Tissue Inhibitor of Metalloproteinases 1
Tissue Inhibitor of Metalloproteinases 1
Tissue Inhibitor of Metalloproteinases 1 (TIMP-1) is a member of a family of secreted proteolytic enzymes that are involved in the biosynthesis of connective tissue. The synthesis and secretion of matrix metalloproteinases (MMPs) is induced in various cell types by a number of cytokines. Metalloproteinases degrade constituents of the basal membrane and the extracellular matrix, including collagens, proteoglycans, gelatin, fibronectin, laminin, and elastin, under physiological and pathological conditions. The biological activities of the proteases are subject to a complex regulation also involving specific inhibitors, called TIMP (Tissue inhibitor of metalloproteinases). Many proforms of these metalloproteinases form complexes with these inhibitors. TIMP-1 is a major regulator of extracellular matrix synthesis and degradation. A certain balance of MMPs and TIMPs is essential for tumor growth and health. It complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. TIMP-1 also mediates erythropoiesis in vitro but, unlike IL-3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. It is known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-16 though it does not act on MMP-14.
Swiss-Prot Accession Number: P01033
Bibliography
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