Asparagine N-linked glycosylation (Homo sapiens)

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63, 105, 117, 155, 161...109114, 16929, 147, 168, 17611, 39, 92, 120, 123...15622, 33, 15072, 97, 12771, 1425, 918, 31, 14471, 14215117014072, 95, 15441, 7311, 39, 92, 120, 123...32, 74, 94, 101, 115...42, 69, 84, 1181357, 112, 1262836, 65, 138103, 16250, 57, 86, 14913255, 7212, 48, 49, 67, 119...16, 98, 1511375, 132, 139874614, 4511742, 69, 84, 1185111, 39, 92, 120, 123...133, 18138, 59, 116, 134, 141...170, 181122, 129131, 137, 17537, 56, 102, 1533, 5210819, 60, 7753, 14582, 1061101731114, 811731732, 47, 80114, 131, 137, 17520, 104, 121, 160, 167...9, 125, 166443523, 62, 90144, 17015817, 64, 85, 15658, 70, 79, 17189, 163, 178131, 137, 17516427, 54, 15924, 7693, 9617, 64, 85, 156991071330, 34, 113130, 13621, 66, 8325, 40, 61, 1281100, 143, 179131, 137, 175endoplasmic reticulum quality control compartmentcytosolendoplasmic reticulum lumenGolgi lumenlysosomal lumenGlcNAc, GlcNGcManNAc S-HNK1 carbohydrate(GlcNAc)2 (Man)8c NGPATP(GlcNAc)2 (Man)8a ALG9(GlcNAc)2 (Man)9 NUDT14RENBP DPM1:DPM2:DPM3CO2TSTA3 DbGP(GlcNAc)2 (Man)7bcE,E-FPPUBC(609-684) ALG1UBB(153-228) (GlcNAc)2 (Man)8b FUCA1 NGP:1,6-GlcNAcDbGP(GlcNAc)2 (Man)7bc UBC(77-152) (GlcNAc)2 (Man)9-5ATPGlc2xGNPNAT1(GlcNAc)2 (Man)8a DOLPS-glyco-LutropinMAN2A2 LMAN1:MCFD2ADP(GlcNAc)2 (Man)5(PP-Dol)1unfolded protein B4GALNT2(GlcNAc)2 (Man)8b H2OUDP-GlcNAcMANEAunfoldedprotein:(GlcNAc)2(Man)8cUDP-GalUBXN1 GDPDOLPCANX DPM1 MGAT1Glycoprotein withGlcNAc in position5(Glc)1 (GlcNAc)2 (Man)8c unfoldedprotein:(GlcNAc)2(Man)8bunfoldedprotein:glycan (noglucose)DOLPunfolded protein UBC(229-304) unfolded protein CALR unfoldedprotein:(Glc)1(GlcNAc)2 (Man)8bCALR:CANXAMDHD2CALR (GlcNAc)3 (Man)5(Asn)1RNF5 H2O(GlcNAc)2 (Man)5 DHDDS MAN1A1/A2/C1UBB(77-152) UMPUDPH2OB4GALT6 ALG13:ALG14unfoldedprotein:glycan:chaperone:ERp57(GlcNAc)2 (Man)9 UGGT1 CALR UBC(533-608) GDP-ManGlcNAc UBA52(1-76) (Glc)3 (GlcNAc)2 (Man)9 (Asn)1 (GlcNAc)2 (Man)8c GlcNGc-6-P (GlcNAc)2 (Man)9(PP-Dol)1Glycoprotein withGlcNAc in position4(Glc)1 (GlcNAc)2 (Man)7bc unfolded protein L-fucoseUBB(153-228) PPiALG13(1-165) (GlcNAc)2 (Man)9 UDP-GalUBC(381-456) CANX ALG10B B4GALT4 unfoldedprotein:GlcNAcPiPMM2 beta-FucPDIA3 MVD dimer(GlcNAc)2 (Man)8c MGAT4C MPICGA ALG8alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-UBC(381-456) GlcMAN2A1 (GlcNAc)2 (Man)5(PP-Dol)1unfolded protein (GlcNAc)2 (Man)5(Asn)1GANAB (GlcNAc)2 (Man)5 B4GALT5 ALG11ADPMGAT3DPM3 UBC(609-684) UBC(229-304) unfoldedprotein:(GlcNAc)2(Man)5GFPT1 NADPHUbVCP DbGPunfoldedprotein:(Glc)1(GlcNAc)2 (Man)9(Asn)1:chaperoneMAN1A2 FUOM dimerunfoldedprotein:(GlcNAc)2(Man)7aa(GlcNAc)2 (Man)9 UBC(457-532) Man1PGDP-ManDERL1 CHST10L-GluGlcN6PH2ONAGK PALM-C36-ASGR1 GFPT2 (GlcNAc)2 (Man)8a (un)foldedprotein:(GlcNAc)2(Man)9DOLPP1UBC(457-532) UDP-GlcNAcunfoldedprotein:(Glc)1(GlcNAc)2 (Man)9UBC(533-608) (Glc)2 (GlcNAc)2 (Man)9 (Asn)1 HNK1 carbohydrateIPPPOS9 (GlcNAc)2 (Man)8a PALM-C36-ASGR1:PALM-C54,58-ASGR2:proteoglycanDOLP-ManUBA52(1-76) B4GALT2 AMFR GDP-DHDManB4GALT1 LysosomaloligosaccharidecatabolismUBC(153-228) ManNAc, ManNGcManNGc PAPDAD1 G1PRFT1MPDU1EDEM1,3ST3GAL4unfolded protein PRKCSH GDP-FucFUOM CDPST8SIA2,3,6RPN1 pPPP phosphataseUBC(153-228) UGGT1,2UDPalpha-D-Man-(1->3)-UBC(381-456) ER to GolgiAnterogradeTransportH2OMAN1A1 ManDOLPN,N'-DCDOLDPglyco-Lutropinunfolded protein FUT8unfolded protein PSMC1 DOLP(GlcNAc)2 (Man)8b (GlcNAc)2 (Man)2(PP-Dol)1FUCA1 tetramer(GlcNAc)2 (Man)9 UDPunfoldedprotein:(Glc)2(GlcNAc)2 (Man)9(Asn)1:malectinMLECFuc1PNeu5AcEDEM3 MGAT4A(1-535) MGAT4B NGPSRD5A3(GlcNAc)3 (Man)3(Asn)1TRIM13 (GlcNAc)2 (Man)8a Sialic acidmetabolismunfoldedprotein:(Glc)1(GlcNAc)2 (Man)9(Asn)1H2OGlcNAc-6-P,GlcNGc-6-PMCFD2 Gal1,3GlcNAc groupRPS27A(1-76) (GlcNAc)2 (Man)8c GMPPA/BALG3CALR,CANXTSTA3 dimerRPS27A(1-76) UAP1 PDIA3DbGPUBC(1-76) UBC(77-152) ADPNAGK dimerDOLPGlycosaminoglycanmetabolismMAGT1 UDPRNF139 UBC(77-152) CANX RPS27A(1-76) (GlcNAc)2 (Man)6(PP-Dol)1alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-unfolded protein (GlcNAc)2 (Man)8c unfoldedprotein:(Glc)3(GlcNAc)2 (Man)9(Asn)1UBC(609-684) CHST8Glycoprotein withgalactoseST6GAL1H2O(Glc)3 (GlcNAc)2(Man)9 (PP-Dol)1unfolded protein(Glc)3 (GlcNAc)2(Man)9 (Asn)1(GlcNAc)2 (Man)8b RAD23B