Tissue inhibitors of metalloproteinases (TIMPs) are a family of ubiquitous, endogenous inhibitors that regulate the activation and activity of matrix metalloproteinases (MMPs). They have been shown in animal models to be capable of the inhibition of tumor cell invasion and metastasis. They may also be involved in other diseases such as arthritis and periodontal disease. TIMP-1 is a 184 amino acid glycoprotein of 28.5 kDa. TIMP-1 preferentially binds and inhibits MMP-9 and MMP-1 through interaction with their catalytic domains. TIMP-2 is a 194 amino acid, nonglycosylated protein of 21 kDa with 43% and 44% homology to TIMP-1 and TIMP-3, respectively. It inhibits the activity of all active MMPs and regulates MMP-2 expression by binding to the C-terminal region of pro-MMP-2 (Kd ~5 nM). As with TIMP-1, TIMP-2 has been shown to have erythroid-potentiating activity and cell growth-promoting activity. TIMP-3 is present in the eye. It is tightly bound to the extracellular matrix and has been shown to inhibit TNF-α converting enzyme (TACE). A mutation in TIMP-3 is found in Sorsby's fundus dystrophy, a dominantlyinherited form of blindness. TIMP-4 blocks the activities of several (MMPs) implicated in the arthritic cartilage erosion.
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