# Patent

## Title
Method of site-specific nucleic acid cleavage

## Abstract

This is a continuation of application Ser. No. 08/174,682, filed Dec. 28, 1993, abandoned, which is a continuation of application Ser. No. 07/917,146, filed Aug. 10, 1992, abandoned.

## Background
The invention relates to the polypeptides associated with the expression of resistance to antibiotics of the glycopeptide family, in particular in Gram-positive bacteria, in particular in the family of the Gram-positive cocci. The invention also relates to a nucleotide sequence coding for these polypeptides. It also relates to the use of these polypeptides and their nucleotide sequence as agents for the in vitro detection of resistance to glycopeptides. Among the Gram-positive cocci, the invention relates most particularly to the enterococci, the streptococci and the staphylococci which are of particular importance for the implementation of the invention.

The glycopeptides, which include vancomycin and teicoplanin are antibiotics which inhibit the synthesis of the bacterial cell wall. These antibiotics are very much used for the treatment of severe infections due to Gram-positive cocci (enterococci, streptococci and staphylococci), in particular in light of allergy and resistance to the penicillins. In spite of long clinical usage of vancomycin, this antibiotic has remained active towards almost all of the strains up to 1986, the date at which the first resistant strains were isolated. Since then, resistance to the glycopeptides has been detected by many microbiologists in Europe and in the United States, in particular in strains isolated from immunodepressive patients, making necessary a systematic evaluation of the sensitivity of the microbes in hospital environments.

The activity of the glycopeptides depends on the formation of a complex between the antibiotic and the precursors of the peptidoglycan, more than on the direct interaction with enzymes of cell wall metabolism. In particular, it has been observed that the glycopeptides bind to the terminal D-alanyl-D-alanine residues (D-ala-D-ala) of the precursors of the peptidoglycan.

The recent emergence of resistance to the glycopeptides, in particular in the enterococci, has led to certain results being obtained with regard to knowledge of the factors conferring this resistance.

For example it has been observed in a particular strain of enterococci, Enterococcus faecium BM4147, that the determinant of resistance to the glycopeptides is localized on a plasmid of 34 kb, the plasmid pIP816. This determinant has been cloned in E.coli (Brisson Noel et al., 1990, Antimicrob Agents Chemother 34, 924-927).

According to the results hitherto obtained, the resistance to the glycopeptides is associated with the production of a protein of molecular weight of about 40 kDa, the synthesis of this protein being induced by sub-inhibitory concentrations of certain glycopeptides such as vancomycin.

By carrying out a more detailed study of the resistance of certain strains of Gram-positive cocci towards glycopeptides, in particular vancomycin or teicoplanin, the inventors have observed that this resistance might be linked to the expression of several proteins or polypeptides encoded in sequences usually borne by plasmids in the resistant strains. The recent results obtained by the inventors also make it possible to distinguish the genes coding for two phenotypes of resistance, on the one hand strains highly resistant to the glycopeptides, and, on the other, strains with a low level of resistance.

By strain with a high level of resistance is meant a strain of bacteria, in particular a strain of Gram-positive cocci, for which the minimal inhibitory concentrations (MIC) of vancomycin and teichoplaninare higher than 32 and 8 .mu.g/ml, respectively. The MIC of vancomycin towards strains with low-level resistance are included between 16 and 32 .mu.g/ml. These strains are apparently sensitive to teicoplanin.

The inventors have isolated and purified, among the components necessary for the expression of the resistance to the glycopeptides, a particular protein designated VANA or VanA which exhibits a certain homology with D-alanine-D-alanine ligases. VanA is nonetheless functionally distinct from the ligases.

In principle, a gene sequence will be designated by "van . . . " and an amino acid sequence by "Van . . . "

The invention relates to polypeptides or proteins implicated in the expression of resistance to antibiotics of the glycopeptide family and, in particular, to vancomycin and/or teicoplanin as well as to the nucleotide sequences coding for such complexes.

The invention also relates to nucleotide probes which can be used for the detection of resistance to the glycopeptides, in particular by means of the polymerase chain reaction (PCR), or by tests involving antibodies.

The invention relates to a composition of polypeptides, characterized in that it contains at least one protein or part of a protein selected from the amino acid sequences identified in the list of the sequences as SEQ ID NO 2 (VanH), SEQ ID NO 4 (VanA), SEQ ID NO 6 (VanX) or SEQ ID NO 8 (VanC), or any protein or part of a protein recognized by the antibodies directed against VanH, VanA, VanX or VanC, or any protein or part of a protein encoded in a sequence hybridizing with one of the nucleotide sequences identified in the list of the sequences as SEQ ID NO 1, SEQ ID NO 3, SEQ ID NO 5 or SEQ ID NO 7 or with one of the following sequences V1 (SEQ ID NO:9) or V2 (SEQ ID NO:10) under stringent or only slightly stringent conditions: ##STR1##

A first particular composition according to the invention implicated in the expression of the resistance to the glycopeptides is characterized in that it comprises at least 3 proteins or any part of one or more of these proteins necessary to confer to Gram-positive bacteria the resistance to antibiotics of the glycopeptide family, in particular to vancomycin and/or teicoplanin or to promote this resistance, in particular in strains of the family of the Gram-positive cocci, these proteins or parts of proteins being identified in the list of the sequences as SEQ ID NO 2, SEQ ID NO 4, SEQ ID NO 6. ID NO 3 or SEQ ID NO 5 or hybridizing with one of these sequences or its complementary sequence or with the sequences V1 (SEQ ID NO:9) or V2 (SEQ ID NO:10), under stringent or only slightly stringent conditions.

These sequences are also designated, respectively, by ORF3, ORF1 containing the gene VanH, vanA (or ORF2); they characterize the proteins responsible for resistance as obtained from the strain Enterococcus faecium BM4147 described by leclerq et al (N. Engl. J. Med. 319:157-161).

Another protein, VanC (SEQ ID NO:8), related to the D-Ala-D-Ala ligases but of different specificity has been characterized in Enterococcus gallinarum BM4173; the vanC gene (SEQ ID NO:7) possesses domains having sufficient homology with the vanA gene for probes corresponding to defined regions of vanA to make possible its detection.

E.gallinarum is a constitutive isolate resistant to low levels of vancomycin (Dutka-Malen et al., Antimicrob. Agents Chemother 34 (1990b) 1875-1879).

By the expression "polypeptides" is meant any sequence of amino acids constituting proteins or being of a size less than that of a protein.

The stringent conditions mentioned above are defined according to the usual conditions pertaining to the hybridization of nucleotide sequences. As an example, in the case of the sequences which hybridize with the sequence of the vanA gene (SEQ ID NO 1) it will be possible to apply the following conditions: 0.1% SDS, 0.7% skimmed milk powder, 6.times.SSC (1.times.SSC=0.15M NaCl and 0.015M sodium citrate at pH=7.0) temperature is 60.degree. C. overnight and the temperature of the washings is 45.degree. C.

The expression of resistance to glycopeptides may be expressed by the persistence of an infection due to microbes usually sensitive to the glycopeptides.

A polypeptide or a protein is necessary for the expression of resistance to the glycopeptides, if its absence makes the strain which contains this polypeptide or this protein more sensitive to the glycopeptides and if this polypeptide or protein is not present in sensitive strains.

Different levels of resistance to the glycopeptides exist in the strains of Gram-positive cocci, in particular.

According to a preferred embodiment of the invention, the polypeptides included in the composition defined above correspond to the combination of the proteins identified in the list of the sequences as SEQ ID NO 2 (VanH), SEQ ID NO 4 (VanA), SEQ ID NO 6 (VanX).

The inventors have thus observed that the expression of resistance to the glycopeptides in Gram-positive bacteria requires the expression of at least three proteins or of polypeptides derived from these proteins.

According to a first particular embodiment of the invention, the polypeptides of the composition are also characterized in that the amino acid sequences necessary for the expression of resistance to antibiotics of the glycopeptide family are under the control of regulatory elements, in particular of the proteins corresponding to the sequences designated by SEQ ID NO 12 and SEQ ID NO 14 in the list of the sequences, and which correspond to a regulatory sequence R and to a sensor sequence S, respectively.

VanS and VanR constitute a two-component regulatory system, VanR being an activator of transcription and VanS stimulating the transcription dependent on VanR. VanS is capable of modulating the level of phosphorylation of VanR in response to the vancomycin present in the external medium and is thus involved in the control of the transcription of the genes for resistance to vancomycin.

These regulatory sequences are in particular capable of increasing the level of resistance, to the extent to which they promote the expression of the proteins responsible for resistance comprised in the polypeptides of the invention.

According to another advantageous embodiment of the invention, the polypeptides of the above composition are encoded in the sequence SEQ ID NO 15 identified in the list of the sequences, which represents the sequence coding for the 5 proteins previously described.

Another sequence according to the invention is designated by SEQ ID NO 16 which contains the sequence SEQ ID NO 15 as well as a sequence upstream from SEQ ID NO 15 coding for a transposase (encoded in the (-) strand of the sequence, and a sequence downstream from SEQ ID NO 15 corresponding to the genes vanY and vanZ and at each end reverse repeated sequences of 38 bp. SEQ ID NO 16 constitutes a transposon, the genes of which are implicated at different levels in the establishment of resistance to the glycopeptides.

The invention also relates to the purified proteins belonging to the composition and to the polypeptides described previously. In particular, the invention relates to the purified protein VanA, characterized in that it corresponds to the amino acid sequence SEQ ID NO 4 in the list of the sequences or a protein VanC, encoded in a gene capable of hybridizing with the vanA gene.

The protein VanA contains 343 amino acids and has a calculated molecular mass of 37400 Da. The protein VanC contains 343 amino acids and has a calculated molecular mass of 37504 Da.

Other interesting proteins in the framework of the invention correspond to the sequences identified as SEQ ID NO 2 (VanH), SEQ ID NO 6 (VanX), SEQ ID NO 12 (VanR), SEQ ID NO 14 (VanS) in the list of the sequences.

The sequence identified by the abbreviation SEQ ID NO 2 contains the protein VanH encoded in the gene vanH, this protein contains 322 amino acids and begins with a methionine. This protein is an enzyme implicated in the synthesis of the peptidoglycan and has a molecular mass of 35,754 kDA. VanH exhibits some similarities to dehydrogenases which catalyze the NAD.sup.+ -dependent oxidation of 2-hydroxy-carboxylic acids to form the corresponding 2-keto-carboxylic acids. In fact, the VanH protein might use NADP.sup.+  rather than NAD.sup.+. The VanH protein also contains several residues of reactive sites which probably participate directly in the binding of the substrate and in catalysis. VanH might be implicated in the synthesis of a substrate of the ligase VanA. This substrate of VanA might be a D-.alpha.-hydroxy-carboxylic acid, which might be condensed by VanA with D-alanine in the place of a D-amino acid, which might affect the binding of the precursor of the peptidoglycan with vancomycin, as a result of the loss of a hydrogen bond because one of the hydrogen bonds formed between vancomycin and N-acetyl-D-Ala-D-Ala occurs with the NH group of the terminal D-alanine residue. Let it be recalled that "Ala" is the abbreviation for "alanine".

The inventors have been able to detect some interactions between the proteins VanA and VanH and have in particular been able to describe the following: the nature of the VanA protein (D-alanine: D-alanine ligase with reduced specificity for its substrate) which has made possible resistance to glycopeptides, implies the biosynthesis by VanA of a novel compound different from D-Ala-D-Ala, a peptide which may be incorporated into the peptidoglycans but which is not recognized by vancomycin. In particular, the observation of similarities between the product of the vanH gene and the D-specific .alpha.-keto-acid reductases has made it possible to determine that this compound cannot be a D-amino acid but is a D hydroxy acid, which when it is bound to D-alanine by VanH, can generate the novel depsipeptide precursor of the peptidoglycan.

The invention also relates to any combination of these different proteins in a resistance complex, as well as to hybrid proteins comprising one or several of the above proteins, or part of these proteins, in combination with a defined amino acid sequence.

Also included in the framework of the invention are nucleotide sequences coding for one of the amino acid sequences described above.

A particular sequence is the nucleotide sequence of about 7.3 kb, corresponding to the HindIII-EcoRI restriction fragment, such as that obtained starting from the plasmid pIP816 described in the publication of Leclerq et al--1988, cited above.

This sequence of 7.3 kb comprises the nucleotide sequence coding for the 3 resistance proteins and the 2 regulatory proteins referred to above. This coding sequence is included in an internal BglII-XbaI fragment. It also comprises a part of the sequences coding for the transposase and the resolvase.

The invention also relates to any nucleotide fragment comprising the above-mentioned restriction fragment as well as any part of the HindIII-EcoRI fragment, in particular the EcoRI-XbaI fragment of about 3.4 kb coding for the 3 resistance proteins or the EcoRV-SacII fragment of about 1.7 kb coding for VanA or also HindIII-EcoRI fragment of about 3.3 kb coding for the 2 regulatory proteins VanR and VanS.

Another definition of a nucleotide sequence of the invention corresponds to a nucleotide fragment containing the following restriction sites in the following order, such as obtained starting from pIP816 mentioned above:

Another nucleotide sequence according to the invention is characterized in that it corresponds to a sequence selected from the sequences identified as SEQ ID NO 15, SEQ ID NO 17, or SEQ ID NO 16, or in that it includes this sequence or any part of this sequence, or also any sequence or part of the sequence of the complementary DNA or any sequence of RNA corresponding to one of these DNAs, capable, resistance to antibiotics of the glycopeptide family, in particular to vancomycin and/or teicoplanin in particular in strains of the family of the Gram-positive cocci, resistance to antibiotics of the glycopeptide family, in particular to vancomycin and/or teicoplanin., in particular in strains of the family of the Gram-positive cocci.

The sequence SEQ ID NO 17 codes for the 3 resistance proteins VanH, VanA and VanX.

The sequence SEQ ID NO 16 includes a transposon shown in FIG. 7a; this transposon contains the genes necessary for the expression of resistance to the glycopeptides as well as the genes associated with this resistance implicated, for example, in the regulation of the expression of the genes necessary to produce the resistance phenotype or implicated in the amount of resistance polypeptide produced.

A specific sequence corresponding to the above definition is one of the following sequences: ##STR2##

V1 and V2 make possible the constitution of probes, if necessary, in combination with other nucleotides, depending on the degree of specificity desired in order to detect vanA and vanC and may also be used as primers in polymerase chain reactions.

Other preferred nucleotide sequences are the sequences SEQ ID NO 1, SEQ ID NO 3, SEQ ID NO 5, SEQ ID NO 7, SEQ ID NO 18 (transposase), SEQ ID NO 20 (resolvase), SEQ ID NO 22 (vanY), SEQ ID NO 24 (vanZ), SEQ ID NO 11 (vanR), SEQ ID NO 13 (vanS) or a variant of one of these sequences provided that it codes for a protein having immunological and/or functional properties similar to those of the proteins encoded in the sequences SEQ ID NO 1 (vanA), SEQ ID NO 3 (vanH), SEQ ID NO 10 (vanX), or SEQ ID NO 21 (vanC), SEQ ID NO 18 (transposase), SEQ ID NO 20 (resolvase), SEQ ID NO 22 (vanY), SEQ ID NO 24 (vanZ), SEQ ID NO 11 (vanR), SEQ ID NO 13 (vanS) or in that it makes possible the detection of strains resistant to antibiotics of the glycopeptide family.

Variants include all of the fragments of the sequences having the following properties.

These sequences code for the resistance proteins VanH, VanA and VanX.

The nucleotide sequence designated by SEQ ID NO 1corresponds to a DNA fragment of 1029 bp situated between the ATG codon at position 377 and the TGA codon at position 1406 on the plasmid pAT214 (FIG. 6).

The invention also relates to a nucleotide sequence coding for the sequence SEQ ID NO 15 corresponding to the sequence coding for the 5 proteins (2 regulatory proteins and 3 resistance proteins), and also comprising the flanking sequences associated with these coding sequences, or comprising this sequence.

Also included in the framework of the invention is a sequence modified with respect to SEQ ID NO 15, characterized in that it lacks the flanking sequences. These flanking sequences are the sequences shown in the following pages and defined as follows: 1476 of the sequence shown in FIG. 5, between the bases 3347 and 3500 of the sequence shown in FIG. 5, 6168 and 7227 of the sequence shown in FIG. 5.

The sequence designated by SEQ ID NO 15 is also characterized by the fragment bearing the restriction sites in the following order:

The location of the regulatory proteins and the resistance proteins is shown in FIG. 3.

The inventors have identified upstream and downstream from the genes vanR, vanS, vanH, vanA and vanX, which are necessary for or associated with the expression of resistance to glycopeptides at a given level, genes coding for a transposase and a resolvase (upstream from the group previously mentioned) and genes vanY and vanZ, downstream from this group. The genes for the transposase and resolvase might be implicated in transposition functions and the vanY gene coding for a D,D-carboxy peptidase might be implicated in the metabolism of the peptidoglycan, and might contribute to resistance to the glycopeptides in E. faecium BM4147 even though vanR, vanS, vanH, vanA and vanX borne by a plasmid in a high number of copies, alone confer a high level of resistance.

Let it be noted that the sequence coding for the transposase (SEQ ID NO:18) is located on the (-) strand of the sequence ID NO 16 which codes for vanR, vanS, vanH, vanA, vanX, vanY, vanZ and the resolvase.

The invention relates not only to the DNA sequences identified in the list of the sequences but also to the complementary DNA sequences and the corresponding RNA sequences. The invention concerns in addition sequences which are equivalent to the former, either in terms of expression of proteins, polypeptides or their fragments described above, or in terms of the capacity to detect, for example by chain polymerization procedures, strains of Gram-positive bacteria exhibiting resistance to antibiotics of the glycopeptide family such as vancomycin or teicoplanin.

Recombinant sequences characterized in that they comprise one of the above nucleotide sequences also form part of the invention.

The invention also relates to a recombinant vector characterized in that it includes one of the above nucleotide sequences at a site inessential for its replication, under the control of regulatory elements likely to be implemented in the expression of the resistance to antibiotics of the glycopeptide family, in particular to vancomycin or teicoplanin in a defined host.

Particularly advantageous recombinant vectors for the implementation of the invention are the following vectors: pAT214 containing the EcoRV-SacII fragment of 1761 bp containing a nucleotide sequence coding for the VanA protein; in these vectors the sequences of the invention are advantageously placed under the control of promoters such as the lac promoter.

The invention also relates to a recombinant cell host containing a nucleotide sequence such as that previously described or a vector such as that described above under conditions which make possible the expression of resistance to antibiotics of the glycopeptide family, in particular resistance to vancomycin and/or this host being for example selected from the bacteria, in particular the Gram-positive cocci.

In certain applications it is also possible to use yeasts, fungi, insect or mammalian cells.

The invention also relates to a nucleotide probe characterized in that it is capable of hybridizing with a sequence previously described, this probe being labelled if necessary. These probes may or may not be specific for the proteins of resistance to glycopeptides.

Labels which can be used for the requirements of the invention are the known radioactive labels as well as other labels such as enzymatic labels or chemoluminescent labels.

Probes thus labelled may be used in hybridization tests in order to detect resistance to glycopeptides in Gram-positive bacteria. In this case, conditions of low stringency will be used.

Nucleotide probes according to the invention may be characterized in that they are specific in Gram-positive bacteria for the sequences coding for a resistance protein to the glycopeptides, in particular to vancomycin and/or teicoplanin these probes being in addition universal among these sequences.

By these specific probes is meant any oligonucleotide hybridizing with a nucleotide sequence coding for one of the proteins according to the invention, such as described in the preceding pages, and not exhibiting a cross hybridization reaction or amplification reaction (PCR) with sequences present in all of the sensitive strains.

The universal character of the oligonucleotide which can be used in PCR is defined by their capacity to promote specifically the amplification of a nucleotide sequence implicated in resistance in any one strain of Gram-positive bacteria, resistant to the antibiotics of the glycopeptide family.

The size of the nucleotide probes according to the invention may vary depending on the use desired. For the oligonucleotides which are used in PCR, recourse will be had to fragments of a length which is usual in this procedure. In order to construct probes, it is possible to take any part of the sequences of the invention, for example probe fragments of 200 nucleotides.

According to a particular embodiment of the invention, a nucleotide probe is selected for its specificity towards a nucleotide sequence coding for a protein necessary for the expression in Gram-positive bacteria of a high level of resistance to antibiotics of the glycopeptide family, in particular to vancomycin and teicoplanin.

As examples, useful probes may be selected from the intragenic part of the vanA gene.

Other useful probes for carrying out the invention are characterized by their universal character, according to the preceding definition, but are not specific for the resistance genes. They may also be used as primers in PCR, and are for example: ##STR3##

V1 and V2 hybridize with vanA and vanC and are capable of leading to the detection of proteins associated with resistance to glycopeptides in other micro-organisms.

Other particular probes of the invention have the specific character of a nucleotide sequence coding for a protein necessary for the expression in Gram-positive bacteria of a low level of resistance to antibiotics of the glycopeptide family, in particular to vancomycin in Gram-positive bacteria.

It should also be mentioned that oligonucleotide probes which might be derived from the sequence of the vanA gene coding for the VanA protein may be used indiscriminantly to detect high-level or low-level resistance.

In a particularly preferred manner, a probe of the invention is characterized in that it hybridizes with a chromosomal or non-chromosomal nucleotide sequence of a Gram-positive strain resistant to glycopeptides, in particular to vancomycin and/or teicoplanin, in particular in that it hybridizes with a chromosomal or non-chromosomal nucleotide sequence of a strain of Gram-positive cocci, for example an enterococcal strain and preferably E. faecium 4147 or E. gallinarum.

In order to distinguish strains with a high level of resistance from strains with a low level of resistance it is possible to carry out a hybridization test using conditions of high stringency.

The oligonucleotides of the invention may be obtained from the sequences of the invention by cutting with restriction enzymes, or by chemical synthesis according to the standard methods.

Furthermore, the invention relates to polyclonal or monoclonal antibodies, characterized in that they recognize the polypeptide(s) described above or an amino acid sequence described above.

These antibodies may be obtained according to standard methods for antibody production. In particular, in the case of the preparation of monoclonal antibodies, recourse will be had to the method of Kohler and Milstein according to which monoclonal antibodies are prepared by cell fusion between myeloma cells and mouse spleen cells previously immunized with a polypeptide or a composition according to the invention, in conformity with the standard procedure.

The antibodies of the invention can advantageously be used for the detection of the presence of proteins characteristic of resistance to the glycopeptides, in particular to vancomycin and teicoplanin.

Particularly useful antibodies are polyclonal or monoclonal antibodies directed against the protein VanA or VanC. Such antibodies advantageously make it possible to detect strains of bacteria, in particular Gram-positive cocci, exhibiting high-level resistance to the antibiotics of the glycopeptide family. If necessary, a step entailing lysis of the cells of the sample undergoing detection is performed prior to the placing in contact of the sample with the antibodies.

In order to carry out this detection, recourse will advantageously be had to antibodies labelled for example with a radioactive substance or other type of label.

Hence, tests for the detection in Gram-positive bacteria of resistance to the glycopeptides, in particular tests making use of the ELISA procedures, are included in the framework of the invention.

A kit for the in vitro diagnosis of the presence of Gram-positive strains, resistant to the glycopeptides, in particular to vancomycin and/or teicoplanin, these strains belonging in particular to the Gram-positive cocci for example enterococci, for example E. faecium or E. gallinarum is characterized in that it comprises: antigen-antibody type, tested.

Furthermore, the agents developed by the inventors offer the very useful advantage of being suitable for the development of a rapid and reliable test or kit for the detection of Gram-positive strains resistant to the glycopeptides by means of the polymerase chain reaction (PCR). Such a test makes it possible to improve the sensitivity of the existing tests which remain rather unreliable and, in certain cases, may make possible the detection of all of the representatives of the family of the genes coding for resistance proteins to the glycopeptides in Gram-positive bacteria.

The carrying out of a test by means of the method of amplification of the genes of these proteins is done by the PCR procedure or by the RPCR procedure (RPCR : abbreviation for reverse polymerase chain reaction).

The RPCR technique makes possible the amplification of the NH.sub.2 and COOH terminal regions of the genes it is desired to detect.

Some specific primers make it possible to amplify the genes of the strains with low-level resistance. These primers are selected, for example, from the sequence coding for the resistance protein VanA.

As examples, the following sequences can be used as primers for the preparation of probes for the detection of an amplification by means of the PCR or RPCR method. ##STR4##

X represents one of the bases A,T,C or G or also corresponds in all cases to inosine.

Naturally, the invention relates to the complementary probes of the oligonucleotides previously described as well as possibly to the RNA probes which correspond to them.

A kit for the in vitro diagnosis of the presence of strains of Gram-positive bacteria resistant to the glycopeptides, in particular resistant to vancomycin and/or teicoplanin these strains belonging in particular to the Gram-positive cocci, in particular that they are strains of enterococci, for example E. faecium or E. gallinarum, is characterized in that it contains: necessary, amplification of the desired sequence,

The invention also relates to a procedure for the in vitro detection of the presence of Gram-positive strains resistant to the glycopeptides, in particular to vancomycin and/or teicoplanin these strains belonging in particular to the family of the Gram-positive cocci, in particular in that they are strains of enterococci, for example E. faecium or E. gallinarum, characterized in that it comprises: strains in contact with a primer constituted by a nucleotide sequence described above, or any part of a sequence previously described, capable of hybridizing with a desired nucleotide sequence necessary for the expression of resistance to the glycopeptides, this sequence being used as matrix in the presence of the 4 different nucleoside triphosphates and a polymerization agent under conditions of hybridization such that for each nucleotide sequence which has hybridized with a primer, an elongation product of each primer complementary to the matrix is synthesized, latter then also being capable of behaving as a matrix, desired nucleotide sequences, sequences.

The detection of the elongation products of the desired sequence may be carried out by a probe identical with the primers used to carry out the PCR or RPCR procedure, or also by a probe different from these primers, this probe being labelled if necessary.

Details relating to the implementation of the PCR procedures may be obtained from the patent applications EP 0229701 and EP 0200362.

Other advantages and characteristics of the invention will become apparent in the examples which follow and from the figures.

FIG. 1: electrophoresis on SDS-polyacrylamide gel (SDS-PAGE) of the proteins of the membrane fractions line 1 and line 4, molecular weight standards; line 2, E. faecium BM4147 placed in culture in the absence of vancomycin; line 3, BM4147 placed in culture in the presence of 10 .mu.g/ml of vancomycin. The head of the arrow indicates the position of the VanA protein.

FIGS. 2A-2B:

FIG. 2A: Restriction maps of the inserts of the plasmids pAT213 and pAT214. The vector and the DNA insert are distinguished by light and dark segments, respectively. The open arrow represents the vanA gene.

FIG. 2B: Strategy for the nucleotide sequencing of the insert of 1761 bp in the plasmid pAT214. The arrows indicate the direction and extent of the sequencing reactions by the dideoxy method. The synthetic oligonucleotide primer (5' ATGCTCCTGTCTCCTTTC 3' OH; SEQ ID NO:27) is complementary to the sequence between the positions 361 and 378. Only the pertinent restriction sites are given.

FIG. 3: position of the sequences R, S, ORF1, ORF2, ORF3.

FIG. 4: representation of SEQ ID NO 15.

FIG. 5: representation of SEQ ID NO 15 and the corresponding protein (SEQ ID NOS:27,28 and 29).

FIG. 6: sequence of the vanA gene and the corresponding protein.

FIGS. 7a-76C:

FIG. 7a: Localization of the genes vanR, vanS, vanH, vanA, vanX, vanY, vanZ of the gene for the transposase and of the gene for the resolvase as well as the repeated reverse terminal sequences of 38 bp at the end of the transposon.

FIGS. 76A-76C: Mapping of the plasmids. (76A) Polylinker pAT29 and derivatives constructed in this study. The arrow labelled P2 indicates the position and orientation of the P2 promoter of aphA-3 (Caillaud et al., 1987, Mol. Gen. Genet. 207:509-513). (76B) Insert pAT80. The white rectangles indicate the DNA of pAT29 but they are not shown to scale. The rectangles terminating in an arrow indicate the coding sequences. The arrows shown in vertical and horizontal full lines indicate the position and orientation, respectively, of the apha-1 gene in the derivatives of pAT80. Restriction sites: Ac, AccI; B, BamHI; Bg, BglII; Bs, BssHII; E, EcoRI; H, HindIII; Hc, HincII; K, KpnI; P, PstI; S, SmaI; SI, SacI, SII, SacII; Sa, SalI; Sp, SphI; Xb, XbaI. (76C) Inserts in pAT86, pAT87, pAT88 and pAT89. The inserts are shown by full lines and the corresponding vectors are indicated in parentheses.

FIG. 8: nucleotide sequence of the transposon shown in FIG. 7 (SEQ ID NOS:16 and 30) and amino acid sequence of the corresponding proteins (SEQ ID NOS:2, 4, 6, 12, 14, 19 and 21). The nucleotide sequence is shown for the (+) strand (SEQ ID NO:16) and for the (-) strand (SEQ ID NO:90) (corresponding to the complementary sequence of the (+) strand for the positions 1 to 3189) on which the coding sequence of the transposase is located.

FIG. 9: Nucleotide sequence of the SacI-PstI fragment of 1347 bp of the plasmid pAT216 containing the vanC gene (SEQ ID NO:31). The numbering starts at the first base G of the SacI restriction site. The potential RBS sequence upstream from the initiation codon ATG of translation at position 215 is underlined. The STOP codon (TGA) is indicated by *. The region coding for the vanC and the deduced amino acid sequence are indicated in bold characters. Sequential overlapping clones were generated by restriction fragments of subcloning of pAT216 in the bacteriophage M13mp10 (Amersham, England). The universal primer (New England Biolabs Beverly Mass.) was used to sequence the insert in the recombinant phages. The sequencing was performed by the enzymatic dideoxy nucleotide method (Sanger et al., 1977 PNAS 74: 5463-5467) by using the T7 DNA polymerase (Sequenase US B CORP, Cleveland, Ohio) and .alpha.-.sup.35 S!dATP (Amersham, England). The reaction products were loaded onto 6% denaturing polyacrylamide gels.

FIG. 10: alignment of the amino acid sequences of VanC (SEQ ID NO:2), VanA (SEQ ID NO:4), DdlA (SEQ ID NO:32) and DdlB (SEQ ID NO:33). The identical (I) amino acids and the conservative (C) substitutions in the 4 sequences are indicated in the alignment. In order to classify the conservative substitutions, the amino acids were grouped as follows: RK, LFPMVI (SEQ ID NO:34), STQNC (SEQ ID NO:35), AGW, H, ED and Y. The regions of high homology corresponding to the domains 1, 2, 3 and 4 are underlined. The sequences corresponding to the peptides 1 and 2 are indicated by the arrows.

FIGS. 11A-11C: description of the oligonucleotides V1 (SEQ ID NO:9) and V2 (SEQ ID NO:10) (FIG. 11A): Amino acid sequence of the peptides 1 (SEQ ID NO:36) and 2 (SEQ ID NO:37) of VanA and of the D-Ala-D-Ala ligases (SEQ ID NO:36-39). The number of amino acids between the N-terminus and peptide 1, between the peptides 1 and 2 and the peptide 2 and the C-terminus is indicated. The identical amino acids between at least 2 of the 3 sequences are indicated in bold characters.

FIG. 11B: Target peptides (SEQ ID NOS:36-39) and deduced nucleotide sequence. X represents any base of the DNA. Peptide 2 in DdlB (SEQ ID NO:39) differs from the target peptide at 2 positions (*).

