BioPAX pathway converted from "HSPG2 (perlecan) degradation by MMP13, CTSS" in the Reactome database. 3.4.21.1 3.4.21.92 3.4.21.73 3.4.21.71 3.4.21.93 3.4.21.94 3.4.21.34 3.4.21.78 3.4.21.9 3.4.21.53 3.4.21.6 3.4.21.75 3.4.24.3 3.4.21.10 3.4.21.54 3.4.21.7 3.4.21.4 3.4.21.59 3.4.21.38 3.4.21.5 3.4.21.35 3.4.21.79 3.4.21.36 3.4.19.1 3.4.21.62 3.4.21.41 3.4.21.61 3.4.21.83 3.4.21.22 3.4.21.88 3.4.21.45 3.4.21.89 3.4.21.20 3.4.21.42 3.4.21.21 3.4.21.43 3.4.21.87 3.4.21.26 3.4.21.48 3.4.24.34 3.4.21.27 3.4.21.46 3.4.21.68 3.4.21.47 3.4.21.69 3.4.21.39 3.4.24.7 3.4.21.102 HSPG2 (perlecan) degradation by MMP13, CTSS HSPG2 (perlecan) degradation by MMP13, CTSS Degradation of perlecan by MMP13, CTSS 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). The core protein of HSPG2 can be cleaved by cathepsin S (Liuzzo et al. 1999). Authored: Jupe, S, 2012-08-08 Reviewed: Ricard-Blum, Sylvie, 2013-08-13 Edited: Jupe, S, 2013-08-13 Reactome DB_ID: 1011570 1 extracellular region GO 0005576 UniProt:P98160 HSPG2 HSPG2 HSPG2 FUNCTION Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development.FUNCTION Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6.FUNCTION The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity.SUBUNIT Purified perlecan has a strong tendency to aggregate in dimers or stellate structures. It interacts with other basement membrane components such as laminin, prolargin and collagen type IV. Interacts with COL13A1, FGFBP1 and VWA1. Interacts (via C-terminus) with ECM1 (via C-terminus).TISSUE SPECIFICITY Found in the basement membranes.PTM Proteolytic processing produces the C-terminal angiogenic peptide, endorepellin. This peptide can be further processed to produce the LG3 peptide.PTM N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Perlecan contains three heparan sulfate chains. The LG3 peptide contains at least three and up to five potential O-glycosylation sites but no N-glycosylation.MISCELLANEOUS The LG3 peptide has been found in the urine of patients with end-stage renal disease and in the amniotic fluid of pregnant women with premature rupture of fetal membranes. Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 UniProt P98160 Chain Coordinates 22 EQUAL 4391 EQUAL Reactome DB_ID: 2534251 1 22 EQUAL -1 EQUAL Reactome DB_ID: 2534246 1 -1 EQUAL 4391 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 2534222 MMP13, CTSS [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CTSS [extracellular region] MMP13 [extracellular region] UniProt P25774 UniProt P45452 GO 0004252 GO molecular function Reactome Database ID Release 83 2534167 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2534167 Reactome Database ID Release 83 2534160 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2534160 Reactome R-HSA-2534160 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2534160.1 10390548 Pubmed 1999 Inflammatory mediators regulate cathepsin S in macrophages and microglia: A role in attenuating heparan sulfate interactions Liuzzo, JP Petanceska, SS Moscatelli, D Devi, LA Mol Med 5:320-33 8626565 Pubmed 1996 The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases Whitelock, JM Murdoch, AD Iozzo, RV Underwood, PA J Biol Chem 271:10079-86