25828, a novel human aminopeptidase and uses therefor
AssigneeMillennium Pharmaceuticals, Inc.
InventorsRajasekhar Bandaru, Aileen Healy
Life of this patent
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Abstract
The invention provides isolated nucleic acids molecules, designated 25828 nucleic acid molecules, which encode a novel aminopeptidase. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 25828 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a 25828 gene has been introduced or disrupted. The invention still further provides isolated 25828 proteins, fusion proteins, antigenic peptides and anti-25828 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.
Claims46
An isolated nucleic acid molecule selected from the group consisting of:
- a) a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to the nucleotide sequence of either of SEQ ID NOs:
- 1 and 3;
- b) a nucleic acid molecule comprising a fragment of at least 300 nucleotides of the nucleotide sequence of either of SEQ ID NOs:
- 1 and 3;
- c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2;
- d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:
- 2;
- and
- e) a nucleic acid molecule which encodes a naturally-occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2, wherein the nucleic acid molecule hybridizes with a nucleic acid molecule comprising one of SEQ ID NO:
- 1, SEQ ID NO:
- 3, and a complement of either of these, under stringent conditions.
An isolated polypeptide selected from the group consisting of:
- a) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of one of SEQ ID NO:
- 1, SEQ ID NO:
- 3, and a complement of either of these;
- b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes with a nucleic acid molecule comprising one of SEQ ID NO:
- 1, SEQ ID NO:
- 3, and a complement of either of these under stringent conditions;
- and
- c) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:
- 2.
A method of modulating the ability of a cell to catalyze cleavage of a polypeptide, the method comprising modulating the activity of 25828 protein in the cell, whereby the ability of the cell to catalyze cleavage of the polypeptide is modulated.
A method for assessing whether a test compound is useful for modulating at least one phenomenon selected from the group consisting of proliferation of hematopoietic cells, differentiation of hematopoietic cells, generation of erythrocytes from precursor cells, thrombosis, tumorigenesis, tumor cell proliferation, and intracellular conversion of a propeptide to an activated polypeptide, the method comprising:
- a) adding the test compound to a first composition comprising a polypeptide that has an amino acid sequence at least 90% identical to SEQ ID NO:
- 2 and that exhibits a 25828 activity;
- and
- b) comparing the 25828 activity in the first composition and in a second composition that is substantially identical to the first composition, except that it lacks the test compound,
- whereby a difference in the 25828 activity in the first and second compositions is an indication that the test compound is useful for modulating the phenomenon.
A method for assessing whether a test compound is useful for modulating at least one phenomenon selected from the group consisting of proliferation of hematopoietic cells, differentiation of hematopoietic cells, generation of erythrocytes from precursor cells, thrombosis, tumorigenesis, tumor cell proliferation, and intracellular conversion of a propeptide to an activated polypeptide, the method comprising:
- a) adding the test compound to a composition comprising a cell which comprises a nucleic acid that encodes a polypeptide that has an amino acid sequence at least 90% identical to SEQ ID NO:
- 2 and exhibits a 25828 activity;
- and
- b) comparing the 25828 activity in the first composition and in a second composition that is substantially identical to the first composition, except that it lacks the test compound,
- whereby a difference in the 25828 activity in the first and second compositions is an indication that the test compound is useful for modulating the phenomenon.
A method for identifying a compound useful for modulating at least one phenomenon selected from the group consisting of proliferation of hematopoietic cells, differentiation of hematopoietic cells, generation of erythrocytes from precursor cells, thrombosis, tumorigenesis, tumor cell proliferation, and intracellular conversion of a propeptide to an activated polypeptide, the method comprising:
- a) contacting the test compound and a polypeptide selected from the group consisting of
- i) a polypeptide which is encoded by a nucleic acid molecule comprising a portion having a nucleotide sequence which is at least 90% identical to one of SEQ ID NOs:
- 1 and 3;
- and
- ii) a fragment of a polypeptide having an amino acid sequence comprising SEQ ID NO:
- 2, wherein the fragment comprises at least 25 contiguous amino acid residues of SEQ ID NO:
- 2
- or a cell that expresses the polypeptide;
- and
- b) determining whether the polypeptide binds with the test compound,
- whereby binding of the polypeptide and the test compound is an indication that the test compound is useful for modulating the phenomenon.
Dependencies are inferred from the claim text.