FIG. 11C: Nucleotide sequence of V1 and V2. Alternate nucleotides and deoxyinosine (I) which may correspond to any base in the DNA, were used at the positions at which the nucleotide sequences coding for the target peptides vary. The arrows indicate the direction of DNA synthesis. The oligonucleotides were synthesized by the methoxy-phosphoramidite method with a Biosystem DNA 380B machine (Applied Biosystem, Foster City, Calif.). The DNA was isolated from bacterial lysates by extraction with hexadecyl trimethyl ammonium bromide (Inst. biotechnologies, Inc., New Haven, Colo.) (Le Bouguenec et al., 1990, J. Bacteriol. 172:727-734) and used as matrix for the amplification by means of PCR with a controlled heating system "Intelligent Heating Block" IBH101 (Hybarid Ltd., GB) according to the description of Mabilat et al. (1990, Plasmid 23:27-34). The amplification products were revealed by electrophoresis on a 0.8% gel, after staining with ethidium bromide.

FIGS. 12A-12C: Inactivation by insertion of vanC. The vanC gene is shown by an open arrow and the internal EcoRI-HincII fragment of 690 bp is hatched. The DNA of pAT114 is shown by a thin line; the chromosomal DNA of PM4174 by a thick line; the arrows indicate the genes for resistance to the antibiotics: aphA-3 is the gene coding for the 3'-aminoglycoside phosphotransferase; erm is the gene coding for the ER.sup.R methyl transferase.

FIG. 12A: The plasmid pAT217 was constructed by litigation of the EcoRI-HincII fragment of pAT216 to the suicide vector pAT114 (Trieu-Cuot et al., 1991, Gene 106:21-27), digested with EcoRI and SmaI.

FIG. 12B: vanC region of the chromosomal DNA of BM4174.

FIG. 12C: vanC region after integration of pAT217.

FIG. 13: Southern blot analysis of the integration of pAT217 into the vanC gene of BM4174. (left hand side): Total DNA of BM4175 (line 2) and BM4174 (line 3) digested with EcoRI and resolved by means of electrophoresis on a 1% agarose gel. The DNA of the bacteriophage lambda digested with PstI was used as molecular mass standard (line 1). The DNA was transferred under vacuum to a Nytran membrane (Schleicher and Schul, Germany) by using a Trans-Vac TE80 apparatus (Hofer Scientific Instruments, San Francisco, Calif.) and bound to the membrane through the intermediary of UV light. The hybridization was carried out with the probe C (Middle) or the probe aphA-3 specific for pAT114 (Lambert et al., 1985, Annales de l'Institut Pasteur/Microbiol. 136(b): 135-150). (right hand side): the probes were labelled with .sup.32 P by nick translation. The molecular masses (kb) are indicated.

FIG. 14: alignment of the deduced amino acid sequences of VanS derived from E. faecium BM4147 (SEQ ID NO:40) and of PhoR (SEQ ID NO:41) and EnvZ (SEQ ID NO:42) from E.coli. The numbers on the left refer to the position of the first amino acid in the alignment. The numbers on the right refer to the position of the last amino acid of the corresponding line. The identical amino acids are placed in boxes. The dotted lines indicate gaps introduced in order to optimize their similarity. The dashes indicate the positions of the amino acid residues conserved in other HPK. The histidine residues in bold characters in section 1 are potential sites of autophosphorylation.

FIG. 15: alignment of the deduced amino acid sequences of VanR from E. faecium BM4147 (SEQ ID NO:43), OmpR (SEQ ID NO:44) and PhoB (SEQ ID NO:45) from E. coli as well as that of CheY from Salmonella typhimurium (SEQ ID NO:46). The numbers on the right indicate the position of the last amino acid of the corresponding line. The identical amino acids are placed in boxes. The dotted lines indicate the gaps introduced in order to optimize the homologies. The residues in bold characters correspond to the amino acids strongly conserved in the effector domains of other RR. The aspartic acid residue 57 of CheY is phosphorylated by the HPK associated with CheA. VanA Gene

Bacterial strains and plasmids

The origin of the plasmids used is given in the table below. Strain or plasmid Source or reference ______________________________________ Escherichia coli JM83             Messing (1979) AR1062           Rambach and Hogness (1977) JM103            Hannshan (1983) ST640            Lugtenberg and van Schijndel van-Dam (1973) Enterococcus faecium BM4147           Leclercq et al (1988) Plasmid pUC18    Norrander et al (1983) pAT213           Brisson-Noel et al (1990) pAT214           Described in this text ______________________________________

Enterococcus faecium BM4147 was cultivated in 500 ml of heart-brain broth (BHI broth medium) until the optical density (OD.sub.600) reached 0.7. Induction was effected with 10 .mu.g/ml of vancomycin (Eli Lilly Indianapolis Ind). The subsequent steps were performed at 4.degree. C. The cells were recovered by centrifugation for 10 minutes at 6000 g, washed with a TE buffer (0.01M TRIS-HCl, 0.002M EDTA, pH 7.0) and lysed by glass beads (100 .mu.m in diameter) in a Braun apparatus for 2 minutes. The cell debris were separated by centrifugation for 10 minutes at 6000 g. The membranes were collected by centrifugation for 1 hour at 65000 g and resuspended in 0.5 ml of TE buffer.

Plasmids were introduced by transformation into the strain E. coli AR1062 prepared in the form of bacterial vesicles. The bacterial vesicles were recovered on sucrose gradients and the proteins were labelled with 50 .mu.Ci of .sup.35 S!-L-methionine (Amersham, Great Britain) according to the method of Rambach and Hogness (1977, P.N.A.S. USA, 74; 5041-5045). coli

E. coli JM83 and strains derived from it were placed in culture in BHI medium until an optical density (OD.sub.600) of 0.7 was attained, washed and suspended in a TE buffer. The cell suspension was treated by sonication (ultrasound) for 20 seconds at doses of 50 W in a cell fragmentation apparatus in a Branson B7 sonication apparatus and the intact cells were removed by centrifugation for 10 minutes at 6000 g. The supernatant was fractionated into membrane and cytoplasmic fractions by means of centrifugation for 1 hour at 100,000 g.

The proteins from the bacterial fractions were separated by means of SDS-PAGE on linear gradients of polyacrylamide gels (7.5% -15%) (Laemmli 1970, Nature 227: 680-685). The electrophoresis was carried out for 1 hour at 200 V, then for 3 hours at 350 V. The gels were stained with Coomassie blue. The proteins of the extracts were separated on 10% polyacrylamide gels and visualized by means of autoradiography. Sequence

The proteins of the membrane fractions of an induced culture of E. faecium BM4147 were separated by means of SDS-PAGE. The gel was electrotransferred for 1 hour at 200 mA to a polyvinylidene difluoride membrane (Immobilon Transfer, Millipore) by using a transfer apparatus (Electrophoresis Unit LKB 2117 Multiphor II) in accordance with the instructions of the manufacturer. The transferred proteins were stained with Ponceau red. The portion of membrane bearing the protein of interest was excised, centered on a Teflon filter and placed in the cartridge of a sequencer (Sequencer Applied Biosystems model 470A). The protein was sequenced by means of the automated Edman degradation (1967, Eur. J. Biochem. 1; 80-81).

The plasmid pAT213 (Brisson-Noel et al., 1990, Antimicrob. Agents Chemother., 34; 924-927) consists of a EcoRI fragment of DNA of 4.0 kb of the enterococcal plasmid pIP816 cloned at the EcoRI site of a Gram-positive-Gram-negative shuttle vector pAT187 (Trieu-Cuot et al., 1987, FEMS Microbiol. Lett. 48; 289-294). In order to construct pAT214, the EcoRV-SacII DNA fragment of 1761 bp of pAT213 was purified, treated with the Klenow fragment of the DNA polymerase I of E. coli and ligated to the DNA of pUC18 which had previously been digested with SmaI and dephosphorylated (FIG. 2). The cloning (Maniatis et al., 1982 Cold Spring Harbor Laboratory Press) was carried out with restriction endonucleases (Boehringer Mannheim and Pharmacia), with the T4 DNA ligase (Pharmacia) and alkaline phosphatase (Pharmacia) according to the instructions of the manufacturer.

The DNA restriction fragments were subcloned in the polylinker of the replicative forms of the derivatives mp18 and mp19 of the bacteriophage M13 (Norrander et al., 1983, Gene 26; 101-106), obtained from Pharmacia P-L Biochemicals. E.coli JM103 was transfected with recombinant phages and the single-stranded DNA was prepared. The nucleotide sequencing was carried out by the enzymatic di-deoxy nucleotide method (Sanger et al., 1977, P.N.A.S. USA 74; 5463-5467) by using a T7 DNA polymerase (Sequenase, United States Biochemical Corporation, Cleveland, Ohio) and .alpha.-.sup.35 S!dATP (Amersham, Great Britain). The reaction products were revealed on 6% polyacrylamide gels containing a denaturing buffer.

The complete DNA sequence was assembled by using the computer programs DBCOMP and DBUTIL (Staden, 1980, Nucleic Acids Res 8; 3673-3694). The protein data bank PSEQIP of the Pasteur Institute was screened using an algorithm developed by Claverie (1984, Nucleic Acids Res 12; 397-407). The alignments between the pairs of amino acid sequences were constructed using the algorithm of Wilbur et al (1983, P.N.A.S. USA 80; 726-730). The statistical significance of the homology was evaluated with the algorithm of Lipman and Pearson (1985, Science 227; 1435-1440).

For each comparison 20 amino acid sequences were used to calculate the mean values and the standard deviations of the random results.

The plasmids were introduced by transformation into E.coli ST640, a temperature-sensitive mutant with an unmodified D-ala-D-ala ligase (Lugtenberg et al 1973, J. Bacteriol 110; 26-34). The transformants were selected at 30.degree. C. on plates containing 100 .mu.g/ml of ampicillin and the presence of the plasmid DNA of the expected size and the restriction maps were verified. Single colonies grown at 30.degree. C. in BHI broth medium containing ampicillin were placed on a BHI agar medium containing both 100 .mu.g/ml of ampicillin and 50 .mu.M of isopropyl-1-thio-.beta.-D-galacto-pyranoside (IPTG) and the plates were incubated at a permissive temperature of 30.degree. C. and at a non-permissive temperature of 42.degree. C. The complementation test was considered to be positive if the colonies were present after 18 hours of incubation at 42.degree. C.

The membrane fractions of the E. faecium BM4147 cells placed in culture, on the one hand, under conditions of induction, and, on the other, in the absence of induction, were analysed by means of SDS-PAGE. The sole difference which could be detected,related to the exposure to sub-inhibitory concentrations of vancomycin, was the marked intensification of a band which corresponded to a protein of an estimated molecular weight of about 40 kDa. In the induced cells and in the non-induced cells, the protein band represents the same protein because this band is absent from membranes of a derivative of BM4147 which has lost the pIP816 plasmid. The inducible protein, designated as VanA, was purified after SDS-PAGE and automated Edman degradation was carried out on a 50 pmol. sample. Nine amino acids of the N-terminal sequence of VanA were identified: Met Asn Arg Ile Lys Val Ala Ile Leu (SEQ ID NO:47).

The insert of 4.0 kb of the plasmid pAT213 bears the determinant for resistance to the glycopeptides of E. faecium BM4147. Various restriction fragments of this insert were subcloned in pUC18 and the recombinant plasmids specific for vanA in E. coli were identified by SDS-PAGE analysis of the proteins of the cytoplasmic and membrane fractions or of the extracts of the bacterial vesicles. This approach was used since E. coli is intrinsically resistant to the glycopeptide. The EcoRV-SacII insert of the pAT214 plasmid (FIG. 2) codes for a unique polypeptide of 40 kDa which migrates together with VanA, derived from the membrane preparations of E. faecium BM4147. Coding Sequence

The nucleotide sequence of the EcoRV-SacII insert of 1761 bp in pAT214 was determined on both strands of the DNA according to the strategy described in FIG. 2. The location of the termination codons (TGA, TAA, TAG) in three reading frames on each DNA strand showed the presence of a unique open reading frame (ORF) which was sufficiently long to code for the VanA protein. This reading frame ORF is located between the TAA codon at position 281 and the TAG codon at position 1406. The amino acid sequence deduced for ORF was compared with that of the N-terminus of VanA. The nine amino acids identified by protein sequencing are encoded in the nucleotide sequence beginning with the ATG (methionine) codon at position 377 (FIG. 3). This codon for the initiation of translation is preceded by a sequence (TGAAAGGAGA (SEQ ID NO:48), characteristic of a ribosomal binding site (RBS) in Gram-positive bacteria which is complementary to the 8 bases of the rRNA of the 16S subunit of Bacillus subtilis in its sequence (3'OH UCUUUCCUCC (SEQ ID NO:49) 5') (Moran et al., 1982, Mol. Gen. Genet. 186; 339-346). In this ORF, there is no other ATG or GTG initiation codon between the positions 281 and 377. The sequence of 1029 bp which extends from the ATG codon at position 377 to the TGA codon at position 1406 codes for a protein containing 343 amino acid residues. The calculated molecular weight of this protein is 37400 Da, which is in agreement with the estimation of 40 kDa obtained by SDS-PAGE analysis. Enzymes

The screening of the protein data bank PSEQIP has shown the existence of a sequence homology between VanA and the D-ala-D-ala ligases of E.coli (ECOALA, Robinson et al., 1986, J. Bacteriol. 167; 809-817) and of Salmonella typhimurium (DALIG, Daub et al., 1988, Biochemistry 27; 3701-3708). The calculated percentage of homology between pairs of proteins was included between 28% and 36% for the identical amino acids and between 48% and 55% by taking into consideration homologous amino acids. VanA (SEQ ID NO:4) and DALIG are more closely related. The statistical significance of these similarities wa evaluated by aligning VANA and sequences containing the same composition of amino acids as DALIG or ECOALA (Lipman and Pearson, 1985, Science 227; 1435-1440).

The E.coli strain ST640 is a thermosensitive mutant exhibiting a deficient D-ala-D-ala ligase activity (Lugtenberg et al., 1973, J. Bacteriol. 113: 96-104). The plasmids pUC18 and pAT214 were introduced into E.coli ST640 by transformation. The strains ST640 and ST640 (pUC18) grew normally only at the permissive temperature (30.degree. C.) whereas E.coli ST640 (pAT214) grew both at the permissive temperature and at the non-permissive temperature (42.degree. C.).

This test shows that VANA is functionally related to the D-Ala-D-Ala ligases in E.coli and is probably capable of catalysing the same ligation reaction as DALIG. Synthesis of Depsipeptides of the Precursor of Peptidoglycans

The restriction fragments of pIP816 (Tra.sup.-, Mob.sup.+, Vm.sup.r) were cloned in derivatives of the vector pAT29 which constitutes a shuttle vector between the Gram-positive and Gram-negative bacteria (oriR pAM.beta.1, oriR pUC, oriT RK2, spc, lacZ) (Trieu-Cuot et al., 1990, Nucleic Acids Res. 18:4296). This vector was constructed by the inventors and used to transform the strain E.coli JM103 ((lac-proAB), supE, thi, strA, sbcB15, endA, hspR4, F traD36, proAB, lacI.sup.q, lacZ M15) (Messing et al., 1983, Methods Enzymol. 101:20-78). The plasmid DNA was prepared by an alkaline lysis protocol on a small scale (Sambrook et al., 1982, Molecular cloning, a laboratory manual. Cold Spring Harbor laboratory, Cold Spring Harbor N.Y.) and introduced by electroporation (Cruz-Rodz A. L. et al., 1990, Mol. Gen. Genet. 224:152-154) in E.faecalis JH2-2 (Fus.sup.R, Rif.sup.R) (Jacob A. E. et al., 1974, J. Bacteriol. 117: 360-372), by using a Gene Pulser apparatus (Bio-Rad Laboratories, Richmond, Calif.). The restriction profiles of the purified plasmids from E. faecalis and E. coli were compared in order to detect possible rearrangements of DNA.

The integrative plasmid pAT113 (Mob.sup.+, Em.sup.R, Km.sup.R, oriR PACYC184, attTn1545, LacZ ) (Trieu-Cuot et al., Gene 106:21-27) carries the joined ends of the transposon Tn1545. This vector does not replicate in Gram-positive bacteria but is integrated into the chromosome of the host by illegitimate recombination mediated by the integrase of Tn1545 or of Tn916 (Trieu-Cuot et al. previously mentioned). The integrative plasmids were introduced into E. faecalis BM4148 (strain JH2-2::Tn916) by means of electroporation. This strain is modified by the transposon Tn917 described by Franque A. E. et al. (1981, J. Bacteriol. 145:494-502).

The cultures were grown in brain-heart broth (BHI--Brain Heart Infusion Broth) or on agar at 37.degree. C. The method of Steers et al (Antibiot. Chemother. Basel. 9:307-311) was used to determine the minimal inhibitory concentrations (MICs) of the antibiotics on a Mueller-Hinton gelose agar medium.

The cleavage of DNA with restriction endonucleases (Boehringer Mannheim and Pharmacia), the purification of the DNA restriction fragments from agarose gels, the conversion of the cohesive ends to blunt ends with the Klenow fragment of the DNA polymerase I of E.coli (Boehringer Mannheim), the dephosphorylation of the ends of the DNA with calf intestinal phosphatase (Boehringer Mannheim), the ligation of the DNA fragments with the T4 DNA ligase (Amersham) were carried out according to the standard methods of Sambrook et al (1982, Molecular Cloning, a Laboratory Manual. Cold Spring Harbor Laboratory. Cold Spring Harbor N.Y.).

The origin of the vectors and the inserts used for the recombinant plasmids constructed here is the following: the cat gene for chloramphenicol acetyltransferase of the plasmid pC194 of Staphylococcus aureus (Horinouchi et al., 1982, J. Bacteriol. 150:815-825) was inserted between the PstI and SphI restriction sites of the shuttle vector pAT29. Amplification by means of the polymerase chain reaction was carried out by means of primers A1 and A2 which were synthesized by the methoxy phoshoramidite method (Mabilat et al., 1990, Plasmid 23:27-34). The sequence of the primer A1 (SEQ ID NO:50) (5' GCTGCAGATAAAAATTTAGGAGG) is composed of a PstI recognition site (underlined) and 18 bases (positions 6 to 23) of pC194 which include the ribosomal binding site (RBS ; AGGAGG positions 18 to 23) of the cat gene. The sequence of the primer A2 (SEQ ID NO:51) (5' CGCATGCTATTATAAAA GCCAGTC) contains the SphI cleavage site (underlined) and is complementary (positions 8 to 24) to 17 bases at the 3' end of the cat gene. The triplet ATT at positions 9 to 11 corresponds to the TAA stop codon of cat. The DNA fragments amplified with the primers A1 and A2 hence consist of an open reading frame (orf) and a ribosomal binding site for CAT (positions 1234 to 1912 according to the numbering of Horinouchi et al. (1982, J. Bacteriol. 150:815-825) flanked by the PstI and SphI sites. The position 1234 is located at the interior of the loop of the secondary structure of the mRNA which blocks translation in the absence of chloramphenicol. Thus, the amplified sequence does not contain the cat promoter nor the sequence complementary to the RBS which is essential for the regulation of translation Ambulos, N. P. et al., 1984, Gene 28:171-176). the P2 promoter of the aphA-3 gene of the enterococcal plasmid pJH1 (Caillaud et al., 1987, Mol. Gen. Genet. 207:509-513) was inserted between the EcoRI and SacI restriction sites of pAT78. of pIP816 was inserted between the BamHI and XbaI sites of pAT78. The resulting plasmid, designated as pAT80 was partially digested with HincII and ligated with the EcoRV fragment containing a gene related to the apha-I gene of the transposon Tn903 (Oka A. et al., 1981, J. Mol.

Biol. 147:217-226. This fragment contains the aphA-I gene which codes for the 3'aminoglycoside phosphotransferase of type I conferring resistance to kanamycin. The insertion of aphAI was carried out at three different sites in pAT80, generating the plasmids pAT81, pAT83 and pAT85. The cassettes BamHI and EcoRI containing aphA-I were inserted at the BamHI (to form the plasmid pAT84) and EcoRI (to form the plasmid pAT82) sites of pAT80. constructed by cloning the EcoRI-SacII fragment of 2.803 bp of pAT80 coding for VanH and VanA at a SmaI site of pAT79. pAT87 was obtained by inserting the EcoRI-XbaI fragment of 3.4 kb of pAT80 upstream from the cat gene of the detection vector of promoter pAT78. The plasmid pAT88 resulted from the ligation of pAT78 digested with EcoRI and BamHI to the EcoRI-BamHI fragment of 1.731 bp of pAT80. The BglII-AccI fragment (positions 1 to 2356) of pAT80 was inserted into the polylinker of the integrative vector pAT113, generating pAT89.

The DNA restriction fragments were subcloned in a polylinker of replicative derivatives of the bacteriophage M13, these derivatives being called mp18 and mp19 (Norrander et al., 1983, Gene 26:101-106). E.coli JM103 was transfected with the recombinant phages and a single-stranded DNA was prepared. The sequencing of the nucleotides was carried out according to the conditions described by Sanger et al. (Proc. Natl. Acad. Sci. USA, 1977, 74:5463-5467) by using the modified T7 DNA polymerase (Sequenase, United States, Biochemical Corporation Cleveland Ohio) and .alpha.-.sup.35 S!dATP (Amersham). The reaction products were resolved on gradient gels of polyacrylamide in a 6% buffer.

The JH2-2 derivatives of E. faecalis were grown to an optical density OD.sub.600 of 0.7 in a BHI broth supplemented with spectinomycin (300 .mu.g/ml). The cells were treated with lysozyme, lysed by sonication and the cell debris were centrifuged for 45 minutes at 100,000 g according to the description given by Courvalin et al. (1978, Antimicrob. Agents Chemother. 13:716-725). The formation of 5-thio-2-nitrobenzoate was measured at 37.degree. C. in the presence and in the absence of chloramphenicol and the specific CAT activity was expressed in micromole per minute and per milligram of proteins (Shaw et al., 1975, Methods Enzymol. 43:737-755).

The vanH and vanA genes of pIP816 were cloned in a plasmid pAT79 under the control of the heterologous promoter P2 (Caillaud et al., 1987, Mol. Gen. Genet. 207:509-513) and the plasmid pAT86 formed did not confer resistance to vancomycin on the strain E. faecalis JH2-2. These genes are thus not sufficient for the synthesis of peptoglycan in the absence of the antibiotic. Different restriction fragments of pIP816 were cloned in the vector pAT78. The BglII-XbaI fragment of 5.5 kb of pAT80 is the smallest fragment obtained which conferred resistance to vancomycin.

The sequence of the insert in pAT80 was determined on both strands of the DNA from the BglII site to the ATG initiation codon for the translation of VanH. Two open reading frames (orf) were detected within the sequence of 2475 bp: the first open reading frame extends from the nucleotide 386 to the nucleotide 1123; at position 431 a sequence characteristic of the RBS sequences in Gram-positive bacteria is found, 6 base pairs upstream from the ATG initiation codon for translation (TGAAAGGGTG (SEQ ID NO:52)); the other initiation codons for translation in this orf are not preceded by this type of sequence. The sequence of 693 bp extending from the ATG codon at position 431 to the TAA codon at position 1124 is capable of coding for a protein of 231 amino acids with a molecular mass of 26,612 Da which is designated as VanR.

In the case of the second open reading frame (from nucleotide 1089 to nucleotide 2255) the amino acid sequence deduced from the first initiation codon in phase (TTG at position 1104) would code for a protein of 384 amino acids having a molecular mass of 43,847 Da and designated as VanS. The TTG codon at position 1116 and the ATG codon at position 1164 are in-phase initiation codons for translation preceded by sequences with low complementarity with the 3'OH terminus of the 16S sub-unit of the rRNA of B. subtilis (GGGGGGTTGG-N8-TTG (SEQ ID NO:53) and AGAACGAAAA-N6-ATG (SEQ ID NO:54), respectively).

Between the last codon of vanS and the initiation codon ATG for the translation of vanH a sequence of 217 bp is to be observed which contains a repeated reverse sequence of 17 bp. This sequence does not function as a terminator of strong transcription.

The comparison of the sequences obtained with data bases has shown that the conserved amino acid residues identified by Stock et al. (1989, Microbiol. Rev. 53:450-490) in the kinase domain of 16 HPK (Histidine Protein Kinase) were detected in the C-terminal part of VanS (SEQ ID NO:14). VanS possesses two groups of hydrophobic amino acids in the N-terminal region. The histidine residue 164 of VAnS is aligned with the residue His216 of PhoR (SEQ ID NO:41) (Makino et al., 1986, J. Mol. Biol. 192: 549-556) and His 243 of EnvZ (SEQ ID NO:42) (Comeau et al., 1985, 164:578-584) which are presumed sites of autophosphorylation in these proteins.

Similarly, the amino acids 1 to 122 of VanR (SEQ ID NO:12) exhibit similarities with the effector domains of response regulators RR. The aspartic acid 53 of VanR might be a phosphorylation site because this residue is aligned with Asp 57 of Che Y (SEQ ID NO:46) which is phosphorylated by HPK associated with CheA and corresponds to an invariant position in other proteins of the RR type (Stock et al previously mentioned). VanR might belong to the sub-class OmpR-PhoB of RR which activates the initiation of transcription mediated by the RNA polymerase containing the 70S factor of E.coli (Stock et al. previously mentioned).

Cassettes of resistance to kanamycin inserted in the group of van genes in the plasmid pAT80 have shown the following: the insertion in vanR suppresses resistance to vancomycin and chloramphenicol; VanR is an activator of transcription necessary for the expression of the genes for resistance to vancomycin. The inactivation of vanS leads to a two-fold reduction of the minimal inhibitory concentration (MIC) of chloramphenicol and to a three-fold reduction of the specific CAT activity but the minimal inhibitory concentration of vancomycin remains unchanged. Hence, VanS is necessary to produce a high level of transcription of the genes for resistance to vancomycin although it is not required for the expression of the phenotype of resistance to vancomycin.

Derivatives of pAT80 bearing insertions in vanH (pAT83), vanA (pAT84) or in the region 1.0 kb downstream from vanA (pAT85) have made it possible to obtain resistance to chloramphenicol but not to vancomycin. This dissociated phenotype corresponds to the inactivation of genes coding for enzymes which synthesize the depsipeptide precursors necessary for the assembly of the bacterial cell walls in the presence of vancomycin.

Downstream from the vanA gene the presence of an inactivated orf has been detected in pAT85 in the region of the sequence of 365 bp after the TGA codon of vanA and before the SacII site and this orf contains an in-phase ATG initiation codon preceded by a RBS-like sequence. This sequence codes for a protein necessary for resistance to the glycopeptide, designated as VanX and which comprises maximally about 330 amino acids.

The integrative plasmid pAT89 coding for VanR and VanS was introduced into the chromosome of E. faecalis BM4138. The plasmid pAT87 bearing the genes vanH, vanA and vanX cloned upstream from the cat gene lacking the promoter for pAT78 conferred resistance to vancomycin on this strain but not to E. faecalis JH2-2. The level of expression of the cat gene of pAT87 in the strains BM4138::pAT89 and JH2-2 indicated that VanR activates the transcription of the reporter gene localized at the 3' end of the group of van genes. Similar levels of CAT synthesis were observed for pAT88 which bears a transcription fusion between the 5' parts of vanA and the cat gene. These results show that in E. faecalis BM4138::pAT89 (pAT87) VanR and VanS encoded in the chromosome activate in a trans manner the transcription of vanA, vanH and vanX of pAT87 making possible the production of resistance to vancomycin.

Moreover, it has been observed that the expression of the gene was essentially constitutive when vanR and vanS were borne by a multicopy plasmid pAT80 and weakly inducible by vancomycin when the genes for the regulatory proteins were present on the chromosome of the host. gallinarum BM4174

Definition and use of universal primers for the amplification of genes coding for D-Ala-D-Ala ligases and related proteins implicated in resistance to vancomycin

The protein VanA necessary for the expression of a high level of resistance to the glycopeptides in E. faecium BM4147 shares a similarity of about 28 to 36% as regards its amino acids with the D-Ala-D-Ala ligases of E.coli but possesses a different substrate specificity from that of these ligases. Peptides designated as 1 and 2 which are conserved in the sequences of the DdlA and DdlB ligases (Zawadzke, 1991 Biochemistry 30:1673-1682) of E.coli and in the protein VanA were selected in order to synthesize universal primers intended to amplify internal fragments of genes coding for D-Ala-D-Ala ligases or related enzymes. The peptide targets GEDG(S/T) (I/L)QG and NT(I/L)PGFT were translated back as is shown in FIG. IV.1 in order to obtain degenerate oligonucleotides V1 and V2. As the peptides 1 and 2 of VanA, DdlA and DdlB are separated by amino acid sequences of similar length, the predicted size for the amplification product was about 640 bp.

Amplification by means of PCR with the DNA of E.coli JM83 and of E. faecium BM4147 made it possible to amplify products corresponding to the expected size which have then been purified and cloned in the bacteriophage M13mp10 (Norrander et al., 1983, Gene 26:101-106). The sequencing of the insert obtained with E.coli JM83 has shown that the product of PCR was an internal fragment of dd1A. A probe generated starting from a recombinant phage obtained with the amplification fragment of BM4147 was used for the Southern blot analysis of a DNA of BM4147 and BM4147-1 which is a derivative of BM4147 sensitive to vancomycin and which lacks the plasmid pIP816 (Leclercq et al., 1988, N. Engl. J. Med. 319:157-161). The probe hybridized with the EcoRI DNA fragment of 4 kb from BM4147 but not with the DNA from E. faecium BM4147-1. As the vanA gene is borne by the EcoRI fragment of 4 kb from pIP816, these results indicate that the primers also make possible the amplification of a part of vanA. Thus the oligonucleotides V1 and V2 may amplify fragments of genes coding for different proteins related to the D-Ala-D-Ala ligases, and may do this in different species.

Amplification by means of PCR was carried out on the total DNA of E. gallinarum BM4174 and the amplification product obtained of about 640 bp was cloned in the bacteriophage M13mp10. The single-stranded DNA isolated from the recombinant phage was used to construct a probe C (Hu et al., 1982, Gene 17:2171-2177). In Southern analysis the probe hybridized with a PstI fragment of 1.7 kb from BM4174 but not with the DNA of BM4147 and BM4147-1.

The DNA of BM4174 was digested with PstI and fragments of 1.5 and 2 kb were purified by electrophoresis on agarose gel and cloned in pUC18 (Norrander et al., 1983, mentioned previously). The recombinant plasmids were introduced into E.coli JM83 by transformation and screened by hybridization on colonies (Sambrook et al., 1989, Molecular cloning, a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.) by using the probe C. A homology was detected with a transformant harbouring a plasmid called pAT216 which contained a PstI insert of 1.7 kb. The sequence of the SacI-PstI part of 1347 bp of the insert of pAT216 was determined on both strands of the DNA. The location of the termination codons in the three reading frames of each strand of DNA revealed the presence of an ORF phase located between the TGA codons at positions 47 and 1244. The initiation codon of transcription ATG at position 215 is preceded by a sequence GAAAGGAAGA characteristic of the RBS sequences complementary to the RNA of the 16S subunit of B. subtilis (Moran et al., 1982, Mol. Gen. Genet. 186:339-346). The sequence of 1029 bp which extends from the ATG codon at position 215 to the TGA codon at position 1244 might code for a protein of 343 amino acids having a calculated molecular mass of 37504 Da designated as VanC. A sequence homology was detected between VanC, VanA and the D-Ala-D-Ala ligases of E.coli. In particular, four domains of strong homology previously found between VanA and the D-Ala-D-Ala ligases of the enterobacteria are also present in VanC. The percentage of identical amino acids calculated for these proteins taken two at a time varied between 29 and 38%. The alignment of the four sequences revealed the presence of 57 invariant amino acids which include the conserved residues of the peptides 1 and 2 used to define the oligonucleotide probes V1 and V2.

