValThrValAsnTyrLeuGlyGln 343534403445 CTCGCCCGCAAGCAATCGAAGCCAAAGGAATGGGTCCTCGCGGTGGGC10658 LeuAlaArgLysGlnSerLysProLysGluTrpValLeuAlaValGly 3450345534603465 GACAACGAATTTGAATACGGACTCATGACTAGCCCAGAGGACAAAGAC10706 AspAsnGluPheGluTyrGlyLeuMetThrSerProGluAspLysAsp 347034753480 CGGAGCTCTTCTGCCGTCGACGTCACGGCCGTGTGTATTGACGGCACT10754 ArgSerSerSerAlaValAspValThrAlaValCysIleAspGlyThr 348534903495 ATGATCATCGATGTGGACAGTGCTTGGAGCCTTGAGGAGAGCGAGCAA10802 MetIleIleAspValAspSerAlaTrpSerLeuGluGluSerGluGln 350035053510 TTCATCTCGAGCATCGAGGAAGGACTGAACAAGATCCTCGACGGCAGG10850 PheIleSerSerIleGluGluGlyLeuAsnLysIleLeuAspGlyArg 351535203525 GCAAGTCAGCAAACCTCGCGATTCCCGGATGTTCCTCAACCGGCGGAG10898 AlaSerGlnGlnThrSerArgPheProAspValProGlnProAlaGlu 3530353535403545 ACATATACGCCGTATTTCGAGTATCTGGAACCTCCACGACAGGGACCG10946 ThrTyrThrProTyrPheGluTyrLeuGluProProArgGlnGlyPro 355035553560 ACGCTGTTCCTGCTGCCGCCGGGCGAAGGAGGCGCCGAGAGTTACTTC10994 ThrLeuPheLeuLeuProProGlyGluGlyGlyAlaGluSerTyrPhe 356535703575 AACAACATCGTCAAGCGCCTGCGTCAGACAAATATGGTGGTCTTCAAC11042 AsnAsnIleValLysArgLeuArgGlnThrAsnMetValValPheAsn 358035853590 AACTACTACTTGCACAGCAAACGCCTGCGCACGTTCGAGGAGCTGGCG11090 AsnTyrTyrLeuHisSerLysArgLeuArgThrPheGluGluLeuAla 359536003605 GAAATGTATCTCGACCAAGTACGCGGCATCCAACCACACGGACCGTAC11138 GluMetTyrLeuAspGlnValArgGlyIleGlnProHisGlyProTyr 3610361536203625 CACTTCATCGGATGGAGCTTCGGAGGAATTCTCGCAATGGAAATGTCG11186 HisPheIleGlyTrpSerPheGlyGlyIleLeuAlaMetGluMetSer 363036353640 CGGCGACTGGTAGCCTCGGACGAGAAGATTGGCTTCCTCGGTATTATC11234 ArgArgLeuValAlaSerAspGluLysIleGlyPheLeuGlyIleIle 364536503655 GACACCTATTTCAACGTGCGGGGAGCGACACGCACCATTGGCTTGGGG11282 AspThrTyrPheAsnValArgGlyAlaThrArgThrIleGlyLeuGly 366036653670 GACACTGAGATTCTGGACCCGATCCATCACATCTACAATCCCGATCCG11330 AspThrGluIleLeuAspProIleHisHisIleTyrAsnProAspPro 367536803685 GCCAACTTCCAACGCCTGCCCTCTGCAACAGATCGCATTGTGCTGTTC11378 AlaAsnPheGlnArgLeuProSerAlaThrAspArgIleValLeuPhe 3690369537003705 AAGGCCATGAGGCCGAACAACAAGTACGAATCCGAGAACCAGCGTCGC11426 LysAlaMetArgProAsnAsnLysTyrGluSerGluAsnGlnArgArg 371037153720 CTGTACGAGTACTATGAC11444 LeuTyrGluTyrTyrAsp (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3727 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: MetThrGlnLeuLysProProAsnGlyThrThrProIleGlyPheSer 151015 AlaThrThrSerLeuAsnAlaSerGlySerSerSerValLysAsnGly 202530 ThrIleLysProSerAsnGlyIlePheLysProSerThrArgAspThr 354045 MetAspProCysSerGlyAsnAlaAlaAspGlySerIleArgValArg 