GMDSGlycoprotein-Neu5AcGTPUGGT2 Gal1,3Fuc1,4GlcNAcgroupGDPManH+unfolded protein SYVN1(1-617) GMPPA DOLDPZn2+ ALG5MDCDDNGLY1 (GlcNAc)2 (Man)9NADP+GlcNAcDOLDPCANX (un)foldedprotein:(GlcNAc)2(Man)9unfoldedprotein:(GlcNAc)2(Man)8a(GlcNAc)2 (Man)8a unfolded protein OST complexGNPNAT1 (GlcNAc)2 (Man)5 (GlcNAc)2 (Man)8glycansglucosidase II(GlcNAc)2 (Man)8b RENBP dimerNADPH(GlcNAc)2 (Man)8c Glycoproteins withMan8 N-glycansRNF103 PRKCSH unfoldedprotein:(Glc)1(GlcNAc)2(Man)9(Asn)1:chaperone:ERp57DHDDS:NUS1CALR MVD CALR GDP-FucUBC(1-76) PDIA3 (Glc)1 (GlcNAc)2 (Man)9 (Glc)1 (GlcNAc)2 (Man)8b (GlcNAc)2 (Man)7(PP-Dol)1(GlcNAc)2 (Man)8a proteoglycan DOLKUBC(305-380) MAN2:Zn2+Glycoproteins withMan8 N-glycansUBC(305-380) GFPT1,2MVA5PPALG6MOGSAc-CoALMAN1 GDPUBC(153-228) PALM-C54,58-ASGR2 DCHOLFPGTALG14 (GlcNAc)2 (Man)3(PP-Dol)1ATPRNF185 SEL1L UMPRPN2 (Glc)1 (GlcNAc)2 (Man)9 (GlcNAc)2 (Man)8c ALG12GDPGlcNGc glucosidase IIGANAB (Glc)1 (GlcNAc)2(Man)9 (PP-Dol)1ALG10 homologueUBB(1-76) MAN1B1,EDEM2ALG2pPPPCCAGDP-ManGDPNUS1 SLC35C1TUSC3(1-348) H2O(Glc)2 (GlcNAc)2 (Man)9 (Asn)1 MAN1C1 alpha-FucAcGlcN1PAcGlcN6PDeglycosylationcomplexunfoldedprotein:(Glc)2(GlcNAc)2 (Man)9(Asn)1NADP+UBC(533-608) GlcNAc-6-P PMM1 Man6PDOLPMLEC MGAT5UBB(77-152) MGAT4s(GlcNAc)2 (Man)8c H2O(Glc)1 (GlcNAc)2 (Man)9 2xUAP1unfolded protein ST8SIA6 CTP(Glc)2 (GlcNAc)2(Man)9 (PP-Dol)1UDP-GlcNAcalpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-(GlcNAc)2 (Man)8c MGAT2unfolded protein ST8SIA2 Ub-unfoldedprotein:(GlcNAc)2(Man)9-5GlcNAc (Man)9-5DOLPunfolded protein (GlcNAc)2 (Man)9 alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-PAPSDDOST MAN1B1 UBB(77-152) L-Glnunfolded protein unfolded protein unfolded protein MARCH6 PALM-C54,58-ASGR2 unfolded protein (GlcNAc)2 (Man)8b FUKPMM1,2unfolded protein UBB(1-76) PAP(GlcNAc)4 (Man)3(Asn)1FUT3(GlcNAc)2 (Man)9 (Glc)1 (GlcNAc)2 (Man)8b S-glyco-LHB unfolded protein unfoldedprotein:(GlcNAc)2(Man)9-5DPM2 PPiUBA52(1-76) (GlcNAc)2 (Man)8b OS9:SEL1:ERAD E3ligases:DERL2UBC(457-532) UBB(153-228) PALM-C36-ASGR1 PPiS-glyco-CGA (un)foldedprotein:(GlcNAc)2(Man)9(GlcNAc)2 (Man)7aa UBC(305-380) H2OPALM-C36-ASGR1:PALM-C54,58-ASGR2PGM3proteoglycanGDP-KDGalUMODunfolded proteinUDP-GlcALG10 CANX Fru(6)PPPi(GlcNAc)2 (Man)5 (GlcNAc)2 (Man)8b DOLP-ManUBC(229-304) GDP-FucGlcNGc-6-PB4GALT3 GTPEDEM2 CoA-SHPAPSPi(GlcNAc)2 (Man)8b H+UDP-GlcNAc(Glc)1 (GlcNAc)2 (Man)9 DPAGT1(GlcNAc)2 (Man)8(PP-Dol)1Sda-UMOD(GlcNAc)2 (Man)8(Asn)1(GlcNAc)2 (Man)5 UBB(1-76) H2O(GlcNAc)2 (Man)9 unfolded protein Glycoprotein withbifurcating GlcNAcin position 3STT3A (Glc)1 (GlcNAc)2 (Man)9 UTPunfolded protein GDPAMFR ENGASEunfolded protein DERL2 UBC(1-76) EDEM1 ST8SIA3 LHB B4GALT1-6 homodimersNGP:1,6-GlcNAcpPNOLunfolded protein (GlcNAc)2 (Man)8a GMPPB Ub-unfoldedprotein:(GlcNAc)2(Man)9-515710, 68, 8843, 78, 14618, 26


Description

N-linked glycosylation is the most important form of post-translational modification for proteins synthesized and folded in the Endoplasmic Reticulum (Stanley et al. 2009). An early study in 1999 revealed that about 50% of the proteins in the Swiss-Prot database at the time were N-glycosylated (Apweiler et al. 1999). It is now established that the majority of the proteins in the secretory pathway require glycosylation in order to achieve proper folding.
The addition of an N-glycan to a protein can have several roles (Shental-Bechor & Levy 2009). First, glycans enhance the solubility and stability of the proteins in the ER, the golgi and on the outside of the cell membrane, where the composition of the medium is strongly hydrophilic and where proteins, that are mostly hydrophobic, have difficulty folding properly. Second, N-glycans are used as signal molecules during the folding and transport process of the protein: they have the role of labels to determine when a protein must interact with a chaperon, be transported to the golgi, or targeted for degradation in case of major folding defects. Third, and most importantly, N-glycans on completely folded proteins are involved in a wide range of processes: they help determine the specificity of membrane receptors in innate immunity or in cell-to-cell interactions, they can change the properties of hormones and secreted proteins, or of the proteins in the vesicular system inside the cell.
