Mmp2

Developmental stage

Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.

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.

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 (By similarity).

PEX, the C-terminal non-catalytic fragment of MMP2, possesses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrin alpha-v/beta-3 on the surface of blood vessels (By similarity).

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.

Post-translational modifications

Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro (By similarity).

The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3) (By similarity). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3 (By similarity).

Sequence Similarities

Belongs to the peptidase M10A family.

Cellular localization

• Isoform 1
• Secreted
• Extracellular space
• Extracellular matrix
• Membrane
• Nucleus
• 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 (By similarity).
• Isoform 2
• Cytoplasm
• Mitochondrion

Alternative names

72 kDa type IV collagenase, 72 kDa gelatinase, Gelatinase A, Matrix metalloproteinase-2, MMP-2, Mmp2

Database links

swissprot:P33434 entrezGene:17390

Other research areas

• Immunology & Infectious Disease
• Neuroscience