alpha-2-macroglobulin-like protein 1 (C3 & PZP-like alpha-2-macroglobulin domain-containing protein 9, A2ML1, CPAMD9)

Function: - able to inhibit all 4 classes of proteinases by a unique 'trapping' mechanism - 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 diminished) - following cleavage in the bait region a thioester bond is hydrolyzed & mediates the covalent binding of the protein to the proteinase (putative) - 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 Structure: - monomer - belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family Compartment: secreted Expression: - in epidermis, expressed predominantly in the granular layer at the apical edge of keratinocytes (at protein level) - also detected in placenta, testis & thymus but not in epithelia of kidney, lung, small intestine or colon - up-regulated during keratinocyte differentiation

General

glycoprotein secreted protein

Properties

SIZE: entity length = 1454 aa MW = 161 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-17} cysteine residue {C40} MODIFICATION: cysteine residue {C78} cysteine residue {C78} MODIFICATION: cysteine residue {C40} N-glycosylation site {N120} cysteine residue {C241} MODIFICATION: cysteine residue {C291} cysteine residue {C259} MODIFICATION: cysteine residue {C279} cysteine residue {C279} MODIFICATION: cysteine residue {C259} N-glycosylation site {N281} cysteine residue {C291} MODIFICATION: cysteine residue {C241} N-glycosylation site {N409} cysteine residue {C464} MODIFICATION: cysteine residue {C557} cysteine residue {C557} MODIFICATION: cysteine residue {C464} cysteine residue {C589} MODIFICATION: cysteine residue {C769} Bait region {695-726} cysteine residue {C769} MODIFICATION: cysteine residue {C589} cysteine residue {C819} MODIFICATION: cysteine residue {C847} cysteine residue {C845} MODIFICATION: cysteine residue {C881} cysteine residue {C847} MODIFICATION: cysteine residue {C819} N-glycosylation site {N857} cysteine residue {C881} MODIFICATION: cysteine residue {C845} cysteine residue {C919} MODIFICATION: cysteine residue {C1307} N-glycosylation site {N1020} cysteine residue {C1075} MODIFICATION: cysteine residue {C1123} cysteine residue {C1123} MODIFICATION: cysteine residue {C1075} cysteine residue {C1307} MODIFICATION: cysteine residue {C919} cysteine residue {C1338} MODIFICATION: cysteine residue {C1453} cysteine residue {C1453} MODIFICATION: cysteine residue {C1338}

Database Correlations

UniProt A8K2U0 PFAM correlations

References

UniProt :accession A8K2U0