BioPAX pathway converted from "Diseases associated with N-glycosylation of proteins" in the Reactome database.Diseases associated with N-glycosylation of proteinsCongenital disorders of glycosylation (CDGs) are a group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. These glycoconjugates play critical roles in processes such as metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity. CDGs are divided into 2 main groups: type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs comprise defects in the trimming and processing of protein-bound glycans (Marquardt & Denecke 2003, Grunewald et al. 2002, Hennet 2012, Cylwik et al. 2013).Authored: Jassal, B, 2013-06-28Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-06-28Defective ALG6 causes ALG6-CDG (CDG-1c)Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG6) normally adds the first glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins (Imbach et al. 1999). Defects in ALG6 can cause congenital disorder of glycosylation 1c (ALG6-CDG, CDG-1c; MIM:603147), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Imbach et al. 1999, Imbach et al. 2000, Westphal et al. 2000, Sun et al. 2005). ALG6 deficiency is accompanied by an accumulation of the N-glycan precursor (GlcNAc)2 (Man)9 (PP-Dol)1 and is the second most common CDG disease subtype after PMM2-CDG (CDG-1a) (Imbach et al. 1999). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency.Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-23LEFT-TO-RIGHT2.4.1Defective ALG6 does not add glucose to the N-glycan precursorDolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG6) normally adds the first glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins (Imbach et al. 1999). Defects in ALG6 can cause congenital disorder of glycosylation 1c (ALG6-CDG, CDG-1c; MIM:603147), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Imbach et al. 1999, Imbach et al. 2000, Westphal et al. 2000, Sun et al. 2005). ALG6 deficiency is accompanied by an accumulation of the N-glycan precursor (GlcNAc)2 (Man)9 (PP-Dol)1 (Imbach et al. 1999). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Mutations that can cause ALG6-CDG are A333V and S478P. The A333V mutation is the most commom mutation seen in ALG6-CDG patients. These mutations result in altered activity of ALG6 but don't completely abolish its activity (Imbach et al. 1999, Imbach et al. 2000, Dercksen et al. 2013). A c.257+5G>A splice site mutation (not shown here) that causes exon 3 skipping leads to a nonfunctional protein (Imbach et al. 2000, Westphal et al. 2000). Two more mutations can cause the build up of the N-glycan precursor (GlcNAc)2 (Man)9 (PP-Dol)1; a three bp deletion (897-899delAAT) in exon 9 and an intronic<br>mutation (680+2T>G) in intron 7 (neither shown here). Transduction of patient fibroblasts with a lentivirus carrying wildtype hALG6 improved the biochemical phenotype of the cells, confirming that these two mutations are disease-causing (Sun et al. 2005).Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-23(GlcNAc)2 (Man)9 (PP-Dol)1alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)Reactome DB_ID: 449371integral component of lumenal side of endoplasmic reticulum membraneGENE ONTOLOGYGO:0071556alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:37637]alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBICHEBI:37637Reactome Database ID Release 73449371Database 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=449371ReactomeR-ALL-4493713Reactome 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-449371.3Reactomehttp://www.reactome.orgDbGPdolichyl beta-D-glucosyl phosphateReactome DB_ID: 532542dolichyl beta-D-glucosyl phosphate [ChEBI:15812]dolichyl beta-D-glucosyl phosphateChEBICHEBI:15812Reactome Database ID Release 73532542Database 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=532542ReactomeR-ALL-5325423Reactome 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-532542.3ACTIVATIONConverted from EntitySet in ReactomeALG6 mutantsReactome DB_ID: 4724300ALG6 A333VDolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferaseALG6_HUMANReactome DB_ID: 4724295endoplasmic reticulum membraneGENE ONTOLOGYGO:0005789UniProt:Q9Y672 ALG6ALG6My046FUNCTION Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man(9)GlcNAc(2)-PP-Dol.PATHWAY Protein modification; protein glycosylation.SIMILARITY Belongs to the ALG6/ALG8 glucosyltransferase family.Homo sapiensNCBI Taxonomy9606UniProtQ9Y672333EQUALL-alanine removalMODMOD:016311EQUAL507EQUALReactome Database ID Release 734724295Database 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=4724295ReactomeR-HSA-47242951Reactome 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-4724295.1ALG6 S478PDolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferaseALG6_HUMANReactome DB_ID: 4724296478EQUALL-serine removalMODMOD:016461EQUAL507EQUALReactome Database ID Release 734724296Database 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=4724296ReactomeR-HSA-47242961Reactome 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-4724296.1Reactome Database ID Release 734724300Database 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=4724300ReactomeR-HSA-47243001Reactome 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-4724300.1GENE ONTOLOGYGO:0004583gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 739631762Database 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=9631762Reactome Database ID Release 734724291Database 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=4724291ReactomeR-HSA-47242912Reactome 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-4724291.210924277Pubmed2000Analysis of multiple mutations in the hALG6 gene in a patient with congenital disorder of glycosylation IcWestphal, VSchottstädt, CMarquardt, TFreeze, H HMol. Genet. Metab. 70:219-2323430515Pubmed2013ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel PatientsDercksen, MCrutchley, A CHoney, E MLippert, M MMatthijs, GMienie, L JSchuman, H CVorster, B CJaeken, JJIMD Rep 8:17-2316007612Pubmed2005Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patientSun, LEklund, EAVan Hove, JLFreeze, HHThomas, JAAm J Med Genet A 137:22-610914684Pubmed2000Multi-allelic origin of congenital disorder of glycosylation (CDG)-IcImbach, TGrünewald, SSchenk, BBurda, PSchollen, EWevers, R AJaeken, Jde Klerk, J BBerger, E GMatthijs, GAebi, MHennet, THum. Genet. 106:538-4510359825Pubmed1999A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-IcImbach, TBurda, PKuhnert, PWevers, RAAebi, MBerger, EGHennet, TProc Natl Acad Sci U S A 96:6982-7Reactome Database ID Release 734724289Database 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=4724289ReactomeR-HSA-47242891Reactome 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-4724289.1Defective ALG3 causes ALG3-CDG (CDG-1d)Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase (ALG3) adds the sixth mannose (although the first to be derived from dolichyl-phosphate-mannose, DOLPman) to the lipid-linked oligosaccharide (LLO) intermediate GlcNAc(2) Man(5) (PPDol)1 (Korner et al. 1999). Defects in ALG3 are associated with congenital disorder of glycosylation 1d (ALG3-CDG, CDG1d; MIM:601110), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Sun et al. 2005).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21LEFT-TO-RIGHT2.4.1Defective ALG3 does not add mannose to the N-glycan precursorDol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase (ALG3) adds the sixth mannose (although the first to be derived from dolichyl-phosphate-mannose, DOLPman) to the lipid-linked oligosaccharide intermediate GlcNAc(2) Man(5) (PPDol)1 (Korner et al. 1999). Defects in ALG3 are associated with congenital disorder of glycosylation 1d (ALG3-CDG, CDG1d; MIM:601110), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. (Sun et al. 2005). Point mutations that cause ALG3-CDG are G118D, R171Q, W71R and M157K (Korner et al. 1999, Sun et al. 2005, Kranz et al. 2007).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21DOLP-ManDolichyl phosphate D-mannosedolichyl D-mannosyl phosphateReactome DB_ID: 449229dolichyl D-mannosyl phosphate [ChEBI:15809]dolichyl D-mannosyl phosphateDolichyl phosphate D-mannoseChEBICHEBI:15809Reactome Database ID Release 73449229Database 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=449229ReactomeR-ALL-4492293Reactome 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-449229.3glycan G00006(GlcNAc)2 (Man)5 (PP-Dol)1Reactome DB_ID: 449298glycan G00006 [ChEBI:53022]glycan G00006ChEBICHEBI:53022Reactome Database ID Release 73449298Database 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=449298ReactomeR-ALL-4492983Reactome 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-449298.3ACTIVATIONConverted from EntitySet in ReactomeALG3 mutantsReactome DB_ID: 4720485ALG3 G118DDolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferaseDolichyl-P-Man:ManALG3_HUMANReactome DB_ID: 4720468UniProt:Q92685 ALG3ALG3NOTNOT56LFUNCTION Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man5GlcNAc2-PP-Dol.PATHWAY Protein modification; protein glycosylation.SIMILARITY Belongs to the glycosyltransferase 58 family.UniProtQ92685118EQUALglycine removalMODMOD:016381EQUAL438EQUALReactome Database ID Release 734720468Database 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=4720468ReactomeR-HSA-47204681Reactome 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-4720468.1ALG3 M157KDolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferaseDolichyl-P-Man:ManALG3_HUMANReactome DB_ID: 4720484157EQUALL-methionine removalMODMOD:016431EQUAL438EQUALReactome Database ID Release 734720484Database 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=4720484ReactomeR-HSA-47204841Reactome 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-4720484.1ALG3 R171QDolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferaseDolichyl-P-Man:ManALG3_HUMANReactome DB_ID: 4720470171EQUALL-arginine removalMODMOD:016321EQUAL438EQUALReactome Database ID Release 734720470Database 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=4720470ReactomeR-HSA-47204701Reactome 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-4720470.1ALG3 W71RDolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferaseDolichyl-P-Man:ManALG3_HUMANReactome DB_ID: 472046671EQUALL-tryptophan removalMODMOD:016481EQUAL438EQUALReactome Database ID Release 734720466Database 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=4720466ReactomeR-HSA-47204661Reactome 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-4720466.1Reactome Database ID Release 734720485Database 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=4720485ReactomeR-HSA-47204851Reactome 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-4720485.1GENE ONTOLOGYGO:0000033Reactome Database ID Release 739631799Database 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=9631799Reactome Database ID Release 734720473Database 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=4720473ReactomeR-HSA-47204732Reactome 