All N-linked glycans are derived from a common 14-sugar oligosaccharide synthesized in the ER, which is attached co-translationally to a protein while this is being translated inside the reticulum. The process of the synthesis of this glycan, known as Synthesis of the N-glycan precursor or LLO, constitutes one of the most conserved pathways in eukaryotes, and has been also observed in some eubacteria. The attachment usually happens on an asparagine residue within the consensus sequence asparagine-X-threonine by an complex called oligosaccharyl transferase (OST).
After being attached to an unfolded protein, the glycan is used as a label molecule in the folding process (also known as Calnexin/Calreticulin cycle) (Lederkremer 2009). The majority of the glycoproteins in the ER require at least one glycosylated residue in order to achieve proper folding, even if it has been shown that a smaller portion of the proteins in the ER can be folded without this modification.
Once the glycoprotein has achieved proper folding, it is transported via the cis-Golgi through all the Golgi compartments, where the glycan is further modified according to the properties of the glycoprotein. This process involves relatively few enzymes but due to its combinatorial nature, can lead to several millions of different possible modifications. The exact topography of this network of reactions has not been established yet, representing one of the major challenges after the sequencing of the human genome (Hossler et al. 2006).
Since N-glycosylation is involved in an great number of different processes, from cell-cell interaction to folding control, mutations in one of the genes involved in glycan assembly and/or modification can lead to severe development problems (often affecting the central nervous system). All the diseases in genes involved in glycosylation are collectively known as Congenital Disorders of Glycosylation (CDG) (Sparks et al. 2003), and classified as CDG type I for the genes in the LLO synthesis pathway, and CDG type II for the others. View original pathway at:Reactome.

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Pathway is converted from Reactome ID: 446203
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Reactome version: 62
Reactome Author 
Reactome Author: Dall'Olio, Giovanni

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Bibliography

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  1. Schenk B, Fernandez F, Waechter CJ.; ''The ins(ide) and out(side) of dolichyl phosphate biosynthesis and recycling in the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  2. Wang Y, Schachter H, Marth JD.; ''Mice with a homozygous deletion of the Mgat2 gene encoding UDP-N-acetylglucosamine:alpha-6-D-mannoside beta1,2-N-acetylglucosaminyltransferase II: a model for congenital disorder of glycosylation type IIa.''; PubMed Europe PMC Scholia
  3. Pearse BR, Gabriel L, Wang N, Hebert DN.; ''A cell-based reglucosylation assay demonstrates the role of GT1 in the quality control of a maturing glycoprotein.''; PubMed Europe PMC Scholia
  4. Bernasconi R, Pertel T, Luban J, Molinari M.; ''A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal.''; PubMed Europe PMC Scholia
  5. Shental-Bechor D, Levy Y.; ''Folding of glycoproteins: toward understanding the biophysics of the glycosylation code.''; PubMed Europe PMC Scholia
  6. Shridas P, Rush JS, Waechter CJ.; ''Identification and characterization of a cDNA encoding a long-chain cis-isoprenyltranferase involved in dolichyl monophosphate biosynthesis in the ER of brain cells.''; PubMed Europe PMC Scholia
  7. Yik JH, Saxena A, Weigel JA, Weigel PH.; ''Nonpalmitoylated human asialoglycoprotein receptors recycle constitutively but are defective in coated pit-mediated endocytosis, dissociation, and delivery of ligand to lysosomes.''; PubMed Europe PMC Scholia
  8. Song Y, Aglipay JA, Bernstein JD, Goswami S, Stanley P.; ''The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progression.''; PubMed Europe PMC Scholia
  9. Hinderlich S, Berger M, Blume A, Chen H, Ghaderi D, Bauer C.; ''Identification of human L-fucose kinase amino acid sequence.''; PubMed Europe PMC Scholia
  10. Kahrizi K, Hu CH, Garshasbi M, Abedini SS, Ghadami S, Kariminejad R, Ullmann R, Chen W, Ropers HH, Kuss AW, Najmabadi H, Tzschach A.; ''Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3.''; PubMed Europe PMC Scholia
  11. Xia G, Evers MR, Kang HG, Schachner M, Baenziger JU.; ''Molecular cloning and expression of the pituitary glycoprotein hormone N-acetylgalactosamine-4-O-sulfotransferase.''; PubMed Europe PMC Scholia
  12. Haeuptle MA, Pujol FM, Neupert C, Winchester B, Kastaniotis AJ, Aebi M, Hennet T.; ''Human RFT1 deficiency leads to a disorder of N-linked glycosylation.''; PubMed Europe PMC Scholia
  13. Oki T, Yamazaki K, Kuromitsu J, Okada M, Tanaka I.; ''cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse.''; PubMed Europe PMC Scholia
  14. Moore SE, Spiro RG.; ''Demonstration that Golgi endo-alpha-D-mannosidase provides a glucosidase-independent pathway for the formation of complex N-linked oligosaccharides of glycoproteins.''; PubMed Europe PMC Scholia
  15. Ong E, Yeh JC, Ding Y, Hindsgaul O, Pedersen LC, Negishi M, Fukuda M.; ''Structure and function of HNK-1 sulfotransferase. Identification of donor and acceptor binding sites by site-directed mutagenesis.''; PubMed Europe PMC Scholia
  16. Breuer W, Klein RA, Hardt B, Bartoschek A, Bause E.; ''Oligosaccharyltransferase is highly specific for the hydroxy amino acid in Asn-Xaa-Thr/Ser.''; PubMed Europe PMC Scholia
  17. Weinstein M, Schollen E, Matthijs G, Neupert C, Hennet T, Grubenmann CE, Frank CG, Aebi M, Clarke JT, Griffiths A, Seargeant L, Poplawski N.; ''CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic features.''; PubMed Europe PMC Scholia
  18. Katiyar S, Joshi S, Lennarz WJ.; ''The retrotranslocation protein Derlin-1 binds peptide:N-glycanase to the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  19. Baysal BE, Willett-Brozick JE, Bacanu SA, Detera-Wadleigh S, Nimgaonkar VL.; ''Common variations in ALG9 are not associated with bipolar I disorder: a family-based study.''; PubMed Europe PMC Scholia
