BioPAX pathway converted from "Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan" in the Reactome database.2.4.1.225Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparanDefective 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 ReactomeReactome DB_ID: 20764651Golgi lumenGO0005796Heparan-PGs [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityHeparan-GPC2 [Golgi lumen]Heparan-SDC1 [Golgi lumen]Heparan-AGRN [Golgi lumen]Heparan-HSPG2 [Golgi lumen]Heparan-SDC3 [Golgi lumen]Heparan-GPC6 [Golgi lumen]Heparan-SDC4 [Golgi lumen]Heparan-SDC2 [Golgi lumen]Heparan-GPC1 [Golgi lumen]Heparan-GPC3 [Golgi lumen]Heparan-GPC4 [Golgi lumen]Heparan-GPC5 [Golgi lumen]Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtQ8N158UniProtP18827UniProtO00468UniProtP98160UniProtO75056UniProtQ9Y625UniProtP31431UniProtP34741UniProtP35052UniProtP51654UniProtO75487UniProtP78333Reactome DB_ID: 18899701UDP-alpha-D-glucuronic acid [ChEBI:17200]UDP-alpha-D-glucuronic acidChEBI17200PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9036278Golgi membraneGO0000139EXT1:EXT2 mutants [Golgi membrane]EXT1:EXT2 mutantsConverted from EntitySet in ReactomeReactome DB_ID: 37311111EXT2 mutants [Golgi membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityEXT2 D227N [Golgi membrane]EXT2 Y222* [Golgi membrane]EXT2 G172* [Golgi membrane]EXT2 V187Pfs*115 [Golgi membrane]EXT2 Q258* [Golgi membrane]EXT2 404fs* [Golgi membrane]UniProtQ93063Reactome DB_ID: 20228971UniProt:Q16394 EXT1EXT1EXT1FUNCTION 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.UniProtQ16394Chain Coordinates1EQUAL746EQUALReactome 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-9036278.1GO0050509GO molecular functionReactome 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