Aggrecan

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Aggrecan, or large aggregating proteoglycan, is a proteoglycan, or a protein modified with carbohydrates; the human form of the protein is 2316 amino acids long and can be expressed in multiple isoforms due to alternative splicing. Along with collagen, aggrecan forms a major structural component of cartilage, particularly articular cartilage. Aggrecan consists of two globular structural domains at the N-terminal end and one globular domain at the C-terminal end, separated by a large domain heavily modified with glycosaminoglycans. The two main modifier moieties are themselves arranged into distinct regions, a chondroitin sulfate and a keratan sulfate region.

The linker domain between the N-terminal globular domains, called the interglobular domain, is highly sensitive to proteolysis. Such degradation has been associated with the development of arthritis. Proteases capable of degrading aggrecans are called aggrecanases, and they are members of the ADAM (A Disintegrin And Metalloprotease) protein family.

East CJ, Stanton H, Golub SB, Rogerson FM, Fosang AJ. (2007). ADAMTS-5 deficiency does not block aggrecanolysis at preferred cleavage sites in the chondroitin sulphate-rich region of aggrecan. J Biol Chem Epub. PMID 17255106
Doege KJ, Sasaki M, Kimura T, Yamada Y. (1991). Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms. J Biol Chem 266(2):894-902. PMID 1985970