Tissue inhibitor of metalloproteinases 2 (TIMP2)

Tissue inhibitor of metalloproteinases 2 (TIMP2) is a secreted, nonglycosylated 21 kDa protein consisting of two domains stabilized by disulfide bridges. As a member of the TIMP family, it potently and broadly inhibits many matrix metalloproteinases, especially MMP2, thereby regulating extracellular matrix integrity and tissue remodeling. Uniquely among TIMPs, TIMP2 also directly suppresses endothelial cell proliferation and interacts with cell surface receptors involved in MMP activation, forming a ternary complex with MMP14 and proMMP2 for proteolytic activation of latent MMP2. It has broad physiological roles beyond MMP inhibition, including regulation of angiogenesis, neurogenesis, dendritic spine plasticity, cellular migration, apoptosis, and modulation of tumor invasion and metastasis. Dysregulation of TIMP2 is implicated in cancer progression, tissue fibrosis, cardiovascular and neurodegenerative diseases.

Other names

Metalloproteinase inhibitor 2TIMP metallopeptidase inhibitor 2TIMP-2

Direct inhibition of MMP catalytic activity by binding to the active site (primarily MMP-2, also MMP-1, MMP-3, MMP-7, MMP-9, MMP-14, etc.); formation of a ternary complex (TIMP2-MMP-14-proMMP2) for activation of latent MMP2; modulation of cell proliferation, migration, and angiogenesis (MMP-independent activity).