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.