Aggrecan

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.cite journal | author = Doege KJ, Sasaki M, Kimura T, Yamada Y | title = Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms | journal = J. Biol. Chem. | volume = 266 | issue = 2 | pages = 894–902 | year = 1991 | pmid = 1985970 | doi = | issn = | url = http://www.jbc.org/cgi/content/abstract/266/2/894 ] 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.cite journal | author = East CJ, Stanton H, Golub SB, Rogerson FM, Fosang AJ | title = ADAMTS-5 deficiency does not block aggrecanolysis at preferred cleavage sites in the chondroitin sulfate-rich region of aggrecan | journal = J. Biol. Chem. | volume = 282 | issue = 12 | pages = 8632–40 | year = 2007 | pmid = 17255106 | doi = 10.1074/jbc.M605750200 | issn = ]

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Watanabe H, Yamada Y, Kimata K |title=Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. |journal=J. Biochem. |volume=124 |issue= 4 |pages= 687–93 |year= 1999 |pmid= 9756610 |doi=
*cite journal | author=Roughley P, Martens D, Rantakokko J, "et al." |title=The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage. |journal=European cells & materials |volume=11 |issue= |pages= 1–7; discussion 7 |year= 2006 |pmid= 16425147 |doi=
*cite journal | author=Fosang AJ, Neame PJ, Last K, "et al." |title=The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B. |journal=J. Biol. Chem. |volume=267 |issue= 27 |pages= 19470–4 |year= 1992 |pmid= 1326552 |doi=
*cite journal | author=Sandy JD, Flannery CR, Neame PJ, Lohmander LS |title=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. |journal=J. Clin. Invest. |volume=89 |issue= 5 |pages= 1512–6 |year= 1992 |pmid= 1569188 |doi=
*cite journal | author=Doege KJ, Sasaki M, Kimura T, Yamada Y |title=Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms. |journal=J. Biol. Chem. |volume=266 |issue= 2 |pages= 894–902 |year= 1991 |pmid= 1985970 |doi=
*cite journal | author=Baldwin CT, Reginato AM, Prockop DJ |title=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. |journal=J. Biol. Chem. |volume=264 |issue= 27 |pages= 15747–50 |year= 1989 |pmid= 2789216 |doi=
*cite journal | author=Kimata K, Barrach HJ, Brown KS, Pennypacker JP |title=Absence of proteoglycan core protein in cartilage from the cmd/cmd (cartilage matrix deficiency) mouse. |journal=J. Biol. Chem. |volume=256 |issue= 13 |pages= 6961–8 |year= 1981 |pmid= 7240256 |doi=
*cite journal | author=Glumoff V, Savontaus M, Vehanen J, Vuorio E |title=Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by northern and in situ hybridization using species specific cDNA probes. |journal=Biochim. Biophys. Acta |volume=1219 |issue= 3 |pages= 613–22 |year= 1994 |pmid= 7524681 |doi=
*cite journal | author=Ilic MZ, Mok MT, Williamson OD, "et al." |title=Catabolism of aggrecan by explant cultures of human articular cartilage in the presence of retinoic acid. |journal=Arch. Biochem. Biophys. |volume=322 |issue= 1 |pages= 22–30 |year= 1995 |pmid= 7574678 |doi= 10.1006/abbi.1995.1431
*cite journal | author=Valhmu WB, Palmer GD, Rivers PA, "et al." |title=Structure of the human aggrecan gene: exon-intron organization and association with the protein domains. |journal=Biochem. J. |volume=309 ( Pt 2) |issue= |pages= 535–42 |year= 1995 |pmid= 7626017 |doi=
*cite journal | author=Barry FP, Neame PJ, Sasse J, Pearson D |title=Length variation in the keratan sulfate domain of mammalian aggrecan. |journal=Matrix Biol. |volume=14 |issue= 4 |pages= 323–8 |year= 1995 |pmid= 7827755 |doi=
*cite journal | author=Fosang AJ, Last K, Neame PJ, "et al." |title=Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan. |journal=Biochem. J. |volume=304 ( Pt 2) |issue= |pages= 347–51 |year= 1995 |pmid= 7998967 |doi=
*cite journal | author=Fosang AJ, Last K, Knäuper V, "et al." |title=Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain. |journal=Biochem. J. |volume=295 ( Pt 1) |issue= |pages= 273–6 |year= 1993 |pmid= 8216228 |doi=
*cite journal | author=Korenberg JR, Chen XN, Doege K, "et al." |title=Assignment of the human aggrecan gene (AGC1) to 15q26 using fluorescence in situ hybridization analysis. |journal=Genomics |volume=16 |issue= 2 |pages= 546–8 |year= 1993 |pmid= 8314595 |doi= 10.1006/geno.1993.1228
*cite journal | author=Dudhia J, Davidson CM, Wells TM, "et al." |title=Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage. |journal=Biochem. J. |volume=313 ( Pt 3) |issue= |pages= 933–40 |year= 1996 |pmid= 8611178 |doi=
*cite journal | author=Fülöp C, Cs-Szabó G, Glant TT |title=Species-specific alternative splicing of the epidermal growth factor-like domain 1 of cartilage aggrecan. |journal=Biochem. J. |volume=319 ( Pt 3) |issue= |pages= 935–40 |year= 1996 |pmid= 8921002 |doi=
*cite journal | author=Kirschfink M, Blase L, Engelmann S, Schwartz-Albiez R |title=Secreted chondroitin sulfate proteoglycan of human B cell lines binds to the complement protein C1q and inhibits complex formation of C1. |journal=J. Immunol. |volume=158 |issue= 3 |pages= 1324–31 |year= 1997 |pmid= 9013976 |doi=
*cite journal | author=Parkar AA, Kahmann JD, Howat SL, "et al." |title=TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage. |journal=FEBS Lett. |volume=428 |issue= 3 |pages= 171–6 |year= 1998 |pmid= 9654129 |doi=
*cite journal | author=Fosang AJ, Last K, Fujii Y, "et al." |title=Membrane-type 1 MMP (MMP-14) cleaves at three sites in the aggrecan interglobular domain. |journal=FEBS Lett. |volume=430 |issue= 3 |pages= 186–90 |year= 1998 |pmid= 9688535 |doi=

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