THERAPEUTIC COMPOSITIONS

Abstract: The present invention relates generally to molecules capable of modulating apoptosis of animal cells. More particularly, the present invention provides cell homologues of viral-derived, apoptotic-inhibiting molecules which are useful in modulating apoptosis of animal cells. The molecules contemplated by the present invention may be used to promote or inhibit cell apoptosis depending on the exigencies of the therapeutic situation.

Description: THERAPEUTTC COMPOSITIONS The present invention relates generally to molecules capable of modulating apoptosis of animal cells. More particularly, the present invention provides cell homologues of viral-derived, apoptotic-inhibiting molecules which are useful in modulating apoptosis of animal cells. The molecules contemplated by the present invention may be used to promote or inhibit cell apoptosis depending on the exigencies of the therapeutic situation. Bibliographic details ofthe publications referred to by author in this specification are collected at the end ofthe description. Sequence Identity numbers (SEQ ID NOs.) for the nucleotide and amino acid sequences referred to in the specification are defined following the Examples. Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers. Apoptosis is a cellular death program that may be initiated by a variety of stimuli and typically leads to characteristic changes in cells, frequently resulting in activation of a endonuclease which catalyses chromatin fragmentation and condensation, membrane blebbing and collapse of the nucleus. The mechanisms for apoptosis have been strongly conserved during evolution (Vaux et al, 1994). For example, proteins resembling Bcl-2 can protect nematode, insect and vertebrate cells from apoptosis (Vaux etal, 1992; Alnemri etal, 1992), and cysteine proteases resembling interleukin- lβ converting enzyme (ICE) are required for apoptosis in both C. elgans and mammals (Ellis and Horvitz, 1986; Miura et al, 1993; Kuida et al, 1995). These apoptosis effector proteases exist as precursors in many cells, but must be cleaved and assembled into tetramers before they are active (Thornberry et al, 1992; Wilson et al, 1994; Walker et al, 1994; Munday e/ α/, 1995). Although many apoptosis effector proteases have been discovered, and numerous stimuli that induce apoptosis have been found, little is known about the signalling and activation pathways that connect the cell death stimuli to the apoptosis effector mechanisms. For example, ligation ofthe cell surface receptor CD95 (Fas/Apo-1) can induce apoptosis in many cell types (Nagata and Golstein, 1995; Krammer et al, 1994), and in T lineage cells, ICE is required for CD95 induced cell death (Kuida et al, 1995), but the molecular pathway(s) that lead(s) from CD95 to ICE activation is/are largely uncharacterised. The cytoplasmic domain of CD95, which bears a motif termed the "death domain" is known to associate with other death domain bearing proteins such as FADD/MORT1 (Boldin et al, 1995; Chinnaiyan et al, 1995) and RTP (Stager et al, 1995) which are believed to participate in signalling from CD95. The downstream targets of FADD and RIP are unknown. Tumour Necrosis Factor (TNF) can also trigger apoptosis, and its receptor resemble CD95 (Beutler and van-Huffel, 1994). The TNF-receptor 1 (p55) is known to bind to TRADD (Hsu et al, 1995) and the TNF-receptor 2 (p75) is known to bind to TNF receptors associated factors (TRAFs) 1 and 2 (Rothe et al, 1994), but how these proteins work has not yet been determined. In work leading up to the present invention, the inventors studied viral anti-apoptosis proteins and the intermediate steps of apoptosis signalling. Apoptosis can be used as a defence against viruses, but many viruses carry genes for anti-apoptosis proteins, presumably to keep the host cell alive while they replicate. Some viral anti-apoptosis proteins resemble known cellular proteins such as Bcl-2 (reviewed in Vaux, 1993). Others, such as the baculovirus p35 proteins, have unknown cellular counterparts, but can function in heterologous systems such as nematodes and mammals where they are thought to act as competitive inhibitors of ICE-like cysteine proteases (Clem et al, 1991; Hay et al, 1994; Rabizadeh et al, 1993; Xue and Horvitz, 1995; Bump et al, 1995). Miller and coworkers identified a family of proteins in baculoviruses they designated "IAPs" because they could inhibit the apoptotic response of insect cells to viral infection (Birnbaum et al, 1994; Crook et al, 1993). Viral IAP proteins typically have two terminal repeats designated baculovirus LAP repeats (BLRs), and a carboxy terminal RING finger domain. Autographa californica nuclear polyhedrosis virus (AcNPW) encodes a IAP protein that does not inhibit apoptosis, so it is possible that IAP proteins also have other functions, for example, regulatory cytokine function. The present inventors sought cellular IAP homologues and chemical analogues including derivatives which function in cell death pathways by screening for gene segments potentially encoding novel IAP proteins. Full length cDNA clones were then obtained and tested for their ability to mediate apoptosis by ICE and by FADD. Accordingly, one aspect of the present invention is directed to a homologue or chemical analogue of a viral derived peptide, polypeptide or protein or a derivative thereof which viral- derived molecule is capable of inhibiting an apoptotic response of cells to viral infection. More particularly, the present invention provides an isolated proteinaceous molecule or derivative of chemical analogue thereof capable of inhibiting an apoptotic response in cells to viral infection, said proteinaceous molecule comprising a cell-derived homologue of a viral inhibitor of apoptosis (IAP). Viral derived IAPSs are polypeptides or proteins. The IAPs represent a family of proteinaceous molecules which inhibit the apoptotic response of cells to viral infection. More particularly, the IAPs inhibit the apoptotic response of insect cells to infection by baculoviruses. The present invention provides, therefore, homologues or chemical analogues of baculovirus IAPs which are useful in modulating apoptosis of animal cells. Preferably, the apoptosis is mediated by ICE or by FADD. Accordingly, another aspect of the present invention contemplates a homologue or chemical analogue of a baculovirus IAP peptide, polypeptide or protein or a derivative thereof. Preferably, the homologue is a animal, cell derived molecule. Examples of particularly preferred animal cells are those from humans, livestock animals (e.g. sheep, pigs, horses, donkeys, cows), companion animals (e.g. dogs, cats), laboratory test animals (e.g. rabbits, mice, rats, guinea pigs), captive wild animals (e.g. foxes, deer, kangaroos), insects (e.g. mosquitoes) and nematodes. Homologous may also be from yeast or fungi. Particularly preferred homologues are for human, murine, insect, yeast or nematode cells. An example of a nematode is Caenorhabditis elegans. In a most preferred embodiment, the mammalian homologues are derived from murine cells and are designated herein MLHA, MLHB, MLHC and MLHE. In a alterative embodiment, the homologue is an insect homologue from Drosophila designated herein DLHA. In a further alternative embodiment the homologue is a C elegans homologue designated herem CLA-1 and CIA-2. In yet a further alternative embodiment the homologue is a yeast homologue designated herein YIA-1. However, the present invention extends to human and other mammalian homologues of baculovirus IAPs or homologues or chemical analogues of MLHA, MLHB, MLHC and/or DLHA. According to another aspect of the present invention, there is provided an isolated molecule having an amino acid sequence comprising: Glu Xaa Xaa Arg Xaa Xaa Thr Phe Xaa Xaa Trp Pro [Xaa] ra [XaaL. Ala Xaa Ala Gly Phe [Xaa] 0 Asp Xaa [Xaa] p Xaa Cys Phe Xaa Cys Xaa Xaa Xaa Leu Xaa Xaa Trp Xaa Xaa Xaa Asp Xaa Pro Xaa Xaa Xaa His Xaa Xaa Xaa Xaa Pro Xaa Cys Xaa [Xaa] q [Xaa] r wherein Xaa is an amino acid residue; [Xaa] m is a series of at least 5 and preferably at least 9 amino acids; [Xaa] n is Met or Leu; [Xaa] 0 is a series of at least 3 and preferably at least 5 amino acids; [Xaa] p is Val or Ala; [Xaa]q is Phe or Tyr; [Xaa] r is Leu or Val; or a homologue, chemical analogue or derivative thereof. More particularly there is provided a isolated molecule designated MLHA having a amino acid sequence substantially as set forth in SEQ LD NO: 2 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. A related aspect of the present invention is directed to a isolated molecule designated MLHB having an amino acid sequence substantially as set forth in SEQ LD NO:4 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. Yet a further related aspect of the present invention relates to a isolated molecule designated MLHC having an amino acid sequence substantially as set forth in SEQ LD NO: 6 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. Still a further related aspect of the present invention provides a isolated molecule designated DLHA having an amino acid sequence substantially as set forth in SEQ LD NO: 8 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. Another related aspect of the present invention provides a isolated molecule designated DLHA having an amino acid sequence substantially as set forth in SEQ LD NO:l 1 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. Still another related aspect of the present invention provides a isolated molecule designated DLHA having an amino acid sequence substantially as set forth in SEQ LD NO: 13 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. A further related aspect ofthe present invention provides a isolated molecule designated DLHA having an amino acid sequence substantially as set forth in SEQ LD NO: 15 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. Yet another related aspect of the present invention provides a isolated molecule designated DLHA having an amino acid sequence substantially as set forth in SEQ LD NO: 17 or having at least 40% similarity to all or part thereof or a homologue, chemical analogue or derivative thereof. The present invention also encompasses nucleic acid molecules encoding IAP homologues such as MLHA, MLHB, MLHC, MLHE, CIA-1, CIA-2, YLA-1 and DLHA. The LAP homologues may or may not bear RING finger domains, for example, MLHA, MHB and MLHC bear the domain whereas MLHE, CIA-1, CIA-2 or YIAY do not bear the domain. The present invention further contemplates a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence comprising: Glu Xaa Xaa Arg Xaa Xaa Thr Phe Xaa Xaa Trp Pro [Xaa] m [XaaL . Ala Xaa Ala Gly Phe [Xaa] 0 Asp Xaa [Xaa] p Xaa Cys Phe Xaa Cys Xaa Xaa Xaa Leu Xaa Xaa Trp Xaa Xaa Xaa Asp Xaa Pro Xaa Xaa Xaa His Xaa Xaa Xaa Xaa Pro Xaa Cys Xaa [Xaa] q [Xaa] r wherein Xaa is an amino acid residue; [Xaa] m is a series of at least 5 and preferably at least 9 amino acids; [Xaa] n is Met or Leu; [Xaa] 0 is a series of at least 3 and preferably at least 5 amino acids; [Xaa] p is Val or Ala; [Xaa]q is Phe or Tyr; [Xaa] r is Leu or Val; or having at least 40% similarity to a nucleotide sequence encoding the above-mentioned amino acid sequence. In particular, the present invention contemplates a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO:2 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO:2. In a related embodiment, there is provided a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO:4 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO:4. In another related embodiment, there is contemplated a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO:6 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO:6. A further embodiment is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 8 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 8. Another related aspect is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 11 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 11. Still another related aspect is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 13 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 13. A further related aspect is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 15 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 15. Yet another related aspect is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 17 or having at least 40% similarity to a nucleotide sequence encoding the amino acid sequence substantially set forth in SEQ LD NO: 17. In yet another embodiment of the present invenuon, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO:l or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO:l under low stringency conditions. In a related embodiment of the present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO:3 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 3 under low stringency conditions. In a further related embodiment of the present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO: 5 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 5 under low stringency conditions. In a still a further related embodiment of the present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO: 7 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 7 under low stringency conditions. In another further related embodiment ofthe present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO: 10 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 10 under low stringency conditions. In a further related embodiment of the present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO: 12 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 12 under low stringency conditions. In a still a further related embodiment ofthe present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO: 14 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 14 under low stringency conditions. In yet another related embodiment of the present invention, there is provided a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in SEQ LD NO: 16 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridising to SEQ LD NO: 16 under low stringency conditions. Reference herein to a low stringency at 42 °C includes and encompasses from at least about 1% v/v to at least about 15% v/v formamide and from at least about IM to at least about 2M salt for hybridisation, and at least about IM to at least about 2M salt for washing conditions. Alternative stringency conditions may be applied where necessary, such as medium stringency, which includes and encompasses from at least about 16% v/v to at least about 30% v/v formamide and from at least about 0.5M to at least about 0.9M salt for hybridisation, and at least about 0.5M to at least about 0.9M salt for washing conditions, or high stringency, which includes and encompasses from at least about 31% v/v to at least about 50% v/v formamide and from at least about 0.0 IM to at least about 0.15M salt for hybridisation, and at least about 0.0 IM to at least about 0.15M salt for washing conditions. The nucleic acid molecules are preferably in isolated form and/or carried by a vector molecule such as an expression vector. The LAP homologues and their derivatives and chemical analogues of the present invention are useful in inhibiting apoptosis and are useful in the treatment of diseases including but not limited to those characterised by apoptosis such as degenerative diseases including Alzheimer's disease, motor neuron disease, neuropathies; ischemic vascular disease including stroke and myocardial infarction; infectious diseases including Acquired Immuno-Deficiency Syndrome caused by HIV. Certain derivatives of the homologues contemplated herein may promote contemplated herein may promote apoptosis or inhibit anti-apoptotic processes and are potentially useful in the treatment of diseases characterised by failure of apoptosis of certain cells including but not limited to cancer or autoimmune disease, alzheimer's and motor neuron diseases. Derivatives of the homologues contemplated herein many promote apoptosis or inhibit anti-apoptotic processes and are useful in the treatment of, for example, certain cancers or in the promotion of the death of malignant cells. Derivatives of the homologues of the present invention include mutants, parts and fragments of the homologue molecules as well as single or multiple amino acid substitutions, deletions