Novel molecules of the PYRIN/NBS/LRR protein family and uses thereof
AssigneeMillennium Pharmaceuticals, Inc.
InventorJohn Bertin
Life of this patent
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Abstract
Novel PYRIN-9 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated PYRIN-9 proteins, the invention further provides PYRIN-9 fusion proteins, antigenic peptides and anti-PYRIN-9 antibodies. The invention also provides PYRIN-9 nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a PYRIN-9 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.
Claims28
An isolated nucleic acid molecule selected from the group consisting of:
- a) a nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:1;
- b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
- c) a nucleic acid molecule which encodes a polypeptide fragment comprising at least 25 amino acids of the amino acid sequence of SEQ ID NO:2, wherein the fragment has at least one biological activity of PYRIN-9;
- d) nucleic acid molecule comprising at least 75 contiguous nucleotides of SEQ ID NO:1, wherein the nucleic acid molecule encodes a polypeptide which has at least one biological activity of PYRIN-9;
- 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 to a nucleic acid molecule comprising SEQ ID NO:1, or a complement thereof, under stringent conditions and the variant has at least one biological activity of PYRIN-9.
An isolated polypeptide selected from the group consisting of:
- a) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:1, or a complement thereof;
- b) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;
- c) 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 to a nucleic acid molecule comprising SEQ ID NO:1, or a complement thereof under stringent conditions and the variant has at least one biological activity of PYRIN-9;
- d) a polypeptide comprising the amino acid sequence of SEQ ID NO:2 wherein up to 10 amino acids are replaced by conservative substitutions;
- and
- e) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 25 contiguous amino acids of SEQ ID NO:2, and the fragment has at least one biological activity of PYRIN-9.
A method for identifying a candidate compound which modulates the CARD-5-mediated activation of NF-κB, the method comprising:
- a) measuring the binding of a first polypeptide comprising the pyrin domain of CARD-5 to a second polypeptide comprising the pyrin domain of PYRIN-9 in the presence of a test compound;
- and
- b) comparing the binding of the first polypeptide to the second polypeptide measured in step (a) to the binding of the first polypeptide to the second polypeptide in the absence of the test compound,
- wherein altered binding of the first polypeptide to the second polypeptide in the presence of the test compound compared the binding in the absence of the test compound indicates that the test compound is candidate compound for modulating the ASC-mediated activation of NF-κB.
Dependencies are inferred from the claim text.