Polynucleotides encoding a novel testis-specific tubulin tyrosine-ligase-like protein, BGS42
AssigneeBristol-Myers Squibb Company
InventorsJohn N. Feder, Thomas C. Nelson, Shujian Wu, Stanley R. Krystek
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Abstract
The present invention provides novel polynucleotides encoding BGS-42 polypeptides, fragments and homologues thereof Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel BGS-42 polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.
Claims23
An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence selected from the group consisting of:
- (a) a polynucleotide fragment of SEQ ID NO:1 or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No:
- PTA-4454, which is hybridizable to SEQ ID NO:1;
- (b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:2 or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No:
- PTA-4454, which is hybridizable to SEQ ID NO:1;
- (c) a polynucleotide encoding a polypeptide domain of SEQ ID NO:2 or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No:
- PTA-4454, which is hybridizable to SEQ ID NO:1;
- (d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:2 or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No:
- PTA-4454, which is hybridizable to SEQ ID NO:1;
- (e) a polynucleotide encoding a polypeptide of SEQ ID NO:2 or the cDNA sequence included in ATCC Deposit No:
- PTA-4454, which is hybridizable to SEQ ID NO:1, having tyrosine tubulin ligase activity;
- (f) a polynucleotide which is a variant of SEQ ID NO:1;
- (g) a polynucleotide which is an allelic variant of SEQ ID NO:1;
- (h) an isolated polynucleotide comprising nucleotides 156 to 1775 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 541 of SEQ ID NO:2 minus the start methionine;
- (i) an isolated polynucleotide comprising nucleotides 153 to 1775 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 541 of SEQ ID NO:2 including the start codon;
- (j) an isolated polynucleotide comprising nucleotides 369 to 1247 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 73 to 365 of SEQ ID NO:2 including the start codon;
- (k) an isolated polynucleotide comprising a polynucleotide that encodes at least 424 contiguous amino acids of SEQ ID NO:2;
- (l) an isolated polynucleotide comprising at least 1272 contiguous nucleotides of SEQ ID NO:1;
- (m) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:1;
- (n) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(m), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues;
- (o) a polynucleotide comprising the BGS-42 gene;
- (p) a polynucleotide comprising the BGS-42 promoter;
- and
- (q) a polynucleotide comprising the nucleotide sequence provided as SEQ ID NO:27.
An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
- (a) a polypeptide fragment of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No:
- PTA-4454;
- (b) a polypeptide fragment of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No:
- PTA-4454, having tyrosine tubulin ligase activity;
- (c) a polypeptide domain of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No:
- PTA-4454;
- (d) a polypeptide epitope of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No:
- PTA-4454;
- (e) a full length protein of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No:
- PTA-4454;
- (f) a polypeptide comprising amino acids 2 to 541 of SEQ ID NO:2, wherein said amino acids 2 to 541 comprising a polypeptide of SEQ ID NO:2 minus the start methionine;
- (g) a polypeptide comprising amino acids 1 to 541 of SEQ ID NO:2;
- (h) a polypeptide comprising amino acids 73 to 365 of SEQ ID NO:2;
- and
- (i) a polypeptide comprising at least 424 contiguous amino acids of SEQ ID NO:2.
An isolated nucleic acid molecule consisting of a polynucleotide having a nucleotide sequence selected from the group consisting of:
- (a) a polynucleotide encoding a polypeptide of SEQ ID NO:2;
- (b) an isolated polynucleotide consisting of nucleotides 156 to 1775 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 541 of SEQ ID NO:2 minus the start codon;
- (c) an isolated polynucleotide consisting of nucleotides 369 to 1247 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 73 to 365 of SEQ ID NO:2 including the start codon;
- (d) a polynucleotide encoding the BGS-42 polypeptide encoded by the cDNA clone contained in ATCC Deposit No. PTA-4454;
- (e) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:1;
- (f) an isolated polynucleotide consisting of a polynucleotide that encodes at least 424 contiguous amino acids of SEQ ID NO:2;
- (g) an isolated polynucleotide consisting of at least 1272 contiguous nucleotides of SEQ ID NO:1;
- (h) a polynucleotide consisting of the BGS-42 gene;
- (i) a polynucleotide consisting of the BGS-42 promoter;
- and
- (j) a polynucleotide comprising the nucleotide sequence provided as SEQ ID NO:27.
An isolated polypeptide consisting of an amino acid sequence selected from the group consisting of:
- (a) a polypeptide fragment of SEQ ID NO:2 having tyrosine tubulin ligase activity;
- (b) a polypeptide domain of SEQ ID NO:2 having tyrosine tubulin ligase activity;
- (c) a full length protein of SEQ ID NO:2;
- (d) a polypeptide corresponding to amino acids 2 to 541 of SEQ ID NO:2, wherein said amino acids 2 to 541 consisting of a polypeptide of SEQ ID NO:2 minus the start methionine;
- (e) a polypeptide corresponding to amino acids 1 to 541 of SEQ ID NO:2;
- (f) a polypeptide corresponding to amino acids 73 to 365 of SEQ ID NO:2;
- and
- (g) a polypeptide encoded by the cDNA contained in ATCC Deposit No. PTA-4454.
A computer for producing a three-dimensional representation of a molecule or molecular complex, wherein said molecule or molecular complex comprises the structural coordinates of the BGS-42 model provided in FIG. 13 in accordance with Table IV wherein said computer comprises:
- (a) A machine-readable data storage medium, comprising a data storage material encoded with machine readable data, wherein the data is defined by the set of structure coordinates of the model;
- (b) a working memory for storing instructions for processing said machine-readable data;
- (c) a central-processing unit coupled to said working memory and to said machine-readable data storage medium for processing said machine readable data into said three-dimensional representation;
- and
- (d) a display coupled to said central-processing unit for displaying said three-dimensional representation.
A method for identifying a mutant with altered biological properties, function, or activity of BGS-42 wherein said method comprises the steps of:
- (a) using a model of said polypeptide according to the structural coordinates of said model to identify amino acids to mutate;
- and
- (b) mutating said amino acids to create a mutant protein with altered biological function or properties.
A method for designing or selecting compounds as potential modulators of BGS-42 wherein said method comprises the steps of:
- (a) identifying a structural or chemical feature of said member using the structural coordinates of said member;
- and
- (b) rationally designing compounds that bind to said feature.
Dependencies are inferred from the claim text.