Novel member of the lysyl oxidase gene family
AssigneeWyeth
InventorsMark J. Evans, Marshall S. Scicchitano, Ashok R. Bapat, Eric Beer, Ramesh A. Bhat, Elissa Ferris, Robert Mastroeni, Jianxiong Zhang, Sotirios K. Karathanasis
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Abstract
The present invention relates to a novel lysyl oxidase genes, termed EER-7. The invention relates to the protein and nucleic acids encoding the protein. The invention further relates to an assay system to identify compounds that selectively modulate EER-7 protein activity by interaction with estrogen receptors.
Claims57
An isolated EER-7 protein having an amino acid sequence comprising at least 10 contiguous amino acids from the sequence depicted in SEQ ID NO:2 or which has at least 60% sequence similarity with SEQ ID NO:2, which EER-7 protein has (i) lysyl oxidase activity;
- (ii) comprises four copies of a SRCR domain having a sequence greater than 80% similar to a sequence selected from the group consisting of SEQ ID NOs:
- 3, 4, 5, and 6;
- and (iii) comprises a conserved catalytic domain of lysyl oxidase enzymes having a sequence as depicted inSEQ ID NO:7.
A polypeptide fragment of an EER-7 protein, wherein the fragment has a property selected from the group consisting of:
- a) comprising from one to four copies of a SRCR domain having a sequence greater than 80% similar to a sequence selected from the group consisting of SEQ ID Nos:
- 3, 4, 5, and 6;
- b) a conserved catalytic domains of lysyl oxidase enzymes having a sequence as depicted in SEQ ID NO:
- 7;
- c) specific binding activity with an anti-EER-7 antibody;
- and
- d) any combination thereof.
A vector comprising a nucleic acid encoding a fragment of an EER-7 protein operatively associated with an expression control sequence, wherein the fragment has a property selected from the group consisting of:
- a) comprising from one to four copies of a SRCR domain having a sequence greater than 80% similar to a sequence selected from the group consisting of SEQ ID Nos:
- 3, 4, 5, and 6;
- b) a conserved catalytic domains of lysyl oxidase enzymes having a sequence as depicted in SEQ ID NO:
- 7;
- c) specific binding activity with an anti-EER-7 antibody;
- and
- d) any combination thereof.
An isolated nucleic acid of at least 20 bases that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence as depicted in SEQ ID NO:
- 1.
A method for detecting expression of EER-7, which method comprises detecting mRNA encoding EER-7 in a sample from a cell suspected of expressing EER-7.
An assay system for identifying selective estrogen receptor ligands, comprising transformed cells that express different functional estrogen receptors, wherein the number of cells is sufficient to transcribe a detectable amount of mRNA encoding EER-7.
A non-human EER-7 knockout animal, wherein endogenous EER-7 expression is suppressed in the animal.
A non-human animal transformed with a vector comprising a nucleic acid encoding a protein that regulates EER-7 expression, wherein the protein is operatively associated with an expression control sequence;
- wherein the animal expresses an EER-7 protein at a detectable level in response to estrogen.
An isolated polypeptide selected from the group consisting of:
- a) 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;
- b) an 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 consisting of SEQ ID NO:
- 1 under stringent conditions;
- c) 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 SEQ ID NO:
- 1;
- d) a polypeptide comprising an amino acid sequence which is at least 60% identical to the amino acid sequence of SEQ ID NO:
- 2.
Dependencies are inferred from the claim text.