  20. Verachtert H, Rodriguez P, Bass ST, Hansen RG.; ''Purification and properties of guanosine diphosphate hexose pyrophosphorylase from mammalian tissues.''; PubMed Europe PMC Scholia
  21. Hauri H, Appenzeller C, Kuhn F, Nufer O.; ''Lectins and traffic in the secretory pathway.''; PubMed Europe PMC Scholia
  22. Hamilton SR, Li H, Wischnewski H, Prasad A, Kerley-Hamilton JS, Mitchell T, Walling AJ, Davidson RC, Wildt S, Gerngross TU.; ''Intact {alpha}-1,2-endomannosidase is a typical type II membrane protein.''; PubMed Europe PMC Scholia
  23. Guo S, Sato T, Shirane K, Furukawa K.; ''Galactosylation of N-linked oligosaccharides by human beta-1,4-galactosyltransferases I, II, III, IV, V, and VI expressed in Sf-9 cells.''; PubMed Europe PMC Scholia
  24. Ellies LG, Ditto D, Levy GG, Wahrenbrock M, Ginsburg D, Varki A, Le DT, Marth JD.; ''Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands.''; PubMed Europe PMC Scholia
  25. Takahashi S, Takahashi K, Kaneko T, Ogasawara H, Shindo S, Kobayashi M.; ''Human renin-binding protein is the enzyme N-acetyl-D-glucosamine 2-epimerase.''; PubMed Europe PMC Scholia
  26. McNeill H, Knebel A, Arthur JS, Cuenda A, Cohen P.; ''A novel UBA and UBX domain protein that binds polyubiquitin and VCP and is a substrate for SAPKs.''; PubMed Europe PMC Scholia
  27. Toth MJ, Huwyler L.; ''Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase.''; PubMed Europe PMC Scholia
  28. Harrison KD, Park EJ, Gao N, Kuo A, Rush JS, Waechter CJ, Lehrman MA, Sessa WC.; ''Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation.''; PubMed Europe PMC Scholia
  29. Nakayama K, Moriwaki K, Imai T, Shinzaki S, Kamada Y, Murata K, Miyoshi E.; ''Mutation of GDP-mannose-4,6-dehydratase in colorectal cancer metastasis.''; PubMed Europe PMC Scholia
  30. Ong E, Yeh JC, Ding Y, Hindsgaul O, Fukuda M.; ''Expression cloning of a human sulfotransferase that directs the synthesis of the HNK-1 glycan on the neural cell adhesion molecule and glycolipids.''; PubMed Europe PMC Scholia
  31. Varki NM, Strobert E, Dick EJ, Benirschke K, Varki A.; ''Biomedical differences between human and nonhuman hominids: potential roles for uniquely human aspects of sialic acid biology.''; PubMed Europe PMC Scholia
  32. Belaya K, Finlayson S, Slater CR, Cossins J, Liu WW, Maxwell S, McGowan SJ, Maslau S, Twigg SR, Walls TJ, Pascual Pascual SI, Palace J, Beeson D.; ''Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates.''; PubMed Europe PMC Scholia
  33. Angata K, Nakayama J, Fredette B, Chong K, Ranscht B, Fukuda M.; ''Human STX polysialyltransferase forms the embryonic form of the neural cell adhesion molecule. Tissue-specific expression, neurite outgrowth, and chromosomal localization in comparison with another polysialyltransferase, PST.''; PubMed Europe PMC Scholia
  34. Sullivan FX, Kumar R, Kriz R, Stahl M, Xu GY, Rouse J, Chang XJ, Boodhoo A, Potvin B, Cumming DA.; ''Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro.''; PubMed Europe PMC Scholia
  35. Proudfoot AE, Turcatti G, Wells TN, Payton MA, Smith DJ.; ''Purification, cDNA cloning and heterologous expression of human phosphomannose isomerase.''; PubMed Europe PMC Scholia
  36. Oguri S, Yoshida A, Minowa MT, Takeuchi M.; ''Kinetic properties and substrate specificities of two recombinant human N-acetylglucosaminyltransferase-IV isozymes.''; PubMed Europe PMC Scholia
  37. Lopez LC, Youakim A, Evans SC, Shur BD.; ''Evidence for a molecular distinction between Golgi and cell surface forms of beta 1,4-galactosyltransferase.''; PubMed Europe PMC Scholia
  38. Crispin M, Aricescu AR, Chang VT, Jones EY, Stuart DI, Dwek RA, Davis SJ, Harvey DJ.; ''Disruption of alpha-mannosidase processing induces non-canonical hybrid-type glycosylation.''; PubMed Europe PMC Scholia
  39. Bischoff J, Libresco S, Shia MA, Lodish HF.; ''The H1 and H2 polypeptides associate to form the asialoglycoprotein receptor in human hepatoma cells.''; PubMed Europe PMC Scholia
  40. Weihofen WA, Berger M, Chen H, Saenger W, Hinderlich S.; ''Structures of human N-Acetylglucosamine kinase in two complexes with N-Acetylglucosamine and with ADP/glucose: insights into substrate specificity and regulation.''; PubMed Europe PMC Scholia
  41. Stanley P.; ''Biological consequences of overexpressing or eliminating N-acetylglucosaminyltransferase-TIII in the mouse.''; PubMed Europe PMC Scholia
  42. Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D.; ''Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex.''; PubMed Europe PMC Scholia
  43. Wu X, Rush JS, Karaoglu D, Krasnewich D, Lubinsky MS, Waechter CJ, Gilmore R, Freeze HH.; ''Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij.''; PubMed Europe PMC Scholia
  44. van Lith M, Karala AR, Bown D, Gatehouse JA, Ruddock LW, Saunders PT, Benham AM.; ''A developmentally regulated chaperone complex for the endoplasmic reticulum of male haploid germ cells.''; PubMed Europe PMC Scholia
  45. Fernandez F, Shridas P, Jiang S, Aebi M, Waechter CJ.; ''Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae.''; PubMed Europe PMC Scholia
  46. Krzewinski-Recchi MA, Julien S, Juliant S, Teintenier-Lelièvre M, Samyn-Petit B, Montiel MD, Mir AM, Cerutti M, Harduin-Lepers A, Delannoy P.; ''Identification and functional expression of a second human beta-galactoside alpha2,6-sialyltransferase, ST6Gal II.''; PubMed Europe PMC Scholia
  47. Sanyal S, Frank CG, Menon AK.; ''Distinct flippases translocate glycerophospholipids and oligosaccharide diphosphate dolichols across the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  48. Hauri HP, Nufer O, Breuza L, Tekaya HB, Liang L.; ''Lectins and protein traffic early in the secretory pathway.''; PubMed Europe PMC Scholia
  49. Katiyar S, Li G, Lennarz WJ.; ''A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins.''; PubMed Europe PMC Scholia
