Aggrecan is a member of large, aggregating proteoglycans (also including, versican, brevican and neurocan) found in articular cartilage. Aggrecan is composed of three major domains: G1, G2, and G3. Between the G1 and G2 domains there is an interglobulin region (IGD). The IGD region is the major site of cleavage by specific proteases like MMPs and ADAMTS.
Aggrecan cleavage has been associated with a number of degenerative diseases including rheumatoid arthritis and osteoarthritis. The C-terminal NITEGE fragment is one of the G1 fragments produced when aggrecan is cleaved with aggrecanase. It is the most abundant fragment found in normal human synovial fluid and articular cartilage, and is the major product produced by aggrecanase cleavage. The NITEGE fragment has also been shown to accumulate rapidly after an acute cartilage injury.
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