# Patent

## Title
Fusion polypeptide having the C protein and E1 protein of hepatitis C virus

## Abstract

This application is a divisional of application Ser. No. 07/956,483, filed Dec. 31, 1992.

## Background
The present invention relates to a method for constructing means needed for the production of new molecules capable of inducing an immunoprotective response against a virus responsible for acquired immunodeficiency syndrome (AIDS).

In an individual, this disease develops following an infection of T-helper lymphocytes by an HIV (human immunodeficiency virus) retrovirus. To date, these retroviruses have been classified in two major types: type HIV-1, which is rife essentially in Europe and North America, and type HIV-2, which is characteristic of African infections. Within a given type, the HIV retroviruses exhibit some degree of variability from one another, which is characterized, for example, by a difference in cellular trophism or by viral proteins that differ slightly from one another. For this reason, when it is desired to refer to a particular HIV retrovirus, the term "viral strain" is preferably employed.

Generally speaking, HIV retroviruses have the following structure: the genomic RNA molecule and various associated proteins are encapsulated in a capsid of protein nature (nucleocapsid). The whole is protected by a membrane of cellular origin which has incorporated the envelope protein of viral origin.

This envelope protein, in various forms, is considered at the present time to be a potential therapeutic component of a vaccine against AIDS.

Under natural conditions, the envelope protein (env) is initially synthesized in the form of a precursor, containing at its N-terminal end a signal sequence which initiates the passage of the precursor into the endoplasmic reticulum (secretion route). This signal peptide is then removed by proteolytic cleavage. The product of this cleavage is a protein referred to as gp160, which is itself subsequently cleaved into a gp40 small subunit and a gp120 large subunit. The N-terminal end of the gp120 corresponds to the N-terminal end of the gp160, while the C-terminal end of the gp40 corresponds to the C-terminal end of the gp160.

Each of these subunits is secreted out of the infected cell. However, the gp40 remains anchored in the cell membrane via its transmembrane domain. Its C-terminal portion (intracytoplasmic domain) remains in contact with the cytoplasm, while its N-terminal portion (extracytoplasmic domain) is at the cell surface. The gp120 subunit is released outside the cell, where it interacts with the extracellular domain of the gp40 subunit. The two subunits of the envelope protein thus remain associated in the form of a complex.

The amino acid sequence of the precursors of the env proteins of various viral strains are now known. As an example, FIG. 1 [SEQ ID NOS: 1-6] presents the sequence of the precursors of the gp160 proteins of the viral strains HIV-1 Bru, HIV-1 MN, HIV-1 ELI, HIV-1 RF, HIV-1 SF2C and HIV-1 SC. Similarly, FIG. 2 [SEQ ID NOS: 7-8] presents the sequence of the precursor of the gp160 of the viral strain HIV-2 Rod.

Hereinafter, and to make the text easier to understand, the sequences of the gp160 proteins other than the gp160 of the strain HIV-1 Bru will be described below by reference to the sequence of the gp160 of the strain HIV-1 Bru (hereinafter referred to as gp160-Bru) as follows: In addition, gp120-Bru corresponds to the sequence of the first 486 amino acids of gp160-Bru, while gp40-Bru corresponds to the sequence beginning with the amino acid at position 487 and ending with the amino acid at position 831. gp160-Bru so as to display maximum homology. For this purpose, gaps may be introduced either into the sequence of gp160-Bru or into the sequence of the gp160 of any kind. By definition, the position of an amino acid in the gp160 of any kind will be specified in identical fashion by the position of the homologous amino acid in gp160-Bru. any kind, opposite the amino acid at position x, there is no amino acid at position x in the sequence of the gp160. However, this amino acid is considered to possess a virtual presence. between the amino acid at position x and the amino acid at position x+1, it is considered that, in the gp160 of any kind, the position covers at least two subpositions x.sub.a, x.sub.b, . . . , x.sub.n, each occupied by an amino acid. By definition, the downstream position x.sub.n represents the position x. upstream of the amino acid at position 1, it is considered that, in the gp160 of any kind, the position 1 covers at least two subpositions 1.sub.a, 1.sub.b, . . . 1.sub.n, each occupied by an amino acid. By definition, the NH.sub.2 -terminal upstream position 1.sub.n represents the position 1. of any kind opposite the NH.sub.2 -terminal amino acid(s) of gp160-Bru, it may be noted that, by definition, the amino acid at the NH.sub.2 -terminal position in the gp160 of any kind holds simultaneously the position 1 and its position of homologous amino acid. of any kind opposite the COOH-terminal amino acid(s) of gp160-Bru, it may be noted that, by definition, the amino acid at the COOH-terminal position in the gp160 of any kind holds simultaneously the position 841 and its position of homologous amino acid.

At the present time, with regard to a vaccine, envelope protein is considered to be a potentially advantageous candidate from a therapeutic standpoint. However, its multichain structure in the original state constitutes a handicap in terms of feasibility. For this reason, it has been seen to be preferable to use a single-chain protein which would retain most of the epitopes of the gp120 and those of the gp40. This type of protein has already been proposed in Patent Application WO 87/6260. It is, more especially, a non-cleavable and soluble gp160 variant.

All the gp160 proteins of type HIV-1 viral strains possess, at positions 483-486, a so-called major cleavage site, recognized by one or more proteolytic enzymes. This cleavage site is the same for all the gp160 proteins described in FIG. 1, and corresponds to the sequence (SEQ ID NO:21) Arg-Glu-Lys-Arg (REKR). The proteolytic enzymes cut immediately downstream of this cleavage site to release a gp120 and a gp40.

When this cleavage site is not there, it has been demonstrated that the proteolytic enzymes recognize, albeit with lower efficiency, a so-called minor cleavage site, and to make [sic] a cut immediately downstream of the latter. Here too, this cleavage site is the same for all the gp160 proteins shown in FIG. 1. It corresponds to the sequence Lys-Arg-Arg (KRR) at positions 477-479, according to some authors or, according to others, the sequence (SEQ ID NO:22) Lys-Ala-Lys-Arg (KAKR) at positions 475-478.

In addition, it may be noted that the gp160 proteins of type HIV-2 viral strains possess only a major cleavage site at positions 475-478, which corresponds to the sequence (SEQ ID NO:23) Lys-Glu-Lys-Arg (KEKR).

A non-cleavable gp160 variant is an artificial analog of a native gp160. Its amino acid sequence corresponds to that of a native gp160 in which the major cleavage site and/or the minor cleavage site has/have been eliminated.

Such a gp160 variant may be synthesized by means of recombinant DNA techniques. It suffices to isolate a DNA fragment coding for a native gp160, and then to modify the region coding for the major cleavage site by directed mutagenesis so as to obtain a DNA fragment coding for a gp160 variant insensitive to proteolytic action. This latter DNA fragment is subsequently expressed under suitable conditions to give said gp160 variant. Such a gp160 variant which no longer contains the major cleavage site is referred to hereinafter as a type A non-cleavable gp160 variant.

Preferably, the region coding for the minor cleavage site can be, in addition, modified for identical purposes. Under these conditions, a type A' non-cleavable gp160 variant, which contains neither the major cleavage site nor the minor cleavage site, is obtained.

For this purpose, it may be noted, as an example, that the cleavage site REKR, KEKR or KAKR (SEQ ID NOS:21-23) and the cleavage site KRR may be replaced, respectively, by the sequences (SEQ ID NO:24) Asn-Glu-His-Gln (NEHQ) and Gln-Asn-His (QNH).

Moreover, it is also necessary for a gp160 to be obtained in soluble form. Such a gp160 corresponds to a native gp160 in which the transmembrane region of hydrophobic nature has been eliminated. This transmembrane region is located in the zone corresponding to the gp40, from the amino acid residue at position 659 to the amino acid residue at position 680. Additionally, but unnecessarily, another hydrophobic region, extending from the amino acid residue at position 487 to the amino acid residue at position 514, could be deleted.

Similarly, the means needed for the synthesis of a soluble gp160 variant obviously include the corresponding DNA fragment, which must be obtained by modification of the original DNA fragment.

A comparison of the sequences of the different gp160 proteins already known has demonstrated at least three domains whose sequence is hypervariable from one gp160 to another. These three domains are commonly referred to as the V.sub.1, V.sub.2 and V.sub.3 domains (or loops).

The first two domains, V.sub.1 and V.sub.2, are located between the cysteine residue at position 96 and the cysteine residue at position 171, while the third domain, V.sub.3, is located from the cysteine residue at position 271 to the cysteine residue at position 306.

There is also a final domain exhibiting some degree of variability, albeit considered to be lesser. This is the site of binding to the CD4 receptor of T-helper lymphocytes; it being located approximately from the amino acid residue at position 340 to the amino acid residue at position 440.

Irrespective of the gp160 under consideration, vaccination experiments have shown that the third hypervariable domain is essential for obtaining appropriate immunity. However, as a result of the hypervariable nature of this domain, the protection developed will be effective only against the viral strain from which the gp160 used is derived.

Lastly, it would appear that the first and the second hypervariable domains, as well as the CD4 receptor binding site, have an influence on the degree of immunity that could be obtained.

A vaccine of general applicability should enable individuals to be protected against the majority of HIV viral strains which are rife in the world. Consequently, a gp160-based vaccine should contain various gp160 proteins, each derived from a different viral strain. In order to employ such a vaccine, it is appropriate, in the first place, to construct the means intended for the production of the non-cleavable and soluble gp160 variant corresponding to each viral strain. As a first approach, this would hence involve cloning in each instance the DNA fragment coding for the gp160 of a particular viral strain, determining its sequence, modifying this DNA fragment in order to eliminate cleavage sites and hydrophobic regions by substitution or deletion and then, lastly, placing this DNA fragment thus modified in suitable conditions of expression. Since this type of operation would have to be repeated for each gp160, the preparation of such a vaccine is anticipated to be lengthy and expensive.

Furthermore, the viral strains can vary with the passage of time, e.g. by mutation. A particular strain which is a major cause of infection in a particular region of the world at a particular time can regress as an infectious agent, and another particular strain appear as a replacement. It is hence important to be able to adapt a vaccine rapidly to the epidemiological conditions and, in the present case, to have a gp160 variant available in the shortest possible time.

For this purpose, a new method has now been found for obtaining a gp160 variant which is suitable irrespective of the viral strain in question. Inasmuch as an expression cassette intended for the production of a non-cleavable and soluble gp160 variant derived from a first viral strain is made available, this method makes it possible to obtain a similar variant derived from a second viral strain while avoiding the complete cloning of the DNA fragment coding the gp160 of the second viral strain, and the modifications which would have to ensue therefrom.

Consequently, the invention proposes a method for constructing an expression cassette containing a DNA unit coding either for a precursor of a non-cleavable and soluble hybrid gp160 variant, or for a non-cleavable and soluble hybrid gp160 variant; said variant having an amino acid sequence comprising: located in this latter gp160 from the amino acid at position X to the amino acid at position Y. X being a number from 1 to 271 and Y being a number from 306 to 482; variant originating from a second strain of HIV virus and located in this latter gp160 variant from the amino acid at position Y+1 to the amino acid at the C-terminal position, Y being as defined above; and second strain of HIV virus and located in this latter gp160 from the amino acid at position 1 to the amino acid at position X-1, X being as defined above;

said method comprising: cassette which comprises: for said third region of the amino acid sequence of said hybrid gp160 variant; and region of the amino acid sequence of said hybrid gp160 variant, and

to obtain an expression cassette containing said DNA unit.

Such an expression cassette is the indispensable tool which enables a soluble and non-cleavable hybrid gp160 variant to be produced in a heterologous expression system.

In the method according to the invention, the DNA fragment coding for said first region may be cloned according to any method in common use. It may be noted, however, that this cloning may be advantageously performed by the PCR technique starting with the genomic DNA of cells infected with said second strain of HIV virus. Insertion of the cloned DNA fragment takes place in restriction sites initially present in the cassette or created for this purpose, for example by the suitable use of a polylinker. An illustration of this method is presented below in the examples.

"DNA unit coding for a polypeptide of any kind" is understood to mean a DNA segment whose first codon at the 5' position and last codon at the 3' position code, respectively, for the first amino acid at the N-terminal position and the last amino acid at the C-terminal position of the polypeptide.

According to a preferred embodiment, the method according to the invention is carried out in order to construct an expression cassette containing a DNA unit coding for a precursor of a non-cleavable and soluble hybrid gp160 variant. "Precursor of a gp160 variant according to the invention" means a polypeptide containing a signal peptide and a mature gp160 variant; the N-terminal end of said variant being combined with the C-terminal end of the signal peptide via a peptide bond. This precursor is the initial product of expression of the DNA unit. It is, in particular, present in the cytoplasm of the host cell, combined at the N-terminal position with a translation initiation methionine residue. The signal peptide enables the transfer of the gp160 variant to the endoplasmic reticulum to be initiated. During this transfer, the signal peptide is relinquished by proteolytic cleavage to give the mature form of the gp160 variant. In the remainder of the text, the term "gp160 variant" refers exclusively to its mature form.

The signal peptide can be any signal peptide in common use. It must, however, be chosen taking into account the host organism intended for the production of the gp160 variant according to the invention. For example, if the host organism is a mammalian cell, the signal peptide may be advantageously selected from the signal peptides of the precursors of the gp160 proteins of the different strains of HIV virus, independently of the origin of the first, second and third regions of the variant according to the invention. Alternatively, synthetic signal peptides may be used. Such signal peptides are, for example, hybrid signal peptides whose N-terminal end is derived from the precursor of the gp160 of said second strain of HIV virus and whose C-terminal end is derived from the precursor of the gp160 of said first strain of HIV virus. As a guide, it may be mentioned furthermore that the signal peptide of the precursor of the glycoprotein of a strain of the rabies virus may also be used. Lastly, a person skilled in the art should understand that this list is non-limiting.

The invention likewise proposes a non-cleavable and soluble hybrid gp160 variant which comprises: located in this latter gp160 from the amino acid at position X to the amino acid at position Y, X being a number from 1 to 271 and Y being a number from 306 to 482; variant originating from a second strain of HIV virus and located in this latter gp160 variant from the amino acid at position Y+1 to the amino acid at the C-terminal position, Y being as defined above; and

iii) when X is other than 1, a third region derived from the gp160 of said second strain of HIV virus and located in this latter gp160 from the amino acid at position 1 to the amino acid at position X-1, X being as defined above.

The first and also the second and third regions of the gp160 variant according to the invention may be derived from the gp160 of any strain of HIV virus, on condition that the first strain is different from the second. Preferably, the first region is derived from the gp160 of a viral strain selected from the strains HIV-2 Rod, HIV-1 Eli, HIV-1 RF, HIV-1 SF2C, HIV-1 SC and HIV-l MN, the latter being more especially preferred. Similarly, the second and third regions preferably originate from the gp160 of the strain HIV-1 Bru.

"Type A non-cleavable gp160 variant" is understood to mean a gp160 variant: containing the major cleavage site, the cleavage site.

When the gp160 variant is derived from a gp160 of a type HIV-1 viral strain, this variant is preferably of type A'; that is to say, containing neither the major cleavage site nor the minor cleavage site.

"Soluble gp160 variant" is understood to mean a gp160 variant derived from a native gp160 which no longer contains a transmembrane region or whose native transmembrane region has been mutated so that it can no longer perform its function of anchorage in the membrane. In addition, it is advantageously possible for such a soluble variant no longer to contain a hydrophobic region.