  50. Freeman DJ, Rupar CA, Carroll KK.; ''Analysis of dolichol in human tissues by high pressure liquid chromatography.''; PubMed Europe PMC Scholia
  51. Ye Y, Shibata Y, Yun C, Ron D, Rapoport TA.; ''A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.''; PubMed Europe PMC Scholia
  52. Molinari M.; ''N-glycan structure dictates extension of protein folding or onset of disposal.''; PubMed Europe PMC Scholia
  53. Hossler P, Goh LT, Lee MM, Hu WS.; ''GlycoVis: visualizing glycan distribution in the protein N-glycosylation pathway in mammalian cells.''; PubMed Europe PMC Scholia
  54. Olzmann JA, Kopito RR, Christianson JC.; ''The mammalian endoplasmic reticulum-associated degradation system.''; PubMed Europe PMC Scholia
  55. Schollen E, Frank CG, Keldermans L, Reyntjens R, Grubenmann CE, Clayton PT, Winchester BG, Smeitink J, Wevers RA, Aebi M, Hennet T, Matthijs G.; ''Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency).''; PubMed Europe PMC Scholia
  56. Cantz M, Gehler J.; ''The mucopolysaccharidoses: inborn errors of glycosaminoglycan catabolism.''; PubMed Europe PMC Scholia
  57. Baysal BE, Willett-Brozick JE, Badner JA, Corona W, Ferrell RE, Nimgaonkar VL, Detera-Wadleigh SD.; ''A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family.''; PubMed Europe PMC Scholia
  58. Dall'Olio F.; ''The sialyl-alpha2,6-lactosaminyl-structure: biosynthesis and functional role.''; PubMed Europe PMC Scholia
  59. Hirao K, Natsuka Y, Tamura T, Wada I, Morito D, Natsuka S, Romero P, Sleno B, Tremblay LO, Herscovics A, Nagata K, Hosokawa N.; ''EDEM3, a soluble EDEM homolog, enhances glycoprotein endoplasmic reticulum-associated degradation and mannose trimming.''; PubMed Europe PMC Scholia
  60. Soh CP, Morgan WT, Watkins WM, Donald AS.; ''The relationship between the N-acetylgalactosamine content and the blood group Sda activity of Tamm and Horsfall urinary glycoprotein.''; PubMed Europe PMC Scholia
  61. Eckert V, Blank M, Mazhari-Tabrizi R, Mumberg D, Funk M, Schwarz RT.; ''Cloning and functional expression of the human GlcNAc-1-P transferase, the enzyme for the committed step of the dolichol cycle, by heterologous complementation in Saccharomyces cerevisiae.''; PubMed Europe PMC Scholia
  62. Völker C, De Praeter CM, Hardt B, Breuer W, Kalz-Füller B, Van Coster RN, Bause E.; ''Processing of N-linked carbohydrate chains in a patient with glucosidase I deficiency (CDG type IIb).''; PubMed Europe PMC Scholia
  63. Sun L, Eklund EA, Van Hove JL, Freeze HH, Thomas JA.; ''Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient.''; PubMed Europe PMC Scholia
  64. Yamaguchi Y, Fujii J, Inoue S, Uozumi N, Yanagidani S, Ikeda Y, Egashira M, Miyoshi O, Niikawa N, Taniguchi N.; ''Mapping of the alpha-1,6-fucosyltransferase gene, FUT8, to human chromosome 14q24.3.''; PubMed Europe PMC Scholia
  65. Schauer R.; ''Achievements and challenges of sialic acid research.''; PubMed Europe PMC Scholia
  66. Ninagawa S, Okada T, Sumitomo Y, Kamiya Y, Kato K, Horimoto S, Ishikawa T, Takeda S, Sakuma T, Yamamoto T, Mori K.; ''EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step.''; PubMed Europe PMC Scholia
  67. Wang J, Liu X, Liang YH, Li LF, Su XD.; ''Acceptor substrate binding revealed by crystal structure of human glucosamine-6-phosphate N-acetyltransferase 1.''; PubMed Europe PMC Scholia
  68. Li Y, Chen X.; ''Sialic acid metabolism and sialyltransferases: natural functions and applications.''; PubMed Europe PMC Scholia
  69. Avezov E, Frenkel Z, Ehrlich M, Herscovics A, Lederkremer GZ.; ''Endoplasmic reticulum (ER) mannosidase I is compartmentalized and required for N-glycan trimming to Man5-6GlcNAc2 in glycoprotein ER-associated degradation.''; PubMed Europe PMC Scholia
  70. Park C, Jin UH, Lee YC, Cho TJ, Kim CH.; ''Characterization of UDP-N-acetylglucosamine:alpha-6-d-mannoside beta-1,6-N-acetylglucosaminyltransferase V from a human hepatoma cell line Hep3B.''; PubMed Europe PMC Scholia
  71. Tan J, D'Agostaro AF, Bendiak B, Reck F, Sarkar M, Squire JA, Leong P, Schachter H.; ''The 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 protein.''; PubMed Europe PMC Scholia
  72. De Praeter CM, Gerwig GJ, Bause E, Nuytinck LK, Vliegenthart JF, Breuer W, Kamerling JP, Espeel MF, Martin JJ, De Paepe AM, Chan NW, Dacremont GA, Van Coster RN.; ''A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency.''; PubMed Europe PMC Scholia
  73. Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C.; ''Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency.''; PubMed Europe PMC Scholia
  74. Pelletier MF, Marcil A, Sevigny G, Jakob CA, Tessier DC, Chevet E, Menard R, Bergeron JJ, Thomas DY.; ''The heterodimeric structure of glucosidase II is required for its activity, solubility, and localization in vivo.''; PubMed Europe PMC Scholia
  75. Lo NW, Shaper JH, Pevsner J, Shaper NL.; ''The expanding beta 4-galactosyltransferase gene family: messages from the databanks.''; PubMed Europe PMC Scholia
  76. Nyfeler B, Nufer O, Matsui T, Mori K, Hauri HP.; ''The cargo receptor ERGIC-53 is a target of the unfolded protein response.''; PubMed Europe PMC Scholia
  77. Tan J, Dunn J, Jaeken J, Schachter H.; ''Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development.''; PubMed Europe PMC Scholia
  78. Dall'Olio F, Malagolini N, Chiricolo M, Trinchera M, Harduin-Lepers A.; ''The expanding roles of the Sd(a)/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2.''; PubMed Europe PMC Scholia
  79. Ning B, Elbein AD.; ''Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase. Evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins.''; PubMed Europe PMC Scholia
  80. Yagi T, Baroja-Fernández E, Yamamoto R, Muñoz FJ, Akazawa T, Hong KS, Pozueta-Romero J.; ''Cloning, expression and characterization of a mammalian Nudix hydrolase-like enzyme that cleaves the pyrophosphate bond of UDP-glucose.''; PubMed Europe PMC Scholia
  81. Helenius J, Ng DT, Marolda CL, Walter P, Valvano MA, Aebi M.; ''Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein.''; PubMed Europe PMC Scholia
