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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
General
matrixin or matrix metalloproteinase
Properties
SIZE: entity length = 606 aa
MW = 67 kD
COMPARTMENT: extracellular matrix
MOTIF: signal sequence {1-38}
Cysteine switch {111-118}
MOTIF: Zn+2-binding site
SITE: 113-113
arginine-rich region {125-128}
MOTIF: arginine residue (SEVERAL)
N-glycosylation site {N140}
Zn+2-binding site
SITE: 251-251
glutamate residue {E252}
Zn+2-binding site
SITE: 255-255
Zn+2-binding site
SITE: 261-261
N-glycosylation site {N321}
cysteine residue {C335}
MODIFICATION: cysteine residue {C526}
Hemopexin-like 1 {339-383}
Hemopexin-like 2 {388-431}
Hemopexin-like 3 {434-480}
Hemopexin-like 4 {482-526}
MOTIF: cysteine residue {C526}
MODIFICATION: cysteine residue {C335}
glycosyl phosphatidylinositol [GPI] membrane anchor {N568}
Database Correlations
OMIM 602285
UniProt Q9ULZ9
PFAM correlations
Entrez Gene 4326
Kegg hsa:4326
References
UniProt :accession Q9ULZ9