matrix metalloproteinase-12 (matrixin-12, macrophage metalloelastase, MMP12, HME)

Function: - role in tissue injury & remodeling - significant elastolytic activity - can accept large & small amino acids at the P1' site, but has a preference for leucine - aromatic or hydrophobic residues are preferred at the P1 site - small hydrophobic residues (preferably alanine) occupy P3 - hydrolysis of soluble & insoluble elastin - specific cleavages are also produced at 14-Ala-|-Leu-15 & 16-Tyr-|-Leu-17 in the B chain of insulin Cofactor: - binds 4 Ca⁺² per subunit binds 2 Zn⁺² per subunit Structure: - conserved Cys present in the cysteine-switch motif binds the catalytic Zn⁺², thus inhibiting the enzyme; dissociation of the Cys from the Zn⁺² upon the activation-peptide release activates the enzyme - belongs to the peptidase M10A family - contains 4 hemopexin-like domains Expression: - found in alveolar macrophage - not found in peripheral blood monocytes - induced by exposure to lipopolysaccharide - inhibited by dexamethasone

General

elastase matrixin or matrix metalloproteinase

Properties

SIZE: entity length = 470 aa MW = 54 kD COMPARTMENT: extracellular matrix MOTIF: signal sequence {1-16} N-glycosylation site {N20} Cysteine switch {90-97} MOTIF: Zn+2-binding site SITE: 92-92 Ca+2-binding site SITE: 124-124 Ca+2-binding site SITE: 158-158 Zn+2-binding site SITE: 168-168 Zn+2-binding site SITE: 170-170 Ca+2-binding site SITE: 175-175 Ca+2-binding site SITE: 176-176 Ca+2-binding site SITE: 178-178 Ca+2-binding site SITE: 180-180 Zn+2-binding site SITE: 183-183 Ca+2-binding site SITE: 190-190 Ca+2-binding site SITE: 192-192 Ca+2-binding site SITE: 194-194 Zn+2-binding site SITE: 196-196 Ca+2-binding site SITE: 198-198 Ca+2-binding site SITE: 199-199 Ca+2-binding site SITE: 201-201 Zn+2-binding site SITE: 218-218 glutamate residue {E219} Zn+2-binding site SITE: 222-222 Zn+2-binding site SITE: 228-228 cysteine residue {C282} MODIFICATION: cysteine residue {C470} N-glycosylation site {N285} Hemopexin-like 1 {288-330} MOTIF: Ca+2-binding site SITE: 289-289 Hemopexin-like 2 {332-375} MOTIF: Ca+2-binding site SITE: 333-333 Hemopexin-like 3 {380-427} MOTIF: Ca+2-binding site SITE: 381-381 Hemopexin-like 4 {429-470} MOTIF: Ca+2-binding site SITE: 430-430 cysteine residue {C470} MODIFICATION: cysteine residue {C282}

Database Correlations

OMIM 601046 UniProt P39900 PFAM correlations Entrez Gene 4321 Kegg hsa:4321 ENZYME 3.4.24.65