MMP2

Matrix metalloproteinase-2 (MMP-2), also known as gelatinase A or 72-kDa gelatinase, is a zinc-dependent endopeptidase in the matrix metalloproteinase family. It degrades components of the extracellular matrix (ECM), particularly type IV collagen, laminin, and gelatin, and participates in remodeling basement membranes during development, wound healing, and angiogenesis.

MMP-2 is encoded by the MMP2 gene in humans, and the protein is synthesized as a secreted proenzyme (pro-MMP-2, 72 kDa) with a signal peptide and a prodomain containing the cysteine switch motif PRCGVPD. The enzyme comprises a catalytic domain with the zinc-binding motif HEXGHXXGXXH, an insert containing fibronectin type II-like repeats, and a C-terminal hemopexin-like domain. These features support substrate binding and specificity.

Activation occurs at the cell surface through a complex involving membrane-type 1 MMP (MT1-MMP/MMP14) and tissue inhibitor of metalloproteinases-2 (TIMP-2), which presents pro-MMP-2 to MT1-MMP for proteolytic activation. Cleavage yields the active enzyme (~62 kDa) capable of degrading ECM components.

Substrates include type IV collagen, gelatin, proteoglycans, and elastin, supporting roles in matrix remodeling, angiogenesis, and cell migration. Regulation of MMP-2 involves transcriptional control by cytokines and growth factors, and post-translational inhibition by TIMPs, particularly TIMP-2 and TIMP-3, which modulate activation and activity.

Clinical and biological significance: MMP-2 participates in normal processes such as development and wound healing, but elevated activity is associated with cancer invasion and metastasis, inflammatory arthritis, atherosclerosis, and fibrotic diseases. It is studied as a biomarker and therapeutic target in various conditions.