matrix metalloproteinase-12; matrixin-12; macrophage elastase; 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 residues 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

More general terms

• matrixin elastase

Database

• UniProt: http://www.uniprot.org/uniprot/P39900.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4321
• OMIM: https://mirror.omim.org/entry/601046
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4321