ADAM, is a disintegrin and metalloproteinase, also name metalloprotease-disintegrins, which is Metalloprotease belongs to the zinc protease superfamily. Most of ADAMs have a modular design, characterized by the presence of metalloprotease and integrin receptor-binding activities, and a cytoplasmic domain that in many family members specifies binding sites for various signal transducing proteins. ADAM is often also referred to as the MDC family, indicating the presence of metalloprotease, disintegrin, and cysteine-rich domains.
ADAMs are implicated in a variety of cellular processes, including processing of proteins, interactions with integrin receptors and with signaling molecules. The ADAMs family has been regulated in the control of membrane fusion, cytokine and growth factor shedding, and cell migration, as well as processes such as muscle development, fertilization, and cell fate determination.
ADAM proteins are able to mediate cell adhesion through their disintegrin domain and selective protein cleavage (e.g. ectodomain shedding) carried out by the metalloprotease domain. ADAM12 is an important sheddase, expressed widely in different tissues. ADAM12 has been associated with e.g. regulation of muscle and adipose tissue differentiation, cell fusion, cell adhesion, and EGFR-ligand activation.
ADAM have been implicated in a variety of human disease processes. For example, tumor cells are known to use matrix metalloproteases to promote their growth and metastasis. Members of the ADAM-TS family are associated with the breakdown of aggrecan seen in osteoarthritis. ADAM17 plays a major role in the development of a variety of inflammatory processes by regulating the shedding of TNF.
|ADAMs (A Disintegrin and Metalloprotease)|
|ADAMTSs (ADAM metalloprotease with ThromboSpondin type 1 motif)|