Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene family. The protein is thought to be a metastasis suppressor.[citation needed]
The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases (MMP), 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.[1] TIMP2 functions as both an MMP inhibitor and an activator. TIMPs inhibit active MMPs, but different TIMPs inhibit different MMPs better than others. For example, TIMP-1 inhibits MMP-7, MMP-9, MMP-1 and MMP-3 better than TIMP-2, and TIMP-2 inhibits MMP-2 more effectively than other TIMPs.[2]
In melanocytic cells TIMP2 gene expression may be regulated by MITF.[3]
A more recent discovery is that TIMP2 plays an important role in hippocampal function and cognitive function. It plays a critical role in the benefit conferred to old mice when given human umbilical cord blood.[4][5]
↑Zucker S, Drews M, Conner C, Foda HD, DeClerck YA, Langley KE, Bahou WF, Docherty AJ, Cao J (January 1998). "Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1-matrix metalloproteinase 1 (MT1-MMP)". J. Biol. Chem. 273 (2): 1216–22. doi:10.1074/jbc.273.2.1216. PMID9422789.
↑Overall CM, Tam E, McQuibban GA, Morrison C, Wallon UM, Bigg HF, King AE, Roberts CR (December 2000). "Domain interactions in the gelatinase A.TIMP-2.MT1-MMP activation complex. The ectodomain of the 44-kDa form of membrane type-1 matrix metalloproteinase does not modulate gelatinase A activation". J. Biol. Chem. 275 (50): 39497–506. doi:10.1074/jbc.M005932200. PMID10991943.
↑Bigg HF, Shi YE, Liu YE, Steffensen B, Overall CM (June 1997). "Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2". J. Biol. Chem. 272 (24): 15496–500. doi:10.1074/jbc.272.24.15496. PMID9182583.
↑Kai HS, Butler GS, Morrison CJ, King AE, Pelman GR, Overall CM (December 2002). "Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. The importance of acidic residues in binding the MMP-2 hemopexin C-domain". J. Biol. Chem. 277 (50): 48696–707. doi:10.1074/jbc.M209177200. PMID12374789.
Stetler-Stevenson WG, Seo DW (2005). "TIMP-2: an endogenous inhibitor of angiogenesis". Trends in Molecular Medicine. 11 (3): 97–103. doi:10.1016/j.molmed.2005.01.007. PMID15760767.
External links
The MEROPS online database for peptidases and their inhibitors: I35.002
