matrix metalloproteinase-17; matrixin 17; MMP-17; membrane-type matrix metalloproteinase 4; MT-MMP 4; membrane-type-4 matrix metalloproteinase; MT4-MMP; Puente (MMP17, MT4MMP)

Function

• endopeptidase
• degrades components of the extracellular matrix, including fibrin
• may play role in activation of membrane-bound precursors of growth factors or inflammatory mediators, such as TNF-alpha
• may or may not proteolytically activate progelatinase A
• does not hydrolyze collagen types: collagen 1, collagen 2, collagen 3, collagen 4, collagen 5
• does not hydrolye gelatin, fibronectin, laminin, decorin, alpha1-antitrypsin
• precursor is cleaved by a furin endopeptidase -cleaves pro TNF-alpha at the 74-Ala-|-Gln-75 site

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 Cys from the Zn+2 upon activation- peptide release activates the enzyme
• belongs to the peptidase M10A family
• contains 4 hemopexin-like domains

Compartment

• isoform long: cell membrane; lipid-anchor, GPI-anchor; extracellular side
• secreted, extracellular space, extracellular matrix

Alternative splicing

named isoforms=2, short isoform is Puente

Expression

• expressed in brain, leukocytes, colon, ovary, testis
• expressed in many transformed & non-transformed cell types

Pathology

• may be involved in tumorigenesis
• expressed in breast cancer

More general terms

• matrixin or matrix metalloproteinase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4326
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4326
• OMIM: https://mirror.omim.org/entry/602285
• UniProt: http://www.uniprot.org/uniprot/Q9ULZ9.html