Glycosylation is the most common postranslational modification. Defects in this pathway lead to autosomal recessive disorders, called congenital disorders of glycosylation (CDG). Up to date about 50 CDGs have been identified and more are expected to be discovered. This category of metabolic disorders can be divided into four basic groups depending on where the glycosylation process occurs on the molecule. The depicts pathway depicts the group of N-glycosylation. Generally, N-glycosylation processes spread over three cellular compartments - cytosol, endoplasmic reticulum and Golgi apparatus. The associated mortality rate in combination with the limited treatment options for CDG, points out the relevance for further investigations of this pathway. Disorders resulting from an enzyme defect are highlighted in pink. This pathway was inspired by Chapter 30 of the book of Blau (ISBN 3642403360 (978-3642403361)).a0eDolichol kinase, Book label: 30.38Labelled in UniProt as Putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13.Found manually through RHEA identifier. This enzyme was not indicated in the Blau Book, but it catalyzes this exact reaction.In UniProt described as UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase.Found manually through RHEA identifier reaction. Not indicated in the Blau Book Chapter 30.In RHEA: N-acetyl-α-D-glucosaminyl-diphosphodolicholAKA mannose-1-phosphate guanylyltransferase [https://en.wikipedia.org/wiki/Mannose-1-phosphate_guanylyltransferase]AKA B4GALT1; beta-1,4-galactosyltransferase 1; book label: 30.34dc2cf1AKA MGAT2; N-acetylglucosaminyltransferase 2; book label: 30.13Function"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." [https://www.uniprot.org/uniprot/Q10469]AKA GCS1; Glucosidase 1; book label: 30.14Function:"Cleaves the distal alpha 1,2-linked glucose residue from the Glc3Man9GlcNAc2 oligosaccharide precursor in a highly specific manner." [https://www.uniprot.org/uniprot/Q13724]AKA TUSC3; oligosaccharyltransferase subunit tusc 3; book label: 30.15b1dAka MAGT1; magnesium transporter 1AKA ALG8; Glucosyltransferase 2; book label: 30.6Aka ALG6; glucosyltransferase 1; book label: 30.3book label: 30.10AKA ALG12, Mannosyltransferase 8; book label: 30.5Aka ;mannosyltransferase 7-9; Book label: 30.10AKA MPDU1; Dol-P-Man utilization 1; Book label: 30.33AKA ALG3, mannosyltransferase 6; Book label: 30.4Function:"Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man5GlcNAc2-PP-Dol" [https://www.uniprot.org/uniprot/Q92685]AKA MPI, phosphomannose isomerase; Book label: 30.2bc9AKA PMM, phosphomannomutase 2; book label: 30.1AKA DPM1, GDP-Man:Dol-P mannosyltransferase subunit 1; book label: 30.31AKA DPM3, GDP-Man:Dol-P mannosyltransferase 3; book label: 30.32"Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit DPM1 to the ER" [https://www.uniprot.org/uniprot/Q9P2X0]cf1In RHEA stated as dolichyl phosphate, and in this reaction it results in a -2 charge.In CheBi known as Dolichol diphosphateKnown as polyprenol reductase, which catalyzes reduction of the alpha-isoprene subunit of polyprenol. But also known to have steroid dehydrogenase activity. Book label:30.39 ebdec3edaChitobiosyldiphosphodolichol
beta-mannosyltransferase mediates the hexosyl group transfer.In Blau Book known as Mannosyltransferase 1, label: 30.9Also known as UDP-N-acetylglucosamine-dolichyl-phosphate
N-acetylglucosaminephosphotransferase, which transfers the hexosyl group. Book label: 30.8GDP-Man:Man(3)GlcNAc(2)-PP-
Dol alpha-1,2-mannosyltransferase; Book label: 30.11fc8f2aFull name in RHEA: di-trans,poly-cis-dolicholbf5e55In RHEA and UniProt known as di-trans,cis-polyprenol. a13babAlpha-1,3/1,6-
mannosyltransferase ALG2; Book label: 30.7a99Aka N-acetylglucosamineALG14d28Added same Rhea ID as for reaction catalyzed through ALG13, however, DPAGT1 is not linked to this interaction in Rhea or UniProt.e70ALG14 may anchor ALG13 to the ERc25d29f5bcf1b63d73cf1f7cf7caf2b10e11de2b29e6de6bd49a5bd60a53e44e9ce16f78f8af78f8af70fe1d4f17986282PubMedNovel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer.Cancer Sci2008Uemura MTamura KChung SHonma SOkuyama ANakamura YNakagawa H20637498PubMedSRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.Cell2010Cantagrel VLefeber DJNg BGGuan ZSilhavy JLBielas SLLehle LHombauer HAdamowicz MSwiezewska EDe Brouwer APBlümel PSykut-Cegielska JHouliston SSwistun DAli BRDobyns WBBabovic-Vuksanovic Dvan Bokhoven HWevers RARaetz CRFreeze HHMorava EAl-Gazali LGleeson JG11901181PubMedDeficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId.J Clin Invest2002Hansske BThiel CLübke THasilik MHöning SPeters VHeidemann PHHoffmann GFBerger EGvon Figura KKörner C12684507PubMed12684507PubMedA new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis.J Biol Chem2003Thiel CSchwarz MPeng JGrzmil MHasilik MBraulke TKohlschütter Avon Figura KLehle LKörner C21334936PubMedPubertal development in ALG6 deficiency (congenital disorder of glycosylation type Ic).Mol Genet Metab2011Miller BSFreeze HHHoffmann GFSarafoglou K12480927PubMedA deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation.J Biol Chem2003Chantret IDancourt JDupré TDelenda CBucher SVuillaumier-Barrot SOgier de Baulny HPeletan CDanos OSeta NDurand GOriol RCodogno PMoore SEaltered carbohydrate metabolic pathwayPW:0000305Pathway Ontology7635144PubMedThe human UDP-N-acetylglucosamine: alpha-6-D-mannoside-beta-1,2- N-acetylglucosaminyltransferase II gene (MGAT2). 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