A disintegrin and metalloproteinase domain-containing protein 17 (ADAM17)

A disintegrin and metalloproteinase domain-containing protein 17 ("ADAM17", also known as TACE), is a membrane-bound zinc-dependent metalloprotease and member of the ADAM family. It acts as a sheddase, responsible for the regulated cleavage (ectodomain shedding) of a wide array of membrane-anchored proteins, including cytokines (e.g., TNF-α), growth factor ligands (e.g., amphiregulin, TGF-α), receptors, and adhesion molecules. ADAM17 plays a key role in inflammatory, immune, developmental, and regenerative processes. Dysregulated ADAM17 activity has been implicated in diseases such as cancer, inflammatory and cardiovascular disorders, and neurodegeneration. Its multi-domain structure includes a prodomain (regulates activation), a catalytic metalloprotease domain (containing the active site), a disintegrin domain (involved in cell adhesion), a cysteine-rich domain, a transmembrane region, and a cytoplasmic tail. Extensive research has sought to develop ADAM17 inhibitors; however, its broad physiological roles have presented significant therapeutic safety challenges[1][3][5][7].

Other names

Tumor necrosis factor-α-converting enzyme (TACE)CD156bCartilage snake venom-like proteasecSVPCSVPNISBDNISBD1TNF-α convertaseTNF-α convertase enzymeTNF-α converting enzymeADAM 17CD156BSnake venom-like protease

Inhibition of metalloprotease (zinc-dependent) activity, preventing cleavage/shedding of substrates such as pro-TNF-α, EGFR ligands and others. Modulation of inflammatory and growth factor signaling by blocking substrate release.