and/or additions to the homologue molecules. Nucleic acid derivatives including single or multiple nucleotide substitutions, deletions and/or additions to the nucleic acid molecules as defined in SEQ LD NO: 1 or SEQ LD NO:3 or SEQ LD NO:5 or SEQ LD NO:7 or SEQ LD NO: 10 or SEQ LD NO: 12 or SEQ LD NO: 14 or SEQ LD NO.16. Chemical analogues ofthe baculovirus IAPs or of their homologues include, but are not limited to, modifications to side chains, incorporation of unnatural amino acids and/or their derivatives during peptide synthesis and the use of crosslinkers and other methods which impose conformational constraints on the peptides or their analogues. Examples of side chain modifications contemplated by the present invention include modifications of amino groups such as by reductive alkylation by reaction with a aldehyde followed by reduction with BBH4; amidination with methylacetimidate; acylation with acetic anhydride; carbamoylation of amino groups with cyanate; triitrobezylation of amino groups with 2, 4, 6, -trinitrobezene sulphonic acid (TBS); acylation of amino groups with succinic anhydride and tetrahydrophthalic anhydride; and pyridoxylation of lysine with pyridoxal-5 '- phosphate followed by reduction with αBHφ The guanidine group of arginine residues may be modified by the formation of heterocyclic condensation products with reagents such as 2,3-butanedione, phenylglyoxal and glyoxal. The carboxyl group may be modified by carbodiimide activation via O-acylisourea formation followed by subsequent derivitisation, for example, to a corresponding amide. Sulphydryl groups may be modified by methods such as carboxymethylation with iodoacetic acid or iodoacetamide; performic acid oxidation to cysteic acid; formation of a mixed disulphides with other thiol compounds; reaction with maleimide, maleic anhydride or other substituted maleimide; formation of mercurial derivatives using 4-chloromercuribezoate, 4- chloromercuripheylsulphonic acid, phenylmercury chloride, 2-chloromercuri-4-nitrophenol and other mercurials; carbamoylation with cyanate at alkaline pH. Tryptophan residues may be modified by, for example, oxidation with -bromosuccinimide or alkylation of the idole ring with 2-hydroxy-5-nitrobenzyl bromide or sulphenyl halides. Tyrosine residues on the other hand, may be altered by nitration with tetranitromethane to form a 3-nitrotyrosine derivative. Modification of the imidazole ring of a hisitidine residue may be accomplished by alkylation with iodoacetic acid derivatives or N-carbethoxylation with diethylpyrocarbonate. Examples of incorporating unnatural amino acids and derivatives during peptide synthesis include, but are not limited to, use of norleucine, 4-amino butyric acid, 4-amino-3-hydroxy-5- phenylpentanoic acid, 6-aminohexanoic acid, t-butylglycine, norvaline, phenylglycine, norithine, sarcosine, 4-amino-3-hydroxy-6-methylheptanoic acid, 2-thienyl alanine and/or D- isomers of amino acids. A list of unnatural amino acids is provided in Table 1. TABLE 1 Non-conventional Code Non-conventional Code amino acid amino acid α-aminobutyric acid Abu L-N-methylalanine Nmala α-amino-o-methylbutyrate Mgabu L-N-me ylarginine Nmarg aminocyclopropane- Cpro L-N-methylasparagine Nmasn carboxylate L-N-methylaspartic acid Nmasp aminoisobutyric acid Aib L-N-methylcysteine Nmcys aminonorbornyl- Norb L-N-methylglutamine Nmgln carboxylate L-N-methylglutamic acid Nmglu cyclohexylalanine Chexa L-N-methylhistidine Nmhis cyclopentylalanine Cpen L-N-methylisolleucine Nmile D-alanine Dal L-N-methylleucine Nmleu D-arginine Darg L-N-methyllysine Nmlys D-aspartic acid Dasp L-N-methylmethionine Nmmet D-cysteine Dcys L-N-methylnorleucine Nmnle D-glutamine Dgln L-N-methylnorvaline Nmnva D-glutamic acid Dglu L-N-methylornithine Nmorn D-histidine Dbis L-N-methylphenylalanine Nmphe D-isoleucine Dile L-N-methylproline Nmpro D-leucine Dleu L-N-methylserine Nmser D-lysine Dlys L-N-methylthreonine Nmthr D-methionine Dmet L-N-methyltryptophan Nmtφ D-ornithine Dorn L-N-methyltyrosine Nmtyr D-phenylalanine Dphe L-N-methylvaline Nmval D-proline Dpro L-N-methylethylglycine Nmetg D-serine Dser L-N-methyl-t-butylglycine Nmtbug D-threonine Dthr L-norleucine Nle D-tryptophan Dtrp L-norvaline Nva D-tyrosine Dtyr α-methyl-aminoisobutyrate Maib D-valine Dval α-methyl-γ-aminobutyrate Mgabu D-α-methylalanine Dmala α-methylcyclohexylalanine Mchexa D-α-metiiylarginine Dmarg «x-methylcylcopentylalanine Mcpen D-α-methylasparagine Dmasn α-methyl-α-napthylalanine Manap D-α-methylaspartate Dmasp α-methylpenicillamine Mpen D-α-methylcysteine Dmcys N-(4-aminobutyl)glycine Nglu D-α-methylglutamine Dmgln N-(2-aminoethyl)glycine Naeg D-α-methylhistidine Dmhis N-(3 -aminopropyl)glycine Norn D-α-methylisoleucine Dmile N-amino-α-methylbutyrate Nmaabu D-α-methylleucine Dmleu α-napmylalanine Anap D-α-methyllysine Dmlys N-benzylglycine Nphe D-α-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln D-α-methylornithine Dmorn N-(carbamylmethyl)glycine Nasn D-α-methylphenylalanine Dmphe N-(2-carboxyethyl)glycine Nglu D-o-methylproline Dmpro N-(carboxymethyl)glycine Nasp D-α-methylserine Dmser N-cyclobutylglycine Ncbut D-α-methylthreonine Dmthr N-cycloheptylglycine Nchep D-α-methyltryptophan Dmtφ N-cyclohexylglycine Nchex D-α-methyltyrosine Dmty N-cyclodecylglycine Ncdec D-α-methylvaline Dmval N-cylcododecylglycine Ncdod D-N-methylalanine Dnmala N-cyclooctylglycine Ncoct D-N-memylarginine Dnmarg N-cyclopropylglycine Ncpro D-N-methylasparagine Dnmasn N-cycloundecylglycine Ncund D-N-methylaspartate Dnmasp N-(2,2-diphenylethyl)glycine Nbhm D-N-methylcysteine Dnmcys N-(3 , 3 -dipheny lpropy l)glycine Nbhe D-N-methylglutamine Dnmgln N-(3 -guanidinopropyl)glycine Narg D-N-methylglutamate Dnmglu N-( 1 -hydroxyethyl)glycine Nthr D-N-methylhistidine Dnmhis N-(hydroxyethyl))glycine Nser D-N-methylisoleucine Dnmile N-(imidazolylethyl))glycine Nhis D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycine Nhtφ D-N-methyllysine Dnmlys N-methyl-γ-aminobutyrate Nmgabu N-methylcyclohexylalanine Nmchexa D-N-methylmethionine Dnmmet D-N-methylomithine Dnmorn N-memylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnmphe N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro N-(l-methylpropyl)glycine Nile D-N-methylserine Dnmser N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr D-N-methyltryptophan Dnmtrp N-( 1 -methylethy l)gly cine Nval D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap D-N-methylvaline Dnmval N-methylpenicillamine Nmpen γ-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr L-/-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillamine Pen L-homophenylalanine Hphe L-α-methylalanine Mala L-α-meώylarginine Marg L-α-methylasparagine Masn L-α-methylaspartate Masp L-α-methyl-t-butylglycine Mtbug L-α-methylcysteine Mcys L-methylethylglycine Metg L-α-methylglutamine Mgln L-α-methylglutamate Mglu L-α-methylhistidine Mhis L-α-methylhomophenylalanine Mhphe L-α-methylisoleucine Mile N-(2-methylthioethyl)glycine Nmet L-α-methylleucine Mleu L-α-methyllysine Mlys L-α-methylmethionine Mmet L-α-methylnorleucine Mnle L-α-methylnorvaline Mnva L-α-methylomithine Morn L-α-methylphenylalanine Mphe L-α-methylproline Mpro L-α-methylserine Mser L-α-methylthreonine Mthr L-α-methyltryptophan Mtrp L-α-methyltyrosine Mtyr L-α-methylvaline Mval L-N-methylhomophenylalanine Nmhphe N-(N-(2,2-diphenylethyl) Nnbhm N-(N-(3,3-diphenylpropyI) Nnbhe carbamylmethyl)glycine carbamylmethyl)glycine 1 -carboxy- l-(2,2-diphenyl- Nmbc ethylamino)cyclopropane Crosslinkers can be used, for example, to stabilise 3D conformations, using homo-bifuctional crosslinkers such as the bifunctional imido esters having (CH ) spacer groups with n=l to n=6, glutaraldehyde, N-hydroxysuccinimide esters and hetero-bifunctional reagents which usually contain an amino-reactive moiety such as N-hydroxysucciriimide and another group specific- reactive moiety such as maleimido or dithio moiety (SH) or carbodiimide (COOH). In addition, peptides can be conformationally constrained by, for example, incoφoration of C α and N α -methylamine acids, introduction of double bonds between C α and C p atoms of amino acids and the formation of cyclic peptides or analogues by introducing covalent bonds such as forming a amide bond between the and C termini, between two side chains or between a side chain and the N or C terminus. The present invention further contemplates a method for modulating cell apoptosis in a animal, said method comprising administering to said animal a cell apoptosis modulating effective amount of a homologue or chemical analogue of a baculovirus IAP or a derivative thereof for a time and under conditions sufficient for said cell apoptosis to be modulated. The terms "modulating" or "modulated" refer to the promotion or enhancement of cell apoptosis or the deminuation, inhibition or reduction of cell apoptosis. Enhancing cell apoptosis may be important in treating certain cancers and cell malignancies; reducing cell apoptosis may be important in the treatment of degenerative disorders such as neuropathies and alzheimer's and motor neuron diseases. Accordingly, the present invention is also directed to therapeutic and pharmaceutical compositions useful for modulating cell apoptosis in a animal. The formation of pharmaceutical compositions is generally known in the art and reference can conveniently be made to Remington's Pharmaceutical Sciences, 17th end., Mack Publishing Co., Easton, Pennsylvania, USA. The present invention, therefore, contemplates a pharmaceutical composition comprising an apoptopic modulating effective amount of an IAP homologue as hereinbefore defined or chemical analogues or derivatives thereof and optionally including one or more other active molecules and one or more pharmaceutically acceptable carriers and/or diluents. The active ingredients of a pharmaceutical composition comprising the IAP homologues or their derivatives are contemplated herein to exhibit excellent therapeutic activity, for example, in modulating apoptosis of animal cells when administered in an amount which depends on the particular case. For example, from about 0.5 μg to about 20 mg per kilogram of body weight per day may be administered. Dosage regime may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily, weekly or monthly, or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. The active compounds may be administered in any convenient manner such as by the oral, intravenous (where water soluble), intramuscular, subcutaneous, intranasal, intradermal or suppository routes or by implanting (eg using slow release molecules), topical administration or following or during surgery or biopsy or other invasive procedure. Depending on the route of administration, the active ingredients which comprise the LAP homologues or chemical analogues or derivatives may be required to be coated in a material to protect said ingredients from the action of enzymes, acids and other natural conditions which may inactivate said ingredients. In order to administer IAP homologues by other than parenteral administration, they will be coated by, or administered with, a material to prevent its inactivation. For example, homologues may be administered in an adjuvant, co¬ administered with enzyme inhibitors or in liposomes. Adjuvants contemplated by the present invention include, but are not limited to, cytokines (e.g. interferons) as well as resorcinols, non-ionic surfactants such as polyoxyethelene oleyl ether and n-hexadecyl polyethylene ether. The active compounds may also be administered parenterally or intraperitoneally. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. In all cases the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of superfactants. The preventions of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thirmerosal and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminium monostearate and gelatin. Sterile injectable solutions are prepared by incoφorating the active compounds in the required amount in the appropriate solvent with various ofthe other ingredients enumerated above, as required, followed by filtered sterilisation. Generally, dispersions are prepared by incoφorating the various sterilised active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and the freeze-drying technique which yield a powder of the active ingredient plus any additional desired ingredient from previously sterile-filtered solution thereof. When the IAP homologues or chemical analogues or derivatives are suitably protected as described above, the active, compound may be orally administered, for example, with an inert diluent or with a assimilable edible carrier, or it may be enclosed in hard or soft shell gelatin capsule, or it may be compressed into tablets, or it may be incoφorated directly with the food of the diet. For oral therapeutic administration, the active compound may be incoφorated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 1 % by weight of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 5 to about 80% of the weight of the unit. The amount of active compound in such therapeutically useful compositions in such that a suitable dosage will be obtained. Preferred compositions or preparations according to the present invention are prepared so that a oral dosage unit form contains between about 0.1 μg and 2000 mg of active compound. The tablets, troches, pills, capsules and the like may also contain the following: A binder such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such a sucrose, lactose or saccharin may be added or a flavouring agent such as peppermint, oil of wintergreen, or cherry flavouring. When the dosage unit form is a capsule, it may contain, in addition to materials ofthe above type, a liquid carrier. Various other materials may be present as coatings or to otherwise modify the physical form ofthe dosage unit. For instance, tablets, pills, or capsules may be coated with shellac, sugar or both. A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavouring such as cherry or orange flavour. Of course, any material used in preparing any dosage unit form should be pharmaceutically pure and substantially non-toxic in the amounts employed. In addition, the active compound may be incoφorated into sustained-release preparations and formulations. A pharmaceutically acceptable carrier and/or diluent includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absoφtion delaying agents and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, use thereof in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the mammalian subjects to be treated; each unit coating a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the novel dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the active material and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such a active material for the treatment of disease in living subjects having a diseased condition in which bodily health is impaired as herein disclosed in detail. The principal active ingredient is compounded for convenient and effective administration in effective amounts with a suitable pharmaceutically acceptable carrier in dosage unit form as hereinbefore disclosed. A unit dosage form can, for example, contain the principal active compound in amounts ranging from 0.5 μg to about 2000 mg. Expressed in proportions, the active compound is generally present in from about 0.5 μg to about 2000 mg/ml of carrier. In the case of compositions coating supplementary active ingredients, the dosages are determined by reference to the usual dose and manner of administration of the said ingredients. The pharmaceutical composition may also comprise genetic molecules such as a vector capable of transfecting target cells where the vector carries a nucleic acid molecule capable of modulating IAP homologue expression or IAP homologue activity. The vector may, for example, be a viral vector. Another aspect ofthe present invention contemplates the use of an animal cell homologue of an baculovirus IAP to modulate apoptosis in animals suffering from a degenerative disease, an infectious disease, cancer or an autoimmune disease. Preferably, the cell homologue is as defined by one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:ll, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO:17 or is a derivative or chemical analogue thereof. The present invention further contemplates