505560 PheArgGlyGlyIleGluArgTrpLysGluCysValAsnGlnValPro 65707580 GluArgCysAspLeuSerGlyLeuThrThrAspSerThrArgTyrGln 859095 LeuAlaSerThrGlyPheGlyAspAlaSerAlaAlaTyrGlnGluArg 100105110 LeuMetThrValProValAspValHisAlaAlaLeuGlnGluLeuCys 115120125 LeuGluArgArgValSerValGlySerValIleAsnPheSerValHis 130135140 GlnMetLeuLysGlyPheGlyAsnGlyThrHisThrIleThrAlaSer 145150155160 LeuHisArgGluGlnAsnLeuGlnAsnSerSerProSerTrpValVal 165170175 SerProThrIleValThrHisGluAsnArgAspGlyTrpSerValAla 180185190 GlnAlaValGluSerIleGluAlaAlaArgGlySerGluLysGluSer 195200205 ValThrAlaIleAspSerAlaSerSerLeuValLysMetGlyLeuPhe 210215220 AspLeuLeuValSerPheValAspAlaAspAspAlaArgIleProCys 225230235240 PheAspPheProLeuAlaValIleValArgGluCysAspAlaAsnLeu 245250255 SerLeuThrLeuArgPheSerAspCysLeuPheAsnGluGluThrIle 260265270 CysAsnPheThrAspAlaLeuAsnIleLeuLeuAlaGluAlaValIle 275280285 GlyArgValThrProValAlaAspIleGluLeuLeuSerAlaGluGln 290295300 LysGlnGlnLeuGluGluTrpAsnAsnThrAspGlyGluTyrProSer 305310315320 SerLysArgLeuHisHisLeuIleGluGluValValGluArgHisGlu 325330335 AspLysIleAlaValValCysAspGluArgGluLeuThrTyrGlyGlu 340345350 LeuAsnAlaGlnGlyAsnSerLeuAlaArgTyrLeuArgSerIleGly 355360365 IleLeuProGluGlnLeuValAlaLeuPheLeuAspLysSerGluLys 370375380 LeuIleValThrIleLeuGlyValTrpLysSerGlyAlaAlaTyrVal 385390395400 ProIleAspProThrTyrProAspGluArgValArgPheValLeuAsp 405410415 AspThrLysAlaArgAlaIleIleAlaSerAsnGlnHisValGluArg 420425430 LeuGlnArgGluValIleGlyAspArgAsnLeuCysIleIleArgLeu 435440445 GluProLeuLeuAlaSerLeuAlaGlnAspSerSerLysPheProAla 450455460 HisAsnLeuAspAspLeuProLeuThrSerGlnGlnLeuAlaTyrVal 465470475480 ThrTyrThrSerGlyThrThrGlyPheProLysGlyIlePheLysGln 485490495 HisThrAsnValValAsnSerIleThrAspLeuSerAlaArgTyrGly 500505510 ValAlaGlyGlnHisHisGluAlaIleLeuLeuPheSerAlaCysVal 515520525 PheGluProPheValArgGlnThrLeuMetAlaLeuValAsnGlyHis 530535540 LeuLeuAlaValIleAsnAspValGluLysTyrAspAlaAspThrLeu 545550555560 LeuProPheIleArgArgHisSerIleThrTyrLeuAsnGlyThrAla 565570575 SerValLeuGlnGluTyrAspPheSerAspCysProSerLeuAsnArg 580585590 IleIleLeuValGlyGluAsnLeuThrGluAlaArgTyrLeuAlaLeu 595600605 ArgGlnArgPheLysAsnArgIleLeuAsnGluTyrGlyPheThrGlu 610615620 SerAlaPheValThrAlaLeuLysIlePheAspProGluSerThrArg 625630635640 LysAspThrSerLeuGlyArgProValArgAsnValLysCysTyrIle 645650655 LeuAsnProSerLeuLysArgValProIleGlyAlaThrGlyGluLeu 660665670 HisIleGlyGlyLeuGlyIleSerLysGlyTyrLeuAsnArgProGlu 675680685 LeuThrProHisArgPheIleProAsnProPheGlnThrAspCysGlu 