matrix metalloproteinase-16 (matrixin-16, membrane-type matrix metalloproteinase 3, MTMMP3, MMPX2 MMP16)

Function: - endopeptidase that degrades various components of the extracellular matrix, such as collagen type 3 & fibronectin - activates progelatinase A - involved in the matrix remodeling of blood vessels - short isoform cleaves fibronectin & also collagen type 3, but at lower rate - no effect on collagen type 1, 2, 4 & 5 - interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan - TIMP-2 shows little inhibitory activity compared to TIMP-1 - TIMP-1 seems to have less binding affinity than TIMP-2 for the short isoform - precursor is cleaved by a furin endopeptidase 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: - isoform long: cell membrane - isoform short: secreted, cell surface - both forms localized at the cell surface of melanoma cells Alternative splicing: named isoforms=2 Expression: - expressed in heart, brain, placenta, ovary & small intestine - the short isoform is found in the ovary - expressed in tissues undergoing reconstruction - present in fetal tissues, especially in brain - expression seems to decline with advanced development Pathology: - upon interaction with CSPG4, may be involved in degradation of collagen type 1 & invasion by melanoma cells - localized at the cell surface of melanoma cells

General

hydrolase matrixin or matrix metalloproteinase membrane protein

Properties

SIZE: entity length = 607 aa MW = 70 kD COMPARTMENT: plasma membrane MOTIF: signal sequence {1-31} N-glycosylation site {N83} Cysteine switch {99-106} MOTIF: Zn+2-binding site SITE: 101-101 Zn+2-binding site SITE: 246-246 glutamate residue {E247} Zn+2-binding site SITE: 250-250 Zn+2-binding site SITE: 256-256 cysteine residue {C343} MODIFICATION: cysteine residue {C532} Hemopexin-like 1 {347-390} Hemopexin-like 2 {392-436} Hemopexin-like 3 {439-485} Hemopexin-like 4 {487-532} MOTIF: cysteine residue {C532} MODIFICATION: cysteine residue {C343} transmembrane domain {565-585}

Database Correlations

OMIM 602262 UniProt P51512 PFAM correlations Entrez Gene 4325 Kegg hsa:4325

References

UniProt :accession P51512