TIMP-2 (TIMP2) Protein

This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

TIMP2: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19. Interacts (via the C-terminal) with MMP2 (via the C- terminal PEX domain); the interaction inhibits the MMP2 activity. Down-regulated by TGFB1. Belongs to the protease inhibitor I35 (TIMP) family.

Protein type: Secreted; Inhibitor; Secreted, signal peptide; Cell development/differentiation; Motility/polarity/chemotaxis; Extracellular matrix

Chromosomal Location of Human Ortholog: 17q25

Cellular Component: proteinaceous extracellular matrix; extracellular space; cell surface; growth cone; cell soma; extracellular region; basement membrane

Molecular Function: metalloendopeptidase inhibitor activity; integrin binding; protein binding; protease binding; metal ion binding; enzyme activator activity

Biological Process: response to drug; regulation of Rap protein signal transduction; extracellular matrix organization and biogenesis; negative regulation of metalloenzyme activity; central nervous system development; response to hormone stimulus; negative regulation of membrane protein ectodomain proteolysis; extracellular matrix disassembly; negative regulation of cell proliferation; positive regulation of MAPKKK cascade; response to cytokine stimulus; negative regulation of Ras protein signal transduction; negative regulation of mitotic cell cycle; positive regulation of adenylate cyclase activity; positive regulation of neuron differentiation; aging