690695700 LysGlnLeuGlyIleAsnSerLeuMetTyrLysThrGlyAspLeuAla 705710715720 ArgTrpLeuProAsnGlyGluValGluTyrLeuGlyArgAlaAspPhe 725730735 GlnIleLysLeuArgGlyIleArgIleGluProGlyGluIleGluThr 740745750 MetLeuAlaMetTyrProArgValArgThrSerLeuValValSerLys 755760765 LysLeuArgAsnGlyProGluGluThrThrAsnGluHisLeuValGly 770775780 TyrTyrValCysAspSerAlaSerValSerGluAlaAspLeuLeuSer 785790795800 PheLeuGluLysLysLeuProArgTyrMetIleProThrArgLeuVal 805810815 GlnLeuSerGlnIleProValAsnValAsnGlyLysAlaAspLeuArg 820825830 AlaLeuProAlaValAspIleSerAsnSerThrGluValArgSerAsp 835840845 LeuArgGlyAspThrGluIleAlaLeuGlyGluIleTrpAlaAspVal 850855860 LeuGlyAlaArgGlnArgSerValSerArgAsnAspAsnPhePheArg 865870875880 LeuGlyGlyHisSerIleThrCysIleGlnLeuIleAlaArgIleArg 885890895 GlnArgGlnArgLeuSerValSerIleSerValGluAspValPheAla 900905910 ThrArgThrLeuGluArgMetAlaAspLeuLeuGlnAsnLysGlnGln 915920925 GluLysCysAspLysProHisGluAlaProThrGluLeuLeuGluGlu 930935940 AsnAlaAlaThrAspAsnIleTyrLeuAlaAsnSerLeuGlnGlnGly 945950955960 PheValTyrHisTyrLeuLysSerMetGluGlnSerAspAlaTyrVal 965970975 MetGlnSerValLeuArgTyrAsnThrThrLeuSerProAspLeuPhe 980985990 GlnArgAlaTrpLysHisAlaGlnGlnSerPheProAlaLeuArgLeu 99510001005 ArgPheSerTrpGluLysGluValPheGlnLeuLeuAspGlnAspPro 101010151020 ProLeuAspTrpArgPheLeuTyrPheThrAspValAlaAlaGlyAla 1025103010351040 ValGluAspArgLysLeuGluAspLeuArgArgGlnAspLeuThrGlu 104510501055 ArgPheLysLeuAspValGlyArgLeuPheArgValTyrLeuIleLys 106010651070 HisSerGluAsnArgPheThrCysLeuPheSerCysHisHisAlaIle 107510801085 LeuAspGlyTrpSerLeuProLeuLeuPheGluLysValHisGluThr 109010951100 TyrLeuGlnLeuLeuHisGlyAspAsnLeuThrSerSerMetAspAsp 1105111011151120 ProTyrThrArgThrGlnArgTyrLeuHisAlaHisArgGluAspHis 112511301135 LeuAspPheTrpAlaGlyValValGlnLysIleAsnGluArgCysAsp 114011451150 MetAsnAlaLeuLeuAsnGluArgSerArgTyrLysValGlnLeuAla 115511601165 AspTyrAspGlnValGlnGluGlnArgHisValThrIleAlaLeuSer 117011751180 GlyAspAlaTrpLeuAlaAspLeuArgGlnThrCysSerAlaGlnGly 1185119011951200 IleThrLeuHisSerIleLeuGlnPheValTrpHisAlaValLeuHis 120512101215 AlaTyrGlyGlyGlyThrHisThrIleThrGlyThrThrIleSerGly 122012251230 ArgAsnLeuProIleLeuGlyIleGluArgAlaValGlyProTyrIle 123512401245 AsnThrLeuProLeuValLeuAspHisSerThrPheLysAspLysThr 125012551260 IleMetGluAlaIleGluAspValGlnAlaLysValAsnValMetAsn 1265127012751280 SerArgGlyAsnValGluLeuGlyArgLeuHisLysThrAspLeuLys 128512901295 HisGlyLeuPheAspSerLeuPheValLeuGluAsnTyrProAsnLeu 130013051310 AspLysSerArgThrLeuGluHisGlnThrGluLeuGlyTyrSerIle 