"Expression cassette" is understood to mean a DNA segment comprising a DNA unit to be expressed, as well as the elements needed for expression of the latter. The expression of a DNA unit is obtained by transcription of this DNA unit into messenger RNA and by translation of this messenger RNA into protein. Consequently, the essential elements are a constitutive or inducible promoter (transcription initiation), a translation initiation codon (ATG codon) and a translation termination codon (TAG, TAA or TGA codon). In addition, an expression cassette can also contain other elements; for example, a transcription terminator.

A person skilled in the art is obviously capable of choosing the appropriate promoter and terminator in accordance with the host organism in which it is desired to express the DNA unit, and in accordance with the vector into which the expression cassette has to be inserted in order to provide for its replication.

In keeping with the foregoing, the invention likewise proposes an expression cassette containing a DNA unit coding either for a precursor of a gp160 variant according to the invention, or for a gp160 variant according to the invention, as well as the elements needed for expression of said DNA unit.

In order to provide for its autonomous application in a host organism, an expression cassette according to the invention may be inserted into different types of vector having an origin of replication suited to the host organism; for example a plasmid or a virus. Viral type vectors have, in particular, the capacity to integrate in their genome a substantial amount of foreign DNA without impairing their capacity for replication. These vectors include, for example, pox viruses such as vaccinia virus, canarypox virus and fowlpox virus; and baculoviruses such as adenoviruses such as Adenovirus-2 or Adenovirus-5.

Apart from their use in a heterologous production system, some of these viral type vectors can be functional as a vaccinating agent. This applies, in particular, to the pox viruses and adenoviruses.

Thus, the invention likewise relates to a viral vector, into the genome of which an expression cassette according to the invention is inserted.

In another aspect of the invention, a cell transformed with an expression cassette according to the invention is also obtained. The expression cassette which transforms the cell may be transported by a plasmid or, alternatively, be integrated in the genome of the host cell.

The host organism intended for the production of the gp160 variant according to the invention can be any type of cell, preferably eukaryotic. This includes, for example: fungi such as yeasts, insect cells and mammalian cells.

The invention proposes, in addition, two alternative processes directed towards the production of a gp160 variant according to the invention: invention and the act of harvesting said variant from the culture, viral vector according to the invention and the act of harvesting said variant from the culture.

A gp160 variant and also a viral vector according to the invention possess a vaccinal activity against an HIV virus, and are consequently useful as pharmaceutical products intended especially for the treatment or prevention of AIDS.

Consequently, the invention proposes: treatment of AIDS, which comprises as therapeutic agent at least one gp160 variant or one viral vector according to the invention the act of administering a therapeutically effective amount of a gp160 variant or of a viral vector according to the invention to a patient needing such a treatment, invention as therapeutic agent intended for the curative or preventative treatment of AIDS.

Preferably, a pharmaceutical composition according to the invention can contain several gp160 variants according to the invention; each gp160 variant possessing at least one third hypervariable domain (V.sub.3 loop) different from the other variants present in the composition. Such a pharmaceutical composition should hence enable an individual to be correctly protected with respect to various HIV strains.

A pharmaceutical composition according to the invention can consist, in addition, of other therapeutic agents such as, for example, a peptide essentially corresponding to the third hypervariable domain of a gp160 (hereinafter referred to as V.sub.3 peptide). Preferably, such a peptide has a sequence substantially identical to the sequence of the third domain of a gp160 variant contained in the pharmaceutical composition according to the invention. Similarly, several V.sub.3 peptides may be present in the composition. In particular, if the pharmaceutical composition according to the invention contains different gp160 variants, the corresponding V.sub.3 peptides can obviously be added thereto.

A pharmaceutical composition according to the invention may be manufactured in a conventional manner. In particular, a gp160 variant according to the invention is combined with a diluent or a vehicle which is acceptable from a pharmaceutical standpoint. Lastly, a composition according to the invention can contain a vaccination adjuvant such as alum. Alternatively, this adjuvant may be added to a composition according to the invention immediately before use.

A composition according to the invention may be administered by any conventional route in common use in the vaccine field, especially subcutaneously, for example in the form of an injectable solution or suspension. The administration can take place in a single dose or a dose repeated one or more times after a certain time interval. The appropriate dosage varies in accordance with various parameters, for example with the individual being treated or the mode of administration.

Alternatively, a pharmaceutical composition according to the invention may be presented as part of a treatment kit. As an example, it may be noted that such a kit can contain: variant according to the invention, and V.sub.3 peptide, or concomitant administration of the pharmaceutical compositions contained in the kit.

The invention is illustrated below by reference to the following figures:

In the examples which follow, to make the text easier to write and to understand, "signal sequence" is understood to mean a signal sequence including the translation initiation methionine residue. M13TG4168

As shown in FIG. 3 [SEQ ID NOS: 9-12], the PstI-PstI DNA fragment of plasmid pTG1163 described in Patent Application EPA 245, 136 contains a DNA sequence coding for a precursor of a non-cleavable and soluble gp160-Bru variant. This PstI-PstI DNA fragment is inserted into the bacteriophage M13mp701 (described by M. P. Kieny et al. Gene (1983) 26:91) previously digested with PstI, to give the bacteriophage M13TG4137 (FIG. 4). The numbering of the nucleotides of the PstI-PstI fragment as shown in FIG. 3 [SEQ ID NOS: 9-12] serves as a reference in the remainder of Example 1.

Plasmid pTG1163 is cut with PstI and KpnI, and the DNA fragment corresponding to nucleotides 1 to 138 (FIG. 3 [SEQ ID NOS: 9-12]) is inserted into the bacteriophage M13TG130 (described by M. P. Kieny et al. (1983), supra) previously digested with PstI and KpnI. The bacteriophage M13TG4147 is thereby obtained (FIG. 4).

The bacteriophage M13TG4137 is cut with BglII, treated with the Klenow enzyme (Boehringer Mannheim) to obtain blunt ends and then cut with EcoRI. The EcoRI-BglII.degree. fragment derived from this digestion and containing the sequence corresponding to nucleotides 1424 to 2644 (FIG. 3) is inserted into the bacteriophage M13TG4147 previously digested with EcoRV and EcoRI. The bacteriophage M13TG4158, which contains: M13TG4147, that is to say ATCGCATGCG (SEQ ID NO:25),

is thereby obtained.

The single-stranded antisense bacteriophage M13TG4158 serves as a template for a mutation-deletion, performed using the Amersham kit and the oligonucleotide OTG2623 whose sequence is as follows (SEQ ID NO:26): SphI      SmaI .vertline.       .vertline. .vertline.      .vertline. GGGGGTGGAAATGGGGCA GCATGC AT CCCGGG CACAGAATCACGTGGTGC.

This mutagenesis makes it possible simultaneously to delete a 184-base pair fragment which contains nucleotides 67 to 138, the sequence ATCGCATGCG and nucleotides 1424 to 1525, and to create the cleavage sites for the enzymes SphI at the 5' end and SmaI at the 3' end, which are inserted between nucleotides 66 and 1526. The bacteriophage M13TG4168, which comprises: sites of the enzymes SphI and Smal, and

is thereby obtained. Bru-MN Hybrid gp160 Variant

As shown in FIG. 5 [SEQ ID NOS:13-14], the DNA fragment coding for the larger part of a precursor of gp120-MN is cloned by the PCR (Polymerase Chain Reaction) gene amplification technique, carried out starting with genomic DNA of CEM human cells infected with the viral strain HIV1-MN. This cloning is performed using the oligonucleotides OTG2624 and OTG2625, which introduce, respectively, a cleavage site for the enzyme SphI at the 5' end of the amplified DNA fragment and a cleavage site for the enzyme SmaI at the 3' end of the amplified DNA fragment. The sequences of these oligonucleotides are as follows (SEQ ID NOS:28-29): SphI .vertline.      .vertline. OTG2624 : GGCA GCATGC TCCTTGGGATATTGATGATCTG SmaI .vertline.      .vertline. OTG2625 : CTTTG CCCGGG TGGGTGCTACTCCTAATGGTTC

The amplified SphI-SmaI DNA fragment corresponds to nucleotides 53 to 1505 shown in FIG. 5 [SEQ ID NOS: 13-14], taking into account the sequence modifications brought about by the oligonucleotides OTG2624 and OTG2625. This fragment is inserted into the bacteriophage M13TG4168 cut with SphI and SmaI. The bacteriophage M13TG4174, which contains a DNA fragment coding for a precursor of a Bru-MN hybrid gp160 protein, is thereby obtained. The PstI fragment of the bacteriophage M13TG4174 which codes for the Bru-MN hybrid gp160 variant is inserted into the transfer plasmid pTG186poly (described by M. P. Kieny et al., Biotechnology, (1986) 4: 790), downstream of the E7.5k promoter and within the vaccinia virus gene coding for thymidine kinase. Plasmid pTG5156 is thereby obtained.

Plasmid pTG5156 is subsequently used to transfer the block for expression of the Bru-MN hybrid gp160 protein into the genome of vaccinia virus, Copenhagen strain, according to the method described by M. P. Kieny et al. Nature (1984), 312, 163-166). The vaccinia vector VVTG5156 is thereby obtained. Bru-Eli Hybrid gp160 Variant

Plasmid pTG186poly is cut with BamHI, treated with the Klenow enzyme, cut with SmaI to delete the larger part of the polylinker and then religated with itself to give plasmid pTG186PE. The polylinker now retains only the cleavage sites for the enzymes PstI, SalI and EcoRI.

The PstI-PstI DNA fragment of the bacteriophage M13TG4168 described above, which contains: shown in FIG. 3 [SEQ ID NOS: 9-12], sites of the enzymes SphI and SmaI, and fragment shown in FIG. 3 [SEQ ID NOS:9-12],

is inserted into plasmid pTG186PE previously cut with PstI, downstream of the E7.5k promoter and within the vaccinia virus gene coding for thymidine kinase. Plasmid pTG5160 is thereby obtained.

As shown in FIG. 6, the DNA fragment coding for the larger part of a precursor of gp120-Eli is cloned by the PCR gene amplification technique, carried out starting with the genomic DNA of CEM human cells infected with HIV1-Eli virus. This cloning is performed using the oligonucleotides OTG2624 and OTG2625, which introduce, respectively, a cleavage site for the enzyme SphI at the 5' end of the amplified DNA fragment and a cleavage site for the enzyme SmaI at the 3' end of the amplified DNA fragment. The amplified SphI-SmaI DNA fragment corresponds to nucleotides 53 to 1490 shown in FIG. 6 [SEQ ID NOS:15-16], taking into account the sequence modifications brought about by the oligonucleotides OTG2624 and OTG2625. This fragment is inserted into the bacteriophage M13TG131 (described by M. P. Kieny et al. (1983), supra) previously cut with SphI and SmaI, to give the bacteriophage M13TG4197. The SphI-SmaI_fragment of the bacteriophage M13TG4197 is then inserted into the transfer plasmid pTG5160 (described above) previously cut with SphI and SmaI. pTG5193 is thereby obtained.

Plasmid pTG5193 is subsequently used to transfer the block for expression of the Bru-Eli hybrid gp160 protein into the genome of vaccinia virus, Copenhagen strain, according to the method described by M. P. Kieny et al. (1984) supra. The vaccinia vector VVTG5193 is thereby obtained. Bru-RF Hybrid gp160 Variant

As shown in FIG. 7 [SEQ ID NOS:17-18], the DNA fragment coding for the larger part of a precursor of a gp120-RF protein is cloned by the PCR gene amplification technique, carried out starting with the genomic DNA of CEM human cells infected with HIV1-RF virus. This cloning is performed using the oligonucleotides OTG2624 and OTG2625, which introduce, respectively, a cleavage site for the enzyme SphI at the 5' end of the amplified DNA fragment and a cleavage site for the enzyme SmaI at the 3' end of the amplified DNA fragment. The amplified SphI-SmaI DNA fragment corresponds to nucleotides 53 to 1523 shown in FIG. 7 [SEQ ID NOS: 17-18], taking into account the sequence modifications brought about by the oligonucleotides OTG2624 and OTG2625. This fragment is inserted into the bacteriophage M13TG131 previously cut with SphI and SmaI, to give the bacteriophage M13TG4198. The SphI-SmaI fragment of the bacteriophage M13TG4198 is then inserted into the transfer plasmid pTG5160 (described in Example 3) previously cut with SphI and SmaI. pTG5194 is thereby obtained.

Plasmid pTG5194 is subsequently used to transfer the block for expression of the Bru-RF hybrid gp160 protein into the genome of vaccinia virus, Copenhagen strain, according to the method described by M. P. Kieny et al. (1984) supra. The vaccinia vector VVTG5194 is thereby obtained. Bru-SF2C Hybrid gp160 Variant

As shown in FIG. 8 [SEQ ID NOS:19-20], the DNA fragment coding for the larger part of a precursor of gp120-SF2C is cloned by the PCR gene amplification technique, carried out starting with the genomic DNA of CEM human cells infected with HIV1-SF2C virus. This cloning is performed using the oligonucleotides OTG2624 and OTG2625, which introduce, respectively, a cleavage site for the enzyme SphI at the 5' end of the amplified DNA fragment and a cleavage site for the enzyme SmaI at the 3' end of the amplified DNA fragment. The amplified SphI-SmaI DNA fragment corresponds to nucleotides 53 to 1493 shown in FIG. 8, taking into account the sequence modifications brought about by the oligonucleotides OTG2624 and OTG2625. This fragment is then inserted into the bacteriophage M13TG131 previously cut with SphI and SmaI, to give the bacteriophage M13TG4199. The SphI-SmaI fragment of the bacteriophage M13TG4199 is inserted into the transfer plasmid pTG5160 (described in Example 3) previously cut with SphI and SmaI. pTG5195 is thereby obtained.

Plasmid pTG5195 is subsequently used to transfer the block for expression of the Bru-SF2C hybrid gp160 protein into the genome of vaccinia virus, Copenhagen strain, according to the method described by M. P. Kieny et al. (1984) supra. The vaccinia vector VVTG5195 is thereby obtained. gp160 Proteins

BHK-21 cells are cultured in a GMEM medium (Gibco) supplemented with 10% of fetal calf serum (FCS). When the cells are at confluence (5.8.times.10.sup.6 cells/ml), the culture medium is removed and the cell lawn is washed twice with 50 ml of PBS (Dubelcco's phosphate buffer salt; Seromed). Fresh GMEM medium without FCS is then added. One of the vaccinia viruses VVTG5156, VVTG5193, VVTG5194 and VVTG5195, described above in Examples 2 to 5, is then added at an infectivity of 1 pfu/cell (plaque forming unit), and infection is continued for 72 h. The lysate is then centrifuged for 20 min at 10,000 g in order to remove cell debris, and the supernatant containing, inter alia, a hybrid gp160 and virions is recovered.