antibodies to the IAP homologues and the derivatives of the present invention. Antibodies are useful in diagnostic assays for the homologues as well as purifying the homologues or isolating the homologues from biological fluid or culture medium. Such antibodies may be monoclonal or polyclonal and may be selected from naturally occurring antibodies to an IAP homologue or may be specifically raised to an IAP homologue or a derivative thereof. In the case of the latter, an IAP homologue or its derivatives may first need to be associated with a carrier molecule. The antibodies and/or recombinant IAP homologue or its derivatives ofthe present invention are particularly useful as therapeutic or diagnostic agents. For example, an LAP homologue and its derivatives can be used to screen for naturally occurring antibodies to the homologue. These may occur, for example in some autoimmune diseases. Alternatively, specific antibodies can be used to screen for an IAP homologue. Techniques for such assays are well known in the art and include, for example, sandwich assays and ELISA. Knowledge of IAP homologue levels may be important for diagnosis of certain cancers or a predisposition to cancers or for monitoring certain therapeutic protocols. Antibodies to an IAP homologue of the present invention may be monoclonal or polyclonal. Alternatively, fragments of antibodies may be used such as Fab fragments. Furthermore, the present invention extends to recombinant and synthetic antibodies and to antibody hybrids. A "synthetic antibody" is considered herein to include fragments and hybrids of antibodies. The antibodies of this aspect of the present invention are particularly useful for immunotherapy and may also be used as a diagnostic tool for assessing apoptosis or monitoring the program of a therapeutic regimen. For example, specific antibodies can be used to screen for an LAP homologues. The latter would be important, for example, as a means for screening for levels of an IAP homologue in a cell extract or other biological fluid or purifying LAP homologue made by recombinant means from culture supernatant fluid. Techniques for the assays contemplated herein are known in the art and include, for example, sandwich assays and ELISA. It is within the scope of this mvention to include any second antibodies (monoclonal, polyclonal or fragments of antibodies or synthetic antibodies) directed to the first mentioned antibodies discussed above. Both the first and second antibodies may be used in detecuon assays or a first antibody may be used with a commercially available anti-immunoglobulin antibody. An antibody as contemplated herein includes any antibody specific to any region of an LAP homologue. An antibody may also be directed to an amino acid sequence such as set forth in SEQ LD NO:9. Both polyclonal and monoclonal antibodies are obtainable by immunization with the enzyme or protein and either type is utilizable for immunoassays. The methods of obtaining both types of sera are well known in the art. Polyclonal sera are less preferred but are relatively easily prepared by injection of a suitable laboratory animal with an effective amount of LAP homologue, or antigenic parts thereof, collecting serum from the animal, and isolating specific sera by any ofthe known immunoadsorbent techniques. Although antibodies produced by this method are utilizable in virtually any type of immunoassay, they are generally less favoured because ofthe potential heterogeneity of the product. The use of monoclonal antibodies in an immunoassay is particularly preferred because ofthe ability to produce them in large quantities and the homogeneity of the product. The preparation of hybridoma cell lines for monoclonal antibody production derived by fusing an immortal cell line and lymphocytes sensitized against the immunogenic preparation can be done by techniques which are well known to those who are skilled in the art. Another aspect of the present invention contemplates a method for detecting an LAP homologue in a biological sample from a subject said method comprising contacting said biological sample with an antibody specific for the IAP homologue or its derivatives or homologues for a time and under conditions sufficient for an antibody-IAP homologue complex to form, and then detecting said complex. The presence of IAP homologue may be accomplished in a number of ways such as by Western blotting and ELISA procedures. A wide range of immunoassay techniques are available as can be seen by reference to US Patent Nos. 4,016,043, 4, 424,279 and 4,018,653. These, of course, includes both single-site and two-site or "sandwich" assays of the non- competitive types, as well as in the traditional competitive binding assays. These assays also include direct binding of a labelled antibody to a target. Sandwich assays are among the most useful and commonly used assays and are favoured for use in the present invention. A number of variations ofthe sandwich assay technique exist, and all are intended to be encompassed by the present invention. Briefly, in a typical forward assay, an unlabelled antibody is immobilized on a solid substrate and the sample to be tested brought into contact with the bound molecule. After a suitable period of incubation, for a period of time sufficient to allow formation of an antibody-antigen complex, a second antibody specific to the antigen, labelled with a reporter molecule capable of producing a detectable signal is then added and incubated, allowing time sufficient for the formation of another complex of antibody-antigen-labelled antibody. Any unreacted material is washed away, and the presence of the antigen is determined by observation of a signal produced by the reporter molecule. The results may either be qualitative, by simple observation of the visible signal, or may be quantitated by comparing with a control sample containing known amounts of hapten. Variations on the forward assay include a simultaneous assay, in which both sample and labelled antibody are added simultaneously to the bound antibody. These techniques are well known to those skilled in the art, including any minor variations as will be readily apparent. In accordance with the present invention the sample is one which might contain an LAP homologue including a cell extract, tissue biopsy or possibly serum, saliva, mucosal secretions, lymph, tissue fluid and respiratory fluid. The sample is, therefore, generally a biological sample comprising biological fluid but also extends to fermentation fluid and supernatant fluid such as from a cell culture. In the typical forward sandwich assay, a first antibody having specificity for the IAP homologue or antigenic parts thereof, is either covalently or passively bound to a solid surface. The solid surface is typically glass or a polymer, the most commonly used polymers being cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride or polypropylene. The solid supports may be in the form of tubes, beads, discs of microplates, or any other surface suitable for conducting an immunoassay. The binding processes are well-known in the art and generally consist of cross-linking covalently binding or physically adsorbing, the polymer- antibody complex is washed in preparation for the test sample. An aliquot ofthe sample to be tested is then added to the solid phase complex and incubated for a period of time sufficient (e.g. 2-40 minutes) and under suitable conditions (e.g. 25 °C) to allow binding of any subunit present in the antibody. Following the incubation period, the antibody subunit solid phase is washed and dried and incubated with a second antibody specific for a portion of the hapten. The second antibody is linked to a reporter molecule which is used to indicate the binding of the second antibody to the hapten. An alternative method involves immobilizing the target molecules in the biological sample and then exposing the immobilized target to specific antibody which may or may not be labelled with a reporter molecule. Depending on the amount of target and the strength of the reporter molecule signal, a bound target may be detectable by direct labelling with the antibody. Alternatively, a second labelled antibody, specific to the first antibody is exposed to the target- first antibody complex to form a target-first antibody-second antibody tertiary complex. The complex is detected by the signal emitted by the reporter molecule. By "reporter molecule" as used in the present specification, is meant a molecule which, by its chemical nature, provides an analytically identifiable signal which allows the detection of antigen-bound antibody. Detection may be either qualitative or quantitative. The most commonly used reporter molecules in this type of assay are either enzymes, fiuorophores or radionuclide containing molecules (i.e. radioisotopes) and chemiluminescent molecules. In the case of an enzyme immunoassay, an enzyme is conjugated to the second antibody, generally by means of glutaraldehyde or periodate. As will be readily recognized, however, a wide variety of different conjugation techniques exist, which are readily available to the skilled artisan. Commonly used enzymes include horseradish peroxidase, glucose oxidase, beta-galactosidase and alkaline phosphatase, amongst others. The substrates to be used with the specific enzymes are generally chosen for the production, upon hydrolysis by the corresponding enzyme, ofa detectable colour change. Examples of suitable enzymes include alkaline phosphatase and peroxidase. It is also possible to employ fluorogenic substrates, which yield a fluorescent product rather than the chromogenic substrates noted above. In all cases, the enzyme-labelled antibody is added to the first antibody hapten complex, allowed to bind, and then the excess reagent is washed away. A solution containing the appropriate substrate is then added to the complex of antibody-antigen-antibody. The substrate will react with the enzyme linked to the second antibody, giving a qualitative visual signal, which may be further quantitated, usually spectrophotometrically, to give an indication ofthe amount of hapten which was present in the sample. "Reporter molecule" also extends to use of cell agglutination or inhibition of agglutination such as red blood cells on latex beads, and the like. Alternately, fluorescent compounds, such as fluorescein and rhodamine, may be chemically coupled to antibodies without altering their binding capacity. When activated by illumination with light of a particular wavelength, the fluorochrome-labelled antibody adsorbs the light energy, inducing a state to excitability in the molecule, followed by emission of the light at a characteristic colour visually detectable with a light microscope. As in the EIA, the fluorescent labelled antibody is allowed to bind to the first antibody-hapten complex. After washing off the unbound reagent, the remaining tertiary complex is then exposed to the light ofthe appropriate wavelength the fluorescence observed indicates the presence ofthe hapten of interest. Immunofluorescene and EIA techniques are both very well established in the art and are particularly preferred for the present method. However, other reporter molecules, such as radioisotope, chemiluminescent or bioluminescent molecules, may also be employed. The present invention also contemplates genetic assays such as involving PCR analysis to detect IAP homolgoue gene or its derivatives. Alternative methods or methods used in conjunction include direct nucleotide sequencing or mutation scanning such as single stranded conformation polymoφhoms analysis (SSCP) as specific oligonucleotide hybridisation, as methods such as direct protein truncation tests. The present invention is further described by the following non-limiting Figures and/or Examples. In the Figures: Figure 1 is a comparison of deduced peptide sequences of LAP proteins. (A) Comparison of MLHA (SEQ LD NO:2), MLHB (SEQ LD NO:4), MLHC (SEQ LD NO:6), and DLHA (SEQ LD NO:8). Amino acids shared by three or more of the proteins are highlighted. Arrows indicate the three BLRs. The RLNG finger domain is indicated by a dashed arrow. (B) Comparison of BLRs of LAP proteins. Strongly conserved residues are highlighted. CPI derives from Cydia pomonella granulosis virus; OpIAP derives from Orgyia pseudotsugata PV; CilAP derives from Chilo iridescent virus; ALP is a candidate gene for SMA; AcIAP derives from Autographa Califoraica PV; ASV derives from IAP- like sequences from African swine fever virus. (C) Comparison of RLNG finger motifs of IAPs and other proteins. Strongly conserved residues are highlighted. CRAF (TRAF3) and TRAF2 are TRAF family members; BCRAl and RAG1 are two mammalian proteins with RING finger motifs; c-CBL is a cellular oncogene and SLI-1 is its C. elgans homologue; cpi derives from Cydia pomonella granulosis virus; OpIAP derives from Orgyia pseudotsugata PV; CilAP derives from Chilo iridescent virus; AcIAP derives from Autographa californica PV; UKMT derives from the Drosophila Unkempt gene; EctV derives from the p28 protein of Ectromelia Virus. Figure 2 is a photographic representation showing mammalian LAP homologues are expressed in a variety of tissues. (A) An adult mouse tissue total RNA Northern blot was probed with the /wMLHA cDNA coding region at high stringency. This Northern was also probed with GAPDH as a indicator of each lane's loading. (B-D) A adult mouse tissue poly (A)+ RNA Northern blot (CLONTECH) was probed with the ΛMLHB CDNA coding region (B) and the ΛMLHC CDNA coding region (C) at low stringency. Figure 3 is a graphical representation showing that MLHA and MLHB protect against death induced by overexpression of ICE, but not FADD. (A) Induction of apoptosis by transfection with ICE. Columns 1-6 (In black) indicate the percentage of dead cells cotransfected with p32ICE-lacZ fusion plasmid and the plasmids bearing either the LAP homologues or controls. Death of cells cotransfected with lacZ only together with the same test plasmids is show in columns 7-12 (in white) and indicates the amount of cell death due to the transfection procedure itself. (B) Induction of apoptosis by transfection with FADD. Plasmids encoding the MLH proteins were cotransfected with a lacZ vector and a construct bearing the FADD coding region (columns 1-6). As with the ICE experiment, background death was monitored in a parallel set of cultures (columns 7-12). Figure 4 is a schematic representation showing a hypothetical and non-limiting cell death model showing the proposed site of action of IAP proteins. Direct interactions are indicated by solid lines, and indirect actions are show as dotted lines. Uncertain interactions are indicated by a question mark. Spontaneous self-association of molecules such as TRAFs and death-domain bearing proteins may generate a intrinsic activation signal that in normal circumstances is insufficient to activate enough cell death proteases to cause apoptosis. Increased amounts of ICE precursor due to transfection could allow activation of enough enzyme to induce apoptosis. IAP proteins may act to decrease the spontaneous activation signals to various extents depending on their affinity for their target(s). According to this model, OpIAP may be able to offer greater protection against FADD than the mammalian LAP homologues because it has greater affinity for its target, but it is not as effective against FADD as it is against pro-ICE because it is required to block a larger intrinsic activation signal in FADD transfected cells. CrmA and p35, which directly inhibit active ICE, are effective inhibitors of ICE mediated apoptosis on matter how ICE is activated. Figure 5 is a representation of the nucleotide sequence and corresponding amino acid sequence of MLHA. Figure 6 is a representation of the nucleotide sequence and correspondmg amino acid sequence of MLHB. Figure 7 is a representation of the nucleotide sequence and corresponding amino acid sequence of MLHC. Figure 8 is a representation of the nucleotide sequence and corresponding amino acid sequence of DLHA. Figure 9A and 9B show protection by MLHA, MLHB and MLHC against death induced by over expression of ICH-1 protease. Figure 10 is a photographic representation of a Western blot of 293T cells transfected with MLHA constructs. The following single and three letter