131513201325 GluGlyGlyThrGluLysLeuAsnTyrProLeuAlaValIleAlaArg 133013351340 GluValGluThrThrGlyGlyPheThrValSerIleCysTyrAlaSer 1345135013551360 GluLeuPheGluGluValMetIleSerGluLeuLeuHisMetValGln 136513701375 AspThrLeuMetGlnValAlaArgGlyLeuAsnGluProValGlySer 138013851390 LeuGluTyrLeuSerSerIleGlnLeuGluGlnLeuAlaAlaTrpAsn 139514001405 AlaThrGluAlaGluPheProAspThrThrLeuHisGluMetPheGlu 141014151420 AsnGluAlaSerGlnLysProAspLysIleAlaValValTyrGluGlu 1425143014351440 ThrSerLeuThrTyrArgGluLeuAsnGluArgAlaAsnArgMetAla 144514501455 HisGlnLeuArgSerAspValSerProAsnProAsnGluValIleAla 146014651470 LeuValMetAspLysSerGluHisMetIleValAsnIleLeuAlaVal 147514801485 TrpLysSerGlyGlyAlaTyrValProIleAspProGlyTyrProAsn 149014951500 AspArgIleGlnTyrIleLeuGluAspThrGlnAlaLeuAlaValIle 1505151015151520 AlaAspSerCysTyrLeuProArgIleLysGlyMetAlaAlaSerGly 152515301535 ThrLeuLeuTyrProSerValLeuProAlaAsnProAspSerLysTrp 154015451550 SerValSerAsnProSerProLeuSerArgSerThrAspLeuAlaTyr 155515601565 IleIleTyrThrSerGlyThrThrGlyArgProLysGlyValThrVal 157015751580 GluHisHisGlyValValAsnLeuGlnValSerLeuSerLysValPhe 1585159015951600 GlyLeuArgAspThrAspAspGluValIleLeuSerPheSerAsnTyr 160516101615 ValPheAspHisPheValGluGlnMetThrAspAlaIleLeuAsnGly 162016251630 GlnThrLeuLeuValLeuAsnAspGlyMetArgGlyAspLysGluArg 163516401645 LeuTyrArgTyrIleGluLysAsnArgValThrTyrLeuSerGlyThr 165016551660 ProSerValValSerMetTyrGluPheSerArgPheLysAspHisLeu 1665167016751680 ArgArgValAspCysValGlyGluAlaPheSerGluProValPheAsp 168516901695 LysIleArgGluThrPheHisGlyLeuValIleAsnGlyTyrGlyPro 170017051710 ThrGluValSerIleThrThrHisLysArgLeuTyrProPheProGlu 171517201725 ArgArgMetAspLysSerIleGlyGlnGlnValHisAsnSerThrSer 173017351740 TyrValLeuAsnGluAspMetLysArgThrProIleGlyAlaValGly 1745175017551760 GluLeuTyrLeuGlyGlyGluGlyValValArgGlyTyrHisAsnArg 176517701775 AlaAspValThrAlaGluArgPheIleProAsnProPheGlnSerGlu 178017851790 GluAspLysArgGluGlyArgAsnSerArgLeuTyrLysThrGlyAsp 179518001805 LeuValArgTrpIleProGlySerSerGlyGluValGluTyrLeuGly 181018151820 ArgAsnAspPheGlnValLysIleArgGlyLeuArgIleGluValGly 1825183018351840 GluIleGluAlaIleLeuSerSerTyrHisGlyIleLysGlnSerVal 184518501855 ValIleAlaLysAspCysArgGluGlyAlaGlnLysPheLeuValGly 186018651870 TyrTyrValAlaAspAlaAlaLeuProSerAlaAlaIleArgArgPhe 187518801885 MetGlnSerArgLeuProGlyTyrMetValProSerArgLeuIleLeu 189018951900 ValSerLysPheProValThrProSerGlyLysLeuAspThrLysAla 1905191019151920 