To 20 ml of culture supernatant obtained as described above, 1.3 ml of 1 M zinc chloride (ZnCl.sub.2) solution is added so as to have a final ZnCl.sub.2 concentration of 60 mM. The mixture is left for 1 h in ice; the precipitation supernatant is then recovered after centrifugation at 3000 rpm for 20 min in a Heraeus RF Minifuge centrifuge. This method removes by precipitation the virions as well as the majority of contaminant proteins. In each case, a purified solution of the hybrid gp160 variant is thereby obtained. (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 29 (2) INFORMATION FOR SEQ ID NO: 1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 861 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..854 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp Gly Trp Lys -30                 -25                 -20 Trp Gly Thr Met Leu Leu Gly Ile Leu Met Ile Cys Ser Ala Thr Glu -15                 -10                 -5 Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala 1               5                   10                  15 Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu 20                  25                  30 Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn 35                  40                  45 Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp 50                  55                  60 Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp 65                  70                  75 Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Ser 80                  85                  90                  95 Leu Lys Cys Thr Asp Leu Gly Asn Ala Thr Asn Thr Asn Ser Ser Asn 100                 105                 110 Thr Asn Ser Ser Ser Gly Glu Met Met Met Glu Lys Gly Glu Ile Lys 115                 120                 125 Asn Cys Ser Phe Asn Ile Ser Thr Ser Ile Arg Gly Lys Val Gln Lys 130                 135                 140 Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp 145                 150                 155 Thr Thr Ser Tyr Thr Leu Thr Ser Cys Asn Thr Ser Val Ile Thr Gln 160                 165                 170                 175 Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala 180                 185                 190 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly 195                 200                 205 Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile 210                 215                 220 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 225                 230                 235 Glu Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp Asn Ala Lys Thr 240                 245                 250                 255 Ile Ile Val Gln Leu Asn Gln Ser Val Glu Ile Asn Cys Thr Arg Pro 260                 265                 270 Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gln Arg Gly Pro Gly Arg 275                 280                 285 Ala Phe Val Thr Ile Gly Lys Ile Gly Asn Met Arg Gln Ala His Cys 290                 295                 300 Asn Ile Ser Arg Ala Lys Trp Asn Ala Thr Leu Lys Gln Ile Ala Ser 305                 310                 315 Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln 320                 325                 330                 335 Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly 340                 345                 350 Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp 355                 360                 365 Phe Asn Ser Thr Trp Ser Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser 370                 375                 380 Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe Ile Asn Met Trp 385                 390                 395 Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile 400                 405                 410                 415 Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly 420                 425                 430 Asn Asn Asn Asn Gly Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Met 435                 440                 445 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile 450                 455                 460 Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln 465                 470                 475 Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Leu Phe Leu Gly Phe Leu 480                 485                 490                 495 Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser Met Thr Leu Thr Val 500                 505                 510 Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu 515                 520                 525 Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp 530                 535                 540 Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu 545                 550                 555 Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile 560                 565                 570                 575 Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu 580                 585                 590 Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu Trp Asp Arg Glu Ile 595                 600                 605 Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn 610                 615                 620 Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala 625                 630                 635 Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys 640                 645                 650                 655 Ile Phe Ile Met Ile Val Gly Gly Leu Val Gly Leu Arg Ile Val Phe 660                 665                 670 Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu 675                 680                 685 Ser Phe Gln Thr His Leu Pro Thr Pro Arg Gly Pro Asp Arg Pro Glu 690                 695                 700 Gly Ile Glu Glu Glu Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Arg 705                 710                 715 Leu Val Asn Gly Ser Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu 720                 725                 730                 735 Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Leu Leu Leu Ile Val Thr 740                 745                 750 Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr 755                 760                 765 Trp Trp Asn Leu Leu Gln Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala 770                 775                 780 Val Ser Leu Leu Asn Ala Thr Ala Ile Ala Val Ala Glu Gly Thr Lys 785                 790                 795 Arg Val Ile Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile 800                 805                 810                 815 Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ile Leu Leu 820                 825 (2) INFORMATION FOR SEQ ID NO: 2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 887 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..854 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2 Met Arg Val Lys Gly Ile Arg Arg Asn Tyr Gln His Xaa Trp Xaa Xaa -30                 -25                 -20 Xaa Trp Gly Trp Gly Thr Met Leu Leu Gly Leu Leu Met Ile Cys Ser -15                 -10                 -5 Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1               5                   10                  15 Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr 20                  25                  30 Asp Thr Glu Val His Asn Val Trp Ala Thr Gln Ala Cys Val Pro Thr 35                  40                  45 Asp Pro Asn Pro Gln Glu Val Glu Leu Val Asn Val Thr Glu Asn Phe 50                  55                  60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile 65                  70                  75 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 80                  85                  90                  95 Cys Val Thr Leu Asn Cys Thr Asp Leu Arg Asn Thr Thr Asn Thr Asn 100                 105                 110 Asn Ser Thr Ala Asn Asn Asn Ser Asn Ser Glu Gly Thr Ile Lys Gly 115                 120                 125 Gly Glu Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp 130                 135                 140 Lys Met Gln Lys Glu Tyr Ala Leu Leu Tyr Lys Leu Asp Ile Val Ser 145                 150                 155 Ile Asp Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Asp Ser Thr Ser Xaa 160                 165                 170                 175 Xaa Xaa Xaa Xaa Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr 180                 185                 190 Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys 195                 200                 205 Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Ser 210                 215                 220 Gly Lys Gly Ser Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly 225                 230                 235 Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 240                 245                 250                 255 Glu Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asp Asn Ala Lys 260                 265                 270 Thr Ile Ile Val His Leu Asn Glu Ser Val Gln Ile Asn Cys Thr Arg 275                 280                 285 Pro Asn Tyr Asn Lys Arg Lys Arg Ile His Ile Xaa Xaa Gly Pro Gly 290                 295                 300 Arg Ala Phe Tyr Thr Thr Lys Asn Ile Ile Gly Thr Ile Arg Gln Ala 305                 310                 315 His Cys Asn Ile Ser Arg Ala Lys Trp Asn Asp Thr Leu Arg Gln Ile 320                 325                 330                 335 Val Ser Lys Leu Lys Glu Gln Phe Xaa Lys Asn Lys Thr Ile Val Xaa 340                 345                 350 Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe 355                 360                 365 Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Pro Leu Phe Asn 370                 375                 380 Ser Thr Trp Asn Gly Asn Asn Thr Trp Asn Xaa Xaa Xaa Xaa Asn Thr 385                 390                 395 Thr Gly Ser Asn Asn Asn Ile Thr Leu Gln Cys Lys Ile Lys Gln Ile 400                 405                 410                 415 Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile 420                 425                 430 Glu Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr 435                 440                 445 Arg Asp Gly Gly Lys Asp Thr Asp Xaa Xaa Xaa Thr Asn Asp Thr Glu 450                 455                 460 Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475 Leu Tyr Lys Tyr Lys Val Val Thr Ile Glu Pro Leu Gly Val Ala Pro 480                 485                 490                 495 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Ala Xaa Xaa 500                 505                 510 Ala Ile Gly Ala Leu Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr 515                 520                 525 Met Gly Ala Ala Ser Val Thr Leu Thr Val Gln Ala Arg Leu Leu Leu 530                 535                 540 Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala 545                 550                 555 Gln Gln His Met Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln 560                 565                 570                 575 Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu 580                 585                 590 Gly Phe Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Thr Val Pro 595                 600                 605 Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Asp Asp Ile Trp Asn Asn 610                 615                 620 Met Thr Trp Met Gln Trp Glu Arg Glu Ile Asp Asn Tyr Thr Ser Leu 625                 630                 635 Ile Tyr Ser Leu Leu Glu Lys Ser Gln Thr Gln Gln Glu Lys Asn Glu 640                 645                 650                 655 Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe 660                 665                 670 Asp Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val 675                 680                 685 Gly Gly Leu Val Gly Leu Arg Ile Val Phe Ala Val Leu Ser Ile Val 690                 695                 700 Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Leu Gln Thr Arg Pro 705                 710                 715 Pro Val Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu Gly 720                 725                 730                 735 Gly Glu Arg Asp Arg Asp Thr Ser Gly Arg Leu Val His Gly Phe Leu 740                 745                 750 Ala Ile Ile Trp Val Asp Leu Arg Ser Leu Phe Leu Phe Ser Tyr His 755                 760                 765 His Xaa Arg Asp Leu Leu Leu Ile Ala Ala Arg Ile Val Glu Leu Leu 770                 775                 780 Gly Arg Arg Gly Trp Glu Val Leu Lys Tyr Trp Trp Asn Leu Leu Gln 785                 790                 795 Tyr Trp Ser Gln Glu Leu Lys Ser Ser Ala Val Ser Leu Leu Asn Ala 800                 805                 810                 815 Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu Val Leu 820                 825                 830 Gln Arg Ala Gly Arg Ala Ile Leu His Ile Pro Thr Arg Ile Arg Gln 835                 840                 845 Gly Leu Glu Arg Ala Leu Leu 850 (2) INFORMATION FOR SEQ ID NO: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 906 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..873 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3 Met Arg Ala Arg Gly Ile Glu Arg Asn Cys Gln Asn Xaa Trp Xaa Xaa -30                 -25                 -20 Xaa Trp Lys Trp Gly Ile Met Leu Leu Gly Ile Leu Met Thr Cys Ser -15                 -10                 -5 Ala Ala Asp Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1               5                   10                  15 Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ser Tyr 20                  25                  30 Glu Thr Glu Ala His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr 35                  40                  45 Asp Pro Asn Pro Gln Glu Ile Ala Leu Glu Asn Val Thr Glu Asn Phe 50                  55                  60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile 65                  70                  75 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 80                  85                  90                  95 Cys Val Thr Leu Asn Cys Ser Asp Glu Leu Arg Asn Asn Gly Thr Met 100                 105                 110 Gly Asn Asn Val Thr Thr Glu Glu Lys Gly Xaa Xaa Xaa Xaa Xaa Xaa 115                 120                 125 Xaa Xaa Met Lys Asn Cys Ser Phe Asn Val Thr Thr Val Leu Lys Asp 130                 135                 140 Lys Lys Gln Gln Val Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro 145                 150                 155 Ile Asp Asn Asp Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Thr 160                 165                 170                 175 Asn Ser Thr Asn Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr 180                 185                 190 Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys 195                 200                 205 Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Arg Asp Lys Lys Phe Asn 210                 215                 220 Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly 225                 230                 235 Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 240                 245                 250                 255 Glu Glu Glu Val Ile Ile Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys 260                 265                 270 Asn Ile Ile Ala His Leu Asn Glu Ser Val Lys Ile Thr Cys Ala Arg 275                 280                 285 Pro Tyr Gln Asn Thr Arg Gln Arg Thr Pro Ile Xaa Xaa Gly Leu Gly 290                 295                 300 Gln Ser Leu Tyr Thr Thr Xaa Arg Ser Arg Ser Ile Ile Gly Gln Ala 305                 310                 315 His Cys Asn Ile Ser Arg Ala Gln Trp Ser Lys Thr Leu Gln Gln Val 320                 325                 330                 335 Ala Arg Lys Leu Gly Thr Leu Leu Xaa Xaa Asn Lys Thr Ile Ile Lys 340                 345                 350 Phe Lys Pro Ser Ser Gly Gly Asp Pro Glu Ile Thr Thr His Ser Phe 355                 360                 365 Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn 370                 375                 380 Ser Thr Trp Asn Ile Xaa Ser Ala Trp Asn Asn Ile Thr Glu Ser Asn 385                 390                 395 Asn Ser Thr Asn Thr Asn Ile Thr Leu Gln Cys Arg Ile Lys Gln Ile 400                 405                 410                 415 Ile Lys Met Xaa Val Ala Gly Arg Lys Ala Ile Tyr Ala Pro Pro Ile 420                 425                 430 Glu Arg Asn Ile Leu Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr 435                 440                 445 Arg Asp Gly Gly Ile Asn Asn Xaa Xaa Xaa Xaa Xaa Ser Thr Asn Glu 450                 455                 460 Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475 Leu Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro Leu Gly Val Ala Pro 480                 485                 490                 495 Thr Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Ile Gly 500                 505                 510 Xaa Leu Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr 515                 520                 525 Met Gly Ala Arg Ser Val Thr Leu Thr Val Gln Ala Arg Gln Leu Met 530                 535                 540 Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala 545                 550                 555 Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln 560                 565                 570                 575 Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu 580                 585                 590 Gly Ile Trp Gly Cys Ser Gly Lys His Ile Cys Thr Thr Asn Val Pro 595                 600                 605 Trp Asn Ser Ser Trp Ser Asn Arg Ser Leu Asn Glu Ile Trp Gln Asn 610                 615                 620 Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr Gly Leu 625                 630                 635 Ile Tyr Ser Leu Ile Glu Glu Ser Gln Thr Gln Gln Glu Lys Asn Glu 640                 645                 650                 655 