  82. Arnold SM, Fessler LI, Fessler JH, Kaufman RJ.; ''Two homologues encoding human UDP-glucose:glycoprotein glucosyltransferase differ in mRNA expression and enzymatic activity.''; PubMed Europe PMC Scholia
  83. Ou WJ, Cameron PH, Thomas DY, Bergeron JJ.; ''Association of folding intermediates of glycoproteins with calnexin during protein maturation.''; PubMed Europe PMC Scholia
  84. Peneff C, Ferrari P, Charrier V, Taburet Y, Monnier C, Zamboni V, Winter J, Harnois M, Fassy F, Bourne Y.; ''Crystal structures of two human pyrophosphorylase isoforms in complexes with UDPGlc(Gal)NAc: role of the alternatively spliced insert in the enzyme oligomeric assembly and active site architecture.''; PubMed Europe PMC Scholia
  85. Matthijs G, Schollen E, Pirard M, Budarf ML, Van Schaftingen E, Cassiman JJ.; ''PMM (PMM1), the human homologue of SEC53 or yeast phosphomannomutase, is localized on chromosome 22q13.''; PubMed Europe PMC Scholia
  86. Schallus T, Jaeckh C, Fehér K, Palma AS, Liu Y, Simpson JC, Mackeen M, Stier G, Gibson TJ, Feizi T, Pieler T, Muhle-Goll C.; ''Malectin: a novel carbohydrate-binding protein of the endoplasmic reticulum and a candidate player in the early steps of protein N-glycosylation.''; PubMed Europe PMC Scholia
  87. Angata K, Fukuda M.; ''Polysialyltransferases: major players in polysialic acid synthesis on the neural cell adhesion molecule.''; PubMed Europe PMC Scholia
  88. Kirchhausen T.; ''Three ways to make a vesicle.''; PubMed Europe PMC Scholia
  89. Grubenmann CE, Frank CG, Hülsmeier AJ, Schollen E, Matthijs G, Mayatepek E, Berger EG, Aebi M, Hennet T.; ''Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik.''; PubMed Europe PMC Scholia
  90. Wang L, Liang Y, Li Z, Cai X, Zhang W, Wu G, Jin J, Fang Z, Yang Y, Zha X.; ''Increase in beta1-6 GlcNAc branching caused by N-acetylglucosaminyltransferase V directs integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721.''; PubMed Europe PMC Scholia
  91. Wedgwood JF, Strominger JL.; ''Enzymatic activities in cultured human lymphocytes that dephosphorylate dolichyl pyrophosphate and dolichyl phosphate.''; PubMed Europe PMC Scholia
  92. Hull E, Sarkar M, Spruijt MP, Höppener JW, Dunn R, Schachter H.; ''Organization and localization to chromosome 5 of the human UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I gene.''; PubMed Europe PMC Scholia
  93. Ohyama C, Smith PL, Angata K, Fukuda MN, Lowe JB, Fukuda M.; ''Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in Lec13 cells.''; PubMed Europe PMC Scholia
  94. Kranz C, Jungeblut C, Denecke J, Erlekotte A, Sohlbach C, Debus V, Kehl HG, Harms E, Reith A, Reichel S, Grobe H, Hammersen G, Schwarzer U, Marquardt T.; ''A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.''; PubMed Europe PMC Scholia
  95. Hardt B, Völker C, Mundt S, Salska-Navarro M, Hauptmann M, Bause E.; ''Human endo-alpha1,2-mannosidase is a Golgi-resident type II membrane protein.''; PubMed Europe PMC Scholia
  96. Schwarz M, Thiel C, Lübbehusen J, Dorland B, de Koning T, von Figura K, Lehle L, Körner C.; ''Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik.''; PubMed Europe PMC Scholia
  97. Frank CG, Grubenmann CE, Eyaid W, Berger EG, Aebi M, Hennet T.; ''Identification and functional analysis of a defect in the human ALG9 gene: definition of congenital disorder of glycosylation type IL.''; PubMed Europe PMC Scholia
  98. Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, Lehle L, Hombauer H, Adamowicz M, Swiezewska E, De Brouwer AP, Blümel P, Sykut-Cegielska J, Houliston S, Swistun D, Ali BR, Dobyns WB, Babovic-Vuksanovic D, van Bokhoven H, Wevers RA, Raetz CR, Freeze HH, Morava E, Al-Gazali L, Gleeson JG.; ''SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.''; PubMed Europe PMC Scholia
  99. Quirk S, Seley KL.; ''Substrate discrimination by the human GTP fucose pyrophosphorylase.''; PubMed Europe PMC Scholia
  100. Christianson JC, Shaler TA, Tyler RE, Kopito RR.; ''OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD.''; PubMed Europe PMC Scholia
  101. Züchner S, Dallman J, Wen R, Beecham G, Naj A, Farooq A, Kohli MA, Whitehead PL, Hulme W, Konidari I, Edwards YJ, Cai G, Peter I, Seo D, Buxbaum JD, Haines JL, Blanton S, Young J, Alfonso E, Vance JM, Lam BL, Peričak-Vance MA.; ''Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa.''; PubMed Europe PMC Scholia
  102. Lederkremer GZ.; ''Glycoprotein folding, quality control and ER-associated degradation.''; PubMed Europe PMC Scholia
  103. Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, Kohlschütter A, von Figura K, Lehle L, Körner C.; ''A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis.''; PubMed Europe PMC Scholia
  104. Wada Y, Sakamoto M.; ''Isolation of the human phosphomannomutase gene (PMM1) and assignment to chromosome 22q13.''; PubMed Europe PMC Scholia
  105. Montiel MD, Krzewinski-Recchi MA, Delannoy P, Harduin-Lepers A.; ''Molecular cloning, gene organization and expression of the human UDP-GalNAc:Neu5Acalpha2-3Galbeta-R beta1,4-N-acetylgalactosaminyltransferase responsible for the biosynthesis of the blood group Sda/Cad antigen: evidence for an unusual extended cytoplasmic domain.''; PubMed Europe PMC Scholia
  106. Burda P, Aebi M.; ''The ALG10 locus of Saccharomyces cerevisiae encodes the alpha-1,2 glucosyltransferase of the endoplasmic reticulum: the terminal glucose of the lipid-linked oligosaccharide is required for efficient N-linked glycosylation.''; PubMed Europe PMC Scholia
  107. Kranz C, Denecke J, Lehle L, Sohlbach K, Jeske S, Meinhardt F, Rossi R, Gudowius S, Marquardt T.; ''Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I.''; PubMed Europe PMC Scholia
  108. Intra J, Perotti ME, Pavesi G, Horner D.; ''Comparative and phylogenetic analysis of alpha-L-fucosidase genes.''; PubMed Europe PMC Scholia
  109. Song BL, Sever N, DeBose-Boyd RA.; ''Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase.''; PubMed Europe PMC Scholia
  110. Wickramasinghe S, Medrano JF.; ''Primer on genes encoding enzymes in sialic acid metabolism in mammals.''; PubMed Europe PMC Scholia
