PMID:14688240

Citation	You, WK, Seo, HJ, Chung, KH and Kim, DS (2003) A novel metalloprotease from Gloydius halys venom induces endothelial cell apoptosis through its protease and disintegrin-like domains. J. Biochem. 134:739-49
Abstract	A novel hemorrhagic metalloprotease, halysase, isolated from the snake venom of Gloydius halys induces apoptosis in endothelial cells. The purified metalloprotease is a monomeric glycoprotein with an isoelectric point of 4.8. Analysis of the cDNA sequence encoding halysase revealed that the enzyme consists of multifunctional domains including a proprotein domain, a protease domain, a disintegrin-like domain and a cysteine-rich domain. The metalloprotease has a DECD sequence in the disintegrin-like domain instead of the typical RGD sequence. Halysase strongly inhibits proliferation of human umbilical vein endothelial cells in a dose-dependent manner as well as adhesion of the cells to extracellular matrix proteins. The enzyme specifically hydrolyzes not only extracellular matrix proteins such as fibronectin, vitronectin, and type IV collagen, but also integrins alpha1beta1 and alpha5beta1. The apoptosis of endothelial cells induced by halysase is closely associated with activation of caspase-3 and decreased level of Bcl-X(L)/Bax. Apohalysase, which lacks metalloprotease activity, is also able to induce the apoptosis. Several lines of experimental evidence suggest that the protease domain and the disintegrin-like domain of halysase cooperatively contribute to the induction of endothelial cell apoptosis.
Links	PubMed
Keywords	Amino Acid Sequence; Animals; Apoptosis/drug effects; Caspase 3; Caspases/metabolism; Cell Adhesion/drug effects; Cell Division/drug effects; Cloning, Molecular; Crotalid Venoms/enzymology; DNA, Complementary/genetics; Disintegrins/chemistry; Endopeptidases/chemistry; Endothelial Cells/cytology; Endothelial Cells/drug effects; Fibroblast Growth Factor 2/pharmacology; Humans; Integrins/metabolism; Metalloendopeptidases; Metalloproteases/chemistry; Metalloproteases/genetics; Metalloproteases/metabolism; Metalloproteases/pharmacology; Molecular Sequence Data; Protein Structure, Tertiary; Sequence Homology, Amino Acid
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
GLOHA:VMHA		GO:0072577: endothelial cell apoptosis	ECO:0000314:		P		Figure 7 shows endothelial cell apoptosis caused by halysase through fluorescence.	complete CACAO 4033

References

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