Lys Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe 660                 665                 670 Ser Ile Thr Gln Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Ile 675                 680                 685 Gly Gly Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser Leu Val 690                 695                 700 Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Leu 705                 710                 715 Pro Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Thr Glu Glu Glu Gly 720                 725                 730                 735 Gly Glu Arg Gly Arg Asp Arg Ser Val Arg Leu Leu Asn Gly Phe Ser 740                 745                 750 Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His 755                 760                 765 Arg Leu Arg Asp Leu Ile Leu Ile Ala Val Arg Ile Val Glu Leu Leu 770                 775                 780 Gly Arg Arg Gly Trp Asp Ile Leu Lys Tyr Leu Trp Asn Leu Leu Gln 785                 790                 795 Tyr Trp Ser Gln Glu Leu Arg Asn Ser Ala Ser Ser Leu Phe Asp Ala 800                 805                 810                 815 Ile Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu Ile Ile 820                 825                 830 Gln Arg Ala Cys Arg Ala Val Leu Asn Ile Pro Arg Arg Ile Arg Gln 835                 840                 845 Gly Leu Glu Arg Ser Leu Leu Asn Gly Trp Gln Met Val Lys Lys Tyr 850                 855                 860 Ser Gly Met Ala Cys Tyr Lys Gly Lys Asn 865                 870 (2) INFORMATION FOR SEQ ID NO: 4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 887 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..854 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4 Met Arg Val Met Glu Met Arg Lys Asn Cys Gln His Leu Trp Lys Trp -30                 -25                 -20 Xaa Xaa Xaa Xaa Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser -15                 -10                 -5 Ala Ala Glu Asp Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1               5                   10                  15 Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Glu Ala Lys Ala Tyr 20                  25                  30 Lys Thr Glu Val His Asn Val Trp Ala Lys His Ala Cys Val Pro Thr 35                  40                  45 Asp Pro Asn Pro Gln Glu Val Leu Leu Glu Asn Val Thr Glu Asn Phe 50                  55                  60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile 65                  70                  75 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 80                  85                  90                  95 Cys Val Thr Leu Asn Cys Thr Asp Xaa Xaa Xaa Xaa Xaa Ala Asn Leu 100                 105                 110 Asn Gly Thr Asn Val Thr Ser Ser Ser Gly Gly Thr Met Met Glu Asn 115                 120                 125 Gly Glu Ile Lys Asn Cys Ser Phe Gln Val Thr Thr Ser Arg Arg Asp 130                 135                 140 Lys Thr Gln Lys Lys Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro 145                 150                 155 Ile Glu Lys Gly Asn Ile Ser Pro Lys Asn Asn Thr Ser Asn Asn Thr 160                 165                 170                 175 Ser Tyr Gly Asn Tyr Thr Leu Ile His Cys Asn Ser Ser Val Ile Thr 180                 185                 190 Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys 195                 200                 205 Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn 210                 215                 220 Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly 225                 230                 235 Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 240                 245                 250                 255 Glu Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asp Asn Val Lys 260                 265                 270 Thr Ile Ile Val Gln Leu Asn Ala Ser Val Gln Ile Asn Cys Thr Arg 275                 280                 285 Pro Asn Asn Asn Thr Arg Lys Ser Ile Thr Xaa Xaa Lys Gly Pro Gly 290                 295                 300 Arg Val Ile Tyr Ala Thr Gly Gln Ile Ile Gly Asp Ile Arg Lys Ala 305                 310                 315 His Cys Asn Leu Ser Arg Ala Gln Trp Asn Asn Thr Leu Lys Gln Val 320                 325                 330                 335 Val Thr Lys Leu Arg Glu Gln Phe Xaa Asp Asn Lys Thr Ile Val Xaa 340                 345                 350 Phe Thr Ser Ser Ser Gly Gly Asp Pro Glu Ile Val Leu His Ser Phe 355                 360                 365 Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn 370                 375                 380 Ser Thr Trp Asn Ser Xaa Xaa Xaa Xaa Xaa Thr Glu Gly Ser Asn Asn 385                 390                 395 Thr Gly Gly Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile 400                 405                 410                 415 Val Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile 420                 425                 430 Ser Gly Gln Ile Lys Cys Ile Ser Asn Ile Thr Gly Leu Leu Leu Thr 435                 440                 445 Arg Asp Gly Gly Glu Asp Thr Xaa Xaa Xaa Xaa Thr Asn Thr Thr Glu 450                 455                 460 Ile Phe Arg Leu Gly Gly Gly Asn Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475 Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro 480                 485                 490                 495 Thr Arg Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Ala Val Gly 500                 505                 510 Thr Ile Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr 515                 520                 525 Met Gly Ala Gly Ser Ile Thr Leu Thr Val Gln Ala Arg His Leu Leu 530                 535                 540 Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala 545                 550                 555 Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln 560                 565                 570                 575 Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu 580                 585                 590 Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Thr Val Pro 595                 600                 605 Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Asn Met Ile Trp Asn Asn 610                 615                 620 Met Thr Trp Met Gln Trp Glu Arg Glu Ile Asp Asn Tyr Thr Gly Ile 625                 630                 635 Ile Tyr Asn Leu Leu Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu 640                 645                 650                 655 Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Asn Leu Trp Asn Trp Phe 660                 665                 670 Asp Ile Thr Gln Trp Leu Trp Tyr Ile Arg Ile Phe Ile Met Ile Val 675                 680                 685 Gly Gly Leu Val Gly Leu Lys Ile Val Phe Ala Val Leu Ser Ile Val 690                 695                 700 Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr His Leu 705                 710                 715 Pro Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Gly Glu Gly 720                 725                 730                 735 Gly Glu Arg Asp Arg Asp Arg Ser Gly Gly Ala Val Asn Gly Phe Leu 740                 745                 750 Thr Leu Ile Trp Asp Asp Leu Trp Thr Leu Cys Ser Phe Ser Tyr His 755                 760                 765 Arg Leu Arg Asp Leu Leu Leu Ile Val Val Arg Ile Val Glu Leu Leu 770                 775                 780 Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Asn Leu Leu Gln 785                 790                 795 Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala Val Ser Leu Leu Asn Thr 800                 805                 810                 815 Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Ile Ile Glu Val Ala 820                 825                 830 Gln Arg Ile Leu Arg Ala Phe Leu His Ile Pro Arg Arg Ile Arg Gln 835                 840                 845 Gly Leu Glu Arg Ala Leu Leu 850 (2) INFORMATION FOR SEQ ID NO: 5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 887 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..854 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5 Met Arg Val Lys Gly Ser Gly Arg Asn Tyr Gln His Leu Trp Arg Trp -30                 -25                 -20 Gly Xaa Xaa Xaa Xaa Thr Met Leu Leu Gly Ile Leu Met Ile Cys Ser -15                 -10                 -5 Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1               5                   10                  15 Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr 20                  25                  30 Asp Thr Glu Val His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr 35                  40                  45 Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn Phe 50                  55                  60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile 65                  70                  75 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 80                  85                  90                  95 Cys Val Thr Leu Asn Cys Thr Asn Leu Arg Asn Asp Thr Ser Thr Asn 100                 105                 110 Xaa Ala Thr Asn Thr Thr Ser Ser Asn Arg Gly Lys Met Xaa Glu Gly 115                 120                 125 Gly Glu Met Thr Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Ser 130                 135                 140 Lys Val Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro 145                 150                 155 Ile Asp Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Thr Ser Xaa 160                 165                 170                 175 Xaa Xaa Xaa Xaa Tyr Thr Leu Ile Asn Cys Asn Thr Ser Val Ile Thr 180                 185                 190 Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys 195                 200                 205 Ala Arg Trp Xaa Phe Ala Ile Leu Asn Cys Asn Asn Lys Lys Phe Asn 210                 215                 220 Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly 225                 230                 235 Ile Arg Pro Val Val Ser Thr His Leu Leu Leu Asn Gly Ser Leu Ala 240                 245                 250                 255 Glu Glu Glu Val Val Leu Arg Ser Glu Asn Phe Thr Asp Asn Ala Lys 260                 265                 270 Thr Ile Ile Val Gln Leu Lys Glu Ala Val Glu Ile Asn Cys Thr Arg 275                 280                 285 Pro Asn Asn Asn Thr Thr Arg Ser Ile His Ile Xaa Xaa Gly Pro Gly 290                 295                 300 Arg Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala 305                 310                 315 His Cys Asn Ile Ser Arg Ala Lys Trp Asn Asn Thr Leu Lys Gln Ile 320                 325                 330                 335 Val Ile Lys Leu Arg Asp Gln Phe Xaa Glu Asn Lys Thr Ile Ile Xaa 340                 345                 350 Phe Asn Arg Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe 355                 360                 365 Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Ser 370                 375                 380 Ser Thr Trp Asn Xaa Xaa Xaa Xaa Xaa Gly Thr Glu Gly Ser Asn Asn 385                 390                 395 Thr Gly Gly Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Glu Ile 400                 405                 410                 415 Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile 420                 425                 430 Lys Gly Gln Val Lys Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr 435                 440                 445 Arg Asp Gly Gly Asn Ser Lys Asn Gly Ser Lys Asn Glu Asn Thr Glu 450                 455                 460 Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475 Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro 480                 485                 490                 495 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Ala Val Gly 500                 505                 510 Thr Ile Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr 515                 520                 525 Met Gly Ala Thr Ser Met Thr Leu Thr Val Gln Ala Arg Leu Leu Leu 530                 535                 540 Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala 545                 550                 555 Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln 560                 565                 570                 575 Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu 580                 585                 590 Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Thr Val Pro 595                 600                 605 Trp Asn Thr Ser Trp Ser Asn Lys Ser Leu Asp Lys Ile Trp Gly Asn 610                 615                 620 Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr Ser Leu 625                 630                 635 Ile Tyr Thr Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu 640                 645                 650                 655 Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe 660                 665                 670 Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val 675                 680                 685 Gly Gly Leu Val Gly Leu Arg Ile Val Phe Thr Val Leu Ser Ile Val 690                 695                 700 Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Arg Leu 705                 710                 715 Pro Ser Gln Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu Gly 720                 725                 730                 735 Gly Glu Arg Asp Arg Asp Arg Ser Gly Arg Leu Val Asp Gly Phe Leu 740                 745                 750 Ala Ile Ile Trp Val Asp Xaa Arg Ser Leu Cys Leu Phe Ser Tyr His 755                 760                 765 Arg Leu Arg Asp Leu Leu Leu Ile Val Thr Arg Ile Val Glu Leu Leu 770                 775                 780 Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Asn Leu Leu Gln 785                 790                 795 Tyr Trp Ser Gln Glu Leu Arg Asn Ser Ala Val Ser Phe Val Asn Ala 800                 805                 810                 815 Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu Leu Leu 820                 825                 830 Gln Arg Ala Phe Arg Ala Ile Leu His Ile Pro Thr Arg Ile Arg Gln 835                 840                 845 Gly Leu Glu Arg Ala Leu Gln 850 (2) INFORMATION FOR SEQ ID NO: 6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 887 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..854 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6 Met Lys Val Lys Gly Thr Arg Arg Asn Tyr Gln His Leu Trp Arg Trp -30                 -25                 -20 Xaa Xaa Xaa Xaa Gly Thr Leu Leu Leu Gly Met Leu Met Ile Cys Ser -15                 -10                 -5 Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1               5                   10                  15 Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Arg Ala Tyr 20                  25                  30 Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr 35                  40                  45 Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn Phe 50                  55                  60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile Ile 65                  70                  75 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 80                  85                  90                  95 Cys Val Thr Leu Asn Cys Thr Asp Leu Gly Lys Ala Thr Asn Thr Asn 100                 105                 110 Xaa Ser Ser Asn Trp Lys Glu Glu Ile Xaa Xaa Xaa Xaa Xaa Xaa Lys 115                 120                 125 Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp 130                 135                 140 Lys Ile Gln Lys Glu Asn Ala Leu Phe Arg Asn Leu Asp Val Val Pro 145                 150                 155 Ile Asp Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Ala Ser Thr Thr Thr 160                 165                 170                 175 Asn Tyr Thr Asn Tyr Arg Leu Ile His Cys Asn Arg Ser Val Ile Thr 180                 185                 190 Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys 195                 200                 205 Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn 210                 215                 220 Gly Lys Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly 225                 230                 235 Ile Arg Pro Ile Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 240                 245                 250                 255 Glu Glu Glu Val Val Ile Arg Ser Asp Asn Phe Thr Asn Asn Ala Lys 260                 265                 270 Thr Ile Ile Val Gln Leu Asn Glu Ser Val Ala Ile Asn Cys Thr Arg 275                 280                 285 Pro Asn Asn Asn Thr Arg Lys Ser Ile Tyr Ile Xaa Xaa Gly Pro Gly 290                 295                 300 Arg Ala Phe His Thr Thr Gly Arg Ile Ile Gly Asp Ile Arg Lys Ala 305                 310                 315 His Cys Asn Ile Ser Arg Ala Gln Trp Asn Asn Thr Leu Glu Gln Ile 320                 325                 330                 335 Val Lys Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Val Xaa 340                 345                 350 Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe 355                 360                 365 Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn 370                 375                 380 Asn Xaa Xaa Xaa Xaa Xaa Xaa Thr Trp Arg Leu Asn His Thr Glu Gly 385                 390                 395 Thr Lys Gly Asn Asp Thr Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile 400                 405                 410                 415 Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile 420                 425                 430 Gly Gly Gln Ile Ser Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr 435                 440                 445 Arg Asp Gly Gly Thr Asn Val Xaa Xaa Xaa Xaa Thr Asn Asp Thr Glu 450                 455                 460 Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475 Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro Leu Gly Ile Ala Pro 480                 485                 