Disintegrin
Disintegrin | |||||||||
---|---|---|---|---|---|---|---|---|---|
OPM superfamily | 227 | ||||||||
OPM protein | 2ao7 | ||||||||
Membranome | 538 | ||||||||
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Disintegrins are a family of small
Operation
Disintegrins work by countering the
Types of disintegrin
Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin,[6] schistatin,[7] echistatin,[8] elegantin, eristicophin, flavoridin,[9] halysin, kistrin, mojastin (Crotalus scutulatus), rubistatin (Crotalus ruber), tergeminin, salmosin,[10] tzabcanin (Crotalus simus tzabcan)[11] and triflavin.
Disintegrins are split into 5 classes: small, medium, large, dimeric, and snake venom metalloproteinases.[12]
Small Disintegrins: 49-51 amino acids, 4 disulfide bonds
Medium Disintegrins: 70 amino acids, 6 disulfide bonds
Large Disintegrins: 84 amino acids, 7 disulfide bonds
Dimeric Disintegrins: 67 amino acids, 4 intra-chain disulfide bonds
Snake Venom Metalloproteinases: 100 amino acids, 8 disulfide bond
Evolution of disintegrin family
Disintegrins evolved via gene duplication of an ancestral protein family, the ADAM family. Small, medium, large, and dimeric disintegrin family are found only in the family Viperidae, suggesting duplication and diversification about 12-20 million years ago. Snake venom metalloproteinases are found through the entire superfamily Colubroidea, suggesting that they evolved before Colubroidea diversified roughly 60 million years ago.[13]
Other sources of disintegrin proteins
Disintegrin-like proteins are found in various species ranging from slime mold to humans. Some other proteins known to contain a disintegrin domain are:
- Some snake venom zinc metalloproteinases[14] 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 and ADAMTSprotein families, which include important protease enzymes.
- The secreted protease ADAMTS13, found in serum, cleaves Von Willebrand factor and acts as a natural, endogenous inhibitor of platelet adhesion and aggregation.
- ADAM2 (beta-fertilin, the beta-subunit of guinea pig sperm surface protein PH30).[15] PH30 is a protein involved in sperm-egg fusion. The beta subunit contains a disintegrin at the N-terminal extremity.
- ADAM7 (Mammalian epididymial apical protein 1, EAP I).[16] ADAM7 is associated with the sperm membrane and may play a role in sperm maturation. Structurally, ADAM7 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.
See also
- ADAM Protein
- Evolution of snake venom
References
- PMC 9185726.
- PMID 15578957.
- PMID 15974889.
- PMID 12050803.
- PMID 16918409.
- PMID 12742023.
- PMID 16101289.
- PMID 15535803.
- PMID 14499613.
- PMID 14661951.
- ^ Saviola, A.J., Modahl, C.M. and Mackessy, S.P., 2015. Disintegrins of Crotalus simus tzabcan venom: Isolation, characterization and evaluation of the cytotoxic and anti-adhesion activities of tzabcanin, a new RGD disintegrin. Biochimie, 116, pp.92-102. https://doi.org/10.1016/j.biochi.2015.07.005
- PMID 15777237.
- PMID 18701431.
- PMID 15962120.
- S2CID 4233338.
- PMID 1417724.
External links
- Disintegrins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)