In order to evaluate the contribution of vanC to resistance to vancomycin in E. gallinarum BM4174, the vanC gene was inactivated by insertion. A EcoRI-HincII fragment of 690 bp, internal to vanC was cloned in pAT114 which does not replicate in Gram-positive bacteria. The resulting pAT217 plasmid was introduced into BM4174 by electroporation (Cruz-Rodz et al., 1990, Mol. Gen. Genet. 224:152-154) and the clones supposed to result from a homologous recombination leading to the integration of pAT217 into vanC were selected on erythromycin. The clone BM4175 was compared with BM4174 by Southern hybridization using the probe C and aphA-3 specific for pAT114. The two probes hybridized with the EcoRI fragment of 8.6 kb from BM4175. The probe C hybridized with a fragment of 2.5 kb from BM4174 whereas no signal was observed with the probe aphA-3. The results indicate that the plasmid pAT217 of 6.1 kb was integrated into the vanC gene. The determination of the minimal inhibitory concentration of vancomycin for BM4174 (16 mg/l) and BM4175 (2 mg/l) indicated that the inactivation by insertion in vanC abolishes resistance to vancomycin.

VanC is thus required for resistance to vancomycin. It may thus be supposed that this protein synthesizes a dipeptide or a depsipeptide which is incorporated into the precursors of peptido-glycans and is not recognized by vancomycin.

The sequences which are the object of the invention are given in the following pages after the list of the sequences containing the description of these sequences. In this list of the sequences, the proteins are identified with respect to the position of the nucleotide bases corresponding to the amino acids of the extremities of the proteins.

(contained in the sequences I (Ia, Ib), II presented below or in the sequence shown in FIG. 5).

Amino acid sequences to the amino acid sequence of the open reading frame No. 3, starting at the base 3501 and terminating at the base 4529, containing the sequence coding for the vanH gene between the bases 3564 and 4529 with respect to the sequence shown in FIG. 5 or corresponding to the sequence between the positions of the nucleotides 6018 and 6983 of the sequence Ia. amino acid sequence of the open reading frame No. 1, starting at the base 4429 and terminating at the base 5553 with respect to the sequence shown in FIG. 5 or corresponding to the sequence between the positions of the nucleotides 6977 and 7807 of the sequence Ia. to the amino acid sequence of the open reading frame No. 3, starting at the base 5526 and terminating at the base 6167 with respect to the sequence shown in FIG. 5 or corresponding to the sequence between the positions of the nucleotides 7816 and 8621 of the sequence Ia. the amino acid sequence of the open reading frame No. 1, starting at the base 1477 and terminating at the base 2214 with respect to the sequence shown in FIG. 5 or corresponding to the sequence between the positions of the nucleotides 3976 and 4668 of the sequence Ia. amino acid sequence of the open reading frame No. 2, starting at the base 2180 and terminating at the base 3346 with respect to the sequence shown in FIG. 5 or corresponding to the sequence between the positions of the nucleotides 4648 and 5800 of the sequence Ia. included between the nucleotides 150 and 3112 of the sequence Ib. between the positions of the nucleotides 3187 and 3759 of the sequence Ia. positions of the nucleotides 9046 and 9960 of the sequence Ia. positions of the nucleotides 10116 and 10598 of the sequence Ia.

