ADAMTS4

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ADAMTS4 is an enzyme in humans encoded by the ADAMTS4 gene. It belongs to the ADAMTS family of proteases, which have a propeptide, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 motif. ADAMTS4 is the shortest member of the family, lacking an extra C-terminal thrombospondin motif and it is not glycosylated. The enzyme can cleave major cartilage proteoglycans, especially aggrecan, and also brevican, neurocan, and versican, helping remodel the extracellular matrix in cartilage and brain. By breaking down aggrecan and brevican, it plays a role in osteoarthritis and may influence the central nervous system and possibly glioma progression. Its activity is inhibited by TIMP-3 and by calcium pentosan polysulfate. ADAMTS4 is expressed in tissues such as ovary, spinal cord, brain, retina, pancreas, and cartilage. In humans, ADAMTS4 is a major enzyme for proteoglycan degradation in articular cartilage, while in mice ADAMTS5 often has a larger role, highlighting species differences. The single thrombospondin motif helps the enzyme bind to the extracellular matrix and determine substrate specificity, with surrounding domains shaping its final structure and activity.