abbreviations are used for amino acid residues: Amino Acid Three-letter One-letter Abbreviation Symbol Alanine Ala A Arginine Arg R Asparagine Asn N Aspartic acid Asp D Cysteine Cys C Glutamine Gin Q Glutamic acid Glu E Glycine Gly G Histidine His H Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Phenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Tφ w Tyrosine Tyr Y Valine Val V Any residue Xaa X A summary of SEQ LD NOs is as follows: SEQ ID NO: DESCRIPTION 1 Nucleotide sequence of MLHA 2 Amino acid sequence of MLHA 3 Nucleotide sequence of MLHB 4 Amino acid sequence of MLHB 5 Nucleotide sequence of MLHC 6 Amino acid sequence of MLHC 7 Nucleotide sequence of DLHA 8 Amino acid sequence of DLHA 9 Concensus amino acid sequence 10 Nucleotide sequence of MLHE 11 Amino acid sequence of MLHE 12 Nucleotide sequence of CIA- 1 13 Amino acid sequence of CIA- 1 14 Nucleotide sequence of CIA-2 15 Amino acid sequence of CIA-2 16 Nucleotide sequence of Yl A- 1 17 Amino acid sequence of YIA- 1 18 Amino acid sequence of MLHA peptide EXAMPLE 1 cDNA CLONING The GenBank database was searched using the GCG Sequence Analysis Software Package (Madison, WI) for translated sequences resembling the OpIAP BLR and RING finger amino acid motifs. A human X chromosome genomic STS thus identified (GenBank :L24579) was used to design PCR primers flanking the putative RLNG finger motif. This region was amplified and used to scree a human genomic DNA library (Stratagene). A fragment isolated from this library was used to probe a mouse liver cDNA library (Stratagene) at low stringency yielding three murine cDNA clones that were designated mammalian LAP homologueA (MLHA). Translations ofthe human EST sequences GenBank:R19628 and GenBank: T96284 were found to resemble the BLR repeats of OpIAP. These sequences were used to design PCR primers within their putative BLR domains which were used to generate probes that were used to scree a human fetal liver cDNA library (Stratagene). The hybridising cDNA clones were designated MLHB and MLHC, respectively. The Drosophila genomic sequence (GenBank:DROCCAAT) was used to design primers to amplify a 900 bp product from Drosophila CDNA. This fragment was subcloned and used to screen an oligo(dT) - primed Drosophila larval cDNA library constructed in lambda ZAP (Stratagene). A 2kb cDNA (DLHA) clone encoding all but the 8 -terminal amino acids was isolated. For peptide sequence comparisons (Figure 1) these residues deduced from the genomic sequence GenBank:DROCCAAT were added. EXAMPLE 2 RNA ANALYSIS Radiolabelled mMLHA and GAPDH were hybridised at high stringency to a mouse tissue Northern blot bearing 5 μg/lane of total RNA. A mouse multiple tissue Northern blot (CLONTECH) bearing 2 μg poly(A)+ RNA was probed with radiolabelled hMLHC at low stringency, stripped, probed with hMLHB at low stringency, stripped again and probed at high stringency to a β-actin probe according to the manufacturer's instructions. EXAMPLE 3 YEAST TWO-HYBRLD SYSTEM The coding regions of MLHA MLHB and MLHC were amplified by PCR using primers incorporating an EcoRI site at the 5 ' end and a BamHl site at the 3 ' end (or a Bglll site in the case of MLHB), such that the proteins would be expressed as in frame fusions with the GAL4 DNA binding domain. The PCR products were the ligated into the pGBT9 vector (CLONTECH). The OpIAP gene from the HindTTl site 17 codons upstream of the initiating ATG was cloned into the pGBT9 vector such that a in frame fusion would result. PCR- derived inserts were sequenced to check for misincoφorations by Taq polymerase. TRAFl, TRAF2 and TRAF3 expression vectors have been previously described (Rothe et al, 1994; Hu et al, 1994b). Vectors with the coding regions of c-jun in GBT9 and fos were used as controls for the detection of interacting proteins. The yeast strain HF7c was transformed with these plasmids using the lithium acetate protocol (Gietz et αl, 1992). EXAMPLE 4 TRANSIENT TRANSFECTION ASSAYS A 1.8 kb Sαcl-EcoRI fragment from a MLHA cDNA clone in pBluescript (Stratagene) was subcloned into pSP72 (Promega) to generate pSPMLHA, and recloned into pEF, a derivative ofthe pEFBOS vector (Mizushima and Nagata, 1990) as a 1.8 kb BαmHL-EcoRV fragment. A 1.64 kb BαmHl-Scαl fragment from the DLHA cDNA was cloned in pEF. Pfu polymerase (Stratagene) was used to amplify the coding regions of MLHB and MLHC. Unique restriction sites were included at the ends ofthe primers for the cloning of these products into pEF. The p32-/αcZ fusion plasmid pβactMl 1Z was as described by Miura et αl (1993). The FADD expression construct FADD-AUl was as described by Chinnaiyan et αl (1995). The coding regions of bcl-2, crmA, p35 from AcPV, and IAP from OpPV were inserted into the pEF vector. The truncated OpIAP plasmid was constructed by digestion of the pEF vector coating full length IAP with ru\ and Smαl, and re-ligating. This deleted sequences 3' of the nil site in the OpIAP gene which encode the RLNG finger domain. EXAMPLE 5 CLONING OF DLHA, MLHA MLHB and MLHC Searches of GenBank revealed a Drosophila genomic sequence (GenBank:DROCCAAT) that resembled baculoviral IAP genes. A Drosophila cDNA library was screened using PCR generated probes and clones isolated which encodes this protein, designated herein Drosophila IAP homologue A (DLHA). The GenBank searches also revealed a number of mammalian sequences that resembled either the BLRs or the RING finger domains of viral IAPs. The first mammalian IAP homologue identified (MLHA), was cloned using a PCR generated probe corresponding to a STS sequence on the X chromosome, HUMSWX595, which when translated encoded a peptide resembUng a baculoviral IAP RING finger motif. The inventors isolated partial length human genomic clones and mouse MLHA cDNA clones compassing the entire coding region. A further pair of closely related human LAP homologues (MLHB and MLHC) were isolated using PCR generated probes corresponding to GenBank EST sequences R19628 and T96284, which encode BLR-like motifs. Figure IA compares the predicted amino acid sequences for DLHA (predicted molecular weight 55 kD), MLHA (56 kD), MLHB (70 kD) and MLHC (68 kD). Start codons were chose as the most 5' methionine with upstream, in frame stop codons. All four proteins bear three BLR repeats in the amino terminal half and a single RING finger domain close to the carboxy terminus. MLHB and MLHC are the most closely related, with 73% amino acid identity. MLHA shares 43% identity and 62% similarity with MLHB and MLHC. DLHA has 36% identity and 57% similarity to MLHC. The BLR repeats of these proteins are compared to each other, the BLR repeats of ALP and the viral IAPs in Figure IB. Among the mammalian IAPs some of the BLRs resemble the analogous BLR from another IAP more closely than they resemble the remaining BLRs in the same protein, indicating that duplication of a primordial BLR was a early event. Four ofthe most highly conserved residues in the BLRs are three cysteines and a histidine in the pattern CX 2 CX, 6 HX 6 C. These may bind metal ions (Birnbaum et al, 1994). Figure IC shows a comparison ofthe C3HC4 RLNG finger domains ofthe IAP molecules with RING fingers from other selected proteins. The RING fingers from IAP proteins resemble each other more than they resemble the RLNG fingers from other proteins, such as TRAF2 (Rothe et /, 1994) and CRAF (Hu et α/, 1994b; Cheng et al, 1995; Sato et al, 1995), that do not bear BLRs. The most similar RING fingers in o-BLR bearing proteins are in the mammalian oncogene, c-Cbl (Blake et al, 1991) and its C. elgans homologue, Sli-1 (Yoon et al, 1995). Like the baculoviral IAP proteins, the RING finger bearing protein p28 of Ectromelia virus is not required for growth, but is essential for virulence (Senkevich et al, 1994). However, p28 does not have BLRs and its function is unknown. EXAMPLE 6 EXPRESSION OF MAMMALIAN HOMOLOGUES The message for murine MLHA is about 7.5 kb, and is expressed in most mouse tissues with the except of skeletal and cardiac muscle. The highest level detected was in the lung, with intermediate levels detected in the brain and kidney, and lower levels in the thymus, liver, bone marrow, skin and testes (Figure 2A). A cDNA probe spaning the coding region of human MLHB hybridised at low stringency to two messages of -4.0 kb and -5.5 kb on a mouse multiple tissue Northern blot (Figure 2B). The upper, less abundant transcript was expressed least in the spleen and skeletal muscle and at higher levels in all other tissues analysed. The more abundant -4.0 kb transcript was expressed at lowest levels in the spleen, intermediate levels in the heart, brain, lung, liver, skeletal muscle and kidney and at highest levels in the testes. A additional transcript of -9.5 kb was detected in the testes but not see in other tissues. A full length human MLHC cDNA probe hybridised at low stringency to two messages of ~3.0 and -4.0 kb (Figure 2C). on 4.0 kb message was detectable in the spleen, high levels were detected in the testes and intermediate levels were detected in all other tissues. The -3.0 kb transcript could be see in the lung and skeletal muscle and very faintly in the spleen, liver, kidney and testes. As the AMLHB and ΛMLHC probes were hybridised at low stringency to mouse RNA, it is possible the upper (4.0 kb) transcript is the same as that detected by the MIHB probe. Some of the transcripts may also represent other closely related mammalian IAP homologues. EXAMPLE 7 PREVENTION OF ICE OR FADD INDUCED APOPTOSIS The mammalian LAP homologues were tested for their ability to prevent apoptosis due to two stimuli, overexpression of p32ICE and overexpression of FADD. Transfection with constructs expressing the Ced-3-like cysteine protease ICE have previously been show to cause apoptosis (Miura et al, 1993). Baculoviral IAP can prevent this death, as can other anti-apoptosis genes such as bcl-2, crmA and p35 (Miura et al, 1993; Xue et al, 1995). The inventors tested MLHA, MLHB and MLHC to determine whether they too could block apoptosis caused by ICE overexpression. HeLa cells were cotransfected with a plasmid bearing a ICE-lacZ fusion construct together with plasmids encoding the IAP homologues or controls. The cells were stained with X-gal to identify those that hand been transfected, and these were assessed visually for viability. As show in Figure 3 A, MLHA, MLHB and OpIAP significantly reduced the amount of death caused by ICE, whereas MLHC did not provide detectable protection. Enforced expression ofthe Cd95 associated protein FADD also causes cell death (Chinnaiyan et al, 1995; Boldin et al, 1995). HeLa cells were cotransfected with three plasmids: a FADD expression construct, a plasmid carrying the lacZ gene and vectors encoding the mammalian LAP homologues or OpIAP. OpIAP provided partial protection against FADD, but it was not as effective as it was against ICE (compare Figure 3 A, lane 2 with Figure 3B, lane 2). The inventors could not detect any reduction in the amount of FADD induced cell death by MLHA, MLHB or MLHC. EXAMPLE 8 INTERACTIONS WITH TRAF FAMILY MEMBERS Two ofthe mammalian LAP homologues, MLHB and MLHC, were isolated as part of a protein complex that binds to the cytoplasmic domain ofthe TNF-R2 (p75) together with the TNF-R2 associated molecules TRAFl and TRAF2 (Rothe et al, 1994). Using the yeast two hybrid system (Fields and Song, 1989), the three mammalian IAP homologues and viral OpIAP were tested for their ability to bind TRAFl, TRAF2 and TRAF3, a related protein also known as CD40BP / CRAF-1 / CAP (Hu et al, 1994b; Cheng et al, 1995; Sato et al, 1995) As show in Table 2, yeast cotransfected with MLHB or MLHC and TRAFl or TRAF2 but not TRAF3 were rendered his+ and lacZ+, indicating that interactions can occur between these proteins within yeast. In contrast, on interactions were detectable in this system between any ofthe TRAFs tested and OpIAP or MLHA. These results show that MLHB and MLHC bind to TRAFl and TRAF2, but suggest that OpIAP and MLHA interact with other proteins. EXAMPLE 9 IDENTIFICATION OF MLHE, CIA-1, CIA-2 and YIA-1 A consensus sequence of baculovirus LAP repeats (BLR) was deduced as follows: Glu Xaa Xaa Arg Xaa Xaa Thr Phe Xaa Xaa Tφ Pro [Xaa] m [Xaa] n Ala Xaa Ala Gly Phe [Xaa] 0 Asp Xaa [Xaa . Xaa Cys Phe Xaa Cys Xaa Xaa Xaa Leu Xaa Xaa Tφ Xaa Xaa Xaa Asp Xaa Pro Xaa Xaa Xaa His Xaa Xaa Xaa Xaa Pro Xaa Cys Xaa [Xaa] q [Xaa] r wherein Xaa is an amino acid residue; [Xaa] m is a series of at least 5 and preferably at least 9 amino acids; [Xaa] n is Met or Leu; [Xaa] 0 is a series of at least 3 and preferably at least 5 amino acids; [Xaa] p is Val or Ala; [Xaa]q is Phe or Tyr; [Xaa], is Leu or Val; or a homologue, chemical analogue or derivative thereof. A database search using this consensus sequence resulted in identification of IAP homologes from mouse (MLHE), yeast (YLA-1) and C. elegans (CIA-1, CIA-2). The nucleotide and corresponding amino acid sequence from these LAP homologes is given in SEQ LD NOS: 10 to 17. Interestingly, MLHE, YLA-1, CIA-1 and CIA-2 do not bear RLNG finger domains. EXAMPLE 10 PROTECTION BY MLHA, MLHB, and MLHC Figures 9A and B shows the protection from MLHA, MLHB and MLHC against death induced by over expression ofthe ICH-1 protease. EXAMPLE 11 WESTERN BLOT A polyclonal rabbit antibody was prepared and affinity purified against the MLHA peptide KDLKKTMEEKIQTSG (SEQ LD NO: 18). This antibody was used in a western blot of 293T cells transfected inter alia MLHA. The results are shown in Figure 10. Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features. TABLE 2 Yeast Two Hybrid Assays for Binding Between TRAFl, TRAF2, TRAF3 and Mammalian LAP Homologues Transformant Growth on Trp DNA binding Activation hybrid Leu- His- Colony hybrid medium Colour OpIAP TRAFl - . MLHA TRAFl - - MLHB TRAFl + ++ MLHC TRAFl + ++ c-jun TRAFl - - OpIAP TRAF2 - - MLHA TRAF2 - - MLHB TRAF2 + + MLHC TRAF2 + + c-jun TRAF2 - - OpIAP TRAF3 - - MLHA TRAF3 - - MLHB TRAF3 - - MLHC TRAF3 - - c-jun TRAF3 - • OpIAP fos - - MLHA fos - - c-IAPl fos - - MLHC fos - - c-jun fos + +++ The yeast strain HF7c was cotransformed with constructs wliich express fusion proteins between the GAL4 DNA-binding domain and the LAP family members or controls, and vectors which encode fusions between the TRAF proteins or controls and the GAM activation domain. Expression from the his and lacZ reporter genes (which indicates interactions) was analysed by growth of double transformants on medium lacking histidine (Column 3), and blue staining of colonies, with X-gal (Column 4), c-jun and fos were used as control genes encoding interacting proteins in the DNA binding vector and activation vector, respectively. 