Nucleotide sequences proteins as well as the flanking sequences, shown in FIG. 5. proteins as well as the flanking sequences and starting at the base 3501 and terminating at the base 6167, shown in FIG. 5. terminating at the base 5553 of the sequence shown in FIG. 5, or corresponding to the nucleotide sequence situated between the nucleotides 6977 and 7807 of the sequence Ia. starting at the base 3501 and terminating at the base 4529, in particular the sequence vanH, the coding sequence of which is located between the bases 3564 and 4529 of the sequence shown in FIG. 5, or corresponding to the nucleotide sequence situated between the nucleotides 6018 and 6983 of the sequence Ia. starting at the base 5526 and terminating at the base 6167 of the sequence shown in FIG. 5, or corresponding to the nucleotide sequence situated between the nucleotides 7816 and 8621 of the sequence Ia. resolvase, vanR, VAnS, VanH, VanA, VanX, VanY and VanZ and containing the repeated reverse sequence of 38 bp at its N- and C-termini and corresponding to the sequence Ia. and terminating at the base 3112 of the sequence Ib. and terminating at the base 3759 of the sequence Ia. terminating at the base 9960 of the sequence Ia. terminating at the base 10598 of the sequence Ia. the protein VanC. starting at the base 1 and terminating at the base 10851. 3976 and terminating at the base 4668 of the sequence Ia. 4648 and terminating at the base 5800 of the sequence Ia. ##STR5## SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 54 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 966 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..966 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: ATGAATAACATCGGCATTACTGTTTATGGATGTGAGCAGGATGAGGCA48 MetAsnAsnIleGlyIleThrValTyrGlyCysGluGlnAspGluAla 151015 GATGCATTCCATGCTCTTTCGCCTCGCTTTGGCGTTATGGCAACGATA96 AspAlaPheHisAlaLeuSerProArgPheGlyValMetAlaThrIle 202530 ATTAACGCCAACGTGTCGGAATCCAACGCCAAATCCGCGCCTTTCAAT144 IleAsnAlaAsnValSerGluSerAsnAlaLysSerAlaProPheAsn 354045 CAATGTATCAGTGTGGGACATAAATCAGAGATTTCCGCCTCTATTCTT192 GlnCysIleSerValGlyHisLysSerGluIleSerAlaSerIleLeu 505560 CTTGCGCTGAAGAGAGCCGGTGTGAAATATATTTCTACCCGAAGCATC240 LeuAlaLeuLysArgAlaGlyValLysTyrIleSerThrArgSerIle 65707580 GGCTGCAATCATATAGATACAACTGCTGCTAAGAGAATGGGCATCACT288 GlyCysAsnHisIleAspThrThrAlaAlaLysArgMetGlyIleThr 859095 GTCGACAATGTGGCGTACTCGCCGGATAGCGTTGCCGATTATACTATG336 ValAspAsnValAlaTyrSerProAspSerValAlaAspTyrThrMet 100105110 ATGCTAATTCTTATGGCAGTACGCAACGTAAAATCGATTGTGCGCTCT384 MetLeuIleLeuMetAlaValArgAsnValLysSerIleValArgSer 115120125 GTGGAAAAACATGATTTCAGGTTGGACAGCGACCGTGGCAAGGTACTC432 ValGluLysHisAspPheArgLeuAspSerAspArgGlyLysValLeu 130135140 AGCGACATGACAGTTGGTGTGGTGGGAACGGGCCAGATAGGCAAAGCG480 SerAspMetThrValGlyValValGlyThrGlyGlnIleGlyLysAla 145150155160 GTTATTGAGCGGCTGCGAGGATTTGGATGTAAAGTGTTGGCTTATAGT528 ValIleGluArgLeuArgGlyPheGlyCysLysValLeuAlaTyrSer 165170175 CGCAGCCGAAGTATAGAGGTAAACTATGTACCGTTTGATGAGTTGCTG576 ArgSerArgSerIleGluValAsnTyrValProPheAspGluLeuLeu 180185190 CAAAATAGCGATATCGTTACGCTTCATGTGCCGCTCAATACGGATACG624 GlnAsnSerAspIleValThrLeuHisValProLeuAsnThrAspThr 195200205 CACTATATTATCAGCCACGAACAAATACAGAGAATGAAGCAAGGAGCA672 HisTyrIleIleSerHisGluGlnIleGlnArgMetLysGlnGlyAla 210215220 TTTCTTATCAATACTGGGCGCGGTCCACTTGTAGATACCTATGAGTTG720 PheLeuIleAsnThrGlyArgGlyProLeuValAspThrTyrGluLeu 225230235240 GTTAAAGCATTAGAAAACGGGAAACTGGGCGGTGCCGCATTGGATGTA768 ValLysAlaLeuGluAsnGlyLysLeuGlyGlyAlaAlaLeuAspVal 245250255 TTGGAAGGAGAGGAAGAGTTTTTCTACTCTGATTGCACCCAAAAACCA816 LeuGluGlyGluGluGluPhePheTyrSerAspCysThrGlnLysPro 260265270 ATTGATAATCAATTTTTACTTAAACTTCAAAGAATGCCTAACGTGATA864 IleAspAsnGlnPheLeuLeuLysLeuGlnArgMetProAsnValIle 275280285 ATCACACCGCATACGGCCTATTATACCGAGCAAGCGTTGCGTGATACC912 IleThrProHisThrAlaTyrTyrThrGluGlnAlaLeuArgAspThr 290295300 GTTGAAAAAACCATTAAAAACTGTTTGGATTTTGAAAGGAGACAGGAG960 ValGluLysThrIleLysAsnCysLeuAspPheGluArgArgGlnGlu 305310315320 CATGAA966 HisGlu (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 322 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: MetAsnAsnIleGlyIleThrValTyrGlyCysGluGlnAspGluAla 151015 AspAlaPheHisAlaLeuSerProArgPheGlyValMetAlaThrIle 202530 IleAsnAlaAsnValSerGluSerAsnAlaLysSerAlaProPheAsn 354045 GlnCysIleSerValGlyHisLysSerGluIleSerAlaSerIleLeu 505560 LeuAlaLeuLysArgAlaGlyValLysTyrIleSerThrArgSerIle 65707580 GlyCysAsnHisIleAspThrThrAlaAlaLysArgMetGlyIleThr 859095 ValAspAsnValAlaTyrSerProAspSerValAlaAspTyrThrMet 100105110 MetLeuIleLeuMetAlaValArgAsnValLysSerIleValArgSer 115120125 ValGluLysHisAspPheArgLeuAspSerAspArgGlyLysValLeu 130135140 SerAspMetThrValGlyValValGlyThrGlyGlnIleGlyLysAla 145150155160 ValIleGluArgLeuArgGlyPheGlyCysLysValLeuAlaTyrSer 165170175 ArgSerArgSerIleGluValAsnTyrValProPheAspGluLeuLeu 180185190 GlnAsnSerAspIleValThrLeuHisValProLeuAsnThrAspThr 195200205 HisTyrIleIleSerHisGluGlnIleGlnArgMetLysGlnGlyAla 210215220 PheLeuIleAsnThrGlyArgGlyProLeuValAspThrTyrGluLeu 225230235240 ValLysAlaLeuGluAsnGlyLysLeuGlyGlyAlaAlaLeuAspVal 245250255 LeuGluGlyGluGluGluPhePheTyrSerAspCysThrGlnLysPro 260265270 IleAspAsnGlnPheLeuLeuLysLeuGlnArgMetProAsnValIle 275280285 IleThrProHisThrAlaTyrTyrThrGluGlnAlaLeuArgAspThr 290295300 ValGluLysThrIleLysAsnCysLeuAspPheGluArgArgGlnGlu 305310315320 HisGlu (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1029 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1029 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: ATGAATAGAATAAAAGTTGCAATACTGTTTGGGGGTTGCTCAGAGGAG48 MetAsnArgIleLysValAlaIleLeuPheGlyGlyCysSerGluGlu 151015 CATGACGTATCGGTAAAATCTGCAATAGAGATAGCCGCTAACATTAAT96 HisAspValSerValLysSerAlaIleGluIleAlaAlaAsnIleAsn 202530 AAAGAAAAATACGAGCCGTTATACATTGGAATTACGAAATCTGGTGTA144 LysGluLysTyrGluProLeuTyrIleGlyIleThrLysSerGlyVal 354045 TGGAAAATGTGCGAAAAACCTTGCGCGGAATGGGAAAACGACAATTGC192 TrpLysMetCysGluLysProCysAlaGluTrpGluAsnAspAsnCys 505560 TATTCAGCTGTACTCTCGCCGGATAAAAAAATGCACGGATTACTTGTT240 TyrSerAlaValLeuSerProAspLysLysMetHisGlyLeuLeuVal 65707580 AAAAAGAACCATGAATATGAAATCAACCATGTTGATGTAGCATTTTCA288 LysLysAsnHisGluTyrGluIleAsnHisValAspValAlaPheSer 859095 GCTTTGCATGGCAAGTCAGGTGAAGATGGATCCATACAAGGTCTGTTT336 AlaLeuHisGlyLysSerGlyGluAspGlySerIleGlnGlyLeuPhe 100105110 GAATTGTCCGGTATCCCTTTTGTAGGCTGCGATATTCAAAGCTCAGCA384 GluLeuSerGlyIleProPheValGlyCysAspIleGlnSerSerAla 115120125 ATTTGTATGGACAAATCGTTGACATACATCGTTGCGAAAAATGCTGGG432 IleCysMetAspLysSerLeuThrTyrIleValAlaLysAsnAlaGly 130135140 ATAGCTACTCCCGCCTTTTGGGTTATTAATAAAGATGATAGGCCGGTG480 IleAlaThrProAlaPheTrpValIleAsnLysAspAspArgProVal 145150155160 GCAGCTACGTTTACCTATCCTGTTTTTGTTAAGCCGGCGCGTTCAGGC528 AlaAlaThrPheThrTyrProValPheValLysProAlaArgSerGly 165170175 TCATCCTTCGGTGTGAAAAAAGTCAATAGCGCGGACGAATTGGACTAC576 SerSerPheGlyValLysLysValAsnSerAlaAspGluLeuAspTyr 180185190 GCAATTGAATCGGCAAGACAATATGACAGCAAAATCTTAATTGAGCAG624 AlaIleGluSerAlaArgGlnTyrAspSerLysIleLeuIleGluGln 195200205 GCTGTTTCGGGCTGTGAGGTCGGTTGTGCGGTATTGGGAAACAGTGCC672 AlaValSerGlyCysGluValGlyCysAlaValLeuGlyAsnSerAla 210215220 GCGTTAGTTGTTGGCGAGGTGGACCAAATCAGGCTGCAGTACGGAATC720 AlaLeuValValGlyGluValAspGlnIleArgLeuGlnTyrGlyIle 225230235240 TTTCGTATTCATCAGGAAGTCGAGCCGGAAAAAGGCTCTGAAAACGCA768 PheArgIleHisGlnGluValGluProGluLysGlySerGluAsnAla 245250255 GTTATAACCGTTCCCGCAGACCTTTCAGCAGAGGAGCGAGGACGGATA816 ValIleThrValProAlaAspLeuSerAlaGluGluArgGlyArgIle 260265270 CAGGAAACGGCAAAAAAAATATATAAAGCGCTCGGCTGTAGAGGTCTA864 GlnGluThrAlaLysLysIleTyrLysAlaLeuGlyCysArgGlyLeu 275280285 GCCCGTGTGGATATGTTTTTACAAGATAACGGCCGCATTGTACTGAAC912 AlaArgValAspMetPheLeuGlnAspAsnGlyArgIleValLeuAsn 290295300 GAAGTCAATACTCTGCCCGGTTTCACGTCATACAGTCGTTATCCCCGT960 GluValAsnThrLeuProGlyPheThrSerTyrSerArgTyrProArg 305310315320 ATGATGGCCGCTGCAGGTATTGCACTTCCCGAACTGATTGACCGCTTG1008 MetMetAlaAlaAlaGlyIleAlaLeuProGluLeuIleAspArgLeu 325330335 ATCGTATTAGCGTTAAAGGGG1029 IleValLeuAlaLeuLysGly 340 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 343 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: MetAsnArgIleLysValAlaIleLeuPheGlyGlyCysSerGluGlu 151015 HisAspValSerValLysSerAlaIleGluIleAlaAlaAsnIleAsn 202530 LysGluLysTyrGluProLeuTyrIleGlyIleThrLysSerGlyVal 354045 TrpLysMetCysGluLysProCysAlaGluTrpGluAsnAspAsnCys 505560 TyrSerAlaValLeuSerProAspLysLysMetHisGlyLeuLeuVal 65707580 LysLysAsnHisGluTyrGluIleAsnHisValAspValAlaPheSer 859095 AlaLeuHisGlyLysSerGlyGluAspGlySerIleGlnGlyLeuPhe 100105110 GluLeuSerGlyIleProPheValGlyCysAspIleGlnSerSerAla 115120125 IleCysMetAspLysSerLeuThrTyrIleValAlaLysAsnAlaGly 130135140 IleAlaThrProAlaPheTrpValIleAsnLysAspAspArgProVal 145150155160 AlaAlaThrPheThrTyrProValPheValLysProAlaArgSerGly 165170175 SerSerPheGlyValLysLysValAsnSerAlaAspGluLeuAspTyr 180185190 AlaIleGluSerAlaArgGlnTyrAspSerLysIleLeuIleGluGln 195200205 AlaValSerGlyCysGluValGlyCysAlaValLeuGlyAsnSerAla 210215220 AlaLeuValValGlyGluValAspGlnIleArgLeuGlnTyrGlyIle 225230235240 PheArgIleHisGlnGluValGluProGluLysGlySerGluAsnAla 245250255 ValIleThrValProAlaAspLeuSerAlaGluGluArgGlyArgIle 260265270 GlnGluThrAlaLysLysIleTyrLysAlaLeuGlyCysArgGlyLeu 275280285 AlaArgValAspMetPheLeuGlnAspAsnGlyArgIleValLeuAsn 290295300 GluValAsnThrLeuProGlyPheThrSerTyrSerArgTyrProArg 305310315320 MetMetAlaAlaAlaGlyIleAlaLeuProGluLeuIleAspArgLeu 325330335 IleValLeuAlaLeuLysGly 340 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 606 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..606 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: ATGGAAATAGGATTTACTTTTTTAGATGAAATAGTACACGGTGTTCGT48 MetGluIleGlyPheThrPheLeuAspGluIleValHisGlyValArg 151015 TGGGACGCTAAATATGCCACTTGGGATAATTTCACCGGAAAACCGGTT96 TrpAspAlaLysTyrAlaThrTrpAspAsnPheThrGlyLysProVal 202530 GACGGTTATGAAGTAAATCGCATTGTAGGGACATACGAGTTGGCTGAA144 AspGlyTyrGluValAsnArgIleValGlyThrTyrGluLeuAlaGlu 354045 TCGCTTTTGAAGGCAAAAGAACTGGCTGCTACCCAAGGGTACGGATTG192 SerLeuLeuLysAlaLysGluLeuAlaAlaThrGlnGlyTyrGlyLeu 505560 CTTCTATGGGACGGTTACCGTCCTAAGCGTGCTGTAAACTGTTTTATG240 LeuLeuTrpAspGlyTyrArgProLysArgAlaValAsnCysPheMet 65707580 CAATGGGCTGCACAGCCGGAAAATAACCTGACAAAGGAAAGTTATTAT288 GlnTrpAlaAlaGlnProGluAsnAsnLeuThrLysGluSerTyrTyr 859095 CCCAATATTGACCGAACTGAGATGATTTCAAAAGGATACGTGGCTTCA336 ProAsnIleAspArgThrGluMetIleSerLysGlyTyrValAlaSer 100105110 AAATCAAGCCATAGCCGCGGCAGTGCCATTGATCTTACGCTTTATCGA384 LysSerSerHisSerArgGlySerAlaIleAspLeuThrLeuTyrArg 115120125 TTAGACACGGGTGAGCTTGTACCAATGGGGAGCCGATTTGATTTTATG432 LeuAspThrGlyGluLeuValProMetGlySerArgPheAspPheMet 130135140 GATGAACGCTCTCATCATGCGGCAAATGGAATATCATGCAATGAAGCG480 AspGluArgSerHisHisAlaAlaAsnGlyIleSerCysAsnGluAla 145150155160 CAAAATCGCAGACGTTTGCGCTCCATCATGGAAAACAGTGGGTTTGAA528 GlnAsnArgArgArgLeuArgSerIleMetGluAsnSerGlyPheGlu 165170175 GCATATAGCCTCGAATGGTGGCACTATGTATTAAGAGACGAACCATAC576 AlaTyrSerLeuGluTrpTrpHisTyrValLeuArgAspGluProTyr 180185190 CCCAATAGCTATTTTGATTTCCCCGTTAAA606 ProAsnSerTyrPheAspPheProValLys 195200 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 202 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: MetGluIleGlyPheThrPheLeuAspGluIleValHisGlyValArg 151015 TrpAspAlaLysTyrAlaThrTrpAspAsnPheThrGlyLysProVal 202530 AspGlyTyrGluValAsnArgIleValGlyThrTyrGluLeuAlaGlu 354045 SerLeuLeuLysAlaLysGluLeuAlaAlaThrGlnGlyTyrGlyLeu 505560 LeuLeuTrpAspGlyTyrArgProLysArgAlaValAsnCysPheMet 65707580 GlnTrpAlaAlaGlnProGluAsnAsnLeuThrLysGluSerTyrTyr 859095 ProAsnIleAspArgThrGluMetIleSerLysGlyTyrValAlaSer 100105110 LysSerSerHisSerArgGlySerAlaIleAspLeuThrLeuTyrArg 115120125 LeuAspThrGlyGluLeuValProMetGlySerArgPheAspPheMet 130135140 AspGluArgSerHisHisAlaAlaAsnGlyIleSerCysAsnGluAla 145150155160 GlnAsnArgArgArgLeuArgSerIleMetGluAsnSerGlyPheGlu 165170175 AlaTyrSerLeuGluTrpTrpHisTyrValLeuArgAspGluProTyr 180185190 ProAsnSerTyrPheAspPheProValLys 195200 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1347 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 215..1243 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: GAGCTCTTCCTTCAACGCACTTCTGTACCAAGAGTTGTTGTCCATTTGATCACTAACAAT60 AGCTTCCCCTGCTTTCTTCAAGCCCTTTGTCATAAAATCGTTAGATTTTCATCATAAAAA120 TACGAGAAAGACAACAGGAAGACCGCAAATTTTCTTTTCTTTTCCTAGGTACACTGAATG180 TAACCTTAAAAGAAAAAAGGAAAGGAAGAAAATGATGAAAAAAATTGCCGTT232 MetLysLysIleAlaVal 15 TTATTTGGAGGGAATTCTCCAGAATACTCAGTGTCACTAACCTCAGCA280 LeuPheGlyGlyAsnSerProGluTyrSerValSerLeuThrSerAla 101520 GCAAGTGTGATCCAAGCTATTGACCCGCTGAAATATGAAGTAATGACC328 AlaSerValIleGlnAlaIleAspProLeuLysTyrGluValMetThr 253035 ATTGGCATCGCACCAACAATGGATTGGTATTGGTATCAAGGAAACCTC376 IleGlyIleAlaProThrMetAspTrpTyrTrpTyrGlnGlyAsnLeu 404550 GCGAATGTTCGCAATGATACTTGGCTAGAAGATCACAAAAACTGTCAC424 AlaAsnValArgAsnAspThrTrpLeuGluAspHisLysAsnCysHis 55606570 CAGCTGACTTTTTCTAGCCAAGGATTTATATTAGGAGAAAAACGAATC472 GlnLeuThrPheSerSerGlnGlyPheIleLeuGlyGluLysArgIle 758085 GTCCCTGATGTCCTCTTTCCAGTCTTGCATGGGAAGTATGGCGAGGAT520 ValProAspValLeuPheProValLeuHisGlyLysTyrGlyGluAsp 9095100 GGCTGTATCCAAGGACTGCTTGAACTAATGAACCTGCCTTATGTTGGT568 GlyCysIleGlnGlyLeuLeuGluLeuMetAsnLeuProTyrValGly 105110115 TGCCATGTCGCTGCCTCCGCATTATGTATGAACAAATGGCTCTTGCAT616 CysHisValAlaAlaSerAlaLeuCysMetAsnLysTrpLeuLeuHis 120125130 CAACTTGCTGATACCATGGGAATCGCTAGTGCTCCCACTTTGCTTTTA664 GlnLeuAlaAspThrMetGlyIleAlaSerAlaProThrLeuLeuLeu 135140145150 TCCCGCTATGAAAACGATCCTGCCACAATCGATCGTTTTATTCAAGAC712 SerArgTyrGluAsnAspProAlaThrIleAspArgPheIleGlnAsp 155160165 CATGGATTCCCGATCTTTATCAAGCCGAATGAAGCCGGTTCTTCAAAA760 HisGlyPheProIlePheIleLysProAsnGluAlaGlySerSerLys 170175180 GGGATCACAAAAGTAACTGACAAAACAGCGCTCCAATCTGCATTAACG808 GlyIleThrLysValThrAspLysThrAlaLeuGlnSerAlaLeuThr 185190195 ACTGCTTTTGCTTACGGTTCTACTGTGTTGATCCAAAAGGCGATAGCG856 ThrAlaPheAlaTyrGlySerThrValLeuIleGlnLysAlaIleAla 200205210 GGTATTGAAATTGGCTGCGGCATCTTAGGAAATGAGCAATTGACGATT904 GlyIleGluIleGlyCysGlyIleLeuGlyAsnGluGlnLeuThrIle 215220225230 GGTGCTTGTGATGCGATTTCTCTTGTCGACGGTTTTTTTGATTTTGAA952 GlyAlaCysAspAlaIleSerLeuValAspGlyPhePheAspPheGlu 235240245 GAGAAATACCAATTAATCAGCGCCACGATCACTGTCCCAGCACCATTG1000 GluLysTyrGlnLeuIleSerAlaThrIleThrValProAlaProLeu 250255260 CCTCTCGCGCTTGAATCACAGATCAAGGAGCAGGCACAGCTGCTTTAT1048 ProLeuAlaLeuGluSerGlnIleLysGluGlnAlaGlnLeuLeuTyr 265270275 CGAAACTTGGGATTGACGGGTCTGGCTCGAATCGATTTTTTCGTCACC1096 ArgAsnLeuGlyLeuThrGlyLeuAlaArgIleAspPhePheValThr 280285290 AATCAAGGAGCGATTTATTTAAACGAAATCAACACCATGCCGGGATTT1144 AsnGlnGlyAlaIleTyrLeuAsnGluIleAsnThrMetProGlyPhe 295300305310 ACTGGGCACTCCCGCTACCCAGCTATGATGGCGGAAGTCGGGTTATCC1192 ThrGlyHisSerArgTyrProAlaMetMetAlaGluValGlyLeuSer 315320325 TACGAAATATTAGTAGAGCAATTGATTGCACTGGCAGAGGAGGACAAA1240 TyrGluIleLeuValGluGlnLeuIleAlaLeuAlaGluGluAspLys 330335340 CGATGAACACATTACAATTGATCAATAAAAACCATCCATTGAAAAAAAATCAA1293 Arg GAGCCCCCGCACTTAGTGCTAGCTCCTTTTAGCGATCACGATGTTTACCTGCAG1347 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 343 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: MetLysLysIleAlaValLeuPheGlyGlyAsnSerProGluTyrSer 151015 ValSerLeuThrSerAlaAlaSerValIleGlnAlaIleAspProLeu 202530 LysTyrGluValMetThrIleGlyIleAlaProThrMetAspTrpTyr 354045 TrpTyrGlnGlyAsnLeuAlaAsnValArgAsnAspThrTrpLeuGlu 505560 AspHisLysAsnCysHisGlnLeuThrPheSerSerGlnGlyPheIle 65707580 LeuGlyGluLysArgIleValProAspValLeuPheProValLeuHis 859095 GlyLysTyrGlyGluAspGlyCysIleGlnGlyLeuLeuGluLeuMet 100105110 AsnLeuProTyrValGlyCysHisValAlaAlaSerAlaLeuCysMet 115120125 AsnLysTrpLeuLeuHisGlnLeuAlaAspThrMetGlyIleAlaSer 130135140 AlaProThrLeuLeuLeuSerArgTyrGluAsnAspProAlaThrIle 145150155160 AspArgPheIleGlnAspHisGlyPheProIlePheIleLysProAsn 165170175 GluAlaGlySerSerLysGlyIleThrLysValThrAspLysThrAla 180185190 LeuGlnSerAlaLeuThrThrAlaPheAlaTyrGlySerThrValLeu 195200205 IleGlnLysAlaIleAlaGlyIleGluIleGlyCysGlyIleLeuGly 210215220 AsnGluGlnLeuThrIleGlyAlaCysAspAlaIleSerLeuValAsp 225230235240 GlyPhePheAspPheGluGluLysTyrGlnLeuIleSerAlaThrIle 245250255 ThrValProAlaProLeuProLeuAlaLeuGluSerGlnIleLysGlu 260265270 GlnAlaGlnLeuLeuTyrArgAsnLeuGlyLeuThrGlyLeuAlaArg 275280285 IleAspPhePheValThrAsnGlnGlyAlaIleTyrLeuAsnGluIle 290295300 AsnThrMetProGlyPheThrGlyHisSerArgTyrProAlaMetMet 305310315320 AlaGluValGlyLeuSerTyrGluIleLeuValGluGlnLeuIleAla 325330335 LeuAlaGluGluAspLysArg 340 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: GGNGARGAYGGNWSNHTNCARGGN24 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: AAYACNHTNCCNGGNTTYAC20 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 693 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..693 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: ATGAGCGATAAAATACTTATTGTGGATGATGAACATGAAATTGCCGAT48 MetSerAspLysIleLeuIleValAspAspGluHisGluIleAlaAsp 151015 TTGGTTGAATTATACTTAAAAAACGAGAATTATACGGTTTTCAAATAC96 LeuValGluLeuTyrLeuLysAsnGluAsnTyrThrValPheLysTyr 202530 TATACCGCCAAAGAAGCATTGGAATGTATAGACAAGTCTGAGATTGAC144 TyrThrAlaLysGluAlaLeuGluCysIleAspLysSerGluIleAsp 354045 CTTGCCATATTGGACATCATGCTTCCCGGCACAAGCGGCCTTACTATC192 LeuAlaIleLeuAspIleMetLeuProGlyThrSerGlyLeuThrIle 505560 TGTCAAAAAATAAGGGACAAGCACACCTATCCGATTATCATGCTGACC240 CysGlnLysIleArgAspLysHisThrTyrProIleIleMetLeuThr 65707580 GGGAAAGATACAGAGGTAGATAAAATTACAGGGTTAACAATCGGCGCG288 GlyLysAspThrGluValAspLysIleThrGlyLeuThrIleGlyAla 859095 GATGATTATATAACGAAGCCCTTTCGCCCACTGGAGTTAATTGCTCGG336 AspAspTyrIleThrLysProPheArgProLeuGluLeuIleAlaArg 100105110 GTAAAGGCCCAGTTGCGCCGATACAAAAAATTCAGTGGAGTAAAGGAG384 ValLysAlaGlnLeuArgArgTyrLysLysPheSerGlyValLysGlu 115120125 CAGAACGAAAATGTTATCGTCCACTCCGGCCTTGTCATTAATGTTAAC432 GlnAsnGluAsnValIleValHisSerGlyLeuValIleAsnValAsn 130135140 ACCCATGAGTGTTATCTGAACGAGAAGCAGTTATCCCTTACTCCCACC480 ThrHisGluCysTyrLeuAsnGluLysGlnLeuSerLeuThrProThr 145150155160 GAGTTTTCAATACTGCGAATCCTCTGTGAAAACAAGGGGAATGTGGTT528 GluPheSerIleLeuArgIleLeuCysGluAsnLysGlyAsnValVal 165170175 AGCTCCGAGCTGCTATTTCATGAGATATGGGGCGACGAATATTTCAGC576 SerSerGluLeuLeuPheHisGluIleTrpGlyAspGluTyrPheSer 180185190 AAGAGCAACAACACCATCACCGTGCATATCCGGCATTTGCGCGAAAAA624 LysSerAsnAsnThrIleThrValHisIleArgHisLeuArgGluLys 195200205 ATGAACGACACCATTGATAATCCGAAATATATAAAAACGGTATGGGGG672 MetAsnAspThrIleAspAsnProLysTyrIleLysThrValTrpGly 210215220 GTTGGTTATAAAATTGAAAAA693 ValGlyTyrLysIleGluLys 225230 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 231 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: MetSerAspLysIleLeuIleValAspAspGluHisGluIleAlaAsp 151015 LeuValGluLeuTyrLeuLysAsnGluAsnTyrThrValPheLysTyr 202530 TyrThrAlaLysGluAlaLeuGluCysIleAspLysSerGluIleAsp 354045 LeuAlaIleLeuAspIleMetLeuProGlyThrSerGlyLeuThrIle 505560 CysGlnLysIleArgAspLysHisThrTyrProIleIleMetLeuThr 65707580 GlyLysAspThrGluValAspLysIleThrGlyLeuThrIleGlyAla 859095 AspAspTyrIleThrLysProPheArgProLeuGluLeuIleAlaArg 100105110 ValLysAlaGlnLeuArgArgTyrLysLysPheSerGlyValLysGlu 115120125 GlnAsnGluAsnValIleValHisSerGlyLeuValIleAsnValAsn 130135140 ThrHisGluCysTyrLeuAsnGluLysGlnLeuSerLeuThrProThr 145150155160 GluPheSerIleLeuArgIleLeuCysGluAsnLysGlyAsnValVal 165170175 SerSerGluLeuLeuPheHisGluIleTrpGlyAspGluTyrPheSer 180185190 LysSerAsnAsnThrIleThrValHisIleArgHisLeuArgGluLys 195200205 MetAsnAspThrIleAspAsnProLysTyrIleLysThrValTrpGly 210215220 ValGlyTyrLysIleGluLys 225230 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1152 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1152 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: TTGGTTATAAAATTGAAAAATAAAAAAAACGACTATTCCAAACTAGAA48 LeuValIleLysLeuLysAsnLysLysAsnAspTyrSerLysLeuGlu 151015 CGAAAACTTTACATGTATATCGTTGCAATTGTTGTGGTAGCAATTGTA96 ArgLysLeuTyrMetTyrIleValAlaIleValValValAlaIleVal 202530 TTCGTGTTGTATATTCGTTCAATGATCCGAGGGAAACTTGGGGATTGG144 PheValLeuTyrIleArgSerMetIleArgGlyLysLeuGlyAspTrp 354045 ATCTTAAGTATTTTGGAAAACAAATATGACTTAAATCACCTGGACGCG192 IleLeuSerIleLeuGluAsnLysTyrAspLeuAsnHisLeuAspAla 505560 ATGAAATTATATCAATATTCCATACGGAACAATATAGATATCTTTATT240 MetLysLeuTyrGlnTyrSerIleArgAsnAsnIleAspIlePheIle 65707580 TATGTGGCGATTGTCATTAGTATTCTTATTCTATGTCGCGTCATGCTT288 TyrValAlaIleValIleSerIleLeuIleLeuCysArgValMetLeu 859095 TCAAAATTCGCAAAATACTTTGACGAGATAAATACCGGCATTGATGTA336 SerLysPheAlaLysTyrPheAspGluIleAsnThrGlyIleAspVal 100105110 CTTATTCAGAACGAAGATAAACAAATTGAGCTTTCTGCGGAAATGGAT384 LeuIleGlnAsnGluAspLysGlnIleGluLeuSerAlaGluMetAsp 115120125 GTTATGGAACAAAAGCTCAACACATTAAAACGGACTCTGGAAAAGCGA432 ValMetGluGlnLysLeuAsnThrLeuLysArgThrLeuGluLysArg 130135140 GAGCAGGATGCAAAGCTGGCCGAACAAAGAAAAAATGACGTTGTTATG480 GluGlnAspAlaLysLeuAlaGluGlnArgLysAsnAspValValMet 145150155160 TACTTGGCGCACGATATTAAAACGCCCCTTACATCCATTATCGGTTAT528 TyrLeuAlaHisAspIleLysThrProLeuThrSerIleIleGlyTyr 165170175 TTGAGCCTGCTTGACGAGGCTCCAGACATGCCGGTAGATCAAAAGGCA576 LeuSerLeuLeuAspGluAlaProAspMetProValAspGlnLysAla 180185190 AAGTATGTGCATATCACGTTGGACAAAGCGTATCGACTCGAACAGCTA624 LysTyrValHisIleThrLeuAspLysAlaTyrArgLeuGluGlnLeu 195200205 ATCGACGAGTTTTTTGAGATTACACGGTATAACCTACAAACGATAACG672 IleAspGluPhePheGluIleThrArgTyrAsnLeuGlnThrIleThr 210215220 CTAACAAAAACGCACATAGACCTATACTATATGCTGGTGCAGATGACC720 LeuThrLysThrHisIleAspLeuTyrTyrMetLeuValGlnMetThr 225230235240 GATGAATTTTATCCTCAGCTTTCCGCACATGGAAAACAGGCGGTTATT768 AspGluPheTyrProGlnLeuSerAlaHisGlyLysGlnAlaValIle 245250255 CACGCCCCCGAGGATCTGACCGTGTCCGGCGACCCTGATAAACTCGCG816 HisAlaProGluAspLeuThrValSerGlyAspProAspLysLeuAla 260265270 AGAGTCTTTAACAACATTTTGAAAAACGCCGCTGCATACAGTGAGGAT864 ArgValPheAsnAsnIleLeuLysAsnAlaAlaAlaTyrSerGluAsp 275280285 AACAGCATCATTGACATTACCGCGGGCCTCTCCGGGGATGTGGTGTCA912 AsnSerIleIleAspIleThrAlaGlyLeuSerGlyAspValValSer 290295300 ATCGAATTCAAGAACACTGGAAGCATCCCAAAAGATAAGCTAGCTGCC960 IleGluPheLysAsnThrGlySerIleProLysAspLysLeuAlaAla 305310315320 ATATTTGAAAAGTTCTATAGGCTGGACAATGCTCGTTCTTCCGATACG1008 IlePheGluLysPheTyrArgLeuAspAsnAlaArgSerSerAspThr 325330335 GGTGGCGCGGGACTTGGATTGGCGATTGCAAAAGAAATTATTGTTCAG1056 GlyGlyAlaGlyLeuGlyLeuAlaIleAlaLysGluIleIleValGln 340345350 CATGGAGGGCAGATTTACGCGGAAAGCAATGATAACTATACGACGTTT1104 HisGlyGlyGlnIleTyrAlaGluSerAsnAspAsnTyrThrThrPhe 355360365 AGGGTAGAGCTTCCAGCGATGCCAGACTTGGTTGATAAAAGGAGGTCC1152 ArgValGluLeuProAlaMetProAspLeuValAspLysArgArgSer 370375380 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 384 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: LeuValIleLysLeuLysAsnLysLysAsnAspTyrSerLysLeuGlu 151015 ArgLysLeuTyrMetTyrIleValAlaIleValValValAlaIleVal 202530 PheValLeuTyrIleArgSerMetIleArgGlyLysLeuGlyAspTrp 354045 IleLeuSerIleLeuGluAsnLysTyrAspLeuAsnHisLeuAspAla 505560 MetLysLeuTyrGlnTyrSerIleArgAsnAsnIleAspIlePheIle 65707580 TyrValAlaIleValIleSerIleLeuIleLeuCysArgValMetLeu 859095 SerLysPheAlaLysTyrPheAspGluIleAsnThrGlyIleAspVal 100105110 LeuIleGlnAsnGluAspLysGlnIleGluLeuSerAlaGluMetAsp 115120125 ValMetGluGlnLysLeuAsnThrLeuLysArgThrLeuGluLysArg 130135140 GluGlnAspAlaLysLeuAlaGluGlnArgLysAsnAspValValMet 145150155160 TyrLeuAlaHisAspIleLysThrProLeuThrSerIleIleGlyTyr 165170175 LeuSerLeuLeuAspGluAlaProAspMetProValAspGlnLysAla 180185190 LysTyrValHisIleThrLeuAspLysAlaTyrArgLeuGluGlnLeu 195200205 IleAspGluPhePheGluIleThrArgTyrAsnLeuGlnThrIleThr 210215220 LeuThrLysThrHisIleAspLeuTyrTyrMetLeuValGlnMetThr 225230235240 AspGluPheTyrProGlnLeuSerAlaHisGlyLysGlnAlaValIle 245250255 HisAlaProGluAspLeuThrValSerGlyAspProAspLysLeuAla 260265270 ArgValPheAsnAsnIleLeuLysAsnAlaAlaAlaTyrSerGluAsp 275280285 AsnSerIleIleAspIleThrAlaGlyLeuSerGlyAspValValSer 290295300 IleGluPheLysAsnThrGlySerIleProLysAspLysLeuAlaAla 305310315320 IlePheGluLysPheTyrArgLeuAspAsnAlaArgSerSerAspThr 325330335 GlyGlyAlaGlyLeuGlyLeuAlaIleAlaLysGluIleIleValGln 340345350 HisGlyGlyGlnIleTyrAlaGluSerAsnAspAsnTyrThrThrPhe 355360365 ArgValGluLeuProAlaMetProAspLeuValAspLysArgArgSer 370375380 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7225 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: AAGCTTTTCTTTTTGCTCATTTGTTAGAGATTTACTAACCGTATTAAATAGCTTCTTTTC60 AGCCATTGCCCTTGCTTCCCACACCATTCTTTCAAGTGTAGTGATAGCAGGCAGTATAAT120 TTTGTTTTTTCTTAGAAAATCTATGCATTCATGCAGTAGATGAATGGCATCACCATTTTC180 CAAAGCTAATTGATGAAGGTACTTAAATGTCATTCGATATTCACTCAGGGTAAAAGTTAC240 AAAGTCGTATTCACTTCGAATTTCTTTCAAATGATCCCAAAGTGTATTTTCCCTTTGAGG300 ATAATGATCAAGCGAGGATGGACTAACACCAATCTGTTTCGATATATATTGTATGACCGA360 ATCTGGGATGCTTTTGATATGAGTGTATGGCCAACCGGGATACCGAAGAACAGCTAATTG420 AACAGCAAATCCTAAACGGTTTTCTTCCCTCCTTCGCTTATTAACTATTTCTAAATCCCG480 TTTGGAAAAAGTGAAGTAGGTCCCCAGTATCCATTCATCTTCAGGGATTTGCATAAAAGC540 CTGTCTCTGTTCCGGTGTAAGCAATTCTCTACCTCTCGCAATTTTCATTCAGTATCATTC600 CATTTCTGTATTTTCAATTTATTAGTTCAATTATATATCAATAGAGTGTACTCTATTGAT660 ACAAATGTAGTAGACTGATAAAATCATAGTTAAGAGCGTCTCATAAGACTTGTCTCAAAA720 ATGAGGTGATATTTTGCGGAAAATCGGTTATATTCGTGTCAGTTCGACTAACCAGAATCC780 TTCAAGACAATTTCAGCAGTTGAACGAGATCGGAATGGATATTATATAAAGAGAAAGTTT840 CAGGAGCAACAAAGGATCGCGAGCAACTTCAAAAAGTGTTAGACGATTTACAGGAAGATG900 ACATCATTTATGTTACAGACTTAACTCGAATCACTCGTAGTACACAAGATCTATTTGAAT960 TAATCGATAACATACGAGATAAAAAGGCAAGTTTAAAATCACTAAAAGATACATGGCTTG1020 ATTTATCAGAAGATAATCCATACAGCCAATTCTTAATTACTGTAATGGCTGGTGTTAACC1080 AATTAGAGCGAGATCTTATTCGGATGAGACAACGTGAAGGGATTGAATTGGCTAAGAAAG1140 AAGGAAAGTTTAAAGGTCGATTAAAGAAGTATCATAAAAATCACGCAGGAATGAATTATG1200 CGGAAAGCTATATAAAGAAGGAAATATGACTGTAAATCAAATTTGTGAAATTACTAATGT1260 ATCTAGGGCTTCATTATACAGGAAATTATCAGAAGTGAATAATTAGCCATTCTGTATTCC1320 GCTAATGGGCAATATTTTTAAAGAAGAAAAGGAAACTATAAAATATTAACAGCCTCCTAG1380 CGATGCCGAAAAGCCCTTTGATAAAAAAAGAATCATCATCTTAAGAAATTCTTAGTCATT1440 TATTATGTAAATGCTTATAAATTCGGCCCTATAATCTGATAAATTATTAAGGGCAAACTT1500 ATGTGAAAGGGTGATAACTATGAGCGATAAAATACTTATTGTGGATGATGAACATGAAAT1560 TGCCGATTTGGTTGAATTATACTTAAAAAACGAGAATTATACGGTTTTCAAATACTATAC1620 CGCCAAAGAAGCATTGGAATGTATAGACAAGTCTGAGATTGACCTTGCCATATTGGACAT1680 CATGCTTCCCGGCACAAGCGGCCTTACTATCTGTCAAAAAATAAGGGACAAGCACACCTA1740 TCCGATTATCATGCTGACCGGGAAAGATACAGAGGTAGATAAAATTACAGGGTTAACAAT1800 CGGCGCGGATGATTATATAACGAAGCCCTTTCGCCCACTGGAGTTAATTGCTCGGGTAAA1860 GGCCCAGTTGCGCCGATACAAAAAATTCAGTGGAGTAAAGGAGCAGAACGAAAATGTTAT1920 CGTCCACTCCGGCCTTGTCATTAATGTTAACACCCATGAGTGTTATCTGAACGAGAAGCA1980 GTTATCCCTTACTCCCACCGAGTTTTCAATACTGCGAATCCTCTGTGAAAACAAGGGGAA2040 TGTGGTTAGCTCCGAGCTGCTATTTCATGAGATATGGGGCGACGAATATTTCAGCAAGAG2100 CAACAACACCATCACCGTGCATATCCGGCATTTGCGCGAAAAAATGAACGACACCATTGA2160 TAATCCGAAATATATAAAAACGGTATGGGGGGTTGGTTATAAAATTGAAAAATAAAAAAA2220 ACGACTATTCCAAACTAGAACGAAAACTTTACATGTATATCGTTGCAATTGTTGTGGTAG2280 CAATTGTATTCGTGTTGTATATTCGTTCAATGATCCGAGGGAAACTTGGGGATTGGATCT2340 TAAGTATTTTGGAAAACAAATATGACTTAAATCACCTGGACGCGATGAAATTATATCAAT2400 ATTCCATACGGAACAATATAGATATCTTTATTTATGTGGCGATTGTCATTAGTATTCTTA2460 TTCTATGTCGCGTCATGCTTTCAAAATTCGCAAAATACTTTGACGAGATAAATACCGGCA2520 TTGATGTACTTATTCAGAACGAAGATAAACAAATTGAGCTTTCTGCGGAAATGGATGTTA2580 TGGAACAAAAGCTCAACACATTAAAACGGACTCTGGAAAAGCGAGAGCAGGATGCAAAGC2640 TGGCCGAACAAAGAAAAAATGACGTTGTTATGTACTTGGCGCACGATATTAAAACGCCCC2700 TTACATCCATTATCGGTTATTTGAGCCTGCTTGACGAGGCTCCAGACATGCCGGTAGATC2760 AAAAGGCAAAGTATGTGCATATCACGTTGGACAAAGCGTATCGACTCGAACAGCTAATCG2820 ACGAGTTTTTTGAGATTACACGGTATAACCTACAAACGATAACGCTAACAAAAACGCACA2880 TAGACCTATACTATATGCTGGTGCAGATGACCGATGAATTTTATCCTCAGCTTTCCGCAC2940 ATGGAAAACAGGCGGTTATTCACGCCCCCGAGGATCTGACCGTGTCCGGCGACCCTGATA3000 AACTCGCGAGAGTCTTTAACAACATTTTGAAAAACGCCGCTGCATACAGTGAGGATAACA3060 GCATCATTGACATTACCGCGGGCCTCTCCGGGGATGTGGTGTCAATCGAATTCAAGAACA3120 CTGGAAGCATCCCAAAAGATAAGCTAGCTGCCATATTTGAAAAGTTCTATAGGCTGGACA3180 ATTCTCGTTCTTCCGATACGGGTGGCGCGGGACTTGGATTGGCGATTGCAAAAGAAATTA3240 TTGTTCAGCATGGAGGGCAGATTTACGCGGAAAGCTATGATAACTATACGACGTTTAGGG3300 TAGAGCTTCCAGCGATGCCAGACTTGGTTGATAAAAGGAGGTCCTAAGAGATGTATATAA3360 TTTTTTAGGAAAATCTCAAGGTTATCTTTACTTTTTCTTAGGAAATTAACAATTTAATAT3420 TAAGAAACGGCTCGTTCTTACACGGTAGACTTAATACCGTAAGAACGAGCCGTTTTCGTT3480 CTTCAGAGAAAGATTTGACAAGATTACCATTGGCATCCCCGTTTTATTTGGTGCCTTTCA3540 CAGAAAGGGTTGGTCTTAATTATGAATAACATCGGCATTACTGTTTATGGATGTGAGCAG3600 