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-4720473.217551933Pubmed2007CDG-Id in two siblings with partially different phenotypesKranz, ChristianSun, LiangwuEklund, Erik AKrasnewich, DonnaCasey, Janet RFreeze, Hudson HAm. J. Med. Genet. A 143:1414-2015840742Pubmed2005Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasiaSun, LEklund, EAChung, WKWang, CCohen, JFreeze, HHJ Clin Endocrinol Metab 90:4371-510581255Pubmed1999Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferaseKörner, CKnauer, RStephani, UMarquardt, TLehle, Lvon Figura, KEMBO J. 18:6816-22Reactome Database ID Release 734720475Database 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=4720475ReactomeR-HSA-47204751Reactome 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-4720475.1Defective MPDU1 causes MPDU1-CDG (CDG-1f)Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15LEFT-TO-RIGHTDefective MPDU1 does not promote transfer of Man to N-glycan precursor (GlcNAc)2 (Man)7 (PP-Dol)1 by ALG12Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15(GlcNAc)2 (Man)7 (PP-Dol)1alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)Reactome DB_ID: 449312alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:59088]alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBICHEBI:59088Reactome Database ID Release 73449312Database 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=449312ReactomeR-ALL-4493123Reactome 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-449312.3Reactome Database ID Release 734686998Database 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=4686998ReactomeR-HSA-46869983Reactome 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-4686998.311733564Pubmed2001MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type IfSchenk, BImbach, TFrank, C GGrubenmann, C ERaymond, G VHurvitz, HKorn-Lubetzki, IRevel-Vik, SRaas-Rotschild, ALuder, A SJaeken, JBerger, E GMatthijs, GHennet, TAebi, MJ. Clin. Invest. 108:1687-9511179430Pubmed2001Requirement of the Lec35 gene for all known classes of monosaccharide-P-dolichol-dependent glycosyltransferase reactions in mammalsAnand, MRush, J SRay, SDoucey, M AWeik, JWare, F EHofsteenge, JWaechter, C JLehrman, M AMol. Biol. Cell 12:487-50111733556Pubmed2001A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If)Kranz, CDenecke, JLehrman, M ARay, SKienz, PKreissel, GSagi, DPeter-Katalinic, JFreeze, H HSchmid, TJackowski-Dohrmann, SHarms, EMarquardt, TJ. Clin. Invest. 108:1613-9ACTIVATIONReactome Database ID Release 739631845Database 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=9631845Converted from EntitySet in ReactomeMPDU1 mutantsReactome DB_ID: 4717371MPDU1 G73EMannose-P-dolichol utilization defect 1 proteinMPU1_HUMANReactome DB_ID: 4717405UniProt:O75352 MPDU1MPDU1FUNCTION Required for normal utilization of mannose-dolichol phosphate (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors.SIMILARITY Belongs to the MPDU1 (TC 2.A.43.3) family.UniProtO7535273EQUAL2EQUAL247EQUALReactome Database ID Release 734717405Database 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=4717405ReactomeR-HSA-47174051Reactome 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-4717405.1MPU1_HUMANMPDU1 L119PMannose-P-dolichol utilization defect 1 proteinReactome DB_ID: 4717365119EQUALL-leucine removalMODMOD:016412EQUAL247EQUALReactome Database ID Release 734717365Database 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=4717365ReactomeR-HSA-47173651Reactome 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-4717365.1MPU1_HUMANMPDU1 L171Sfs*42Mannose-P-dolichol utilization defect 1 proteinReactome DB_ID: 4717376Replacement of residues 171 to 211 by SRQPPTTTTGTQASSQPSQSSCCLGAPWPESSLPFRKPEIP2EQUAL247EQUALReactome Database ID Release 734717376Database 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=4717376ReactomeR-HSA-47173761Reactome 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-4717376.1MPDU1 L74SMannose-P-dolichol utilization defect 1 proteinMPU1_HUMANReactome DB_ID: 471735874EQUAL2EQUAL247EQUALReactome Database ID Release 734717358Database 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=4717358ReactomeR-HSA-47173581Reactome 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-4717358.1MPDU1 M1TMannose-P-dolichol utilization defect 1 proteinMPU1_HUMANReactome DB_ID: 47173811EQUAL2EQUAL247EQUALReactome Database ID Release 734717381Database 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=4717381ReactomeR-HSA-47173811Reactome 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-4717381.1Reactome Database ID Release 734717371Database 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=4717371ReactomeR-HSA-47173711Reactome 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-4717371.1LEFT-TO-RIGHTDefective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)8 (PP-Dol)1 by ALG9Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15(GlcNAc)2 (Man)8 (PP-Dol)1alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->3)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)Reactome DB_ID: 449365alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->3)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:59091]alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->3)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBICHEBI:59091Reactome Database ID Release 73449365Database 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=449365ReactomeR-ALL-4493653Reactome 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-449365.3Reactome Database ID Release 739036020Database 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=9036020ReactomeR-HSA-90360202Reactome 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-9036020.2ACTIVATIONReactome Database ID Release 739631911Database 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=9631911LEFT-TO-RIGHTDefective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)6 (PP-Dol)1 by ALG9Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15glycan G10595(GlcNAc)2 (Man)6 (PP-Dol)1Reactome DB_ID: 449315glycan G10595 [ChEBI:53023]glycan G10595ChEBICHEBI:53023Reactome Database ID Release 73449315Database 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=449315ReactomeR-ALL-4493153Reactome 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-449315.3Reactome Database ID Release 739036021Database 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=9036021ReactomeR-HSA-90360212Reactome 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-9036021.2ACTIVATIONReactome Database ID Release 739631732Database 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=9631732LEFT-TO-RIGHTDefective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)5 (PP-Dol)1 by ALG3Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15Reactome Database ID Release 739036025Database 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=9036025ReactomeR-HSA-90360252Reactome 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-9036025.2ACTIVATIONReactome Database ID Release 739631953Database 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=9631953Reactome Database ID Release 734687000Database 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=4687000ReactomeR-HSA-46870002Reactome 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-4687000.2Defective ALG12 causes ALG12-CDG (CDG-1g)Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase (ALG12) (Chantret et al. 2002) normally tranfers the 8th mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG12 are associated with congenital disorder of glycosylation 1g (ALG12-CDG, CDG1g; MIM:607143), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Chantret et al. 2002, Grubenmann et al. 2002). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency.Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21LEFT-TO-RIGHT2.4.1Defective ALG12 does not add mannose to the N-glycan precursorDol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase (ALG12) (Chantret et al. 2002) normally tranfers the 8th mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG12 are associated with congenital disorder of glycosylation 1g (ALG12-CDG, CDG1g; MIM:607143), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Chantret et al. 2002, Grubenmann et al. 2002). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Point mutations that can cause ALG12-CDG are F142V, T67M, R146Q, G101R, L158P and Y414* (Chantret et al. 2002, Grubenmann et al. 2002).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21ACTIVATIONConverted from EntitySet in ReactomeALG12 mutantsReactome DB_ID: 4722114ALG12 F142VDolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferaseALG12_HUMANReactome DB_ID: 4722108UniProt:Q9BV10 ALG12ALG12PP14673FUNCTION Adds the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation.PATHWAY Protein modification; protein glycosylation.TISSUE SPECIFICITY Expressed in fibroblasts.SIMILARITY Belongs to the glycosyltransferase 22 family.UniProtQ9BV10142EQUALL-phenylalanine removalMODMOD:016441EQUAL488EQUALReactome Database ID Release 734722108Database 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=4722108ReactomeR-HSA-47221081Reactome 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-4722108.1ALG12 G101RDolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferaseALG12_HUMANReactome DB_ID: 4722101101EQUAL1EQUAL488EQUALReactome Database ID Release 734722101Database 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=4722101ReactomeR-HSA-47221011Reactome 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-4722101.1ALG12 L158PDolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferaseALG12_HUMANReactome DB_ID: 4722115158EQUAL1EQUAL488EQUALReactome Database ID Release 734722115Database 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=4722115ReactomeR-HSA-47221151Reactome 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-4722115.1ALG12 R146QDolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferaseALG12_HUMANReactome DB_ID: 4722098146EQUAL1EQUAL488EQUALReactome Database ID Release 734722098Database 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=4722098ReactomeR-HSA-47220981Reactome 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-4722098.1ALG12 T67MDolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferaseALG12_HUMANReactome DB_ID: 472211867EQUALL-threonine removalMODMOD:016471EQUAL488EQUALReactome Database ID Release 734722118Database 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=4722118ReactomeR-HSA-47221181Reactome 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-4722118.1ALG12 Y414*Dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferaseALG12_HUMANReactome DB_ID: 4722121414EQUALL-tyrosine removalMODMOD:016491EQUAL488EQUALReactome Database ID Release 734722121Database 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=4722121ReactomeR-HSA-47221211Reactome 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-4722121.1Reactome Database ID Release 734722114Database 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=4722114ReactomeR-HSA-47221141Reactome 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-4722114.1GENE ONTOLOGYGO:0000030Reactome Database ID Release 739631930Database 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=9631930Reactome Database ID Release 734720497Database 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=4720497ReactomeR-HSA-47204972Reactome 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-4720497.212217961Pubmed2002ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lgGrubenmann, Claudia EFrank, Christian GKjaergaard, SusanneBerger, Eric GAebi, MHennet, ThierryHum. Mol. Genet. 