BioPAX pathway converted from "Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan" in the Reactome database.LEFT-TO-RIGHT2.4.1.225Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparanExostosin 1 and 2 (EXT1 and 2) are dual-specific glycosyltransferases required to form heparan sulfate (HS) which is involved in regulating various body functions during development, homeostasis and pathology including blood clotting, angiogenesis and metastasis of cancer cells. They are able to transfer N-acetylglucosamine (GlcNAc) and glucuronate (GlcA) to HS during its synthesis. Defects in EXT2 cause exostoses 2 (MIM:133701), an autosomal dominant disorder characterised by multiple projections of bone capped by cartilage resulting in deformed legs, forearms and hands. Mutations causing exostoses 2 are V187Pfs*115, 404fs*, D227N, G172*, Q258* and Y222* (Stickens et al. 1996, Wyuts et al. 1996, Philippe et al. 1997, Heinritz et al. 2009).Authored: Jassal, B, 2013-05-31Reviewed: Spillmann, Dorothe, 2014-07-09Edited: Jassal, B, 2013-05-31Converted from EntitySet in ReactomeHeparan-PGsReactome DB_ID: 2076465AgrinHeparan-AGRNGlcA-Gal-Gal-Xyl-AGRNAGRIN_HUMANReactome DB_ID: 2076530Golgi lumenGENE ONTOLOGYGO:0005796UniProt:O00468 AGRNAGRNAGRINFUNCTION Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms.FUNCTION Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial cell differentiation.SUBUNIT Monomer (By similarity). Interacts (N-terminal subunit) with TGF-beta family members, BMP2 AND BMP4; the interactions inhibit the activity of these growth factors. Interacts with TGFB1; the interaction enhances the activity of TGFB1 (By similarity). Component of the AGRN-LRP4 complex that consists of a tetramer of two AGRN-LRP4 heterodimers. Interacts (via the laminin G-like 3 domain) directly with LRP4; the interaction is required for activation of MUSK and clustering of AChR and requires the 'z8' insert present in the z(+8) isoforms. Interacts with DAG1; the interaction is influenced by cell surface glycosaminoglycans and by alternative splicing of AGRN.TISSUE SPECIFICITY Expressed in basement membranes of lung and kidney. Muscle- and neuron-specific isoforms are found. Isoforms (y+) with the 4 AA insert and (z+8) isoforms with the 8 AA insert are all neuron-specific. Isoforms (z+11) are found in both neuronal and non-neuronal tissues.DOMAIN The NtA domain, absent in TM-agrin, is required for binding laminin and connecting to basal lamina.DOMAIN Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan/DAG1 binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding (By similarity).PTM Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked oligosaccharides. Glycosaminoglycans (GAGs), present in the N-terminal 110 kDa fragment, are required for induction of filopodia in hippocampal neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains heparan sulfate (HS) chains and the second cluster (Ser/Thr-rich), contains chondroitin sulfate (CS) chains. Heparin and heparin sulfate binding in the G3 domain is independent of calcium ions. Binds heparin with a stoichiometry of 2:1. Binds sialic acid with a stoichiometry of 1:1 and binding requires calcium ions (By similarity).PTM At synaptic junctions, cleaved at two conserved sites, alpha and beta, by neurotrypsin. Cleavage at the alpha-site produces the agrin N-terminal 110-kDa subunit and the agrin C-terminal 110-kDa subunit. Further cleavage of agrin C-terminal 110-kDa subunit at the beta site produces the C-terminal fragments, agrin C-terminal 90 kDa fragment and agrin C-terminal 22 kDa fragment. Excessive cleavage at the beta-site releases large amounts of the agrin C-terminal 22 kDa fragment leading to destabilization at the neuromuscular junction (NMJ).MISCELLANEOUS Cleaved C-terminal fragments may be used as a biomarker for sarcopenia, age-related progressive loss of skeletal muscle.CAUTION The unknown residue 'x' in the transmembrane isoform is probably a proline residue by similarity to mouse and rat sequences.Homo sapiensNCBI Taxonomy9606UniProtO00468O-xylosyl-L-serineMODMOD:0081430EQUAL2045EQUALReactome Database ID Release 752076530Database 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=2076530ReactomeR-HSA-20765301Reactome 