GATGAGGCAGATGCATTCCATGCTCTTTCGCCTCGCTTTGGCGTTATGGCAACGATAATT3660 AACGCCAACGTGTCGGAATCCAACGCCAAATCCGCGCCTTTCAATCAATGTATCAGTGTG3720 GGACATAAATCAGAGATTTCCGCCTCTATTCTTCTTGCGCTGAAGAGAGCCGGTGTGAAA3780 TATATTTCTACCCGAAGCATCGGCTGCAATCATATAGATACAACTGCTGCTAAGAGAATG3840 GGCATCACTGTCGACAATGTGGCGTACTCGCCGGATAGCGTTGCCGATTATACTATGATG3900 CTAATTCTTATGGCAGTACGCAACGTAAAATCGATTGTGCGCTCTGTGGAAAAACATGAT3960 TTCAGGTTGGACAGCGACCGTGGCAAGGTACTCAGCGACATGACAGTTGGTGTGGTGGGA4020 ACGGGCCAGATAGGCAAAGCGGTTATTGAGCGGCTGCGAGGATTTGGATGTAAAGTGTTG4080 GCTTATAGTCGCAGCCGAAGTATAGAGGTAAACTATGTACCGTTTGATGAGTTGATGCAA4140 AATAGCGATATCGTTACGCTTCATGTGCCGCTCAATACGGATACGCACTATATTATCAGC4200 CACGAACAAATACAGAGAATGAAGCAAGGAGCATTTCTTATCAATACTGGGCGCGGTCCA4260 CTTGTAGATACCTATGAGTTGGTTAAAGCATTAGAAAACGGGAAACTGGGCGGTGCCGCA4320 TTGGATGTATTGGAAGGAGAGGAAGAGTTTTTCTACTCTGATTGCACCCAAAAACCAATT4380 GATAATCAATTTTTACTTAAACTTCAAAGAATGCCTAACGTGATAATCACACCGCATACG4440 GCCTATTATACCGAGCAAGCGTTGCGTGATACCGTTGAAAAAACCATTAAAAACTGTTTG4500 GATTTTGAAAGGAGACAGGAGCATGAATAGAATAAAAGTTGCAATACTGTTTGGGGGTTG4560 CTCAGAGGAGCATGACGTATCGGTAAAATCTGCAATAGAGATAGCCGCTAACATTAATAA4620 AGAAAAATACGAGCCGTTATACATTGGAATTACGAAATCTGGTGTATGGAAAATGTGCGA4680 AAAACCTTGCGCGGAATGGGAAAACGACAATTGCTATTCAGCTGTACTCTCGCCGGATAA4740 AAAAATGCACGGATTACTTGTTAAAAAGAACCATGAATATGAAATCAACCATGTTGATGT4800 AGCATTTTCAGCTTTGCATGGCAAGTCAGGTGAAGATGGATCCATACAAGGTCTGTTTGA4860 ATTGTCCGGTATCCCTTTTGTAGGCTGCGATATTCAAAGCTCAGCAATTTGTATGGACAA4920 ATCGTTGACATACATCGTTGCGAAAAATGCTGGGATAGCTACTCCCGCCTTTTGGGTTAT4980 TAATAAAGATGATAGGCCGGTGGCAGCTACGTTTACCTATCCTGTTTTTGTTAAGCCGGC5040 GCGTTCAGGCTCATCCTTCGGTGTGAAAAAAGTCAATAGCGCGGACGAATTGGACTACGC5100 AATTGAATCGGCAAGACAATATGACAGCAAAATCTTAATTGAGCAGGCTGTTTCGGGCTG5160 TGAGGTCGGTTGTGCGGTATTGGGAAACAGTGCCGCGTTAGTTGTTGGCGAGGTGGACCA5220 AATCAGGCTGCAGTACGGAATCTTTCGTATTCATCAGGAAGTCGAGCCGGAAAAAGGCTC5280 TGAAAACGCAGTTATAACCGTTCCCGCAGACCTTTCAGCAGAGGAGCGAGGACGGATACA5340 GGAAACGGCAAAAAAAATATATAAAGCGCTCGGCTGTAGAGGTCTAGCCCGTGTGGATAT5400 GTTTTTACAAGATAACGGCCGCATTGTACTGAACGAAGTCAATACTCTGCCCGGTTTCAC5460 GTCATACAGTCGTTATCCCCGTATGATGGCCGCTGCAGGTATTGCACTTCCCGAACTGAT5520 TGACCGCTTGATCGTATTAGCGTTAAAGGGGTGATAAGCATGGAAATAGGATTTACTTTT5580 TTAGATGAAATAGTACACGGTGTTCGTTGGGACGCTAAATATGCCACTTGGGATAATTTC5640 ACCGGAAAACCGGTTGACGGTTATGAAGTAAATCGCATTGTAGGGACATACGAGTTGGCT5700 GAATCGCTTTTGAAGGCAAAAGAACTGGCTGCTACCCAAGGGTACGGATTGCTTCTATGG5760 GACGGTTACCGTCCTAAGCGTGCTGTAAACTGTTTTATGCAATGGGCTGCACAGCCGGAA5820 AATAACCTGACAAAGGAAAGTTATTATCCCAATATTGACCGAACTGAGATGATTTCAAAA5880 GGATACGTGGCTTCAAAATCAAGCCATAGCCGCGGCAGTGCCATTGATCTTACGCTTTAT5940 CGATTAGACACGGGTGAGCTTGTACCAATGGGGAGCCGATTTGATTTTATGGATGAACGC6000 TCTCATCATGCGGCAAATGGAATATCATGCAATGAAGCGCAAAATCGCAGACGTTTGCGC6060 TCCATCATGGAAAACAGTGGGTTTGAAGCATATAGCCTCGAATGGTGGCACTATGTATTA6120 AGAGACGAACCATACCCCAATAGCTATTTTGATTTCCCCGTTAAATAAACTTTTAACCGT6180 TGCACGGACAAACTATATAAGCTAACTCTTTCGGCAGGAAACCCGACGTATGTAACTGGT6240 TCTTAGGGAATTTATATATAGTAGATAGTATTGAAGATGTAAGGCAGAGCGATATTGCGG6300 TCATTATCTGCGTGCGCTGCGGCAAGATAGCCTGATAATAAGACTGATCGCATAGAGGGG6360 TGGTATTTCACACCGCCCATTGTCAACAGGCAGTTCAGCCTCGTTAAATTCAGCATGGGT6420 ATCACTTATGAAAATTCATCTACATTGGTGATAATAGTAAATCCAGTAGGGCGAAATAAT6480 TGACTGTAATTTACGGGGCAAAACGGCACAATCTCAAACGAGATTGTGCCGTTTAAGGGG6540 AAGATTCTAGAAATATTTCATACTTCCAACTATATAGTTAAGGAGGAGACTGAAAATGAA6600 GAAGTTGTTTTTTTTATTGTTATTGTTATTCTTAATATACTTAGGTTATGACTACGTTAA6660 TGAAGCACTGTTTTCTCAGGAAAAAGTCGAATTTCAAAATTATGATCAAAATCCCAAAGA6720 ACATTTAGAAAATAGTGGGACTTCTGAAAATACCCAAGAGAAAACAATTACAGAAGAACA6780 GGTTTATCAAGGAAATCTGCTATTAATCAATAGTAAATATCCTGTTCGCCAAGAAGTGTG6840 AAGTCAGATATCGTGAATTTATCTAAACATGACGAATTAATAAATGGATACGGGTTGCTT6900 GATAGTAATATTTATATGTCAAAAGAAATAGCACAAAAATTTTCAGAGATGGTCAATGAT6960 GCTGTAAAGGGTGGCGTTAGTCATTTTATTATTAATAGTGGCTATCGAGACTTTGATGAG7020 CAAAGTGTGCTTTACCAAGAAATGGGGGCTGAGTATGCCTTACCAGCAGGTTATAGTGAG7080 CATAATTCAGGTTTATCACTAGATGTAGGATCAAGCTTGACGAAAATGGAACGAGCCCCT7140 GAAGGAAAGTGGATAGAAGAAAATGCTTGGAAATACGGGTTCATTTTACGTTATCCAGAG7200 GACAAAACAGAGTTAACAGGAATTC7225 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10851 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: GGGGTAGCGTCAGGAAAATGCGGATTTACAACGCTAAGCCTATTTTCCTGACGAATCCCT60 CGTTTTTAACAACGTTAAGAAAGTTTTAGTGGTCTTAAAGAATTTAATGAGACTACTTTC120 TCTGAGTTAAAATGGTATTCTCCTAGTAAATTAATATGTTCCCAACCTAAGGGCGACATA180 TGGTGTAACAAATCTTCATTAAAGCTACCTGTCCGTTTTTTATATTCAACTGCTGTTGTT240 AGGTGGAGAGTATTCCAAATACTTATAGCATTGATAATTATGTTTAAAGCACTGGCTCTT300 TGCAATTGATGCTGTATGGTGCGTTCTCTAAGCTCACCTTGTTTTCCGAAGAAAATAGCT360 CTTGCCAATCCATTCATGGCTTCTCCTTTATTCAATCCTCTTTGTATTTTTCTTCTTAAT420 GATTCATCCGATATATAATTCAAAATAAAGATCGTTTTTTCTATTCGGCCCATCTCACGT480 AAGGCTGTAGCTAAGCTGTTTTGTCTTGAATAGGAACCTAGCTTCCCCATAATAAGGGAT540 GCTGAAACTGTTCCCTCCCTTATAGAATGAGCTAATCGCAAAACATCCTCATAATTTTCT600 TTAATGACCTTTGTATTTATTTGTCCACGTAAAATGGCTTCTAGTTTTGGATACTCACTT660 GCTTTATCTATCGTAAATAATTTTGAGTCCGATAAATCCCTTATTCTTGGGGCAAATTTA720 AATCCTAATAAATGAGTCAGTCCGAATATTTGGTCAGTGTAACCGGCAGTGTCTGTATAA780 TGTTCCTCTATGTTTAGATCCGTCTCATGATGTAACAAACCATCCAAAACATGAATCGCA840 TCTCTTGAATTAGTATGAATAATCTTTGTGTAGTAAGAAGAGAATTGATCACTTGTAAAT900 CGGTAGATGGTGGCTCCTTTTCCAGTTCCATAATGTGGATTTGCATCTGCATGTAGTGAT960 GAAACACCTAGCTGCATTCTCATACCATCTGACGAAGATGTTGTACCGTCGCCCCAATAG1020 AAAGGCAATTGTAATTTATGATGAAAGTTTACTAATATGGCTTGGGCTTTATTCATGGCA1080 TCTTCATACATGCGCCATTGAGATACATTGGCTAGTTGCTTATATGTAAGTCCGGGTGTG1140 GCTTCGGCCATCTTGCTCAAGCCAATATTCATTCCCATTCCTAAAAGGGCAGCCATGATA1200 ATGATTGTTTCTTCCTTATCTGGTTTTCGATTATTGGAAGCATGAGTGAATTGCTCATGA1260 AATCCTGTTATATGGGCCACATCCATGAGTAAATCAGTTAATTTTATTCTTGGTAGCATC1320 TGATAAAGGCTTGCACTAAATTTTTTTGCTTCTTCTGGAACATCTTTTTCTAAGCGTGCA1380 AGTGATAGCTTTCCTTTTTCAAGAGAAACCCCATCTAACTTATTGGAATTGGCAGCTAAC1440 CACTTTAACCTTTCATTAAAGCTGCTGGTTCTCTCCGTTATATAATCTTCGAATGATAAA1500 CTAACTGATAATCTCGTATTCCCCTTCGATTGATTCCATGTATCTTCCGAAAACAAATAT1560 TCCTCAAAATCCCTATATTGTCTGCTGCCAACAATGGAAACATCTCCTGCCCGAACATGC1620 TCCCGAAGTTCTGTTAAAACAGCCATTTCATAGTAATGACGATTAATTGTTGTACCATCA1680 TCCTCGTATAAATGTCTTTTCCATCGTTTTGAAATAAAATCCACAGGTGAGTCATCAGGC1740 ACTTTTCGCTTTCCAGATTCGTTCATTCCTCGGATAATCTCAACAGCTTGTAAAAGTGGC1800 TCATTTGCCTTTGTAGAATGAAATTCCAATACTCTTAATAGCGTTGGCGTATATTTTCTT1860 AGTGAATAAAACCGTTTTTGCAGTAAGTCTAAATAATCATAGTCGGCAGGACGTGCAAGT1920 TCCTGAGCCTCTTCTACTGAAGAGACAAAGGTATTCCATTCAATAACCGATTCTAAAACC1980 TTAAAAACGTCTAATTTTTCCTCTCTTGCTTTAATTAATGCTTGTCCGATGTTCGTAAAG2040 TGTATAACTTTCTCATTTAGCTTTTTACCGTTTTGTTTCTGGATTTCCTCTTGAGCCTTA2100 CGACCTTTTGATAACAAACTAAGTATTTGCCTATCATGAATTTCAAACGCTTTATCCGTT2160 AGCTCCTGAGTAAGTTGTAATAAATAGATGGTTAATATCGAATAACGTTTATTTTCTTGA2220 AAGTCACGGAATGCATACGGCTCGTATCTTGAGCCTAAGCGAGACAGCTGCAACAGGCGG2280 TTACGGTGCAAATGACTAATTTGCACTGTTTCTAAATCCATTCCTCGTATGTATTCGAGT2340 CGTTCTATTATTTTTAGAAAAGTTTCGGGTGAAGGATGACCCGGTGGCTCTTTTAACCAA2400 CCCAATATCGTTTTATTGGATTCGGATGGATGCTGCGAGGTAATAATCCCTTCAAGCTTT2460 TCTTTTTGCTCATTTGTTAGAGATTTACTAACCGTATTAAATAGCTTCTTTTCAGCCATT2520 GCCCTTGCTTCCCACACCATTCTTTCAAGTGTAGTGATAGCAGGCAGTATAATTTTGTTT2580 TTTCTTAGAAAATCTATGCATTCATGCAGTAGATGAATGGCATCACCATTTTCCAAAGCT2640 AATTGATGAAGGTACTTAAATGTCATTCGATATTCACTCAGGGTAAAAGTTACAAAGTCG2700 TATTCACTTCGAATTTCTTTCAAATGATCCCAAAGTGTATTTTCCCTTTGAGGATAATGA2760 TCAAGCGAGGATGGACTAACACCAATCTGTTTCGATATATATTGTATGACCGAATCTGGG2820 ATGCTTTTGATATGAGTGTATGGCCAACCGGGATACCGAAGAACAGCTAATTGAACAGCA2880 AATCCTAAACGGTTTTCTTCCCTCCTTCGCTTATTAACTATTTCTAAATCCCGTTTGGAA2940 AAAGTGAAGTAGGTCCCCAGTATCCATTCATCTTCAGGGATTTGCATAAAAGCCTGTCTC3000 TGTTCCGGTGTAAGCAATTCTCTACCTCTCGCAATTTTCATTCAGTATCATTCCATTTCT3060 GTATTTTCAATTTATTAGTTCAATTATATATCAATAGAGTGTACTCTATTGATACAAATG3120 TAGTAGACTGATAAAATCATAGTTAAGAGCGTCTCATAAGACTTGTCTCAAAAATGAGGT3180 GATATTTTGCGGAAAATCGGTTATATTCGTGTCAGTTCGACTAACCAGAATCCTTCAAGA3240 CAATTTCAGCAGTTGAACGAGATCGGAATGGATATTATATATGAAGAGAAAGTTTCAGGA3300 GCAACAAAGGATCGCGAGCAACTTCAAAAAGTGTTAGACGATTTACAGGAAGATGACATC3360 ATTTATGTTACAGACTTAACTCGAATCACTCGTAGTACACAAGATCTATTTGAATTAATC3420 GATAACATACGAGATAAAAAGGCAAGTTTAAAATCACTAAAAGATACATGGCTTGATTTA3480 TCAGAAGATAATCCATACAGCCAATTCTTAATTACTGTAATGGCTGGTGTTAACCAATTA3540 GAGCGAGATCTTATTCGGATGAGACAACGTGAAGGGATTGAATTGGCTAAGAAAGAAGGA3600 AAGTTTAAAGGTCGATTAAAGAAGTATCATAAAAATCACGCAGGAATGAATTATGCGGTA3660 AAGCTATATAAAGAAGGAAATATGACTGTAAATCAAATTTGTGAAATTACTAATGTATCT3720 AGGGCTTCATTATACAGGAAATTATCAGAAGTGAATAATTAGCCATTCTGTATTCCGCTA3780 ATGGGCAATATTTTTAAAGAAGAAAAGGAAACTATAAAATATTAACAGCCTCCTAGCGAT3840 GCCGAAAAGCCCTTTGATAAAAAAAGAATCATCATCTTAAGAAATTCTTAGTCATTTATT3900 ATGTAAATGCTTATAAATTCGGCCCTATAATCTGATAAATTATTAAGGGCAAACTTATGT3960 GAAAGGGTGATAACTATGAGCGATAAAATACTTATTGTGGATGATGAACATGAAATTGCC4020 GATTTGGTTGAATTATACTTAAAAAACGAGAATTATACGGTTTTCAAATACTATACCGCC4080 AAAGAAGCATTGGAATGTATAGACAAGTCTGAGATTGACCTTGCCATATTGGACATCATG4140 CTTCCCGGCACAAGCGGCCTTACTATCTGTCAAAAAATAAGGGACAAGCACACCTATCCG4200 ATTATCATGCTGACCGGGAAAGATACAGAGGTAGATAAAATTACAGGGTTAACAATCGGC4260 GCGGATGATTATATAACGAAGCCCTTTCGCCCACTGGAGTTAATTGCTCGGGTAAAGGCC4320 CAGTTGCGCCGATACAAAAAATTCAGTGGAGTAAAGGAGCAGAACGAAAATGTTATCGTC4380 CACTCCGGCCTTGTCATTAATGTTAACACCCATGAGTGTTATCTGAACGAGAAGCAGTTA4440 TCCCTTACTCCCACCGAGTTTTCAATACTGCGAATCCTCTGTGAAAACAAGGGGAATGTG4500 GTTAGCTCCGAGCTGCTATTTCATGAGATATGGGGCGACGAATATTTCAGCAAGAGCAAC4560 AACACCATCACCGTGCATATCCGGCATTTGCGCGAAAAAATGAACGACACCATTGATAAT4620 CCGAAATATATAAAAACGGTATGGGGGGTTGGTTATAAAATTGAAAAATAAAAAAAACGA4680 CTATTCCAAACTAGAACGAAAACTTTACATGTATATCGTTGCAATTGTTGTGGTAGCAAT4740 TGTATTCGTGTTGTATATTCGTTCAATGATCCGAGGGAAACTTGGGGATTGGATCTTAAG4800 TATTTTGGAAAACAAATATGACTTAAATCACCTGGACGCGATGAAATTATATCAATATTC4860 CATACGGAACAATATAGATATCTTTATTTATGTGGCGATTGTCATTAGTATTCTTATTCT4920 ATGTCGCGTCATGCTTTCAAAATTCGCAAAATACTTTGACGAGATAAATACCGGCATTGA4980 TGTACTTATTCAGAACGAAGATAAACAAATTGAGCTTTCTGCGGAAATGGATGTTATGGA5040 ACAAAAGCTCAACACATTAAAACGGACTCTGGAAAAGCGAGAGCAGGATGCAAAGCTGGC5100 CGAACAAAGAAAAAATGACGTTGTTATGTACTTGGCGCACGATATTAAAACGCCCCTTAC5160 ATCCATTATCGGTTATTTGAGCCTGCTTGACGAGGCTCCAGACATGCCGGTAGATCAAAA5220 GGCAAAGTATGTGCATATCACGTTGGACAAAGCGTATCGACTCGAACAGCTAATCGACGA5280 GTTTTTTGAGATTACACGGTATAACCTACAAACGATAACGCTAACAAAAACGCACATAGA5340 CCTATACTATATGCTGGTGCAGATGACCGATGAATTTTATCCTCAGCTTTCCGCACATGG5400 AAAACAGGCGGTTATTCACGCCCCCGAGGATCTGACCGTGTCCGGCGACCCTGATAAACT5460 CGCGAGAGTCTTTAACAACATTTTGAAAAACGCCGCTGCATACAGTGAGGATAACAGCAT5520 CATTGACATTACCGCGGGCCTCTCCGGGGATGTGGTGTCAATCGAATTCAAGAACACTGG5580 AAGCATCCCAAAAGATAAGCTAGCTGCCATATTTGAAAAGTTCTATAGGCTGGACAATGC5640 TCGTTCTTCCGATACGGGTGGCGCGGGACTTGGATTGGCGATTGCAAAAGAAATTATTGT5700 TCAGCATGGAGGGCAGATTTACGCGGAAAGCAATGATAACTATACGACGTTTAGGGTAGA5760 GCTTCCAGCGATGCCAGACTTGGTTGATAAAAGGAGGTCCTAAGAGATGTATATAATTTT5820 TTAGGAAAATCTCAAGGTTATCTTTACTTTTTCTTAGGAAATTAACAATTTAATATTAAG5880 AAACGGCTCGTTCTTACACGGTAGACTTAATACCGTAAGAACGAGCCGTTTTCGTTCTTC5940 AGAGAAAGATTTGACAAGATTACCATTGGCATCCCCGTTTTATTTGGTGCCTTTCACAGA6000 AAGGGTTGGTCTTAATTATGAATAACATCGGCATTACTGTTTATGGATGTGAGCAGGATG6060 AGGCAGATGCATTCCATGCTCTTTCGCCTCGCTTTGGCGTTATGGCAACGATAATTAACG6120 CCAACGTGTCGGAATCCAACGCCAAATCCGCGCCTTTCAATCAATGTATCAGTGTGGGAC6180 ATAAATCAGAGATTTCCGCCTCTATTCTTCTTGCGCTGAAGAGAGCCGGTGTGAAATATA6240 TTTCTACCCGAAGCATCGGCTGCAATCATATAGATACAACTGCTGCTAAGAGAATGGGCA6300 TCACTGTCGACAATGTGGCGTACTCGCCGGATAGCGTTGCCGATTATACTATGATGCTAA6360 TTCTTATGGCAGTACGCAACGTAAAATCGATTGTGCGCTCTGTGGAAAAACATGATTTCA6420 GGTTGGACAGCGACCGTGGCAAGGTACTCAGCGACATGACAGTTGGTGTGGTGGGAACGG6480 GCCAGATAGGCAAAGCGGTTATTGAGCGGCTGCGAGGATTTGGATGTAAAGTGTTGGCTT6540 ATAGTCGCAGCCGAAGTATAGAGGTAAACTATGTACCGTTTGATGAGTTGCTGCAAAATA6600 GCGATATCGTTACGCTTCATGTGCCGCTCAATACGGATACGCACTATATTATCAGCCACG6660 AACAAATACAGAGAATGAAGCAAGGAGCATTTCTTATCAATACTGGGCGCGGTCCACTTG6720 TAGATACCTATGAGTTGGTTAAAGCATTAGAAAACGGGAAACTGGGCGGTGCCGCATTGG6780 ATGTATTGGAAGGAGAGGAAGAGTTTTTCTACTCTGATTGCACCCAAAAACCAATTGATA6840 ATCAATTTTTACTTAAACTTCAAAGAATGCCTAACGTGATAATCACACCGCATACGGCCT6900 ATTATACCGAGCAAGCGTTGCGTGATACCGTTGAAAAAACCATTAAAAACTGTTTGGATT6960 TTGAAAGGAGACAGGAGCATGAATAGAATAAAAGTTGCAATACTGTTTGGGGGTTGCTCA7020 GAGGAGCATGACGTATCGGTAAAATCTGCAATAGAGATAGCCGCTAACATTAATAAAGAA7080 AAATACGAGCCGTTATACATTGGAATTACGAAATCTGGTGTATGGAAAATGTGCGAAAAA7140 CCTTGCGCGGAATGGGAAAACGACAATTGCTATTCAGCTGTACTCTCGCCGGATAAAAAA7200 ATGCACGGATTACTTGTTAAAAAGAACCATGAATATGAAATCAACCATGTTGATGTAGCA7260 TTTTCAGCTTTGCATGGCAAGTCAGGTGAAGATGGATCCATACAAGGTCTGTTTGAATTG7320 TCCGGTATCCCTTTTGTAGGCTGCGATATTCAAAGCTCAGCAATTTGTATGGACAAATCG7380 TTGACATACATCGTTGCGAAAAATGCTGGGATAGCTACTCCCGCCTTTTGGGTTATTAAT7440 AAAGATGATAGGCCGGTGGCAGCTACGTTTACCTATCCTGTTTTTGTTAAGCCGGCGCGT7500 TCAGGCTCATCCTTCGGTGTGAAAAAAGTCAATAGCGCGGACGAATTGGACTACGCAATT7560 GAATCGGCAAGACAATATGACAGCAAAATCTTAATTGAGCAGGCTGTTTCGGGCTGTGAG7620 GTCGGTTGTGCGGTATTGGGAAACAGTGCCGCGTTAGTTGTTGGCGAGGTGGACCAAATC7680 AGGCTGCAGTACGGAATCTTTCGTATTCATCAGGAAGTCGAGCCGGAAAAAGGCTCTGAA7740 AACGCAGTTATAACCGTTCCCGCAGACCTTTCAGCAGAGGAGCGAGGACGGATACAGGAA7800 ACGGCAAAAAAAATATATAAAGCGCTCGGCTGTAGAGGTCTAGCCCGTGTGGATATGTTT7860 TTACAAGATAACGGCCGCATTGTACTGAACGAAGTCAATACTCTGCCCGGTTTCACGTCA7920 TACAGTCGTTATCCCCGTATGATGGCCGCTGCAGGTATTGCACTTCCCGAACTGATTGAC7980 CGCTTGATCGTATTAGCGTTAAAGGGGTGATAAGCATGGAAATAGGATTTACTTTTTTAG8040 ATGAAATAGTACACGGTGTTCGTTGGGACGCTAAATATGCCACTTGGGATAATTTCACCG8100 GAAAACCGGTTGACGGTTATGAAGTAAATCGCATTGTAGGGACATACGAGTTGGCTGAAT8160 CGCTTTTGAAGGCAAAAGAACTGGCTGCTACCCAAGGGTACGGATTGCTTCTATGGGACG8220 GTTACCGTCCTAAGCGTGCTGTAAACTGTTTTATGCAATGGGCTGCACAGCCGGAAAATA8280 ACCTGACAAAGGAAAGTTATTATCCCAATATTGACCGAACTGAGATGATTTCAAAAGGAT8340 ACGTGGCTTCAAAATCAAGCCATAGCCGCGGCAGTGCCATTGATCTTACGCTTTATCGAT8400 TAGACACGGGTGAGCTTGTACCAATGGGGAGCCGATTTGATTTTATGGATGAACGCTCTC8460 ATCATGCGGCAAATGGAATATCATGCAATGAAGCGCAAAATCGCAGACGTTTGCGCTCCA8520 TCATGGAAAACAGTGGGTTTGAAGCATATAGCCTCGAATGGTGGCACTATGTATTAAGAG8580 ACGAACCATACCCCAATAGCTATTTTGATTTCCCCGTTAAATAAACTTTTAACCGTTGCA8640 CGGACAAACTATATAAGCTAACTCTTTCGGCAGGAAACCCGACGTATGTAACTGGTTCTT8700 AGGGAATTTATATATAGTAGATAGTATTGAAGATGTAAGGCAGAGCGATATTGCGGTCAT8760 TATCTGCGTGCGCTGCGGCAAGATAGCCTGATAATAAGACTGATCGCATAGAGGGGTGGT8820 ATTTCACACCGCCCATTGTCAACAGGCAGTTCAGCCTCGTTAAATTCAGCATGGGTATCA8880 CTTATGAAAATTCATCTACATTGGTGATAATAGTAAATCCAGTAGGGCGAAATAATTGAC8940 TGTAATTTACGGGGCAAAACGGCACAATCTCAAACGAGATTGTGCCGTTTAAGGGGAAGA9000 TTCTAGAAATATTTCATACTTCCAACTATATAGTTAAGGAGGAGACTGAAAATGAAGAAG9060 TTGTTTTTTTTATTGTTATTGTTATTCTTAATATACTTAGGTTATGACTACGTTAATGAA9120 GCACTGTTTTCTCAGGAAAAAGTCGAATTTCAAAATTATGATCAAAATCCCAAAGAACAT9180 TTAGAAAATAGTGGGACTTCTGAAAATACCCAAGAGAAAACAATTACAGAAGAACAGGTT9240 TATCAAGGAAATCTGCTATTAATCAATAGTAAATATCCTGTTCGCCAAGAAAGTGTGAAG9300 TCAGATATCGTGAATTTATCTAAACATGACGAATTAATAAATGGATACGGGTTGCTTGAT9360 AGTAATATTTATATGTCAAAAGAAATAGCACAAAAATTTTCAGAGATGGTCAATGATGCT9420 GTAAAGGGTGGCGTTAGTCATTTTATTATTAATAGTGGCTATCGAGACTTTGATGAGCAA9480 AGTGTGCTTTACCAAGAAATGGGGGCTGAGTATGCCTTACCAGCAGGTTATAGTGAGCAT9540 AATTCAGGTTTATCACTAGATGTAGGATCAAGCTTGACGAAAATGGAACGAGCCCCTGAA9600 GGAAAGTGGATAGAAGAAAATGCTTGGAAATACGGGTTCATTTTACGTTATCCAGAGGAC9660 AAAACAGAGTTAACAGGAATTCAATATGAACCATGGCATATTCGCTATGTTGGTTTACCA9720 CATAGTGCGATTATGAAAGAAAAGAATTTCGTTCTCGAGGAATATATGGATTACCTAAAA9780 GAAGAAAAAACCATTTCTGTTAGTGTAAATGGGGAAAAATATGAGATCTTTTATTATCCT9840 GTTACTAAAAATACCACCATTCATGTGCCGACTAATCTTCGTTATGAGATATCAGGAAAC9900 AATATAGACGGTGTAATTGTGACAGTGTTTCCCGGATCAACACATACTAATTCAAGGAGG9960 TAAGGATGGCGGAATGAAACCAACGAAATTAATGAACAGCATTATTGTACTAGCACTTTT10020 GGGGTAACGTTAGCTTTTTAATTTAAAACCCACGTTAACTAGGACATTGCTATACTAATG10080 ATACAACTTAAACAAAAGAATTAGAGGAAATTATATTGGGAAAAATATTATCTAGAGGAT10140 TGCTAGCTTTATATTTAGTGACACTAATCTGGTTAGTGTTATTCAAATTACAATACAATA10200 TTTTATCAGTATTTAATTATCATCAAAGAAGTCTTAACTTGACTCCATTTACTGCTACTG10260 GGAATTTCAGAGAGATGATAGATAATGTTATAATCTTTATTCCATTTGGCTTGCTTTTGA10320 ATGTCAATTTTAAAGAAATCGGATTTTTACCTAAGTTTGCTTTTGTACTGGTTTTAAGTC10380 TTACTTTTGAAATAATTCAATTTATCTTCGCTATTGGAGCGACAGACATAACAGATGTAA10440 TTACAAATACTGTTGGAGGCTTTCTTGGACTGAAATTATATGGTTTAAGCAATAAGCATA10500 TGAATCAAAAAAAATTAGACAGAGTTATTATTTTTGTAGGTATACTTTTGCTCGTATTAT10560 TGCTCGTTTACCGTACCCATTTAAGAATAAATTACGTGTAAGATGTCTAAATCAAGCAAT10620 CTGATCTTTCATACACATAAAGATATTGAATGAATTGGATTAGATGGAAAACGGGATGTG10680 GGGAAACTCGCCCGTAGGTGTGAAGTGAGGGGAAAACCGGTGATAAAGTAAAAAGCTTAC10740 CTAACACTATAGTAACAAAGAAAGCCCAATTATCAATTTTAGTGCTGAGGAATTGGTCTC10800 TTTAATAAATTTCCTTAACGTTGTAAATCCGCATTTTCCTGACGGTACCCC10851 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2667 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: CAAGATTACCATTGGCATCCCCGTTTTATTTGGTGCCTTTCACAGAAAGGGTTGGTCTTA60 ATTATGAATAACATCGGCATTACTGTTTATGGATGTGAGCAGGATGAGGCAGATGCATTC120 CATGCTCTTTCGCCTCGCTTTGGCGTTATGGCAACGATAATTAACGCCAACGTGTCGGAA180 TCCAACGCCAAATCCGCGCCTTTCAATCAATGTATCAGTGTGGGACATAAATCAGAGATT240 TCCGCCTCTATTCTTCTTGCGCTGAAGAGAGCCGGTGTGAAATATATTTCTACCCGAAGC300 ATCGGCTGCAATCATATAGATACAACTGCTGCTAAGAGAATGGGCATCACTGTCGACAAT360 GTGGCGTACTCGCCGGATAGCGTTGCCGATTATACTATGATGCTAATTCTTATGGCAGTA420 CGCAACGTAAAATCGATTGTGCGCTCTGTGGAAAAACATGATTTCAGGTTGGACAGCGAC480 CGTGGCAAGGTACTCAGCGACATGACAGTTGGTGTGGTGGGAACGGGCCAGATAGGCAAA540 GCGGTTATTGAGCGGCTGCGAGGATTTGGATGTAAAGTGTTGGCTTATAGTCGCAGCCGA600 AGTATAGAGGTAAACTATGTACCGTTTGATGAGTTGATGCAAAATAGCGATATCGTTACG660 CTTCATGTGCCGCTCAATACGGATACGCACTATATTATCAGCCACGAACAAATACAGAGA720 ATGAAGCAAGGAGCATTTCTTATCAATACTGGGCGCGGTCCACTTGTAGATACCTATGAG780 TTGGTTAAAGCATTAGAAAACGGGAAACTGGGCGGTGCCGCATTGGATGTATTGGAAGGA840 GAGGAAGAGTTTTTCTACTCTGATTGCACCCAAAAACCAATTGATAATCAATTTTTACTT900 AAACTTCAAAGAATGCCTAACGTGATAATCACACCGCATACGGCCTATTATACCGAGCAA960 GCGTTGCGTGATACCGTTGAAAAAACCATTAAAAACTGTTTGGATTTTGAAAGGAGACAG1020 GAGCATGAATAGAATAAAAGTTGCAATACTGTTTGGGGGTTGCTCAGAGGAGCATGACGT1080 ATCGGTAAAATCTGCAATAGAGATAGCCGCTAACATTAATAAAGAAAAATACGAGCCGTT1140 ATACATTGGAATTACGAAATCTGGTGTATGGAAAATGTGCGAAAAACCTTGCGCGGAATG1200 GGAAAACGACAATTGCTATTCAGCTGTACTCTCGCCGGATAAAAAAATGCACGGATTACT1260 TGTTAAAAAGAACCATGAATATGAAATCAACCATGTTGATGTAGCATTTTCAGCTTTGCA1320 TGGCAAGTCAGGTGAAGATGGATCCATACAAGGTCTGTTTGAATTGTCCGGTATCCCTTT1380 TGTAGGCTGCGATATTCAAAGCTCAGCAATTTGTATGGACAAATCGTTGACATACATCGT1440 TGCGAAAAATGCTGGGATAGCTACTCCCGCCTTTTGGGTTATTAATAAAGATGATAGGCC1500 GGTGGCAGCTACGTTTACCTATCCTGTTTTTGTTAAGCCGGCGCGTTCAGGCTCATCCTT1560 CGGTGTGAAAAAAGTCAATAGCGCGGACGAATTGGACTACGCAATTGAATCGGCAAGACA1620 ATATGACAGCAAAATCTTAATTGAGCAGGCTGTTTCGGGCTGTGAGGTCGGTTGTGCGGT1680 ATTGGGAAACAGTGCCGCGTTAGTTGTTGGCGAGGTGGACCAAATCAGGCTGCAGTACGG1740 AATCTTTCGTATTCATCAGGAAGTCGAGCCGGAAAAAGGCTCTGAAAACGCAGTTATAAC1800 CGTTCCCGCAGACCTTTCAGCAGAGGAGCGAGGACGGATACAGGAAACGGCAAAAAAAAT1860 ATATAAAGCGCTCGGCTGTAGAGGTCTAGCCCGTGTGGATATGTTTTTACAAGATAACGG1920 CCGCATTGTACTGAACGAAGTCAATACTCTGCCCGGTTTCACGTCATACAGTCGTTATCC1980 CCGTATGATGGCCGCTGCAGGTATTGCACTTCCCGAACTGATTGACCGCTTGATCGTATT2040 AGCGTTAAAGGGGTGATAAGCATGGAAATAGGATTTACTTTTTTAGATGAAATAGTACAC2100 GGTGTTCGTTGGGACGCTAAATATGCCACTTGGGATAATTTCACCGGAAAACCGGTTGAC2160 GGTTATGAAGTAAATCGCATTGTAGGGACATACGAGTTGGCTGAATCGCTTTTGAAGGCA2220 AAAGAACTGGCTGCTACCCAAGGGTACGGATTGCTTCTATGGGACGGTTACCGTCCTAAG2280 CGTGCTGTAAACTGTTTTATGCAATGGGCTGCACAGCCGGAAAATAACCTGACAAAGGAA2340 AGTTATTATCCCAATATTGACCGAACTGAGATGATTTCAAAAGGATACGTGGCTTCAAAA2400 TCAAGCCATAGCCGCGGCAGTGCCATTGATCTTACGCTTTATCGATTAGACACGGGTGAG2460 CTTGTACCAATGGGGAGCCGATTTGATTTTATGGATGAACGCTCTCATCATGCGGCAAAT2520 GGAATATCATGCAATGAAGCGCAAAATCGCAGACGTTTGCGCTCCATCATGGAAAACAGT2580 GGGTTTGAAGCATATAGCCTCGAATGGTGGCACTATGTATTAAGAGACGAACCATACCCC2640 AATAGCTATTTTGATTTCCCCGTTAAA2667 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2964 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..2964 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: ATGAAAATTGCGAGAGGTAGAGAATTGCTTACACCGGAACAGAGACAG48 MetLysIleAlaArgGlyArgGluLeuLeuThrProGluGlnArgGln 151015 GCTTTTATGCAAATCCCTGAAGATGAATGGATACTGGGGACCTACTTC96 AlaPheMetGlnIleProGluAspGluTrpIleLeuGlyThrTyrPhe 202530 ACTTTTTCCAAACGGGATTTAGAAATAGTTAATAAGCGAAGGAGGGAA144 ThrPheSerLysArgAspLeuGluIleValAsnLysArgArgArgGlu 354045 GAAAACCGTTTAGGATTTGCTGTTCAATTAGCTGTTCTTCGGTATCCC192 GluAsnArgLeuGlyPheAlaValGlnLeuAlaValLeuArgTyrPro 505560 GGTTGGCCATACACTCATATCAAAAGCATCCCAGATTCGGTCATACAA240 GlyTrpProTyrThrHisIleLysSerIleProAspSerValIleGln 65707580 TATATATCGAAACAGATTGGTGTTAGTCCATCCTCGCTTGATCATTAT288 TyrIleSerLysGlnIleGlyValSerProSerSerLeuAspHisTyr 859095 CCTCAAAGGGAAAATACACTTTGGGATCATTTGAAAGAAATTCGAAGT336 ProGlnArgGluAsnThrLeuTrpAspHisLeuLysGluIleArgSer 100105110 GAATACGACTTTGTAACTTTTACCCTGAGTGAATATCGAATGACATTT384 GluTyrAspPheValThrPheThrLeuSerGluTyrArgMetThrPhe 115120125 AAGTACCTTCATCAATTAGCTTTGGAAAATGGTGATGCCATTCATCTA432 LysTyrLeuHisGlnLeuAlaLeuGluAsnGlyAspAlaIleHisLeu 130135140 CTGCATGAATGCATAGATTTTCTAAGAAAAAACAAAATTATACTGCCT480 LeuHisGluCysIleAspPheLeuArgLysAsnLysIleIleLeuPro 145150155160 GCTATCACTACACTTGAAAGAATGGTGTGGGAAGCAAGGGCAATGGCT528 AlaIleThrThrLeuGluArgMetValTrpGluAlaArgAlaMetAla 165170175 GAAAAGAAGCTATTTAATACGGTTAGTAAATCTCTAACAAATGAGCAA576 GluLysLysLeuPheAsnThrValSerLysSerLeuThrAsnGluGln 180185190 AAAGAAAAGCTTGAAGGGATTATTACCTCGCAGCATCCATCCGAATCC624 LysGluLysLeuGluGlyIleIleThrSerGlnHisProSerGluSer 195200205 AATAAAACGATATTGGGTTGGTTAAAAGAGCCACCGGGTCATCCTTCA672 AsnLysThrIleLeuGlyTrpLeuLysGluProProGlyHisProSer 210215220 CCCGAAACTTTTCTAAAAATAATAGAACGACTCGAATACATACGAGGA720 ProGluThrPheLeuLysIleIleGluArgLeuGluTyrIleArgGly 225230235240 ATGGATTTAGAAACAGTGCAAATTAGTCATTTGCACCGTAACCGCCTG768 MetAspLeuGluThrValGlnIleSerHisLeuHisArgAsnArgLeu 245250255 TTGCAGCTGTCTCGCTTAGGCTCAAGATACGAGCCGTATGCATTCCGT816 LeuGlnLeuSerArgLeuGlySerArgTyrGluProTyrAlaPheArg 260265270 GACTTTCAAGAAAATAAACGTTATTCGATATTAACCATCTATTTATTA864 AspPheGlnGluAsnLysArgTyrSerIleLeuThrIleTyrLeuLeu 275280285 CAACTTACTCAGGAGCTAACGGATAAAGCGTTTGAAATTCATGATAGG912 GlnLeuThrGlnGluLeuThrAspLysAlaPheGluIleHisAspArg 290295300 CAAATACTTAGTTTGTTATCAAAAGGTCGTAAGGCTCAAGAGGAAATC960 GlnIleLeuSerLeuLeuSerLysGlyArgLysAlaGlnGluGluIle 305310315320 CAGAAACAAAACGGTAAAAAGCTAAATGAGAAAGTTATACACTTTACG1008 GlnLysGlnAsnGlyLysLysLeuAsnGluLysValIleHisPheThr 325330335 AACATCGGACAAGCATTAATTAAAGCAAGAGAGGAAAAATTAGACGTT1056 AsnIleGlyGlnAlaLeuIleLysAlaArgGluGluLysLeuAspVal 340345350 TTTAAGGTTTTAGAATCGGTTATTGAATGGAATACCTTTGTCTCTTCA1104 PheLysValLeuGluSerValIleGluTrpAsnThrPheValSerSer 355360365 GTAGAAGAGGCTCAGGAACTTGCACGTCCTGCCGACTATGATTATTTA1152 ValGluGluAlaGlnGluLeuAlaArgProAlaAspTyrAspTyrLeu 370375380 GACTTACTGCAAAAACGGTTTTATTCACTAAGAAAATATACGCCAACG1200 AspLeuLeuGlnLysArgPheTyrSerLeuArgLysTyrThrProThr 385390395400 CTATTAAGAGTATTGGAATTTCATTCTACAAAGGCAAATGAGCCACTT1248 LeuLeuArgValLeuGluPheHisSerThrLysAlaAsnGluProLeu 405410415 TTACAAGCTGTTGAGATTATCCGAGGAATGAACGAATCTGGAAAGCGA1296 LeuGlnAlaValGluIleIleArgGlyMetAsnGluSerGlyLysArg 420425430 AAAGTGCCTGATGACTCACCTGTGGATTTTATTTCAAAACGATGGAAA1344 LysValProAspAspSerProValAspPheIleSerLysArgTrpLys 435440445 AGACATTTATACGAGGATGATGGTACAACAATTAATCGTCATTACTAT1392 ArgHisLeuTyrGluAspAspGlyThrThrIleAsnArgHisTyrTyr 450455460 GAAATGGCTGTTTTAACAGAACTTCGGGAGCATGTTCGGGCAGGAGAT1440 GluMetAlaValLeuThrGluLeuArgGluHisValArgAlaGlyAsp 465470475480 GTTTCCATTGTTGGCAGCAGACAATATAGGGATTTTGAGGAATATTTG1488 ValSerIleValGlySerArgGlnTyrArgAspPheGluGluTyrLeu 485490495 TTTTCGGAAGATACATGGAATCAATCGAAGGGGAATACGAGATTATCA1536 PheSerGluAspThrTrpAsnGlnSerLysGlyAsnThrArgLeuSer 500505510 GTTAGTTTATCATTCGAAGATTATATAACGGAGAGAACCAGCAGCTTT1584 ValSerLeuSerPheGluAspTyrIleThrGluArgThrSerSerPhe 515520525 AATGAAAGGTTAAAGTGGTTAGCTGCCAATTCCAATAAGTTAGATGGG1632 AsnGluArgLeuLysTrpLeuAlaAlaAsnSerAsnLysLeuAspGly 530535540 GTTTCTCTTGAAAAAGGAAAGCTATCACTTGCACGCTTAGAAAAAGAT1680 ValSerLeuGluLysGlyLysLeuSerLeuAlaArgLeuGluLysAsp 545550555560 GTTCCAGAAGAAGCAAAAAAATTTAGTGCAAGCCTTTATCAGATGCTA1728 ValProGluGluAlaLysLysPheSerAlaSerLeuTyrGlnMetLeu 565570575 CCAAGAATAAAATTAACTGATTTACTCATGGATGTGGCCCATATAACA1776 ProArgIleLysLeuThrAspLeuLeuMetAspValAlaHisIleThr 580585590 GGATTTCATGAGCAATTCACTCATGCTTCCAATAATCGAAAACCAGAT1824 GlyPheHisGluGlnPheThrHisAlaSerAsnAsnArgLysProAsp 595600605 AAGGAAGAAACAATCATTATCATGGCTGCCCTTTTAGGAATGGGAATG1872 LysGluGluThrIleIleIleMetAlaAlaLeuLeuGlyMetGlyMet 610615620 AATATTGGCTTGAGCAAGATGGCCGAAGCCACACCCGGACTTACATAT1920 AsnIleGlyLeuSerLysMetAlaGluAlaThrProGlyLeuThrTyr 625630635640 AAGCAACTAGCCAATGTATCTCAATGGCGCATGTATGAAGATGCCATG1968 LysGlnLeuAlaAsnValSerGlnTrpArgMetTyrGluAspAlaMet 645650655 AATAAAGCCCAAGCCATATTAGTAAACTTTCATCATAAATTACAATTG2016 AsnLysAlaGlnAlaIleLeuValAsnPheHisHisLysLeuGlnLeu 660665670 CCTTTCTATTGGGGCGACGGTACAACATCTTCGTCAGATGGTATGAGA2064 ProPheTyrTrpGlyAspGlyThrThrSerSerSerAspGlyMetArg 675680685 ATGCAGCTAGGTGTTTCATCACTACATGCAGATGCAAATCCACATTAT2112 MetGlnLeuGlyValSerSerLeuHisAlaAspAlaAsnProHisTyr 690695700 GGAACTGGAAAAGGAGCCACCATCTACCGATTTACAAGTGATCAATTC2160 GlyThrGlyLysGlyAlaThrIleTyrArgPheThrSerAspGlnPhe 705710715720 TCTTCTTACTACACAAAGATTATTCATACTAATTCAAGAGATGCGATT2208 SerSerTyrTyrThrLysIleIleHisThrAsnSerArgAspAlaIle 725730735 CATGTTTTGGATGGTTTGTTACATCATGAGACGGATCTAAACATAGAG2256 HisValLeuAspGlyLeuLeuHisHisGluThrAspLeuAsnIleGlu 740745750 GAACATTATACAGACACTGCCGGTTACACTGACCAAATATTCGGACTG2304 GluHisTyrThrAspThrAlaGlyTyrThrAspGlnIlePheGlyLeu 755760765 ACTCATTTATTAGGATTTAAATTTGCCCCAAGAATAAGGGATTTATCG2352 ThrHisLeuLeuGlyPheLysPheAlaProArgIleArgAspLeuSer 770775780 GACTCAAAATTATTTACGATAGATAAAGCAAGTGAGTATCCAAAACTA2400 AspSerLysLeuPheThrIleAspLysAlaSerGluTyrProLysLeu 785790795800 GAAGCCATTTTACGTGGACAAATAAATACAAAGGTCATTAAAGAAAAT2448 GluAlaIleLeuArgGlyGlnIleAsnThrLysValIleLysGluAsn 805810815 TATGAGGATGTTTTGCGATTAGCTCATTCTATAAGGGAGGGAACAGTT2496 TyrGluAspValLeuArgLeuAlaHisSerIleArgGluGlyThrVal 820825830 TCAGCATCCCTTATTATGGGGAAGCTAGGTTCCTATTCAAGACAAAAC2544 SerAlaSerLeuIleMetGlyLysLeuGlySerTyrSerArgGlnAsn 835840845 AGCTTAGCTACAGCCTTACGTGAGATGGGCCGAATAGAAAAAACGATC2592 SerLeuAlaThrAlaLeuArgGluMetGlyArgIleGluLysThrIle 850855860 TTTATTTTGAATTATATATCGGATGAATCATTAAGAAGAAAAATACAA2640 PheIleLeuAsnTyrIleSerAspGluSerLeuArgArgLysIleGln 865870875880 AGAGGATTGAATAAAGGAGAAGCCATGAATGGATTGGCAAGAGCTATT2688 ArgGlyLeuAsnLysGlyGluAlaMetAsnGlyLeuAlaArgAlaIle 885890895 TTCTTCGGAAAACAAGGTGAGCTTAGAGAACGCACCATACAGCATCAA2736 PhePheGlyLysGlnGlyGluLeuArgGluArgThrIleGlnHisGln 900905910 TTGCAAAGAGCCAGTGCTTTAAACATAATTATCAATGCTATAAGTATT2784 LeuGlnArgAlaSerAlaLeuAsnIleIleIleAsnAlaIleSerIle 915920925 TGGAATACTCTCCACCTAACAACAGCAGTTGAATATAAAAAACGGACA2832 TrpAsnThrLeuHisLeuThrThrAlaValGluTyrLysLysArgThr 930935940 GGTAGCTTTAATGAAGATTTGTTACACCATATGTCGCCCTTAGGTTGG2880 GlySerPheAsnGluAspLeuLeuHisHisMetSerProLeuGlyTrp 945950955960 GAACATATTAATTTACTAGGAGAATACCATTTTAACTCAGAGAAAGTA2928 GluHisIleAsnLeuLeuGlyGluTyrHisPheAsnSerGluLysVal 965970975 GTCTCATTAAATTCTTTAAGACCACTAAAACTTTCT2964 ValSerLeuAsnSerLeuArgProLeuLysLeuSer 980985 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 988 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: MetLysIleAlaArgGlyArgGluLeuLeuThrProGluGlnArgGln 151015 AlaPheMetGlnIleProGluAspGluTrpIleLeuGlyThrTyrPhe 202530 ThrPheSerLysArgAspLeuGluIleValAsnLysArgArgArgGlu 354045 GluAsnArgLeuGlyPheAlaValGlnLeuAlaValLeuArgTyrPro 505560 GlyTrpProTyrThrHisIleLysSerIleProAspSerValIleGln 65707580 TyrIleSerLysGlnIleGlyValSerProSerSerLeuAspHisTyr 859095 ProGlnArgGluAsnThrLeuTrpAspHisLeuLysGluIleArgSer 100105110 GluTyrAspPheValThrPheThrLeuSerGluTyrArgMetThrPhe 115120125 LysTyrLeuHisGlnLeuAlaLeuGluAsnGlyAspAlaIleHisLeu 130135140 LeuHisGluCysIleAspPheLeuArgLysAsnLysIleIleLeuPro 145150155160 AlaIleThrThrLeuGluArgMetValTrpGluAlaArgAlaMetAla 165170175 GluLysLysLeuPheAsnThrValSerLysSerLeuThrAsnGluGln 180185190 LysGluLysLeuGluGlyIleIleThrSerGlnHisProSerGluSer 195200205 AsnLysThrIleLeuGlyTrpLeuLysGluProProGlyHisProSer 210215220 ProGluThrPheLeuLysIleIleGluArgLeuGluTyrIleArgGly 225230235240 MetAspLeuGluThrValGlnIleSerHisLeuHisArgAsnArgLeu 245250255 LeuGlnLeuSerArgLeuGlySerArgTyrGluProTyrAlaPheArg 260265270 AspPheGlnGluAsnLysArgTyrSerIleLeuThrIleTyrLeuLeu 