A disintegrin and metalloproteinase domain 17 (ADAM17 (TACE))

A disintegrin and metalloproteinase domain 17 (ADAM17, also known as TACE) is a transmembrane enzyme of the ADAM family, containing multiple domains including a signal peptide, pro-domain, metalloprotease catalytic domain (which binds zinc), disintegrin domain, cysteine-rich domain, epidermal growth factor–like region, transmembrane domain, and a cytoplasmic tail[2][3][4][5]. It catalyzes the cleavage of membrane-anchored proteins, releasing their soluble extracellular domains; this is especially important for turning membrane-bound pro-TNF-α into soluble TNF-α, which is a key mediator in inflammation and immunity[1][2][4][5]. Beyond TNF-α, ADAM17 can process many substrates, including EGFR ligands, cell adhesion molecules, Notch receptors, and viral receptors such as ACE2. Its activity is tightly regulated by interactions with iRhoms and is implicated in cancer progression, chronic inflammatory and autoimmune diseases, tissue regeneration, and viral pathogenesis[3][4]. Therapeutic targeting of ADAM17 is complex due to its critical physiological functions and broad substrate range, raising safety concerns with systemic inhibition[3][4][5].

Other names

Tumor necrosis factor-α converting enzymeTACECD156bADA17MGC71956

Inhibition of proteolytic activity to block TNF-α and EGFR ligand release (neutralizing antibodies/biologics) Allosteric modulation via inhibitors targeting regulatory binding sites or partner interfaces (e.g. iRhom2 interaction) Zinc chelation in the active site