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-2076530.1Reactomehttp://www.reactome.orgGlypican-1Heparan-GPC1GlcA-Gal-Gal-Xyl-GPC1Secreted glypican-1GPC1_HUMANReactome DB_ID: 2076567UniProt:P35052 GPC1GPC1FUNCTION Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling.PTM S-nitrosylated in a Cu(2+)-dependent manner. Nitric acid (NO) is released from the nitrosylated cysteines by ascorbate or by some other reducing agent, in a Cu(2+) or Zn(2+) dependent manner. This free nitric oxide is then capable of cleaving the heparan sulfate side chains.PTM N- and O-glycosylated. N-glycosylation is mainly of the complex type containing sialic acid. O-glycosylated with heparan sulfate. The heparan sulfate chains can be cleaved either by the action of heparanase or, degraded by a deaminative process that uses nitric oxide (NO) released from the S-nitrosylated cysteines. This process is triggered by ascorbate, or by some other reducing agent, in a Cu(2+)- or Zn(2+) dependent manner. Cu(2+) ions are provided by ceruloproteins such as APP, PRNP or CP which associate with GCP1 in intracellular compartments or lipid rafts.PTM This cell-associated glypican is further processed to give rise to a medium-released species.DISEASE Associates (via the heparan sulfate side chains) with fibrillar APP amyloid-beta peptides in primitive and classic amyloid plaques and may be involved in the deposition of these senile plaques in the Alzheimer disease (AD) brain (PubMed:15084524).DISEASE Misprocessing of GPC1 is found in fibroblasts of patients with Niemann-Pick Type C1 disease. This is due to the defective deaminative degradation of heparan sulfate chains (PubMed:16645004).SIMILARITY Belongs to the glypican family.UniProtP3505224EQUAL530EQUALReactome Database ID Release 752076567Database 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=2076567ReactomeR-HSA-20765671Reactome 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-2076567.1GPC2Heparan-GPC2GlcA-Gal-Gal-Xyl-GPC2Glypican-2 component recommendedName: Secreted glypican-2 /componentGPC2_HUMANReactome DB_ID: 2076293UniProt:Q8N158 GPC2GPC2FUNCTION Cell surface proteoglycan that bears heparan sulfate. May fulfill a function related to the motile behaviors of developing neurons (By similarity).SUBUNIT Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2. Interacts (heparan sulfate chain) with MDK; this interaction is inhibited by heparin followed by chondroitin sulfate E; this interaction induces GPC2 clustering through heparan sulfate chain; this interaction induces neuronal cell adhesion and neurite outgrowth (By similarity).SIMILARITY Belongs to the glypican family.UniProtQ8N15824EQUAL554EQUALReactome Database ID Release 752076293Database 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=2076293ReactomeR-HSA-20762931Reactome 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-2076293.1GPC3Heparan-GPC3GlcA-Gal-Gal-Xyl-GPC3Glypican-3GPC3_HUMANReactome DB_ID: 2076477UniProt:P51654 GPC3GPC3OCI5FUNCTION Cell surface proteoglycan that bears heparan sulfate (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (By similarity). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (By similarity). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (PubMed:16227623, PubMed:24496449). Positively regulates the non-canonical Wnt signaling pathway (By similarity). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Inhibits the dipeptidyl peptidase activity of DPP4 (PubMed:17549790). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (By similarity). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (By similarity). Required for coronary vascular development (By similarity). Plays a role in regulating cell movements during gastrulation (By similarity).SUBUNIT Heterodimer; disulfide-linked (PubMed:14610063). Cleavage by a furin-like convertase results in production of alpha and beta chains which form a disulfide-linked heterodimer (PubMed:14610063). Interacts with DPP4 (PubMed:17549790). Interacts with FGF2 (By similarity). Interacts with WNT5A (PubMed:14610063). Also interacts with WNT3A and WNT7B (PubMed:16227623). Interacts with hedgehog protein SHH; the heparan sulfate chains are not required for the interaction (By similarity). Also interacts with hedgehog protein IHH (By