Anti-ADAM17 (human) (blocking), clone D1(A12)

Protein function: Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. 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. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2. [The UniProt Consortium] This cross-domain human antibody is a selective ADAM17 (TACE) antagonist and provides a unique alternative to small molecule metalloprotease inhibition. ADAM multidomain topology was exploited by first isolating an inhibitory human antibody (D1) that bound ADAM17-specific non-catalytic regions exclusively through its variable heavy (VH) domain. A D1-VH biased scFv phage-display library was then used to selectively isolate a new variable light (VL) chain that could simultaneously bind to the ADAM17 catalytic domain.