  111. Aronson NN, Kuranda MJ.; ''Lysosomal degradation of Asn-linked glycoproteins.''; PubMed Europe PMC Scholia
  112. Kudo T, Nakagawa H, Takahashi M, Hamaguchi J, Kamiyama N, Yokoo H, Nakanishi K, Nakagawa T, Kamiyama T, Deguchi K, Nishimura S, Todo S.; ''N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma.''; PubMed Europe PMC Scholia
  113. Nauseef WM, McCormick SJ, Clark RA.; ''Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase.''; PubMed Europe PMC Scholia
  114. Furukawa T, Youssef EM, Yatsuoka T, Yokoyama T, Makino N, Inoue H, Fukushige S, Hoshi M, Hayashi Y, Sunamura M, Horii A.; ''Cloning and characterization of the human UDP-N-acetylglucosamine: alpha-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV-homologue (hGnT-IV-H) gene.''; PubMed Europe PMC Scholia
  115. Vleugels W, Schollen E, Foulquier F, Matthijs G.; ''Screening for OST deficiencies in unsolved CDG-I patients.''; PubMed Europe PMC Scholia
  116. Lubas WA, Spiro RG.; ''Evaluation of the role of rat liver Golgi endo-alpha-D-mannosidase in processing N-linked oligosaccharides.''; PubMed Europe PMC Scholia
  117. Kasapkara CS, Tümer L, Ezgü FS, Hasanoğlu A, Race V, Matthijs G, Jaeken J.; ''SRD5A3-CDG: a patient with a novel mutation.''; PubMed Europe PMC Scholia
  118. McKnight GL, Mudri SL, Mathewes SL, Traxinger RR, Marshall S, Sheppard PO, O'Hara PJ.; ''Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase.''; PubMed Europe PMC Scholia
  119. Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, Moremen KW.; ''Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control.''; PubMed Europe PMC Scholia
  120. Tremblay LO, Herscovics A.; ''Characterization of a cDNA encoding a novel human Golgi alpha 1, 2-mannosidase (IC) involved in N-glycan biosynthesis.''; PubMed Europe PMC Scholia
  121. Angata K, Suzuki M, McAuliffe J, Ding Y, Hindsgaul O, Fukuda M.; ''Differential biosynthesis of polysialic acid on neural cell adhesion molecule (NCAM) and oligosaccharide acceptors by three distinct alpha 2,8-sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III.''; PubMed Europe PMC Scholia
  122. Schollen E, Dorland L, de Koning TJ, Van Diggelen OP, Huijmans JG, Marquardt T, Babovic-Vuksanovic D, Patterson M, Imtiaz F, Winchester B, Adamowicz M, Pronicka E, Freeze H, Matthijs G.; ''Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib).''; PubMed Europe PMC Scholia
  123. Sun L, Eklund EA, Chung WK, Wang C, Cohen J, Freeze HH.; ''Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia.''; PubMed Europe PMC Scholia
  124. Suzuki T, Yano K, Sugimoto S, Kitajima K, Lennarz WJ, Inoue S, Inoue Y, Emori Y.; ''Endo-beta-N-acetylglucosaminidase, an enzyme involved in processing of free oligosaccharides in the cytosol.''; PubMed Europe PMC Scholia
  125. Timson DJ, Reece RJ.; ''Identification and characterisation of human aldose 1-epimerase.''; PubMed Europe PMC Scholia
  126. Senderek J, Müller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hübner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmüller H.; ''Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect.''; PubMed Europe PMC Scholia
  127. Suzuki T, Huang C, Fujihira H.; ''The cytoplasmic peptide:N-glycanase (NGLY1) - Structure, expression and cellular functions.''; PubMed Europe PMC Scholia
  128. Gao XD, Tachikawa H, Sato T, Jigami Y, Dean N.; ''Alg14 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 glycosylation.''; PubMed Europe PMC Scholia
  129. Sasaki N, Manya H, Okubo R, Kobayashi K, Ishida H, Toda T, Endo T, Nishihara S.; ''beta4GalT-II is a key regulator of glycosylation of the proteins involved in neuronal development.''; PubMed Europe PMC Scholia
  130. Takahashi S, Hori K, Takahashi K, Ogasawara H, Tomatsu M, Saito K.; ''Effects of nucleotides on N-acetyl-d-glucosamine 2-epimerases (renin-binding proteins): comparative biochemical studies.''; PubMed Europe PMC Scholia
  131. Yamaguchi Y, Ikeda Y, Takahashi T, Ihara H, Tanaka T, Sasho C, Uozumi N, Yanagidani S, Inoue S, Fujii J, Taniguchi N.; ''Genomic structure and promoter analysis of the human alpha1, 6-fucosyltransferase gene (FUT8).''; PubMed Europe PMC Scholia
  132. Wolf MJ, Rush JS, Waechter CJ.; ''Golgi-enriched membrane fractions from rat brain and liver contain long-chain polyisoprenyl pyrophosphate phosphatase activity.''; PubMed Europe PMC Scholia
  133. Clarke LA.; ''The mucopolysaccharidoses: a success of molecular medicine.''; PubMed Europe PMC Scholia
  134. Petrescu AJ, Milac AL, Petrescu SM, Dwek RA, Wormald MR.; ''Statistical analysis of the protein environment of N-glycosylation sites: implications for occupancy, structure, and folding.''; PubMed Europe PMC Scholia
  135. Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, Samyn-Petit B, Julien S, Delannoy P.; ''The human sialyltransferase family.''; PubMed Europe PMC Scholia
  136. Cameron HS, Szczepaniak D, Weston BW.; ''Expression of human chromosome 19p alpha(1,3)-fucosyltransferase genes in normal tissues. Alternative splicing, polyadenylation, and isoforms.''; PubMed Europe PMC Scholia
  137. Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E.; ''Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).''; PubMed Europe PMC Scholia
  138. Bergfeld AK, Pearce OM, Diaz SL, Pham T, Varki A.; ''Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating the intracellular fate of the non-human sialic acid N-glycolylneuraminic acid.''; PubMed Europe PMC Scholia
  139. Harada Y, Masahara-Negishi Y, Suzuki T.; ''Cytosolic-free oligosaccharides are predominantly generated by the degradation of dolichol-linked oligosaccharides in mammalian cells.''; PubMed Europe PMC Scholia
  140. Winchester B.; ''Lysosomal metabolism of glycoproteins.''; PubMed Europe PMC Scholia
  141. O'Reilly MK, Zhang G, Imperiali B.; ''In vitro evidence for the dual function of Alg2 and Alg11: essential mannosyltransferases in N-linked glycoprotein biosynthesis.''; PubMed Europe PMC Scholia
