matrix metalloproteinase-14 (matrixin-14, membrane-type matrix metalloproteinase 1, MMP14, MTMMP1, MT1MMP, MMP- X1, MT1-MMP)

Function

• seems to specifically activate progelatinase A
• precursor is cleaved by a furin endopeptidase
• endopeptidase activity
• activates progelatinase A by cleavage of the propeptide at 37-Asn-|-Leu-38
• other bonds hydrolyzed include 35-gly-|-Ile-36 in the propeptide of collagenase 3, & 341-Asn-|-Phe-342, 441-Asp-|-Leu-442 & 354-Gln-|-Thr-355 in the aggrecan interglobular domain
• can cleave elastin

Cofactor:

• binds 1 Zn+2 per subunit (putative)
• Ca+2 (putative)

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

Compartment

• membrane, melanosome
• identified by mass spectrometry in melanosome fractions from stage 1 to stage 4

Expression

stromal cells of colon, breast, & head & neck

Pathology

• may thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface

More general terms

• matrixin elastase
• collagenase
• membrane protein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4323
• OMIM: https://mirror.omim.org/entry/600754
• UniProt: http://www.uniprot.org/uniprot/P50281.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4323