BioPAX pathway converted from "Reactions specific to the hybrid N-glycan synthesis pathway" in the Reactome database.Reactions specific to the hybrid N-glycan synthesis pathwayThe transfer of a bisecting GlcNAc by MGAT3 commits the pathway toward the synthesis of hybrid glycans, because MAN2 is not able to operate on bisected oligosaccharides (Schachter et al 2000, Priatel JJ et al, 1997). The expression of MGAT3 over MGAT2 in a tissue can regulate the synthesis of hybrid toward complex N-glycans. The addition of a GlcNAc between the two arms also prevents the action of MGAT4, MGAT5 and FUT8.Authored: Dall'Olio, GM, 2009-11-10Reviewed: Gagneux, P, 2010-11-18Edited: Jassal, B, 2010-09-30LEFT-TO-RIGHT2.4.1.144Addition of a bifurcating GlcNAc to the N-glycan by MGAT3The addition of a bisecting GlcNAc to a complex N-glycan by MGAT3 is one of the most important regulatory steps in N-glycosylation, directing the pathway toward the synthesis of complex and hybrid N-glycans. This addition changes the structure of the N-glycan and inhibits further modification by MGAT2, MGAT4, MGAT5A/B and FUT8. Defects in MGAT3 have been shown to be associated with predisposition to cancer and several developmental defects (Song et al 2010; Stanley 2002).Authored: Dall'Olio, GM, 2009-11-10Reviewed: Gagneux, P, 2010-11-18Edited: Jassal, B, 2010-10-08UDP-GlcNAcUDP-N-acetyl-D-glucosamineUDP-N-acetyl-alpha-D-glucosamineUDP-N-acetylglucosamineReactome DB_ID: 914003Golgi lumenGENE ONTOLOGYGO:0005796UDP-N-acetyl-alpha-D-glucosamine [ChEBI:16264]UDP-N-acetyl-alpha-D-glucosamineChEBICHEBI:16264Reactome Database ID Release 75914003Database 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=914003ReactomeR-ALL-9140033Reactome 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-914003.3Reactomehttp://www.reactome.orgNGPN-glycoproteinN-glycanReactome DB_ID: 975910N-glycan [ChEBI:59520]N-glycanChEBICHEBI:59520Reactome Database ID Release 75975910Database 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=975910ReactomeR-ALL-9759103Reactome 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-975910.3Glycoprotein with bifurcating GlcNAc in position 3Reactome DB_ID: 981613Reactome Database ID Release 75981613Database 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=981613ReactomeR-ALL-9816132Reactome 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-981613.2ChEBI33837additional informationMIMI:0361ACTIVATIONMGAT3Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferaseMGAT3_HUMANReactome DB_ID: 975897Golgi membraneGENE ONTOLOGYGO:0000139UniProt:Q09327 MGAT3MGAT3GGNT3FUNCTION It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked sugar chains, called bisecting N-acetylglucosamine (GlcNAc). It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. The addition of this bisecting GlcNAc residue alters not only the composition, but also the conformation of the N-glycan. The introduction of the bisecting GlcNAc residue results in the suppression of further processing and elongation of N-glycans, precluding the formation of beta-1,6 GlcNAc branching, catalyzed by MGAT5 since it is unable to use the bisected oligosaccharide as a substrate (PubMed:19403558). Addition of bisecting N-acetylglucosamine to CDH1/E-cadherin modulates CDH1 cell membrane location (PubMed:19403558). Inhibits NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc- formation which modulates sialylation levels and plays a role in cell migration regulation (PubMed:26801611). In brain, addition of bisecting N-acetylglucosamine to BACE1 blocks its lysosomal targeting in response to oxidative stress and further degradation which increases its location to early endosome and the APP cleavage (By similarity).PATHWAY Protein modification; protein glycosylation.SUBUNIT Interacts with MGAT4D.INDUCTION Expression is up-regulated by CDH1/E-cadherin-mediated cell-cell interaction.SIMILARITY Belongs to the glycosyltransferase 17 family.Homo sapiensNCBI Taxonomy9606UniProtQ093271EQUAL533EQUALReactome Database ID Release 75975897Database 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=975897ReactomeR-HSA-9758971Reactome 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-975897.1GENE ONTOLOGYGO:0003830gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 75975892Database 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=975892Reactome Database ID Release 75975926Database 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=975926ReactomeR-HSA-9759261Reactome 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-975926.112417419Pubmed2002Biological consequences of overexpressing or eliminating N-acetylglucosaminyltransferase-TIII in the mouseStanley, PBiochim Biophys Acta 1573:363-820395209Pubmed2010The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progressionSong, YAglipay, JABernstein, JDGoswami, SStanley, PCancer Res 70:3361-71Reactome Database ID Release 75975574Database 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=975574ReactomeR-HSA-9755741Reactome 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-975574.111421343Pubmed2000The joys of HexNAc. The synthesis and function of N- and O-glycan branchesSchachter, HGlycoconj J 17:465-839061364Pubmed1997Isolation, characterization and inactivation of the mouse Mgat3 gene: the bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears dispensable for viability and reproductionPriatel, JJSarkar, MSchachter, HMarth, JDGlycobiology 7:45-56