Alpha-2-macroglobulin-like protein 1 (A2ML1)

Alpha-2-macroglobulin-like protein 1 (A2ML1) is a secreted, N-glycosylated, monomeric member of the alpha-macroglobulin superfamily, primarily functioning as a broad-spectrum protease inhibitor[1][2]. Its inhibitory mechanism involves a unique 'trapping' process: a protease cleaves a specific 'bait region' on A2ML1, triggering a conformational change that covalently traps the protease and sterically hinders access to large substrates[1][2]. A2ML1 can inhibit several proteases including chymotrypsin, papain, thermolysin, subtilisin A, and human neutrophil elastase, but not trypsin[1][2]. It plays a suspected physiological role in regulating extracellular proteases during epidermal processes such as keratinocyte differentiation and desquamation[1]. A2ML1 is implicated in disease states, notably acting as the p170 antigen in paraneoplastic pemphigus and reported in certain cases of otitis media and Noonan syndrome[2]. Although it is not generally regarded as a direct therapeutic target, its clinical significance lies mainly in immune-mediated or proteolytic disease contexts.

Other names

Alpha-2-macroglobulin like 1CPAMD9FLJ25179p170C3 and PZP-like alpha-2-macroglobulin domain-containing protein 9OMSp170 antigenC3 and PZP-like, alpha-2-macroglobulin domain containing 9

Protease trapping via bait region cleavage and thioester bond formation