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

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=4327
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4327
• OMIM: https://mirror.omim.org/entry/601807
• UniProt: http://www.uniprot.org/uniprot/Q99542.html