275280285 GlnLeuThrGlnGluLeuThrAspLysAlaPheGluIleHisAspArg 290295300 GlnIleLeuSerLeuLeuSerLysGlyArgLysAlaGlnGluGluIle 305310315320 GlnLysGlnAsnGlyLysLysLeuAsnGluLysValIleHisPheThr 325330335 AsnIleGlyGlnAlaLeuIleLysAlaArgGluGluLysLeuAspVal 340345350 PheLysValLeuGluSerValIleGluTrpAsnThrPheValSerSer 355360365 ValGluGluAlaGlnGluLeuAlaArgProAlaAspTyrAspTyrLeu 370375380 AspLeuLeuGlnLysArgPheTyrSerLeuArgLysTyrThrProThr 385390395400 LeuLeuArgValLeuGluPheHisSerThrLysAlaAsnGluProLeu 405410415 LeuGlnAlaValGluIleIleArgGlyMetAsnGluSerGlyLysArg 420425430 LysValProAspAspSerProValAspPheIleSerLysArgTrpLys 435440445 ArgHisLeuTyrGluAspAspGlyThrThrIleAsnArgHisTyrTyr 450455460 GluMetAlaValLeuThrGluLeuArgGluHisValArgAlaGlyAsp 465470475480 ValSerIleValGlySerArgGlnTyrArgAspPheGluGluTyrLeu 485490495 PheSerGluAspThrTrpAsnGlnSerLysGlyAsnThrArgLeuSer 500505510 ValSerLeuSerPheGluAspTyrIleThrGluArgThrSerSerPhe 515520525 AsnGluArgLeuLysTrpLeuAlaAlaAsnSerAsnLysLeuAspGly 530535540 ValSerLeuGluLysGlyLysLeuSerLeuAlaArgLeuGluLysAsp 545550555560 ValProGluGluAlaLysLysPheSerAlaSerLeuTyrGlnMetLeu 565570575 ProArgIleLysLeuThrAspLeuLeuMetAspValAlaHisIleThr 580585590 GlyPheHisGluGlnPheThrHisAlaSerAsnAsnArgLysProAsp 595600605 LysGluGluThrIleIleIleMetAlaAlaLeuLeuGlyMetGlyMet 610615620 AsnIleGlyLeuSerLysMetAlaGluAlaThrProGlyLeuThrTyr 625630635640 LysGlnLeuAlaAsnValSerGlnTrpArgMetTyrGluAspAlaMet 645650655 AsnLysAlaGlnAlaIleLeuValAsnPheHisHisLysLeuGlnLeu 660665670 ProPheTyrTrpGlyAspGlyThrThrSerSerSerAspGlyMetArg 675680685 MetGlnLeuGlyValSerSerLeuHisAlaAspAlaAsnProHisTyr 690695700 GlyThrGlyLysGlyAlaThrIleTyrArgPheThrSerAspGlnPhe 705710715720 SerSerTyrTyrThrLysIleIleHisThrAsnSerArgAspAlaIle 725730735 HisValLeuAspGlyLeuLeuHisHisGluThrAspLeuAsnIleGlu 740745750 GluHisTyrThrAspThrAlaGlyTyrThrAspGlnIlePheGlyLeu 755760765 ThrHisLeuLeuGlyPheLysPheAlaProArgIleArgAspLeuSer 770775780 AspSerLysLeuPheThrIleAspLysAlaSerGluTyrProLysLeu 785790795800 GluAlaIleLeuArgGlyGlnIleAsnThrLysValIleLysGluAsn 805810815 TyrGluAspValLeuArgLeuAlaHisSerIleArgGluGlyThrVal 820825830 SerAlaSerLeuIleMetGlyLysLeuGlySerTyrSerArgGlnAsn 835840845 SerLeuAlaThrAlaLeuArgGluMetGlyArgIleGluLysThrIle 850855860 PheIleLeuAsnTyrIleSerAspGluSerLeuArgArgLysIleGln 865870875880 ArgGlyLeuAsnLysGlyGluAlaMetAsnGlyLeuAlaArgAlaIle 885890895 PhePheGlyLysGlnGlyGluLeuArgGluArgThrIleGlnHisGln 900905910 LeuGlnArgAlaSerAlaLeuAsnIleIleIleAsnAlaIleSerIle 915920925 TrpAsnThrLeuHisLeuThrThrAlaValGluTyrLysLysArgThr 930935940 GlySerPheAsnGluAspLeuLeuHisHisMetSerProLeuGlyTrp 945950955960 GluHisIleAsnLeuLeuGlyGluTyrHisPheAsnSerGluLysVal 965970975 ValSerLeuAsnSerLeuArgProLeuLysLeuSer 980985 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 573 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..573 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: TTGCGGAAAATCGGTTATATTCGTGTCAGTTCGACTAACCAGAATCCT48 LeuArgLysIleGlyTyrIleArgValSerSerThrAsnGlnAsnPro 151015 TCAAGACAATTTCAGCAGTTGAACGAGATCGGAATGGATATTATATAT96 SerArgGlnPheGlnGlnLeuAsnGluIleGlyMetAspIleIleTyr 202530 GAAGAGAAAGTTTCAGGAGCAACAAAGGATCGCGAGCAACTTCAAAAA144 GluGluLysValSerGlyAlaThrLysAspArgGluGlnLeuGlnLys 354045 GTGTTAGACGATTTACAGGAAGATGACATCATTTATGTTACAGACTTA192 ValLeuAspAspLeuGlnGluAspAspIleIleTyrValThrAspLeu 505560 ACTCGAATCACTCGTAGTACACAAGATCTATTTGAATTAATCGATAAC240 ThrArgIleThrArgSerThrGlnAspLeuPheGluLeuIleAspAsn 65707580 ATACGAGATAAAAAGGCAAGTTTAAAATCACTAAAAGATACATGGCTT288 IleArgAspLysLysAlaSerLeuLysSerLeuLysAspThrTrpLeu 859095 GATTTATCAGAAGATAATCCATACAGCCAATTCTTAATTACTGTAATG336 AspLeuSerGluAspAsnProTyrSerGlnPheLeuIleThrValMet 100105110 GCTGGTGTTAACCAATTAGAGCGAGATCTTATTCGGATGAGACAACGT384 AlaGlyValAsnGlnLeuGluArgAspLeuIleArgMetArgGlnArg 115120125 GAAGGGATTGAATTGGCTAAGAAAGAAGGAAAGTTTAAAGGTCGATTA432 GluGlyIleGluLeuAlaLysLysGluGlyLysPheLysGlyArgLeu 130135140 AAGAAGTATCATAAAAATCACGCAGGAATGAATTATGCGGTAAAGCTA480 LysLysTyrHisLysAsnHisAlaGlyMetAsnTyrAlaValLysLeu 145150155160 TATAAAGAAGGAAATATGACTGTAAATCAAATTTGTGAAATTACTAAT528 TyrLysGluGlyAsnMetThrValAsnGlnIleCysGluIleThrAsn 165170175 GTATCTAGGGCTTCATTATACAGGAAATTATCAGAAGTGAATAAT573 ValSerArgAlaSerLeuTyrArgLysLeuSerGluValAsnAsn 180185190 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 191 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: LeuArgLysIleGlyTyrIleArgValSerSerThrAsnGlnAsnPro 151015 SerArgGlnPheGlnGlnLeuAsnGluIleGlyMetAspIleIleTyr 202530 GluGluLysValSerGlyAlaThrLysAspArgGluGlnLeuGlnLys 354045 ValLeuAspAspLeuGlnGluAspAspIleIleTyrValThrAspLeu 505560 ThrArgIleThrArgSerThrGlnAspLeuPheGluLeuIleAspAsn 65707580 IleArgAspLysLysAlaSerLeuLysSerLeuLysAspThrTrpLeu 859095 AspLeuSerGluAspAsnProTyrSerGlnPheLeuIleThrValMet 100105110 AlaGlyValAsnGlnLeuGluArgAspLeuIleArgMetArgGlnArg 115120125 GluGlyIleGluLeuAlaLysLysGluGlyLysPheLysGlyArgLeu 130135140 LysLysTyrHisLysAsnHisAlaGlyMetAsnTyrAlaValLysLeu 145150155160 TyrLysGluGlyAsnMetThrValAsnGlnIleCysGluIleThrAsn 165170175 ValSerArgAlaSerLeuTyrArgLysLeuSerGluValAsnAsn 180185190 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 909 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..909 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: ATGAAGAAGTTGTTTTTTTTATTGTTATTGTTATTCTTAATATACTTA48 MetLysLysLeuPhePheLeuLeuLeuLeuLeuPheLeuIleTyrLeu 151015 GGTTATGACTACGTTAATGAAGCACTGTTTTCTCAGGAAAAAGTCGAA96 GlyTyrAspTyrValAsnGluAlaLeuPheSerGlnGluLysValGlu 202530 TTTCAAAATTATGATCAAAATCCCAAAGAACATTTAGAAAATAGTGGG144 PheGlnAsnTyrAspGlnAsnProLysGluHisLeuGluAsnSerGly 354045 ACTTCTGAAAATACCCAAGAGAAAACAATTACAGAAGAACAGGTTTAT192 ThrSerGluAsnThrGlnGluLysThrIleThrGluGluGlnValTyr 505560 CAAGGAAATCTGCTATTAATCAATAGTAAATATCCTGTTCGCCAAGAA240 GlnGlyAsnLeuLeuLeuIleAsnSerLysTyrProValArgGlnGlu 65707580 AGTGTGAAGTCAGATATCGTGAATTTATCTAAACATGACGAATTAATA288 SerValLysSerAspIleValAsnLeuSerLysHisAspGluLeuIle 859095 AATGGATACGGGTTGCTTGATAGTAATATTTATATGTCAAAAGAAATA336 AsnGlyTyrGlyLeuLeuAspSerAsnIleTyrMetSerLysGluIle 100105110 GCACAAAAATTTTCAGAGATGGTCAATGATGCTGTAAAGGGTGGCGTT384 AlaGlnLysPheSerGluMetValAsnAspAlaValLysGlyGlyVal 115120125 AGTCATTTTATTATTAATAGTGGCTATCGAGACTTTGATGAGCAAAGT432 SerHisPheIleIleAsnSerGlyTyrArgAspPheAspGluGlnSer 130135140 GTGCTTTACCAAGAAATGGGGGCTGAGTATGCCTTACCAGCAGGTTAT480 ValLeuTyrGlnGluMetGlyAlaGluTyrAlaLeuProAlaGlyTyr 145150155160 AGTGAGCATAATTCAGGTTTATCACTAGATGTAGGATCAAGCTTGACG528 SerGluHisAsnSerGlyLeuSerLeuAspValGlySerSerLeuThr 165170175 AAAATGGAACGAGCCCCTGAAGGAAAGTGGATAGAAGAAAATGCTTGG576 LysMetGluArgAlaProGluGlyLysTrpIleGluGluAsnAlaTrp 180185190 AAATACGGGTTCATTTTACGTTATCCAGAGGACAAAACAGAGTTAACA624 LysTyrGlyPheIleLeuArgTyrProGluAspLysThrGluLeuThr 195200205 GGAATTCAATATGAACCATGGCATATTCGCTATGTTGGTTTACCACAT672 GlyIleGlnTyrGluProTrpHisIleArgTyrValGlyLeuProHis 210215220 AGTGCGATTATGAAAGAAAAGAATTTCGTTCTCGAGGAATATATGGAT720 SerAlaIleMetLysGluLysAsnPheValLeuGluGluTyrMetAsp 225230235240 TACCTAAAAGAAGAAAAAACCATTTCTGTTAGTGTAAATGGGGAAAAA768 TyrLeuLysGluGluLysThrIleSerValSerValAsnGlyGluLys 245250255 TATGAGATCTTTTATTATCCTGTTACTAAAAATACCACCATTCATGTG816 TyrGluIlePheTyrTyrProValThrLysAsnThrThrIleHisVal 260265270 CCGACTAATCTTCGTTATGAGATATCAGGAAACAATATAGACGGTGTA864 ProThrAsnLeuArgTyrGluIleSerGlyAsnAsnIleAspGlyVal 275280285 ATTGTGACAGTGTTTCCCGGATCAACACATACTAATTCAAGGAGG909 IleValThrValPheProGlySerThrHisThrAsnSerArgArg 290295300 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 303 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: MetLysLysLeuPhePheLeuLeuLeuLeuLeuPheLeuIleTyrLeu 151015 GlyTyrAspTyrValAsnGluAlaLeuPheSerGlnGluLysValGlu 202530 PheGlnAsnTyrAspGlnAsnProLysGluHisLeuGluAsnSerGly 354045 ThrSerGluAsnThrGlnGluLysThrIleThrGluGluGlnValTyr 505560 GlnGlyAsnLeuLeuLeuIleAsnSerLysTyrProValArgGlnGlu 65707580 SerValLysSerAspIleValAsnLeuSerLysHisAspGluLeuIle 859095 AsnGlyTyrGlyLeuLeuAspSerAsnIleTyrMetSerLysGluIle 100105110 AlaGlnLysPheSerGluMetValAsnAspAlaValLysGlyGlyVal 115120125 SerHisPheIleIleAsnSerGlyTyrArgAspPheAspGluGlnSer 130135140 ValLeuTyrGlnGluMetGlyAlaGluTyrAlaLeuProAlaGlyTyr 145150155160 SerGluHisAsnSerGlyLeuSerLeuAspValGlySerSerLeuThr 165170175 LysMetGluArgAlaProGluGlyLysTrpIleGluGluAsnAlaTrp 180185190 LysTyrGlyPheIleLeuArgTyrProGluAspLysThrGluLeuThr 195200205 GlyIleGlnTyrGluProTrpHisIleArgTyrValGlyLeuProHis 210215220 SerAlaIleMetLysGluLysAsnPheValLeuGluGluTyrMetAsp 225230235240 TyrLeuLysGluGluLysThrIleSerValSerValAsnGlyGluLys 245250255 TyrGluIlePheTyrTyrProValThrLysAsnThrThrIleHisVal 260265270 ProThrAsnLeuArgTyrGluIleSerGlyAsnAsnIleAspGlyVal 275280285 IleValThrValPheProGlySerThrHisThrAsnSerArgArg 290295300 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 483 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..483 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: TTGGGAAAAATATTATCTAGAGGATTGCTAGCTTTATATTTAGTGACA48 LeuGlyLysIleLeuSerArgGlyLeuLeuAlaLeuTyrLeuValThr 151015 CTAATCTGGTTAGTGTTATTCAAATTACAATACAATATTTTATCAGTA96 LeuIleTrpLeuValLeuPheLysLeuGlnTyrAsnIleLeuSerVal 202530 TTTAATTATCATCAAAGAAGTCTTAACTTGACTCCATTTACTGCTACT144 PheAsnTyrHisGlnArgSerLeuAsnLeuThrProPheThrAlaThr 354045 GGGAATTTCAGAGAGATGATAGATAATGTTATAATCTTTATTCCATTT192 GlyAsnPheArgGluMetIleAspAsnValIleIlePheIleProPhe 505560 GGCTTGCTTTTGAATGTCAATTTTAAAGAAATCGGATTTTTACCTAAG240 GlyLeuLeuLeuAsnValAsnPheLysGluIleGlyPheLeuProLys 65707580 TTTGCTTTTGTACTGGTTTTAAGTCTTACTTTTGAAATAATTCAATTT288 PheAlaPheValLeuValLeuSerLeuThrPheGluIleIleGlnPhe 859095 ATCTTCGCTATTGGAGCGACAGACATAACAGATGTAATTACAAATACT336 IlePheAlaIleGlyAlaThrAspIleThrAspValIleThrAsnThr 100105110 GTTGGAGGCTTTCTTGGACTGAAATTATATGGTTTAAGCAATAAGCAT384 ValGlyGlyPheLeuGlyLeuLysLeuTyrGlyLeuSerAsnLysHis 115120125 ATGAATCAAAAAAAATTAGACAGAGTTATTATTTTTGTAGGTATACTT432 MetAsnGlnLysLysLeuAspArgValIleIlePheValGlyIleLeu 130135140 TTGCTCGTATTATTGCTCGTTTACCGTACCCATTTAAGAATAAATTAC480 LeuLeuValLeuLeuLeuValTyrArgThrHisLeuArgIleAsnTyr 145150155160 GTG483 Val (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 161 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: LeuGlyLysIleLeuSerArgGlyLeuLeuAlaLeuTyrLeuValThr 151015 LeuIleTrpLeuValLeuPheLysLeuGlnTyrAsnIleLeuSerVal 202530 PheAsnTyrHisGlnArgSerLeuAsnLeuThrProPheThrAlaThr 354045 GlyAsnPheArgGluMetIleAspAsnValIleIlePheIleProPhe 505560 GlyLeuLeuLeuAsnValAsnPheLysGluIleGlyPheLeuProLys 65707580 PheAlaPheValLeuValLeuSerLeuThrPheGluIleIleGlnPhe 859095 IlePheAlaIleGlyAlaThrAspIleThrAspValIleThrAsnThr 100105110 ValGlyGlyPheLeuGlyLeuLysLeuTyrGlyLeuSerAsnLysHis 115120125 MetAsnGlnLysLysLeuAspArgValIleIlePheValGlyIleLeu 130135140 LeuLeuValLeuLeuLeuValTyrArgThrHisLeuArgIleAsnTyr 145150155160 Val (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: ATGCTCCTGTCTCCTTTC18 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2296 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: LysLeuPhePheLeuLeuIleCysArgPheThrAsnArgIleLysLeu 151015 LeuPheSerHisCysProCysPheProHisHisSerPheLysCysSer 202530 AspSerArgGlnTyrAsnPheValPheSerLysIleTyrAlaPheMet 354045 GlnMetAsnGlyIleThrIlePheGlnSerLeuMetLysValLeuLys 505560 CysHisSerIlePheThrGlnGlyLysSerTyrLysValValPheThr 65707580 SerAsnPhePheGlnMetIleProLysCysIlePheProLeuArgIle 859095 MetIleLysArgGlyTrpThrAsnThrAsnLeuPheArgTyrIleLeu 100105110 TyrAspArgIleTrpAspAlaPheAspMetSerValTrpProThrGly 115120125 IleProLysAsnSerLeuAsnSerLysSerThrValPhePheProPro 130135140 SerLeuIleAsnTyrPheIleProPheGlyLysSerGluValGlyPro 145150155160 GlnTyrProPheIlePheArgAspLeuHisLysSerLeuSerLeuPhe 165170175 ArgCysLysGlnPheSerThrSerArgAsnPheHisSerValSerPhe 180185190 HisPheCysIlePheAsnLeuLeuValGlnLeuTyrIleAsnArgVal 195200205 TyrSerIleAspThrAsnValValAspAsnHisSerGluArgLeuIle 210215220 ArgLeuValSerLysMetArgTyrPheAlaGluAsnArgLeuTyrSer 225230235240 CysGlnPheAspProGluSerPheLysThrIleSerAlaValGluArg 245250255 AspArgAsnGlyTyrTyrIleLysArgLysPheGlnGluGlnGlnArg 260265270 IleAlaSerAsnPheLysLysCysThrIleTyrArgLysMetThrSer 275280285 PheMetLeuGlnThrLeuGluSerLeuValValHisLysIleTyrLeu 290295300 AsnSerIleThrTyrGluIleLysArgGlnValAsnHisLysIleHis 305310315320 GlyLeuIleTyrGlnLysIleIleHisThrAlaAsnSerLeuLeuTrp 325330335 LeuValLeuThrAsnSerGluIleLeuPheGlyAspAsnValLysGly 340345350 LeuAsnTrpLeuArgLysLysGluSerLeuLysValAspArgSerIle 355360365 IleLysIleThrGlnGluIleMetArgArgLysLeuTyrLysGluGly 370375380 AsnMetThrValAsnGlnIleCysGluIleThrAsnValSerArgAla 385390395400 SerLeuTyrArgLysLeuSerGluValAsnAsnProPheCysIlePro 405410415 LeuMetGlyAsnIlePheLysGluGluLysGluThrIleLysTyrGln 420425430 ProProSerAspAlaGluLysProPheAspLysLysArgIleIleIle 435440445 LeuArgAsnSerSerPheIleMetMetLeuIleAsnSerAlaLeuSer 450455460 AspLysLeuLeuArgAlaAsnLeuCysGluArgValIleThrMetSer 465470475480 AspLysIleLeuIleValAspAspGluHisGluIleAlaAspLeuVal 485490495 GluLeuTyrLeuLysAsnGluAsnTyrThrValPheLysTyrTyrThr 500505510 AlaLysGluAlaLeuGluCysIleAspLysSerGluIleAspLeuAla 515520525 IleLeuAspIleMetLeuProGlyThrSerGlyLeuThrIleCysGln 530535540 LysIleArgAspLysHisThrTyrProIleIleMetLeuThrGlyLys 545550555560 AspThrGluValAspLysIleThrGlyLeuThrIleGlyAlaAspAsp 565570575 TyrIleThrLysProPheArgProLeuGluLeuIleAlaArgValLys 580585590 AlaGlnLeuArgArgTyrLysLysPheSerGlyValLysGluGlnAsn 595600605 GluAsnValIleValHisSerGlyLeuValIleAsnValAsnThrHis 610615620 GluCysTyrLeuAsnGluLysGlnLeuSerLeuThrProThrGluPhe 625630635640 SerIleLeuArgIleLeuCysGluAsnLysGlyAsnValValSerSer 645650655 GluLeuLeuPheHisGluIleTrpGlyAspGluTyrPheSerLysSer 660665670 AsnAsnThrIleThrValHisIleArgHisLeuArgGluLysMetAsn 675680685 AspThrIleAspAsnProLysTyrIleLysThrValTrpGlyValGly 690695700 TyrLysIleGluLysLysLysArgLeuPheGlnThrArgThrLysThr 705710715720 LeuHisValTyrArgCysAsnCysCysGlySerAsnCysIleArgVal 725730735 ValTyrSerPheAsnAspProArgGluThrTrpGlyLeuAspLeuLys 740745750 TyrPheGlyLysGlnIleLeuLysSerProGlyArgAspGluIleIle 755760765 SerIlePheHisThrGluGlnTyrArgTyrLeuTyrLeuCysGlyAsp 770775780 CysHisTyrSerTyrSerMetSerArgHisAlaPheLysIleArgLys 785790795800 IleLeuArgAspLysTyrArgHisCysThrTyrSerGluArgArgThr 805810815 AsnAlaPheCysGlyAsnGlyCysTyrGlyThrLysAlaGlnHisIle 820825830 LysThrAspSerGlyLysAlaArgAlaGlyCysLysAlaGlyArgThr 835840845 LysLysLysArgCysTyrValLeuGlyAlaArgTyrAsnAlaProTyr 850855860 IleHisTyrArgLeuPheGluProAlaArgGlySerArgHisAlaGly 865870875880 ArgSerLysGlyLysValCysAlaTyrHisValGlyGlnSerValSer 885890895 ThrArgThrAlaAsnArgArgValPheAspTyrThrValProThrAsn 900905910 AspAsnAlaAsnLysAsnAlaHisArgProIleLeuTyrAlaGlyAla 915920925 AspAspArgIleLeuSerSerAlaPheArgThrTrpLysThrGlyGly 930935940 TyrSerArgProArgGlySerAspArgValArgArgProThrArgGlu 945950955960 SerLeuGlnHisPheGluLysArgArgCysIleGlnGlyGlnHisHis 965970975 HisTyrArgGlyProLeuArgGlyCysGlyValAsnArgIleGlnGlu 980985990 HisTrpLysHisProLysArgAlaSerCysHisIleLysValLeuAla 99510001005 GlyGlnPheSerPhePheArgTyrGlyTrpArgGlyThrTrpIleGly 101010151020 AspCysLysArgAsnTyrCysSerAlaTrpArgAlaAspLeuArgGly 1025103010351040 LysLeuLeuTyrAspValGlyArgAlaSerSerAspAlaArgLeuGly 104510501055 LysGluValLeuArgAspValTyrAsnPheLeuGlyLysSerGlnGly 106010651070 TyrLeuTyrPhePheLeuGlyAsnGlnPheAsnIleLysLysArgLeu 107510801085 ValLeuThrArgThrTyrArgLysAsnGluProPheSerPhePheArg 109010951100 GluArgPheAspLysIleThrIleGlyIleProValLeuPheGlyAla 1105111011151120 PheHisArgLysGlyTrpSerLeuIleThrSerAlaLeuLeuPheMet 112511301135 AspValSerArgMetArgGlnMetHisSerMetLeuPheArgLeuAla 114011451150 LeuAlaLeuTrpGlnArgLeuThrProThrCysArgAsnProThrPro 115511601165 AsnProArgLeuSerIleAsnValSerValTrpAspIleAsnGlnArg 117011751180 PheProProLeuPhePheLeuArgArgGluProValAsnIlePheLeu 1185119011951200 ProGluAlaSerAlaAlaIleIleIleGlnLeuLeuLeuArgGluTrp 120512101215 AlaSerLeuSerThrMetTrpArgThrArgArgIleAlaLeuProIle 122012251230 IleLeuCysPheLeuTrpGlnTyrAlaThrAsnArgLeuCysAlaLeu 123512401245 TrpLysAsnMetIleSerGlyTrpThrAlaThrValAlaArgTyrSer 125012551260 AlaThrGlnLeuValTrpTrpGluArgAlaArgAlaLysArgLeuLeu 1265127012751280 SerGlyCysGluAspLeuAspValLysCysTrpLeuIleValAlaAla 128512901295 GluValArgThrMetTyrArgLeuMetSerCysCysLysIleAlaIle 130013051310 SerLeuArgPheMetCysArgSerIleArgIleArgThrIleLeuSer 131513201325 AlaThrAsnLysTyrArgGluSerLysGluHisPheLeuSerIleLeu 133013351340 GlyAlaValHisLeuIleProMetSerTrpLeuLysHisLysThrGly 1345135013551360 AsnTrpAlaValProHisTrpMetTyrTrpLysGluArgLysSerPhe 136513701375 SerThrLeuIleAlaProLysAsnGlnLeuIleIleAsnPheTyrLeu 138013851390 AsnPheLysGluCysLeuThrSerHisArgIleArgProIleIlePro 139514001405 SerLysArgCysValIleProLeuLysLysProLeuLysThrValTrp 141014151420 IleLeuLysGlyAspArgSerMetAsnArgIleLysValAlaIleLeu 1425143014351440 PheGlyGlyCysSerGluGluHisAspValSerValLysSerAlaIle 144514501455 GluIleAlaAlaAsnIleAsnLysGluLysTyrGluProLeuTyrIle 146014651470 GlyIleThrLysSerGlyValTrpLysMetCysGluLysProCysAla 147514801485 GluTrpGluAsnAspAsnCysTyrSerAlaValLeuSerProAspLys 149014951500 LysMetHisGlyLeuLeuValLysLysAsnHisGluTyrGluIleAsn 1505151015151520 HisValAspValAlaPheSerAlaLeuHisGlyLysSerGlyGluAsp 152515301535 GlySerIleGlnGlyLeuPheGluLeuSerGlyIleProPheValGly 154015451550 CysAspIleGlnSerSerAlaIleCysMetAspLysSerLeuThrTyr 155515601565 IleValAlaLysAsnAlaGlyIleAlaThrProAlaPheTrpValIle 157015751580 AsnLysAspAspArgProValAlaAlaThrPheThrTyrProValPhe 1585159015951600 ValLysProAlaArgSerGlySerSerPheGlyValLysLysValAsn 160516101615 SerAlaAspGluLeuAspTyrAlaIleGluSerAlaArgGlnTyrAsp 162016251630 SerLysIleLeuIleGluGlnAlaValSerGlyCysGluValGlyCys 163516401645 AlaValLeuGlyAsnSerAlaAlaLeuValValGlyGluValAspGln 165016551660 IleArgLeuGlnTyrGlyIlePheArgIleHisGlnGluValGluPro 1665167016751680 GluLysGlySerGluAsnAlaValIleThrValProAlaAspLeuSer 168516901695 AlaGluGluArgGlyArgIleGlnGluThrAlaLysLysIleTyrLys 170017051710 AlaLeuGlyCysArgGlyLeuAlaArgValAspMetPheLeuGlnAsp 171517201725 AsnGlyArgIleValLeuAsnGluValAsnThrLeuProGlyPheThr 173017351740 SerTyrSerArgTyrProArgMetMetAlaAlaAlaGlyIleAlaLeu 1745175017551760 ProGluLeuIleAspArgLeuIleValLeuAlaLeuLysGlyAlaTrp 176517701775 LysAspLeuLeuPheMetLysTyrThrValPheValGlyThrLeuAsn 178017851790 MetProLeuGlyIleIleSerProGluAsnArgLeuThrValMetLys 179518001805 IleAlaLeuGlyHisThrSerTrpLeuAsnArgPheArgGlnLysAsn 181018151820 TrpLeuLeuProLysGlyThrAspCysPheTyrGlyThrValThrVal 1825183018351840 LeuSerValLeuThrValLeuCysAsnGlyLeuHisSerArgLysIle 184518501855 ThrGlnArgLysValIleIleProIleLeuThrGluLeuArgPheGln 186018651870 LysAspThrTrpLeuGlnAsnGlnAlaIleAlaAlaAlaValProLeu 187518801885 IleLeuArgPheIleAspThrArgValSerLeuTyrGlnTrpGlyAla 189018951900 AspLeuIleLeuTrpMetAsnAlaLeuIleMetArgGlnMetGluTyr 1905191019151920 HisAlaMetLysArgLysIleAlaAspValCysAlaProSerTrpLys 192519301935 ThrValGlyLeuLysHisIleAlaSerAsnGlyGlyThrMetTyrGlu 194019451950 ThrAsnHisThrProIleAlaIleLeuIleSerProLeuAsnLysLeu 195519601965 LeuThrValAlaArgThrAsnTyrIleSerLeuPheArgGlnGluThr 197019751980 ArgArgMetLeuValLeuArgGluPheIleTyrSerArgTyrArgCys 1985199019952000 LysAlaGluArgTyrCysGlyHisTyrLeuArgAlaLeuArgGlnAsp 200520102015 SerLeuIleIleArgLeuIleAlaArgGlyGlyIleSerHisArgPro 202020252030 LeuSerThrGlySerSerAlaSerLeuAsnSerAlaTrpValSerLeu 203520402045 MetLysIleHisLeuHisTrpIleGlnGlyGluIleIleAspCysAsn 205020552060 LeuArgGlyLysThrAlaGlnSerGlnThrArgLeuCysArgLeuArg 2065207020752080 GlyArgPheLysTyrPheIleLeuProThrIleLeuArgArgArgLeu 208520902095 LysMetLysLysLeuPhePheLeuLeuLeuLeuLeuPheLeuIleTyr 210021052110 LeuGlyTyrAspTyrValAsnGluAlaLeuPheSerGlnGluLysVal 211521202125 GluPheGlnAsnTyrAspGlnAsnProLysGluHisLeuGluAsnSer 213021352140 GlyThrSerGluAsnThrGlnGluLysThrIleThrGluGluGlnVal 2145215021552160 TyrGlnGlyAsnLeuLeuLeuIleAsnSerLysTyrProValArgGln 216521702175 GluValSerGlnIleSerIleTyrLeuAsnMetThrAsnMetAspThr 218021852190 GlyCysLeuIleValIlePheIleCysGlnLysLysHisLysAsnPhe 219522002205 GlnArgTrpSerMetMetLeuArgValAlaLeuValIleLeuLeuLeu 221022152220 IleValAlaIleGluThrLeuMetSerLysValCysPheThrLysLys 2225223022352240 TrpGlyLeuSerMetProTyrGlnGlnValIleValSerIleIleGln 224522502255 ValTyrHisMetAspGlnAlaArgLysTrpAsnGluProLeuLysGlu 226022652270 SerGlyLysLysMetLeuGlyAsnThrGlySerPheTyrValIleGln 227522802285 ArgThrLysGlnSerGlnGluPhe 22902295 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2254 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: SerPheSerPheCysSerPheValArgAspLeuLeuThrValLeuAsn 151015 SerPhePheSerAlaIleAlaLeuAlaSerHisThrIleLeuSerSer 202530 ValValIleAlaGlySerIleIleLeuPhePheLeuArgLysSerMet 354045 HisSerCysSerArgMetAlaSerProPheSerLysAlaAsnArgTyr 505560 LeuAsnValIleArgTyrSerLeuArgValLysValThrLysSerTyr 65707580 SerLeuArgIleSerPheLysSerGlnSerValPheSerLeuGlySer 859095 SerGluAspGlyLeuThrProIleCysPheAspIleTyrCysMetThr 100105110 GluSerGlyMetLeuLeuIleValTyrGlyGlnProGlyTyrArgArg 115120125 ThrAlaAsnThrAlaAsnProLysArgPheSerSerLeuLeuArgLeu 130135140 LeuThrIleSerLysSerArgLeuGluLysValLysValProSerIle 145150155160 HisSerSerSerGlyIleCysIleLysAlaCysLeuCysSerGlyVal 165170175 SerAsnSerLeuProLeuAlaIlePheIleGlnTyrHisSerIleSer 180185190 ValPheSerIleTyrPheAsnTyrIleSerIleGluCysThrLeuLeu 195200205 IleGlnMetThrAspLysIleIleValLysSerValSerAspLeuSer 210215220 GlnLysGlyAspIleLeuArgLysIleGlyTyrIleArgValSerSer 225230235240 ThrAsnGlnAsnProSerArgGlnPheGlnGlnLeuAsnGluIleGly 245250255 MetAspIleIleArgGluSerPheArgSerAsnLysGlySerArgAla 260265270 ThrSerLysSerValArgArgPheThrGlyArgHisHisLeuCysTyr 275280285 ArgLeuAsnSerAsnHisSerTyrThrArgSerIleIleAsnArgHis 290295300 ThrArgLysGlyLysPheLysIleThrLysArgTyrMetAlaPheIle 305310315320 ArgArgSerIleGlnProIleLeuAsnTyrCysAsnGlyTrpCysPro 325330335 IleArgAlaArgSerTyrSerAspGluThrThrArgAspIleGlyGlu 340345350 ArgArgLysValArgSerIleLysGluValSerLysSerArgArgAsn 355360365 GluLeuCysGlyGluSerTyrIleLysLysGluIleLeuIleLysPhe 370375380 ValLysLeuLeuMetTyrLeuGlyLeuHisTyrThrGlyAsnTyrGln 385390395400 LysIleIleSerHisSerValPheArgTrpAlaIlePheLeuLysLys 405410415 LysArgLysLeuAsnIleAsnSerLeuLeuAlaMetProLysSerPro 420425430 LeuIleLysLysGluSerSerSerGluIleLeuSerHisLeuLeuCys 435440445 LysCysLeuIleArgProTyrAsnLeuIleAsnTyrGlyGlnThrTyr 450455460 ValLysGlyLeuAlaIleLysTyrLeuLeuTrpMetMetAsnMetLys 465470475480 LeuProIleTrpLeuAsnTyrThrLysThrArgIleIleArgPheSer 485490495 AsnThrIleProProLysLysHisTrpAsnValThrSerLeuArgLeu 500505510 ThrLeuProTyrTrpThrSerCysPheProAlaGlnAlaAlaLeuLeu 515520525 SerValLysLysGlyThrSerThrProIleArgLeuSerCysProGly 530535540 LysIleGlnArgIleLysLeuGlnGlyGlnSerAlaArgMetIleIle 545550555560 ArgSerProPheAlaHisTrpSerLeuLeuGlyArgProSerCysAla 565570575 AspThrLysAsnSerValGluArgSerArgThrLysMetLeuSerSer 580585590 ThrProAlaLeuSerLeuMetLeuThrProMetSerValIleThrArg 595600605 SerSerTyrProLeuLeuProProSerPheGlnTyrCysGluSerSer 610615620 ValLysThrArgGlyMetTrpLeuAlaProSerCysTyrPheMetArg 625630635640 TyrGlyAlaThrAsnIleSerAlaArgAlaThrThrProSerProCys 645650655 IleSerGlyIleCysAlaLysLysThrThrProLeuIleIleArgAsn 660665670 IleLysArgTyrGlyGlyLeuValIleLysLeuLysAsnLysLysAsn 675680685 AspTyrSerLysLeuGluArgLysLeuTyrMetTyrIleValAlaIle 690695700 ValValValAlaIleValPheValLeuTyrIleArgSerMetIleArg 705710715720 GlyLysLeuGlyAspTrpIleLeuSerIleLeuGluAsnLysTyrAsp 725730735 LeuAsnHisLeuAspAlaMetLysLeuTyrGlnTyrSerIleArgAsn 740745750 AsnIleAspIlePheIleTyrValAlaIleValIleSerIleLeuIle 755760765 LeuCysArgValMetLeuSerLysPheAlaLysTyrPheAspGluIle 770775780 AsnThrGlyIleAspValLeuIleGlnAsnGluAspLysGlnIleGlu 785790795800 LeuSerAlaGluMetAspValMetGluGlnLysLeuAsnThrLeuLys 805810815 ArgThrLeuGluLysArgGluGlnAspAlaLysLeuAlaGluGlnArg 820825830 LysAsnAspValValMetTyrLeuAlaHisAspIleLysThrProLeu 835840845 ThrSerIleIleGlyTyrLeuSerLeuLeuAspGluAlaProAspMet 850855860 ProValAspGlnLysAlaLysTyrValHisIleThrLeuAspLysAla 865870875880 TyrArgLeuGluGlnLeuIleAspGluPhePheGluIleThrArgTyr 885890895 AsnLeuGlnThrIleThrLeuThrLysThrHisIleAspLeuTyrTyr 900905910 MetLeuValGlnMetThrAspGluPheTyrProGlnLeuSerAlaHis 915920925 GlyLysGlnAlaValIleHisAlaProGluAspLeuThrValSerGly 930935940 AspProAspLysLeuAlaArgValPheAsnAsnIleLeuLysAsnAla 945950955960 AlaAlaTyrSerGluAspAsnSerIleIleAspIleThrAlaGlyLeu 965970975 SerGlyAspValValSerIleGluPheLysAsnThrGlySerIlePro 980985990 LysAspLysLeuAlaAlaIlePheGluLysPheTyrArgLeuAspAsn 99510001005 SerArgSerSerAspThrGlyGlyAlaGlyLeuGlyLeuAlaIleAla 101010151020 LysGluIleIleValGlnHisGlyGlyGlnIleTyrAlaGluSerTyr 1025103010351040 AspAsnTyrThrThrPheArgValGluLeuProAlaMetProAspLeu 104510501055 ValAspLysArgArgSerGluMetTyrIleIlePheGluAsnLeuLys 106010651070 ValIlePheThrPheSerGluIleAsnAsnLeuIleLeuArgAsnGly 107510801085 SerPheLeuHisGlyArgLeuAsnThrValArgThrSerArgPheArg 109010951100 SerSerGluLysAspLeuThrArgLeuProLeuAlaSerProPheTyr 1105111011151120 LeuValProPheThrGluArgValGlyLeuAsnTyrGluHisArgHis 112511301135 TyrCysLeuTrpMetAlaGlyGlyArgCysIleProCysSerPheAla 114011451150 SerLeuTrpArgTyrGlyAsnAspAsnArgGlnArgValGlyIleGln 115511601165 ArgGlnIleArgAlaPheGlnSerMetTyrGlnCysGlyThrIleArg 117011751180 AspPheArgLeuTyrSerSerCysAlaGluGluSerArgCysGluIle 1185119011951200 TyrPheTyrProLysHisArgLeuGlnSerTyrArgTyrAsnCysCys 120512101215 GluAsnGlyHisHisCysArgGlnCysGlyValLeuAlaGlyArgCys 122012251230 ArgLeuTyrTyrAspAlaAsnSerTyrGlySerThrGlnArgLysIle 123512401245 AspCysAlaLeuCysGlyLysThrPheGlnValGlyGlnArgProTrp 125012551260 GlnGlyThrGlnArgHisAspSerTrpCysGlyGlyAsnGlyProAsp 1265127012751280 ArgGlnSerGlyTyrAlaAlaAlaArgIleTrpMetSerValGlyLeu 128512901295 SerGlnProLysTyrArgGlyLysLeuCysThrValValAlaAlaLys 130013051310 ArgTyrArgTyrAlaSerCysAlaAlaGlnTyrGlyTyrAlaLeuTyr 131513201325 TyrGlnProArgThrAsnThrGluAsnGluAlaArgSerIleSerTyr 133013351340 GlnTyrTrpAlaArgSerThrCysArgTyrLeuValGlySerIleArg 1345135013551360 LysArgGluThrGlyArgCysArgIleGlyCysIleGlyArgArgGly 136513701375 ArgValPheLeuLeuLeuHisProLysThrAsnSerIlePheThrThr 138013851390 SerLysAsnAlaArgAspAsnHisThrAlaTyrGlyLeuLeuTyrArg 139514001405 AlaSerValAlaTyrArgLysAsnHisLysLeuPheGlyPheLysGlu 141014151420 ThrGlyAlaIleGluLysLeuGlnTyrCysLeuGlyValAlaGlnArg 1425143014351440 SerMetThrTyrArgAsnLeuGlnArgProLeuThrLeuIleLysLys 144514501455 AsnThrSerArgTyrThrLeuGluLeuArgAsnLeuValTyrGlyLys 146014651470 CysAlaLysAsnLeuAlaArgAsnGlyLysThrThrIleAlaIleGln 147514801485 LeuTyrSerArgArgIleLysLysCysThrAspTyrLeuLeuLysArg 149014951500 ThrMetAsnMetLysSerThrMetLeuMetHisPheGlnLeuCysMet 1505151015151520 AlaSerGlnValLysMetAspProTyrLysValCysLeuAsnCysPro 152515301535 ValSerLeuLeuAlaAlaIlePheLysAlaGlnGlnPheValTrpThr 154015451550 AsnArgHisThrSerLeuArgLysMetLeuGlyLeuLeuProProPhe 155515601565 GlyLeuLeuIleLysMetIleGlyArgTrpGlnLeuArgLeuProIle 157015751580 LeuPheLeuLeuSerArgArgValGlnAlaHisProSerValLysLys 1585159015951600 SerIleAlaArgThrAsnTrpThrThrGlnLeuAsnArgGlnAspAsn 160516101615 MetThrAlaLysSerLeuSerArgLeuPheArgAlaValArgSerVal 162016251630 ValArgTyrTrpGluThrValProArgLeuLeuAlaArgTrpThrLys 163516401645 SerGlyCysSerThrGluSerPheValPheIleArgLysSerSerArg 165016551660 LysLysAlaLeuLysThrGlnLeuProPheProGlnThrPheGlnGln 1665167016751680 ArgSerGluAspGlyTyrArgLysArgGlnLysLysTyrIleLysArg 168516901695 SerAlaValGluValProValTrpIleCysPheTyrLysIleThrAla 170017051710 AlaLeuTyrThrLysSerIleLeuCysProValSerArgHisThrVal 171517201725 ValIleProValTrpProLeuGlnValLeuHisPheProAsnLeuThr 173017351740 AlaSerTyrArgArgGlyAspLysHisGlyAsnArgIleTyrPhePhe 1745175017551760 ArgAsnSerThrArgCysSerLeuGlyArgIleCysHisLeuGlyPhe 176517701775 HisArgLysThrGlyArgLeuSerLysSerHisCysArgAspIleArg 178017851790 ValGlyIleAlaPheGluGlyLysArgThrGlyCysTyrProArgVal 179518001805 ArgIleAlaSerMetGlyArgLeuProSerAlaCysCysLysLeuPhe 181018151820 TyrAlaMetGlyCysThrAlaGlyLysProAspLysGlyLysLeuLeu 1825183018351840 SerGlnTyrProAsnAspAspPheLysArgIleArgGlyPheLysIle 184518501855 LysProProArgGlnCysHisSerTyrAlaLeuSerIleArgHisGly 186018651870 AlaCysThrAsnGlyGluProIlePheTyrGlyThrLeuSerSerCys 187518801885 GlyLysTrpAsnIleMetGlnSerAlaLysSerGlnThrPheAlaLeu 189018951900 HisHisGlyLysGlnTrpValSerIleProArgMetValAlaLeuCys 1905191019151920 IleLysArgArgThrIleProGlnLeuPhePheProArgIleAsnPhe 192519301935 ProLeuHisGlyGlnThrIleAlaAsnSerPheGlyArgLysProAsp 194019451950 ValCysAsnTrpPheLeuGlyAsnLeuTyrIleValAspSerIleGlu 195519601965 AspValArgGlnSerAspIleAlaValIleIleCysValArgCysGly 197019751980 