|PROSITE documentation PDOC00351 [for PROSITE entry PS50214]|
Disintegrins [1,2] are snake venom proteins which inhibit fibrinogen interaction with platelet receptors expressed on the glycoprotein IIb-IIIa complex. They act by binding to the integrin glycoprotein IIb-IIIa receptor on the platelet surface and inhibit aggregation induced by ADP, thrombin, platelet-activating factor and collagen.
Disintegrins are peptides of about 70 amino acid residues that contain many cysteines all involved in disulfide bonds . Disintegrins contain an Arg-Gly-Asp (RGD) sequence, a recognition site of many adhesion proteins. The RGD sequence of disintegrins is postulated to interact with the glycoprotein IIb-IIIa complex.
The sequences of disintegrins from different snake species are known. These proteins are known as: albolabrin, applagin, barbourin, batroxostatin, bitistatin, echistatin, elegantin, eristicophin, flavoridin, halysin, kistrin, tergeminin and triflavin.
Some other proteins are known to contain a disintegrin domain:
The schematic representation of the structure of a typical disintegrin domain is shown below:
+-----+ +-------------|-----|--+ +------------------+ | | | | | | xxxxxCxCxxxxxxCCxxxxCxxxxxxxCxxxxCCxxCxxxxxxxxCxxxRGDxxxxxCxxxxxxCxxxxxxx | | | | *****|************** | +-|-------|----+ +------------------------+ +-------+
'C': conserved cysteine involved in a disulfide bond. '*': position of the pattern.
Short disintegrins lack the N-terminal of the domain.
As a signature pattern for the disintegrin domain, we selected a conserved central region that contains five of the cysteines involved in disulfide bonds. A profile was also developed that spans the whole domain.Last update:
April 2006 / Pattern revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Williams J. Rucinski B. Holt J. Niewiarowski S.|
|Title||Elegantin and albolabrin purified peptides from viper venoms: homologies with the RGDS domain of fibrinogen and von Willebrand factor.|
|Source||Biochim. Biophys. Acta 1039:81-89(1990).|
|2||Authors||Dennis M.S. Henzel W.J. Pitti R.M. Lipari M.T. Napier M.A. Deisher T.A. Bunting S. Lazarus R.A.|
|Title||Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms: evidence for a family of platelet-aggregation inhibitors.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 87:2471-2475(1990).|
|3||Authors||Calvete J.J. Schafer W. Soszka T. Lu W.Q. Cook J.J. Jameson B.A. Niewiarowski S.|
|Title||Identification of the disulfide bond pattern in albolabrin, an RGD-containing peptide from the venom of Trimeresurus albolabris: significance for the expression of platelet aggregation inhibitory activity.|
|4||Authors||Hite L.A. Fox J.W. Bjarnason J.B.|
|Title||A new family of proteinases is defined by several snake venom metalloproteinases.|
|Source||Biol. Chem. Hoppe-Seyler 373:381-385(1992).|
|5||Authors||Blobel C.P. Wolfsberg T.G. Turck C.W. Myles D.G. Primakoff P. White J.M.|
|Title||A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion.|
|6||Authors||Perry A.C.F. Jones R. Barker P.J. Hall L.|
|Title||A mammalian epididymal protein with remarkable sequence similarity to snake venom haemorrhagic peptides.|
|Source||Biochem. J. 286:671-675(1992).|