LeuProProAlaGluGluGluSerGluIleAspValValProProArg 192519301935 SerGluIleGluArgSerLeuCysAspIleTrpAlaGluLeuLeuGlu 194019451950 MetHisProGluGluIleGlyIleTyrSerAspPhePheSerLeuGly 195519601965 GlyAspSerLeuLysSerThrLysLeuSerPheMetIleHisGluSer 197019751980 PheAsnArgAlaValSerValSerAlaLeuPheCysHisArgThrVal 1985199019952000 GluAlaGlnThrHisLeuIleLeuAsnAspAlaAlaAspValHisGlu 200520102015 IleThrProIleAspCysAsnAspThrGlnMetIleProValSerArg 202020252030 AlaGlnGluArgLeuLeuPheIleHisGluPheGluAsnGlySerAsn 203520402045 AlaTyrAsnIleAspAlaAlaPheGluLeuProGlySerValAspAla 205020552060 SerLeuLeuGluGlnAlaLeuArgGlyAsnLeuAlaArgHisGluAla 2065207020752080 LeuArgThrLeuLeuValLysAspHisAlaThrGlyIleTyrLeuGln 208520902095 LysValLeuSerProAspGluAlaGlnGlyMetPheSerValAsnVal 210021052110 AspThrAlaLysGlnValGluArgLeuAspGlnGluIleAlaSerLeu 211521202125 SerGlnHisValPheArgLeuAspAspGluLeuProTrpGluAlaArg 213021352140 IleLeuLysLeuGluSerGlyGlyLeuTyrLeuIleLeuAlaPheHis 2145215021552160 HisThrCysPheAspAlaTrpSerLeuLysValPheGluGlnGluLeu 216521702175 ArgAlaLeuTyrAlaAlaLeuGlnLysThrLysSerAlaAlaAsnLeu 218021852190 ProAlaLeuLysAlaGlnTyrLysGluTyrAlaLeuTyrHisArgArg 219522002205 GlnLeuSerGlyAspArgMetArgAsnLeuSerAspPheTrpLeuArg 221022152220 LysLeuIleGlyLeuGluProLeuGlnLeuIleThrAspArgProArg 2225223022352240 ProValGlnPheLysTyrAspGlyAspAspLeuSerIleGluLeuSer 224522502255 LysLysGluThrGluAsnLeuArgGlyValAlaLysArgCysLysSer 226022652270 SerLeuTyrValValLeuValSerValTyrCysValMetLeuAlaSer 227522802285 TyrAlaAsnGlnSerAspValSerValGlyIleProValSerHisArg 229022952300 ThrHisProGlnPheGlnSerValIleGlyPhePheValAsnLeuVal 2305231023152320 ValLeuArgValAspIleSerGlnSerAlaIleCysGlyLeuIleArg 232523302335 ArgValMetLysGluLeuValAspAlaGlnLeuHisGlnAspMetPro 234023452350 PheGlnGluValThrLysLeuLeuGlnValAspAsnAspProSerArg 235523602365 HisProLeuValGlnAsnValPheAsnPheGluSerArgAlaAsnGly 237023752380 GluHisAspAlaArgSerGluAspGluGlySerLeuAlaPheAsnGln 2385239023952400 TyrArgProValGlnProValAspSerValAlaLysPheAspLeuAsn 240524102415 AlaThrValThrGluLeuGluSerGlyLeuArgValAsnPheAsnTyr 242024252430 AlaThrSerLeuPheAsnLysSerThrIleGlnGlyPheLeuHisThr 243524402445 TyrGluTyrLeuLeuArgGlnLeuSerGluLeuSerAlaGluGlyIle 245024552460 AsnGluAspThrGlnLeuSerLeuValArgProThrGluAsnGlyAsp 2465247024752480 LeuHisLeuProLeuAlaGlnSerProLeuAlaThrThrAlaGluGlu 248524902495 GlnLysValAlaSerLeuAsnGlnAlaPheGluArgGluAlaPheLeu 250025052510 AlaAlaGluLysIleAlaValValGlnGlyAspArgAlaLeuSerTyr 251525202525 