Polynucleotide encoding a novel human G-protein coupled receptor, HGPRBMY30

• US 20030166540A1
• Filed: 05/30/2002
• Published: 09/04/2003
• Est. Priority Date: 05/30/2001
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Mintier, Gabriel A., Feder, John N., Ramanathan, Chandra S.
• Application Number:
  US10/159,339
• Publication Number:
  US 20030166540A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748

Abstract

The present invention provides novel polynucleotides encoding HGPRBMY30 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 HGPRBMY30 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.

Claims

1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95.0% identical to a 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;

XXXXX, 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;

XXXXX, 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;

XXXXX, 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;

XXXXX, 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;

XXXXX, which is hybridizable to SEQ ID NO;

1, having G-protein coupled receptor activity;

(f) an isolated polynucleotide comprising nucleotides 4 to 2562 of SEQ ID NO;

1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 854 of SEQ ID NO;

2 minus the start codon;

(g) an isolated polynucleotide comprising nucleotides 1 to 2562 of SEQ ID NO;

1, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 854 of SEQ ID NO;

2 including the start codon;

(j) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO;

1; and

(k) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(j), 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.

2. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a human G-protein coupled receptor protein.

3. A recombinant vector comprising the isolated nucleic acid molecule of claim 1.

4. A recombinant host cell comprising the vector sequences of claim 3.

12. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:

(a) determining the presence or absence of a mutation in the polynucleotide of claim 1;

and

(b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.

5. An isolated polypeptide comprising an amino acid sequence at least 95.0% identical to a 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;

XXXXX;

(b) a polypeptide fragment of SEQ ID NO;

2 or the encoded sequence included in ATCC Deposit No;

XXXXX, having G-protein coupled receptor activity;

(c) a polypeptide domain of SEQ ID NO;

2 or the encoded sequence included in ATCC Deposit No;

XXXXX;

(d) a polypeptide epitope of SEQ ID NO;

2 or the encoded sequence included in ATCC Deposit No;

XXXXX;

(e) a full length protein of SEQ ID NO;

2 or the encoded sequence included in ATCC Deposit No;

XXXXX;

(f) a polypeptide comprising amino acids 2 to 854 of SEQ ID NO;

2, wherein said amino acids 2 to 854 comprise a polypeptide of SEQ ID NO;

2 minus the start methionine; and

(g) a polypeptide comprising amino acids 1 to 854 of SEQ ID NO;

2.

6. The isolated polypeptide of claim 5, wherein the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.

7. An isolated antibody that binds specifically to the isolated polypeptide of claim 5.

8. A recombinant host cell that expresses the isolated polypeptide of claim 5.

9. A method of making an isolated polypeptide comprising:

(a) culturing the recombinant host cell of claim 8 under conditions such that said polypeptide is expressed; and

(b) recovering said polypeptide.

10. The polypeptide produced by claim 9.

11. A method for preventing, treating, or ameliorating a medical condition, comprising the step of administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 5.

13. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:

(a) determining the presence or amount of expression of the polypeptide of claim 5 in a biological sample; and

(b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.

19. The method for preventing, treating, or ameliorating a medical condition of claim 11, wherein the medical condition is selected from the group consisting of an immune disorder;

a cardiovascular disorder;

an inflammatory disorder in which G-protein coupled receptors are either directly, or indirectly, associated with the disorder;

a metabolic disorder;

a reproductive disorder;

a male reproductive disorder;

testicular cancer;

a neural disorder;

an endocrine disorder;

gastrointestinal disorder;

a disorder associated with aberrant glutamate activity/regulation;

a gastrointestinal disorder associated with aberrant water, and/or bicarbonate regulation;

hypocalciuric hypercalcemia (FHH);

neonatal severe hyperparathyroidism (NSHPT);

autosomal dominant hypocalcemia (ADH);

autosomal dominant hypoparathyroidism (ADHP);

conditions related to aberrant calcium homeostasis;

hypercalcemia;

aberrant levels of PTH;

skeletal demineralization;

hypocalcemia;

hyperphosphatemia; and

parathyroid hyperplasia.

14. 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 4 to 2562 of SEQ ID NO;

1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 854 of SEQ ID NO;

2 minus the start codon;

(c) an isolated polynucleotide consisting of nucleotides 1 to 2562 of SEQ ID NO;

1, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 854 of SEQ ID NO;

2 including the start codon;

(d) a polynucleotide encoding the HGPRBMY30 polypeptide encoded by the cDNA clone contained in ATCC Deposit No. XXXXX; and

(e) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO;

1.

15. The isolated nucleic acid molecule of claim 14, wherein the polynucleotide comprises a nucleotide sequence encoding a human G-protein coupled receptor protein.

16. A recombinant vector comprising the isolated nucleic acid molecule of claim 15.

17. A recombinant host cell comprising the recombinant vector of claim 16.

18. 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 G-protein coupled receptor activity;

(b) a polypeptide domain of SEQ ID NO;

2 having G-protein coupled receptor activity;

(c) a full length protein of SEQ ID NO;

2;

(d) a polypeptide corresponding to amino acids 2 to 854 of SEQ ID NO;

2, wherein said amino acids 2 to 854 consisting of a polypeptide of SEQ ID NO;

2 minus the start methionine;

(e) a polypeptide corresponding to amino acids 1 to 854 of SEQ ID NO;

2; and

(f) a polypeptide encoded by the cDNA contained in ATCC Deposit No. XXXXX;