MGP Database

MGP001936

UniProt Annotations

Entry Information

Gene Name	matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)
Protein Entry	MMP2_HUMAN
UniProt ID	P08253
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P08253-1; Sequence=Displayed; Name=2; IsoId=P08253-2; Sequence=VSP_044631; Note=Induced by oxidative stress.; Name=3; IsoId=P08253-3; Sequence=VSP_045704; Note=No experimental confirmation available.;
Catalytic Activity	Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-\|- Ile-Ala-Gly-Gln.
Cofactor	Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 4 Ca(2+) ions per subunit.;
Cofactor	Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 2 Zn(2+) ions per subunit.;
Disease	Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600]: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. {ECO:0000269\|PubMed:11431697, ECO:0000269\|PubMed:15691365, ECO:0000269\|PubMed:16542393}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Domain	The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Enzyme Regulation	Inhibited by histatin-3 1/24 (histatin-5). {ECO:0000269\|PubMed:11179305}.
Function	Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro- inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
Function	PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.
Function	Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-\|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.
Induction	Aspirin appears to inhibit expression. {ECO:0000269\|PubMed:18971601}.
Interaction	Q8IX30:SCUBE3; NbExp=2; IntAct=EBI-1033518, EBI-4479975;
Ptm	Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. {ECO:0000269\|PubMed:17435175}.
Ptm	The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT- MMP3). Autocatalytic cleavage in the C-terminal produces the anti- angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3. {ECO:0000269\|PubMed:12879005, ECO:0000269\|PubMed:9119036}.
Similarity	Belongs to the peptidase M10A family. {ECO:0000305}.
Similarity	Contains 3 fibronectin type-II domains. {ECO:0000255\|PROSITE-ProRule:PRU00479}.
Similarity	Contains 4 hemopexin repeats. {ECO:0000305}.
Subcellular Location	Isoform 1: Secreted, extracellular space, extracellular matrix. Membrane. Nucleus. Note=Colocalizes with integrin alphaV/beta3 at the membrane surface in angiogenic blood vessels and melanomas. Found in mitochondria, along microfibrils, and in nuclei of cardiomyocytes.
Subcellular Location	Isoform 2: Cytoplasm. Mitochondrion.
Subunit	Interacts (via the C-terminal hemopexin-like domains- containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B. {ECO:0000269\|PubMed:11320090, ECO:0000269\|PubMed:11710594, ECO:0000269\|PubMed:11751392, ECO:0000269\|PubMed:11928808, ECO:0000269\|PubMed:12032297, ECO:0000269\|PubMed:12147339, ECO:0000269\|PubMed:1655733, ECO:0000269\|PubMed:19493954}.
Tissue Specificity	Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate. {ECO:0000269\|PubMed:11751392}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MMP2ID41396ch16q13.html";
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mmp2/";