AlaAspLeuAsnGlyGlnAlaAsnGlnLeuAlaArgTyrIleGlnSer 253025352540 ValSerCysIleGlyAlaAspAspGlyIleAlaLeuMetLeuGluLys 2545255025552560 SerIleAspThrIleIleCysIleLeuAlaIleTrpLysAlaGlyAla 256525702575 AlaTyrValProLeuAspProThrTyrProProGlyArgValGlnLeu 258025852590 IleLeuGluGluIleLysAlaLysAlaValLeuValHisSerSerHis 259526002605 AlaSerLysCysGluArgHisGlyAlaLysValIleAlaValAspSer 261026152620 ProAlaIleGluThrAlaValSerGlnGlnSerAlaAlaAspLeuPro 2625263026352640 ThrIleAlaSerLeuGlyAsnLeuAlaTyrIleIlePheThrSerGly 264526502655 ThrSerGlyLysProLysGlyValLeuValGluGlnLysAlaValLeu 266026652670 LeuLeuArgAspAlaLeuArgGluArgTyrPheGlyArgAspCysThr 267526802685 LysHisHisGlyValLeuPheLeuSerAsnTyrValPheAspPheSer 269026952700 ValGluGlnLeuValLeuSerValLeuSerGlyHisLysLeuIleVal 2705271027152720 ProProAlaGluPheValAlaAspAspGluPheTyrArgMetAlaSer 272527302735 ThrHisGlyLeuSerTyrLeuSerGlyThrProSerLeuLeuGlnLys 274027452750 IleAspLeuAlaArgLeuAspHisLeuGlnValValThrAlaAlaGly 275527602765 GluGluLeuHisAlaThrGlnTyrGluLysMetArgArgArgPheAsn 277027752780 GlyProIleTyrAsnAlaTyrGlyValThrGluThrThrValTyrAsn 2785279027952800 IleIleAlaGluPheThrThrAsnSerIlePheGluAsnAlaLeuArg 280528102815 GluValLeuProGlyThrArgAlaTyrValLeuThrAlaAlaLeuGln 282028252830 ProValProPheAspAlaValGlyGluLeuTyrLeuAlaGlyAspThr 283528402845 ValThrArgGlyTyrLeuAsnGlnProLeuLeuThrAspGlnArgPhe 285028552860 IleProAsnProPheCysLysGluGluAspIleAlaMetGlyArgPhe 2865287028752880 AlaArgLeuTyrLysThrGlyAspLeuValArgSerArgPheAsnArg 288528902895 GlnGlnGlnProGlnLeuGluTyrLeuGlyArgGlyAspLeuGlnIle 290029052910 LysMetArgGlyTyrArgIleGluIleSerGluValGlnAsnValLeu 291529202925 ThrSerSerProGlyValArgGluGlyAlaValValAlaLysTyrGlu 293029352940 AsnAsnAspThrTyrSerArgThrAlaHisSerLeuValGlyTyrTyr 2945295029552960 ThrThrAspAsnGluThrValSerGluAlaAspIleLeuThrPheMet 296529702975 LysAlaArgLeuProThrTyrMetValProSerHisLeuCysCysLeu 298029852990 GluGlyAlaLeuProValThrIleAsnGlyLysLeuAspValArgArg 299530003005 LeuProGluIleIleAsnAspSerAlaGlnSerSerTyrSerProPro 301030153020 ArgAsnIleIleGluAlaLysMetCysArgLeuTrpGluSerAlaLeu 3025303030353040 GlyMetGluArgCysGlyIleAspAspAspLeuPheLysLeuGlyGly 304530503055 AspSerIleThrSerLeuHisLeuValAlaGlnIleHisAsnGlnVal 306030653070 GlyCysLysIleThrValArgAspIlePheGluHisArgThrAlaArg 307530803085 AlaLeuHisAspHisValPheMetLysAspSerAspArgSerAsnVal 309030953100 ThrGlnPheArgThrGluGlnGlyProValIleGlyGluAlaProLeu 3105311031153120 LeuProIleGlnAspTrpPheLeuSerLysAlaLeuGlnHisProMet 312531303135 