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