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matrix metalloproteinase-19; MMP-19; matrix metalloproteinase RASI; MMP-18 (MMP19, MMP18, RASI)
Function:
- endopeptidase
- degrades various components of extracellular matrix, such as aggrecan & cartilage oligomeric matrix protein (COMP), during development, hemostasis & disease (arthritis)
- may also play a role in neovascularization or angiogenesis
- hydrolyzes collagen type 4, laminin, nidogen, nascin-C isoform, fibronectin, & type I gelatin
- strongly inhibited by TIMP-2, TIMP-3 & TIMP-4; TIMP-1 is less efficient
- activated by autolytic cleavage after Lys-97
- cleaves aggrecan at the 360-Ser-|-Phe-361 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 Zn+2 upon the activation- peptide release activates the enzyme
- belongs to the peptidase M10A family
- contains 4 hemopexin-like domains
Compartment:
- secreted, extracellular space, extracellular matrix (putative)
Alternative splicing: named isoforms=4
additional isoforms seem to exist
Expression:
- expressed in mammary gland, placenta, lung, pancreas, ovary, small intestine, spleen, thymus, prostate, testis colon, heart & blood vessel walls
- not detected in brain & peripheral blood leukocytes
- found in synovial fluid of normal & rheumatoid arthritis patients
Pathology:
- may play a role in rheumatoid arthritis
- autoantibodies against MMP19 (anti-MMP19) are frequent in patients with rheumatoid arthritis
General
matrixin or matrix metalloproteinase
Properties
SIZE: entity length = 508 aa
MW = 57 kD
COMPARTMENT: extracellular matrix
MOTIF: signal sequence {1-18}
Cysteine switch {83-90}
MOTIF: Zn+2-binding site
SITE: 85-85
Zn+2-binding site
SITE: 212-212
glutamate residue {E213}
Zn+2-binding site
SITE: 216-216
Zn+2-binding site
SITE: 222-222
glutamate-rich region {265-271}
MOTIF: glutamate residue (SEVERAL)
cysteine residue {C289}
MODIFICATION: cysteine residue {C472}
Hemopexin-like 1 {293-335}
Hemopexin-like 2 {337-378}
Hemopexin-like 3 {380-427}
Hemopexin-like 4 {429-472}
MOTIF: N-glycosylation site {N464}
cysteine residue {C472}
MODIFICATION: cysteine residue {C289}
Database Correlations
OMIM 601807
UniProt Q99542
PFAM correlations
Entrez Gene 4327
Kegg hsa:4327
References
- UniProt :accession Q99542
- NIEHS-SNPs
http://egp.gs.washington.edu/data/mmp19/