LysIleAlaAspSerHisArgGlyValValPheHisThrAlaHisCys 1985199019952000 GlnGlnAlaValGlnProArgIleGlnHisGlyTyrHisLeuLysPhe 200520102015 IleTyrIleGlyAspAsnSerLysSerSerArgAlaLysLeuThrVal 202020252030 IleTyrGlyAlaLysArgHisAsnLeuLysArgAspCysAlaValGly 203520402045 GluAspSerArgAsnIleSerTyrPheGlnLeuTyrSerGlyGlyAsp 205020552060 LysArgSerCysPhePheTyrCysTyrCysTyrSerTyrThrValMet 2065207020752080 ThrThrLeuMetLysHisCysPheLeuArgLysLysSerAsnPheLys 208520902095 IleMetIleLysIleProLysAsnIleLysIleValGlyLeuLeuLys 210021052110 IleProLysArgLysGlnLeuGlnLysAsnArgPheIleLysGluIle 211521202125 CysTyrSerIleValAsnIleLeuPheAlaLysLysCysGluValArg 213021352140 TyrArgGluPheIleThrArgIleAsnLysTrpIleArgValAlaTyr 2145215021552160 LeuTyrValLysArgAsnSerThrLysIlePheArgAspGlyGlnCys 216521702175 CysLysGlyTrpArgSerPheTyrTyrTrpLeuSerArgLeuAlaLys 218021852190 CysAlaLeuProArgAsnGlyGlyValCysLeuThrSerArgLeuAla 219522002205 PheArgPheIleThrArgCysArgIleLysLeuAspGluAsnGlyThr 221022152220 SerProArgLysValAspArgArgLysCysLeuGluIleArgValHis 2225223022352240 PheThrLeuSerArgGlyGlnAsnArgValAsnArgAsnSer 22452250 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2291 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: AlaPheLeuPheAlaHisLeuLeuGluIleTyrProTyrIleAlaSer 151015 PheGlnProLeuProLeuLeuProThrProPhePheGlnValGlnAla 202530 ValPheCysPhePheLeuGluAsnLeuCysIleHisAlaValAspGlu 354045 TrpHisHisHisPheProLysLeuIleAspGluGlyThrMetSerPhe 505560 AspIleHisSerGlyLysLeuGlnSerArgIleHisPheGluPheLeu 65707580 SerAsnAspProLysValTyrPheProPheGluAspAsnAspGlnAla 859095 ArgMetAspHisGlnSerValSerIleTyrIleValProAsnLeuGly 100105110 CysPheTyrGluCysMetAlaAsnArgAspThrGluGluGlnLeuIle 115120125 GluGlnGlnIleLeuAsnGlyPheLeuProSerPheAlaTyrLeuPhe 130135140 LeuAsnProValTrpLysLysSerArgSerProValSerIleHisLeu 145150155160 GlnGlyPheAlaLysProValSerValProValAlaIleLeuTyrLeu 165170175 SerGlnPheSerPheSerIleIleProPheLeuTyrPheGlnPheIle 180185190 SerSerIleIleTyrGlnSerValLeuTyrTyrLysCysSerArgLeu 195200205 IleLysSerLeuArgAlaSerHisLysThrCysLeuLysAsnGluVal 210215220 IlePheCysGlyLysSerValIlePheValSerValArgLeuThrArg 225230235240 IleLeuGlnAspAsnPheSerSerThrArgSerGluTrpIleLeuTyr 245250255 LysGluLysValSerGlyAlaThrLysAspArgGluGlnLeuGlnLys 260265270 ValLeuAspAspLeuGlnGluAspAspIleIleTyrValThrAspLeu 275280285 ThrArgIleThrArgSerThrGlnAspLeuPheGluLeuIleAspAsn 290295300 IleArgAspLysLysAlaSerLeuLysSerLeuLysAspThrTrpLeu 305310315320 AspLeuSerGluAspAsnProTyrSerGlnPheLeuIleThrValMet 325330335 AlaGlyValAsnGlnLeuGluArgAspLeuIleArgMetArgGlnArg 340345350 GluGlyIleGluLeuAlaLysLysGluGlyLysPheLysGlyArgLeu 355360365 LysLysTyrHisLysAsnHisAlaGlyMetAsnTyrAlaAlaLysAla 370375380 IleArgArgLysTyrAspCysLysSerAsnLeuAsnTyrCysIleGly 385390395400 PheIleIleGlnGluIleIleArgSerGluLeuAlaIleLeuTyrSer 405410415 AlaAsnGlyGlnTyrPheArgArgLysGlyAsnTyrLysIleLeuThr 420425430 AlaSerArgCysArgLysAlaLeuLysLysAsnHisHisLeuLysLys 435440445 PheLeuValIleTyrTyrValAsnAlaTyrLysPheGlyProIleIle 450455460 IleIleLysGlyLysLeuMetLysGlyAspAsnTyrGluArgAsnThr 465470475480 TyrCysGlyThrAsnCysArgPheGlyIleIleLeuLysLysArgGlu 485490495 LeuTyrGlyPheGlnIleLeuTyrArgGlnArgSerIleGlyMetTyr 500505510 ArgGlnValAspProCysHisIleGlyHisHisAlaSerArgHisLys 515520525 ArgProTyrTyrLeuSerLysAsnLysGlyGlnAlaHisLeuSerAsp 530535540 TyrHisAlaAspArgGluArgTyrArgGlyArgAsnTyrArgValAsn 545550555560 AsnArgArgGlyLeuTyrAsnGluAlaLeuSerProThrGlyValAsn 565570575 CysSerGlyLysGlyProValAlaProIleGlnLysIleGlnTrpSer 580585590 LysGlyAlaGluArgLysCysTyrArgProLeuArgProCysHisCys 595600605 HisProValLeuSerGluArgGluAlaValIleProTyrSerHisArg 610615620 ValPheAsnThrAlaAsnProLeuLysGlnGlyGluCysGlyLeuArg 625630635640 AlaAlaIleSerAspMetGlyArgArgIlePheGlnGlnGluGlnGln 645650655 HisHisHisArgAlaTyrProAlaPheAlaArgLysAsnGluArgHis 660665670 HisSerGluIleTyrLysAsnGlyMetGlyGlyTrpLeuAsnLysIle 675680685 LysLysThrThrIleProAsnAsnGluAsnPheThrCysIleSerLeu 690695700 GlnLeuLeuTrpGlnLeuTyrSerCysCysIlePheValGlnSerGlu 705710715720 GlyAsnLeuGlyIleGlySerValPheTrpLysThrAsnMetThrIle 725730735 ThrTrpThrArgAsnTyrIleAsnIleProTyrGlyThrIleIleSer 740745750 LeuPheMetTrpArgLeuSerLeuValPheLeuPheTyrValAlaSer 755760765 CysPheGlnAsnSerGlnAsnThrLeuThrArgIleProAlaLeuMet 770775780 TyrLeuPheArgThrLysIleAsnLysLeuSerPheLeuArgLysTrp 785790795800 MetLeuTrpAsnLysSerSerThrHisAsnGlyLeuTrpLysSerGlu 805810815 SerArgMetGlnSerTrpProAsnLysGluLysMetThrLeuLeuCys 820825830 ThrTrpArgThrIleLeuLysArgProLeuHisProLeuSerValIle 835840845 AlaCysLeuThrArgLeuGlnThrCysArgIleLysArgGlnSerMet 850855860 CysIleSerArgTrpThrLysArgIleAspSerAsnSerSerThrSer 865870875880 PheLeuArgLeuHisGlyIleThrTyrLysArgArgGlnLysArgThr 885890895 ThrTyrThrIleCysTrpCysArgProMetAsnPheIleLeuSerPhe 900905910 ProHisMetGluAsnArgArgLeuPheThrProProArgIleProCys 915920925 ProAlaThrLeuIleAsnSerArgGluSerLeuThrThrPheLysThr 930935940 ProLeuHisThrValArgIleThrAlaSerLeuThrLeuProArgAla 945950955960 SerProGlyMetTrpCysGlnSerAsnSerArgThrLeuGluAlaSer 965970975 GlnLysIleSerLeuProTyrLeuLysSerSerIleGlyTrpThrIle 980985990 LeuValLeuProIleArgValAlaArgAspLeuAspTrpArgLeuGln 99510001005 LysLysLeuLeuPheSerMetGluGlyArgPheThrArgLysAlaMet 101010151020 IleThrIleArgArgLeuGlySerPheGlnArgCysGlnThrTrpLeu 1025103010351040 IleLysGlyGlyProLysArgCysIlePhePheArgLysIleSerArg 104510501055 LeuSerLeuLeuPheLeuArgLysLeuThrIleTyrGluThrAlaArg 106010651070 SerTyrThrValAspLeuIleProGluArgAlaValPheValLeuGln 107510801085 ArgLysIleGlnAspTyrHisTrpHisProArgPheIleTrpCysLeu 109010951100 SerGlnLysGlyLeuValLeuIleMetAsnAsnIleGlyIleThrVal 1105111011151120 TyrGlyCysGluGlnAspGluAlaAspAlaPheHisAlaLeuSerPro 112511301135 ArgPheGlyValMetAlaThrIleIleAsnAlaAsnValSerGluSer 114011451150 AsnAlaLysSerAlaProPheAsnGlnCysIleSerValGlyHisLys 115511601165 SerGluIleSerAlaSerIleLeuLeuAlaLeuLysArgAlaGlyVal 117011751180 LysTyrIleSerThrArgSerIleGlyCysAsnHisIleAspThrThr 1185119011951200 AlaAlaLysArgMetGlyIleThrValAspAsnValAlaTyrSerPro 120512101215 AspSerValAlaAspTyrThrMetMetLeuIleLeuMetAlaValArg 122012251230 AsnValLysSerIleValArgSerValGluLysHisAspPheArgLeu 123512401245 AspSerAspArgGlyLysValLeuSerAspMetThrValGlyValVal 125012551260 GlyThrGlyGlnIleGlyLysAlaValIleGluArgLeuArgGlyPhe 1265127012751280 GlyCysLysValLeuAlaTyrSerArgSerArgSerIleGluValAsn 128512901295 TyrValProPheAspGluLeuLeuGlnAsnSerAspIleValThrLeu 130013051310 HisValProLeuAsnThrAspThrHisTyrIleIleSerHisGluGln 131513201325 IleGlnArgMetLysGlnGlyAlaPheLeuIleAsnThrGlyArgGly 133013351340 ProLeuValAspThrTyrGluLeuValLysAlaLeuGluAsnGlyLys 1345135013551360 LeuGlyGlyAlaAlaLeuAspValLeuGluGlyGluGluGluPhePhe 136513701375 TyrSerAspCysThrGlnLysProIleAspAsnGlnPheLeuLeuLys 138013851390 LeuGlnArgMetProAsnValIleIleThrProHisThrAlaTyrTyr 139514001405 ThrGluGlnAlaLeuArgAspThrValGluLysThrIleLysAsnCys 141014151420 LeuAspPheGluArgArgGlnGluHisGluAsnLysSerCysAsnThr 1425143014351440 ValTrpGlyLeuLeuArgGlyAlaArgIleGlyLysIleCysAsnArg 144514501455 AspSerArgHisArgLysIleArgAlaValIleHisTrpAsnTyrGlu 146014651470 IleTrpCysMetGluAsnValArgLysThrLeuArgGlyMetGlyLys 147514801485 ArgGlnLeuLeuPheSerCysThrLeuAlaGlyLysAsnAlaArgIle 149014951500 ThrCysLysGluProIleAsnGlnProCysCysSerIlePheSerPhe 1505151015151520 AlaTrpGlnValArgArgTrpIleHisThrArgSerValIleValArg 152515301535 TyrProPheCysArgLeuArgTyrSerLysLeuSerAsnLeuTyrGly 154015451550 GlnIleValAspIleHisArgCysGluLysCysTrpAspSerTyrSer 155515601565 ArgLeuLeuGlyTyrArgAlaGlyGlySerTyrValTyrLeuSerCys 157015751580 PheCysAlaGlyAlaPheArgLeuIleLeuArgCysGluLysSerGln 1585159015951600 ArgGlyArgIleGlyLeuArgAsnIleGlyLysThrIleGlnGlnAsn 160516101615 LeuAsnAlaGlyCysPheGlyLeuGlyArgLeuCysGlyIleGlyLys 162016251630 GlnCysArgValSerCysTrpArgGlyGlyProAsnGlnAlaAlaVal 163516401645 ArgAsnLeuSerTyrSerSerGlySerArgAlaGlyLysArgLeuLys 165016551660 ArgSerTyrAsnArgSerArgArgProPheSerArgGlyAlaArgThr 1665167016751680 AspThrGlyAsnGlyLysLysAsnIleSerAlaArgLeuArgSerSer 168516901695 ProCysGlyTyrValPheThrArgArgProHisCysThrGluArgSer 170017051710 GlnTyrSerAlaArgPheHisValIleGlnSerLeuSerProTyrAsp 171517201725 GlyArgCysArgTyrCysThrSerArgThrAspProLeuAspArgIle 173017351740 SerValLysGlyValIleSerMetGluIleGlyPheThrPheLeuAsp 1745175017551760 GluIleValHisGlyValArgTrpAspAlaLysTyrAlaThrTrpAsp 176517701775 AsnPheThrGlyLysProValAspGlyTyrGluValAsnArgIleVal 178017851790 GlyThrTyrGluLeuAlaGluSerLeuLeuLysAlaLysGluLeuAla 179518001805 AlaThrGlnGlyTyrGlyLeuLeuLeuTrpAspGlyTyrArgProLys 181018151820 ArgAlaValAsnCysPheMetGlnTrpAlaAlaGlnProGluAsnAsn 1825183018351840 LeuThrLysGluSerTyrTyrProAsnIleAspArgThrGluMetIle 184518501855 SerLysGlyTyrValAlaSerLysSerSerHisSerArgGlySerAla 186018651870 IleAspLeuThrLeuTyrArgLeuAspThrGlyGluLeuValProMet 187518801885 GlySerArgPheAspPheMetAspGluArgSerHisHisAlaAlaAsn 189018951900 GlyIleSerCysAsnGluAlaGlnAsnArgArgArgLeuArgSerIle 1905191019151920 MetGluAsnSerGlyPheGluAlaTyrSerLeuGluTrpTrpHisTyr 192519301935 ValLeuArgAspGluProTyrProAsnSerTyrPheAspPheProVal 194019451950 LysThrPheAsnArgCysThrAspLysLeuTyrLysLeuThrLeuSer 195519601965 AlaGlyAsnProThrTyrValThrGlySerGlyIleTyrIleIleVal 197019751980 LeuLysMetGlyArgAlaIleLeuArgSerLeuSerAlaCysAlaAla 1985199019952000 AlaArgProAspAsnLysThrAspArgIleGluGlyTrpTyrPheThr 200520102015 ProProIleValAsnArgGlnPheSerLeuValLysPheSerMetGly 202020252030 IleThrTyrGluAsnSerSerThrLeuValIleIleValAsnProVal 203520402045 GlyArgAsnAsnLeuPheThrGlyGlnAsnGlyThrIleSerAsnGlu 205020552060 IleValProPheLysGlyLysIleLeuGluIlePheHisThrSerAsn 2065207020752080 TyrIleValLysGluGluThrGluAsnGluGluValValPhePheIle 208520902095 ValIleValIleLeuAsnIleLeuArgLeuLeuArgSerThrValPhe 210021052110 SerGlyLysSerArgIleSerLysLeuSerLysSerGlnArgThrPhe 211521202125 ArgLysTrpAspPheLysTyrProArgGluAsnAsnTyrArgArgThr 213021352140 GlyLeuSerArgLysSerAlaIleAsnGlnIleSerCysSerProArg 2145215021552160 SerValLysSerAspIleValAsnLeuSerLysHisAspGluLeuIle 216521702175 AsnGlyTyrGlyLeuLeuAspSerAsnIleTyrMetSerLysGluIle 218021852190 AlaGlnLysPheSerGluMetValAsnAspAlaValLysGlyGlyVal 219522002205 SerHisPheIleIleAsnSerGlyTyrArgAspPheAspGluGlnSer 221022152220 ValLeuTyrGlnGluMetGlyAlaGluTyrAlaLeuProAlaGlyTyr 2225223022352240 SerGluHisAsnSerGlyLeuSerLeuAspValGlySerSerLeuThr 224522502255 LysMetGluArgAlaProGluGlyLysTrpIleGluGluAsnAlaTrp 226022652270 LysTyrGlyPheIleLeuArgTyrProGluAspLysThrGluLeuThr 227522802285 GlyIleGln 2290 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3190 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: CAAAATATCACCTCATTTTTGAGACAAGTCTTATGAGACGCTCTTAACTATGATTTTATC60 AGTCTACTACATTTGTATCAATAGAGTACACTCTATTGATATATAATTGAACTAATAAAT120 TGAAAATACAGAAATGGAATGATACTGAAATGAAAATTGCGAGAGGTAGAGAATTGCTTA180 CACCGGAACAGAGACAGGCTTTTATGCAAATCCCTGAAGATGAATGGATACTGGGGACCT240 ACTTCACTTTTTCCAAACGGGATTTAGAAATAGTTAATAAGCGAAGGAGGGAAGAAAACC300 GTTTAGGATTTGCTGTTCAATTAGCTGTTCTTCGGTATCCCGGTTGGCCATACACTCATA360 TCAAAAGCATCCCAGATTCGGTCATACAATATATATCGAAACAGATTGGTGTTAGTCCAT420 CCTCGCTTGATCATTATCCTCAAAGGGAAAATACACTTTGGGATCATTTGAAAGAAATTC480 GAAGTGAATACGACTTTGTAACTTTTACCCTGAGTGAATATCGAATGACATTTAAGTACC540 TTCATCAATTAGCTTTGGAAAATGGTGATGCCATTCATCTACTGCATGAATGCATAGATT600 TTCTAAGAAAAAACAAAATTATACTGCCTGCTATCACTACACTTGAAAGAATGGTGTGGG660 AAGCAAGGGCAATGGCTGAAAAGAAGCTATTTAATACGGTTAGTAAATCTCTAACAAATG720 AGCAAAAAGAAAAGCTTGAAGGGATTATTACCTCGCAGCATCCATCCGAATCCAATAAAA780 CGATATTGGGTTGGTTAAAAGAGCCACCGGGTCATCCTTCACCCGAAACTTTTCTAAAAA840 TAATAGAACGACTCGAATACATACGAGGAATGGATTTAGAAACAGTGCAAATTAGTCATT900 TGCACCGTAACCGCCTGTTGCAGCTGTCTCGCTTAGGCTCAAGATACGAGCCGTATGCAT960 TCCGTGACTTTCAAGAAAATAAACGTTATTCGATATTAACCATCTATTTATTACAACTTA1020 CTCAGGAGCTAACGGATAAAGCGTTTGAAATTCATGATAGGCAAATACTTAGTTTGTTAT1080 CAAAAGGTCGTAAGGCTCAAGAGGAAATCCAGAAACAAAACGGTAAAAAGCTAAATGAGA1140 AAGTTATACACTTTACGAACATCGGACAAGCATTAATTAAAGCAAGAGAGGAAAAATTAG1200 ACGTTTTTAAGGTTTTAGAATCGGTTATTGAATGGAATACCTTTGTCTCTTCAGTAGAAG1260 AGGCTCAGGAACTTGCACGTCCTGCCGACTATGATTATTTAGACTTACTGCAAAAACGGT1320 TTTATTCACTAAGAAAATATACGCCAACGCTATTAAGAGTATTGGAATTTCATTCTACAA1380 AGGCAAATGAGCCACTTTTACAAGCTGTTGAGATTATCCGAGGAATGAACGAATCTGGAA1440 AGCGAAAAGTGCCTGATGACTCACCTGTGGATTTTATTTCAAAACGATGGAAAAGACATT1500 TATACGAGGATGATGGTACAACAATTAATCGTCATTACTATGAAATGGCTGTTTTAACAG1560 AACTTCGGGAGCATGTTCGGGCAGGAGATGTTTCCATTGTTGGCAGCAGACAATATAGGG1620 ATTTTGAGGAATATTTGTTTTCGGAAGATACATGGAATCAATCGAAGGGGAATACGAGAT1680 TATCAGTTAGTTTATCATTCGAAGATTATATAACGGAGAGAACCAGCAGCTTTAATGAAA1740 GGTTAAAGTGGTTAGCTGCCAATTCCAATAAGTTAGATGGGGTTTCTCTTGAAAAAGGAA1800 AGCTATCACTTGCACGCTTAGAAAAAGATGTTCCAGAAGAAGCAAAAAAATTTAGTGCAA1860 GCCTTTATCAGATGCTACCAAGAATAAAATTAACTGATTTACTCATGGATGTGGCCCATA1920 TAACAGGATTTCATGAGCAATTCACTCATGCTTCCAATAATCGAAAACCAGATAAGGAAG1980 AAACAATCATTATCATGGCTGCCCTTTTAGGAATGGGAATGAATATTGGCTTGAGCAAGA2040 TGGCCGAAGCCACACCCGGACTTACATATAAGCAACTAGCCAATGTATCTCAATGGCGCA2100 TGTATGAAGATGCCATGAATAAAGCCCAAGCCATATTAGTAAACTTTCATCATAAATTAC2160 AATTGCCTTTCTATTGGGGCGACGGTACAACATCTTCGTCAGATGGTATGAGAATGCAGC2220 TAGGTGTTTCATCACTACATGCAGATGCAAATCCACATTATGGAACTGGAAAAGGAGCCA2280 CCATCTACCGATTTACAAGTGATCAATTCTCTTCTTACTACACAAAGATTATTCATACTA2340 ATTCAAGAGATGCGATTCATGTTTTGGATGGTTTGTTACATCATGAGACGGATCTAAACA2400 TAGAGGAACATTATACAGACACTGCCGGTTACACTGACCAAATATTCGGACTGACTCATT2460 TATTAGGATTTAAATTTGCCCCAAGAATAAGGGATTTATCGGACTCAAAATTATTTACGA2520 TAGATAAAGCAAGTGAGTATCCAAAACTAGAAGCCATTTTACGTGGACAAATAAATACAA2580 AGGTCATTAAAGAAAATTATGAGGATGTTTTGCGATTAGCTCATTCTATAAGGGAGGGAA2640 CAGTTTCAGCATCCCTTATTATGGGGAAGCTAGGTTCCTATTCAAGACAAAACAGCTTAG2700 CTACAGCCTTACGTGAGATGGGCCGAATAGAAAAAACGATCTTTATTTTGAATTATATAT2760 CGGATGAATCATTAAGAAGAAAAATACAAAGAGGATTGAATAAAGGAGAAGCCATGAATG2820 GATTGGCAAGAGCTATTTTCTTCGGAAAACAAGGTGAGCTTAGAGAACGCACCATACAGC2880 ATCAATTGCAAAGAGCCAGTGCTTTAAACATAATTATCAATGCTATAAGTATTTGGAATA2940 CTCTCCACCTAACAACAGCAGTTGAATATAAAAAACGGACAGGTAGCTTTAATGAAGATT3000 TGTTACACCATATGTCGCCCTTAGGTTGGGAACATATTAATTTACTAGGAGAATACCATT3060 TTAACTCAGAGAAAGTAGTCTCATTAAATTCTTTAAGACCACTAAAACTTTCTTAACGTT3120 GTTAAAAACGAGGGATTCGTCAGGAAAATAGGCTTAGCGTTGTAAATCCGCATTTTCCTG3180 ACGCTACCCC3190 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1347 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: GAGCTCTTCCTTCAACGCACTTCTGTACCAAGAGTTGTTGTCCATTTGATCACTAACAAT60 AGCTTCCCCTGCTTTCTTCAAGCCCTTTGTCATAAAATCGTTAGATTTTCATCATAAAAA120 TACGAGAAAGACAACAGGAAGACCGCAAATTTTCTTTTCTTTTCCTAGGTACACTGAATG180 TAACCTTAAAAGAAAAAAGGAAAGGAAGAAAATGATGAAAAAAATTGCCGTTTTATTTGG240 AGGGAATTCTCCAGAATACTCAGTGTCACTAACCTCAGCAGCAAGTGTGATCCAAGCTAT300 TGACCCGCTGAAATATGAAGTAATGACCATTGGCATCGCACCAACAATGGATTGGTATTG360 GTATCAAGGAAACCTCGCGAATGTTCGCAATGATACTTGGCTAGAAGATCACAAAAACTG420 TCACCAGCTGACTTTTTCTAGCCAAGGATTTATATTAGGAGAAAAACGAATCGTCCCTGA480 TGTCCTCTTTCCAGTCTTGCATGGGAAGTATGGCGAGGATGGCTGTATCCAAGGACTGCT540 TGAACTAATGAACCTGCCTTATGTTGGTTGCCATGTCGCTGCCTCCGCATTATGTATGAA600 CAAATGGCTCTTGCATCAACTTGCTGATACCATGGGAATCGCTAGTGCTCCCACTTTGCT660 TTTATCCCGCTATGAAAACGATCCTGCCACAATCGATCGTTTTATTCAAGACCATGGATT720 CCCGATCTTTATCAAGCCGAATGAAGCCGGTTCTTCAAAAGGGATCACAAAAGTAACTGA780 CAAAACAGCGCTCCAATCTGCATTAACGACTGCTTTTGCTTACGGTTCTACTGTGTTGAT840 CCAAAAGGCGATAGCGGGTATTGAAATTGGCTGCGGCATCTTAGGAAATGAGCAATTGAC900 GATTGGTGCTTGTGATGCGATTTCTCTTGTCGACGGTTTTTTTGATTTTGAAGAGAAATA960 CCAATTAATCAGCGCCACGATCACTGTCCCAGCACCATTGCCTCTCGCGCTTGAATCACA1020 GATCAAGGAGCAGGCACAGCTGCTTTATCGAAACTTGGGATTGACGGGTCTGGCTCGAAT1080 CGATTTTTTCGTCACCAATCAAGGAGCGATTTATTTAAACGAAATCAACACCATGCCGGG1140 ATTTACTGGGCACTCCCGCTACCCAGCTATGATGGCGGAAGTCGGGTTATCCTACGAAAT1200 ATTAGTAGAGCAATTGATTGCACTGGCAGAGGAGGACAAACGATGAACACATTACAATTG1260 ATCAATAAAAACCATCCATTGAAAAAAAATCAAGAGCCCCCGCACTTAGTGCTAGCTCCT1320 TTTAGCGATCACGATGTTTACCTGCAG1347 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 364 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: MetGluLysLeuArgValGlyIleValGlyGlyGlyLysSerAlaGlu 151015 HisGluValSerLeuGlnSerAlaLysAsnIleValAspAlaIleAsp 202530 LysSerArgPheAspValValLeuLeuGlyIleAspLysGlnGlyGln 354045 TrpHisValSerAspAlaSerAsnTyrLeuLeuAsnAlaAspAspPro 505560 AlaHisIleAlaLeuArgProSerAlaThrSerLeuAlaGlnValPro 65707580 GlyLysHisGluHisGlnLeuIleAspAlaGlnAsnGlyGlnProLeu 859095 ProThrValAspValIlePheProIleValHisGlyThrLeuGlyGlu 100105110 AspGlySerLeuGlnGlyMetLeuArgValAlaAsnLeuProPheVal 115120125 GlySerAspValLeuAlaSerAlaAlaCysMetAspLysAspValThr 130135140 LysArgLeuLeuArgAspAlaGlyLeuAsnIleAlaProPheIleThr 145150155160 LeuThrArgAlaAsnArgHisAsnIleSerPheAlaGluValGluSer 165170175 LysLeuGlyLeuProLeuPheValLysProAlaAsnGlnGlySerSer 180185190 ValGlyValSerLysValThrSerGluGluGlnTyrAlaThrAlaVal 195200205 AlaLeuAlaPheGluPheAspHisLysValIleValGluGlnGlyIle 210215220 LysGlyArgGluIleGluCysAlaValLeuGlyAsnAspAsnProGln 225230235240 AlaSerThrCysGlyGluIleValLeuThrSerAspPheTyrAlaTyr 245250255 AspThrLysTyrIleAspGluAspGlyAlaLysValValValProAla 260265270 AlaIleAlaProGluIleAsnAspLysIleArgAlaIleAlaValGln 275280285 AlaTyrGlnThrLeuGlyCysAlaGlyMetAlaArgValAspValPhe 290295300 LeuThrProGluAsnGluValValIleAsnGluIleAsnThrLeuPro 305310315320 GlyPheThrAsnIleSerMetTyrProLysLeuTrpGlnAlaSerGly 325330335 LeuGlyTyrThrAspLeuIleThrArgLeuIleGluLeuAlaLeuGlu 340345350 ArgHisAlaAlaAsnAsnAlaLeuLysThrThrMet 355360 (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 306 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: MetThrAspLysIleAlaValLeuLeuGlyGlyThrSerAlaGluArg 151015 GluValSerLeuAsnSerGlyAlaAlaValLeuAlaGlyLeuArgGlu 202530 GlyGlyIleAspAlaTyrProValAspProLysGluValAspValThr 354045 GlnLeuLysSerMetGlyPheGlnLysValPheIleAlaLeuHisGly 505560 ArgGlyGlyGluAspGlyThrLeuGlnGlyMetLeuGluLeuMetGly 65707580 LeuProTyrThrGlySerGlyValMetAlaSerAlaLeuSerMetAsp 859095 LysLeuArgSerLysLeuLeuTrpGlnGlyAlaGlyLeuProValAla 100105110 ProTrpValAlaLeuThrArgAlaGluPheGluLysGlyLeuSerAsp 115120125 LysGlnLeuAlaGluIleSerAlaLeuGlyLeuProValIleValLys 130135140 ProSerArgGluGlySerSerValGlyMetSerLysValValAlaGlu 145150155160 AsnAlaLeuGlnAspAlaLeuArgLeuAlaPheGlnHisAspGluGlu 165170175 ValLeuIleGluLysTrpLeuSerGlyProGluPheThrValAlaIle 180185190 LeuGlyGluGluIleLeuProSerIleArgIleGlnProSerGlyThr 195200205 PheTyrAspTyrGluAlaLysTyrLeuSerAspGluThrGlnTyrPhe 210215220 CysProAlaGlyLeuGluAlaSerGlnGluAlaAsnLeuGlnAlaLeu 225230235240 ValLeuLysAlaTrpThrThrLeuGlyCysLysGlyTrpGlyArgIle 245250255 AspValMetLeuAspSerAspGlyGlnPheTyrLeuLeuGluAlaAsn 260265270 ThrSerProGlyMetThrSerHisSerLeuValProMetAlaAlaArg 275280285 GlnAlaGlyMetSerPheSerGlnLeuValValArgIleLeuGluLeu 290295300 AlaAsp 305 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: LeuPheProMetValIle 15 (2) INFORMATION FOR SEQ ID NO:35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: SerThrGlnAsnCys 15 (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: GlyGluAspGlySerIleGlnGly 15 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: AsnThrLeuProGlyPheThr 15 (2) INFORMATION FOR SEQ ID NO:38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: GlyGluAspGlyThrLeuGlnGly 15 (2) INFORMATION FOR SEQ ID NO:39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: AsnThrSerProGlyMetThr 15 (2) INFORMATION FOR SEQ ID NO:40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 259 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: E. faecium (B) STRAIN: BM4147 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: GluMetAspValMetGluGlnLysLeuAsnThrLeuLysArgThrLeu 151015 GluLysArgGluGlnAspAlaLysLeuAlaGluGlnArgLysAsnAsp 202530 ValValMetTyrLeuAlaHisAspIleLysThrProLeuThrSerIle 354045 IleGlyTyrLeuSerLeuLeuAspGluAlaProAspMetProValAsp 505560 GlnLysAlaLysTyrValHisIleThrLeuAspLysAlaTyrArgLeu 65707580 GluGlnLeuIleAspGluPhePheGluIleThrArgTyrAsnLeuGln 859095 ThrIleThrLeuThrLysThrHisIleAspLeuTyrTyrMetLeuVal 100105110 GlnMetThrAspGluPheTyrProGlnLeuSerAlaHisGlyLysGln 115120125 AlaValIleHisAlaProGluAspLeuThrValSerGlyAspProAsp 130135140 LysLeuAlaArgValPheAsnAsnIleLeuLysAsnAlaAlaAlaTyr 145150155160 SerGluAspAsnSerIleIleAspIleThrAlaGlyLeuSerGlyAsp 165170175 ValValSerIleGluPheLysAsnThrGlySerIleProLysAspLys 180185190 LeuAlaAlaIlePheGluLysPheTyrArgLeuAspAsnAlaArgSer 195200205 SerAspThrGlyGlyAlaGlyLeuGlyLeuAlaIleAlaLysGluIle 210215220 IleValGlnHisGlyGlyGlnIleTyrAlaGluSerAsnAspAsnTyr 225230235240 ThrThrPheArgValGluLeuProAlaMetProAspLeuValAspLys 245250255 ArgArgSer (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 256 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: Escherichia coli (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: GluIleArgValMetProTyrThrHisLysGlnLeuLeuMetValAla 151015 ArgAspValThrGlnMetHisGlnLeuGluGlyAlaArgArgAsnPhe 202530 PheAlaAsnValSerHisGluLeuArgThrProLeuThrValLeuGln 354045 GlyTyrLeuGluMetMetAsnGluGlnProLeuGluGlyAlaValArg 505560 GluLysAlaLeuHisThrMetArgGluGlnThrGlnArgMetGluGly 65707580 LeuValLysGlnLeuLeuThrLeuSerLysIleGluAlaAlaProThr 859095 HisLeuLeuAsnGluLysValAspValProMetMetLeuArgValVal 100105110 GluArgGluAlaGlnThrLeuSerGlnLysLysGlnThrPheThrPhe 115120125 GluIleAspAsnGlyLeuLysValSerGlyAsnGluAspGlnLeuArg 130135140 SerAlaIleSerAsnLeuValTyrAsnAlaValAsnHisThrProGlu 145150155160 GlyThrHisIleThrValArgTrpGlnArgValProHisGlyAlaGlu 165170175 PheSerValGluAspAsnGlyProGlyIleAlaProGluHisIlePro 180185190 ArgLeuThrGluArgPheTyrArgValAspLysAlaArgSerArgGln 195200205 ThrGlyGlySerGlyLeuGlyLeuAlaIleValLysHisAlaValAsn 210215220 HisHisGluSerArgLeuAsnIleGluSerThrValGlyLysGlyThr 225230235240 ArgPheSerPheValIleProGluArgLeuIleAlaLysAsnSerAsp 245250255 (2) INFORMATION FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 241 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (v) FRAGMENT TYPE: internal (vi) ORIGINAL SOURCE: (A) ORGANISM: Escherichia coli (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: AlaSerGluValArgSerValThrArgAlaPheAsnHisMetAlaAla 151015 GlyValLysGlnLeuAlaAspAspArgThrLeuLeuMetAlaGlyVal 202530 SerHisAspLeuArgThrProLeuThrArgIleArgLeuAlaThrGlu 354045 MetMetSerGluGlnAspGlyTyrLeuAlaGluSerIleAsnLysAsp 505560 IleGluGluCysAsnAlaIleIleGluGlnPheIleAspTyrLeuArg 65707580 ThrGlyGlnGluMetProMetGluMetAlaAspLeuAsnAlaValLeu 859095 GlyGluValIleAlaAlaGluSerGlyTyrGluArgGluIleGluThr 100105110 AlaLeuTyrProGlySerIleGluValLysMetHisProLeuSerIle 115120125 LysArgAlaValAlaAsnMetValValAsnAlaAlaArgTyrGlyAsn 130135140 GlyTrpIleLysValSerSerGlyThrGluProAsnArgAlaTrpPhe 145150155160 GlnValGluAspAspGlyProGlyIleAlaProGluGlnArgLysHis 165170175 LeuPheGlnProPheValArgGlyAspSerAlaArgThrIleSerGly 180185190 ThrGlyLeuGlyLeuAlaIleValGlnArgIleValAspAsnHisAsn 195200205 GlyMetLeuGluLeuGlyThrSerGluArgGlyGlyLeuSerIleArg 210215220 AlaTrpLeuProValProValThrArgAlaGlnGlyThrThrLysGlu 225230235240 Gly (2) INFORMATION FOR SEQ ID NO:43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 231 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: E. faecium (B) STRAIN: BM4147 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: MetSerAspLysIleLeuIleValAspAspGluHisGluIleAlaAsp 151015 LeuValGluLeuTyrLeuLysAsnGluAsnTyrThrValPheLysTyr 202530 TyrThrAlaLysGluAlaLeuGluCysIleAspLysSerGluIleAsp 354045 LeuAlaIleLeuAspIleMetLeuProGlyThrSerGlyLeuThrIle 505560 CysGlnLysIleArgAspLysHisThrTyrProIleIleMetLeuThr 65707580 GlyLysAspThrGluValAspLysIleThrGlyLeuThrIleGlyAla 859095 AspAspTyrIleThrLysProPheArgProLeuGluLeuIleAlaArg 100105110 ValLysAlaGlnLeuArgArgTyrLysLysPheSerGlyValLysGlu 115120125 GlnAsnGluAsnValIleValHisSerGlyLeuValIleAsnValAsn 130135140 ThrHisGluCysTyrLeuAsnGluLysGlnLeuSerLeuThrProThr 145150155160 GluPheSerIleLeuArgIleLeuCysGluAsnLysGlyAsnValVal 165170175 SerSerGluLeuLeuPheHisGluIleTrpGlyAspGluTyrPheSer 180185190 LysSerAsnAsnThrIleThrValHisIleArgHisLeuArgGluLys 195200205 MetAsnAspThrIleAspAsnProLysTyrIleLysThrValTrpGly 210215220 ValGlyTyrLysIleGluLys 225230 (2) INFORMATION FOR SEQ ID NO:44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 239 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: Escherichia coli (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: MetGlnGluAsnTyrLysIleLeuValValAspAspAspMetArgLeu 151015 ArgAlaLeuLeuGluArgTyrLeuThrGluGlnGlyPheGlnValArg 202530 SerValAlaAsnAlaGluGlnMetAspArgLeuLeuThrArgGluSer 354045 PheHisLeuMetValLeuAspLeuMetLeuProGlyGluAspGlyLeu 505560 SerIleCysArgArgLeuArgSerGlnSerAsnProMetProIleIle 65707580 MetValThrAlaLysGlyGluGluValAspArgIleValGlyLeuGlu 859095 IleGlyAlaAspAspTyrIleProLysProPheAsnProArgGluLeu 100105110 LeuAlaArgIleArgAlaValLeuArgArgGlnAlaAsnGluLeuPro 115120125 GlyAlaProSerGlnGluGluAlaValIleAlaPheGlyLysPheLys 130135140 LeuAsnLeuGlyThrArgGluMetPheArgGluAspGluProMetPro 145150155160 LeuThrSerGlyGluPheAlaValLeuLysAlaLeuValSerHisPro 165170175 ArgGluProIleSerArgAspLysLeuMetAsnLeuAlaArgGlyArg 180185190 GluTyrSerAlaMetGluArgSerIleAspValGlnIleSerArgLeu 195200205 ArgArgMetValGluGluAspProAlaHisProArgTyrIleGlnThr 210215220 ValTrpGlyLeuGlyTyrValPheValProAspGlySerLysAla 225230235 (2) INFORMATION FOR SEQ ID NO:45: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 229 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: Escherichia coli (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: MetAlaArgArgIleLeuValValGluAspGluAlaProIleArgGlu 151015 MetValCysPheValLeuGluGlnAsnGlyPheGlnProValGluAla 202530 GluAspTyrAspSerAlaValAsnGlnLeuAsnGluProTrpProAsp 354045 LeuIleLeuLeuAspTrpMetLeuProGlyGlySerGlyIleGlnPhe 505560 IleLysHisLeuLysArgGluSerMetThrArgAspIleProValVal 65707580 MetLeuThrAlaArgGlyGluGluGluAspArgValArgGlyLeuGlu 859095 ThrGlyAlaAspAspTyrIleThrLysProPheSerProLysGluLeu 100105110 ValAlaArgIleLysAlaValMetArgArgIleSerProMetAlaVal 115120125 GluGluValIleGluMetGlnGlyLeuSerLeuAspProThrSerHis 130135140 ArgValMetAlaGlyGluGluProLeuGluMetGlyProThrGluPhe 145150155160 LysLeuLeuHisPhePheMetThrHisProGluArgValTyrSerArg 165170175 GluGlnLeuLeuAsnHisValTrpGlyThrAsnValTyrValGluAsp 180185190 ArgThrValAspValHisIleArgArgLeuArgLysAlaLeuGluPro 195200205 GlyGlyHisAspArgMetValGlnThrValArgGlyThrGlyTyrArg 210215220 PheSerThrArgPhe 225 (2) INFORMATION FOR SEQ ID NO:46: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 129 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: Escherichia coli (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: MetAlaAspLysGluLeuLysPheLeuValValAspAspPheSerThr 151015 MetArgArgIleValArgAsnLeuLeuLysGluLeuCysPheAsnAsn 202530 ValGluGluAlaGluAspGlyValAspAlaLeuAsnLysLeuGlnAla 354045 GlyGlyPheGlyPheIleIleSerAspTrpAsnMetProAsnMetAsp 505560 GlyLeuGluLeuLeuLysThrIleArgAlaAspSerAlaMetSerAla 65707580 LeuProValLeuMetValThrAlaGluAlaLysLysGluAsnIleIle 859095 AlaAlaAlaGlnAlaGlyAlaSerGlyTyrValValLysProPheThr 100105110 AlaAlaThrLeuGluGluLysLeuAsnLysIlePheGluLysLeuGly 115120125 Met (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (v) FRAGMENT TYPE: N-terminal (vi) ORIGINAL SOURCE: (A) ORGANISM: E. faecium (B) STRAIN: BM4147 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: MetAsnArgIleLysValAlaIleLeu 15 (2) INFORMATION FOR SEQ ID NO:48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: RBS (B) LOCATION: 1..10 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: TGAAAGGAGA10 (2) INFORMATION FOR SEQ ID NO:49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: UCUUUCCUCC10 (2) INFORMATION FOR SEQ ID NO:50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: GCTGCAGATAAAAATTTAGGAGG23 (2) INFORMATION FOR SEQ ID NO:51: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: CGCATGCTATTATAAAAGCCAGTC24 (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: TGAAAGGGTG10 (2) INFORMATION FOR SEQ ID NO:53: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: rRNA (vi) ORIGINAL SOURCE: (A) ORGANISM: B. subtilis (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: GGGGGGTTGGNNNNNNNNTTG21 (2) INFORMATION FOR SEQ ID NO:54: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: unknown (D) TOPOLOGY: linear (ii) MOLECULE TYPE: rRNA (vi) ORIGINAL SOURCE: (A) ORGANISM: B. subtilis (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: AGAACGAAAANNNNNNATG19 __________________________________________________________________________

