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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 [3]. 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:

• Some snake venom zinc metalloproteinases [4] consist of an N-terminal catalytic domain fused to a disintegrin domain. Such is the case for trimerelysin I (HR1B), atrolysin e (Ht-e) and trigramin. It has been suggested that these proteinases are able to cleave themselves from the disintegrin domains and that the latter may arise from such a post- translational processing.
• ADAM type metalloproteases (see <PDOC50215>).
• Mammalian epididymial protein 1 (EAP I) [6]. EAP I is associated with the sperm membrane and may play a role in sperm maturation. Structurally, EAP I consists of an N-terminal domain, followed by a zinc metalloproteinase domain, a disintegrin domain, and a large C-terminal domain that contains a transmembrane region.

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.

April 2006 / Pattern revised.

PROSITE methods (with tools and information) covered by this documentation:

DISINTEGRIN_2, PS50214; Disintegrin domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Domain architecture view of Swiss-Prot proteins matching PS50214 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50214 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50214 • Scan Swiss-Prot/TrEMBL entries against PS50214 • view ligand binding statistics

Matching PDB structures: 1FVL 1J2L 1L3X 1N4Y ... [ALL]

DISINTEGRIN_1, PS00427; Disintegrins signature  (PATTERN)

Consensus pattern: C-x(2)-[GS]-x-C-C-x(1,2)-[NQRSEKD]-C-x-[FMYLVI]-x(6)-C-[RKNQ] The 5 C's are involved in disulfide bonds Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00427 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00427 • Scan Swiss-Prot/TrEMBL entries against PS00427 • view ligand binding statistics

Matching PDB structures: 1FVL 1J2L 1L3X 1N4Y ... [ALL]

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).
	PubMed ID	2191722

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).
	PubMed ID	2320569

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.
	Source	Biochemistry 30:5225-5229(1991).
	PubMed ID	2036389

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).
	PubMed ID	1515064

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.
	Source	Nature 356:248-252(1992).
	PubMed ID	1552944
	DOI	10.1038/356248a0

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).
	PubMed ID	1417724

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