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Description

Disintegrin and metalloproteinase domain-containing protein 17 (UniProt: P78536, also known as EC:3.4.24.86, ADAM 17, Snake venom-like protease, TNF-alpha convertase, TNF-alpha-converting enzyme, TACE, CD156b) is encoded by the ADAM17 (also known as CSVP, TACE) gene (Gene ID: 6868) in human. TACE is a membrane-bound metalloprotease responsible for solubilizing many pathologically significant membrane substrates. Mature ADAM-family ectodomains contain a globular metalloprotease catalytic domain, a disulfide-dependent disintegrin cysteine rich (Dis-Cys) domain, and, in some cases, an epidermal growth factor (EGF)-like domain. ADAM17 activity is regulated by multiple post-translational modifications. It has three phosphorylation sites on its C-terminal cytoplasmic domain (T735, S791, and (S819). ERK1/2-mediated T735 phosphorylation is reported to regulate ADAM17 maturation and surface expression. TACE displays a narrow endopeptidase specificity. It cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form and is also responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Clone D1(A12) exhibits high affinity (Kd = 0.46 nM) for the TACE ectodomain and is the most selectively potent cell-surface ADAM inhibitor. It can independently bind both the complete TACE ectodomain and the isolated catalytic domain (Kd = 5.21 nM). It is shown to be about 5-fold more potent than N-TIMP3 in inhibiting cell surface TACE. Mutations in ADAM17 gene are known to cause inflammatory skin and bowel disease, neonatal, 1 (NISBD1) that is characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut.