Claims
- 1. 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-4175, 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-4175, 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-4175, 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-4175, 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-4175, which is hybridizable to SEQ ID NO:1, having calcium channel activity; (f) an isolated polynucleotide comprising nucleotides 4 to 4662 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1554 of SEQ ID NO:2 minus the start codon; (g) an isolated polynucleotide comprising nucleotides 1 to 4662 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1554 of SEQ ID NO:2 including the start codon; (h) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:1; (i) (a) a polynucleotide fragment of SEQ ID NO:3 or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:3; (j) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:4 or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:3; (k) a polynucleotide encoding a polypeptide domain of SEQ ID NO:4 or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:3; (l) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:4 or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:3; (m) a polynucleotide encoding a polypeptide of SEQ ID NO:4 or the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:3, having calcium channel activity; (n) an isolated polynucleotide comprising nucleotides 4 to 4698 of SEQ ID NO:3, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1566 of SEQ ID NO:4 minus the start codon; (o) an isolated polynucleotide comprising nucleotides 1 to 4698 of SEQ ID NO:3, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1566 of SEQ ID NO:4 including the start codon; (p) an isolated polynucleotide comprising nucleotides 1174 to 1212 of SEQ ID NO:3, wherein said nucleotides encode a polypeptide corresponding to amino acids 392 to 404 of SEQ ID NO:4; (q) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:3; (r) (a) a polynucleotide fragment of SEQ ID NO:5 or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:5; (s) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:6 or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:5; (t) a polynucleotide encoding a polypeptide domain of SEQ ID NO:6 or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:5; (u) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:6 or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:5; (v) a polynucleotide encoding a polypeptide of SEQ ID NO:6 or the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:5, having calcium channel activity; (w) an isolated polynucleotide comprising nucleotides 4 to 4698 of SEQ ID NO:5, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1566 of SEQ ID NO:6 minus the start codon; (x) an isolated polynucleotide comprising nucleotides 1 to 4698 of SEQ ID NO:5, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1566 of SEQ ID NO:6 including the start codon; (y) an isolated polynucleotide comprising nucleotides 2728 to 2766 of SEQ ID NO:5, wherein said nucleotides encode a polypeptide corresponding to amino acids 910 to 922 of SEQ ID NO:6; (z) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:5; (aa) (a) a polynucleotide fragment of SEQ ID NO:8 or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:8; (bb) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:9 or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:8; (cc) a polynucleotide encoding a polypeptide domain of SEQ ID NO:9 or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:8; (dd) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:9 or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:8; (ee) a polynucleotide encoding a polypeptide of SEQ ID NO:9 or the cDNA sequence included in ATCC Deposit No: PTA-4175, which is hybridizable to SEQ ID NO:8, having calcium channel activity; (ff) an isolated polynucleotide comprising nucleotides 4 to 4668 of SEQ ID NO:8, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1556 of SEQ ID NO:9 minus the start codon; (gg) an isolated polynucleotide comprising nucleotides 1 to 4668 of SEQ ID NO:8, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1556 of SEQ ID NO:9 including the start codon; (hh) an isolated polynucleotide comprising nucleotides 1174 to 1212 of SEQ ID NO:8, wherein said nucleotides encode a polypeptide corresponding to amino acids 392 to 404 of SEQ ID NO:9; (ii) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:8; and (jj) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(h), 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 consists of a nucleotide sequence encoding a human transient receptor potential channel.
- 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.
