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Details on Person Aggrecan (large aggregating proteoglycan, chondroitin sulfat...

Class:Id	Summation:1592340
_displayName	Aggrecan (large aggregating proteoglycan, chondroitin sulfat...
_timestamp	2013-07-05 15:51:32
created	[InstanceEdit:1592294] Jupe, S, 2011-09-09
literatureReference	[LiteratureReference:2533985] Mechanisms involved in cartilage proteoglycan catabolism [LiteratureReference:3791333] Proteases involved in cartilage matrix degradation in osteoarthritis [LiteratureReference:1592344] ADAMTS-5 deficiency does not block aggrecanolysis at preferred cleavage sites in the chondroitin sulfate-rich region of aggrecan [LiteratureReference:2533996] Aggrecanase and aggrecan degradation in osteoarthritis: a review [LiteratureReference:3791275] Cleavage of cartilage proteoglycan between G1 and G2 domains by stromelysins [LiteratureReference:3791303] The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B [LiteratureReference:3791297] Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain [LiteratureReference:3791253] Degradation of cartilage aggrecan by collagenase-3 (MMP-13) [LiteratureReference:2534002] MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein [LiteratureReference:3791309] 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 [LiteratureReference:3791324] Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4 [LiteratureReference:3791326] Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family [LiteratureReference:3791258] Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins [LiteratureReference:3791257] ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan [LiteratureReference:3791310] ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitors [LiteratureReference:3791288] Characterization of ADAMTS-9 and ADAMTS-20 as a distinct ADAMTS subfamily related to Caenorhabditis elegans GON-1 [LiteratureReference:3791306] ADAMTS-8 exhibits aggrecanase activity and is expressed in human articular cartilage [LiteratureReference:3791307] Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18 [LiteratureReference:3791323] Matrix metalloproteinases: role in arthritis
modified	[InstanceEdit:2533987] Jupe, S, 2012-10-22 [InstanceEdit:2984194] Jupe, S, 2013-01-15 [InstanceEdit:3791337] Jupe, S, 2013-07-05
text	Aggrecan (large aggregating proteoglycan, chondroitin sulfate proteoglycan 1) is a major structural component of cartilage, particularly articular cartilage. The core protein has over 100 chains of chondroitin sulphate and keratan sulphate giving a MWt of about 250 kDa. The core protein has 2 N-terminal globular domains G1 and G2 and a C-terminal globular G3 domain. G2 and G3 are separated by a region heavily modified with negatively charged glycosaminoglycans (GAGs). The two main modifier moieties keratan sulfate (KS) and chondroitin sulfate (CS) are arranged into two CS regions and a KS-rich region. The 15-kDa interglobular linker (IGD) between the N-terminal G1 and G2 domains is particularly susceptible to proteolysis (Caterson et al. 2000). Degradation in this region is associated with the development of osteoarthritis (Troeberg & Nagase 2012). Members of the ADAM (A Disintegrin And Metalloprotease) protein family are responsible for this cleavage (East et al. 2007, Huang & Wu 2008). Matrix metalloproteinase (MMP) 3 was the first protease found to degrade aggrecan. It preferentially cleaves the Asn341~Phe342 bond (Fosang et al. 1991). MMP2, 7, 9 (Fosang et al. 1992), 1, 8 (Fosang et al. 1993), 13 (Fosang et al. 1996) and 12 (Durigova et al. 2011) were all found to be able to cleave this site as well as others towards the C-terminus. However, the the majority of aggrecan fragments present in synovial fluid of OA patients are cleaved at Glu392-Ala373 (numbered here according to the UniProt sequence, these residues referred to as Glu373-Ala374 in most literature) in the IGD (Sandy et al. 1992). ADAMTS5 (aggrecanase-2, Abbaszade et al. 1999) and to a lesser extent ADAMTS4 (aggrecanase-1, Tortorella et al. 1999) are primarrily responsible (Gendron et al. 2007) though the preferred cleavage sites of these are in the CS-2 domain. ADAMTS1 (Kuno et al. 2000, Rodriques-Manzaneque et al. 2002), 9, (Somerville et al. 2003), 8 (Colins-Racie 2004), 16 and 18 (Zeng et al. 2006) can also degrade aggrecan in vitro.
(summation)	[Reaction:1592310] Aggrecan degradation by ADAMTSs [Homo sapiens]
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