||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 (By similarity). Displays inhibitory activity against chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser extent, elastase but not trypsin. May play an important role during desquamation by inhibiting extracellular proteases.
|Gene References into Functions
- The functional assessment supported the pathogenicity of the RAF1 and RIT1 variants of unknown significance (VUSs), while the significance of two VUSs in A2ML1 remained unclear. PMID: 29402968
- The indigenous Filipino population has a ~50% prevalence of otitis media. A2ML1 genotype is the primary risk factor for otitis media and main determinant of disease progression, although age, the middle ear microbiome, and social clusters might modulate the effect of the A2ML1 genotype. PMID: 27484237
- A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome. PMID: 27799062
- Studies support a role for alpha-2-macroglobulin-like 1 protein (A2ML1) in the pathophysiology of otitis media. PMID: 26121085
- our results provide evidence that mutations in A2ML1 are a cause of Noonan-like syndrome, with a variable phenotype ranging from severe to very mild. PMID: 24939586
- a new class of target antigens in a paraneoplastic autoimmune multiorgan syndrome PMID: 20805888
- alpha2ML1 is the first alpha2macroglobulin family member detected in the epidermis, where it may play an important role during desquamation by inhibiting extracellular proteases. PMID: 16298998
- alpha2ML1 binding to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis PMID: 18648652
||Protease inhibitor I39 (alpha-2-macroglobulin) family
||In the epidermis, expressed predominantly in the granular layer at the apical edge of keratinocytes (at protein level). Also detected in placenta, testis and thymus but not in epithelia of kidney, lung, small intestine or colon.