- 5. 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-4175; (b) a polypeptide fragment of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No: PTA-4175, having calcium channel activity; (c) a polypeptide domain of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No: PTA-4175; (d) a polypeptide epitope of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No: PTA-4175; (e) a full length protein of SEQ ID NO:2 or the encoded sequence included in ATCC Deposit No: PTA-4175; (f) a polypeptide comprising amino acids 2 to 1554 of SEQ ID NO:2, wherein said amino acids 2 to 1554 comprising a polypeptide of SEQ ID NO:2 minus the start methionine; (g) a polypeptide comprising amino acids 1 to 1554 of SEQ ID NO:2; (h) a polypeptide fragment of SEQ ID NO:4 or the encoded sequence included in ATCC Deposit No: PTA-4175; (i) a polypeptide fragment of SEQ ID NO:4 or the encoded sequence included in ATCC Deposit No: PTA-4175, having calcium channel activity; (j) a polypeptide domain of SEQ ID NO:4 or the encoded sequence included in ATCC Deposit No: PTA-4175; (k) a polypeptide epitope of SEQ ID NO:4 or the encoded sequence included in ATCC Deposit No: PTA-4175; (l) a full length protein of SEQ ID NO:4 or the encoded sequence included in ATCC Deposit No: PTA-4175; (m) a polypeptide comprising amino acids 2 to 1566 of SEQ ID NO:4, wherein said amino acids 2 to 1566 comprising a polypeptide of SEQ ID NO:4 minus the start methionine; (n) a polypeptide comprising amino acids 1 to 1566 of SEQ ID NO:4; (o) a polypeptide comprising amino acids 392 to 404 of SEQ ID NO:4; (p) a polypeptide fragment of SEQ ID NO:6 or the encoded sequence included in ATCC Deposit No: PTA-4175; (q) a polypeptide fragment of SEQ ID NO:6 or the encoded sequence included in ATCC Deposit No: PTA-4175, having calcium channel activity; (r) a polypeptide domain of SEQ ID NO:6 or the encoded sequence included in ATCC Deposit No: PTA-4175; (s) a polypeptide epitope of SEQ ID NO:6 or the encoded sequence included in ATCC Deposit No: PTA-4175; (t) a full length protein of SEQ ID NO:6 or the encoded sequence included in ATCC Deposit No: PTA-4175; (u) a polypeptide comprising amino acids 2 to 1566 of SEQ ID NO:6, wherein said amino acids 2 to 1566 comprising a polypeptide of SEQ ID NO:6 minus the start methionine; (v) a polypeptide comprising amino acids 1 to 1566 of SEQ ID NO:6; (w) a polypeptide comprising amino acids 910 to 922 of SEQ ID NO:6; (x) a polypeptide fragment of SEQ ID NO:9 or the encoded sequence included in ATCC Deposit No: PTA-4175; (y) a polypeptide fragment of SEQ ID NO:9 or the encoded sequence included in ATCC Deposit No: PTA-4175, having calcium channel activity; (z) a polypeptide domain of SEQ ID NO:9 or the encoded sequence included in ATCC Deposit No: PTA-4175; (aa) a polypeptide epitope of SEQ ID NO:9 or the encoded sequence included in ATCC Deposit No: PTA-4175; (bb) a full length protein of SEQ ID NO:9 or the encoded sequence included in ATCC Deposit No: PTA-4175; (cc) a polypeptide comprising amino acids 2 to 1556 of SEQ ID NO:9, wherein said amino acids 2 to 1556 comprising a polypeptide of SEQ ID NO:9 minus the start methionine; (dd) a polypeptide comprising amino acids 1 to 1556 of SEQ ID NO:9; and (ec) a polypeptide comprising amino acids 392 to 404 of SEQ ID NO:9.
- 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, or a modulator thereof.
- 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.
- 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.