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SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: AMRAD OPERATIONS PTY LTD (US ONLY): DAV D LAURENCE VAUX (ii) TITLE OF INVENTION: THERAPEUTIC COMPOSITIONS (iii) NUMBER OF SEQUENCES: 18 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: DAVLES COLLISON CAVE (B) STREET: 1 LITTLE COLLINS STREET (C) CITY: MELBOURNE (D) STATE: VICTORIA (E) COUNTRY: AUSTRALIA (F) ZLP: 3000 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: BM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.25 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: PCT INTERNATIONAL (B) FILING DATE: 20-DEC-1996 (vi) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: [AU] PN 7275 (B) FILING DATE. 22-DEC-1995 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: HUGHES DR, E JOHN L (C) REFERENCE/DOCKET NUMBER: EJH/EK (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: +61 3 9254 2777 (B) TELEFAX: +61 3 9254 2770 (2) INFORMATION FOR SEQ ID Nθ:l: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1988 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 212..1702 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1 : GAATTCCTGC AGTTAGTTGT ATTGCTGTGG TAGGGGGTCT AAAGATTCTA CATACAGTGA 60 TACACATTTG GAATTTTTGT ACTTGGCAAA TTGAGGCAGG AAGCTAACGT TTTCCAGAAC 120 GGCCTGGGCT GCTTTTGAGA GCTCCGATCT CAGAGAAGAA GCACTAAAAG ATGAATATGA 180 AAAGGTGGAC AAGTCCTATT TTCCAGAGAA G ATG ACT TTT AAC AGT TTT GAA 232 Met Thr Phe Asn Ser Phe Glu 1 5 GGA ACT AGA ACT TTT GTA CTT GCA GAC ACC AAT AAG GAT GAA GAA TTT 280 Gly Thr Arg Thr Phe Val Leu Ala Asp Thr Asn Lys Asp Glu Glu Phe 10 15 20 GTA GAA GAG TTT AAT AGA TTA AAA ACA TTT GCT AAC TTC CCA AGC AGT 328 Val Glu Glu Phe Asn Arg Leu Lys Thr Phe Ala Asn Phe Pro Ser Ser 25 30 35 AGT CCT GTT TCA GCA TCA ACA TTG GCG CGA GCT GGG TTT CTT TAT ACC 376 Ser Pro Val Ser Ala Ser Thr Leu Ala Arg Ala Gly Phe Leu Tyr Thr 40 45 50 55 GGT GAA GGA GAC ACC GTG CAA TGT TTC AGT TGT CAT GCG GCA ATA GAT 424 Gly Glu Gly Asp Thr Val Gin Cys Phe Ser Cys His Ala Ala Ile Asp 60 65 70 AGA TGG CAG TAT GGA GAC TCA GCT GTT GGA AGA CAC AGG AGA ATA TCC 472 Arg Trp Gin Tyr Gly Asp Ser Ala Val Gly Arg His Arg Arg Ile Ser 75 80 85 CCA AAT TGC AGA TTT ATC AAT GGT TTT TAT TTC GAA AAT GGT GCT GCA 520 Pro Asn Cys Arg Phe Ile Asn Gly Phe Tyr Phe Glu Asn Gly Ala Ala 90 95 100 CAG TCT ACA AAT CCT GGT ATC CAA AAT GGC CAG TAC AAA TCT GAA AAC 568 Gin Ser Thr Asn Pro Gly Ile Gin Asn Gly Gin Tyr Lys Ser Glu Asn 105 110 115 TGT GTG GGA AAT AGA AAT CCT TTT GCC CCT GAC AGG CCA CCT GAG ACT 616 Cys Val Gly Asn Arg Asn Pro Phe Ala Pro Asp Arg Pro Pro Glu Thr 120 125 130 135 CAT GCT GAT TAT CTC TTG AGA ACT GGA CAG GTT GTA GAT ATT TCA GAC 664 His Ala Asp Tyr Leu Leu Arg Thr Gly Gin Val Val Asp Ile Ser Asp 140 145 150 ACC ATA TAC CCG AGG AAC CCT GCC ATG TGT AGT GAA GAA GCC AGA TTG 712 Thr Ile Tyr Pro Arg Asn Pro Ala Met Cys Ser Glu Glu Ala Arg Leu 155 160 165 AAG TCA TTT CAG AAC TGG CCG GAC TAT GCT CAT TTA ACC CCC AGA GAG 760 Lys Ser Phe Gin Asn Trp Pro Asp Tyr Ala His Leu Thr Pro Arg Glu 170 175 180 TTA GCT AGT GCT GGC CTC TAC TAC ACA GGG GCT GAT GAT CAA GTG CAA 808 Leu Ala Ser Ala Gly Leu Tyr Tyr Thr Gly Ala Asp Asp Gin Val Gin 185 190 195 TGC TTT TGT TGT GGG GGA AAA CTG GAA AAT TGG GAA CCC TGT GAT CGT 856 Cys Phe Cys Cys Gly Gly Lys Leu Glu Asn Trp Glu Pro Cys Asp Arg 200 205 210 215 GCC TGG TCA GAA CAC AGG AGA CAC TTT CCC AAT TGC TTT TTT GTT TTG 904 Ala Trp Ser Glu His Arg Arg His Phe Pro Asn Cys Phe Phe Val Leu 220 225 230 GGC CGG AAC GTT AAT GTT CGA AGT GAA TCT GGT GTG AGT TCT GAT AGG 952 Gly Arg Asn Val Asn Val Arg Ser Glu Ser Gly Val Ser Ser Asp Arg 235 240 245 AAT TTC CCA AAT TCA ACA AAC TCT CCA AGA AAT CCA GCC ATG GCA GAA 1000 Asn Phe Pro Asn Ser Thr Asn Ser Pro Arg Asn Pro Ala Met Ala Glu 250 255 260 TAT GAA GCA CGG ATC GTT ACT TTT GGA ACA TGG ACA TCC TCA GTT AAC 1048 Tyr Glu Ala Arg Ile Val Thr Phe Gly Thr Trp Thr Ser Ser Val Asn 265 270 275 AAG GAG CAG CTT GCA AGA GCT GGA TTT TAT GCT TTA GGT GAA GGC GAT 1096 Lys Glu Gin Leu Ala Arg Ala Gly Phe Tyr Ala Leu Gly Glu Gly Asp 280 285 290 295 AAA GTG AAG TGC TTT CAC TGT GGA GGA GGG CTC ACG GAT TGG AAG CCA 1144 Lys Val Lys Cys Phe His Cys Gly Gly Gly Leu Thr Asp Trp Lyε Pro 300 305 310 AGT GAA GAC CCT TGG GAA CAG CAT GCG AAG TGG TAC CCA GGG TGC AAA 1192 Ser Glu Asp Pro Trp Glu Gin His Ala Lys Trp Tyr Pro Gly Cys Lys 315 320 325 TAC CTA TTG GAT GAG AAG GGG CAA GAA TAT ATA AAT AAT ATT CAT TTA 1240 Tyr Leu Leu Asp Glu Lys Gly Gin Glu Tyr Ile Asn Asn Ile His Leu 330 335 340 ACC CAT TCA CTT GAG GAA TCT TTG GGA AGA ACT GCT GAA AAA ACA CCA 1288 Thr His Ser Leu Glu Glu Ser Leu Gly Arg Thr Ala Glu Lys Thr Pro 345 350 355 TCG CTA ACT AAA AAA ATC GAT GAT ACC ATC TTC CAG AAT CCT ATG GTG 1336 Ser Leu Thr Lys Lys Ile Asp Asp Thr Ile Phe Gin Asn Pro Met Val 360 365 370 375 CAA GAA GCT ATA CGA ATG GGA TTT AGC TTC AAG GAC ATT AAG AAA ACA 1384 Gin Glu Ala Ile Arg Met Gly Phe Ser Phe Lys Asp Ile Lys Lys Thr 380 385 390 ATG GAA GAA AAA ATC CAA ACA TCC GGG AGC AGC TAT CTA TCA CTT GAG 1432 Met Glu Glu Lys Ile Gin Thr Ser Gly Ser Ser Tyr Leu Ser Leu Glu 395 400 405 GTC CTG ATT GCA GAT CTT GTG AGT GCT CAG AAA GAT AAT ACG GAG GAT 1480 Val Leu Ile Ala Asp Leu Val Ser Ala Gin Lys Asp Asn Thr Glu Asp 410 415 420 GAG TCA AGT CAA ACT TCA TTG CAG AAA GAC ATT AGT ACT GAA GAG CAG 1528 Glu Ser Ser Gin Thr Ser Leu Gin Lys Asp Ile Ser Thr Glu Glu Gin 425 430 435 CTA AGG CGC CTA CAA GAG GAG AAG CTT TGC AAA ATC TGT ATG GAT AGA 1576 Leu Arg Arg Leu Gin Glu Glu Lys Leu Cys Lys Ile Cys Met Asp Arg 440 445 450 455 AAT ATT GCT ATC GTT TTT GTT CCT TGT GGA CAT CTG GTC ACT TGT AAA 1624 Asn Ile Ala Ile Val Phe Val Pro Cys Gly His Leu Val Thr Cys Lys 460 465 470 CAG TGT GCA GAA GCA GTT GAC AAA TGT CCC ATG TGC TAC ACC GTC ATT 1672 Gin Cys Ala Glu Ala Val Asp Lys Cys Pro Met Cys Tyr Thr Val Ile 475 480 485 ACG TTC AAG CAA AAA ATT TTT ATG TCT TAGTGGGGCA CCACATGTTA 1719 Thr Phe Lys Gin Lys Ile Phe Met Ser 490 495 TGTTCTTCTT GCTCTAATTG AATGTGTGAT GGGAGCGAAC TTTAAGTAAT CTGCATTGCA 1779 TTCCATTAGC ATCTGCTGTT TCCAAATGGA GACCAATGCT AACAGCACTG TTTCCGTCTA 1839 AACATTCAAT TTCTGGATCT TTCGAGTTAT CAGCTGTATC ATTTAGCCAG TGTTTTACTC 1899 GATTGAAACC TTAGACAGAG AAGCATTTTA TAGCTTTTCA CATGTATATT GGTAGTACAC 1959 TGACTTGATT TCTATATGTA AGTGAATTC 1988 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 496 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Met Thr Phe Asn Ser Phe Glu Gly Thr Arg Thr Phe Val Leu Ala Asp 1 5 10 15 Thr Asn Lys Asp Glu Glu Phe Val Glu Glu Phe Asn Arg Leu Lys Thr 20 25 30 Phe Ala Asn Phe Pro Ser Ser Ser Pro Val Ser Ala Ser Thr Leu Ala 35 40 45 Arg Ala Gly Phe Leu Tyr Thr Gly Glu Gly Asp Thr Val Gin Cys Phe 50 55 60 Ser Cys His Ala Ala Ile Asp Arg Trp Gin Tyr Gly Asp Ser Ala Val 65 70 75 80 Gly Arg His Arg Arg Ile Ser Pro Asn Cys Arg Phe lie Asn Gly Phe 85 90 95 Tyr Phe Glu Asn Gly Ala Ala Gin Ser Thr Asn Pro Gly Ile Gin Asn 100 105 110 Gly Gin Tyr Lys Ser Glu Asn Cys Val Gly Asn Arg Asn Pro Phe Ala 115 120 125 Pro Asp Arg Pro Pro Glu Thr His Ala Asp Tyr Leu Leu Arg Thr Gly 130 135 140 Gin Val Val Asp Ile Ser Asp Thr Ile Tyr Pro Arg Asn Pro Ala Met 145 150 155 160 Cys Ser Glu Glu Ala Arg Leu Lys Ser Phe Gin Asn Trp Pro Asp Tyr 165 170 175 Ala His Leu Thr Pro Arg Glu Leu Ala Ser Ala Gly Leu Tyr Tyr Thr 180 185 190 Gly Ala Asp Asp Gin Val Gin Cys Phe Cys Cys Gly Gly Lys Leu Glu 195 200 205 Asn Trp Glu Pro Cys Asp Arg Ala Trp Ser Glu His Arg Arg His Phe 210 215 220 Pro Asn Cys Phe Phe Val Leu Gly Arg Asn Val Asn Val Arg Ser Glu 225 230 235 240 Ser Gly Val Ser Ser Asp Arg Asn Phe Pro Asn Ser Thr Asn Ser Pro 245 250 255 Arg Asn Pro Ala Met Ala Glu Tyr Glu Ala Arg Ile Val Thr Phe Gly 260 265 270 Thr Trp Thr Ser Ser Val Asn Lys Glu Gin Leu Ala Arg Ala Gly Phe 275 280 285 Tyr Ala Leu Gly Glu Gly Asp Lys Val Lys Cys Phe His Cys Gly Gly 290 295 300 Gly Leu Thr Asp Trp Lys Pro Ser Glu Asp Pro Trp Glu Gin His Ala 305 310 315 320 Lys Trp Tyr Pro Gly Cys Lys Tyr Leu Leu Asp Glu Lys Gly Gin Glu 325 330 335 Tyr Ile Asn Asn Ile His Leu Thr His Ser Leu Glu Glu Ser Leu Gly 340 345 350 Arg Thr Ala Glu Lys Thr Pro Ser Leu Thr Lys Lys Ile Asp Asp Thr 355 360 365 Ile Phe Gin Asn Pro Met Val Gin Glu Ala Ile Arg Met Gly Phe Ser 370 375 380 Phe Lys Asp Ile Lys Lys Thr Met Glu Glu Lys Ile Gin Thr Ser Gly 385 390 395 400 Ser Ser Tyr Leu Ser Leu Glu Val Leu Ile Ala Asp Leu Val Ser Ala 405 410 415 Gin Lys Asp Asn Thr Glu Asp Glu Ser Ser Gin Thr Ser Leu Gin Lys 420 425 430 Asp Ile Ser Thr Glu Glu Gin Leu Arg Arg Leu Gin Glu Glu Lys Leu 435 440 445 Cys Lys Ile Cys Met Asp Arg Asn Ile Ala Ile Val Phe Val Pro Cys 450 455 460 Gly His Leu Val Thr Cys Lys Gin Cys Ala Glu Ala Val Asp Lys Cys 465 470 475 480 Pro Met Cys Tyr Thr Val Ile Thr Phe Lys Gin Lys Ile Phe Met Ser 485 490 495 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3532 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1160..3016 (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:3: GAATTCTATG GAGTGTAATT TTGTGTATGA ATTATATTTT TAAAACATTG AAGAGTTTTC 60 AGAAAGAAGG CTAGTAGAGT TGATTACTGA TACTTTATGC TAAGCAGTAC TTTTTTGGTA 120 GTACAATATT TTGTTAGGCG TTTCTGATAA CACTAGAAAG GACAAGTTTT ATCTTGTGAT 180 AAATTGATTA ATGTTTACAA CATGACTGAT AATTATAGCT GAATAGTCCT TAAATGATGA 240 ACAGGTTATT TAGTTTTTAA ATGCAGTGTA AAAAGTGTGC TGTGGAAATT TTATGGCTAA 300 CTAAGTTTAT GGAGAAAATA CCTTCAGTTG ATCAAGAATA ATAGTGGTAT ACAAAGTTAG 360 GAAGAAAGTC AACATGATGC TGCAGGAAAT GGAAACAAAT ACAAATGATA TTTAACAAAG 420 ATAGAGTTTA CAGTTTTTGA ACTTTAAGCC AAATTCATTT GACATCAAGC ACTATAGCAG 480 GCACAGGTTC AACAAAGCTT GTGGGTATTG ACTTCCCCCA AAAGTTGTCA GCTGAAGTAA 540 TTTAGCCCAC TTAAGTAAAT ACTATGATGA TAAGCTGTGT GAACTTAGCT TTTAAATAGT 600 GTGACCATAT GAAGGTTTTA ATTACTTTTG TTTATTGGAA TAAAATGAGA TTTTTTGGGT 660 TGTCATGTTA AAGTGCTTAT AGGGAAAGAA GCCTGCATAT AATTTTTTAC CTTGTGGCAT 720 AATCAGTAAT TGGTCTGTTA TTCAGGCTTC ATAGCTTGTA ACCAAATATA AATAAAAGGC 780 ATAATTTAGG TATTCTATAG TTGCTTAGAA TTTTGTTAAT ATAAATCTCT GTGAAAAATC 840 AAGGAGTTTT AATATTTTCA GAAGTGCATC CACCTTTCAG GGCTTTAAGT TAGTATTACT 900 CAAGATTATG AACAAATAGC ACTTAGGTTA CCTGAAAGAG TTACTACAAC CCCAAAGAGT 960 TGTGTTCTAA GTAGTATCTT GGTAATTCAG AGAGATACTC ATCCTACCTG AATATAAACT 1020 GAGATAAATC CAGTAAAGAA AGTGTAGTAA ATTCTACATA AGAGTCTATC ATTGATTTCT 1080 TTTTGTGGTA AAAATCTTAG TTCATGTGAA GAAATTTCAT GTGAATGTTT TAGCTATCAA 1140 ACAGTACTGT CACCTACTC ATG CAC AAA ACT GCC TCC CAA AGA CTT TTC CCA 1192 Met His Lys Thr Ala Ser Gin Arg Leu Phe Pro 1 5 10 GGT CCC TCG TAT CAA AAC ATT AAG AGT ATA ATG GAA GAT AGC ACG ATC 1240 Gly Pro Ser Tyr Gin Asn Ile Lys Ser Ile Met Glu Asp Ser Thr Ile 15 20 25 TTG TCA GAT TGG ACA AAC AGC AAC AAA CAA AAA ATG AAG TAT GAC TTT 1288 Leu Ser Asp Trp Thr Asn Ser Asn Lys Gin Lys Met Lys Tyr Asp Phe 30 35 40 TCC TGT GAA CTC TAC AGA ATG TCT ACA TAT TCA ACT TTC CCC GCC GGG 1336 Ser Cys Glu Leu Tyr Arg Met Ser Thr Tyr Ser Thr Phe Pro Ala Gly 45 50 55 GTG CCT GTC TCA GAA AGG AGT CTT GCT CGT GCT GGT TTT TAT TAT ACT 1384 Val Pro Val Ser Glu Arg Ser Leu Ala Arg Ala Gly Phe Tyr Tyr Thr 60 65 70 75 GGT GTG AAT GAC AAG GTC AAA TGC TTC TGT TGT GGC CTG ATG CTG GAT 1432 Gly Val Asn Asp Lys Val Lys Cys Phe Cys Cys Gly Leu Met Leu Asp 80 85 90 AAC TGG AAA CTA GGA GAC AGT CCT ATT CAA AAG CAT AAA CAG CTA TAT 1480 Asn Trp Lys Leu Gly Asp Ser Pro Ile Gin Lys His Lys Gin Leu Tyr 95 100 105 CCT AGC TGT AGC TTT ATT CAG AAT CTG GTT TCA GCT AGT CTG GGA TCC 1528 Pro Ser Cys Ser Phe Ile Gin Asn Leu Val Ser Ala Ser Leu Gly Ser 110 115 120 ACC TCT AAG AAT ACG TCT CCA ATG AGA AAC AGT TTT GCA CAT TCA TTA 1576 Thr Ser Lys Asn Thr Ser Pro Met Arg Asn Ser Phe Ala His Ser Leu 125 130 135 TCT CCC ACC TTG GAA CAT AGT AGC TTG TTC AGT GGT TCT TAC TCC AGC 1624 Ser Pro Thr Leu Glu His Ser Ser Leu Phe Ser Gly Ser Tyr Ser Ser 140 145 150 155 CTT TCT CCA AAC CCT CTT AAT TCT AGA GCA GTT GAA GAC ATC TCT TCA 1672 Leu Ser Pro Asn Pro Leu Asn Ser Arg Ala Val Glu Asp Ile Ser Ser 160 165 170 TCG AGG ACT AAC CCC TAC AGT TAT GCA ATG AGT ACT GAA GAA GCC AGA 1720 Ser Arg Thr Asn Pro Tyr Ser Tyr Ala Met Ser Thr Glu Glu Ala Arg 175 180 185 TTT CTT ACC TAC CAT ATG TGG CCA TTA ACT TTT TTG TCA CCA TCA GAA 1768 Phe Leu Thr Tyr His Met Trp Pro Leu Thr Phe Leu Ser Pro Ser Glu 190 195 200 TTG GCA AGA GCT GGT TTT TAT TAT ATA GGA CCT GGA GAT AGG GTA GCC 1816 Leu Ala Arg Ala Gly Phe Tyr Tyr Ile Gly Pro Gly Asp Arg Val Ala 205 210 215 TGC TTT GCC TGT GGT GGG AAG CTC AGT AAC TGG GAA CCA AAG GAT GAT 1864 Cys Phe Ala Cys Gly Gly Lys Leu Ser Asn Trp Glu Pro Lys Asp Asp 220 225 230 235 GCT ATG TCA GAA CAC CGG AGG CAT TTT CCC AAC TGT CCA TTT TTG GAA 1912 Ala Met Ser Glu His Arg Arg His Phe Pro Asn Cys Pro Phe Leu Glu 240 245 250 AAT TCT CTA GAA ACT CTG AGG TTT AGC ATT TCA AAT CTG AGC ATG CAG 1960 Asn Ser Leu Glu Thr Leu Arg Phe Ser Ile Ser Asn Leu Ser Met Gin 255 260 265 ACA CAT GCA GCT CGA ATG AGA ACA TTT ATG TAC TGG CCA TCT AGT GTT 2008 Thr His Ala Ala Arg Met Arg Thr Phe Met Tyr Trp Pro Ser Ser Val 270 275 280 CCA GTT CAG CCT GAG CAG CTT GCA AGT GCT GGT TTT TAT TAT GTG GGT 2056 Pro Val Gin Pro Glu Gin Leu Ala Ser Ala Gly Phe Tyr Tyr Val Gly 285 290 295 CGC AAT GAT GAT GTC AAA TGC TTT TGT TGT GAT GGT GGC TTG AGG TGT 2104 Arg Asn Asp Asp Val Lys Cys Phe Cys Cys Asp Gly Gly Leu Arg Cys 300 305 310 315 TGG GAA TCT GGA GAT GAT CCA TGG GTA GAA CAT GCC AAG TGG TTT CCA 2152 Trp Glu Ser Gly Asp Asp Pro Trp Val Glu His Ala Lys Trp Phe Pro 320 325 330 AGG TGT GAG TTC TTG ATA CGA ATG AAA GGC CAA GAG TTT GTT GAT GAG 2200 Arg Cys Glu Phe Leu Ile Arg Met Lys Gly Gin Glu Phe Val Asp Glu 335 340 345 ATT CAA GGT AGA TAT CCT CAT CTT CTT GAA CAG CTG TTG TCA ACT TCA 2248 Ile Gin Gly Arg Tyr Pro His Leu Leu Glu Gin Leu Leu Ser Thr Ser 350 355 360 GAT ACC ACT GGA GAA GAA AAT GCT GAC CCA CCA ATT ATT CAT TTT GGA 2296 Asp Thr Thr Gly Glu Glu Asn Ala Asp Pro Pro Ile Ile His Phe Gly 365 370 375 CCT GGA GAA AGT TCT TCA GAA GAT GCT GTC ATG ATG AAT ACA CCT GTG 2344 Pro Gly Glu Ser Ser Ser Glu Asp Ala Val Met Met Asn Thr Pro Val 380 385 390 395 GTT AAA TCT GCC TTG GAA ATG GGC TTT AAT AGA GAC CTG GTG AAA CAA 2392 Val Lys Ser Ala Leu Glu Met Gly Phe Asn Arg Asp Leu Val Lys Gin 400 405 410 ACA GTT CAA AGT AAA ATC CTG ACA ACT GGA GAG AAC TAT AAA ACA GTT 2440 Thr Val Gin Ser Lys Ile Leu Thr Thr Gly Glu Asn Tyr Lys Thr Val 415 420 425 AAT GAT ATT GTG TCA GCA CTT CTT AAT GCT GAA GAT GAA AAA AGA GAA 2488 Asn Asp Ile Val Ser Ala Leu Leu Asn Ala Glu Asp Glu Lys Arg Glu 430 435 440 GAG GAG AAG GAA AAA CAA GCT GAA GAA ATG GCA TCA GAT GAT TTG TCA 2536 Glu Glu Lys Glu Lys Gin Ala Glu Glu Met Ala Ser Asp Asp Leu Ser 445 450 455 TTA ATT CGG AAG AAC AGA ATG GCT CTC TTT CAA CAA TTG ACA TGT GTG 2584 Leu Ile Arg Lys Asn Arg Met Ala Leu Phe Gin Gin Leu Thr Cys Val 460 465 470 475 CTT CCT ATC CTG GAT AAT CTT TTA AAG GCC AAT GTA ATT AAT AAA CAG 2632 Leu Pro Ile Leu Asp Asn Leu Leu Lys Ala Asn Val Ile Asn Lys Gin 480 485 490 GAA CAT GAT ATT ATT AAA CAA AAA ACA CAG ATA CCT TTA CAA GCG AGA 2680 Glu His Asp Ile Ile Lys Gin Lys Thr Gin Ile Pro Leu Gin Ala Arg 495 500 505 GAA CTG ATT GAT ACC ATT TTG GTT AAA GGA AAT GCT GCG GCC AAC ATC 2728 Glu Leu Ile Asp Thr Ile Leu Val Lys Gly Asn Ala Ala Ala Asn Ile 510 515 520 TTC AAA AAC TGT CTA AAA GAA ATT GAC TCT ACA TTG TAT AAG AAC TTA 2776 Phe Lys Asn Cys Leu Lys Glu Ile Asp Ser Thr Leu Tyr Lys Asn Leu 525 530 535 TTT GTG GAT AAG AAT ATG AAG TAT ATT CCA ACA GAA GAT GTT TCA GGT 2824 Phe Val Asp Lys Asn Met Lys Tyr Ile Pro Thr Glu Asp Val Ser Gly 540 545 550 555 CTG TCA CTG GAA GAA CAA TTG AGG AGG TTG CAA GAA GAA CGA ACT TGT 2872 Leu Ser Leu Glu Glu Gin Leu Arg Arg Leu Gin Glu Glu Arg Thr Cys 560 565 570 AAA GTG TGT ATG GAC AAA GAA GTT TCT GTT GTA TTT ATT CCT TGT GGT 2920 Lys Val Cys Met Asp Lys Glu Val Ser Val Val Phe Ile Pro Cys Gly 575 580 585 CAT CTG GTA GTA TGC CAG GAA TGT GCC CCT TCT CTA AGA AAA TGC CCT 2968 His Leu Val Val Cys Gin Glu Cys Ala Pro Ser Leu Arg Lys Cys Pro 590 595 600 ATT TGC AGG GGT ATA ATC AAG GGT ACT GTT CGT ACA TTT CTC TCT TAAAGAAAAA 3023 Ile Cys Arg Gly Ile Ile Lys Gly Thr Val Arg Thr Phe Leu Ser 605 610 615 TAGTCTATAT TTTAACCTGC ATAAAAAGGT CTTTAAAATA TTGTTGAACA CTTGAAGCCA 3083 TCTAAAGTAA AAAGGGAATT ATGAGTTTTT CAATTAGTAA CATTCATGTT CTAGTCTGCT 3143 TTGGTACTAA TAATCTTGTT TCTGAAAAGA TGGTATCATA TATTTAATCT TAATCTGTTT 3203 ATTTACAAGG GAAGATTTAT GTTTGGTGAA CTATATTAGT ATGTATGTGT ACCTAAGGGA 3263 GTAGTGTCAC TGCTTGTTAT GCATCATTTC AGGAGTTACT GGATTTGTTG TTCTTTCAGA 3323 AAGCTTTGAA TACTAAATTA TAGTGTAGAA AAGAACTGGA AACCAGGAAC TCTGGAGTTC 3383 ATCAGAGTTA TGGTGCCGAA TTGTCTTTGG TGCTTTTCAC TTGTGTTTTA AAATAAGGAT 3443 TTTTCTCTTA TTTCTCCCCC TAGTTTGTGA GAAACATCTC AATAAAGTGC TTTCCAAAAA 3503 AAAAAAAAAG TCGACGCGGC CGCGAATTC 3532 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 618 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:4: Met His Lys Thr Ala Ser Gin Arg Leu Phe Pro Gly Pro Ser Tyr Gin 1 5 10 15 Asn Ile Lys Ser Ile Met Glu Asp Ser Thr Ile Leu Ser Asp Trp Thr 20 25 30 Asn Ser Asn Lys Gin Lys Met Lys Tyr Asp Phe Ser Cys Glu Leu Tyr 35 40 45 Arg Met Ser Thr Tyr Ser Thr Phe Pro Ala Gly Val Pro Val Ser Glu 50 55 60 Arg Ser Leu Ala Arg Ala Gly Phe Tyr Tyr Thr Gly Val Asn Asp Lys 65 70 75 80 Val Lys Cys Phe Cys Cys Gly Leu Met Leu Asp Asn Trp Lys Leu Gly 85 90 95 Asp Ser Pro Ile Gin Lys His Lys Gin Leu Tyr Pro Ser Cys Ser Phe 100 105 110 Ile Gin Asn Leu Val Ser Ala Ser Leu Gly Ser Thr Ser Lys Asn Thr 115 120 125 Ser Pro Met Arg Asn Ser Phe Ala His Ser Leu Ser Pro Thr Leu Glu 130 135 140 His Ser Ser Leu Phe Ser Gly Ser Tyr Ser Ser Leu Ser Pro Asn Pro 145 150 155 160 Leu Asn Ser Arg Ala Val Glu Asp Ile Ser Ser Ser Arg Thr Asn Pro 165 170 175 Tyr Ser Tyr Ala Met Ser Thr Glu Glu Ala Arg Phe Leu Thr Tyr His 180 185 190 Met Trp Pro Leu Thr Phe Leu Ser Pro Ser Glu Leu Ala Arg Ala Gly 195 200 205 Phe Tyr Tyr Ile Gly Pro Gly Asp Arg Val Ala Cys Phe Ala Cys Gly 210 215 220 Gly Lys Leu Ser Asn Trp Glu Pro Lys Asp Asp Ala Met Ser Glu His 225 230 235 240 Arg Arg His Phe Pro Asn Cys Pro Phe Leu Glu Asn Ser Leu Glu Thr 245 250 255 Leu Arg Phe Ser Ile Ser Asn Leu Ser Met Gin Thr His Ala Ala Arg 260 265 270 Met Arg Thr Phe Met Tyr Trp Pro Ser Ser Val Pro Val Gin Pro Glu 275 280 285 Gin Leu Ala Ser Ala Gly Phe Tyr Tyr Val Gly Arg Asn Asp Asp Val 290 295 300 Lys Cys Phe Cys Cys Asp Gly Gly Leu Arg Cys Trp Glu Ser Gly Asp 305 310 315 320 Asp Pro Trp Val Glu His Ala Lys Trp Phe Pro