similarity). Interacts with CD81 (By similarity). Interacts with Wnt receptors FZD4, FZD7 and FZD8; the heparan sulfate chains are required for the interaction (PubMed:24496449).TISSUE SPECIFICITY Highly expressed in lung, liver and kidney.PTM O-glycosylated; contains heparan sulfate.PTM Cleaved intracellularly by a furin-like convertase to generate 2 subunits, alpha and beta, which remain associated through disulfide bonds and are associated with the cell surface via the GPI-anchor (PubMed:14610063). This processing is essential for its role in inhibition of hedgehog signaling (PubMed:25653284). A second proteolytic event may result in cleavage of the protein on the cell surface, separating it from the GPI-anchor and leading to its shedding from the cell surface (PubMed:14610063).MISCELLANEOUS Used as a marker for hepatocellular carcinoma (HCC) as it is expressed in HCC but is not detectable in hepatocytes from normal or benign liver diseases (PubMed:12851874). When attached to the cell surface, stimulates the growth of HCC cells by increasing canonical Wnt signaling (PubMed:16024626). Cleavage is not required for stimulation of Wnt signaling or HCC growth (PubMed:16227623).SIMILARITY Belongs to the glypican family.UniProtP5165425EQUAL-1EQUALReactome Database ID Release 752076477Database 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=2076477ReactomeR-HSA-20764771Reactome 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-2076477.1GPC4Heparan-GPC4GlcA-Gal-Gal-Xyl-GPC4Glypican-4GPC4_HUMANReactome DB_ID: 2076475UniProt:O75487 GPC4GPC4UNQ474/PRO937FUNCTION Cell surface proteoglycan that bears heparan sulfate. May be involved in the development of kidney tubules and of the central nervous system (By similarity).SIMILARITY Belongs to the glypican family.UniProtO7548719EQUAL529EQUALReactome Database ID Release 752076475Database 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=2076475ReactomeR-HSA-20764751Reactome 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-2076475.1GPC5Heparan-GPC5GlcA-Gal-Gal-Xyl-GPC5Glypican-5 component recommendedName: Secreted glypican-5 /componentGPC5_HUMANReactome DB_ID: 2076472UniProt:P78333 GPC5GPC5FUNCTION Cell surface proteoglycan that bears heparan sulfate.TISSUE SPECIFICITY In adult, primarily expressed in the brain. Also detected in fetal brain, lung and liver.SIMILARITY Belongs to the glypican family.UniProtP7833325EQUAL-1EQUALReactome Database ID Release 752076472Database 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=2076472ReactomeR-HSA-20764721Reactome 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-2076472.1GPC6Heparan-GPC6GlcA-Gal-Gal-Xyl-GPC6Glypican-6 component recommendedName: Secreted glypican-6 /componentGPC6_HUMANReactome DB_ID: 2076534UniProt:Q9Y625 GPC6GPC6UNQ369/PRO705FUNCTION Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases (By similarity). Enhances migration and invasion of cancer cells through WNT5A signaling.TISSUE SPECIFICITY Widely expressed. High expression in fetal kidney and lung and lower expressions in fetal liver and brain. In adult tissues, very abundant in ovary, high levels also observed in liver, kidney, small intestine and colon. Not detected in peripheral blood leukocytes. Detected in breast cancer cells (at protein level).INDUCTION Expression is induced by NFATC2.SIMILARITY Belongs to the glypican family.UniProtQ9Y62524EQUAL529EQUALReactome Database ID Release 752076534Database 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=2076534ReactomeR-HSA-20765341Reactome 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-2076534.1PerlecanHeparan-HSPG2GlcA-Gal-Gal-Xyl-HSPG2Reactome DB_ID: 2076367UniProt:P98160 HSPG2HSPG2FUNCTION 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.UniProtP9816022EQUAL4391EQUALReactome Database ID Release 752076367Database 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=2076367ReactomeR-HSA-20763671Reactome 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-2076367.1syndecan 1Heparan-SDC1GlcA-Gal-Gal-Xyl-SDC1Reactome DB_ID: 2076561UniProt:P18827 SDC1SDC1SDCFUNCTION Cell surface proteoglycan that bears both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413).SUBUNIT Interacts with CDCP1. Interacts (via C-terminus) with TIAM1 (via PDZ domain). Interacts