- 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 4662 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1554 of SEQ ID NO:2 minus the start codon; (c) an isolated polynucleotide consisting of nucleotides 1 to 4662 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1554 of SEQ ID NO:2 including the start codon; (d) a polynucleotide encoding the LTRPC3 polypeptide encoded by the cDNA clone contained in ATCC Deposit No. PTA-4175; (e) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:1; (f) a polynucleotide encoding a polypeptide of SEQ ID NO:4; (g) an isolated polynucleotide consisting of nucleotides 4 to 4698 of SEQ ID NO:3, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1566 of SEQ ID NO:4 minus the start codon; (h) an isolated polynucleotide consisting of nucleotides 1 to 4698 of SEQ ID NO:3, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1566 of SEQ ID NO:4 including the start codon; (i) a polynucleotide encoding the LTRPC3b polypeptide encoded by the cDNA clone contained in ATCC Deposit No. PTA-4175; (j) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:3; (k) an isolated polynucleotide consisting of nucleotides 1174 to 1212 of SEQ ID NO:3, wherein said nucleotides encode a polypeptide corresponding to amino acids 392 to 404 of SEQ ID NO:4; (l) a polynucleotide encoding a polypeptide of SEQ ID NO:6; (m) an isolated polynucleotide consisting of nucleotides 4 to 4698 of SEQ ID NO:5, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1566 of SEQ ID NO:6 minus the start codon; (n) an isolated polynucleotide consisting of nucleotides 1 to 4698 of SEQ ID NO:5, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1566 of SEQ ID NO:6 including the start codon; (o) a polynucleotide encoding the LTRPC3c polypeptide encoded by the cDNA clone contained in ATCC Deposit No. PTA-4175; (p) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:5; (q) an isolated polynucleotide consisting of nucleotides 2728 to 2766 of SEQ ID NO:5, wherein said nucleotides encode a polypeptide corresponding to amino acids 910 to 922 of SEQ ID NO:6; (r) a polynucleotide encoding a polypeptide of SEQ ID NO:9; (s) an isolated polynucleotide consisting of nucleotides 4 to 4668 of SEQ ID NO:8, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 1556 of SEQ ID NO:9 minus the start codon; (t) an isolated polynucleotide consisting of nucleotides 1 to 4668 of SEQ ID NO:8, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 1556 of SEQ ID NO:9 including the start codon; (u) a polynucleotide encoding the LTRPC3e polypeptide encoded by the cDNA clone contained in ATCC Deposit No. PTA-4175; (v) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:8; and (w) an isolated polynucleotide consisting of nucleotides 1174 to 1212 of SEQ ID NO:8, wherein said nucleotides encode a polypeptide corresponding to amino acids 392 to 404 of SEQ ID NO:9.
- 15. The isolated nucleic acid molecule of claim 14, wherein the polynucleotide comprises a nucleotide sequence encoding a human transient receptor potential channel.
- 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 calcium channel activity; (b) a polypeptide domain of SEQ ID NO:2 having calcium channel activity; (c) a full length protein of SEQ ID NO:2; (d) a polypeptide corresponding to amino acids 2 to 1554 of SEQ ID NO:2, wherein said amino acids 2 to 1554 consisting of a polypeptide of SEQ ID NO:2 minus the start methionine; (e) a polypeptide corresponding to amino acids 1 to 1554 of SEQ ID NO:2; (f) a polypeptide encoded by the cDNA contained in ATCC Deposit No. PTA-4175; (g) a polypeptide fragment of SEQ ID NO:4 having calcium channel activity; (h) a polypeptide domain of SEQ ID NO:4 having calcium channel activity; (i) a full length protein of SEQ ID NO:4; a polypeptide corresponding to amino acids 2 to 1566 of SEQ ID NO:4, wherein said amino acids 2 to 1566 consisting of a polypeptide of SEQ ID NO:4 minus the start methionine; (k) a polypeptide corresponding to amino acids 1 to 1566 of SEQ ID NO:4; (l) a polypeptide encoded by the cDNA contained in ATCC Deposit No. PTA-4175; (m) a polypeptide consisting of amino acids 392 to 404 of SEQ ID NO:4; (n) a polypeptide fragment of SEQ ID NO:6 having calcium channel activity; (o) a polypeptide domain of SEQ ID NO:6 having calcium channel activity; (p) a full length protein of SEQ ID NO:6; (q) a polypeptide corresponding to amino acids 2 to 1566 of SEQ ID NO:6, wherein said amino acids 2 to 1566 consisting of a polypeptide of SEQ ID NO:6 minus the start methionine; (r) a polypeptide corresponding to amino acids 1 to 1566 of SEQ ID NO:6; (s) a polypeptide encoded by the cDNA contained in ATCC Deposit No. PTA-4175; (t) a polypeptide consisting of amino acids 910 to 922 of SEQ ID NO:6; (u) a polypeptide fragment of SEQ ID NO:9 having calcium channel activity; (v) a polypeptide domain of SEQ ID NO:9 having calcium channel activity; (w) a full length protein of SEQ ID NO:9; (x) a polypeptide corresponding to amino acids 2 to 1556 of SEQ ID NO:9, wherein said amino acids 2 to 1556 consisting of a polypeptide of SEQ ID NO:9 minus the start methionine; (y) a polypeptide corresponding to amino acids 1 to 1556 of SEQ ID NO:9; (z) a polypeptide encoded by the cDNA contained in ATCC Deposit No. PTA-4175; and (aa) a polypeptide consisting of amino acids 392 to 404 of SEQ ID NO:9.
