PROSITE documentation PDOC50215ADAM type metalloprotease domain profile
ADAMs are transmembrane proteins containing both a disintegrin (see <PDOC00351>) and a metalloprotease domain [1]. About two third of the proteins with an ADAM type metalloprotease domain also contain the zinc protease pattern (see <PDOC00129>) which locates the active site of these proteases. As they contain an adhesion domain and a protease domain, ADAM proteins potentially have both cell adhesion and protease activities. They play a role in various biological processes, including fertilization, neurogenesis, myogenesis, embryonic TGF-α release and inflammatory response [2].
ADAMTS proteins [3] form a closely related family of proteases. In these proteins, the metalloprotease and disintegrin domains are flanked by thrombospondin type I (TSP1) repeat (see <PDOC50092>). ADAMTS proteins are soluble, extracellular matrix proteases those known substrates are other extracellular matrix proteins [2].
ADAM proteins also share the metalloprotease and disintegrin domains with the disintegrin class of peptides that are present in snake venom [2,4]. Together, they form the adamlysin/reprolysin subfamily of the metzincin superfamily of Zn-dependent metalloproteinases [4].
Some proteins known to contain an ADAM metalloprotease domain are listed below:
- Human ADAM 1 and 2 (fertilin α and β). Fertilins are sperm surface membrane proteins that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. They lack proteolytic activity.
- Human ADAM 8. It may be involved in immune function.
- Drosophila Kuzbanian. It is involved in neurogenesis. Kuzbanian is a sheddase that has been found to release a soluble form of Delta, a Notch ligand.
- Vertebrate ADAM 10, the homologue of Kuzbanian.
- Caenorhabditis elegans Sup-17, the homologue of Kuzbanian. It is involved in Lin-12/NOTCH signaling.
- Human ADAM 12 (meltrin α). It may be involved in myogenesis.
- Several snake venom metalloproteinases of the disintegrin family. They are not transmembrane proteins.
- Mammalian ADAMTS-1. Protease those expression is associated with acute inflammation as well as development of cancer cachexia.
December 2001 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Wolfsberg T.G. Straight P.D. Gerena R.L. Huovila A.P. Primakoff P. Myles D.G. White J.M. |
| Title | ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain. | |
| Source | Dev. Biol. 169:378-383(1995). | |
| PubMed ID | 7750654 |
| 2 | Authors | Primakoff P. Myles D.G. |
| Title | The ADAM gene family: surface proteins with adhesion and protease activity. | |
| Source | Trends Genet. 16:83-87(2000). | |
| PubMed ID | 10652535 |
| 3 | Authors | Tang B.L. Hong W. |
| Title | ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats. | |
| Source | FEBS Lett. 445:223-225(1999). | |
| PubMed ID | 10094461 |
| 4 | Authors | Black R.A. White J.M. |
| Title | ADAMs: focus on the protease domain. | |
| Source | Curr. Opin. Cell Biol. 10:654-659(1998). | |
| PubMed ID | 9818177 |
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