Brevican degradation by ADAMTS4, ADAMTS5

Stable Identifier
R-HSA-3788075
Type
Reaction [transition]
Species
Homo sapiens
Compartment
extracellular region
ReviewStatus
5/5
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Brevican degradation by ADAMTS4, ADAMTS5
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Brevican, a member of the lectican family, is one of the most abundant proteoglycans in normal adult brain tissues. It is thought to form lattice structures by linking hyaluronan and tenascin-R through its N- and C-terminal globular domains, respectively. As brain extracellular matrix (ECM) contains no collagen fibrils, this matrix of hyaluronan/brevican/tenascin-R is considered essential to maintain the integrity of brain ECM. Degradation of brevican by proteinases disrupts ECM structures and facilitates invasion of glioma cells (Yamaguchi 2000). The major brevican cleavage site observed under physiological conditions (Yamada et al. 1994) and during glioma invasion (Zhang et al. 1998) is the Glu395-Ser396 bond present within the central domain of the core protein, forming an ~50-kDa N-terminal fragment. This bond is cleaved by ADAMTS4 and 5 (Nakamura et al. 2000, Matthews et al. 2000, Nakada et al. 2005). Matrix metalloproteinases that digest brevican preferentially cleave the Ala360-Phe361 bond. (Nakamura et al. 2000, Nakada et al. 2005, Lettau et al. 2010).
Literature References
PubMed ID Title Journal Year
16133547 Human glioblastomas overexpress ADAMTS-5 that degrades brevican

Kita, D, Yamaguchi, Y, Miura, R, Yamashita, J, Takahashi, T, Miyamori, H, Sato, H, Okada, Y, Nakada, M

Acta Neuropathol. 2005
10986281 Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites

Miura, R, Sugimoto, K, Inoki, I, Fujii, Y, Okada, Y, Tanzawa, K, Matsuki, H, Nakamura, H, Yamaguchi, Y

J. Biol. Chem. 2000
Participants
Input
Output
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as an event of
Catalyst Activity

metalloendopeptidase activity of ADAMTS4, ADAMTS5 [extracellular region]

Physical Entity
ADAMTS4, ADAMTS5 [extracellular region] (Homo sapiens)
Activity
metalloendopeptidase activity (GO:0004222)
Orthologous Events
Brevican degradation by ADAMTS4, ADAMTS5 (Bos taurus)
Brevican degradation by ADAMTS4, ADAMTS5 (Canis familiaris)
Brevican degradation by ADAMTS4, ADAMTS5 (Gallus gallus)
Brevican degradation by ADAMTS4, ADAMTS5 (Mus musculus)
Brevican degradation by ADAMTS4, ADAMTS5 (Rattus norvegicus)
Brevican degradation by ADAMTS4, ADAMTS5 (Sus scrofa)
Brevican degradation by ADAMTS4, ADAMTS5 (Xenopus tropicalis)
Authored
Jupe, S  (2012-08-08)
Reviewed
Ricard-Blum, S  (2013-08-13)
Created
Jupe, S  (2013-07-04)
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