This gene can be found on chromosome 16 at location: 54,070,604-54,097,652

The DNA sequence contains 13 exons and the transcript length: 3,069 bps translated to a 660 residues protein.

MMP2 is a Zn⁺² dependent endopeptidase, synthesized and secreted in zymogen form. The nascent form of the protein shows an N-terminal signal sequence ("pre" domain) that directs the protein to the endoplasmic reticulum. The pre domain is followed by a propeptide-"pro" domain that maintains enzyme-latency until cleaved or disrupted, and a catalytic domain that contains the conserved zinc-binding region. A hemopexin/vitronectin-like domain is also seen, that is connected to the catalytic domain by a hinge or linker region. The hemopexin domain is involved in TIMP (Tissue Inhibitors of Metallo-Proteinases) binding, the binding of certain substrates, membrane activation, and some proteolytic activities. It also shows a series of three head-to-tail cysteine-rich repeats within its catalytic domain. These inserts resemble the collagen-binding type II repeats of fibronectin and are required to bind and cleave collagen and elastin.

The regulation of MMP-2 activity occurs at many levels, of which regulation through TIMP-2 and its cell surface receptor, MT1-MMP (MMP14) is critically decisive. At higher levels of TIMP-2, MT1-MMP forms a ternary complex with MMP-2 through, leaving no free MT1-MMP receptors, thereby inhibiting the activation of pro-MMP-2 by MT1-MMP. But at lower levels of TIMP-2, due to availability of free MT1-MMP, MT1-MMP mediated activation of MMP-2 is observed. Further data also indicates that expression of TIMP-2, MMP-2 and MT1-MMP (MMP-14) is co-regulated transcriptionally, demonstrating an intricate network of regulation. Pro-MMP-2 activation is also seen by complex signaling induced by ECM proteins like osteopontin, various cytokines for example IL-8 in endothelial cells and other factors.

MMP2 is tightly regulated at the transcriptional and post-transcriptional levels.

Peri/extracellular

Primary function is degradation of proteins in the extracellular matrix. It proteolytically digests gelatin (denatured collagen), and types IV, V, VII, IX and X collagen. Physiologically, MMP-2 in coordination with other MMPs, play a role in normal tissue remodeling events such as embryonic development, angiogenesis, ovulation, mammary gland involution and wound healing. MMP2 is also involved in osteoblastic bone formation and/or inhibits osteoclastic bone resorption.

Homology in amino acid sequence is seen with the other members of Metalloproteinase family especially with MMP-9.

A G-to-A transition in codon 101 of exon 2 of MMP2 gene was detected in a Saudi family with idiopathic multicentric osteolysis. This mutation showed a replacement of an arginine by histidine (R101H) in the prodomain, a region highly conserved across species and other members of the MMP gene family that is involved in autoproteolytic activation of MMP2.
In a case of Winchester Syndrome, a homozygous 1210G-A transition in exon 8 of the MMP2 gene, leads to glu-to-lys (E404K) substitution in the catalytic domain of the protein. The glutamic acid at codon 404 is believed to be essential for the peptidase activity of all metalloproteinases, as its carboxyl group catalyzes 2 proton transfers, helps stabilize the transition state, and triggers the release of the products.