with MDK (By similarity).PTM Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3.SIMILARITY Belongs to the syndecan proteoglycan family.UniProtP1882723EQUAL310EQUALReactome Database ID Release 752076561Database 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=2076561ReactomeR-HSA-20765611Reactome 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-2076561.1HSPGHeparan-SDC2GlcA-Gal-Gal-Xyl-SDC2SDC2_HUMANHeparan sulfate proteoglycan core proteinReactome DB_ID: 2076608UniProt:P34741 SDC2SDC2HSPG1FUNCTION Cell surface proteoglycan that bears heparan sulfate. Regulates dendritic arbor morphogenesis (By similarity).SUBUNIT Interacts (via cytoplasmic domain) with SARM1 (By similarity). Forms a complex with SDCBP and PDCD6IP (PubMed:22660413).PTM O-glycosylated with core 1 or possibly core 8 glycans. Contains heparan sulfate.SIMILARITY Belongs to the syndecan proteoglycan family.UniProtP3474119EQUAL201EQUALReactome Database ID Release 752076608Database 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=2076608ReactomeR-HSA-20766081Reactome 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-2076608.1SDC3Heparan-SDC3GlcA-Gal-Gal-Xyl-SDC3Syndecan-3SDC3_HUMANReactome DB_ID: 2076462UniProt:O75056 SDC3SDC3KIAA0468FUNCTION Cell surface proteoglycan that may bear heparan sulfate (By similarity). May have a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism.SUBUNIT Interacts with TIAM1 (PubMed:23395182). Interacts with PTN (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment (By similarity). Interacts with MDK; this interaction induces SDC3 clustering; this interaction induces neuronal cell adhesion and neurite outgrowth (By similarity).TISSUE SPECIFICITY Expressed in the nervous system, the adrenal gland, and the spleen.PTM O-glycosylated within the Thr/Ser-rich region which could interact with lectin domains on other molecules.SIMILARITY Belongs to the syndecan proteoglycan family.UniProtO750561EQUAL442EQUALReactome Database ID Release 752076462Database 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=2076462ReactomeR-HSA-20764621Reactome 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-2076462.1SDC4Heparan-SDC4GlcA-Gal-Gal-Xyl-SDC4Syndecan-4SDC4_HUMANReactome DB_ID: 2076374UniProt:P31431 SDC4SDC4FUNCTION Cell surface proteoglycan that bears heparan sulfate. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413).SUBUNIT Homodimer. Interacts (via its cytoplasmic domain) with GIPC (via its PDZ domain). Interacts (via its cytoplasmic domain) with NUDT16L1 (By similarity). Interacts with CDCP1 and SDCBP.TISSUE SPECIFICITY Expressed in epithelial and fibroblastic cells.PTM Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3.SIMILARITY Belongs to the syndecan proteoglycan family.UniProtP3143119EQUAL198EQUALReactome Database ID Release 752076374Database 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=2076374ReactomeR-HSA-20763741Reactome 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-2076374.1Reactome Database ID Release 752076465Database 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=2076465ReactomeR-HSA-20764651Reactome 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-2076465.1UDP-GlcAUDP-glucuronic acidUDP-alpha-D-glucuronic acidReactome DB_ID: 1889970UDP-alpha-D-glucuronic acid [ChEBI:17200]UDP-alpha-D-glucuronic acidChEBICHEBI:17200Reactome Database ID Release 751889970Database 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=1889970ReactomeR-ALL-18899703Reactome 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-ALL-1889970.3COMPOUNDC00167additional informationMIMI:0361ACTIVATIONEXT1:EXT2 mutantsReactome DB_ID: 9036278Golgi membraneGENE ONTOLOGYGO:0000139Converted from EntitySet in ReactomeEXT2 mutantsReactome DB_ID: 3731111EXT2_HUMANEXT2 404fs*Exostosin-2Reactome DB_ID: 3731083UniProt:Q93063 EXT2EXT2FUNCTION Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a tumor suppressor. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).PATHWAY Protein modification; protein glycosylation.SUBUNIT Forms a homo/hetero-oligomeric complex with EXT1. Interacts with GALNT5. Interacts with NDST1.TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the glycosyltransferase 47 family.UniProtQ93063Deletion of residues 361 to 3911EQUAL718EQUALReactome Database ID Release 753731083Database 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=3731083ReactomeR-HSA-37310831Reactome 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-3731083.1EXT2 D227NExostosin-2EXT2_HUMANReactome DB_ID: 3731072227EQUALL-aspartic acid removalMODMOD:016341EQUAL718EQUALReactome Database ID Release 753731072Database 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=3731072ReactomeR-HSA-37310721Reactome 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-3731072.1EXT2 G172*Exostosin-2EXT2_HUMANReactome DB_ID: 3731079172EQUALglycine removalMODMOD:016381EQUAL718EQUALReactome Database ID Release 753731079Database 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=3731079ReactomeR-HSA-37310791Reactome 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-3731079.1EXT2 Q258*Exostosin-2EXT2_HUMANReactome DB_ID: 3731107258EQUALL-glutamine removalMODMOD:016371EQUAL718EQUALReactome Database ID Release 753731107Database 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=3731107ReactomeR-HSA-37311071Reactome 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-3731107.1EXT2 Y222*Exostosin-2EXT2_HUMANReactome DB_ID: 3731060222EQUALL-tyrosine removalMODMOD:016491EQUAL718EQUALReactome Database ID Release 753731060Database 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=3731060ReactomeR-HSA-37310601Reactome 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-3731060.1EXT2_HUMANEXT2 V187Pfs*115Exostosin-2Reactome DB_ID: 3731088Replacement of residues 187 to 300 by PPSMCLTRTHCASRRQHKRWPSSLGGIEVRITCCSTCCLEVPQIITQPWMSPETGPCWLVAAFLRGLTGKATMSAFLSIVHCQLRWIFQRKDQVHGNTSSCHLRWVSILSTERT1EQUAL300EQUALReactome Database ID Release 753731088Database 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=3731088ReactomeR-HSA-37310881Reactome 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-3731088.1Reactome Database ID Release 753731111Database 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=3731111ReactomeR-HSA-37311111Reactome 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-3731111.11EXT1Exostosin-1EXT1_HUMANReactome DB_ID: 2022897UniProt:Q16394 EXT1EXT1FUNCTION Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a tumor suppressor. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).PATHWAY Protein modification; protein glycosylation.SUBUNIT Forms a homo/hetero-oligomeric complex with EXT2.TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the glycosyltransferase 47 family.UniProtQ163941EQUAL746EQUALReactome Database ID Release 752022897Database 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=2022897ReactomeR-HSA-20228971Reactome 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-2022897.11Reactome Database ID Release 759036278Database 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=9036278ReactomeR-HSA-90362781Reactome 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-9036278.1GENE ONTOLOGYGO:0050509gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 759631922Database 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=9631922Reactome Database ID Release 759036289Database 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=9036289ReactomeR-HSA-90362892Reactome 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-9036289.29326317Pubmed1997Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostosesPhilippe, CPorter, D EEmerton, M EWells, D ESimpson, A HMonaco, A PAm. J. Hum. Genet. 61:520-88894688Pubmed1996Positional cloning of a gene involved in hereditary multiple exostosesWuyts, WVan Hul, WWauters, JNemtsova, MReyniers, EVan Hul, E VDe Boulle, Kde Vries, B BHendrickx, JHerrygers, IBossuyt, PBalemans, WFransen, EVits, LCoucke, PNowak, N JShows, Thomas BMallet, Lvan den Ouweland, A MMcGaughran, JHalley, Dicky JWillems, P JHum. Mol. Genet. 5:1547-578782816Pubmed1996The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genesStickens, DClines, GBurbee, DRamos, PThomas, SHogue, DHecht, J TLovett, MEvans, G ANat. Genet. 14:25-3219344451Pubmed2009New mutations of EXT1 and EXT2 genes in German patients with Multiple OsteochondromasHeinritz, WolframHüffmeier, UlrikeStrenge, SibylleMiterski, BiancaZweier, ChristianeLeinung, SteffenBohring, AxelMitulla, BeatePeters, UshaFroster, Ursula GAnn. Hum. Genet. 73:283-91