HSPG2 (perlecan) degradation by MMP3, plasmin, (MMP12)

Stable Identifier
R-HSA-1592314
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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HSPG2 protein (perlecan) consists of a core protein of molecular weight 470 kDa with three long glycosaminoglycan (GAG) chains attached, each approximately 70-100 kDa. These are usually heparan sulphate (HS), but can be chondroitin sulphate (CS). The core protein consists of five distinct structural domains. The N-terminal domain I (aa ~1-195) contains attachment sites for GAG chains. Although GAG chains are not required for correct folding and secretion of the protein, lack of GAG or decreased sulfation can decrease perlecan's ability to interact with matrix proteins. Removal of GAG chains may affect matrix organization and endothelial barrier function. The GAG chains of HSPG2 bind growth factors in the ECM, and serve as co-ligands or ligand enhancers when bound to receptors. For example, HS-bound FGF was released from cultured cells by treatments with MMP3, rat MMP13, and plasmin (Whitelock et al. 1996). Other MMPs reported to degrade HSPG2 include MMP14 and MMP15 (d'Ortho et al. 1997). MMP12 releases chondroitin sulphate and heparan sulphate from basement membranes (Gronski et al. 1997) and degrades the related aggrecan (Durigova et al. 2011) so may degrade perlecan. Corneal epithelium explant growth correlates with MMP2 expression, an initial degradation of the original basement membrane, and an initial upregulation followed by downregulation of MMP9. However this may not result from direct cleavage of HSPG2 by these MMPs, they may modulate some factor involved in the maturation of basement membrane (Li et al. 2006). The core protein of HSPG2 can be cleaved by cathepsin S (Liuzzo et al. 1999).

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Catalyst Activity
Title
serine-type endopeptidase activity of MMP3, plasmin, (MMP12) [extracellular region]
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Activity
Orthologous Events
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