TyrTrpAsnHisThrPheTyrValArgThrProGluLeuAspValAsp 314031453150 SerLeuSerAlaAlaValArgAspLeuGlnGlnTyrHisAspValPhe 315531603165 ArgMetArgLeuLysArgGluGluValGlyPheValGlnSerPheAla 317031753180 GluAspPheSerProAlaGlnLeuArgValLeuAsnValLysAspVal 3185319031953200 AspGlySerAlaAlaValAsnGluIleLeuAspGlyTrpGlnSerGly 320532103215 PheAsnLeuGluAsnGlyProIleGlySerIleGlyTyrLeuHisGly 322032253230 TyrGluAspArgSerAlaArgValTrpPheSerValHisHisMetAla 323532403245 IleAspThrValSerTrpGlnIleLeuValArgAspLeuGlnThrLeu 325032553260 TyrArgAsnGlySerLeuGlySerLysGlySerSerPheArgGlnTrp 3265327032753280 AlaGluAlaIleGlnAsnTyrLysAlaSerAspSerGluArgAsnHis 328532903295 TrpAsnLysLeuValMetGluThrAlaSerSerIleSerAlaLeuPro 330033053310 ThrSerThrGlySerArgValArgLeuSerArgSerLeuSerProGlu 331533203325 LysThrAlaSerLeuIleGlnGlyGlyIleAspArgGlnAspValSer 333033353340 ValTyrAspSerLeuLeuThrSerValGlyLeuAlaLeuGlnHisIle 3345335033553360 AlaProThrGlyProSerMetValThrIleGluGlyHisGlyArgGlu 336533703375 GluValAspGlnThrLeuAspValSerArgThrMetGlyTrpPheThr 338033853390 ThrMetTyrProPheGluIleProArgLeuSerThrGluAsnIleVal 339534003405 GlnGlyValValAlaValSerGluArgPheArgGlnValProAlaArg 341034153420 GlyValGlyTyrGlyThrLeuTyrGlyTyrThrGlnHisProLeuPro 3425343034353440 GlnValThrValAsnTyrLeuGlyGlnLeuAlaArgLysGlnSerLys 344534503455 ProLysGluTrpValLeuAlaValGlyAspAsnGluPheGluTyrGly 346034653470 LeuMetThrSerProGluAspLysAspArgSerSerSerAlaValAsp 347534803485 ValThrAlaValCysIleAspGlyThrMetIleIleAspValAspSer 349034953500 AlaTrpSerLeuGluGluSerGluGlnPheIleSerSerIleGluGlu 3505351035153520 GlyLeuAsnLysIleLeuAspGlyArgAlaSerGlnGlnThrSerArg 352535303535 PheProAspValProGlnProAlaGluThrTyrThrProTyrPheGlu 354035453550 TyrLeuGluProProArgGlnGlyProThrLeuPheLeuLeuProPro 355535603565 GlyGluGlyGlyAlaGluSerTyrPheAsnAsnIleValLysArgLeu 357035753580 ArgGlnThrAsnMetValValPheAsnAsnTyrTyrLeuHisSerLys 3585359035953600 ArgLeuArgThrPheGluGluLeuAlaGluMetTyrLeuAspGlnVal 360536103615 ArgGlyIleGlnProHisGlyProTyrHisPheIleGlyTrpSerPhe 362036253630 GlyGlyIleLeuAlaMetGluMetSerArgArgLeuValAlaSerAsp 363536403645 GluLysIleGlyPheLeuGlyIleIleAspThrTyrPheAsnValArg 365036553660 GlyAlaThrArgThrIleGlyLeuGlyAspThrGluIleLeuAspPro 3665367036753680 IleHisHisIleTyrAsnProAspProAlaAsnPheGlnArgLeuPro 368536903695 SerAlaThrAspArgIleValLeuPheLysAlaMetArgProAsnAsn 370037053710 LysTyrGluSerGluAsnGlnArgArgLeuTyrGluTyrTyrAsp 371537203725 __________________________________________________________________________

