MMP2

This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Matrix Metallopeptidase 2

Matrix Metallopeptidase 2; Matrix Metalloproteinase-2; EC 3.4.24.24; CLG4A; MMP-2; TBE-1; Matrix Metalloproteinase 2 (Gelatinase A, 72kDa Gelatinase, 72kDa Type IV Collagenase); Matrix Metallopeptidase 2 (Gelatinase A, 72kDa Gelatinase, 72kDa Type IV Collagenase); Matrix Metalloproteinase-II; 72 KDa Type IV Collagenase;

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.

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.

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.

Aging Source: Ensembl
Angiogenesis Source: UniProtKB-KW
Blood vessel maturation Source: Ensembl
Bone trabecula formation Source: Ensembl
Cell migration Source: Ensembl
Cellular protein metabolic process Source: Reactome
Cellular response to amino acid stimulus Source: Ensembl
Cellular response to estradiol stimulus Source: Ensembl
Cellular response to fluid shear stress Source: Ensembl
Cellular response to interleukin-1 Source: Ensembl
Cellular response to reactive oxygen species Source: Ensembl
Cellular response to UV-A Source: UniProtKB
Collagen catabolic process Source: GO_Central
Embryo implantation Source: Ensembl
Endodermal cell differentiation Source: UniProtKB
Ephrin receptor signaling pathway Source: Reactome
Extracellular matrix disassembly Source: ParkinsonsUK-UCL
Extracellular matrix organization Source: GO_Central
Face morphogenesis Source: Ensembl
Heart development Source: Ensembl
Intramembranous ossification Source: Ensembl
Luteinization Source: Ensembl
Negative regulation of cell adhesion Source: Ensembl
Negative regulation of vasoconstriction Source: Ensembl
Ovarian follicle development Source: Ensembl
Ovulation from ovarian follicle Source: Ensembl
Parturition Source: Ensembl
Peripheral nervous system axon regeneration Source: Ensembl
Positive regulation of apoptotic process Source: Ensembl
Positive regulation of cell migration Source: Ensembl
Positive regulation of vascular associated smooth muscle cell proliferation Source: BHF-UCL
Prostate gland epithelium morphogenesis Source: Ensembl
Proteolysis Source: ParkinsonsUK-UCL
Response to activity Source: Ensembl
Response to amyloid-beta Source: ARUK-UCL
Response to electrical stimulus Source: Ensembl
Response to estrogen Source: Ensembl
Response to hydrogen peroxide Source: Ensembl
Response to hyperoxia Source: Ensembl
Response to hypoxia Source: GO_Central
Response to mechanical stimulus Source: Ensembl
Response to nicotine Source: Ensembl
Response to retinoic acid Source: Ensembl
Response to xenobiotic stimulus Source: Ensembl
Tissue remodeling Source: GO_Central

Isoform 1:
Nucleus
Extracellular region or secreted
extracellular matrix
Other locations
Membrane
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.
Isoform 2:
Cytoplasm
Mitochondrion

Multicentric osteolysis, nodulosis, and arthropathy (MONA):
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.

Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro.
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.