11:2331-911983712Pubmed2002Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferaseChantret, IDupré, TDelenda, CBucher, SDancourt, JBarnier, ACharollais, AHeron, DBader-Meunier, BDanos, OSeta, NDurand, GOriol, RCodogno, PMoore, SEJ Biol Chem 277:25815-22Reactome Database ID Release 734720489Database 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=4720489ReactomeR-HSA-47204891Reactome 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-4720489.1Defective ALG8 causes ALG8-CDG (CDG-1h)The probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG8) (Stanchi et al. 2001, Chantret et al. 2003) normally adds the second glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG8 can cause congenital disorder of glycosylation 1h (ALG8-CDG, CDG-1h; MIM:608104), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Chantret et al. 2003, Schollen et al. 2004). ALG8 deficiency is accompanied by an accumulation of the N-glycan precursor (Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency.Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-23LEFT-TO-RIGHT2.4.1Defective ALG8 does not add glucose to the N-glycan precursorThe probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG8) (Chantret et al. 2003) normally adds the second glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG8 can cause congenital disorder of glycosylation 1h (ALG8-CDG, CDG-1h; MIM:608104), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Chantret et al. 2003, Schollen et al. 2004). ALG8 deficiency is accompanied by an accumulation of the N-glycan precursor (Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1. Mutations that can cause ALG8-CDG include T47P, G275D, V133Sfs*3 and T138Kfs*19 (Chantret et al. 2003, Schollen et al. 2004).Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-23(Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1alpha-Gal-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)Reactome DB_ID: 449649alpha-Gal-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:59081]alpha-Gal-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBICHEBI:59081Reactome Database ID Release 73449649Database 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=449649ReactomeR-ALL-4496493Reactome 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-449649.3ACTIVATIONConverted from EntitySet in ReactomeALG8 mutantsReactome DB_ID: 4724315ALG8 G275DProbable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferaseALG8_HUMANReactome DB_ID: 4724304UniProt:Q9BVK2 ALG8ALG8HUSSY-02FUNCTION Adds the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(1)Man(9)GlcNAc(2)-PP-Dol before it is transferred to the nascent peptide (By similarity). Required for PKD1/Polycystin-1 maturation and localization to the plasma membrane of the primary cilia (By similarity).PATHWAY Protein modification; protein glycosylation.SIMILARITY Belongs to the ALG6/ALG8 glucosyltransferase family.UniProtQ9BVK2275EQUAL1EQUAL526EQUALReactome Database ID Release 734724304Database 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=4724304ReactomeR-HSA-47243041Reactome 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-4724304.1ALG8_HUMANALG8 T138Kfs*19Probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferaseReactome DB_ID: 4724312Replacement of residues 138 to 155 by KKSQNLFCRYYFCGTSGY1EQUAL155EQUALReactome Database ID Release 734724312Database 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=4724312ReactomeR-HSA-47243121Reactome 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-4724312.1ALG8 T47PProbable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferaseALG8_HUMANReactome DB_ID: 472433447EQUAL1EQUAL526EQUALReactome Database ID Release 734724334Database 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=4724334ReactomeR-HSA-47243341Reactome 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-4724334.1ALG8_HUMANALG8 V133Sfs*3Probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferaseReactome DB_ID: 4724313Replacement of residues 133 to 134 by SG1EQUAL134EQUALReactome Database ID Release 734724313Database 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=4724313ReactomeR-HSA-47243131Reactome 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-4724313.1Reactome Database ID Release 734724315Database 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=4724315ReactomeR-HSA-47243151Reactome 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-4724315.1Reactome Database ID Release 739631887Database 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=9631887Reactome Database ID Release 734724330Database 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=4724330ReactomeR-HSA-47243302Reactome 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-4724330.215235028Pubmed2004Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency)Schollen, EFrank, CGKeldermans, LReyntjens, RGrubenmann, CEClayton, Peter TWinchester, BGSmeitink, JWevers, RAAebi, MHennet, TMatthijs, GJ Med Genet 41:550-612480927Pubmed2003A deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylationChantret, IsabelleDancourt, JuliaDupré, ThierryDelenda, ChristopheBucher, StéphanieVuillaumier-Barrot, SandrineOgier de Baulny, HélènePeletan, CelineDanos, OlivierSeta, NathalieDurand, GenevièveOriol, RafaelCodogno, PatriceMoore, Stuart E HJ. Biol. Chem. 278:9962-71Reactome Database ID Release 734724325Database 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=4724325ReactomeR-HSA-47243251Reactome 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-4724325.111124703Pubmed2001Characterization of 16 novel human genes showing high similarity to yeast sequencesStanchi, FBertocco, EToppo, SDioguardi, RSimionati, BCannata, NZimbello, RLanfranchi, GValle, GYeast 18:69-80Defective ALG2 causes ALG2-CDG (CDG-1i)Alpha 1,3/1,6 mannosyltransferase ALG2 (ALG2) is a bifunctional mannosyltransferase normally tranfers a mannose moiety to the lipid linked oligosaccharide (LLO aka N glycan precursor) which is required for subsequent N glycosylation of proteins. Defects in ALG2 can cause congenital disorder of glycosylation 1i (ALG2-CDG, previously known as CDG1i; MIM:607906), a multisystem disorder characterised by under glycosylated serum glycoproteins. CDG type 1 diseases result in a wide phenotypic spectrum, from poor neurological development, psychomotor retardation and dysmorphic features to hypotonia, coagulation abnormalities and immunodeficiency (Thiel et al. 2003). Defect in ALG2 can also cause congenital myasthenic syndrome (ALG2-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al. 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG2-CMS include p.V68G and p.72_75delinsSPR (Cossins et al. 2013). Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12LEFT-TO-RIGHT2.4.1Defective ALG2 does not transfer a second Man to N-glycan precursorAlpha 1,3/1,6 mannosyltransferase ALG2 (ALG2) is a bifunctional mannosyltransferase which normally transfers a mannose moiety to the lipid linked oligosaccharide (LLO aka N glycan precursor) which is required for subsequent N glycosylation of proteins. Defects in ALG2 can cause congenital disorder of glycosylation 1i (ALG2-CDG, previously known as CDG1i; MIM:607906), a multisystem disorder characterised by under glycosylated serum glycoproteins. Two mutations causing ALG2-CDG have been identified in a patient; a compound heterozygote where one mutation is a 1-bp deletion (G) at 1040 (p.G347Vfs*27) and the other a G-T transversion at 393 (not shown) (Thiel et al. 2003). Defect in ALG2 can also cause congenital myasthenic syndrome (ALG2-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al., 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG2-CMS include p.V68G and p.72_75delinsSPR (Cossins et al., 2013).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12MDCDDbeta-D-mannosyldiacetylchitobiosyldiphosphodolicholReactome DB_ID: 449283integral component of cytoplasmic side of endoplasmic reticulum membraneGENE ONTOLOGYGO:0071458beta-D-mannosyldiacetylchitobiosyldiphosphodolichol [ChEBI:18396]beta-D-mannosyldiacetylchitobiosyldiphosphodolicholChEBICHEBI:18396Reactome Database ID Release 73449283Database 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=449283ReactomeR-ALL-4492833Reactome 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-449283.3GDP-Manguanosine 5'-(3-(alpha-D-mannopyranosyl) dihydrogen diphosphate)GDP-alpha-D-mannoseReactome DB_ID: 162860cytosolGENE ONTOLOGYGO:0005829GDP-alpha-D-mannose [ChEBI:15820]GDP-alpha-D-mannoseChEBICHEBI:15820Reactome Database ID Release 73162860Database 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=162860ReactomeR-ALL-1628603Reactome 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-162860.3ACTIVATIONConverted from EntitySet in ReactomeALG2 mutantsReactome DB_ID: 5633219ALG2_HUMANALG2 G347Vfs*27Alpha-1,3-mannosyltransferase ALG2Reactome DB_ID: 4549361UniProt:Q9H553 ALG2ALG2UNQ666/PRO1298FUNCTION Mannosylates Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate.PATHWAY Protein modification; protein glycosylation.SIMILARITY Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.UniProtQ9H553Replacement of residues 347 to 372 by VDPWSPLTTVSQGFCVSLTRCTSQKQ1EQUAL372EQUALReactome Database ID Release 734549361Database 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=4549361ReactomeR-HSA-45493611Reactome 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-4549361.1ALG2 V68GAlpha-1,3-mannosyltransferase ALG2ALG2_HUMANReactome DB_ID: 563323668EQUALL-valine removalMODMOD:016501EQUAL416EQUALReactome Database ID Release 735633236Database 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=5633236ReactomeR-HSA-56332361Reactome 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-5633236.1ALG2_HUMANALG2 72-75delinsSPRAlpha-1,3-mannosyltransferase ALG2Reactome DB_ID: 5633223Replacement of residues 72 to 75 by SPR1EQUAL416EQUALReactome Database ID Release 735633223Database 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=5633223ReactomeR-HSA-56332231Reactome 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-5633223.1Reactome Database ID Release 735633219Database 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=5633219ReactomeR-HSA-56332191Reactome 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-5633219.1Reactome Database ID Release 739631942Database 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=9631942Reactome Database ID Release 734549368Database 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=4549368ReactomeR-HSA-45493682Reactome 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-4549368.212684507Pubmed2003A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesisThiel, CSchwarz, MPeng, JGrzmil, MHasilik, MBraulke, TKohlschütter, Avon Figura, KLehle, LKörner, CJ Biol Chem 278:22498-505Reactome Database ID Release 734549349Database 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=4549349ReactomeR-HSA-45493491Reactome 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-4549349.123404334Pubmed2013Congenital myasthenic syndromes due to mutations in ALG2 and ALG14Cossins, JudithBelaya, KatsiarynaHicks, DebbieSalih, Mustafa AFinlayson, SarahCarboni, NicolaLiu, Wei WeiMaxwell, SusanZoltowska, KatarzynaFarsani, Golara TorabiLaval, StevenSeidhamed, Mohammed ZainBrain 136:944-56Defective DPAGT1 causes DPAGT1-CDG (CDG-1j) and CMSTA2UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the initial committed step in the biosynthesis of dolichyl pyrophosphate-oligosaccharides. Defects in DPAGT1 cause congenital disorder of glycosylation 1j (DPAGT1-CDG, previously known as CDG-1j; MIM:608093), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Wu et al. 2003, Timal et al. 2012). Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Defects in DPAGT1 can also cause myasthenic syndrome, congenital, with tubular aggregates, 2 (CMSTA2; MIM:614750), characterised by muscle weakness of mainly the proximal limb muscles, with tubular aggregates present on muscle biopsy. Sufferers find walking difficult and fall frequently. Younger sufferers show hypotonia and poor head control. A disorder of neuromuscular transmission is detected on electromyography (Belaya et al. 2012, Finlayson et al. 2013).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12LEFT-TO-RIGHT2.7.8.15Defective DPAGT1 does not transfer GlcNAc to DOLPIn the first committed step of N-glycan precursor (LLO) synthesis, UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) normally catalyses the transfer of N-acetylglucosamine (GlcNAc), via an alpha-1,3 linkage, to a molecule of dolichyl phosphate (DOLP). Defects in DPAGT1 can cause congenital disorder of glycosylation, type 1j (DPAGT1-CDG, previously called CDG1j; MIM:608093), a multisystem disorder characterised by under-glycosylated serum glycoproteins. Clinical features include defective nervous system development, psychomotor retardation, coagulation diorders and immunodeficiency. Mutations causing DPAGT1-CDG include Y170C, I69N and a G-A transition in intron 1 (not shown here) which results in degradation of the mutant mRNA (Wu et al. 2003, Timal et al. 2012). Defects in DPAGT1 can also cause myasthenic syndrome, congenital, with tubular aggregates, 2 (CMSTA2; MIM:614750 a syndrome that arises from impaired neuromuscular transmission and characterised by muscle weakness, especially of the limb-girdle. Mutations causing CMSTA2 include V117I, M108I, L120M, T234Hfs*116 and V264G (Belaya et al. 2012). Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12DOLPDolichol phosphatedolichyl phosphateReactome DB_ID: 449299dolichyl phosphate [ChEBI:16214]dolichyl phosphateDolichol phosphateDolichyl monophosphatedolichol monophosphateChEBICHEBI:16214Reactome Database ID Release 73449299Database 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=449299ReactomeR-ALL-4492993Reactome 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-449299.3UDP-GlcNAcUDP-N-acetyl-D-glucosamineUDP-N-acetyl-alpha-D-glucosamineUDP-N-acetylglucosamineReactome DB_ID: 162756UDP-N-acetyl-alpha-D-glucosamine [ChEBI:16264]UDP-N-acetyl-alpha-D-glucosamineChEBICHEBI:16264Reactome Database ID Release 73162756Database 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=162756ReactomeR-ALL-1627563Reactome 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-162756.3ACTIVATIONConverted from EntitySet in ReactomeDPAGT1 mutantsReactome DB_ID: 4549346GPT_HUMANDPAGT1 I65NUDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549352UniProt:Q9H3H5 DPAGT1DPAGT1DPAGT2FUNCTION Catalyzes the initial step of dolichol-linked oligosaccharide biosynthesis in N-linked protein glycosylation pathway: transfers GlcNAc-1-P from UDP-GlcNAc onto the carrier lipid dolichyl phosphate (P-dolichol), yielding GlcNAc-P-P-dolichol.ACTIVITY REGULATION Activated by mannosylphosphoryldolichol and phospholipids such as phosphatidylglycerol and phosphatidylcholine (Probable). Inhibited by natural nucleoside antibiotic tunicamycin, which acts as a structural analog and competitor of UDP-GlcNAc (PubMed:9451016, PubMed:29459785, PubMed:30388443).PATHWAY Protein modification; protein glycosylation.SUBUNIT Homodimer.SIMILARITY Belongs to the glycosyltransferase 4 family.UniProtQ9H3H565EQUALL-isoleucine removalMODMOD:016401EQUAL408EQUALReactome Database ID Release 734549352Database 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=4549352ReactomeR-HSA-45493521Reactome 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-4549352.1GPT_HUMANDPAGT1 L120MUDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549318120EQUAL1EQUAL408EQUALReactome Database ID Release 734549318Database 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=4549318ReactomeR-HSA-45493181Reactome 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-4549318.1GPT_HUMANDPAGT1 M108IUDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549374108EQUAL1EQUAL408EQUALReactome Database ID Release 734549374Database 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=4549374ReactomeR-HSA-45493741Reactome 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-4549374.1GPT_HUMANDPAGT1 T234Hfs*116UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549354Replacement of residues 234 to 348 by HHFGIALPQLVPITGVCGRYLLLLCWHDLCRGGHLGTLQQDHATILHAPGVQLPLLTASAPAYHPLPSPPHTQTQYQDRQTGDELFQVQDQEPLFLGHLYFKGGREPPAGDSTPE1EQUAL408EQUALReactome Database ID Release 734549354Database 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=4549354ReactomeR-HSA-45493541Reactome 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-4549354.1GPT_HUMANDPAGT1 V117IUDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549376117EQUAL1EQUAL408EQUALReactome Database ID Release 734549376Database 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=4549376ReactomeR-HSA-45493761Reactome 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-4549376.1GPT_HUMANDPAGT1 V264GUDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549333264EQUAL1EQUAL408EQUALReactome Database ID Release 734549333Database 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=4549333ReactomeR-HSA-45493331Reactome 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-4549333.1GPT_HUMANDPAGT1 Y170CUDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferaseReactome DB_ID: 4549365170EQUAL1EQUAL408EQUALReactome Database ID Release 734549365Database 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=4549365ReactomeR-HSA-45493651Reactome 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-4549365.1Reactome Database ID Release 734549346Database 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=4549346ReactomeR-HSA-45493461Reactome 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-4549346.1GENE ONTOLOGYGO:0003975Reactome Database ID Release 739631918Database 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=9631918Reactome Database ID Release 734549334Database 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=4549334ReactomeR-HSA-45493342Reactome 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-4549334.212872255Pubmed2003Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type IjWu, XRush, JSKaraoglu, DKrasnewich, DLubinsky, MSWaechter, CJGilmore, RFreeze, HHHum Mutat 22:144-5022492991Pubmed2012Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencingTimal, SharitaHoischen, AlexanderLehle, LudwigAdamowicz, MaciejHuijben, KarinSykut-Cegielska, JolantaPaprocka, JustynaJamroz, Ewavan Spronsen, Francjan JKörner, ChristianGilissen, ChristianRodenburg, Richard JEidhof, IlseVan den Heuvel, LambertThiel, ChristianWevers, RAMorava, EvaVeltman, JorisLefeber, Dirk JHum. Mol. Genet. 21:4151-6122742743Pubmed2012Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregatesBelaya, KatsiarynaFinlayson, SarahSlater, Clarke RCossins, JudithLiu, Wei WeiMaxwell, SusanMcGowan, SJMaslau, SiarheiTwigg, SRWalls, Timothy JPascual Pascual, Samuel IPalace, JacquelineBeeson, DavidAm. J. Hum. Genet. 91:193-201Reactome Database ID Release 734549356Database 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=4549356ReactomeR-HSA-45493561Reactome 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-4549356.123447650Pubmed2013Clinical features of congenital myasthenic syndrome due to mutations in DPAGT1Finlayson, SarahPalace, JacquelineBelaya, KatsiarynaWalls, Timothy JNorwood, FionaBurke, GeorginaHolton, Janice LPascual-Pascual, Samuel ICossins, JudithBeeson, DavidJ. Neurol. Neurosurg. Psychiatr. 84:1119-25Defective ALG1 causes ALG1-CDG (CDG-1k)Chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) normally tranfers a mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG1 can cause congenital disorder of glycosylation 1k (ALG1-CDG, previously known as CDG1k; MIM:608540), a multisystem disorder characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Compared to other CDGs, ALG1-CDG has a very severe phenotype, which can result in an early death (Schwarz et al. 2004, Kranz et al. 2004, Dupre et al. 2010).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12LEFT-TO-RIGHT2.4.1.142Defective ALG1 does not transfer the first Man to the N-glycan precursorChitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) normally tranfers a mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG1 can cause congenital disorder of glycosylation 1k (ALG1-CDG, previously known as CDG1k; MIM:608540), a multisystem disorder characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Compared to other CDGs, ALG1-CDG has a very severe phenotype, which can result in an early death. Mutations in ALG1 causing ALG1-CDG include S258L, G342P, S150R, M377V, G145D, C396* and R276W (Schwarz et al. 2004, Kranz et al. 2004, Grubenmann et al. 2004, Dupre et al. 2010).