490                 495 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Ala Val Gly 500                 505                 510 Ile Val Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr 515                 520                 525 Met Gly Ala Val Ser Leu Thr Leu Thr Val Gln Ala Arg Gln Leu Leu 530                 535                 540 Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala 545                 550                 555 Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln 560                 565                 570                 575 Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu 580                 585                 590 Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro 595                 600                 605 Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Asp Ile Trp Asp Asn 610                 615                 620 Met Thr Trp Met Gln Trp Glu Arg Glu Ile Asp Asn Tyr Thr Asn Thr 625                 630                 635 Ile Tyr Thr Leu Leu Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu 640                 645                 650                 655 Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe 660                 665                 670 Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val 675                 680                 685 Gly Gly Leu Val Gly Leu Arg Ile Val Phe Ala Val Leu Ser Ile Val 690                 695                 700 Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Arg Leu 705                 710                 715 Pro Val Pro Arg Gly Pro Asp Arg Pro Asp Gly Ile Glu Glu Glu Gly 720                 725                 730                 735 Gly Glu Arg Asp Arg Asp Arg Ser Val Arg Leu Val Asp Gly Phe Leu 740                 745                 750 Ala Leu Ile Trp Glu Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr Arg 755                 760                 765 Arg Leu Arg Asp Leu Leu Leu Ile Ala Ala Arg Thr Val Glu Ile Leu 770                 775                 780 Gly His Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Ser Leu Leu Gln 785                 790                 795 Tyr Trp Ile Gln Glu Leu Lys Asn Ser Ala Val Ser Trp Leu Asn Ala 800                 805                 810                 815 Thr Ala Ile Ala Val Thr Glu Gly Thr Asp Arg Val Ile Glu Val Ala 820                 825                 830 Gln Arg Ala Tyr Arg Ala Ile Leu His Ile His Arg Arg Ile Arg Gln 835                 840                 845 Gly Leu Glu Arg Leu Leu Leu 850 (2) INFORMATION FOR SEQ ID NO: 7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 861 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..831 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp Gly Trp Lys -30                 -25                 -20                 -15 Trp Gly Thr Met Leu Leu Gly Ile Leu Met Ile Cys Ser Ala Thr Glu -10                 -5                  1 Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala 5                   10                  15 Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu 20                  25                  30 Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn 35                  40                  45                  50 Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp 55                  60                  65 Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp 70                  75                  80 Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Ser 85                  90                  95 Leu Lys Cys Thr Asp Leu Gly Asn Ala Thr Asn Thr Asn Ser Ser Asn 100                 105                 110 Thr Asn Ser Ser Ser Gly Glu Met Met Met Glu Lys Gly Glu Ile Lys 115                 120                 125                 130 Asn Cys Ser Phe Asn Ile Ser Thr Ser Ile Arg Gly Lys Val Gln Lys 135                 140                 145 Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp 150                 155                 160 Thr Thr Ser Tyr Thr Leu Thr Ser Cys Asn Thr Ser Val Ile Thr Gln 165                 170                 175 Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala 180                 185                 190 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly 195                 200                 205                 210 Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile 215                 220                 225 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 230                 235                 240 Glu Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp Asn Ala Lys Thr 245                 250                 255 Ile Ile Val Gln Leu Asn Gln Ser Val Glu Ile Asn Cys Thr Arg Pro 260                 265                 270 Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gln Arg Gly Pro Gly Arg 275                 280                 285                 290 Ala Phe Val Thr Ile Gly Lys Ile Gly Asn Met Arg Gln Ala His Cys 295                 300                 305 Asn Ile Ser Arg Ala Lys Trp Asn Ala Thr Leu Lys Gln Ile Ala Ser 310                 315                 320 Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln 325                 330                 335 Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly 340                 345                 350 Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp 355                 360                 365                 370 Phe Asn Ser Thr Trp Ser Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser 375                 380                 385 Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe Ile Asn Met Trp 390                 395                 400 Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile 405                 410                 415 Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly 420                 425                 430 Asn Asn Asn Asn Gly Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Met 435                 440                 445                 450 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile 455                 460                 465 Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln 470                 475                 480 Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Leu Phe Leu Gly Phe Leu 485                 490                 495 Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser Met Thr Leu Thr Val 500                 505                 510 Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu 515                 520                 525                 530 Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp 535                 540                 545 Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu 550                 555                 560 Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile 565                 570                 575 Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu 580                 585                 590 Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu Trp Asp Arg Glu Ile 595                 600                 605                 610 Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn 615                 620                 625 Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala 630                 635                 640 Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys 645                 650                 655 Ile Phe Ile Met Ile Val Gly Gly Leu Val Gly Leu Arg Ile Val Phe 660                 665                 670 Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu 675                 680                 685                 690 Ser Phe Gln Thr His Leu Pro Thr Pro Arg Gly Pro Asp Arg Pro Glu 695                 700                 705 Gly Ile Glu Glu Glu Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Arg 710                 715                 720 Leu Val Asn Gly Ser Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu 725                 730                 735 Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Leu Leu Leu Ile Val Thr 740                 745                 750 Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr 755                 760                 765                 770 Trp Trp Asn Leu Leu Gln Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala 775                 780                 785 Val Ser Leu Leu Asn Ala Thr Ala Ile Ala Val Ala Glu Gly Thr Asp 790                 795                 800 Arg Val Ile Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile 805                 810                 815 Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ile Leu Leu 820                 825                 830 (2) INFORMATION FOR SEQ ID NO: 8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 915 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: Protein (B) LOCATION:  1..883 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8 Met Met Xaa Xaa Xaa Xaa Xaa Asn Gln Leu Leu Ile Xaa Xaa Xaa Xaa -30                 -25                 -20 Xaa Xaa Ala Ile Leu Leu Ala Ser Ala Cys Leu Val Tyr Cys Xaa Xaa -15                 -10                 -5 Thr Gln Xaa Xaa Tyr Val Thr Val Phe Tyr Gly Val Pro Thr Trp Lys 1               5                   10                  15 Asn Ala Thr Ile Pro Leu Phe Cys Ala Thr Arg Asn Arg Xaa Xaa Xaa 20                  25                  30 Xaa Xaa Xaa Xaa Asp Thr Trp Gly Thr Ile Gln Cys Leu Pro Asp Asn 35                  40                  45 Asp Asp Tyr Gln Glu Ile Thr Leu Xaa Asn Val Thr Glu Ala Phe Asp 50                  55                  60 Ala Trp Asn Asn Thr Val Thr Glu Gln Ala Ile Glu Asp Val Trp His 65                  70                  75                  80 Leu Phe Glu Thr Ser Ile Lys Pro Cys Val Lys Leu Thr Pro Leu Cys 85                  90                  95 Val Ala Met Lys Cys Ser Ser Thr Glu Ser Ser Thr Gly Asn Asn Thr 100                 105                 110 Thr Ser Lys Ser Thr Ser Thr Thr Thr Thr Thr Pro Thr Asp Gln Glu 115                 120                 125 Gln Glu Ile Ser Glu Asp Thr Pro Cys Ala Arg Ala Asp Asn Cys Ser 130                 135                 140 Gly Leu Gly Glu Glu Glu Thr Ile Asn Cys Gln Phe Asn Met Thr Gly 145                 150                 155                 160 Leu Glu Arg Asp Lys Xaa Lys Lys Gln Tyr Asn Glu Thr Trp Tyr Ser 165                 170                 175 Lys Asp Val Val Cys Glu Thr Asn Asn Ser Thr Asn Gln Thr Gln Cys 180                 185                 190 Tyr Met Asn His Cys Asn Thr Ser Val Ile Thr Glu Ser Cys Asp Lys 195                 200                 205 His Tyr Trp Asp Ala Ile Arg Phe Arg Tyr Cys Ala Pro Pro Gly Tyr 210                 215                 220 Ala Leu Leu Arg Cys Asn Asp Thr Asn Tyr Ser Gly Phe Ala Pro Asn 225                 230                 235                 240 Cys Ser Lys Val Val Ala Ser Thr Cys Thr Arg Met Met Glu Thr Gln 245                 250                 255 Thr Ser Thr Trp Phe Gly Phe Asn Gly Thr Arg Ala Glu Asn Arg Thr 260                 265                 270 Tyr Ile Xaa Xaa Xaa Tyr Trp His Gly Arg Asp Asn Arg Thr Ile Ile 275                 280                 285 Ser Leu Asn Lys Tyr Tyr Asn Leu Ser Leu His Cys Lys Arg Pro Gly 290                 295                 300 Asn Lys Thr Val Lys Gln Ile Met Leu Met Ser Gly His Val Phe His 305                 310                 315                 320 Ser His Tyr Gln Pro Ile Asn Lys Xaa Xaa Arg Pro Arg Gln Ala Trp 325                 330                 335 Cys Trp Phe Xaa Lys Gly Lys Trp Lys Asp Ala Met Gln Glu Val Lys 340                 345                 350 Glu Thr Leu Ala Lys His Pro Arg Tyr Arg Gly Thr Asn Asp Thr Arg 355                 360                 365 Asn Ile Ser Phe Ala Ala Pro Gly Lys Gly Ser Asp Pro Glu Val Ala 370                 375                 380 Tyr Met Trp Thr Asn Cys Arg Gly Glu Phe Leu Tyr Cys Asn Met Thr 385                 390                 395                 400 Xaa Xaa Xaa Xaa Xaa Xaa Trp Phe Leu Asn Xaa Trp Ile Glu Asn Lys 405                 410                 415 Thr His Arg Asn Tyr Ala Xaa Xaa Xaa Xaa Xaa Xaa Pro Cys His Ile 420                 425                 430 Lys Gln Ile Ile Asn Thr Trp His Lys Val Gly Arg Asn Val Tyr Leu 435                 440                 445 Pro Pro Arg Glu Gly Glu Leu Ser Cys Asn Ser Thr Val Thr Ser Ile 450                 455                 460 Ile Ala Asn Met Asp Trp Gln Asn Asn Asn Gln Thr Asn Ile Thr Phe 465                 470                 475                 480 Ser Ala Glu Val Ala Glu Leu Xaa Xaa Xaa Tyr Arg Leu Glu Leu Gly 485                 490                 495 Asp Tyr Lys Leu Val Glu Ile Thr Pro Ile Gly Phe Ala Pro Thr Lys 500                 505                 510 Glu Lys Arg Tyr Ser Ser Ala His Gly Arg His Thr Arg Gly Val Phe 515                 520                 525 Val Leu Gly Phe Leu Gly Phe Leu Ala Thr Ala Gly Ser Ala Met Gly 530                 535                 540 Ala Ala Ser Leu Thr Val Ser Ala Gln Ser Arg Thr Leu Leu Ala Gly 545                 550                 555                 560 Ile Val Gln Gln Gln Gln Gln Leu Leu Asp Val Val Lys Arg Gln Gln 565                 570                 575 Glu Leu Leu Arg Leu Thr Val Trp Gly Thr Lys Asn Leu Gln Ala Arg 580                 585                 590 Val Thr Ala Ile Glu Lys Tyr Leu Gln Asp Gln Ala Arg Leu Asn Ser 595                 600                 605 Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp Xaa 610                 615                 620 Xaa Xaa Xaa Val Asn Asp Ser Leu Ala Pro Asp Trp Asp Asn Met Thr 625                 630                 635                 640 Trp Gln Glu Trp Glu Lys Gln Val Arg Tyr Leu Glu Ala Asn Ile Ser 645                 650                 655 Lys Ser Leu Glu Gln Ala Gln Ile Gln Gln Glu Lys Asn Met Tyr Glu 660                 665                 670 Leu Gln Lys Leu Asn Ser Trp Asp Ile Phe Gly Asn Trp Phe Asp Leu 675                 680                 685 Thr Ser Trp Val Lys Tyr Ile Gln Tyr Gly Val Leu Ile Ile Val Ala 690                 695                 700 Val Ile Ala Leu Arg Ile Val Ile Tyr Val Val Gln Met Leu Ser Arg 705                 710                 715                 720 Leu Arg Lys Gly Tyr Arg Pro Val Phe Ser Ser Pro Pro Gly Tyr Ile 725                 730                 735 Gln Gln Ile His Ile His Lys Asp Arg Gly Gln Pro Ala Asn Glu Glu 740                 745                 750 Thr Glu Glu Asp Gly Gly Ser Asn Gly Gly Asp Arg Tyr Trp Pro Trp 755                 760                 765 Pro Ile Ala Tyr Ile His Phe Leu Ile Arg Gln Leu Ile Arg Leu Leu 770                 775                 780 Thr Arg Leu Tyr Ser Ile Cys Arg Asp Leu Leu Ser Arg Ser Phe Leu 785                 790                 795                 800 Thr Leu Gln Leu Ile Tyr Gln Asn Leu Xaa Xaa Arg Asp Trp Xaa Xaa 805                 810                 815 Leu Arg Leu Arg Thr Ala Phe Leu Gln Tyr Gly Cys Glu Trp Ile Gln 820                 825                 830 Glu Ala Phe Gln Ala Ala Ala Arg Ala Thr Arg Glu Thr Leu Ala Gly 835                 840                 845 Ala Cys Arg Gly Leu Trp Arg Val Leu Glu Arg Ile Gly Xaa Xaa Xaa 850                 855                 860 Arg Gly Ile Leu Ala Val Pro Arg Arg Ile Arg Gln Gly Ala Glu Ile 865                 870                 875                 880 Ala Leu Leu (2) INFORMATION FOR SEQ ID NO: 9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2644 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION:  12..2600 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9 CTGCAGTGAC A ATG AGA GTG AAG GAG AAA TAT CAG CAC TTG TGG AGA TGG      50 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp 1               5                  10 GGG TGG AAA TGG GGC ACC ATG CTC CTT GGG ATA TTG ATG ATC TGT AGT       98 Gly Trp Lys Trp Gly Thr Met Leu Leu Gly Ile Leu Met Ile Cys Ser 15                  20                  25 GCT ACA GAA AAA TTG TGG GTC ACA GTC TAT TAT GGG GTA CCT GTG TGG      146 Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 30                  35                  40                  45 AAG GAA GCA ACC ACC ACT CTA TTT TGT GCA TCA GAT GCT AAA GCA TAT      194 Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr 50                  55                  60 GAT ACA GAG GTA CAT AAT GTT TGG GCC ACA CAT GCC TGT GTA CCC ACA      242 Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr 65                  70                  75 GAC CCC AAC CCA CAA GAA GTA GTA TTG GTA AAT GTG ACA GAA AAT TTT      290 Asp Pro Asn Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe 80                  85                  90 AAC ATG TGG AAA AAT GAC ATG GTA GAA CAG ATG CAT GAG GAT ATA ATC      338 Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile 95                 100                 105 AGT TTA TGG GAT CAA AGC CTA AAG CCA TGT GTA AAA TTA ACC CCA CTC      386 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 110                 115                 120                 125 TGT GTT AGT TTA AAG TGC ACT GAT TTG GGG AAT GCT ACT AAT ACC AAT      434 Cys Val Ser Leu Lys Cys Thr Asp Leu Gly Asn Ala Thr Asn Thr Asn 130                 135                 140 AGT AGT AAT ACC AAT AGT AGT AGC GGG GAA ATG ATG ATG GAG AAA GGA      482 Ser Ser Asn Thr Asn Ser Ser Ser Gly Glu Met Met Met Glu Lys Gly 145                 150                 155 GAG ATA AAA AAC TGC TCT TTC AAT ATC AGC ACA AGC ATA AGA GGT AAG      530 Glu Ile Lys Asn Cys Ser Phe Asn Ile Ser Thr Ser Ile Arg Gly Lys 160                 165                 170 GTG CAG AAA GAA TAT GCA TTT TTT TAT AAA CTT GAT ATA ATA CCA ATA      578 Val Gln Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile 175                 180                 185 GAT AAT GAT ACT ACC AGC TAT ACG TTG ACA AGT TGT AAC ACC TCA GTC      626 Asp Asn Asp Thr Thr Ser Tyr Thr Leu Thr Ser Cys Asn Thr Ser Val 190                 195                 200                 205 ATT ACA CAG GCC TGT CCA AAG GTA TCC TTT GAG CCA ATT CCC ATA CAT      674 Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His 210                 