proMMP2

proMMP-2, or pro-MMP-2, is the inactive zymogen form of matrix metalloproteinase-2 (MMP-2), a secreted zinc-dependent enzyme in the gelatinase subgroup of the matrix metalloproteinase family. As a latent enzyme, proMMP-2 contains an N-terminal propeptide that maintains latency by the cysteine switch, a motif such as PRCGVPD that coordinates the catalytic zinc and prevents substrate binding. The mature enzyme is produced by proteolytic removal of the propeptide.

Activation of proMMP-2 occurs at the cell surface through a ternary complex involving membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) and tissue inhibitor of metalloproteinases-2 (TIMP-2). TIMP-2 binds MT1-MMP, proMMP-2 binds to this complex, and MT1-MMP then cleaves the pro-domain of proMMP-2 to yield active MMP-2. This activation event localizes proteolysis to the pericellular environment and enables targeted remodeling of the extracellular matrix.

MMP-2 cleaves several extracellular matrix components, most notably type IV collagen and gelatin, contributing to basement membrane remodeling, tissue turnover, angiogenesis, and wound healing. It also participates in physiological processes such as development and morphogenesis, as well as pathological contexts including cancer invasion, metastasis, and fibrotic diseases when its activity is dysregulated.

Structurally, proMMP-2 comprises a signal peptide, a pro-domain, a catalytic domain containing the zinc-binding motif HEXGHXXGXXH, and a hemopexin-like C-terminal domain that mediates substrate recognition and interactions with TIMPs and MT1-MMP.

The MMP2 gene encodes this enzyme and is widely expressed across tissues, reflecting diverse roles in tissue remodeling and homeostasis.