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12N,N'-DCDOLDPN,N'-diacetylchitobiosyldiphosphodolicholdiacetylchitobiosyldiphosphodolicholReactome DB_ID: 449293diacetylchitobiosyldiphosphodolichol [ChEBI:18341]diacetylchitobiosyldiphosphodolicholChEBICHEBI:18341Reactome Database ID Release 73449293Database 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=449293ReactomeR-ALL-4492933Reactome 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-449293.3ACTIVATIONConverted from EntitySet in ReactomeALG1 mutantsReactome DB_ID: 4549394ALG1 C396*Chitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549314UniProt:Q9BT22 ALG1ALG1HMAT1HMT1PSEC0061UNQ861/PRO1870FUNCTION Participates in the formation of the lipid-linked precursor oligosaccharide for N-glycosylation. Involved in assembling the dolichol-pyrophosphate-GlcNAc(2)-Man(5) intermediate on the cytoplasmic surface of the ER.PATHWAY Protein modification; protein glycosylation.SIMILARITY Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 33 subfamily.UniProtQ9BT22396EQUALL-cysteine removalMODMOD:016351EQUAL464EQUALReactome Database ID Release 734549314Database 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=4549314ReactomeR-HSA-45493141Reactome 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-4549314.1ALG1 E342PChitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549371342EQUALL-glutamic acid removalMODMOD:016361EQUAL464EQUALReactome Database ID Release 734549371Database 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=4549371ReactomeR-HSA-45493711Reactome 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-4549371.1ALG1 G145DChitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549398145EQUAL1EQUAL464EQUALReactome Database ID Release 734549398Database 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=4549398ReactomeR-HSA-45493981Reactome 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-4549398.1ALG1 M377VChitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549402377EQUAL1EQUAL464EQUALReactome Database ID Release 734549402Database 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=4549402ReactomeR-HSA-45494021Reactome 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-4549402.1ALG1 R276WChitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549401276EQUAL1EQUAL464EQUALReactome Database ID Release 734549401Database 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=4549401ReactomeR-HSA-45494011Reactome 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-4549401.1ALG1 S150RChitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549311150EQUAL1EQUAL464EQUALReactome Database ID Release 734549311Database 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=4549311ReactomeR-HSA-45493111Reactome 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-4549311.1ALG1 S258LChitobiosyldiphosphodolichol beta-mannosyltransferaseALG1_HUMANGDP-Man:GlcNAc2-PP-dolichol mannosyltransferaseReactome DB_ID: 4549385258EQUAL1EQUAL464EQUALReactome Database ID Release 734549385Database 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=4549385ReactomeR-HSA-45493851Reactome 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-4549385.1Reactome Database ID Release 734549394Database 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=4549394ReactomeR-HSA-45493941Reactome 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-4549394.1GENE ONTOLOGYGO:0004578Reactome Database ID Release 739631741Database 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=9631741Reactome Database ID Release 734549382Database 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=4549382ReactomeR-HSA-45493822Reactome 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-4549382.214973782Pubmed2004Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase IKranz, CDenecke, JLehle, LSohlbach, KJeske, SMeinhardt, FRossi, RGudowius, SMarquardt, TAm J Hum Genet 74:545-5114973778Pubmed2004Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type IkSchwarz, MThiel, CLübbehusen, JDorland, Bde Koning, Tvon Figura, KLehle, LKörner, CAm J Hum Genet 74:472-8120679665Pubmed2010Guanosine diphosphate-mannose:GlcNAc2-PP-dolichol mannosyltransferase deficiency (congenital disorders of glycosylation type Ik): five new patients and seven novel mutationsDupré, TVuillaumier-Barrot, SChantret, IYayé, H SLe Bizec, CAfenjar, AAltuzarra, CBarnérias, CBurglen, Lde Lonlay, PFeillet, FNapuri, SSeta, NMoore, S E HJ. Med. Genet. 47:729-3514709599Pubmed2004Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type IkGrubenmann, CEFrank, CGHülsmeier, AJSchollen, EMatthijs, GMayatepek, EBerger, EGAebi, MHennet, THum Mol Genet 13:535-42Reactome Database ID Release 734549380Database 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=4549380ReactomeR-HSA-45493801Reactome 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-4549380.1Defective ALG9 causes ALG9-CDG (CDG-1l)Alpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21LEFT-TO-RIGHT2.4.1Defective ALG9 does not add the seventh mannose to the N-glycan precursorAlpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004). Point mutations that can cause ALG9-CDG are E523K and Y286C (Frank et al. 2004, Weinstein et al. 2005).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21ACTIVATIONConverted from EntitySet in ReactomeALG9 mutantsReactome DB_ID: 4720499ALG9 E523KAlpha-1,2-mannosyltransferase ALG9ALG9_HUMANReactome DB_ID: 4720482UniProt:Q9H6U8 ALG9ALG9DIBD1FUNCTION Catalyzes the transfer of mannose from Dol-P-Man to lipid-linked oligosaccharides.PATHWAY Protein modification; protein glycosylation.TISSUE SPECIFICITY Ubiquitously expressed; with highest levels in heart, liver and pancreas.DISEASE A chromosomal aberration involving ALG9 is found in a family with bipolar affective disorder. Translocation t(9;11)(p24;q23). However, common variations in ALG9 do not play a major role in predisposition to bipolar affective disorder.SIMILARITY Belongs to the glycosyltransferase 22 family.UniProtQ9H6U8523EQUAL1EQUAL611EQUALReactome Database ID Release 734720482Database 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=4720482ReactomeR-HSA-47204821Reactome 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-4720482.1ALG9 Y286CAlpha-1,2-mannosyltransferase ALG9ALG9_HUMANReactome DB_ID: 4720474286EQUAL1EQUAL611EQUALReactome Database ID Release 734720474Database 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=4720474ReactomeR-HSA-47204741Reactome 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-4720474.1Reactome Database ID Release 734720499Database 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=4720499ReactomeR-HSA-47204991Reactome 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-4720499.1GENE ONTOLOGYGO:0000026Reactome Database ID Release 739631913Database 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=9631913Reactome Database ID Release 734720478Database 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=4720478ReactomeR-HSA-47204783Reactome 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-4720478.315148656Pubmed2004Identification and functional analysis of a defect in the human ALG9 gene: definition of congenital disorder of glycosylation type ILFrank, CGGrubenmann, CEEyaid, WBerger, EGAebi, MHennet, TAm J Hum Genet 75:146-5015945070Pubmed2005CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic featuresWeinstein, MSchollen, EMatthijs, GNeupert, CHennet, TGrubenmann, CEFrank, CGAebi, MClarke, JTGriffiths, ASeargeant, LPoplawski, NAm J Med Genet A 136:194-7LEFT-TO-RIGHT2.4.1Defective ALG9 does not add the last mannose to the N-glycan precursorAlpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004). Point mutations that can cause ALG9-CDG are E523K and Y286C (Frank et al. 2004, Weinstein et al. 2005).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21ACTIVATIONReactome Database ID Release 739631867Database 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=9631867Reactome Database ID Release 739035514Database 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=9035514ReactomeR-HSA-90355142Reactome 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-9035514.2Reactome Database ID Release 734720454Database 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=4720454ReactomeR-HSA-47204542Reactome 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-4720454.2Defective RFT1 causes RFT1-CDG (CDG-1n)The N-glycan precursor is flipped across the ER membrane, moving it from the cytosolic side to the ER lumenal side. The exact mechanism of this translocation is not well understood but protein RFT1 homolog (RFT1) is known to be involved (Helenius et al. 2002). Defects in RFT1 are associated with congenital disorder of glycosylation 1n (RFT1-CDG, CDG-1n). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Early-onset developmental retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency are reported features of this disorder (Haeuptle et al. 2008).Authored: Jassal, B, 2013-09-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-23LEFT-TO-RIGHTDefective RFT1 does not flip the N-glycan precursorThe N-glycan precursor is flipped across the ER membrane, moving it from the cytosolic side to the ER lumenal side. The exact mechanism of this translocation is not well understood but protein RFT1 homolog (RFT1) is known to be involved (Helenius et al. 2002). Defects in RFT1 are associated with congenital disorder of glycosylation 1n (RFT1-CDG, CDG-1n). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Early-onset developmental retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency are reported features of this disorder. In a patient with RFT1-CDG, Haeuptle et al. identified a homozygous C-T transition at nucleotide 199, resulting in a substitution of cysteine for arginine at codon 67 (R67C) (Haeuptle et al. 2008).Authored: Jassal, B, 2013-09-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-23glycan G00006(GlcNAc)2 (Man)5 (PP-Dol)1Reactome DB_ID: 449332Reactome Database ID Release 73449332Database 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=449332ReactomeR-ALL-4493323Reactome 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-449332.3ACTIVATIONRFT1 R67CProtein RFT1 homologRFT1_HUMANReactome DB_ID: 4570578UniProt:Q96AA3 RFT1RFT1FUNCTION May be involved in N-linked oligosaccharide assembly. May participate in the translocation of oligosaccharide from the cytoplasmic side to the lumenal side of the endoplasmic reticulum membrane.SIMILARITY Belongs to the RFT1 family.UniProtQ96AA367EQUALL-asparagine removalMODMOD:016331EQUAL541EQUALReactome Database ID Release 734570578Database 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=4570578ReactomeR-HSA-45705781Reactome 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-4570578.1GENE ONTOLOGYGO:0034202Reactome Database ID Release 739631742Database 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=9631742Reactome Database ID Release 734570573Database 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=4570573ReactomeR-HSA-45705732Reactome 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-4570573.211807558Pubmed2002Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 proteinHelenius, JNg, DTMarolda, CLWalter, PValvano, MAAebi, MNature 415:447-5018313027Pubmed2008Human RFT1 deficiency leads to a disorder of N-linked glycosylationHaeuptle, MAPujol, FMNeupert, CWinchester, BKastaniotis, AJAebi, MHennet, TAm J Hum Genet 82:600-6Reactome Database ID Release 734570571Database 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=4570571ReactomeR-HSA-45705711Reactome 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-4570571.1Defective ALG11 causes ALG11-CDG (CDG-1p)GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11) transfers the fourth and fifth mannoses (Man) to the N-glycan precursor in an alpha-1,2 orientation. These additions are the last two on the cytosolic side of the ER membrane before the N-glycan is flipped to the luminal side of the membrane. Recently discovered defects in ALG11 have been linked to congential disorder of glycosylation, type 1p (ALG11-CDG, CGD1p) (Rind et al. 2010, Thiel et al. 2012). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Early-onset developmental retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency are reported features of this disorder (Rind et al. 2010, Thiel et al. 2012).Authored: Jassal, B, 2013-09-13Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-13LEFT-TO-RIGHT2.4.1Defective ALG11 does not transfer Man to the N-glycan precursorGDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11) transfers the fourth and fifth mannoses (Man) to the N-glycan precursor in an alpha-1,2 orientation. These additions are the last two on the cytosolic side of the ER membrane before the N-glycan is flipped to the luminal side of the membrane. Recently discovered defects in ALG11 have been linked to congential disorder of glycosylation, type 1p (ALG11-CDG, CGD1p) (Rind et al. 2010, Thiel et al. 2012). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Mutations causing ALG11-CDG include E398K, L381S, L86S, Q318P and Y279S (Rind et al. 2010, Thiel et al. 2012).Authored: Jassal, B, 2013-09-13Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-132(GlcNAc)2 (Man)3 (PP-Dol)1alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-2-alpha-D-GlcNAc(PP-Dol)Reactome DB_ID: 449243alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-2-alpha-D-GlcNAc(PP-Dol) [ChEBI:53742]alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-2-alpha-D-GlcNAc(PP-Dol)ChEBICHEBI:53742Reactome Database ID Release 73449243Database 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=449243ReactomeR-ALL-4492433Reactome 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-449243.3ACTIVATIONConverted from EntitySet in ReactomeALG11 mutantsReactome DB_ID: 4570572ALG11 E398KAsparagine-linked glycosylation protein 11 homologALG11_HUMANReactome DB_ID: 4570576UniProt:Q2TAA5 ALG11ALG11GT8FUNCTION Mannosyltransferase involved in the last steps of the synthesis of Man5GlcNAc(2)-PP-dolichol core oligosaccharide on the cytoplasmic face of the endoplasmic reticulum. Catalyzes the addition of the 4th and 5th mannose residues to the dolichol-linked oligosaccharide chain.SIMILARITY Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.UniProtQ2TAA5398EQUAL1EQUAL492EQUALReactome Database ID Release 734570576Database 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=4570576ReactomeR-HSA-45705761Reactome 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-4570576.1ALG11 L381SAsparagine-linked glycosylation protein 11 homologALG11_HUMANReactome DB_ID: 4570581381EQUAL1EQUAL492EQUALReactome Database ID Release 734570581Database 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=4570581ReactomeR-HSA-45705811Reactome 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-4570581.1ALG11 L86SAsparagine-linked glycosylation protein 11 homologALG11_HUMANReactome DB_ID: 457058086EQUAL1EQUAL492EQUALReactome Database ID Release 734570580Database 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=4570580ReactomeR-HSA-45705801Reactome 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-4570580.1ALG11 Q318PAsparagine-linked glycosylation protein 11 homologALG11_HUMANReactome DB_ID: 4570582318EQUALL-glutamine removalMODMOD:016371EQUAL492EQUALReactome Database ID Release 734570582Database 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=4570582ReactomeR-HSA-45705821Reactome 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-4570582.1ALG11 Y279SAsparagine-linked glycosylation protein 11 homologALG11_HUMANReactome DB_ID: 4570575279EQUAL1EQUAL492EQUALReactome Database ID Release 734570575Database 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=4570575ReactomeR-HSA-45705751Reactome 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-4570575.1Reactome Database ID Release 734570572Database 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=4570572ReactomeR-HSA-45705721Reactome 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-4570572.1Reactome Database ID Release 739631975Database 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=9631975Reactome Database ID Release 734551297Database 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=4551297ReactomeR-HSA-45512973Reactome 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-4551297.322213132Pubmed2012Improved diagnostics lead to identification of three new patients with congenital disorder of glycosylation-IpThiel, ChristianRind, NinaPopovici, DianaHoffmann, GFHanson, KristenConway, Robert LAdamski, Craig RButler, ElizabethScanlon, RhondaLambert, MApeshiotis, NeophytosThiels, CharlotteMatthijs, GertKörner, ChristianHum. Mutat. 33:485-720080937Pubmed2010A severe human metabolic disease caused by deficiency of the endoplasmatic mannosyltransferase hALG11 leads to congenital disorder of glycosylation-IpRind, NinaSchmeiser, VerenaThiel, ChristianAbsmanner, BirgitLübbehusen, JürgenHocks, JuliaApeshiotis, NeophytosWilichowski, EkkehardLehle, LudwigKörner, ChristianHum. Mol. Genet. 19:1413-24Reactome Database ID Release 734551295Database 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=4551295ReactomeR-HSA-45512951Reactome 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-4551295.1Defective MGAT2 causes MGAT2-CDG (CDG-2a)Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2) normally catalyses the transfer of a GlcNAc moiety onto the alpha-1,6 mannose of an alpha-1,4 branch of oligomannose N-glycans to form complex N-glycans (Tan et al. 1995). Defects in MGAT2 are associated with congenital disorder of glycosylation type IIa (MGAT2-CDG, CDG-2a; MIM:212066), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Tan et al. 1996, Cormier-Daire et al. 2000, Alkuraya 2010, Alazami et al. 2012). Type II CDGs refer to defects in the trimming and processing of protein-bound glycans.Authored: Jassal, B, 2013-10-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29LEFT-TO-RIGHT2.4.1.143Defective MGAT2 does not transfer GlcNAc to N-glycansAlpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2) normally catalyses the transfer of a GlcNAc moiety onto the alpha,1,6 mannose of an alpha,1,4 branch of oligomannose N-glycans to form complex N-glycans (Tan et al. 1995). Defects in MGAT2 are associated with congenital disorder of glycosylation type IIa (MGAT2-CDG, CDG-2a; MIM:212066), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. Mutations that can cause MGAT2-CDG are S290F, H262R, C339*, N318D and K237N (Tan et al. 1996, Cormier-Daire et al. 2000, Alkuraya 2010, Alazami et al. 2012).Authored: Jassal, B, 2013-10-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29UDP-GlcNAcUDP-N-acetyl-D-glucosamineUDP-N-acetyl-alpha-D-glucosamineUDP-N-acetylglucosamineReactome DB_ID: 914003Golgi lumenGENE ONTOLOGYGO:0005796Reactome Database ID Release 73914003Database 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-914003.3(GlcNAc)3 (Man)3 (Asn)1N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residueReactome DB_ID: 975819N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residue [ChEBI:60615]N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residueChEBICHEBI:60615Reactome Database ID Release 73975819Database 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=975819ReactomeR-ALL-9758193Reactome 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-975819.3ACTIVATIONConverted from EntitySet in ReactomeMGAT2 mutantsReactome DB_ID: 4839790MGAT2 C339*Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferaseMGAT2_HUMANReactome DB_ID: 4839829Golgi membraneGENE ONTOLOGYGO:0000139UniProt:Q10469 MGAT2MGAT2FUNCTION Plays an essential role in protein N-glycosylation. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) onto the free terminal mannose moiety in the core structure of the nascent N-linked glycan chain, giving rise to the second branch in complex glycans.PATHWAY Protein modification; protein glycosylation.SUBUNIT Homodimer.SIMILARITY Belongs to the glycosyltransferase 16 (GT16) protein family.UniProtQ10469339EQUAL1EQUAL447EQUALReactome Database ID Release 734839829Database 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=4839829ReactomeR-HSA-48398291Reactome 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-4839829.1MGAT2 H262RAlpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferaseMGAT2_HUMANReactome DB_ID: 4839821262EQUALL-histidine removalMODMOD:016391EQUAL447EQUALReactome Database ID Release 734839821Database 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=4839821ReactomeR-HSA-48398211Reactome 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-4839821.1MGAT2 K237NAlpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferaseMGAT2_HUMANReactome DB_ID: 4839784237EQUALL-lysine removalMODMOD:016421EQUAL447EQUALReactome Database ID Release 734839784Database 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=4839784ReactomeR-HSA-48397841Reactome 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-4839784.1MGAT2 N318DAlpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferaseMGAT2_HUMANReactome DB_ID: 4839827318EQUAL1EQUAL447EQUALReactome Database ID Release 734839827Database 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=4839827ReactomeR-HSA-48398271Reactome 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-4839827.1MGAT2 S290FAlpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferaseMGAT2_HUMANReactome DB_ID: 4839804290EQUAL1EQUAL447EQUALReactome Database ID Release 734839804Database 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=4839804ReactomeR-HSA-48398041Reactome 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-4839804.1Reactome Database ID Release 734839790Database 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=4839790ReactomeR-HSA-48397901Reactome 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-4839790.1GENE ONTOLOGYGO:0008455Reactome Database ID Release 739631739Database 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=9631739Reactome Database ID Release 734793955Database 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=4793955ReactomeR-HSA-47939552Reactome 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-4793955.28808595Pubmed1996Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain developmentTan, JDunn, JJaeken, JSchachter, HAm J Hum Genet 59:810-711228641Pubmed2000Congenital disorders of glycosylation IIa cause growth retardation, mental retardation, and facial dysmorphismCormier-Daire, VAmiel, JVuillaumier-Barrot, STan, JDurand, GMunnich, ALe Merrer, MSeta, NJ. Med. Genet. 