- 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 a renal disorder; a disorder related to aberrant calcium regulation; a reproductive disorder; a neural disorder; cerebellum disorders; various choroid plexus neoplasms; choroid plexus papilloma; Alzheimer's disease; prion disorders; multiple sclerosis; movement disorders that involve the cerebellum; a proliferative kidney or renal disorder; solitary metastasis of the kidney; renal cell carcinoma; ovarian cancer or related proliferative condition of the ovary; testicular cancer or related proliferative condition of the testis; kidney cancer or related proliferative condition of the kidney; a disorder that maps to or is associated with chromosome locus 9q21.11-21.31; amyotrophic lateral sclerosis with frontotemporal dementia; early-onset pulverulent cataract; infantile nephronophthisis; hypomagnesemia with secondary hypocalcemia and/or familial hemophagocytic lymphohistiocytosis; a disorder associated with disturbances in Ca2+ homeostasis including osteoporosis; hypercalciuric stone disease; chronic renal failure; a condition that would benefit from modulation of intracellular Ca++ ion concentrations; a condition that would benefit from modulation of Ca++ ion flux; a condition that would benefit from modulation of stored intracellular Ca++ ion concentrations; a condition that would benefit from modulation of Ca++ ion pump activity; a condition that would benefit from modulation of Ca++ ion flow into a cell; a condition that would benefit from modulation of Ca++ ion flow out of cells; a condition that would benefit from activation of Ca++ senstive proteins; a condition that would benefit from the activation of Ca++ senstive signaling pathways; the activation of kinase-activatible proteins; a condition that would benefit from the activation of kinase-dependent signaling pathways; DNA-repair deficiencies, particularly base-excision repair deficiencies; Xeroderma pigmentosum; skin cancer; melanoma; UV senstivity; alkylation sensivity; gamma irradiation sensitivity; pyrimidine dimer sensitivity; chemical mutagenesis; lymphomas, leukemias; photosensitivity; Bloom's syndrone; Fanconi's anemia; ataxia telangiectasia; chromosomal aberrations; blood vessel dilation aberrations in the skin; blood vessel dilation aberrations in the eye; conditions involving increased levels of apurinic sites; conditions involving increased levels of apyrimidinic sites; conditions involving increased levels of abasic sites; disorders related to aberrant signal transduction; proliferating disorders; cancers; a disorder related to misregulation of FEN1 expression or activity; a disorder that would benefit from increasing mammalian base excision repair activity; increasing mammalian single-nucleotide base excision repair activity; and increasing mammalian long patch base excision repair activity.
- 20. The method of diagnosing a pathological condition of claim 13 wherein the pathological condition is a member of the group consisting of: a proliferative disorder, ovarian cancer, testicular cancer, and kidney cancer.
- 21. A method of increasing the expression of FEN1 in human cells or tissues comprising contacting said cells or tissues in vitro with an antisense compound that specifically hybridizes to a nucleic acid molecule encoding the human LTRPC3 polypeptide having the sequence set forth in SEQ ID NO:2 so that expression of the LTRPC3 polypeptide is inhibited.
Parent Case Info
[0001] This application claims benefit to provisional application U.S. Serial No. 60/309,544 filed Aug. 2, 2001. The entire teachings of the referenced application are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60309544 |
Aug 2001 |
US |