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. Highest expression in liver, medium expression in ovary, heart and stomach. Low expression in lung, kidney and uterus. Protein found in plasma. Unlike the rat protein, which is an acute phase protein, this protein is always in circulation at high levels. Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.