Biolegend, 788208, Recombinant Mouse TIMP-2 (carrier-free)

TIMPs (tissue inhibitors of metalloproteinases) are endogenous inhibitors of MMPs (matrix metalloproteinases). The human TIMPs consist of structurally and functionally distinct N- and C-terminal domains, each of which is stabilized by three disulfide bonds. The N-terminal domain binds to the active site of MMPs, inhibiting their proteolytic activities. The bidentate coordination of the zinc ion in the active site of an MMP by the N-terminal α-amino group and carbonyl group of the Cys residue in the "cysteine switch" motif is a key mechanism of inhibition with MMPs. The C-terminal domain is known to bind the hemopexin-like domain of pro-MMPs. TIMPs are broad-spectrum inhibitors of MMPs, but there are some differences in specificity among them. Human metalloproteinase inhibitor 2 (TIMP-2) expression is regulated by the melanoma oncogene MITF (micropthalmia-associated transcription factor) in melanocytes. Besides inhibitory functions, TIMP-2 also has erythroid potentiating and cell growth promoting activities. Interestingly, TIMP-2-deficient mice demonstrated increased tumor growth, enhanced expression of angiogenic marker αvβ3 in tumor and endothelial cells, and significantly higher serum vascular endothelial growth factor A levels. Tumor-bearing TIMP-2 -/- mice showed a significant number of inflammatory cells in their tumors, upregulation of inflammation mediators, NF-κB, and Annexin A1 as well as higher levels of serum IL-6. TIMP-2 is widely expressed in many mammalian tissues, notably in the reproductive organs. TIMP-2 is able to promote cell proliferation in a wide range of cell types and may also have an anti-apoptotic function. It has anti-angiogenic activity by preventing endothelial cell migration.