Arg Cys Glu Phe Leu 325 330 335 Ile Arg Met Lys Gly Gin Glu Phe Val Asp Glu lie Gin Gly Arg Tyr 340 345 350 Pro His Leu Leu Glu Gin Leu Leu Ser Thr Ser Asp Thr Thr Gly Glu 355 360 365 Glu Asn Ala Asp Pro Pro Ile Ile His Phe Gly Pro Gly Glu Ser Ser 370 375 380 Ser Glu Asp Ala Val Met Met Asn Thr Pro Val Val Lys Ser Ala Leu 385 390 395 400 Glu Met Gly Phe Asn Arg Asp Leu Val Lys Gin Thr Val Gin Ser Lys 405 410 415 Ile Leu Thr Thr Gly Glu Asn Tyr Lys Thr Val Asn Asp Ile Val Ser 420 425 430 Ala Leu Leu Asn Ala Glu Asp Glu Lys Arg Glu Glu Glu Lys Glu Lys 435 440 445 Gin Ala Glu Glu Met Ala Ser Asp Asp Leu Ser Leu Ile Arg Lys Asn 450 455 460 Arg Met Ala Leu Phe Gin Gin Leu Thr Cys Val Leu Pro Ile Leu Asp 465 470 475 480 Asn Leu Leu Lys Ala Asn Val Ile Asn Lys Gin Glu His Asp Ile Ile 485 490 495 Lys Gin Lys Thr Gin Ile Pro Leu Gin Ala Arg Glu Leu Ile Asp Thr 500 505 510 Ile Leu Val Lys Gly Asn Ala Ala Ala Asn Ile Phe Lys Asn Cys Leu 515 520 525 Lys Glu Ile Asp Ser Thr Leu Tyr Lys Asn Leu Phe Val Asp Lys Asn 530 535 540 Met Lys Tyr Ile Pro Thr Glu Asp Val Ser Gly Leu Ser Leu Glu Glu 545 550 555 560 Gin Leu Arg Arg Leu Gin Glu Glu Arg Thr Cys Lys Val Cys Met Asp 565 570 575 Lys Glu Val Ser Val Val Phe Ile Pro Cys Gly His Leu Val Val Cys 580 585 590 Gin Glu Cys Ala Pro Ser Leu Arg Lys Cys Pro Ile Cys Arg Gly Ile 595 600 605 Ile Lys Gly Thr Val Arg Thr Phe Leu Ser 610 615 (2) INFORMATION FOR SEQ ID NO:5: <i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3076 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 725..2539 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: GAATTCAAAA TGTCTTCAGT TGTAAATCTT ACCATTATTT TACGTACCTC TAAGAAATAA 60 AAGTGCTTCT AATTAAAATA TGATGTCATT AATTATGAAA TACTTCTTGA TAACAGAAGT 120 TTTAAAATAG CCATCTTAGA ATCAGTGAAA TATGGTAATG TATTATTTTC CTCCTTTGAG 180 TTAGGTCTTG TGCTTTTTTT TCCTGGCCAC TAAATTTCAC AATTTCCAAA AAGCAAAATA 240 AACATATTCT GAATATTTTT GCTGTGAAAC ACTTGACAGC AGAGCTTTCC ACCATGAAAA 300 GAAGCTTCAT GAGTCACACA TTACATCTTT GGGTTGATTG AATGCCACTG AAACATTCTA 360 GTAGCCTGGA GAAGTTGACC TACCTGTGGA GATGCCTGCC ATTAAATGGC ATCCTGATGG 420 CTTAATACAC ATCACTCTTC TGTGAAGGGT TTTAATTTTC AACACAGCTT ACTCTGTAGC 480 ATCATGTTTA CATTGTATGT ATAAAGATTA TACAAAGGTG CAATTGTGTA TTTCTTCCTT 540 AAAATGTATC AGTATAGGAT TTAGAATCTC CATGTTGAAA CTCTAAATGC ATAGAAATAA 600 AAATAATAAA AAATTTTTCA TTTTGGCTTT TCAGCCTAGT ATTAAAACTG ATAAAAGCAA 660 AGCCATGCAC AAAACTACCT CCCTAGAGAA AGGCTAGTCC CTTTTCTTCC CCATTCATTT 720 CATT ATG AAC ATA GTA GAA AAC AGC ATA TTC TTA TCA AAT TTG ATG AAA 769 Met Asn Ile Val Glu Asn Ser Ile Phe Leu Ser Asn Leu Met Lys 1 5 10 15 AGC GCC AAC ACG TTT GAA CTG AAA TAC GAC TTG TCA TGT GAA CTG TAC 817 Ser Ala Asn Thr Phe Glu Leu Lys Tyr Asp Leu Ser Cys Glu Leu Tyr 20 25 30 CGA ATG TCT ACG TAT TCC ACT TTT CCT GCT GGG GTT CCT GTC TCA GAA 865 Arg Met Ser Thr Tyr Ser Thr Phe Pro Ala Gly Val Pro Val Ser Glu 35 40 45 AGG AGT CTT GCT CGT GCT GGT TTC TAT TAC ACT GGT GTG AAT GAC AAG 913 Arg Ser Leu Ala Arg Ala Gly Phe Tyr Tyr Thr Gly Val Asn Asp Lys 50 55 60 GTC AAA TGC TTC TGT TGT GGC CTG ATG CTG GAT AAC TGG AAA AGA GGA 961 Val Lys Cys Phe Cys Cys Gly Leu Met Leu Asp Asn Trp Lys Arg Gly 65 70 75 GAC AGT CCT ACT GAA AAG CAT AAA AAG TTG TAT CCT AGC TGC AGA TTC 1009 Asp Ser Pro Thr Glu Lys His Lys Lys Leu Tyr Pro Ser Cys Arg Phe 80 85 90 95 GTT CAG AGT CTA AAT TCC GTT AAC AAC TTG GAA GCT ACC TCT CAG CCT 1057 Val Gin Ser Leu Asn Ser Val Asn Asn Leu Glu Ala Thr Ser Gin Pro 100 105 110 ACT TTT CCT TCT TCA GTA ACA AAT TCC ACA CAC TCA TTA CTT CCG GGT 1105 Thr Phe Pro Ser Ser Val Thr Asn Ser Thr His Ser Leu Leu Pro Gly 115 120 125 ACA GAA AAC AGT GGA TAT TTC CGT GGC TCT TAT TCA AAC TCT CCA TCA 1153 Thr Glu Asn Ser Gly Tyr Phe Arg Gly Ser Tyr Ser Asn Ser Pro Ser 130 135 140 AAT CCT GTA AAC TCC AGA GCA AAT CAA GAT TTT TCT GCC TTG ATG AGA 1201 Asn Pro Val Asn Ser Arg Ala Asn Gin Asp Phe Ser Ala Leu Met Arg 145 150 155 AGT TCC TAC CAC TGT GCA ATG AAT AAC GAA AAT GCC AGA TTA CTT ACT 1249 Ser Ser Tyr His Cys Ala Met Asn Asn Glu Asn Ala Arg Leu Leu Thr 160 165 170 175 TTT CAG ACA TGG CCA TTG ACT TTT CTG TCG CCA ACA GAT CTG GCA AAA 1297 Phe Gin Thr Trp Pro Leu Thr Phe Leu Ser Pro Thr Asp Leu Ala Lys 180 185 190 GCA GGC TTT TAC TAC ATA GGA CCT GGA GAC AGA GTG GCT TGC TTT GCC 1345 Ala Gly Phe Tyr Tyr Ile Gly Pro Gly Asp Arg Val Ala Cys Phe Ala 195 200 205 TGT GGT GGA AAA TTG AGC AAT TGG GAA CCG AAG GAT AAT GCT ATG TCA 1393 Cys Gly Gly Lys Leu Ser Asn Trp Glu Pro Lys Asp Asn Ala Met Ser 210 215 220 GAA CAC CTG AGA CAT TTT CCC AAA TGC CCA TTT ATA GAA AAT CAG CTT 1441 Glu His Leu Arg His Phe Pro Lys Cys Pro Phe Ile Glu Asn Gin Leu 225 230 235 CAA GAC ACT TCA AGA TAC ACA GTT TCT AAT CTG AGC ATG CAG ACA CAT 1489 Gin Asp Thr Ser Arg Tyr Thr Val Ser Asn Leu Ser Met Gin Thr His 240 245 250 255 GCA GCC CGC TTT AAA ACA TTC TTT AAC TGG CCC TCT AGT GTT CTA GTT 1537 Ala Ala Arg Phe Lys Thr Phe Phe Asn Trp Pro Ser Ser Val Leu Val 260 265 270 AAT CCT GAG CAG CTT GCA AGT GCG GGT TTT TAT TAT GTG GGT AAC AGT 1585 Asn Pro Glu Gin Leu Ala Ser Ala Gly Phe Tyr Tyr Val Gly Asn Ser 275 280 285 GAT GAT GTC AAA TGC TTT TGC TGT GAT GGT GGA CTC AGG TGT TGG GAA 1633 Asp Asp Val Lys Cys Phe Cys Cys Asp Gly Gly Leu Arg Cys Trp Glu 290 295 300 TCT GGA GAT GAT CCA TGG GTT CAA CAT GCC AAG TGG TTT CCA AGG TGT 1681 Ser Gly Asp Asp Pro Trp Val Gin His Ala Lys Trp Phe Pro Arg Cys 305 310 315 GAG TAC TTG ATA AGA ATT AAA GGA CAG GAG TTC ATC CGT CAA GTT CAA 1729 Glu Tyr Leu Ile Arg Ile Lys Gly Gin Glu Phe Ile Arg Gin Val Gin 320 325 330 335 GCC AGT TAC CCT CAT CTA CTT GAA CAG CTG CTA TCC ACA TCA GAC AGC 1777 Ala Ser Tyr Pro His Leu Leu Glu Gin Leu Leu Ser Thr Ser Asp Ser 340 345 350 CCA GGA GAT GAA AAT GCA GAG TCA TCA ATT ATC CAT TTT GAA CCT GGA 1825 Pro Gly Asp Glu Asn Ala Glu Ser Ser Ile Ile His Phe Glu Pro Gly 355 360 365 GAA GAC CAT TCA GAA GAT GCA ATC ATG ATG AAT ACT CCT GTG ATT AAT 1873 Glu Asp His Ser Glu Asp Ala Ile Met Met Asn Thr Pro Val Ile Asn 370 375 380 GCT GCC GTG GAA ATG GGC TTT AGT AGA AGC CTG GTA AAA CAG ACA GTT 1921 Ala Ala Val Glu Met Gly Phe Ser Arg Ser Leu Val Lys Gin Thr Val 385 390 395 CAA AGA AAA ATC CTA GCA ACT GGA GAG AAT TAT AGA CTA GTC AAT GAT 1969 Gin Arg Lys Ile Leu Ala Thr Gly Glu Asn Tyr Arg Leu Val Asn Asp 400 405 410 415 CTT GTG TTA GAC TTA CTC AAT GCA GAA GAT GAA ATA AGG GAA GAG GAG 2017 Leu Val Leu Asp Leu Leu Asn Ala Glu Asp Glu Ile Arg Glu Glu Glu 420 425 430 AGA GAA AGA GCA ACT GAG GAA AAA GAA TCA AAT GAT TTA TTA TTA ATC 2065 Arg Glu Arg Ala Thr Glu Glu Lys Glu Ser Asn Asp Leu Leu Leu Ile 435 440 445 CGG AAG AAT AGA ATG GCA CTT TTT CAA CAT TTG ACT TGT GTA ATT CCA 2113 Arg Lys Asn Arg Met Ala Leu Phe Gin His Leu Thr Cys Val Ile Pro 450 455 460 ATC CTG GAT AGT CTA CTA ACT GCC GGA ATT ATT AAT GAA CAA GAA CAT 2161 Ile Leu Asp Ser Leu Leu Thr Ala Gly Ile Ile Asn Glu Gin Glu His 465 470 475 GAT GTT ATT AAA CAG AAG ACA CAG ACG TCT TTA CAA GCA AGA GAA CTG 2209 Asp Val Ile Lys Gin Lys Thr Gin Thr Ser Leu Gin Ala Arg Glu Leu 480 485 490 495 ATT GAT ACG ATT TTA GTA AAA GGA AAT ATT GCA GCC ACT GTA TTC AGA 2257 Ile Asp Thr Ile Leu Val Lys Gly Asn Ile Ala Ala Thr Val Phe Arg 500 505 510 AAC TCT CTG CAA GAA GCT GAA GCT GTG TTA TAT GAG CAT TTA TTT GTG 2305 Asn Ser Leu Gin Glu Ala Glu Ala Val Leu Tyr Glu His Leu Phe Val 515 520 525 CAA CAG GAC ATA AAA TAT ATT CCC ACA GAA GAT GTT TCA GAT CTA CCA 2353 Gin Gin Asp Ile Lys Tyr Ile Pro Thr Glu Asp Val Ser Asp Leu Pro 530 535 540 GTG GAA GAA CAA TTG CGG AGA CTA CAA GAA GAA AGA ACA TGT AAA GTG 2401 Val Glu Glu Gin Leu Arg Arg Leu Gin Glu Glu Arg Thr Cys Lys Val 545 550 555 TGT ATG GAC AAA GAA GTG TCC ATA GTG TTT ATT CCT TGT GGT CAT CTA 2449 Cys Met Asp Lys Glu Val Ser Ile Val Phe Ile Pro Cys Gly His Leu 560 565 570 575 GTA GTA TGC AAA GAT TGT GCT CCT TCT TTA AGA AAG TGT CCT ATT TGT 2497 Val Val Cys Lys Asp Cys Ala Pro Ser Leu Arg Lys Cys Pro lie Cys 580 585 590 AGG AGT ACA ATC AAG GGT ACA GTT CGT ACA TTT CTT TCA TGAAGAAGAA 2546 Arg Ser Thr Ile Lys Gly Thr Val Arg Thr Phe Leu Ser 595 600 605 CCAAAACATC ATCTAAACTT TAGAATTAAT TTATTAAATG TATTATAACT TTAACTTTTA 2606 TCCTAATTTG GTTTCCTTAA AATTTTTATT TATTTACAAC TCAAAAAACA TTGTTTTGTG 2666 TAACATATTT ATATATGTAT CTAAACCATA TGAACATATA TTTTTTAGAA ACTAAGAGAA 2726 TGATAGGCTT TTGTTCTTAT GAACGAAAAA GAGGTAGCAC TACAAACACA ATATTCAATC 2786 AAAATTTCAG CATTATTGAA ATTGTAAGTG AAGTAAAACT TAAGATATTT GAGTTAACCT 2846 TTAAGAATTT TAAATATTTT GGCATTGTAC TAATACCTGG TTTTTTTTTT GTTTTGTTTT 2906 TTTGTACAGA CAGGGCAGCA TACTGAGACC CTGCCTTTAA AAACAAACAG AACAAAAACA 2966 AAACACCAGG GACACATTTC TCTGTCTTTT TTGATCAGTG TCCTATACAT CGAAGGTGTG 3026 CATATATGTT GAATGACATT TTAGGGACAT GGTGTTTTTA TAAAGAATTC 3076 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 604 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6; Met Asn Ile Val Glu Asn Ser Ile Phe Leu Ser Asn Leu Met Lys Ser 1 5 10 15 Ala Asn Thr Phe Glu Leu Lys Tyr Asp Leu Ser Cys Glu Leu Tyr Arg 20 25 30 Met Ser Thr Tyr Ser Thr Phe Pro Ala Gly Val Pro Val Ser Glu Arg 35 40 45 Ser Leu Ala Arg Ala Gly Phe Tyr Tyr Thr Gly Val Asn Asp Lys Val 50 55 60 Lys Cys Phe Cys Cys Gly Leu Met Leu Asp Asn Trp Lys Arg Gly Asp 65 70 75 80 Ser Pro Thr Glu Lys His Lys Lys Leu Tyr Pro Ser Cys Arg Phe Val 85 90 95 Gin Ser Leu Asn Ser Val Asn Asn Leu Glu Ala Thr Ser Gin Pro Thr 100 105 110 Phe Pro Ser Ser Val Thr Asn Ser Thr His Ser Leu Leu Pro Gly Thr 115 120 125 Glu Asn Ser Gly Tyr Phe Arg Gly Ser Tyr Ser Asn Ser Pro Ser Asn 130 135 140 Pro Val Asn Ser Arg Ala Asn Gin Asp Phe Ser Ala Leu Met Arg Ser 145 150 155 160 Ser Tyr His Cys Ala Met Asn Asn Glu Asn Ala Arg Leu Leu Thr Phe 165 170 175 Gin Thr Trp Pro Leu Thr Phe Leu Ser Pro Thr Asp Leu Ala Lys Ala 180 185 190 Gly Phe Tyr Tyr Ile Gly Pro Gly Asp Arg Val Ala Cys Phe Ala Cys 195 200 205 Gly Gly Lys Leu Ser Asn Trp Glu Pro Lys Asp Asn Ala Met Ser Glu 210 215 220 His Leu Arg His Phe Pro Lys Cys Pro Phe Ile Glu Asn Gin Leu Gin 225 230 235 240 Asp Thr Ser Arg Tyr Thr Val Ser Asn Leu Ser Met Gin Thr His Ala 245 250 255 Ala Arg Phe Lys Thr Phe Phe Asn Trp Pro Ser Ser Val Leu Val Asn 260 265 270 Pro Glu Gin Leu Ala Ser Ala Gly Phe Tyr Tyr Val Gly Asn Ser Asp 275 280 285 Asp Val Lys Cys Phe Cys Cys Asp Gly Gly Leu Arg Cys Trp Glu Ser 290 295 300 Gly Asp Asp Pro Trp Val Gin His Ala Lys Trp Phe Pro Arg Cys Glu 305 310 315 320 Tyr Leu Ile Arg Ile Lys Gly Gin Glu Phe Ile Arg Gin Val Gin Ala 325 330 335 Ser Tyr Pro His Leu Leu Glu Gin Leu Leu Ser Thr Ser Asp Ser Pro 340 345 350 Gly Asp Glu Asn Ala Glu Ser Ser Ile Ile His Phe Glu Pro Gly Glu 355 360 365 Asp His Ser Glu Asp Ala Ile Met Met Asn Thr Pro Val Ile Asn Ala 370 375 380 Ala Val Glu Met Gly Phe Ser Arg Ser Leu Val Lys Gin Thr Val Gin 385 390 395 400 Arg Lys Ile Leu Ala Thr Gly Glu Asn Tyr Arg Leu Val Asn Asp Leu 405 410 415 Val Leu Asp Leu Leu Asn Ala Glu Asp Glu Ile Arg Glu Glu Glu Arg 420 425 430 Glu Arg Ala Thr Glu Glu Lys Glu Ser Asn Asp Leu Leu Leu Ile Arg 435 440 445 Lys Asn Arg Met Ala Leu Phe Gin His Leu Thr Cys Val Ile Pro Ile 450 455 460 Leu Asp Ser Leu Leu Thr Ala Gly Ile Ile Asn Glu Gin Glu His Asp 465 470 475 480 Val Ile Lys Gin Lys Thr Gin Thr Ser Leu Gin Ala Arg Glu Leu Ile 485 490 495 Asp Thr Ile Leu Val Lys Gly Asn Ile Ala Ala Thr Val Phe Arg Asn 500 505 510 Ser Leu Gin Glu Ala Glu Ala Val Leu Tyr Glu His Leu Phe Val Gin 515 520 525 Gin Asp Ile Lys Tyr Ile Pro Thr Glu Asp Val Ser Asp Leu Pro Val 530 535 540 Glu Glu Gin Leu Arg Arg Leu Gin Glu Glu Arg Thr Cys Lys Val Cys 545 550 555 560 Met Asp Lys Glu Val Ser Ile Val Phe Ile Pro Cys Gly His Leu Val 565 570 575 Val Cys Lys Asp Cys Ala Pro Ser Leu Arg Lys Cys Pro Ile Cys Arg 580 585 590 Ser Thr Ile Lys Gly Thr Val Arg Thr Phe Leu Ser 595 600 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1552 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 6..1502 (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:7: CCACG ATG ACG GAG CTG GGC ATG GAG CTG GAG AGC GTT CGC CTG GCG 47 Met Thr Glu Leu Gly Met Glu Leu Glu Ser Val Arg Leu Ala 1 5 10 ACA TTT GGG GAA TGG CCC CTG AAT GCC CCA GTT TCC GCG GAG GAT CTG 95 Thr Phe Gly Glu Trp Pro Leu Asn Ala Pro Val Ser Ala Glu Asp Leu 15 20 25 30 GTC GCC AAT GGT TTC TTT GCC ACG GGA AAC TGG CTG GAG GCC GAG TGC 143 Val Ala Asn Gly Phe Phe Ala Thr Gly Asn Trp Leu Glu Ala Glu Cys 35 40 45 CAT TTC TGC CAC GTG CGC ATC GAC CGC TGG GAA TAC GGC GAT CAA GTG 191 His Phe Cys His Val Arg Ile Asp Arg Trp Glu Tyr Gly Asp Gin Val 50 55 60 GCG GAG CGC CAT CGC CGC TCC TCG CCC ATC TGC TCC ATG GTT CTG GCT 239 Ala Glu Arg His Arg Arg Ser Ser Pro Ile Cys Ser Met Val Leu Ala 65 70 75 CCC AAT CAC TGC GGC AAT GTT CCC AGG AGC CAG GAG AGC GAC AAC GAG 287 Pro Asn His Cys Gly Asn Val Pro Arg Ser Gin Glu Ser Asp Asn Glu 80 85 90 GGA AAC AGC GTA GTG GAC AGC CCG GAG TCC TGC TCT TGT CCC GAT CTC 335 Gly Asn Ser Val Val Asp Ser Pro Glu Ser Cys Ser Cys Pro Asp Leu 95 100 105 110 TTG TTG GAG GCC AAT CGA TTG GTA ACT TTC AAG GAC TGG CCG AAT CCC 383 Leu Leu Glu Ala Asn Arg Leu Val Thr Phe Lys Asp Trp Pro Asn Pro 115 120 125 AAC ATC ACG CCG CAG GCT CTG GCA AAG GCA GGT TTC TAC TAC CTG AAC 431 Asn Ile Thr Pro Gin Ala Leu Ala Lys Ala Gly Phe Tyr Tyr Leu Asn 130 135 140 CGT CTG GAT CAC GTG AAG TGT GTT TGG TGC AAC GGA GTG ATT GCC AAG 479 Arg Leu Asp His Val Lys Cys Val Trp Cys Asn Gly Val Ile Ala Lys 145 150 155 TGG GAG AAG AAC GAC AAT GCC TTT GAA GAG CAC AAG CGC TTT TTT CCC 527 Trp Glu Lys Asn Asp Asn Ala Phe Glu Glu His Lys Arg Phe Phe Pro 160 165 170 CAA TGT CCT CGT GTG CAA ATG GGC CCC CTT ATA GAG TTT GCC ACC GGG 575 Gin Cys Pro Arg Val Gin Met Gly Pro Leu Ile Glu Phe Ala Thr Gly 175 180 185 190 AAG AAC CTG GAT GAG CTG GGC ATC CAG CCC ACC ACT CTG CCA CTG CGT 623 Lys Asn Leu Asp Glu Leu Gly Ile Gin Pro Thr Thr Leu Pro Leu Arg 195 200 205 CCC AAG TAC GCC TGC GTG GAC GCC AGA TTG AGA ACC TTC ACC GAT TGG 671 Pro Lys Tyr Ala Cys Val Asp Ala Arg Leu Arg Thr Phe Thr Asp Trp 210 215 220 CCC ATT TCC AAT ATT CAG CCC GCT TCG GCT TTG GCG CAG GCT GGC CTA 719 Pro Ile Ser Asn Ile Gin Pro Ala Ser Ala Leu Ala Gin Ala Gly Leu 225 230 235 TAT TAT CAG AAA ATA GGC GAC CAG GTG CGC TGT TTC CAC TGC AAC ATT 767 Tyr Tyr Gin Lys Ile Gly Asp Gin Val Arg Cys Phe His Cys Asn Ile 240 245 250 GGA TTG CGC TCC TGG CAG AAG GAG GAC GAG CCA TGG TTC GAA CAC GCC 815 Gly Leu Arg Ser Trp Gin Lys Glu Asp Glu Pro Trp Phe Glu His Ala 255 260 265 270 AAG TGG TCG CCA AAG TGT CAG TTC GTT TTG CTG GAC AAG GGT CCA GCC 863 Lys Trp Ser Pro Lys Cys Gin Phe Val Leu Leu Asp Lys Gly Pro Ala 275 280 285 TAT GTA AGC GAA GTG CTC GCG ACA ACA GCT GCC AAC GCC AGT TCC CCG 911 Tyr Val Ser Glu Val Leu Ala Thr Thr Ala Ala Asn Ala Ser Ser Pro 290 295 300 ACA GCA ACT GCT CCG GCT CCA ACG CTC CAA GCA GAC GTA CTG ATG GAT 959 Thr Ala Thr Ala Pro Ala Pro Thr Leu Gin Ala Asp Val Leu Met Asp 305 310 315 GAA GCT CCG GCC AAG GAG GCC CTA GCC TTG GGT ATC GAT GGA GGA GTT 1007 Glu Ala Pro Ala Lys Glu Ala Leu Ala Leu Gly Ile Asp Gly Gly Val 320 325 330 GTG CGC AAT GCC ATC CAG CGC AAG CTC TTG AGT TCC GGC TGC GCT TTC 1055 Val Arg Asn Ala Ile Gin Arg Lys Leu Leu Ser Ser Gly Cys Ala Phe 335 340 345 350 TCT ACG TTG GAC GAA CTA TTG CAT GAC ATC TTT GAC GAT GCC GGC GCA 1103 Ser Thr Leu Asp Glu Leu Leu His Asp Ile Phe Asp Asp Ala Gly Ala 355 360 365 GGA GCT GCA CTG GAG GTG CGC GAG CCG CCG GAG CCA AGT GCT CCT TTT 1151 Gly Ala Ala Leu Glu Val Arg Glu Pro Pro Glu Pro Ser Ala Pro Phe 370 375 380 ATT GAA CCA TGT CAG GCC ACC ACC AGC AAG GCG GCA TCT GTG CCA ATA 1199 Ile Glu Pro Cys Gin Ala Thr Thr Ser Lys Ala Ala Ser Val Pro Ile 385 390 395 CCG GTG GCC GAT TCC ATC CCA GCC AAA CCA CAG GCA GCT GAA GCA GTG 1247 Pro Val Ala Asp Ser Ile Pro Ala Lys Pro Gin Ala Ala Glu Ala Val 400 405 410 GCG AAT ATA TCG AAA ATC ACA GAC GAA ATA CAA AAG ATG TCG GTG GCC 1295 Ala Asn Ile Ser Lys Ile Thr Asp Glu Ile Gin Lys Met Ser Val Ala 415 420 425 430 ACG CCG AAC GGA AAC CTG TCG CTG GAG GAG GAA AAC CGC CAG CTG AAG 1343 Thr Pro Asn Gly Asn Leu Ser Leu Glu Glu Glu Asn Arg Gin Leu Lys 435 440 445 GAT GCA CGC TTA TGC AAG GTA TGC TTG GAC GAG GAG GTT GGC GTA GTG 1391 Asp Ala Arg Leu Cys Lys Val Cys Leu Asp Glu Glu Val Gly Val Val 450 455 460 TTC CTG CCC TGC GGC CAC TTG GCC ACC TGC AAT CAG TGC GCC CCC AGT 1439 Phe Leu Pro Cys Gly His Leu Ala Thr Cys Asn Gin Cys Ala Pro Ser 465 470 475 GTA GCC AAT TGT CCC ATG TGC CGC GCA GAC ATC AAG GGA TTC GTG CGC 1487 Val Ala Asn Cys Pro Met Cys Arg Ala Asp Ile Lys Gly Phe Val Arg 480 485 490 ACG TTC CTT TCG TGAAGTGCAT ATCGACATCA TTTAGAGTTC ACCAGCTAGT 1539 Thr Phe Leu Ser 495 TAGCAGTTAA GCA 1552 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 498 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: Met Thr Glu Leu Gly Met Glu Leu Glu Ser