Macroglobulin domain (IPR002890)

Short name: MG2

Overlapping homologous superfamilies


Domain relationships



The proteinase-binding alpha-macroglobulins (A2M) [PMID: 2473064] are large glycoproteins found in the plasma of vertebrates, in the hemolymph of some invertebrates and in reptilian and avian egg white. A2M-like proteins are able to inhibit all four classes of proteinases by a 'trapping' mechanism. They have a peptide stretch, called the 'bait region', which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein, thus trapping the proteinase. The entrapped enzyme remains active against low molecular weight substrates, whilst its activity toward larger substrates is greatly reduced, due to steric hindrance. Following cleavage in the bait region, a thiol ester bond, formed between the side chains of a cysteine and a glutamine, is cleaved and mediates the covalent binding of the A2M-like protein to the proteinase.

This entry represents the MG2 (macroglobulin) domain of alpha-2-macroglobulin [PMID: 16177781]. A2M-like proteins have been identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain is termed macroglobulin-like (MG) domain 2 and in Salmonella enterica ser A2Ms, this is domain 4 [PMID: 25221932, PMID: 22290936].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004866 endopeptidase inhibitor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.