Follistatin-3
AssigneeHuman Genome Sciences, Inc.
InventorsD. Roxanne Duan, Steven M. Ruben
Life of this patent
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Abstract
The present invention relates to a novel follistatin-3 protein which is a member of the family of inhibin-related proteins. In particular, isolated nucleic acid molecules are provided encoding the human follistatin-3 protein. Follistatin-3 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of follistatin-3 activity. Also provided are diagnostic methods for detecting reproductive system-related disorders and disorders of the regulation of cell growth and differentiation and therapeutic methods for treating reproductive system-related disorders and disorders of the regulation of cell growth and differentiation.
Claims28
An isolated nucleic acid molecule nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding the follistatin-3 polypeptide having the complete amino acid sequence in SEQ ID NO:2 (i.e., positions −26 to 237 of SEQ ID NO:2);
- (b) a nucleotide sequence encoding the follistatin-3 polypeptide having the complete amino acid sequence in SEQ ID NO:2 excepting the N-terminal methionine (i.e., positions −25 to 237 of SEQ ID NO:2);
- (c) a nucleotide sequence encoding the predicted mature follistatin-3 polypeptide having the amino acid sequence at positions 1 to 237 in SEQ ID NO:2;
- (d) a nucleotide sequence encoding the follistatin-3 polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- (e) a nucleotide sequence encoding the follistatin-3 polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- (f) a nucleotide sequence encoding the mature follistatin-3 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- and
- (g) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e) or (f) above.
An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues n-237 of SEQ ID NO:2, where n is an integer in the range of -26-12;
- (b) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues −26-m of SEQ ID NO:2, where m is an integer in the range of −26-m of 207 to 237;
- (c) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n-m of SEQ ID NO:2, where n and m are integers as defined respectively in (a) and (b) above;
- and
- (d) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete follistatin-3 amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199 wherein said portion excludes from 1 to about 37 amino acids from the amino terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- (e) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete follistatin-3 amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199 wherein said portion excludes from 1 to about 20 amino acids from the carboxy terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- and
- (f) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete follistatin-3 amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199 wherein said portion include a combination of any of the amino terminal and carboxy terminal deletions in (d) and (e), above.
An isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) the amino acid sequence of the full-length follistatin-3 polypeptide having the complete amino acid sequence shown in SEQ ID NO:2 (i.e., positions −26 to 237 of SEQ ID NO:2);
- (b) the amino acid sequence of the full-length follistatin-3 polypeptide having the complete amino acid sequence shown in SEQ ID NO:2 excepting the N-terminal methionine (i.e., positions −25 to 237 of SEQ ID NO:2);
- (c) the amino acid sequence of the predicted mature follistatin-3 polypeptide having the amino acid sequence at positions 1 to 237 in SEQ ID NO:2;
- (d) the amino acid sequence of the full-length follistatin-3 polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- (e) the amino acid sequence of the full-length follistatin-3 polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209199;
- and
- (f) the amino acid sequence of the mature follistatin-3 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209199.
An isolated polypeptide comprising an epitope-bearing portion of the follistatin-3 protein, wherein said portion is selected from the group consisting of:
- a polypeptide comprising amino acid residues Leu-14 to Ala-20 of SEQ ID NO:2;
- a polypeptide comprising amino acid residues Ser-46 to Ile-55 of SEQ ID NO:2;
- a polypeptide comprising amino acid residues Gly-88 to Pro-97 of SEQ ID NO:2;
- a polypeptide comprising amino acid residues Gly-113 to Leu-133 of SEQ ID NO:2;
- a polypeptide comprising amino acid residues Arg-138 to Glu-146 of SEQ ID NO:2;
- a polypeptide comprising amino acid residues Pro-177 to Thr-191 of SEQ ID NO:2;
- and a polypeptide comprising amino acid residues Gly-219 to Val-237 of SEQ ID NO:2.
An isolated nucleic acid molecule comprising a polynucleotide having a sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) the nucleotide sequence of SEQ ID NO:4;
- (b) the nucleotide sequence of SEQ ID NO:5;
- (c) the nucleotide sequence of SEQ ID NO:6;
- (d) the nucleotide sequence of SEQ ID NO:7;
- (e) the nucleotide sequence of SEQ ID NO:8;
- (f) the nucleotide sequence of SEQ ID NO:9;
- (g) the nucleotide sequence of SEQ I. NO:
- 10;
- (h) the nucleotide sequence of SEQ ID NO:
- 11;
- (i) the nucleotide sequence of a portion of the sequence shown in FIGS. 1A, 1B, and 1C (SEQ ID NO:
- 1) wherein said portion comprises at least 50 contiguous nucleotides from nucleotide 1 to 500;
- and
- (J) the nucleotide sequence of a portion of the sequence shown in FIGS. 1A, 1B, and 1C (SEQ ID NO:
- 1) wherein said portion consists of nucleotides 100-500, 200-500, 300-500, 400-500, 100-400, 200-400, 300-400, 100-300, 200-300, 100-200, 100-2495, 250-2495, 500-2495, 1000-2495, 1500-2495, 2000-2495, 100-2000, 250-2000, 500-2000, 1000-2000, 1500-2000, 100-1500, 250-1500, 500-1500, 1000-1500, 100-1000, 250-1000, and 500-1000 of SEQ ID NO:1;
- and
- (k) a nucleotide sequence complementary to any of the nucleotide sequences in (a) through (j) above.
Dependencies are inferred from the claim text.