Val Arg Leu Ala Thr Phe 1 5 10 15 Gly Glu Trp Pro Leu Asn Ala Pro Val Ser Ala Glu Asp Leu Val Ala 20 25 30 Asn Gly Phe Phe Ala Thr Gly Asn Trp Leu Glu Ala Glu Cys His Phe 35 40 45 Cys His Val Arg Ile Asp Arg Trp Glu Tyr Gly Asp Gin Val Ala Glu 50 55 60 Arg His Arg Arg Ser Ser Pro Ile Cys Ser Met Val Leu Ala Pro Asn 65 70 75 80 His Cys Gly Asn Val Pro Arg Ser Gin Glu Ser Asp Asn Glu Gly Asn 85 90 95 Ser Val Val Asp Ser Pro Glu Ser Cys Ser Cys Pro Asp Leu Leu Leu 100 105 110 Glu Ala Asn Arg Leu Val Thr Phe Lys Asp Trp Pro Asn Pro Asn Ile 115 120 125 Thr Pro Gin Ala Leu Ala Lys Ala Gly Phe Tyr Tyr Leu Asn Arg Leu 130 135 140 Asp His Val Lys Cys Val Trp Cys Asn Gly Val Ile Ala Lys Trp Glu 145 150 155 160 Lys Asn Asp Asn Ala Phe Glu Glu His Lys Arg Phe Phe Pro Gin Cys 165 170 175 Pro Arg Val Gin Met Gly Pro Leu Ile Glu Phe Ala Thr Gly Lys Asn 180 185 190 Leu Asp Glu Leu Gly Ile Gin Pro Thr Thr Leu Pro Leu Arg Pro Lys 195 200 205 Tyr Ala Cys Val Asp Ala Arg Leu Arg Thr Phe Thr Asp Trp Pro Ile 210 215 220 Ser Asn Ile Gin Pro Ala Ser Ala Leu Ala Gin Ala Gly Leu Tyr Tyr 225 230 235 240 Gin Lys Ile Gly Asp Gin Val Arg Cys Phe His Cys Asn Ile Gly Leu 245 250 255 Arg Ser Trp Gin Lys Glu Asp Glu Pro Trp Phe Glu His Ala Lys Trp 260 265 270 Ser Pro Lys Cys Gin Phe Val Leu Leu Asp Lys Gly Pro Ala Tyr Val 275 280 285 Ser Glu Val Leu Ala Thr Thr Ala Ala Asn Ala Ser Ser Pro Thr Ala 290 295 300 Thr Ala Pro Ala Pro Thr Leu Gin Ala Asp Val Leu Met Asp Glu Ala 305 310 315 320 Pro Ala Lys Glu Ala Leu Ala Leu Gly Ile Asp Gly Gly Val Val Arg 325 330 335 Asn Ala Ile Gin Arg Lys Leu Leu Ser Ser Gly Cys Ala Phe Ser Thr 340 345 350 Leu Asp Glu Leu Leu His Asp Ile Phe Asp Asp Ala Gly Ala Gly Ala 355 360 365 Ala Leu Glu Val Arg Glu Pro Pro Glu Pro Ser Ala Pro Phe Ile Glu 370 375 380 Pro Cys Gin Ala Thr Thr Ser Lys Ala Ala Ser Val Pro Ile Pro Val 385 390 395 400 Ala Asp Ser Ile Pro Ala Lys Pro Gin Ala Ala Glu Ala Val Ala Asn 405 410 415 Ile Ser Lys Ile Thr Asp Glu Ile Gin Lys Met Ser Val Ala Thr Pro 420 425 430 Asn Gly Asn Leu Ser Leu Glu Glu Glu Asn Arg Gin Leu Lys Asp Ala 435 440 445 Arg Leu Cys Lys Val Cys Leu Asp Glu Glu Val Gly Val Val Phe Leu 450 455 460 Pro Cys Gly His Leu Ala Thr Cys Asn Gin Cys Ala Pro Ser Val Ala 465 470 475 480 Asn Cys Pro Met Cys Arg Ala Asp Ile Lys Gly Phe Val Arg Thr Phe 485 490 495 Leu Ser (2) INFORMATION FOR SEQ ID NO:9 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 55 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: Glu Xaa Xaa Arg Xaa Xaa Thr Phe Xaa Xaa Trp Pro Xaa,. Xaa. Ala Xaa Ala Gly Phe Xaa 0 Asp Xaa Xaa p Xaa Cys Phe Xaa Cys Xaa Xaa Xaa Leu Xaa Xaa Trp Xaa Xaa Xaa Asp Xaa Pro Xaa Xaa Xaa His Xaa Xaa Xaa Xaa Pro Xaa Cys Xaa Xaa. Xaa r (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 500 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 48..467 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: TGAATCCGCG TTTGAGTCGT CTTGGCGGAG GTTGTGGTGA CGCCATC ATG GGA GCT 56 Met Gly Ala 1 CCG GCG CTG CCC CAG ATC TGG CAG CTG TAC CTC AAG AAC TAC CGC ATC 104 Pro Ala Leu Pro Gin Ile Trp Gin Leu Tyr Leu Lys Asn Tyr Arg Ile 5 10 15 GCC ACC TTC AAG AAC TGG CCC TTC CTG GAG GAC TGC GCC TGC ACC CCA 152 Ala Thr Phe Lys Asn Trp Pro Phe Leu Glu Asp Cys Ala Cys Thr Pro 20 25 30 35 GAG CGA ATG GCG GAG GCT GGC TTC ATC CAC TGC CCT ACC GAG AAC GAG 200 Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr Glu Asn Glu 40 45 50 CCT GAT TTG GCC CAG TGT TTT TTC TGC TTT AAG GAA TTG GAA GGC TGG 248 Pro Asp Leu Ala Gin Cys Phe Phe Cys Phe Lys Glu Leu Glu Gly Trp 55 60 65 GAA CCC GAT GAC AAC CCG ATA GAG GAG CAT AGA AAG CAC TCC CCT GGC 296 Glu Pro Asp Asp Asn Pro Ile Glu Glu His Arg Lys His Ser Pro Gly 70 75 80 TGC GCC TTC CTC ACT GTC AAG AAG CAG ATG GAA GAA CTA ACC GTC AGT 344 Cys Ala Phe Leu Thr Val Lys Lys Gin Met Glu Glu Leu Thr Val Ser 85 90 95 GAA TTC TTG AAA CTG GAC AGA CAG AGA GCC AAG AAC AAA ATT GCA AAG 392 Glu Phe Leu Lys Leu Asp Arg Gin Arg Ala Lys Asn Lys Ile Ala Lys 100 105 110 115 GAG ACC AAC AAC AAG CAA AAA GAG TTT GAA GAG ACT GCA AAG ACT ACC 440 Glu Thr Asn Asn Lys Gin Lys Glu Phe Glu Glu Thr Ala Lys Thr Thr 120 125 130 CGT CAG TCA ATT GAG CAG CTG GCT GCC TAATGCTGAG CGTTTGCTGA G 488 Arg Gin Ser Ile Glu Gin Leu Ala Ala * 135 140 ATA ACT TGG ACG 500 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 140 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:ll: Met Gly Ala Pro Ala Leu Pro Gin Ile Trp Gin Leu Tyr Leu Lys Asn 1 5 10 15 Tyr Arg Ile Ala Thr Phe Lys Asn Trp Pro Phe Leu Glu Asp Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gin Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asn Pro Ile Glu Glu His Arg Lys His 65 70 75 80 Ser Pro Gly Cys Ala Phe Leu Thr Val Lys Lys Gin Met Glu Glu Leu 85 90 95 Thr Val Ser Glu Phe Leu Lys Leu Asp Arg Gin Arg Ala Lys Asn Lys 100 105 110 Ile Ala Lys Glu Thr Asn Asn Lys Gin Lys Glu Phe Glu Glu Thr Ala 115 120 125 Lys Thr Thr Arg Gin Ser Ile Glu Gin Leu Ala Ala * 130 135 140 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1075 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 18..941 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: GAATTCGGCA CGAGAGA ATG CCA TAT ACA TTC GAG AAC TCA GAA GCT CTG 50 Met Pro Tyr Thr Phe Glu Asn Ser Glu Ala Leu 1 5 10 CTC AAA AAC TTG AAA GAC GCG GCT CCG TAC ATA TCA GCT GCC GAA CGC 98 Leu Lys Asn Leu Lys Asp Ala Ala Pro Tyr Ile Ser Ala Ala Glu Arg 15 20 25 TTT GCA TCT TTC AAA GGA TTC GTT TAT GAT AAG AGA ATT AAC ATC GCC 146 Phe Ala Ser Phe Lys Gly Phe Val Tyr Asp Lys Arg Ile Asn Ile Ala 30 35 40 TGT ACT TCC GAA AAG CTT GCA CGT GCA GGA TTC TAT TCG ACA GCC TCA 194 Cys Thr Ser Glu Lys Leu Ala Arg Ala Gly Phe Tyr Ser Thr Ala Ser 45 50 55 CCA GAA TTC CCC GCT TCA GCC AAA TGC CCG TTT TGT ATG CTG GAA ATC 242 Pro Glu Phe Pro Ala Ser Ala Lys Cys Pro Phe Cys Met Leu Glu Ile 60 65 70 75 AAT TTC GAA CAG TGC GAC GAT CCA TGG GAG AAA CAC AAA TCA GGA AGC 290 Asn Phe Glu Gin Cys Asp Asp Pro Trp Glu Lys His Lys Ser Gly Ser 80 85 90 CCA CAC TGT GAA TTT GTC ATG ATT GGA GAA ATC GAA GAA AGT GAA CTT 338 Pro His Cys Glu Phe Val Met lie Gly Glu Ile Glu Glu Ser Glu Leu 95 100 105 TCT TTC CGA ATC ATA TCC AAT CTT GCG ATA CGA CAC GCA ACA GTG AGA 386 Ser Phe Arg Ile Ile Ser Asn Leu Ala Ile Arg His Ala Thr Val Arg 110 115 120 CTT TAC GAA GAG CTA CTT GGA ATC GTA GCG ACA TTG GAA AAT GGA GAC 434 Leu Tyr Glu Glu Leu Leu Gly lie Val Ala Thr Leu Glu Asn Gly Asp 125 130 135 ATT GCT AAT GAA AAC CCG ATT ACC CGC GCT GAC GCC ACC AGG AAA TTG 482 lie Ala Asn Glu Asn Pro Ile Thr Arg Ala Asp Ala Thr Arg Lys Leu 140 145 150 155 ATT TCA TTC CGA TCT TCT AGC AAG CTT CTC ACT TTT GAT CAT CGA CTT 530 Ile Ser Phe Arg Ser Ser Ser Lys Leu Leu Thr Phe Asp His Arg Leu 160 165 170 GCC ACA TTC CAA AAT TTC ATT TTC GAC AAA AAA AGG AAT GTA AAA TGC 578 Ala Thr Phe Gin Asn Phe Ile Phe Asp Lys Lys Arg Asn Val Lys Cys 175 180 185 ACT TCA AAG AAG CTC GCC AAA GCT GGA TGG TTT TCT ATT GCC AAC AAA 626 Thr Ser Lys Lys Leu Ala Lys Ala Gly Trp Phe Ser Ile Ala Asn Lys 190 195 200 AAA GAT AAA ACT TCT GCA AAA TGT CCA TTC TGC CTT GTT GAG CTG GAC 674 Lys Asp Lys Thr Ser Ala Lys Cys Pro Phe Cys Leu Val Glu Leu Asp 205 210 215 TTT GAC GAA TCA GAT GAT CCG TGG GAA GAG CAT CAG AAG TTC AGT GCA 722 Phe Asp Glu Ser Asp Asp Pro Trp Glu Glu His Gin Lys Phe Ser Ala 220 225 230 235 TCC TGC GAT TTT ATC AAA CTA GGC AAG CTT GAT GAG AAA AAA TGG ACT 770 Ser Cys Asp Phe Ile Lys Leu Gly Lys Leu Asp Glu Lys Lys Trp Thr 240 245 250 GAA AAT GAA GCA TTA ATG CTG GGA GCA AGA ATC ACG ATT ATG CAA AAA 818 Glu Asn Glu Ala Leu Met Leu Gly Ala Arg Ile Thr Ile Met Gin Lys 255 260 265 TAC GAA AAA GGA AGT TGG TTG ATT GAC GAA CTC GAG AAA GAA AAT AGA 866 Tyr Glu Lys Gly Ser Trp Leu lie Asp Glu Leu Glu Lys Glu Asn Arg 270 275 280 ATT GAT GAA ATA ATC AAG ATT CGA AAA ATT ATG ATC AAA CCA AAT CAT 914 Ile Asp Glu Ile Ile Lys Ile Arg Lys Ile Met Ile Lys Pro Asn His 285 290 295 GTT CTC AAA CGA CGT CGA TGC AGT ATT TAA TTTATATTTC GACTTTTTAT 944 Val Leu Lys Arg Arg Arg Cys Ser Ile * 300 305 CTGTAAACTT TTGCCTCCCT CCCCGACCTG TTTAACATCC GTAATTCATT CCAAAAATGT 1004 TCTAATTCGA ATGAATATGT TTTCCTAAAA AAAAAAAAAA AAAAACTCGA G 1055 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 308 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: Met Pro Tyr Thr Phe Glu Asn Ser Glu Ala Leu Leu Lys Asn Leu Lys 10 15 Asp Ala Ala Pro Tyr Ile Ser Ala Ala Glu Arg Phe Ala Ser Phe Lys 20 25 30 Gly Phe Val Tyr Asp Lys Arg Ile Asn lie Ala Cys Thr Ser Glu Lys 35 40 45 Leu Ala Arg Ala Gly Phe Tyr Ser Thr Ala Ser Pro Glu Phe Pro Ala 50 55 60 Ser Ala Lys Cys Pro Phe Cys Met Leu Glu Ile Asn Phe Glu Gin Cys 65 70 75 80 Asp Asp Pro Trp Glu Lys His Lys Ser Gly Ser Pro His Cys Glu Phe 85 90 95 Val Met Ile Gly Glu Ile Glu Glu Ser Glu Leu Ser Phe Arg Ile Ile 100 105 110 Ser Asn Leu Ala Ile Arg His Ala Thr Val Arg Leu Tyr Glu Glu Leu 115 120 125 Leu Gly Ile Val Ala Thr Leu Glu Asn Gly Asp Ile Ala Asn Glu Asn 130 135 140 Pro Ile Thr Arg Ala Asp Ala Thr Arg Lys Leu Ile Ser Phe Arg Ser 145 150 155 160 Ser Ser Lys Leu Leu Thr Phe Asp His Arg Leu Ala Thr Phe Gin Asn 165 170 175 Phe Ile Phe Asp Lys Lys Arg Asn Val Lys Cys Thr Ser Lys Lys Leu 180 185 190 Ala Lys Ala Gly Trp Phe Ser Ile Ala Asn Lys Lys Asp Lys Thr Ser 195 200 205 Ala Lys Cys Pro Phe Cys Leu Val Glu Leu Asp Phe Asp Glu Ser Asp 210 215 220 Asp Pro Trp Glu Glu His Gin Lys Phe Ser Ala Ser Cys Asp Phe Ile 225 230 235 240 Lys Leu Gly Lys Leu Asp Glu Lys Lys Trp Thr Glu Asn Glu Ala Leu 245 250 255 Met Leu Gly Ala Arg Ile Thr Ile Met Gin Lys Tyr Glu Lys Gly Ser 260 265 270 Trp Leu Ile Asp Glu Leu Glu Lys Glu Asn Arg lie Asp Glu Ile Ile 275 280 285 Lys Ile Arg Lys Ile Met Ile Lys Pro Asn His Val Leu Lys Arg Arg 290 295 300 Arg Cys Ser Ile 305 (2) INFORMATION FOR SEQ ID Nθ:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 512 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..123 (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 168..512 (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:14: ATG GCA CCC GGG ACC AAA AAA AAG TCG GAT ATG GCA AAA TTC ACA TTC 48 Met Ala Pro Gly Thr Lys Lys Lys Ser Asp Met Ala Lys Phe Thr Phe 1 5 10 15 TAC AAA GAT CGC TTG ATG ACA TTC AAA AAT TTC GAA TAT GAT AGA GAC 96 Tyr Lys Asp Arg Leu Met Thr Phe Lys Asn Phe Glu Tyr Asp Arg Asp 20 25 30 CCG GAT GCA AAA TGC ACG TCT CAA GCG GTTTGTCCAT TTTCGTGTTT 143 Pro Asp Ala Lys Cys Thr Ser Gin Ala 35 40 TAAATAAAAT TATTCTTGTT TTAG GTT GCT CAA GCC GGA TTT TAC TGC ACC 194 Val Ala Gin Ala Gly Phe Tyr Cys Thr 1 5 GGT CCT CAG TCT GGC AAA TGT GCA TTT TGC AAC AAG GAA CTT GAT TTT 242 Gly Pro Gin Ser Gly Lys Cys Ala Phe Cys Asn Lys Glu Leu Asp Phe 10 15 20 25 GAC CCA GAA GAC GAT CCG TGG TAC GAG CAC ACG AAA CGT GAT GAA CCG 290 Asp Pro Glu Asp Asp Pro Trp Tyr Glu His Thr Lys Arg Asp Glu Pro 30 35 40 TGC GAG TTT GTA CGG ATT GGA AAG CTC GAT GAC TCG GAA TTA ACT ATT 338 Cys Glu Phe Val Arg Ile Gly Lys Leu Asp Asp Ser Glu Leu Thr Ile 45 50 55 AAC GAT ACC GTT CGT CTC TCA CAA ACC GCC ATG ATT ATG ACT AAA CTC 386 Asn Asp Thr Val Arg Leu Ser Gin Thr Ala Met Ile Met Thr Lys Leu 60 65 70 TTT GAG CAT GAG ATG ATG ATA AAT AAT TTG TCT AAT CAT TCT TCT TCT 434 Phe Glu His Glu Met Met Ile Asn Asn Leu Ser Asn His Ser Ser Ser 75 80 85 GAT GCT CTC TTC GAT CAG CTG AAA AAA GTA CCG AAC ACA GCA TCG ACA 482 Asp Ala Leu Phe Asp Gin Leu Lys Lys Val Pro Asn Thr Ala Ser Thr 90 95 100 105 ACA AAA TCT AAC AGC CGC CGC GGC AAA TA 512 Thr Lys Ser Asn Ser Arg Arg Gly Lys 110 115 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 155 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: Met Ala Pro Gly Thr Lys Lys Lys Ser Asp Met Ala Lys Phe Thr Phe 1 5 10 15 Tyr Lys Asp Arg Leu Met Thr Phe Lys Asn Phe Glu Tyr Asp Arg Asp 20 25 30 Pro Asp Ala Lys Cys Thr Ser Gin Ala Val Ala Gin Ala Gly Phe Tyr 35 40 45 Cys Thr Gly Pro Gin Ser Gly Lys Cys Ala Phe Cys Asn Lys Glu Leu 50 55 60 Asp Phe Asp Pro Glu Asp Asp Pro Trp Tyr Glu His Thr Lys Arg Asp 65 70 75 80 Glu Pro Cys Glu Phe Val Arg Ile Gly Lys Leu Asp Asp Ser Glu Leu 85 90 95 Thr Ile Asn Asp Thr Val Arg Leu Ser Gin Thr Ala Met Ile Met Thr 100 105 110 Lys Leu Phe Glu His Glu Met Met Ile Asn Asn Leu Ser Asn His Ser 115 120 125 Ser Ser Asp Ala Leu Phe Asp Gin Leu Lys Lys Val Pro Asn Thr Ala 130 135 140 Ser Thr Thr Lys Ser Asn Ser Arg Arg Gly Lys 145 150 155 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2866 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..2863 (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:16: ATG GAT GGT CAA ATA GAT AAA ATG GAG AAG CGA TAT AGC ATG ACC AAA 48 Met Asp Gly Gin Ile Asp Lys Met Glu Lys Arg Tyr Ser Met Thr Lys 1 5 10 15 CTG GAG AAT AGG TTA AGG ACT TTC CAA GAT GGT GTT GCA CTT GAA AAA 96 Leu Glu Asn Arg Leu Arg Thr Phe Gin Asp Gly Val Ala Leu Glu Lys 20 25 30 AAA AAG TTA AAG TGG AGT TTT AAA GTT ATT CCG TAT CAG GCA ATG GCC 144 Lys Lys Leu Lys Trp Ser Phe Lys Val Ile Pro Tyr Gin Ala Met Ala 35 40 45 AAG CTT GGA TTT TAC TTT GAT CCA GTG ATC GAT CCT AAG ACA TCT AAA 192 Lys Leu Gly Phe Tyr Phe Asp Pro Val Ile Asp Pro Lys Thr Ser Lys 50 55 60 CTG AAA AAA GAC TCT GTA AGA TGT TGC TAT TGT CAT CGT CAA ACA TAC 240 Leu Lys Lys Asp Ser Val Arg Cys Cys Tyr Cys His Arg Gin Thr Tyr 65 70 75 80 AAT GTG AGA GAC TGC AGA TCC AAA AGA AAA GAT GTT CTT GAG ACT CTA 288 Asn Val Arg Asp Cys Arg Ser Lys Arg Lys Asp Val Leu Glu Thr Leu 85 90 95 AGC AAT ATA ATG AGG CAA CAT CTG ACT GTT ACT GAT AAC AAA CAA GTT 336 Ser Asn Ile Met Arg Gin His Leu Thr Val Thr Asp Asn Lys Gin Val 100 105 110 TGC CTC CTT ATT TAC TTG CGC AAT AAG CTA TTG ACG GAC TAT AGC TTC 384 Cys Leu Leu Ile Tyr Leu Arg Asn Lys Leu Leu Thr Asp Tyr Ser Phe 115 120 125 CAT ATG GGG GTT TCG GAC TGG AAA AAT GAC AAG TAC TTC AGC AAT CCA 432 His Met Gly Val Ser Asp Trp Lys Asn Asp Lys Tyr Phe Ser Asn Pro 130 135 140 GAT GAT GAA AAC GTG ATA AAC CTA AGA AAA TTT ACT TTT CAA GAT AAC 480 Asp Asp Glu Asn Val Ile Asn Leu Arg Lys Phe Thr Phe Gin Asp Asn 145 150 155 160 TGG CCT CAC AGT GGT TCT CAA AAT GAA CAT CCG CTG GGT ATA GAA AAG 528 Trp Pro His Ser Gly Ser Gin Asn Glu His Pro Leu Gly Ile Glu Lys 165 170 175 ATG GTG AAT GCA GGA CTC ATG CGA TAC GAC TCC AGC ATA GAA GGC TTA 576 Met Val Asn Ala Gly Leu Met Arg Tyr Asp Ser Ser Ile Glu Gly Leu 180 185 190 GGC GAT CCA AGC ATG GAT AAA ACA CTT ATG AAC GAT ACC TGT TAT TGT 624 Gly Asp Pro Ser Met Asp Lys Thr Leu Met Asn Asp Thr Cys Tyr Cys 195 200 205 ATT TAT TGC AAA CAG TTG TTA CAA GGT TGG TCA ATA AAT GAC GAT CCG 672 Ile Tyr Cys Lys Gin Leu Leu Gin Gly Trp Ser Ile Asn Asp Asp Pro 210 215 220 ATG AGC CGA CAT TAT AAG GTT TCT CAA AAT GGG AAC TGT TAT TTC TTT 720 Met Ser Arg His Tyr Lys Val Ser Gin Asn Gly Asn Cys Tyr Phe Phe 225 230 235 240 CAG ACA CGT AAT CGA TTT GAG AGA ATA AAA AAT GAC AAT GAC AGT ATC 768 Gin Thr Arg Asn Arg Phe Glu Arg lie Lys Asn Asp Asn Asp Ser Ile 245 250 255 ACG AAA AAT TGC GAA GTC TCT CCA ACT TTA GGC GAA AAT GGG AAA AGA 816 Thr Lys Asn Cys Glu Val Ser Pro Thr Leu Gly Glu Asn Gly Lys Arg 260 265 270 GAA GTG ATC AAC ACG AAA ACC GCT TCT CAA AGG CAG TGT CCT TTA TTT 864 Glu Val Ile Asn Thr Lye Thr Ala Ser Gin Arg Gin Cys Pro Leu Phe 275 280 285 GAG TCA CCT CCA TCT AGT ACT GGT CCT CAA CTT GAC GAT TAT AAT GAG 912 Glu Ser Pro Pro Ser Ser Thr Gly Pro Gin Leu Asp Asp Tyr Asn Glu 290 295 300 AAG ACA GAT ATA TCT GTT ATT CAA CAT AAT ATA AGT GTG CTT GAT GGA 960 Lys Thr Asp Ile Ser Val Ile Gin His Asn Ile Ser Val Leu Asp Gly 305 310 315 320 GCA CAA GGC GAA AAT GTA AAA CGT AAT AGT GTG GAA GAA AAA GAA CAA 1008 Ala Gin Gly Glu Asn Val Lys Arg Asn Ser Val Glu Glu Lys Glu Gin 325 330 335 ATC AAC ATG GAA AAT GGA AGC ACT ACA TTA GAA GAG GGC AAT ATA AAT 1056 Ile Asn Met Glu Asn Gly Ser Thr Thr Leu Glu Glu Gly Asn Ile Asn 340 345 350 CGT GAT GTT TTA GCA GAT AAG AAA GAA GTT ATT TCG ACA CCA ACT GCA 1104 Arg Asp Val Leu Ala Asp Lys Lys Glu Val Ile Ser Thr Pro Thr Ala 355 360 365 AAA GAA ATC AAA CGT CCA AAT GTC CAG CTA ACC CAA TCA TCG TCA CCT 1152 Lys Glu Ile Lys Arg Pro Asn Val Gin Leu Thr Gin Ser Ser Ser Pro 370 375 380 ATA AAA AAG AAA AGA AAG TTT AAG AGA ATA TCG CCT AGA AAA ATC TTT 1200 Ile Lys Lys Lys Arg Lys Phe Lys Arg Ile Ser Pro Arg Lys Ile Phe 385 390 395 400 GAT GAG GAA GAT AGC GAA CAC TCC CTT AAT AAT AAT TCT GCC AAC GGA 1248 Asp Glu Glu Asp Ser Glu His Ser Leu Asn Asn Asn Ser Ala Asn Gly 405 410 415 GAC AAC AAA GAT AAG GAT TTG GTT ATA GAT TTT ACA AGC CAT ATC ATA 1296 Asp Asn Lys Asp Lys Asp Leu Val Ile Asp Phe Thr Ser His Ile Ile 420 425 430 AAA AAT AGA GAT GTA GGG AGA AAG AAT GCT ATT TTA GAT GAC AGC ACA 1344 Lys Asn Arg Asp Val Gly Arg Lys Asn Ala Ile Leu Asp Asp Ser Thr 435 440 445 GAT GAA TTC AGT TTC AGT AAC CAA GGA CAT AAC ACA TTT GAC ATA CCT 1392 Asp Glu Phe Ser