## Claims

1. An expression cassette comprising as operably linked components, in the direction of transcription; frame encoding the enzyme .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase which (i) has a restriction map as indicated in FIG. 3, FIG. 4, or FIG. 16, HM193, pPCV02, pSLACV-01, pSLACV-03A, and pSLACV-03B; promoter and terminator.

2. The expression cassette according to claim 1, wherein said promoter is active in the presence of glucose.

3. The expression cassette according to claim 1, wherein said promoter is selected from the group consisting of a Penicillium chrysogenum pgk promoter, an E. coli trp promoter, a Streptomyces aph promoter, and a tyrosinase promoter.

4. The expression cassette according to claim 1, wherein said promoter is functional in a filamentous fungus or a prokaryotic cell.

5. The expression cassette according to claim 1, wherein said enzyme encoded by said open reading frame exhibits .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase activity.

6. A transformed host cell comprising:

7. The cell according to claim 6, wherein said cell is selected from the group consisting of a prokaryotic cell and a filamentous fingus.

8. The cell according to claim 6, wherein said promoter is active in the presence of glucose.

9. The cell according to claim 6, wherein said promoter is selected from the group consisting of a Penicillium chrysogenum pgk promoter, an E. coli trp promoter, a Streptomyces aph promoter and a tyrosinase promoter.

10. The cell according to claim 6, wherein said cell is selected from the group consisting of a Penicillium chrysogenum, Acremonium chrysogenum, Aspergillus nidulans, and Streptomyces cell.

11. The cell according to claim 6, wherein said DNA is transcribed to RNA, and said RNA is translated.

12. A method for producing a .beta.-lactam antibiotic, said method comprising: fermentation conditions to produce said .beta.-lactam antibiotic, and optionally isolating said .beta.-lactam antibiotic.

13. A method for increasing production of .beta.-lactam antibiotics in a microbial host cell, said method comprising: with the expression cassette of claim 1 whereby transformed cells are obtained; expression cassette; increased amounts of .beta.-lactam antibiotics as compared to untransformed cells and isolating said enhanced expressers; .beta.-lactam antibiotics in a microbial host is obtained;

14. A method for producing .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase in a host cell, said method comprising: ACVS is produced and optionally isolated.

15. The method according to any one of claims 12, 13, or 14, wherein said host cell is a Streptomyces or a filamentous fungus.

16. The method according to claim 15, wherein said filamentous fungus is selected from the group consisting of Penicillium chrysogenum, Acremonium chrysogenum, and Aspergillus nidulans.

17. In a method for in vitro synthesis of .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine using a cell-free extract obtained from cells which produce .beta.-lactam antibiotics, the improvement which comprises: obtained according to the method of claim 14 to said cell-free extract.

18. An isolated DNA of fewer than 15 kbp consisting essentially of an open reading frame encoding the enzyme .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase which has a restriction map as indicated in FIG. 3 or FIG. 4.

19. An isolated DNA of fewer than 15 kbp consisting essentially of an open reading frame encoding the enzyme .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase which has a restriction map as indicated in FIG. 16.

20. An isolated DNA of fewer than 15 kbp consisting essentially of an open reading frame encoding the enzyme .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase wherein said DNA encodes the sequence of SEQ ID NO: 25.

21. An isolated DNA of fewer than 15 kbp consisting essentially of an open reading frame encoding the enzyme .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase which is contained in a vector selected from the group consisting of HM193, pPCV02, pSLACV-01, pSLACV-03A, and pSLACV-03B.

22. The DNA according to any of claims 18, 19, 20 or 21, wherein said DNA is obtained from a filamentous fungus species selected from the group consisting of Penicillium chrysogenum, Acremonium chrysogenum, and Aspergillus nidulans.

23. The DNA according to any one of claims 18, 19, 20 or 21, wherein said DNA is obtained from a bacterium belonging to the genus Flavobacterium or Streptomyces.

24. The DNA according to any one of claims 18, 19, 20 or 21, wherein said enzyme encoded by said open reading frame exhibits .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase activity.

25. An isolated DNA comprising: chrysogenum pgk promoter, a trp promoter, a Streptomyces aph promoter, and a tyrosinase promoter.

26. Plasmid pPCV02, pPCV03, pMA-ACVS, pSLACV-01, pSLACV-03A or pSLACV-03B.

27. A transformed E. coli cell comprising plasmid pMA-ACVS.

28. A transformed Streptomyces cell comprising plasmid pSLACV-01, pSLACV-03A or pSLACV-03B.

29. A transformed Penicillium chrysogenum cell or Acremonium chrysogenum or Aspergillus nidulans cell comprising plasmid pPCV02 or pPCV03.

30. The cell according to claim 6, wherein said cell is a eukaryotic cell.