Alpha 2 Macroglobulin (A2M) Protein

Alpha-2-macroglobulin is a protease inhibitor and cytokine transporter. It inhibits many proteases, including trypsin, thrombin and collagenase. A2M is implicated in Alzheimer disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits. [provided by RefSeq, Jul 2008]

A2M: Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has 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 which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase. Belongs to the protease inhibitor I39 (alpha-2- macroglobulin) family.

Protein type: Inhibitor; Secreted; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 12p13.31

Cellular Component: extracellular region; cytosol

Molecular Function: serine-type endopeptidase inhibitor activity; protein binding; enzyme binding; protease binding; growth factor binding; interleukin-8 binding; interleukin-1 binding; calcium-dependent protein binding; tumor necrosis factor binding; receptor binding

Biological Process: negative regulation of complement activation, lectin pathway; extracellular matrix disassembly; platelet activation; regulation of small GTPase mediated signal transduction; extracellular matrix organization and biogenesis; platelet degranulation; small GTPase mediated signal transduction; stem cell differentiation; blood coagulation; blood coagulation, intrinsic pathway

Disease: Alzheimer Disease; Alpha-2-macroglobulin Deficiency