Phe Ser Asn Gin Gly His Asn Thr Phe Asp Ile Pro 450 455 460 ATA CCA ACC TCA TCA CAT TTG CTC AAA GGT ATA GAT TCA GAT AAT GAC 1440 Ile Pro Thr Ser Ser His Leu Leu Lys Gly Ile Asp Ser Asp Asn Asp 465 470 475 480 AAT GTT ATA CGA GAA GAT GAT ACT GGC ATA AAT ACA GAC ACA AAA GGA 1488 Asn Val Ile Arg Glu Asp Asp Thr Gly Ile Asn Thr Asp Thr Lys Gly 485 490 495 GCG TCT TCT AAA CAC GAA AAA TTT TCT GTT AAT TCT GAA GAA GAT TTA 1536 Ala Ser Ser Lys His Glu Lys Phe Ser Val Asn Ser Glu Glu Asp Leu 500 505 510 AAT TTC AGT GAA GTG AAA CTC ACA GGT AGA GAC AGT AGT ACT AAT ATT 1584 Asn Phe Ser Glu Val Lys Leu Thr Gly Arg Asp Ser Ser Thr Asn Ile 515 520 525 CTT ATA AGA ACG CAA ATT GTA GAT CAG AAT TTG GGT GAT ATC GAC AGA 1632 Leu Ile Arg Thr Gin Ile Val Asp Gin Asn Leu Gly Asp Ile Asp Arg 530 535 540 GAT AAG GTC CCC AAT GGT GGA TCC CCA GAA GTT CCA AAG ACA CAT GAG 1680 Asp Lys Val Pro Asn Gly Gly Ser Pro Glu Val Pro Lys Thr His Glu 545 550 555 560 TTA ATT AGA GAT AAC TCT GAA AAG AGG GAA GCA CAA AAC GGG GAA TTT 1728 Leu Ile Arg Asp Asn Ser Glu Lys Arg Glu Ala Gin Asn Gly Glu Phe 565 570 575 CGA CAT CAA AAA GAT TCA ACT GTA CGG CAA TCT CCA GAT ATA TTA CAT 1776 Arg His Gin Lys Asp Ser Thr Val Arg Gin Ser Pro Asp Ile Leu His 580 585 590 TCT AAT AAA AGT GGT GAT AAT TCC AGT AAT ATT ACC GCA ATA CCC AAA 1824 Ser Asn Lys Ser Gly Asp Asn Ser Ser Asn Ile Thr Ala Ile Pro Lys 595 600 605 GAG GAA CAA AGG AGA GGC AAT AGC AAA ACA TCC AGC ATT CCC GCT GAT 1872 Glu Glu Gin Arg Arg Gly Asn Ser Lys Thr Ser Ser Ile Pro Ala Asp 610 615 620 ATT CAT CCT AAA CCA AGG AAA AAC TTG CAA GAA CCA AGA AGC CTA TCA 1920 Ile His Pro Lys Pro Arg Lys Asn Leu Gin Glu Pro Arg Ser Leu Ser 625 630 635 640 ATA AGT GGA AAA GTT GTT CCA ACA GAA AGA AAA TTA GAT AAC ATC AAT 1968 Ile Ser Gly Lys Val Val Pro Thr Glu Arg Lys Leu Asp Asn Ile Asn 645 650 655 ATA GAT CTA AAT TTT TCG GCG TCC GAT TTT TCA CCA TCA TCA CAA TCT 2016 Ile Asp Leu Asn Phe Ser Ala Ser Asp Phe Ser Pro Ser Ser Gin Ser 660 665 670 GAG CAA TCA TCA AAA AGC TCA AGC GTT ATT TCA ACG CCG GTA GCG AGC 2064 Glu Gin Ser Ser Lys Ser Ser Ser Val lie Ser Thr Pro Val Ala Ser 675 680 685 CCT AAA ATT AAT CTC ACA CGC AGT TTG CAT GCA GTC AAA GAG CTT TCT 2112 Pro Lys Ile Asn Leu Thr Arg Ser Leu His Ala Val Lys Glu Leu Ser 690 695 700 GGC CTC AAA AAA GAA ACT GAC GAT GGT AAG TAT TTT ACT AAT AAG CAG 2160 Gly Leu Lys Lys Glu Thr Asp Asp Gly Lys Tyr Phe Thr Asn Lys Gin 705 710 715 720 GAA ACT ATA AAA ATA CTG GAA GAT GTG TCT GTG AAG AAT GAG ACC CCA 2208 Glu Thr Ile Lys Ile Leu Glu Asp Val Ser Val Lys Asn Glu Thr Pro 725 730 735 AAT AAT GAA ATG TTA CTT TTT GAG ACT GGA ACC CCG ATC GCA TCT CAA 2256 Asn Asn Glu Met Leu Leu Phe Glu Thr Gly Thr Pro Ile Ala Ser Gin 740 745 750 GAA AAC AAG TCA AGA AAA TTA TTT GAT GAA GAG TTT TCT GGG AAG GAA 2304 Glu Asn Lys Ser Arg Lys Leu Phe Asp Glu Glu Phe Ser Gly Lys Glu 755 760 765 TTG GAT ATA CCT ATA GAT TCA TCA ACT GTA GAA ATA AAA AAG GTT ATT 2352 Leu Asp Ile Pro Ile Asp Ser Ser Thr Val Glu lie Lys Lys Val Ile 770 775 780 AAA CCC GAA TTT GAG CCA GTC CCA TCA GTT GCA AGG AAT TTG GTG TCT 2400 Lys Pro Glu Phe Glu Pro Val Pro Ser Val Ala Arg Asn Leu Val Ser 785 790 795 800 GGA ACC TCT TCA TAT CCA CGG AAT TCA CGT TTA GAA GAA CAA AGA AAG 2448 Gly Thr Ser Ser Tyr Pro Arg Asn Ser Arg Leu Glu Glu Gin Arg Lys 805 810 815 GAA ACA AGC ACA AGT TTG GCT GAT AAT TCT AAG AAA GGA AGT TCA TTT 2496 Glu Thr Ser Thr Ser Leu Ala Asp Asn Ser Lys Lys Gly Ser Ser Phe 820 825 830 AAT GAG GGC AAC AAC GAA AAA GAA CCG AAT GCA GCA GAA TGG TTT AAA 2544 Asn Glu Gly Asn Asn Glu Lys Glu Pro Asn Ala Ala Glu Trp Phe Lys 835 840 845 ATT GAT GAA AAT AGA CAC CTT GTA AAA AAT TAC TTC CAT GAT TTG TTA 2592 Ile Asp Glu Asn Arg His Leu Val Lys Asn Tyr Phe His Asp Leu Leu 850 855 860 AAA TAT ATA AAT AAT AAT GAT GCT ACG CTA GCT AAT GAC AAA GAC GGT 2640 Lys Tyr Ile Asn Asn Asn Asp Ala Thr Leu Ala Asn Asp Lys Asp Gly 865 870 875 880 GAT CTG GCT TTT TTG ATT AAG CAA ATG CCT GCA GAA GAG TTG GAC ATG 2688 Asp Leu Ala Phe Leu Ile Lys Gin Met Pro Ala Glu Glu Leu Asp Met 885 890 895 ACA TTC AAC AAT TGG GTG AAC CTA AAA GTG CAA TCT ATT AAG CGC GAA 2736 Thr Phe Asn Asn Trp Val Asn Leu Lys Val Gin Ser Ile Lys Arg Glu 900 905 910 TTT ATA GAT GAC TGT GAT AAG AAA TTG GAC ATA TTG AGA AGG GAT TAC 2784 Phe Ile Asp Asp Cys Asp Lys Lys Leu Asp Ile Leu Arg Arg Asp Tyr 915 920 925 TAT ACT GCC ACA AAT TTT ATT GAA ACT TTG GAA GAT GAC AAT CAA TTG 2832 Tyr Thr Ala Thr Asn Phe Ile Glu Thr Leu Glu Asp Asp Asn Gin Leu 930 935 940 ATC GAT ATT GCT AAG AAA ATG GGC ATT TTA TAG 2865 Ile Asp Ile Ala Lys Lys Met Gly Ile Leu * 945 950 955 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 954 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: Met Asp Gly Gin Ile Asp Lys Met Glu Lys Arg Tyr Ser Met Thr Lys 1 5 10 15 Leu Glu Asn Arg Leu Arg Thr Phe Gin Asp Gly Val Ala Leu Glu Lys 20 25 30 Lys Lys Leu Lys Trp Ser Phe Lys Val Ile Pro Tyr Gin Ala Met Ala 35 40 45 Lys Leu Gly Phe Tyr Phe Asp Pro Val Ile Asp Pro Lys Thr Ser Lys 50 55 60 Leu Lys Lys Asp Ser Val Arg Cys Cys Tyr Cys His Arg Gin Thr Tyr 65 70 75 80 Asn Val Arg Asp Cys Arg Ser Lys Arg Lys Asp Val Leu Glu Thr Leu 85 90 95 Ser Asn Ile Met Arg Gin His Leu Thr Val Thr Asp Asn Lys Gin Val 100 105 110 Cys Leu Leu Ile Tyr Leu Arg Asn Lys Leu Leu Thr Asp Tyr Ser Phe 115 120 125 His Met Gly Val Ser Asp Trp Lys Asn Asp Lys Tyr Phe Ser Asn Pro 130 135 140 Asp Asp Glu Asn Val Ile Asn Leu Arg Lys Phe Thr Phe Gin Asp Asn 145 150 155 160 Trp Pro His Ser Gly Ser Gin Asn Glu His Pro Leu Gly Ile Glu Lys 165 170 175 Met Val Asn Ala Gly Leu Met Arg Tyr Asp Ser Ser Ile Glu Gly Leu 180 185 190 Gly Asp Pro Ser Met Asp Lys Thr Leu Met Asn Asp Thr Cys Tyr Cys 195 200 205 Ile Tyr Cys Lys Gin Leu Leu Gin Gly Trp Ser Ile Asn Asp Asp Pro 210 215 220 Met Ser Arg His Tyr Lys Val Ser Gin Asn Gly Asn Cys Tyr Phe Phe 225 230 235 240 Gin Thr Arg Asn Arg Phe Glu Arg Ile Lys Asn Asp Asn Asp Ser Ile 245 250 255 Thr Lys Asn Cys Glu Val Ser Pro Thr Leu Gly Glu Asn Gly Lye Arg 260 265 270 Glu Val Ile Asn Thr Lys Thr Ala Ser Gin Arg Gin Cys Pro Leu Phe 275 280 285 Glu Ser Pro Pro Ser Ser Thr Gly Pro Gin Leu Asp Asp Tyr Asn Glu 290 295 300 Lys Thr Asp Ile Ser Val Ile Gin His Asn Ile Ser Val Leu Asp Gly 305 310 315 320 Ala Gin Gly Glu Asn Val Lys Arg Asn Ser Val Glu Glu Lys Glu Gin 325 330 335 Ile Asn Met Glu Asn Gly Ser Thr Thr Leu Glu Glu Gly Asn Ile Asn 340 345 350 Arg Asp Val Leu Ala Asp Lys Lys Glu Val Ile Ser Thr Pro Thr Ala 355 360 365 Lys Glu Ile Lys Arg Pro Asn Val Gin Leu Thr Gin Ser Ser Ser Pro 370 375 380 Ile Lys Lys Lys Arg Lys Phe Lys Arg Ile Ser Pro Arg Lys Ile Phe 385 390 395 400 Asp Glu Glu Asp Ser Glu His Ser Leu Asn Asn Asn Ser Ala Asn Gly 405 410 415 Asp Asn Lys Asp Lys Asp Leu Val Ile Asp Phe Thr Ser His Ile Ile 420 425 430 Lys Asn Arg Asp Val Gly Arg Lys Asn Ala Ile Leu Asp Asp Ser Thr 435 440 445 Asp Glu Phe Ser Phe Ser Asn Gin Gly His Asn Thr Phe Asp Ile Pro 450 455 460 Ile Pro Thr Ser Ser His Leu Leu Lys Gly Ile Asp Ser Asp Asn Asp 465 470 475 480 Asn Val Ile Arg Glu Asp Asp Thr Gly Ile Asn Thr Asp Thr Lys Gly 485 490 495 Ala Ser Ser Lys His Glu Lys Phe Ser Val Asn Ser Glu Glu Asp Leu 500 505 510 Asn Phe Ser Glu Val Lys Leu Thr Gly Arg Asp Ser Ser Thr Asn Ile 515 520 525 Leu Ile Arg Thr Gin Ile Val Asp Gin Asn Leu Gly Asp Ile Asp Arg 530 535 540 Asp Lys Val Pro Asn Gly Gly Ser Pro Glu Val Pro Lys Thr His Glu 545 550 555 560 Leu Ile Arg Asp Asn Ser Glu Lys Arg Glu Ala Gin Asn Gly Glu Phe 565 570 575 Arg His Gin Lys Asp Ser Thr Val Arg Gin Ser Pro Asp Ile Leu His 580 585 590 Ser Asn Lys Ser Gly Asp Asn Ser Ser Asn Ile Thr Ala Ile Pro Lys 595 600 605 Glu Glu Gin Arg Arg Gly Asn Ser Lys Thr Ser Ser Ile Pro Ala Asp 610 615 620 Ile His Pro Lys Pro Arg Lys Asn Leu Gin Glu Pro Arg Ser Leu Ser 625 630 635 640 Ile Ser Gly Lys Val Val Pro Thr Glu Arg Lys Leu Asp Asn Ile Asn 645 650 655 Ile Asp Leu Asn Phe Ser Ala Ser Asp Phe Ser Pro Ser Ser Gin Ser 660 665 670 Glu Gin Ser Ser Lys Ser Ser Ser Val Ile Ser Thr Pro Val Ala Ser 675 680 685 Pro Lys Ile Asn Leu Thr Arg Ser Leu His Ala Val Lys Glu Leu Ser 690 695 700 Gly Leu Lys Lys Glu Thr Asp Asp Gly Lys Tyr Phe Thr Asn Lys Gin 705 710 715 720 Glu Thr Ile Lys Ile Leu Glu Asp Val Ser Val Lys Asn Glu Thr Pro 725 730 735 Asn Asn Glu Met Leu Leu Phe Glu Thr Gly Thr Pro Ile Ala Ser Gin 740 745 750 Glu Asn Lys Ser Arg Lys Leu Phe Asp Glu Glu Phe Ser Gly Lys Glu 755 760 765 Leu Asp Ile Pro lie Asp Ser Ser Thr Val Glu Ile Lys Lys Val Ile 770 775 780 Lys Pro Glu Phe Glu Pro Val Pro Ser Val Ala Arg Asn Leu Val Ser 785 790 795 800 Gly Thr Ser Ser Tyr Pro Arg Asn Ser Arg Leu Glu Glu Gin Arg Lys 805 810 815 Glu Thr Ser Thr Ser Leu Ala Asp Asn Ser Lys Lys Gly Ser Ser Phe 820 825 830 Asn Glu Gly Asn Asn Glu Lys Glu Pro Asn Ala Ala Glu Trp Phe Lys 835 840 845 Ile Asp Glu Asn Arg His Leu Val Lys Asn Tyr Phe His Asp Leu Leu 850 855 860 Lys Tyr Ile Asn Asn Asn Asp Ala Thr Leu Ala Asn Asp Lys Asp Gly 865 870 875 880 Asp Leu Ala Phe Leu Ile Lys Gin Met Pro Ala Glu Glu Leu Asp Met 885 890 895 Thr Phe Asn Asn Trp Val Asn Leu Lys Val Gin Ser Ile Lys Arg Glu 900 905 910 Phe Ile Asp Asp Cys Asp Lys Lys Leu Asp Ile Leu Arg Arg Asp Tyr 915 920 925 Tyr Thr Ala Thr Asn Phe Ile Glu Thr Leu Glu Asp Asp Asn Gin Leu 930 935 940 Ile Asp Ile Ala Lys Lys Met Gly Ile Leu 945 950 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein Lys Asp Ile Lys Lys Thr Met Glu Glu Lys Ile Gin Thr Ser Gly 5 10 15

Claims: CLAIMS: 1. An isolated proteinaceous molecule or derivative of chemical analogue thereof capable of inhibiting an apoptotic response in cells to viral infection, said proteinaceous molecule comprising a cell-derived homologue of a viral inhibitor of apoptosis (IAP). 2. An isolated proteinaceous molecule according to claim 1 wherein said molecule is a homologue of baculovirus IAP. 3. An isolated proteinaceous molecule according to claim 2 wherein the baculovirus IAP inhibits apoptosis mediated by an interleukin - lβ converting enzyme (ICE) protease or death domain bearing protein FADD. 4. An isolated proteinaceous molecule according to claim 1 wherein the homologue is from an animal cell. 5. An isolated proteinaceous molecule according to claim 4 wherein the cell is from a mammal, nematode, yeast or insect. 6. An isolated proteinaceious molecule according to claim 5 having the amino acid sequence: Glu Xaa Xaa Arg Xaa Xaa Thr Phe Xaa Xaa Trp Pro [Xaa] m [Xaa] n Ala Xaa Ala Gly Phe [Xaa] 0 Asp Xaa [Xaa] p Xaa Cys Phe Xaa Cys Xaa Xaa Xaa Leu Xaa Xaa Tφ Xaa Xaa Xaa Asp Xaa Pro Xaa Xaa Xaa His Xaa Xaa Xaa Xaa Pro Xaa Cys Xaa [Xaa] q [Xaa] r wherein Xaa is an amino acid residue; [Xaa] m is a series of at least 5 and preferably at least 9 amino acids; [Xaa] n is Met or Leu; [Xaa]„ is a series of at least 3 and preferably at least 5 amino acids; [Xaa] p is Val or Ala; [Xaa]q is Phe or Tyr; [Xaa] r is Leu or Val; or a homologue, chemical analogue or derivative thereof. 7. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 2 or having at least 40% similarly thereto. 8. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 4 or having at least 40% similarly thereto. 9. An isolated proteinaceous molecule accordmg to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 6 or having at least 40% similarly thereto. 10. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 8 or having at least 40% similarly thereto. 11. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 11 or having at least 40% similarly thereto. 12. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 13 or having at least 40% similarly thereto. 13. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 15 or having at least 40% similarly thereto. 14. An isolated proteinaceous molecule according to claim 6 having an amino acid sequence substantially as set forth in SEQ ID NO: 17 or having at least 40% similarly thereto. 15. An isolated nucleic acid molecule encoding the proteinaceous molecule according to any one of claims 1 to 14. 16. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID NO: 2 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 2. 17. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID NO: 4 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 4. 18. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID No: 6 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 6. 19. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID No: 8 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 8. 20. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID No: 11 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 11. 21. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID No: 13 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 13. 22. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID No: 15 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 15. 23. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides encoding or complementary to a sequence encoding the amino acid sequence set forth in SEQ ID No: 17 or having at least 40% similarity to a nucleotide sequence encoding to amino acid sequence substantially set forth in SEQ ID NO: 17. 24. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set form in SEQ ID NO: 1 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 1 under low stringency conditions. 25. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 3 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 3 under low stringency conditions. 26. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 5 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 5 under low stringency conditions. 27. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 7 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 7 under low stringency conditions. 28. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 10 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 10 under low stringency conditions. 29. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 12 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 12 under low stringency conditions. 30. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 14 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 14 under low stringency conditions. 31. An isolated nucleic acid molecule according to claim 15 comprising a sequence of nucleotides substantially as set forth in SEQ ID NO: 16 or having at least 40% similarity thereto or is a nucleic acid molecule capable of hybridizing to SEQ ID NO: 16 under low stringency conditions. 32. A method for modulating cell apoptosis in an animal said method comprising administering to said animal a cell apoptosis modulating effective amount of a proteinaceous molecule or derivative or chemical analogue thereof according to any one of claims 1 to 14 for a time and under conditions sufficient for said cell apoptosis to be modulated. 33. A method according to claim 32 in the treatment of a degenerative disease, an infectious disease, cancer or an autoimmune disease. 34. A pharmaceutical composition comprising a proteinaceous molecule or a derivative or chemical analogue thereof according to any one of claims 1 to 14 and one or more pharmaceutical carriers and/or diluents. 35. Use of an animal cell homologue of an baculovirus IAP to modulate apoptosis in animals suffering from a degenerative disease, an infectious disease, cancer or an autoimmune disease. 36. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 2 or has at least about 40% similarity thereto. 37. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 4 or has at least about 40% similarity thereto. 38. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 6 or has at least about 40% similarity thereto. 39. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 8 or has at least about 40% similarity thereto. 40. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 11 or has at least about 40% similarity thereto. 41. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 13 or has at least about 40% similarity thereto. 42. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 15 or has at least about 40% similarity thereto. 43. Use according to claim 35 wherein the cell homologue comprises an amino acid sequence substantially as set forth in SEQ ID NO: 17 or has at least about 40% similarity thereto.

Inventors: VAUX DAVID LAURENCE, VAUX, DAVID, LAURENCE
Applicants: AMRAD OPERATIONS PTY LTD, VAUX DAVID LAURENCE, AMRAD OPERATIONS PTY. LTD., VAUX, DAVID, LAURENCE
Application year: 1996
Main classification: C07K14
IPC codes: A61K31, A61K38, A61P31, A61P35, A61P37, A61P43, C07K14, C12N15