215                 220 TAT TGT GCC CCG GCT GGT TTT GCG ATT CTA AAA TGT AAT AAT AAG ACG      722 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr 225                 230                 235 TTC AAT GGA ACA GGA CCA TGT ACA AAT GTC AGC ACA GTA CAA TGT ACA      770 Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr 240                 245                 250 CAT GGA ATT AGG CCA GTA GTA TCA ACT CAA CTG CTG TTG AAT GGC AGT      818 His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser 255                 260                 265 CTA GCA GAA GAA GAG GTA GTA ATT AGA TCT GCC AAT TTC ACA GAC AAT      866 Leu Ala Glu Glu Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp Asn 270                 275                 280                 285 GCT AAA ACC ATA ATA GTA CAG CTG AAC CAA TCT GTA GAA ATT AAT TGT      914 Ala Lys Thr Ile Ile Val Gln Leu Asn Gln Ser Val Glu Ile Asn Cys 290                 295                 300 ACA AGA CCC AAC AAC AAT ACA AGA AAA AGT ATC CGT ATC CAG AGG GGA      962 Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gln Arg Gly 305                 310                 315 CCA GGG AGA GCA TTT GTT ACA ATA GGA AAA ATA GGA AAT ATG AGA CAA     1010 Pro Gly Arg Ala Phe Val Thr Ile Gly Lys Ile Gly Asn Met Arg Gln 320                 325                 330 GCA CAT TGT AAC ATT AGT AGA GCA AAA TGG AAT GCC ACT TTA AAA CAG     1058 Ala His Cys Asn Ile Ser Arg Ala Lys Trp Asn Ala Thr Leu Lys Gln 335                 340                 345 ATA GCT AGC AAA TTA AGA GAA CAA TTT GGA AAT AAT AAA ACA ATA ATC     1106 Ile Ala Ser Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Ile 350                 355                 360                 365 TTT AAG CAA TCC TCA GGA GGG GAC CCA GAA ATT GTA ACG CAC AGT TTT     1154 Phe Lys Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe 370                 375                 380 AAT TGT GGA GGG GAA TTT TTC TAC TGT AAT TCA ACA CAA CTG TTT AAT     1202 Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn 385                 390                 395 AGT ACT TGG TTT AAT AGT ACT TGG AGT ACT GAA GGG TCA AAT AAC ACT     1250 Ser Thr Trp Phe Asn Ser Thr Trp Ser Thr Glu Gly Ser Asn Asn Thr 400                 405                 410 GAA GGA AGT GAC ACA ATC ACA CTC CCA TGC AGA ATA AAA CAA TTT ATA     1298 Glu Gly Ser Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe Ile 415                 420                 425 AAC ATG TGG CAG GAA GTA GGA AAA GCA ATG TAT GCC CCT CCC ATC AGC     1346 Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser 430                 435                 440                 445 GGA CAA ATT AGA TGT TCA TCA AAT ATT ACA GGG CTG CTA TTA ACA AGA     1394 Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg 450                 455                 460 GAT GGT GGT AAT AAC AAC AAT GGG TCC GAG ATC TTC AGA CCT GGA GGA     1442 Asp Gly Gly Asn Asn Asn Asn Gly Ser Glu Ile Phe Arg Pro Gly Gly 465                 470                 475 GGA GAT ATG AGG GAC AAT TGG AGA AGT GAA TTA TAT AAA TAT AAA GTA     1490 Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val 480                 485                 490 GTA AAA ATT GAA CCA TTA GGA GTA GCA CCC ACC AAG GCA CAG AAT CAC     1538 Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Gln Asn His 495                 500                 505 GTG GTG CAG AAT GAA CAC CAA GCA GTG GGA ATA GGA GCT TTG TTC CTT     1586 Val Val Gln Asn Glu His Gln Ala Val Gly Ile Gly Ala Leu Phe Leu 510                 515                 520                 525 GGG TTC TTG GGA GCA GCA GGA AGC ACT ATG GGC GCA CGG TCA ATG ACG     1634 Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser Met Thr 530                 535                 540 CTG ACG GTA CAG GCC AGA CAA TTA TTG TCT GGT ATA GTG CAG CAG CAG     1682 Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln 545                 550                 555 AAC AAT TTG CTG AGG GCT ATT GAG GCG CAA CAG CAT CTG TTG CAA CTC     1730 Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu 560                 565                 570 ACA GTC TGG GGC ATC AAG CAG CTC CAG GCA AGA ATC CTG GCT GTG GAA     1778 Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu 575                 580                 585 AGA TAC CTA AAG GAT CAA CAG CTC CTG GGG ATT TGG GGT TGC TCT GGA     1826 Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly 590                 595                 600                 605 AAA CTC ATT TGC ACC ACT GCT GTG CCT TGG AAT GCT AGT TGG AGT AAT     1874 Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn 610                 615                 620 AAA TCT CTG GAA CAG ATT TGG AAT AAC ATG ACC TGG ATG GAG TGG GAC     1922 Lys Ser Leu Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu Trp Asp 625                 630                 635 AGA GAA ATT AAC AAT TAC ACA AGC TTA ATA CAT TCC TTA ATT GAA GAA     1970 Arg Glu Ile Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu 640                 645                 650 TCG CAA AAC CAG CAA GAA AAG AAT GAA CAA GAA TTA TTG GAA TTA GAT     2018 Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp 655                 660                 665 AAA TGG GCA AGT TTG TGG AAT TGG TTT AAC ATA ACA AAT TGG CTG TGG     2066 Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp 670                 675                 680                 685 TAT ATA AAA AAT AGA GTT AGG CAG GGA TAT TCA CCA TTA TCG TTT CAG     2114 Tyr Ile Lys Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln 690                 695                 700 ACC CAC CTC CCA ACC CCG AGG GGA CCC GAC AGG CCC GAA GGA ATA GAA     2162 Thr His Leu Pro Thr Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu 705                 710                 715 GAA GAA GGT GGA GAG AGA GAC AGA GAC AGA TCC ATT CGA TTA GTG AAC     2210 Glu Glu Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Arg Leu Val Asn 720                 725                 730 GGA TCC TTA GCA CTT ATC TGG GAC GAT CTG CGG AGC CTG TGC CTC TTC     2258 Gly Ser Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe 735                 740                 745 AGC TAC CAC CGC TTG AGA GAC TTA CTC TTG ATT GTA ACG AGG ATT GTG     2306 Ser Tyr His Arg Leu Arg Asp Leu Leu Leu Ile Val Thr Arg Ile Val 750                 755                 760                 765 GAA CTT CTG GGA CGC AGG GGG TGG GAA GCC CTC AAA TAT TGG TGG AAT     2354 Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Asn 770                 775                 780 CTC CTA CAG TAT TGG AGT CAG GAA CTA AAG AAT AGT GCT GTT AGC TTG     2402 Leu Leu Gln Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala Val Ser Leu 785                 790                 795 CTC AAT GCC ACA GCC ATA GCA GTA GCT GAG GGG ACA GAT AGG GTT ATA     2450 Leu Asn Ala Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile 800                 805                 810 GAA GTA GTA CAA GGA GCT TGT AGA GCT ATT CGC CAC ATA CCT AGA AGA     2498 Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg Arg 815                 820                 825 ATA AGA CAG GGC TTG GAA AGG ATT TTG CTA TAA GAT GGG TGG CAA GTG     2546 Ile Arg Gln Gly Leu Glu Arg Ile Leu Leu  *  Asp Gly Trp Gln Val 830                 835                 840                 845 GTC AAA AAG TAG TGT GGT TGG ATG GCC TAC TGT AAG GGA AAG AAT GAG     2594 Val Lys Lys  *  Cys Gly Trp Met Ala Tyr Cys Lys Gly Lys Asn Glu 850                 855                 860 ACG AGC TGAGCCAGCA GCAGATGGGG TGGGAGCAGC ATCTCGACCT GCAG            2644 Thr Ser (2) INFORMATION FOR SEQ ID NO: 10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 839 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp Gly Trp Lys 1               5                   10                  15 Trp Gly Thr Met Leu Leu Gly Ile Leu Met Ile Cys Ser Ala Thr Glu 20                  25                  30 Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala 35                  40                  45 Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu 50                  55                  60 Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn 65                  70                  75                  80 Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp 85                  90                  95 Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp 100                 105                 110 Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Ser 115                 120                 125 Leu Lys Cys Thr Asp Leu Gly Asn Ala Thr Asn Thr Asn Ser Ser Asn 130                 135                 140 Thr Asn Ser Ser Ser Gly Glu Met Met Met Glu Lys Gly Glu Ile Lys 145                 150                 155                 160 Asn Cys Ser Phe Asn Ile Ser Thr Ser Ile Arg Gly Lys Val Gln Lys 165                 170                 175 Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp 180                 185                 190 Thr Thr Ser Tyr Thr Leu Thr Ser Cys Asn Thr Ser Val Ile Thr Gln 195                 200                 205 Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala 210                 215                 220 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly 225                 230                 235                 240 Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile 245                 250                 255 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 260                 265                 270 Glu Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp Asn Ala Lys Thr 275                 280                 285 Ile Ile Val Gln Leu Asn Gln Ser Val Glu Ile Asn Cys Thr Arg Pro 290                 295                 300 Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gln Arg Gly Pro Gly Arg 305                 310                 315                 320 Ala Phe Val Thr Ile Gly Lys Ile Gly Asn Met Arg Gln Ala His Cys 325                 330                 335 Asn Ile Ser Arg Ala Lys Trp Asn Ala Thr Leu Lys Gln Ile Ala Ser 340                 345                 350 Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln 355                 360                 365 Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly 370                 375                 380 Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp 385                 390                 395                 400 Phe Asn Ser Thr Trp Ser Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser 405                 410                 415 Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe Ile Asn Met Trp 420                 425                 430 Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile 435                 440                 445 Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly 450                 455                 460 Asn Asn Asn Asn Gly Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Met 465                 470                 475                 480 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile 485                 490                 495 Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Gln Asn His Val Val Gln 500                 505                 510 Asn Glu His Gln Ala Val Gly Ile Gly Ala Leu Phe Leu Gly Phe Leu 515                 520                 525 Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser Met Thr Leu Thr Val 530                 535                 540 Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu 545                 550                 555                 560 Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp 565                 570                 575 Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu 580                 585                 590 Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile 595                 600                 605 Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu 610                 615                 620 Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu Trp Asp Arg Glu Ile 625                 630                 635                 640 Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn 645                 650                 655 Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala 660                 665                 670 Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys 675                 680                 685 Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr His Leu 690                 695                 700 Pro Thr Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu Gly 705                 710                 715                 720 Gly Glu Arg Asp Arg Asp Arg Ser Ile Arg Leu Val Asn Gly Ser Leu 725                 730                 735 Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His 740                 745                 750 Arg Leu Arg Asp Leu Leu Leu Ile Val Thr Arg Ile Val Glu Leu Leu 755                 760                 765 Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Asn Leu Leu Gln 770                 775                 780 Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala Val Ser Leu Leu Asn Ala 785                 790                 795                 800 Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu Val Val 805                 810                 815 Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg Arg Ile Arg Gln 820                 825                 830 Gly Leu Glu Arg Ile Leu Leu 835 (2) INFORMATION FOR SEQ ID NO: 11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11 Asp Gly Trp Gln Val Val Lys Lys 1               5 (2) INFORMATION FOR SEQ ID NO: 12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12 Cys Gly Trp Met Ala Tyr Cys Lys Gly Lys Asn Glu Thr Ser 1               5                   10 (2) INFORMATION FOR SEQ ID NO: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1539 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION:  1..1539 (ix) FEATURE: (A) NAME/KEY: mat_peptide (B) LOCATION:  1..1539 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13 ATG AGA GTG AAG GGG ATC AGG AGG AAT TAT CAG CAC TGG TGG GGA TGG       48 Met Arg Val Lys Gly Ile Arg Arg Asn Tyr Gln His Trp Trp Gly Trp 1               5                  10                  15 GGC ACG ATG CTC CTT GGG TTA TTA ATG ATC TGT AGT GCT ACA GAA AAA       96 Gly Thr Met Leu Leu Gly Leu Leu Met Ile Cys Ser Ala Thr Glu Lys 20                  25                  30 TTG TGG GTC ACA GTC TAT TAT GGG GTA CCT GTG TGG AAA GAA GCA ACC      144 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 ACC ACT CTA TTT TGT GCA TCA GAT GCT AAA GCA TAT GAT ACA GAG GTA      192 Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val 50                  55                  60 CAT AAT GTT TGG GCC ACA CAA GCC TGT GTA CCC ACA GAC CCC AAC CCA      240 His Asn Val Trp Ala Thr Gln Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 CAA GAA GTA GAA TTG GTA AAT GTG ACA GAA AAT TTT AAC ATG TGG AAA      288 Gln Glu Val Glu Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 AAT AAC ATG GTA GAA CAG ATG CAT GAG GAT ATA ATC AGT TTA TGG GAT      336 Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 CAA AGC CTA AAG CCA TGT GTA AAA TTA ACC CCA CTC TGT GTT ACT TTA      384 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 AAT TGC ACT GAT TTG AGG AAT ACT ACT AAT ACC AAT AAT AGT ACT GCT      432 Asn Cys Thr Asp Leu Arg Asn Thr Thr Asn Thr Asn Asn Ser Thr Ala 130                 135                 140 AAT AAC AAT AGT AAT AGC GAG GGA ACA ATA AAG GGA GGA GAA ATG AAA      480 Asn Asn Asn Ser Asn Ser Glu Gly Thr Ile Lys Gly Gly Glu Met Lys 145                 150                 155                 160 AAC TGC TCT TTC AAT ATC ACC ACA AGC ATA AGA GAT AAG ATG CAG AAA      528 Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Met Gln Lys 165                 170                 175 GAA TAT GCA CTT CTT TAT AAA CTT GAT ATA GTA TCA ATA GAT AAT GAT      576 Glu Tyr Ala Leu Leu Tyr Lys Leu Asp Ile Val Ser Ile Asp Asn Asp 180                 185                 190 AGT ACC AGC TAT AGG TTG ATA AGT TGT AAT ACC TCA GTC ATT ACA CAA      624 Ser Thr Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln 195                 200                 205 GCT TGT CCA AAG ATA TCC TTT GAG CCA ATT CCC ATA CAC TAT TGT GCC      672 Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala 210                 215                 220 CCG GCT GGT TTT GCG ATT CTA AAA TGT AAC GAT AAA AAG TTC AGT GGA      720 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Ser Gly 225                 230                 235                 240 AAA GGA TCA TGT AAA AAT GTC AGC ACA GTA CAA TGT ACA CAT GGA ATT      768 Lys Gly Ser Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile 245                 250                 255 AGG CCA GTA GTA TCA ACT CAA CTG CTG TTA AAT GGC AGT CTA GCA GAA      816 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 260                 265                 270 GAA GAG GTA GTA ATT AGA TCT GAG AAT TTC ACT GAT AAT GCT AAA ACC      864 Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asp Asn Ala Lys Thr 275                 280                 285 ATC ATA GTA CAT CTG AAT GAA TCT GTA CAA ATT AAT TGT ACA AGA CCC      912 Ile Ile Val His Leu Asn Glu Ser Val Gln Ile Asn Cys Thr Arg Pro 290                 295                 300 AAC TAC AAT AAA AGA AAA AGG ATA CAT ATA GGA CCA GGG AGA GCA TTT      960 Asn Tyr Asn Lys Arg Lys Arg Ile His Ile Gly Pro Gly Arg Ala Phe 305                 310                 315                 320 TAT ACA ACA AAA AAT ATA ATA GGA ACT ATA AGA CAA GCA CAT TGT AAC     1008 Tyr Thr Thr Lys Asn Ile Ile Gly Thr Ile Arg Gln Ala His Cys Asn 325                 330                 335 ATT AGT AGA GCA AAA TGG AAT GAC ACT TTA AGA CAG ATA GTT AGC AAA     1056 Ile Ser Arg Ala Lys Trp Asn Asp Thr Leu Arg Gln Ile Val Ser Lys 340                 345                 350 TTA AAA GAA CAA TTT AAG AAT AAA ACA ATA GTC TTT AAT CAA TCC TCA     1104 Leu Lys Glu Gln Phe Lys Asn Lys Thr Ile Val Phe Asn Gln Ser Ser 355                 360                 365 GGA GGG GAC CCA GAA ATT GTA ATG CAC AGT TTT