ADAM-9

ADAM9, also known as MDC9 or meltrin γ, is a member of the ADAM family that contains a disintegrin and metalloprotease-like domain. Like other membrane-anchored ADAMs, ADAM9 consists of a pro domain with a cysteine switch and furin cleavage sequence, a catalytic domain with the zinc-binding site and Metturn expected for reprolysins, a disintegrin like domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and the cytoplasmic domain. ADAM9 is able to cleave peptides corresponding to cleavage sites of tumor necrosis factorα (TNFα), the p75 TNF receptor, the β-amyloid protein precursor, and the c-kit ligand1, implying that it may participate in shedding of these membrane proteins. In fact, ADAM9 has been shown to shed membrane-anchored heparin-binding EGF-like growth factor. In addition, it also cleaves oxidized insulin B-chain and fibronectin. Besides its catalytic activity, ADAM9 functions as an adhesion molelcule through binding of its disintegrin domain to integrins such as αvβ5 and α6β1. The cytoplasmic domain of ADAM9 interacts with Src homology 3 (SH3) containing proteins and protein kinase C, and may mediate different signaling pathways. ADAM9 is widely expressed in tissues.