37:875-720684000Pubmed2010Mental retardation, growth retardation, unusual nose, and open mouth: an autosomal recessive entityAlkuraya, Fowzan SAm. J. Med. Genet. A 152:2160-322105986Pubmed2012Congenital disorder of glycosylation IIa: the trouble with diagnosing a dysmorphic inborn error of metabolismAlazami, Anas MMonies, DorotaMeyer, Brian FAlzahrani, FatemaHashem, MaisSalih, Mustafa AAlkuraya, Fowzan SAm. J. Med. Genet. A 158:245-67635144Pubmed1995The human UDP-N-acetylglucosamine: alpha-6-D-mannoside-beta-1,2- N-acetylglucosaminyltransferase II gene (MGAT2). Cloning of genomic DNA, localization to chromosome 14q21, expression in insect cells and purification of the recombinant proteinTan, JD'Agostaro, AFBendiak, BReck, FSarkar, MSquire, JALeong, PSchachter, HEur J Biochem 231:317-28Reactome Database ID Release 734793952Database 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=4793952ReactomeR-HSA-47939521Reactome 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-4793952.1Defective MOGS causes MOGS-CDG (CDG-2b)After the lipid-linked oligosaccharide (LLO) precursor is attached to the protein, the outer alpha-1,2-linked glucose is removed by by mannosyl-oligosaccharide glucosidase (MOGS). This is a mandatory step for protein folding control and glycan extension. Defects in MOGS are associated with congenital disorder of glycosylation type IIb (CDGIIb), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (De Praeter et al. 2000, Voelker et al. 2002). Type II CDGs refer to defects in the trimming and processing of protein-bound glycans.Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29LEFT-TO-RIGHT3.2.1.106Defective MOGS does not cleave glucose from an N-glycosylated proteinAfter the lipid-linked oligosaccharide (LLO) precursor is attached to the protein, the outer alpha-1,2-linked glucose is removed by by mannosyl-oligosaccharide glucosidase (MOGS). This is a mandatory step for protein folding control and glycan extension. Defects in MOGS are associated with congenital disorder of glycosylation type IIb (MOGS-CDG, CDGIIb; MIM:606056), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. Mutations causing MOGS-CDG are R486T and F652L. Kinetic studies using cultured fibroblasts showed that the by mannosyl-oligosaccharide glucosidase activity in the patient's cells was < 1% of control activity (De Praeter et al. 2000, Voelker et al. 2002). Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29unfolded protein:(Glc)3 (GlcNAc)2 (Man)9 (Asn)1Reactome DB_ID: 532534endoplasmic reticulum lumenGENE ONTOLOGYGO:0005788(Glc)3 (GlcNAc)2 (Man)9 (Asn)1N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-L-Asn residueReactome DB_ID: 532673N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-L-Asn residue [ChEBI:59084]N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-L-Asn residueChEBICHEBI:59084Reactome Database ID Release 73532673Database 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=532673ReactomeR-ALL-5326733Reactome 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-532673.31unfolded proteinReactome DB_ID: 381130Reactome Database ID Release 73381130Database 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=381130ReactomeR-HSA-3811302Reactome 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-381130.2ChEBI36080additional informationMIMI:03611Reactome Database ID Release 73532534Database 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=532534ReactomeR-HSA-5325341Reactome 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-532534.1ACTIVATIONConverted from EntitySet in ReactomeMOGS mutantsReactome DB_ID: 4839809MOGS F652LMannosyl-oligosaccharide glucosidaseMOGS_HUMANReactome DB_ID: 4839779UniProt:Q13724 MOGSMOGSGCS1FUNCTION Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner.PATHWAY Glycan metabolism; N-glycan degradation.SIMILARITY Belongs to the glycosyl hydrolase 63 family.UniProtQ13724652EQUAL1EQUAL837EQUALReactome Database ID Release 734839779Database 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=4839779ReactomeR-HSA-48397791Reactome 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-4839779.1MOGS R486TMannosyl-oligosaccharide glucosidaseMOGS_HUMANReactome DB_ID: 4839818486EQUAL1EQUAL837EQUALReactome Database ID Release 734839818Database 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=4839818ReactomeR-HSA-48398181Reactome 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-4839818.1Reactome Database ID Release 734839809Database 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=4839809ReactomeR-HSA-48398091Reactome 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-4839809.1GENE ONTOLOGYGO:0004573Reactome Database ID Release 739631931Database 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=9631931Reactome Database ID Release 734793947Database 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=4793947ReactomeR-HSA-47939472Reactome 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-4793947.210788335Pubmed2000A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiencyDe Praeter, CMGerwig, GJBause, ENuytinck, LKVliegenthart, JFBreuer, WKamerling, JPEspeel, MFMartin, JJDe Paepe, AMChan, NWDacremont, GAVan Coster, RNAm J Hum Genet 66:1744-5612145188Pubmed2002Processing of N-linked carbohydrate chains in a patient with glucosidase I deficiency (CDG type IIb)Völker, CDe Praeter, CMHardt, BBreuer, WKalz-Füller, BVan Coster, RNBause, EGlycobiology 12:473-83Reactome Database ID Release 734793954Database 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=4793954ReactomeR-HSA-47939541Reactome 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-4793954.1Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)Congenital disorders of glycosylation (CDG, previously called carbohydrate-deficient glycoprotein syndromes, CDGSs), are a group of hereditary multisystem disorders. They are characterized biochemically by hypoglycosylation of glycoproteins, diagnosed by isoelectric focusing (IEF) of serum transferrin. There are two types of CDG, types I and II. Type I CDG has defects in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. Clinical symptoms are dominated by severe psychomotor and mental retardation, as well as blood coagulation abnormalities (Jaeken 2013). B4GALT1-CDG (CDG type IId) is a multisystem disease, characterized by dysmorphic features, hydrocephalus, hypotonia and blood clotting abnormalities (Hansske et al. 2002).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29LEFT-TO-RIGHT2.4.1.38Defective B4GALT1 does not add Gal to N-glycanThe family of beta 4-galactosyltransferases (B4GALTs) is composed by at least six known members that mediate the transfer of galactose to N-glycan structures and either to begin or elongate keratan chains. Defective B4GALT1 is associated with congenital disorder of glycosylation type IId (B4GALT1-CDG, CDG-2d; MIM:607091), in which clinical symptoms are dominated by dysmorphic features, psychomotor and mental retardation, hypotonia, as well as blood coagulation abnormalities (Hansske et al. 2002). The mutant R345Kfs*6 results in a truncated, inactive polypeptide. Analysis of oligosaccharides from serum transferrin from these patients reveals loss of sialic acid and galactose residues (Hansske et al. 2002).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29UDP-GalUDPgalactoseUDP-D-galactoseUDP-D-galactopyranoseReactome DB_ID: 735682UDP-D-galactose [ChEBI:18307]UDP-D-galactoseUDPgalactoseUDP-D-galactopyranoseChEBICHEBI:18307Reactome Database ID Release 73735682Database 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=735682ReactomeR-ALL-7356823Reactome 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-735682.3COMPOUNDC00052NGPN-glycoproteinN-glycanReactome DB_ID: 975910N-glycan [ChEBI:59520]N-glycanChEBICHEBI:59520Reactome Database ID Release 73975910Database 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-975910.3ACTIVATIONB4GT1_HUMANB4GALT1 R345Kfs*6Beta-1,4-galactosyltransferase 1Reactome DB_ID: 3656417UniProt:P15291 B4GALT1B4GALT1GGTB2PATHWAY Protein modification; protein glycosylation.SUBUNIT Homodimer; and heterodimer with alpha-lactalbumin to form lactose synthase. Interacts (via N-terminal cytoplasmic domain) with UBE2Q1 (via N-terminus); the interaction is direct (By similarity).TISSUE SPECIFICITY Ubiquitously expressed, but at very low levels in fetal and adult brain.PTM The soluble form derives from the membrane forms by proteolytic processing.SIMILARITY Belongs to the glycosyltransferase 7 family.UniProtP15291Replacement of residues 345 to 349 by KRQEK1EQUAL349EQUALReactome Database ID Release 733656417Database 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=3656417ReactomeR-HSA-36564171Reactome 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-3656417.1GENE ONTOLOGYGO:0003831Reactome Database ID Release 739631981Database 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=9631981Reactome Database ID Release 734793956Database 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=4793956ReactomeR-HSA-47939563Reactome 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-4793956.311901181Pubmed2002Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IIdHansske, BThiel, CLübke, THasilik, MHöning, SPeters, VHeidemann, PHHoffmann, GFBerger, EGvon Figura, KKörner, CJ Clin Invest 109:725-33Reactome Database ID Release 734793953Database 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=4793953ReactomeR-HSA-47939531Reactome 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-4793953.123622397Pubmed2013Congenital disorders of glycosylationJaeken, JHandb Clin Neurol 113:1737-43Defective MAN1B1 causes MRT15Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycoyslated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29LEFT-TO-RIGHT3.2.1.113Defective MAN1B1 does not hydrolyse 1,2-linked mannose (a branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011). Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29(un)folded protein:(GlcNAc)2 (Man)9Reactome DB_ID: 912283endoplasmic reticulum quality control compartmentGENE ONTOLOGYGO:0044322unfolded proteinReactome DB_ID: 912296Reactome Database ID Release 73912296Database 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=912296ReactomeR-HSA-9122962Reactome 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-912296.2ChEBI360801(GlcNAc)2 (Man)9N-{alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->2)]-alpha-Man-(1->3)]-beta-Man-(1->4)-beta-GlcnAc-(1->4)-beta-GlcNAc}-L-Asn residueReactome DB_ID: 912288N-{alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->2)]-alpha-Man-(1->3)]-beta-Man-(1->4)-beta-GlcnAc-(1->4)-beta-GlcNAc}-L-Asn residue [ChEBI:59092]N-{alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->2)]-alpha-Man-(1->3)]-beta-Man-(1->4)-beta-GlcnAc-(1->4)-beta-GlcNAc}-L-Asn residueChEBICHEBI:59092Reactome Database ID Release 73912288Database 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=912288ReactomeR-ALL-9122883Reactome 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-912288.31Reactome Database ID Release 73912283Database 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=912283ReactomeR-HSA-9122831Reactome 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-912283.1H2OwaterReactome DB_ID: 6781870water [ChEBI:15377]waterChEBICHEBI:15377Reactome Database ID Release 736781870Database 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=6781870ReactomeR-ALL-67818703Reactome 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-6781870.3COMPOUNDC00001ACTIVATIONConverted from EntitySet in ReactomeMAN1B1 mutantsReactome DB_ID: 4960920MA1B1_HUMANMAN1B1 E397KEndoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidaseReactome DB_ID: 4960922UniProt:Q9UKM7 MAN1B1MAN1B1UNQ747/PRO1477FUNCTION Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2).ACTIVITY REGULATION Inhibited by both 1-deoxymannojirimycin (dMNJ) and kifunensine.PATHWAY Protein modification; protein glycosylation.TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the glycosyl hydrolase 47 family.CAUTION It is uncertain whether Met-1 or Met-37 is the initiator.UniProtQ9UKM7397EQUAL1EQUAL699EQUALReactome Database ID Release 734960922Database 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=4960922ReactomeR-HSA-49609221Reactome 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-4960922.1MA1B1_HUMANMAN1B1 R334CEndoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidaseReactome DB_ID: 4960924334EQUAL1EQUAL699EQUALReactome Database ID Release 734960924Database 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=4960924ReactomeR-HSA-49609241Reactome 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-4960924.1MA1B1_HUMANMAN1B1 W473*Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidaseReactome DB_ID: 4960927473EQUAL1EQUAL699EQUALReactome Database ID Release 734960927Database 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=4960927ReactomeR-HSA-49609271Reactome 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-4960927.1Reactome Database ID Release 734960920Database 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=4960920ReactomeR-HSA-49609201Reactome 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-4960920.1GENE ONTOLOGYGO:0004571Reactome Database ID Release 739631749Database 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=9631749Reactome Database ID Release 734793949Database 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=4793949ReactomeR-HSA-47939493Reactome 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-4793949.320345473Pubmed2010Mapping of three novel loci for non-syndromic autosomal recessive mental retardation (NS-ARMR) in consanguineous families from PakistanRafiq, M AAnsar, MMarshall, C RNoor, AShaheen, NMowjoodi, AKhan, M AAli, GAmin-ud-Din, MFeuk, LVincent, J BScherer, S WClin. Genet. 78:478-8321763484Pubmed2011Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disabilityRafiq, Muhammad ArshadKuss, Andreas WPuettmann, LuciaNoor, AbdulRamiah, AnnapooraniAli, GhazanfarHu, HaoKerio, Nadir AliXiang, YongGarshasbi, MasoudKhan, Muzammil AhmadIshak, Gisele EWeksberg, RosannaUllmann, ReinhardTzschach, AndreasKahrizi, KimiaMahmood, KhalidNaeem, FarooqAyub, MuhammadMoremen, Kelley WVincent, John BRopers, Hans HilgerAnsar, MuhammadNajmabadi, HosseinAm. J. Hum. Genet. 89:176-82LEFT-TO-RIGHT3.2.1.113Defective MAN1B1 does not hydrolyse a second 1,2-linked mannose (a branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29unfolded protein:(GlcNAc)2 (Man)8aReactome DB_ID: 9122851(GlcNAc)2 (Man)8aN(4)-{alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlaNAc-(1->4)-beta-D-GlcNAc}-Asn residueN(4)-{alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residueReactome DB_ID: 912298N(4)-{alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residue [ChEBI:60627]N(4)-{alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residueChEBICHEBI:60627Reactome Database ID Release 73912298Database 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=912298ReactomeR-ALL-9122983Reactome 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-912298.31Reactome Database ID Release 73912285Database 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=912285ReactomeR-HSA-9122851Reactome 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-912285.1ACTIVATIONReactome Database ID Release 739631832Database 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=9631832Reactome Database ID Release 739036008Database 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=9036008ReactomeR-HSA-90360082Reactome 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-9036008.2LEFT-TO-RIGHT3.2.1.113Defective MAN1B1 does not hydrolyse 1,2-linked mannose (b branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29ACTIVATIONReactome Database ID Release 739631736Database 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=9631736Reactome Database ID Release 739036011Database 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=9036011ReactomeR-HSA-90360112Reactome 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-9036011.2LEFT-TO-RIGHT3.2.1.113Defective MAN1B1 does not hydrolyse 1,2-linked mannose (c branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29ACTIVATIONReactome Database ID Release 739631798Database 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=9631798Reactome Database ID Release 739036012Database 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=9036012ReactomeR-HSA-90360122Reactome 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-9036012.2Reactome Database ID Release 734793950Database 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=4793950ReactomeR-HSA-47939502Reactome 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-4793950.2Defective ALG14 causes congenital myasthenic syndrome (ALG14-CMS)UDP-N-acetylglucosamine transferase subunit ALG14 homolog (ALG14) forms a complex with ALG13 protein and is required for the addition of the second N-acetylglucosamine (GlcNAc) to the lipid linked oligosaccharide (LLO) intermediate (GlcNAcDOLDP) (Gao et al. 2005). Defects in ALG14 can cause congenital myasthenic syndrome (ALG14-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al. 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG14-CMS include p.P65L and p.R104* (Cossins et al. 2013).Authored: Jassal, Bijay, 2014-10-31Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, Bijay, 2014-10-31LEFT-TO-RIGHT2.4.1.141Defective ALG14 does not transfer GlcNAc from UDP-GlcNAc to GlcNAcDOLPUDP-N-acetylglucosamine transferase subunit ALG14 homolog (ALG14) forms a complex with ALG13 protein and is required for the addition of the second N-acetylglucosamine (GlcNAc) to the lipid linked oligosaccharide (LLO) intermediate (GlcNAcDOLDP) (Gao et al. 2005). Defects in ALG14 can cause congenital myasthenic syndrome (ALG14-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al. 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG14-CMS include p.P65L and p.R104* (Cossins et al. 2013).Authored: Jassal, Bijay, 2014-10-31Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, Bijay, 2014-10-31GlcNAcDOLDPN-acetyl-D-glucosaminyl-diphosphodolicholN-acetyl-D-glucosaminyldiphosphodolicholReactome DB_ID: 449222N-acetyl-D-glucosaminyldiphosphodolichol [ChEBI:18278]N-acetyl-D-glucosaminyldiphosphodolicholChEBICHEBI:18278Reactome Database ID Release 73449222Database 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=449222ReactomeR-ALL-4492223Reactome 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-449222.3ACTIVATIONALG13:ALG14 mutantsReactome DB_ID: 5633244Converted from EntitySet in ReactomeALG14 mutantsReactome DB_ID: 5633238ALG14 P65LUDP-N-acetylglucosamine transferase subunit ALG14 homologALG14_HUMANReactome DB_ID: 5633218UniProt:Q96F25 ALG14ALG14FUNCTION May be involved in protein N-glycosylation. May play a role in the second step of the dolichol-linked oligosaccharide pathway. May anchor the catalytic subunit ALG13 to the ER.SUBUNIT Heterodimer with ALG13 isoform 2 to form a functional enzyme.SIMILARITY Belongs to the ALG14 family.UniProtQ96F2565EQUALL-proline removalMODMOD:016451EQUAL216EQUALReactome Database ID Release 735633218Database 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=5633218ReactomeR-HSA-56332181Reactome 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-5633218.1ALG14 R104*UDP-N-acetylglucosamine transferase subunit ALG14 homologALG14_HUMANReactome DB_ID: 5633229104EQUAL1EQUAL216EQUALReactome Database ID Release 735633229Database 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=5633229ReactomeR-HSA-56332291Reactome 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-5633229.1Reactome Database ID Release 735633238Database 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=5633238ReactomeR-HSA-56332381Reactome 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-5633238.11ALG13ALG13(1-165)UDP-N-acetylglucosamine transferase subunit ALG13 homologALG13_HUMANReactome DB_ID: 449329UniProt:Q9NP73 ALG13ALG13CXorf45GLT28D1MDS031SUBUNIT Isoform 2 may interact with ALG14.DOMAIN Contains 1 OTU domain with intact active sites. No deubiquitinase activity has been detected when tested (PubMed:23827681).SIMILARITY Belongs to the glycosyltransferase 28 family.UniProtQ9NP731EQUAL165EQUALReactome Database ID Release 73449329Database 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=449329ReactomeR-HSA-4493291Reactome 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-449329.11Reactome Database ID Release 735633244Database 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=5633244ReactomeR-HSA-56332441Reactome 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-5633244.1GENE ONTOLOGYGO:0004577Reactome Database ID Release 739631825Database 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=9631825Reactome Database ID Release 735633241Database 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=5633241ReactomeR-HSA-56332412Reactome 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-5633241.216100110Pubmed2005Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form a novel bipartite UDP-N-acetylglucosamine transferase required for the second step of N-linked glycosylationGao, XDTachikawa, HSato, TJigami, YDean, NJ Biol Chem 280:36254-62Reactome Database ID Release 735633231Database 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=5633231ReactomeR-HSA-56332312Reactome 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-5633231.2Reactome Database ID Release 733781860Database 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=3781860ReactomeR-HSA-37818601Reactome 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-3781860.112409504Pubmed2002Congenital disorders of glycosylation: a reviewGrunewald, StephanieMatthijs, GertJaeken, JaakPediatr. Res. 52:618-2423730680Pubmed2013Congenital disorders of glycosylation. Part I. Defects of protein N-glycosylationCylwik, BogdanNaklicki, MarcinChrostek, LechGruszewska, EwaActa Biochim. Pol. 60:151-6122343051Pubmed2012Diseases of glycosylation beyond classical congenital disorders of glycosylationHennet, ThierryBiochim. Biophys. Acta 1820:1306-1712756558Pubmed2003Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapiesMarquardt, TDenecke, JEur. J. Pediatr. 162:359-79