AAT TGT GGA GGG GAA     1152 Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu 370                 375                 380 TTT TTC TAC TGT AAT ACA TCA CCA CTG TTT AAT AGT ACT TGG AAT GGT     1200 Phe Phe Tyr Cys Asn Thr Ser Pro Leu Phe Asn Ser Thr Trp Asn Gly 385                 390                 395                 400 AAT AAT ACT TGG AAT AAT ACT ACA GGG TCA AAT AAC AAT ATC ACA CTT     1248 Asn Asn Thr Trp Asn Asn Thr Thr Gly Ser Asn Asn Asn Ile Thr Leu 405                 410                 415 CAA TGC AAA ATA AAA CAA ATT ATA AAC ATG TGG CAG GAA GTA GGA AAA     1296 Gln Cys Lys Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys 420                 425                 430 GCA ATG TAT GCC CCT CCC ATT GAA GGA CAA ATT AGA TGT TCA TCA AAT     1344 Ala Met Tyr Ala Pro Pro Ile Glu Gly Gln Ile Arg Cys Ser Ser Asn 435                 440                 445 ATT ACA GGG CTA CTA TTA ACA AGA GAT GGT GGT AAG GAC ACG GAC ACG     1392 Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Lys Asp Thr Asp Thr 450                 455                 460 AAC GAC ACC GAG ATC TTC AGA CCT GGA GGA GGA GAT ATG AGG GAC AAT     1440 Asn Asp Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn 465                 470                 475                 480 TGG AGA AGT GAA TTA TAT AAA TAT AAA GTA GTA ACA ATT GAA CCA TTA     1488 Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Thr Ile Glu Pro Leu 485                 490                 495 GGA GTA GCA CCC ACC AAG GCA AAG AGA AGA GTG GTG CAG AGA GAA AAA     1536 Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys 500                 505                 510 AGA                                                                 1539 Arg (2) INFORMATION FOR SEQ ID NO: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 513 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14 Met Arg Val Lys Gly Ile Arg Arg Asn Tyr Gln His Trp Trp Gly Trp 1               5                  10                  15 Gly Thr Met Leu Leu Gly Leu Leu Met Ile Cys Ser Ala Thr Glu Lys 20                  25                  30 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val 50                  55                  60 His Asn Val Trp Ala Thr Gln Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 Gln Glu Val Glu Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 Asn Cys Thr Asp Leu Arg Asn Thr Thr Asn Thr Asn Asn Ser Thr Ala 130                 135                 140 Asn Asn Asn Ser Asn Ser Glu Gly Thr Ile Lys Gly Gly Glu Met Lys 145                 150                 155                 160 Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Met Gln Lys 165                 170                 175 Glu Tyr Ala Leu Leu Tyr Lys Leu Asp Ile Val Ser Ile Asp Asn Asp 180                 185                 190 Ser Thr Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln 195                 200                 205 Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala 210                 215                 220 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Ser Gly 225                 230                 235                 240 Lys Gly Ser Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile 245                 250                 255 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 260                 265                 270 Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asp Asn Ala Lys Thr 275                 280                 285 Ile Ile Val His Leu Asn Glu Ser Val Gln Ile Asn Cys Thr Arg Pro 290                 295                 300 Asn Tyr Asn Lys Arg Lys Arg Ile His Ile Gly Pro Gly Arg Ala Phe 305                 310                 315                 320 Tyr Thr Thr Lys Asn Ile Ile Gly Thr Ile Arg Gln Ala His Cys Asn 325                 330                 335 Ile Ser Arg Ala Lys Trp Asn Asp Thr Leu Arg Gln Ile Val Ser Lys 340                 345                 350 Leu Lys Glu Gln Phe Lys Asn Lys Thr Ile Val Phe Asn Gln Ser Ser 355                 360                 365 Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu 370                 375                 380 Phe Phe Tyr Cys Asn Thr Ser Pro Leu Phe Asn Ser Thr Trp Asn Gly 385                 390                 395                 400 Asn Asn Thr Trp Asn Asn Thr Thr Gly Ser Asn Asn Asn Ile Thr Leu 405                 410                 415 Gln Cys Lys Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys 420                 425                 430 Ala Met Tyr Ala Pro Pro Ile Glu Gly Gln Ile Arg Cys Ser Ser Asn 435                 440                 445 Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Lys Asp Thr Asp Thr 450                 455                 460 Asn Asp Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn 465                 470                 475                 480 Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Thr Ile Glu Pro Leu 485                 490                 495 Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys 500                 505                 510 Arg (2) INFORMATION FOR SEQ ID NO: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1524 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION:  1..1524 (ix) FEATURE: (A) NAME/KEY: mat_peptide (B) LOCATION:  1..1524 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15 ATG AGA GCG AGG GGG ATA GAG AGA AAT TGT CAA AAC TGG TGG AAA TGG       48 Met Arg Ala Arg Gly Ile Glu Arg Asn Cys Gln Asn Trp Trp Lys Trp 1               5                  10                  15 GGC ATC ATG CTC CTT GGG ATA TTG ATG ACC TGT AGT GCT GCA GAC AAT       96 Gly Ile Met Leu Leu Gly Ile Leu Met Thr Cys Ser Ala Ala Asp Asn 20                  25                  30 CTG TGG GTC ACA GTT TAT TAT GGG GTG CCT GTA TGG AAG GAA GCA ACC      144 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 ACC ACT CTA TTT TGT GCA TCA GAT GCT AAA TCA TAT GAA ACA GAG GCA      192 Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ser Tyr Glu Thr Glu Ala 50                  55                  60 CAT AAT ATC TGG GCC ACA CAT GCC TGT GTA CCC ACG GAC CCC AAC CCA      240 His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 CAA GAA ATA GCA CTG GAA AAT GTG ACA GAA AAC TTT AAC ATG TGG AAA      288 Gln Glu Ile Ala Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 AAT AAC ATG GTG GAA CAG ATG CAT GAG GAT ATA ATC AGT TTA TGG GAT      336 Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 CAA AGC CTA AAA CCA TGT GTA AAA TTA ACC CCA CTC TGT GTC ACT TTA      384 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 AAC TGT AGT GAT GAA TTG AGG AAC AAT GGC ACT ATG GGG AAC AAT GTC      432 Asn Cys Ser Asp Glu Leu Arg Asn Asn Gly Thr Met Gly Asn Asn Val 130                 135                 140 ACT ACA GAG GAG AAA GGA ATG AAA AAC TGC TCT TTC AAT GTA ACC ACA      480 Thr Thr Glu Glu Lys Gly Met Lys Asn Cys Ser Phe Asn Val Thr Thr 145                 150                 155                 160 GTA CTA AAA GAT AAG AAG CAG CAA GTA TAT GCA CTT TTT TAT AGA CTT      528 Val Leu Lys Asp Lys Lys Gln Gln Val Tyr Ala Leu Phe Tyr Arg Leu 165                 170                 175 GAT ATA GTA CCA ATA GAC AAT GAT AGT AGT ACC AAT AGT ACC AAT TAT      576 Asp Ile Val Pro Ile Asp Asn Asp Ser Ser Thr Asn Ser Thr Asn Tyr 180                 185                 190 AGG TTA ATA AAT TGT AAT ACC TCA GCC ATT ACA CAG GCT TGT CCA AAG      624 Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys 195                 200                 205 GTA TCC TTT GAG CCA ATT CCC ATA CAT TAT TGT GCC CCA GCT GGT TTT      672 Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe 210                 215                 220 GCG ATT CTA AAG TGT AGA GAT AAG AAG TTC AAT GGA ACA GGC CCA TGC      720 Ala Ile Leu Lys Cys Arg Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys 225                 230                 235                 240 ACA AAT GTC AGC ACA GTA CAA TGT ACA CAT GGA ATT AGG CCA GTG GTG      768 Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val 245                 250                 255 TCA ACT CAA CTG CTG TTG AAT GGC AGT CTA GCA GAA GAA GAG GTC ATA      816 Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Ile 260                 265                 270 ATT AGA TCC GAA AAT CTC ACA AAC AAT GCT AAA AAC ATA ATA GCA CAT      864 Ile Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Asn Ile Ile Ala His 275                 280                 285 CTT AAT GAA TCT GTA AAA ATT ACC TGT GCA AGG CCC TAT CAA AAT ACA      912 Leu Asn Glu Ser Val Lys Ile Thr Cys Ala Arg Pro Tyr Gln Asn Thr 290                 295                 300 AGA CAA AGA ACA CCT ATA GGA CTA GGG CAA TCA CTC TAT ACT ACA AGA      960 Arg Gln Arg Thr Pro Ile Gly Leu Gly Gln Ser Leu Tyr Thr Thr Arg 305                 310                 315                 320 TCA AGA TCA ATA ATA GGA CAA GCA CAT TGT AAT ATT AGT AGA GCA CAA     1008 Ser Arg Ser Ile Ile Gly Gln Ala His Cys Asn Ile Ser Arg Ala Gln 325                 330                 335 TGG AGT AAA ACT TTA CAA CAA GTA GCT AGA AAA TTA GGA ACC CTT CTT     1056 Trp Ser Lys Thr Leu Gln Gln Val Ala Arg Lys Leu Gly Thr Leu Leu 340                 345                 350 AAC AAA ACA ATA ATA AAG TTT AAA CCA TCC TCA GGA GGG GAC CCA GAA     1104 Asn Lys Thr Ile Ile Lys Phe Lys Pro Ser Ser Gly Gly Asp Pro Glu 355                 360                 365 ATT ACA ACA CAC AGT TTT AAT TGT GGA GGG GAA TTC TTC TAC TGT AAT     1152 Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn 370                 375                 380 ACA TCA GGA CTG TTT AAT AGT ACA TGG AAT ATT AGT GCA TGG AAT AAT     1200 Thr Ser Gly Leu Phe Asn Ser Thr Trp Asn Ile Ser Ala Trp Asn Asn 385                 390                 395                 400 ATT ACA GAG TCA AAT AAT AGC ACA AAC ACA AAC ATC ACA CTC CAA TGC     1248 Ile Thr Glu Ser Asn Asn Ser Thr Asn Thr Asn Ile Thr Leu Gln Cys 405                 410                 415 AGA ATA AAA CAA ATT ATA AAG ATG GTG GCA GGC AGG AAA GCA ATA TAT     1296 Arg Ile Lys Gln Ile Ile Lys Met Val Ala Gly Arg Lys Ala Ile Tyr 420                 425                 430 GCC CCT CCT ATC GAA AGA AAC ATT CTA TGT TCA TCA AAT ATT ACA GGG     1344 Ala Pro Pro Ile Glu Arg Asn Ile Leu Cys Ser Ser Asn Ile Thr Gly 435                 440                 445 CTA CTA TTG ACA AGA GAT GGT GGT ATA AAT AAT AGT ACT AAC GAG ACC     1392 Leu Leu Leu Thr Arg Asp Gly Gly Ile Asn Asn Ser Thr Asn Glu Thr 450                 455                 460 TTT AGA CCT GGA GGA GGA GAT ATG AGG GAC AAT TGG AGA AGT GAA TTA     1440 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu 465                 470                 475                 480 TAT AAA TAT AAG GTA GTA CAA ATT GAA CCA CTA GGA GTA GCA CCC ACC     1488 Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro Leu Gly Val Ala Pro Thr 485                 490                 495 AGG GCA AAG AGA AGA GTG GTG GAA AGA GAA AAA AGA                     1524 Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg 500                 505 (2) INFORMATION FOR SEQ ID NO: 16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 508 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16 Met Arg Ala Arg Gly Ile Glu Arg Asn Cys Gln Asn Trp Trp Lys Trp 1               5                  10                  15 Gly Ile Met Leu Leu Gly Ile Leu Met Thr Cys Ser Ala Ala Asp Asn 20                  25                  30 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ser Tyr Glu Thr Glu Ala 50                  55                  60 His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 Gln Glu Ile Ala Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 Asn Cys Ser Asp Glu Leu Arg Asn Asn Gly Thr Met Gly Asn Asn Val 130                 135                 140 Thr Thr Glu Glu Lys Gly Met Lys Asn Cys Ser Phe Asn Val Thr Thr 145                 150                 155                 160 Val Leu Lys Asp Lys Lys Gln Gln Val Tyr Ala Leu Phe Tyr Arg Leu 165                 170                 175 Asp Ile Val Pro Ile Asp Asn Asp Ser Ser Thr Asn Ser Thr Asn Tyr 180                 185                 190 Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys 195                 200                 205 Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe 210                 215                 220 Ala Ile Leu Lys Cys Arg Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys 225                 230                 235                 240 Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val 245                 250                 255 Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Ile 260                 265                 270 Ile Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Asn Ile Ile Ala His 275                 280                 285 Leu Asn Glu Ser Val Lys Ile Thr Cys Ala Arg Pro Tyr Gln Asn Thr 290                 295                 300 Arg Gln Arg Thr Pro Ile Gly Leu Gly Gln Ser Leu Tyr Thr Thr Arg 305                 310                 315                 320 Ser Arg Ser Ile Ile Gly Gln Ala His Cys Asn Ile Ser Arg Ala Gln 325                 330                 335 Trp Ser Lys Thr Leu Gln Gln Val Ala Arg Lys Leu Gly Thr Leu Leu 340                 345                 350 Asn Lys Thr Ile Ile Lys Phe Lys Pro Ser Ser Gly Gly Asp Pro Glu 355                 360                 365 Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn 370                 375                 380 Thr Ser Gly Leu Phe Asn Ser Thr Trp Asn Ile Ser Ala Trp Asn Asn 385                 390                 395                 400 Ile Thr Glu Ser Asn Asn Ser Thr Asn Thr Asn Ile Thr Leu Gln Cys 405                 410                 415 Arg Ile Lys Gln Ile Ile Lys Met Val Ala Gly Arg Lys Ala Ile Tyr 420                 425                 430 Ala Pro Pro Ile Glu Arg Asn Ile Leu Cys Ser Ser Asn Ile Thr Gly 435                 440                 445 Leu Leu Leu Thr Arg Asp Gly Gly Ile Asn Asn Ser Thr Asn Glu Thr 450                 455                 460 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu 465                 470                 475                 480 Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro Leu Gly Val Ala Pro Thr 485                 490                 495 Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg 500                 505 (2) INFORMATION FOR SEQ ID NO: 17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1557 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION:  1..1557 (ix) FEATURE: (A) NAME/KEY: mat_peptide (B) LOCATION:  1..1557 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17 ATG AGA GTG ATG GAG ATG AGG AAG AAT TGT CAG CAC TTG TGG AAA TGG       48 Met Arg Val Met Glu Met Arg Lys Asn Cys Gln His Leu Trp Lys Trp 1               5                  10                  15 GGC ACC ATG CTC CTT GGG ATG TTG ATG ATC TGT AGT GCT GCA GAG GAC       96 Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Ala Glu Asp 20                  25                  30 TTG TGG GTC ACA GTC TAT TAT GGG GTA CCT GTG TGG AAA GAA GCA ACC      144 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 ACC ACT CTA TTT TGT GCA TCA GAA GCT AAA GCA TAT AAA ACA GAG GTA      192 Thr Thr Leu Phe Cys Ala Ser Glu Ala Lys Ala Tyr Lys Thr Glu Val 50                  55                  60 CAT AAT GTC TGG GCC AAA CAT GCT TGT GTA CCT ACA GAC CCC AAC CCA      240 His Asn Val Trp Ala Lys His Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 CAA GAA GTA CTA TTG GAA AAT GTG ACA GAA AAT TTT AAC ATG TGG AAA      288 Gln Glu Val Leu Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 AAT AAC ATG GTA GAA CAG ATG CAT GAG GAT ATA ATC AGT TTA TGG GAT      336 Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 CAA AGC CTA AAG CCA TGT GTA AAA TTA ACC CCA CTC TGT GTT ACT TTA      384 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 AAT TGC ACT GAT GCT AAC TTG AAT GGT ACT AAT GTC ACT AGT AGT AGC      432 Asn Cys Thr Asp Ala Asn Leu Asn Gly Thr Asn Val Thr Ser Ser Ser 130                 135                 140 GGG GGA ACA ATG ATG GAG AAC GGA GAA ATA AAA AAC TGC TCT TTC CAA      480 Gly Gly Thr Met Met Glu Asn Gly Glu Ile Lys Asn Cys Ser Phe Gln 145                 150                 155                 160 GTT ACC ACA AGT AGA AGA GAT AAG ACG CAG AAA AAA TAT GCA CTT TTT      528 Val Thr Thr Ser Arg Arg Asp Lys Thr Gln Lys Lys Tyr Ala Leu Phe 165                 170                 175 TAT AAA CTT GAT GTG GTA CCA ATA GAG AAG GGT AAT ATT AGC CCT AAG      576 Tyr Lys Leu Asp Val Val Pro Ile Glu Lys Gly Asn Ile Ser Pro Lys 180                 185                 190 AAT AAT ACT AGC AAT AAT ACT AGC TAT GGT AAC TAT ACA TTG ATA CAT      624 Asn Asn Thr Ser Asn Asn Thr Ser Tyr Gly Asn Tyr Thr Leu Ile His 195                 200                 205 TGT AAT TCC TCA GTC ATT ACA CAG GCC TGT CCA AAG GTA TCC TTT GAG      672 Cys Asn Ser Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu 210                 215                 220 CCA ATT CCC ATA CAT TAT TGC ACC CCG GCT GGT TTT GCG ATT CTA AAG      720 Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys 225                 230                 235                 240 TGT AAT GAT AAG AAG TTC AAT GGA ACA GGA CCA TGT AAA AAT GTC AGC      768 Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser 245                 250                 255 ACA GTA CAA TGT ACA CAT GGA ATT AGG CCA GTA GTG TCA ACT CAA CTG      816 Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu 260                 265                 270 CTG TTA AAT GGC AGT CTA GCA GAA GAA GAG GTA GTA ATT AGA TCT GAA      864 Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu 275                 280                 285 AAT TTC ACG GAC AAT GTT AAA ACC ATA ATA GTA CAG CTG AAT GCA TCT      912 Asn Phe Thr Asp Asn Val Lys Thr Ile Ile Val Gln Leu Asn Ala Ser 290                 295                 300 GTA CAA ATT AAT TGT ACA AGA CCC AAC AAC AAT ACA AGA AAA AGT ATA      960 Val Gln Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile 305                 310                 315                 320 ACT AAG GGA CCA GGG AGA GTA ATT TAT GCA