Nucleic acids encoding endotheliases, endotheliases and uses thereof
First Claim
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1. A substantially purified protein, consisting of a protease domain of an endotheliase protein that has catalytic activity, wherein:
- the protease domain of the endotheliase is selected from the group consisting of;
a) a polypeptide consisting of the sequence of amino acid residues set forth as amino acids 320-562 of SEQ ID No. 4;
b) a polypeptide consisting of the sequence of amino acid residues set forth as amino acids 320-688 of SEQ ID No. 6; and
c) a protease domain of an endotheliase protein consisting of a sequence of amino acid residues that has at least 95% sequence identity to the sequence of amino acids set forth as amino acid residues 320-562 in SEQ IN No. 4 or amino acid residues set forth as amino acid residues 320-688 of SEQ ID No.6.
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Abstract
Provided herein are endotheliases and portions, particularly, the protease domains, and nucleic acids that encode the endotheliases. The endotheliases are transmembrane proteases expressed in endothelial cells. The nucleic acids and encoded proteins and protease domain portions thereof are used in a variety of prognostic, diagnostic, therapeutic and screening methods, including methods for screening for compounds that modulate angiogenesis.
60 Citations
32 Claims
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1. A substantially purified protein, consisting of a protease domain of an endotheliase protein that has catalytic activity, wherein:
the protease domain of the endotheliase is selected from the group consisting of; a) a polypeptide consisting of the sequence of amino acid residues set forth as amino acids 320-562 of SEQ ID No. 4; b) a polypeptide consisting of the sequence of amino acid residues set forth as amino acids 320-688 of SEQ ID No. 6; and c) a protease domain of an endotheliase protein consisting of a sequence of amino acid residues that has at least 95% sequence identity to the sequence of amino acids set forth as amino acid residues 320-562 in SEQ IN No. 4 or amino acid residues set forth as amino acid residues 320-688 of SEQ ID No.6. - View Dependent Claims (4, 5, 8, 10, 11, 13, 15)
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2. An isolated substantially purified endotheliase 1 protease domain, consisting of the sequence of amino acid residues as set forth in SEQ ID No. 2 or the sequence of amino acid residues set forth as residues 190-422 of SEQ ID No. 27, wherein the isolated purified endotheliase 1 protease domain has protease activity.
- 3. A substantially purified protein, comprising an endotheliase protein, wherein the endotheliase protein is an endotheliase 2 that comprises the sequence of amino acid residues set forth in SEQ ID No. 4 or 6.
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6. A substantially purified endotheliase protein, comprising:
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the sequence of amino acids set forth in SEQ ID No. 4 or 6;
ora sequence of amino acid residues that has at least 95% sequence identity to the sequence of amino acids set forth as SEQ ID No. 4 or 6, wherein the endotheliase protein is catalytically active. - View Dependent Claims (7, 9, 12, 25)
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17. A substantially purified endotheliase 2 that is encoded by SEQ ID No. 3 or SEQ ID No. 5.
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18. A substantially purified endotheliase 2, comprising the sequence of amino acids set forth in SEQ ID No. 6 or consisting of amino acids 320-688 of SEQ ID No. 6.
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19. A substantially purified endotheliase 2, comprising the sequence of amino acids set forth in SEQ ID No. 4 or consisting of amino acids 320-562 of SEQ ID No. 4.
- 20. A substantially purified endotheliase that has at least about 97% sequence identity with a protein that comprises the sequence of amino acids set forth in SEQ ID No. 4 or 6, wherein the substantially purified endotheliase comprises a catalytic triad.
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22. An endotheliase protein, wherein the protease domain comprises the sequence of amino acids set forth in amino acids 321-562 of SEQ ID No. 4.
- 23. A substantially purified isolated polypeptide, consisting of an endotheliase protease domain that has at least 95% sequence identity with the sequence of amino acids set forth in SEQ ID No. 2 or amino acids 190-422 of SEQ ID No. 27 or a contiguous portion thereof that exhibits protease activity.
- 30. A substantially purified protein, comprising the sequence of amino acid residues set forth in SEQ ID NO. 4 or 6.
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32. A substantially purified protein, comprising the sequence of amino acid residues set forth in SEQ ID NO. 4.
Specification