## Claims

1. An isolated polynucleotide consisting of SEQ ID NO:9 or SEQ ID NO:10.

2. An isolated polynucleotide probe, which is optionally labelled and which hybridizes under the following conditions: a reaction temperature of 65.degree. C. overnight in a solution containing 0.1% SDS, 0.7% skimmed milk powder and 6.times.SSC followed by washing at 65.degree. C. in 2.times.SSC and 0.1% SDS; or 0.1% SDS, 0.7% skimmed milk powder, 6.times.SSC followed by washing at 45.degree. C. in 2.times.SSC and 0.1% SDS; NO:6 (VanX), SEQ ID NO:8 (VanC), SEQ ID NO:12 (VanR), SEQ ID NO:14 (VanS), SEQ ID NO:19 (transposase), SEQ ID NO:21 (resolvase), SEQ ID NO:23 (VanY) or SEQ ID NO:25 (VanZ) or a combination thereof; or consisting of a HindIII-EcoRI restriction fragment of about 7.3 kb in length, an EcoRI-XbaI restriction fragment of about 3.4 kb in length, and EcoRV-SacII restriction fragment of about 1.7 kb in length or a HindIII-EcoRI restriction fragment of about 3.3 kb in length, polynucleotide in a gram-positive bacterium having a sequence encoding a protein for resistance to vancomycin, teicoplanin, or both vancomycin and teicoplanin.

3. An isolated polynucleotide probe consisting essentially of a polynucleotide consisting of SEQ ID NO:9 or SEQ ID NO:10.

4. The probe of claim 2, wherein said gram-positive bacterium is a strain of enterococcus.

5. The probe of claim 4, wherein said strain of enterococcus is E. faecium 4147.

6. A process for detecting in a strain of bacteria the presence of a gene encoding a D-Ala-D-Ala ligase or a related enzyme involved in resistance to vancomycin, teicoplanin, or both vancomycin and teicoplanin, comprising: a primer consisting essentially of the polynucleotide of claim 1, dTTP and dGTP to produce a double stranded polynucleotide, amplified polynucleotide, and said stain of bacteria of a gene encoding a D-Ala-D-Ala ligase or a related enzyme involved in resistance to vancomycin, teicoplanin, or both vancomycin and teicoplanin.

7. The process of claim 6, wherein the amplified product is obtained from a strain of bacteria resistant to vancomycin, teicoplanin, or both vancomycin and teicoplanin.

8. An isolated polynucleotide probe, which is optionally labelled and is selected from the group consisting of: NO:6 (VanX), SEQ ID NO:8 (VanC), SEQ ID NO:12 (VanR), SEQ ID NO:14 (VanS), SEQ ID NO:19 (transposase), SEQ ID NO:21 (resolvase), SEQ ID NO:23 (VanY) or SEQ ID NO:25 (VanZ) or a combination thereof; consisting of a HindIII-EcoRI restriction fragment of about 7.3 kb in length, an EcoRI-XbaI restriction fragment of about 3.4 kb in length, and EcoRV-SacII restriction fragment of about 1.7 kb in length or a HindIII-EcoRI restriction fragment of about 3.3 kb in length; polynucleotide in a gram-positive bacterium having a sequence encoding a protein for resistance to vancomycin, teicoplanin, or both vancomycin and teicoplanin.