ACA GGA CAA ATA ATA GGA     1008 Thr Lys Gly Pro Gly Arg Val Ile Tyr Ala Thr Gly Gln Ile Ile Gly 325                 330                 335 GAT ATA AGA AAA GCA CAT TGT AAC CTT AGT AGA GCA CAA TGG AAT AAC     1056 Asp Ile Arg Lys Ala His Cys Asn Leu Ser Arg Ala Gln Trp Asn Asn 340                 345                 350 ACT TTA AAA CAG GTA GTT ACA AAA TTA AGA GAA CAA TTT GAC AAT AAA     1104 Thr Leu Lys Gln Val Val Thr Lys Leu Arg Glu Gln Phe Asp Asn Lys 355                 360                 365 ACA ATA GTC TTT ACG TCA TCC TCA GGA GGG GAC CCA GAA ATT GTA CTT     1152 Thr Ile Val Phe Thr Ser Ser Ser Gly Gly Asp Pro Glu Ile Val Leu 370                 375                 380 CAC AGT TTT AAT TGT GGA GGG GAA TTT TTC TAC TGT AAT ACA ACA CAA     1200 His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln 385                 390                 395                 400 CTG TTT AAT AGT ACT TGG AAT AGT ACT GAA GGG TCA AAT AAC ACT GGA     1248 Leu Phe Asn Ser Thr Trp Asn Ser Thr Glu Gly Ser Asn Asn Thr Gly 405                 410                 415 GGA AAT GAC ACA ATC ACA CTC CCA TGC AGA ATA AAA CAA ATT GTA AAC     1296 Gly Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn 420                 425                 430 ATG TGG CAG GAA GTA GGA AAA GCA ATG TAT GCC CCT CCC ATC AGT GGA     1344 Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly 435                 440                 445 CAA ATT AAA TGT ATA TCA AAT ATT ACA GGG CTA CTA TTA ACA AGA GAT     1392 Gln Ile Lys Cys Ile Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp 450                 455                 460 GGG GGT GAA GAT ACA ACT AAT ACT ACA GAG ATC TTC AGA CTT GGA GGA     1440 Gly Gly Glu Asp Thr Thr Asn Thr Thr Glu Ile Phe Arg Leu Gly Gly 465                 470                 475                 480 GGA AAT ATG AGG GAC AAT TGG AGA AGT GAA TTA TAT AAA TAT AAA GTG     1488 Gly Asn Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val 485                 490                 495 GTA AGA ATT GAG CCA TTA GGA GTG GCA CCC ACT AGG GCA AAG AGA AGA     1536 Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr Arg Ala Lys Arg Arg 500                 505                 510 GTG GTG CAA AGA GAA AAA AGA                                         1557 Val Val Gln Arg Glu Lys Arg 515 (2) INFORMATION FOR SEQ ID NO: 18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 519 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18 Met Arg Val Met Glu Met Arg Lys Asn Cys Gln His Leu Trp Lys Trp 1               5                  10                  15 Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Ala Glu Asp 20                  25                  30 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 Thr Thr Leu Phe Cys Ala Ser Glu Ala Lys Ala Tyr Lys Thr Glu Val 50                  55                  60 His Asn Val Trp Ala Lys His Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 Gln Glu Val Leu Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 Asn Cys Thr Asp Ala Asn Leu Asn Gly Thr Asn Val Thr Ser Ser Ser 130                 135                 140 Gly Gly Thr Met Met Glu Asn Gly Glu Ile Lys Asn Cys Ser Phe Gln 145                 150                 155                 160 Val Thr Thr Ser Arg Arg Asp Lys Thr Gln Lys Lys Tyr Ala Leu Phe 165                 170                 175 Tyr Lys Leu Asp Val Val Pro Ile Glu Lys Gly Asn Ile Ser Pro Lys 180                 185                 190 Asn Asn Thr Ser Asn Asn Thr Ser Tyr Gly Asn Tyr Thr Leu Ile His 195                 200                 205 Cys Asn Ser Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu 210                 215                 220 Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys 225                 230                 235                 240 Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser 245                 250                 255 Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu 260                 265                 270 Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu 275                 280                 285 Asn Phe Thr Asp Asn Val Lys Thr Ile Ile Val Gln Leu Asn Ala Ser 290                 295                 300 Val Gln Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile 305                 310                 315                 320 Thr Lys Gly Pro Gly Arg Val Ile Tyr Ala Thr Gly Gln Ile Ile Gly 325                 330                 335 Asp Ile Arg Lys Ala His Cys Asn Leu Ser Arg Ala Gln Trp Asn Asn 340                 345                 350 Thr Leu Lys Gln Val Val Thr Lys Leu Arg Glu Gln Phe Asp Asn Lys 355                 360                 365 Thr Ile Val Phe Thr Ser Ser Ser Gly Gly Asp Pro Glu Ile Val Leu 370                 375                 380 His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln 385                 390                 395                 400 Leu Phe Asn Ser Thr Trp Asn Ser Thr Glu Gly Ser Asn Asn Thr Gly 405                 410                 415 Gly Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn 420                 425                 430 Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly 435                 440                 445 Gln Ile Lys Cys Ile Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp 450                 455                 460 Gly Gly Glu Asp Thr Thr Asn Thr Thr Glu Ile Phe Arg Leu Gly Gly 465                 470                 475                 480 Gly Asn Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val 485                 490                 495 Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr Arg Ala Lys Arg Arg 500                 505                 510 Val Val Gln Arg Glu Lys Arg 515 (2) INFORMATION FOR SEQ ID NO: 19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1527 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION:  1..1527 (ix) FEATURE: (A) NAME/KEY: mat_peptide (B) LOCATION:  1..1527 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19 ATG AAA GTG AAG GGG ACC AGG AGG AAT TAT CAG CAC TTG TGG AGA TGG       48 Met Lys Val Lys Gly Thr Arg Arg Asn Tyr Gln His Leu Trp Arg Trp 1               5                  10                  15 GGC ACC TTG CTC CTT GGG ATG TTG ATG ATC TGT AGT GCT ACA GAA AAA       96 Gly Thr Leu Leu Leu Gly Met Leu Met Ile Cys Ser Ala Thr Glu Lys 20                  25                  30 TTG TGG GTC ACA GTT TAT TAT GGA GTA CCT GTG TGG AAA GAA GCA ACT      144 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 ACC ACT CTA TTT TGT GCA TCA GAT GCT AGA GCA TAT GAT ACA GAG GTA      192 Thr Thr Leu Phe Cys Ala Ser Asp Ala Arg Ala Tyr Asp Thr Glu Val 50                  55                  60 CAT AAT GTT TGG GCC ACA CAT GCC TGT GTA CCC ACA GAC CCC AAC CCA      240 His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 CAA GAA GTA GTA TTG GGA AAT GTG ACA GAA AAT TTT AAC ATG TGG AAA      288 Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 AAT AAC ATG GTA GAA CAG ATG CAG GAG GAT ATA ATC AGT TTA TGG GAT      336 Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 CAA AGC CTA AAG CCA TGT GTA AAA TTA ACC CCA CTC TGT GTT ACT TTA      384 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 AAT TGC ACT GAT TTG GGG AAG GCT ACT AAT ACC AAT AGT AGT AAT TGG      432 Asn Cys Thr Asp Leu Gly Lys Ala Thr Asn Thr Asn Ser Ser Asn Trp 130                 135                 140 AAA GAA GAA ATA AAA GGA GAA ATA AAA AAC TGC TCT TTC AAT ATC ACC      480 Lys Glu Glu Ile Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr 145                 150                 155                 160 ACA AGC ATA AGA GAT AAG ATT CAG AAA GAA AAT GCA CTT TTT CGT AAC      528 Thr Ser Ile Arg Asp Lys Ile Gln Lys Glu Asn Ala Leu Phe Arg Asn 165                 170                 175 CTT GAT GTA GTA CCA ATA GAT AAT GCT AGT ACT ACT ACC AAC TAT ACC      576 Leu Asp Val Val Pro Ile Asp Asn Ala Ser Thr Thr Thr Asn Tyr Thr 180                 185                 190 AAC TAT AGG TTG ATA CAT TGT AAC AGA TCA GTC ATT ACA CAG GCC TGT      624 Asn Tyr Arg Leu Ile His Cys Asn Arg Ser Val Ile Thr Gln Ala Cys 195                 200                 205 CCA AAG GTA TCA TTT GAG CCA ATT CCC ATA CAT TAT TGT ACC CCG GCT      672 Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala 210                 215                 220 GGT TTT GCG ATT CTA AAG TGT AAT AAT AAA ACG TTC AAT GGA AAA GGA      720 Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Lys Gly 225                 230                 235                 240 CCA TGT ACA AAT GTC AGC ACA GTA CAA TGT ACA CAT GGA ATT AGG CCA      768 Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro 245                 250                 255 ATA GTG TCA ACT CAA CTG CTG TTA AAT GGC AGT CTA GCA GAA GAA GAG      816 Ile Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu 260                 265                 270 GTA GTA ATT AGA TCT GAC AAT TTC ACG AAC AAT GCT AAA ACC ATA ATA      864 Val Val Ile Arg Ser Asp Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile 275                 280                 285 GTA CAG CTG AAT GAA TCT GTA GCA ATT AAC TGT ACA AGA CCC AAC AAC      912 Val Gln Leu Asn Glu Ser Val Ala Ile Asn Cys Thr Arg Pro Asn Asn 290                 295                 300 AAT ACA AGA AAA AGT ATC TAT ATA GGA CCA GGG AGA GCA TTT CAT ACA      960 Asn Thr Arg Lys Ser Ile Tyr Ile Gly Pro Gly Arg Ala Phe His Thr 305                 310                 315                 320 ACA GGA AGA ATA ATA GGA GAT ATA AGA AAA GCA CAT TGT AAC ATT AGT     1008 Thr Gly Arg Ile Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser 325                 330                 335 AGA GCA CAA TGG AAT AAC ACT TTA GAA CAG ATA GTT AAA AAA TTA AGA     1056 Arg Ala Gln Trp Asn Asn Thr Leu Glu Gln Ile Val Lys Lys Leu Arg 340                 345                 350 GAA CAG TTT GGG AAT AAT AAA ACA ATA GTC TTT AAT CAA TCC TCA GGA     1104 Glu Gln Phe Gly Asn Asn Lys Thr Ile Val Phe Asn Gln Ser Ser Gly 355                 360                 365 GGG GAC CCA GAA ATT GTA ATG CAC AGT TTT AAT TGT AGA GGG GAA TTT     1152 Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Arg Gly Glu Phe 370                 375                 380 TTC TAC TGT AAT ACA ACA CAA CTG TTT AAT AAT ACA TGG AGG TTA AAT     1200 Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Asn Thr Trp Arg Leu Asn 385                 390                 395                 400 CAC ACT GAA GGA ACT AAA GGA AAT GAC ACA ATC ATA CTC CCA TGT AGA     1248 His Thr Glu Gly Thr Lys Gly Asn Asp Thr Ile Ile Leu Pro Cys Arg 405                 410                 415 ATA AAA CAA ATT ATA AAC ATG TGG CAG GAA GTA GGA AAA GCA ATG TAT     1296 Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr 420                 425                 430 GCC CCT CCC ATT GGA GGA CAA ATT AGT TGT TCA TCA AAT ATT ACA GGG     1344 Ala Pro Pro Ile Gly Gly Gln Ile Ser Cys Ser Ser Asn Ile Thr Gly 435                 440                 445 CTG CTA TTA ACA AGA GAT GGT GGT ACA AAT GTA ACT AAT GAC ACC GAG     1392 Leu Leu Leu Thr Arg Asp Gly Gly Thr Asn Val Thr Asn Asp Thr Glu 450                 455                 460 GTC TTC AGA CCT GGA GGA GGA GAT ATG AGG GAC AAT TGG AGA AGT GAA     1440 Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475                 480 TTA TAT AAA TAT AAA GTA ATA AAA ATT GAA CCA TTA GGA ATA GCA CCC     1488 Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro Leu Gly Ile Ala Pro 485                 490                 495 ACC AAG GCA AAG AGA AGA GTG GTG CAG AGA GAA AAA AGA                 1527 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 500                 505 (2) INFORMATION FOR SEQ ID NO: 20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 509 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20 Met Lys Val Lys Gly Thr Arg Arg Asn Tyr Gln His Leu Trp Arg Trp 1               5                  10                  15 Gly Thr Leu Leu Leu Gly Met Leu Met Ile Cys Ser Ala Thr Glu Lys 20                  25                  30 Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr 35                  40                  45 Thr Thr Leu Phe Cys Ala Ser Asp Ala Arg Ala Tyr Asp Thr Glu Val 50                  55                  60 His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro 65                  70                  75                  80 Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn Phe Asn Met Trp Lys 85                  90                  95 Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile Ile Ser Leu Trp Asp 100                 105                 110 Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu 115                 120                 125 Asn Cys Thr Asp Leu Gly Lys Ala Thr Asn Thr Asn Ser Ser Asn Trp 130                 135                 140 Lys Glu Glu Ile Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr 145                 150                 155                 160 Thr Ser Ile Arg Asp Lys Ile Gln Lys Glu Asn Ala Leu Phe Arg Asn 165                 170                 175 Leu Asp Val Val Pro Ile Asp Asn Ala Ser Thr Thr Thr Asn Tyr Thr 180                 185                 190 Asn Tyr Arg Leu Ile His Cys Asn Arg Ser Val Ile Thr Gln Ala Cys 195                 200                 205 Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala 210                 215                 220 Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Lys Gly 225                 230                 235                 240 Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro 245                 250                 255 Ile Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu 260                 265                 270 Val Val Ile Arg Ser Asp Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile 275                 280                 285 Val Gln Leu Asn Glu Ser Val Ala Ile Asn Cys Thr Arg Pro Asn Asn 290                 295                 300 Asn Thr Arg Lys Ser Ile Tyr Ile Gly Pro Gly Arg Ala Phe His Thr 305                 310                 315                 320 Thr Gly Arg Ile Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser 325                 330                 335 Arg Ala Gln Trp Asn Asn Thr Leu Glu Gln Ile Val Lys Lys Leu Arg 340                 345                 350 Glu Gln Phe Gly Asn Asn Lys Thr Ile Val Phe Asn Gln Ser Ser Gly 355                 360                 365 Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Arg Gly Glu Phe 370                 375                 380 Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Asn Thr Trp Arg Leu Asn 385                 390                 395                 400 His Thr Glu Gly Thr Lys Gly Asn Asp Thr Ile Ile Leu Pro Cys Arg 405                 410                 415 Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr 420                 425                 430 Ala Pro Pro Ile Gly Gly Gln Ile Ser Cys Ser Ser Asn Ile Thr Gly 435                 440                 445 Leu Leu Leu Thr Arg Asp Gly Gly Thr Asn Val Thr Asn Asp Thr Glu 450                 455                 460 Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465                 470                 475                 480 Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro Leu Gly Ile Ala Pro 485                 490                 495 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 500                 505 (2) INFORMATION FOR SEQ ID NO: 21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21 Arg Glu Lys Arg 1 (2) INFORMATION FOR SEQ ID NO: 22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22 Lys Ala Lys Arg 1 (2) INFORMATION FOR SEQ ID NO: 23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23 Lys Glu Arg Lys 1 (2) INFORMATION FOR SEQ ID NO: 24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: Not Relevant (D) TOPOLOGY: Not Relevant (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24 Asn Glu His Gln 1 (2) INFORMATION FOR SEQ ID NO: 25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25 ATCGCATGCG                                                            10 (2) INFORMATION FOR SEQ ID NO: 26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 50 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26 GGGGGTGGAA ATGGGGCAGC ATGCATCCCG GGCACAGAAT CACGTGGTGC                50 (2) INFORMATION FOR SEQ ID NO: 27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27 GCATGCATCC CG                                                         12 (2) INFORMATION FOR SEQ ID NO: 28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 32 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28 GGCAGCATGC TCCTTGGGAT ATTGATGATC TG                                   32 (2) INFORMATION FOR SEQ ID NO: 29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: not provided (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29 CTTTGCCCGG GTGGGTGCTA CTCCTAATGG TTC                                  33

## Claims

1. An immunogenic composition capable of eliciting human immunodeficiency virus type 1 (HIV-1) gp160-specific antibodies in a mammal comprising a soluble, non-cleavable, chimeric HIV-1 gp160 variant, said variant comprising the following regions: consisting of amino acids X to Y, wherein X is a number from 1 to 271 and Y is a number from 306 to 482; consisting of amino acids Y+1 to the carboxyl terminus of the envelope, wherein said second region fails to contain functional major and minor proteolytic cleavage sites (amino acids 483-486 and 475-479, respectively) and functional major and minor hydrophobic domains (amino acids 487-516 and 659-680, respectively); and region derived from the gp160 of said second strain of HIV-1 and consisting of amino acids 1 to X-1, wherein the numbering scheme of X and Y is based upon the numbering scheme of the HIV-1 isolate BRU.

2. The immunogenic composition of claim 1 wherein said second strain of HIV-1 is selected from the group of HIV-1 strains consisting of BRU and MN.

3. The immunogenic composition of claim 1 wherein said first strain of HIV-1 is selected from the group of HIV-1 strains consisting of MN, ELI, RF, SF2C, and SC.