The domain within your query sequence starts at position 736 and ends at position 826; the E-value for the A2M domain shown below is 2.11e-33.



Alpha-2-macroglobulin family
SMART accession number:SM01360
Description: This family includes the C-terminal region of the alpha-2-macroglobulin family.
Interpro abstract (IPR001599):

This entry contains serum complement C3 and C4 precursors and alpha-macrogrobulins.

The alpha-macroglobulin (aM) family of proteins includes protease inhibitors [ (PUBMED:2473064) ], typified by the human tetrameric a2-macroglobulin (a2M); they belong to the MEROPS proteinase inhibitor family I39, clan IL. These protease inhibitors share several defining properties, which include (i) the ability to inhibit proteases from all catalytic classes, (ii) the presence of a 'bait region' and a thiol ester, (iii) a similar protease inhibitory mechanism and (iv) the inactivation of the inhibitory capacity by reaction of the thiol ester with small primary amines. aM protease inhibitors inhibit by steric hindrance [ (PUBMED:2472396) ]. The mechanism involves protease cleavage of the bait region, a segment of the aM that is particularly susceptible to proteolytic cleavage, which initiates a conformational change such that the aM collapses about the protease. In the resulting aM-protease complex, the active site of the protease is sterically shielded, thus substantially decreasing access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely (i) the h-cysteinyl-g-glutamyl thiol ester becomes highly reactive and (ii) a major conformational change exposes a conserved COOH-terminal receptor binding domain [ (PUBMED:2469470) ] (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation [ (PUBMED:2430968) ]. Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified [ (PUBMED:9914899) (PUBMED:10426429) ].

GO function:endopeptidase inhibitor activity (GO:0004866)
Family alignment:
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There are 15149 A2M domains in 15090 proteins in SMART's nrdb database.

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