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.[1] Along with Type-II 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.[2]
Interactions
Aggrecan has been shown to interact with Versican.[3]
References
- ^ 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. http://www.jbc.org/cgi/content/abstract/266/2/894.
- ^ 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 sulfate-rich region of aggrecan". J. Biol. Chem. 282 (12): 8632–40. doi:10.1074/jbc.M605750200. PMID 17255106.
- ^ Matsumoto, Kazu; Shionyu Masafumi, Go Mitiko, Shimizu Katsuji, Shinomura Tamayuki, Kimata Koji, Watanabe Hideto (Oct. 2003). "Distinct interaction of versican/PG-M with hyaluronan and link protein". J. Biol. Chem. (United States) 278 (42): 41205-12. doi:10.1074/jbc.M305060200. ISSN 0021-9258. PMID 12888576.
Further reading
- Watanabe H, Yamada Y, Kimata K (1999). "Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function.". J. Biochem. 124 (4): 687–93. PMID 9756610.
- Roughley P, Martens D, Rantakokko J, et al. (2006). "The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage.". European cells & materials 11: 1–7; discussion 7. PMID 16425147.
- Fosang AJ, Neame PJ, Last K, et al. (1992). "The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B.". J. Biol. Chem. 267 (27): 19470–4. PMID 1326552.
- Sandy JD, Flannery CR, Neame PJ, Lohmander LS (1992). "The structure of aggrecan fragments in human synovial fluid. Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain.". J. Clin. Invest. 89 (5): 1512–6. doi:10.1172/JCI115742. PMID 1569188.
- 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.
- Baldwin CT, Reginato AM, Prockop DJ (1989). "A new epidermal growth factor-like domain in the human core protein for the large cartilage-specific proteoglycan. Evidence for alternative splicing of the domain.". J. Biol. Chem. 264 (27): 15747–50. PMID 2789216.
- Kimata K, Barrach HJ, Brown KS, Pennypacker JP (1981). "Absence of proteoglycan core protein in cartilage from the cmd/cmd (cartilage matrix deficiency) mouse.". J. Biol. Chem. 256 (13): 6961–8. PMID 7240256.
- Glumoff V, Savontaus M, Vehanen J, Vuorio E (1994). "Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by northern and in situ hybridization using species specific cDNA probes.". Biochim. Biophys. Acta 1219 (3): 613–22. PMID 7524681.
- Ilic MZ, Mok MT, Williamson OD, et al. (1995). "Catabolism of aggrecan by explant cultures of human articular cartilage in the presence of retinoic acid.". Arch. Biochem. Biophys. 322 (1): 22–30. doi:10.1006/abbi.1995.1431. PMID 7574678.
- Valhmu WB, Palmer GD, Rivers PA, et al. (1995). "Structure of the human aggrecan gene: exon-intron organization and association with the protein domains.". Biochem. J. 309 ( Pt 2): 535–42. PMID 7626017.
- Barry FP, Neame PJ, Sasse J, Pearson D (1995). "Length variation in the keratan sulfate domain of mammalian aggrecan.". Matrix Biol. 14 (4): 323–8. doi:10.1016/0945-053X(94)90198-8. PMID 7827755.
- Fosang AJ, Last K, Neame PJ, et al. (1995). "Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan.". Biochem. J. 304 ( Pt 2): 347–51. PMID 7998967.
- Fosang AJ, Last K, Knäuper V, et al. (1993). "Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain.". Biochem. J. 295 ( Pt 1): 273–6. PMID 8216228.
- Korenberg JR, Chen XN, Doege K, et al. (1993). "Assignment of the human aggrecan gene (AGC1) to 15q26 using fluorescence in situ hybridization analysis.". Genomics 16 (2): 546–8. doi:10.1006/geno.1993.1228. PMID 8314595.
- Dudhia J, Davidson CM, Wells TM, et al. (1996). "Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage.". Biochem. J. 313 ( Pt 3): 933–40. PMID 8611178.
- Fülöp C, Cs-Szabó G, Glant TT (1996). "Species-specific alternative splicing of the epidermal growth factor-like domain 1 of cartilage aggrecan.". Biochem. J. 319 ( Pt 3): 935–40. PMID 8921002.
- Kirschfink M, Blase L, Engelmann S, Schwartz-Albiez R (1997). "Secreted chondroitin sulfate proteoglycan of human B cell lines binds to the complement protein C1q and inhibits complex formation of C1.". J. Immunol. 158 (3): 1324–31. PMID 9013976.
- Parkar AA, Kahmann JD, Howat SL, et al. (1998). "TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage.". FEBS Lett. 428 (3): 171–6. doi:10.1016/S0014-5793(98)00523-7. PMID 9654129.
- Fosang AJ, Last K, Fujii Y, et al. (1998). "Membrane-type 1 MMP (MMP-14) cleaves at three sites in the aggrecan interglobular domain.". FEBS Lett. 430 (3): 186–90. doi:10.1016/S0014-5793(98)00667-X. PMID 9688535.
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