  142. Pang H, Koda Y, Soejima M, Kimura H.; ''Identification of human phosphoglucomutase 3 (PGM3) as N-acetylglucosamine-phosphate mutase (AGM1).''; PubMed Europe PMC Scholia
  143. Alanen HI, Williamson RA, Howard MJ, Hatahet FS, Salo KE, Kauppila A, Kellokumpu S, Ruddock LW.; ''ERp27, a new non-catalytic endoplasmic reticulum-located human protein disulfide isomerase family member, interacts with ERp57.''; PubMed Europe PMC Scholia
  144. Kumar R, Yang J, Larsen RD, Stanley P.; ''Cloning and expression of N-acetylglucosaminyltransferase I, the medial Golgi transferase that initiates complex N-linked carbohydrate formation.''; PubMed Europe PMC Scholia
  145. Akama TO, Nakagawa H, Wong NK, Sutton-Smith M, Dell A, Morris HR, Nakayama J, Nishimura S, Pai A, Moremen KW, Marth JD, Fukuda MN.; ''Essential and mutually compensatory roles of {alpha}-mannosidase II and {alpha}-mannosidase IIx in N-glycan processing in vivo in mice.''; PubMed Europe PMC Scholia
  146. Brynedal B, Wojcik J, Esposito F, Debailleul V, Yaouanq J, Martinelli-Boneschi F, Edan G, Comi G, Hillert J, Abderrahim H.; ''MGAT5 alters the severity of multiple sclerosis.''; PubMed Europe PMC Scholia
  147. Kelleher DJ, Gilmore R.; ''An evolving view of the eukaryotic oligosaccharyltransferase.''; PubMed Europe PMC Scholia
  148. Hinderlich S, Berger M, Schwarzkopf M, Effertz K, Reutter W.; ''Molecular cloning and characterization of murine and human N-acetylglucosamine kinase.''; PubMed Europe PMC Scholia
  149. Oriol R, Martinez-Duncker I, Chantret I, Mollicone R, Codogno P.; ''Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides as donor substrate.''; PubMed Europe PMC Scholia
  150. Chantret I, Dupré T, Delenda C, Bucher S, Dancourt J, Barnier A, Charollais A, Heron D, Bader-Meunier B, Danos O, Seta N, Durand G, Oriol R, Codogno P, Moore SE.; ''Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase.''; PubMed Europe PMC Scholia
  151. Hansske B, Thiel C, Lübke T, Hasilik M, Höning S, Peters V, Heidemann PH, Hoffmann GF, Berger EG, von Figura K, Körner C.; ''Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId.''; PubMed Europe PMC Scholia
  152. Granovsky M, Fata J, Pawling J, Muller WJ, Khokha R, Dennis JW.; ''Suppression of tumor growth and metastasis in Mgat5-deficient mice.''; PubMed Europe PMC Scholia
  153. Imbach T, Burda P, Kuhnert P, Wevers RA, Aebi M, Berger EG, Hennet T.; ''A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic.''; PubMed Europe PMC Scholia
  154. Kämpf M, Absmanner B, Schwarz M, Lehle L.; ''Biochemical characterization and membrane topology of Alg2 from Saccharomyces cerevisiae as a bifunctional alpha1,3- and 1,6-mannosyltransferase involved in lipid-linked oligosaccharide biosynthesis.''; PubMed Europe PMC Scholia
  155. Mi Y, Fiete D, Baenziger JU.; ''Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice.''; PubMed Europe PMC Scholia
  156. Tian H, Miyoshi E, Kawaguchi N, Shaker M, Ito Y, Taniguchi N, Tsujimoto M, Matsuura N.; ''The implication of N-acetylglucosaminyltransferase V expression in gastric cancer.''; PubMed Europe PMC Scholia
  157. Serafini-Cessi F, Conte R.; ''Precipitin reaction between Sda-active human Tamm-Horsfall glycoprotein and anti-Sda-serum.''; PubMed Europe PMC Scholia
  158. Takahashi T, Honda R, Nishikawa Y.; ''Cloning of the human cDNA which can complement the defect of the yeast mannosyltransferase I-deficient mutant alg 1.''; PubMed Europe PMC Scholia
  159. Maeda Y, Tanaka S, Hino J, Kangawa K, Kinoshita T.; ''Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3.''; PubMed Europe PMC Scholia
  160. Hiraoka N, Misra A, Belot F, Hindsgaul O, Fukuda M.; ''Molecular cloning and expression of two distinct human N-acetylgalactosamine 4-O-sulfotransferases that transfer sulfate to GalNAc beta 1-->4GlcNAc beta 1-->R in both N- and O-glycans.''; PubMed Europe PMC Scholia
  161. Tonetti M, Sturla L, Bisso A, Benatti U, De Flora A.; ''Synthesis of GDP-L-fucose by the human FX protein.''; PubMed Europe PMC Scholia
  162. Gonzalez DS, Karaveg K, Vandersall-Nairn AS, Lal A, Moremen KW.; ''Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis.''; PubMed Europe PMC Scholia
  163. Arnold SM, Kaufman RJ.; ''The noncatalytic portion of human UDP-glucose: glycoprotein glucosyltransferase I confers UDP-glucose binding and transferase function to the catalytic domain.''; PubMed Europe PMC Scholia
  164. Saxena A, Yik JH, Weigel PH.; ''H2, the minor subunit of the human asialoglycoprotein receptor, trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid.''; PubMed Europe PMC Scholia
  165. Clarke JL, Watkins WM.; ''Expression of human alpha-l-fucosyltransferase gene homologs in monkey kidney COS cells and modification of potential fucosyltransferase acceptor substrates by an endogenous glycosidase.''; PubMed Europe PMC Scholia
  166. Ide Y, Miyoshi E, Nakagawa T, Gu J, Tanemura M, Nishida T, Ito T, Yamamoto H, Kozutsumi Y, Taniguchi N.; ''Aberrant expression of N-acetylglucosaminyltransferase-IVa and IVb (GnT-IVa and b) in pancreatic cancer.''; PubMed Europe PMC Scholia
  167. Cipollo JF, Trimble RB, Chi JH, Yan Q, Dean N.; ''The yeast ALG11 gene specifies addition of the terminal alpha 1,2-Man to the Man5GlcNAc2-PP-dolichol N-glycosylation intermediate formed on the cytosolic side of the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  168. Apweiler R, Hermjakob H, Sharon N.; ''On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database.''; PubMed Europe PMC Scholia
  169. Kinoshita T, Inoue N.; ''Dissecting and manipulating the pathway for glycosylphos-phatidylinositol-anchor biosynthesis.''; PubMed Europe PMC Scholia
  170. Lo Presti L, Cabuy E, Chiricolo M, Dall'Olio F.; ''Molecular cloning of the human beta1,4 N-acetylgalactosaminyltransferase responsible for the biosynthesis of the Sd(a) histo-blood group antigen: the sequence predicts a very long cytoplasmic domain.''; PubMed Europe PMC Scholia
  171. Alcock F, Swanton E.; ''Mammalian OS-9 is upregulated in response to endoplasmic reticulum stress and facilitates ubiquitination of misfolded glycoproteins.''; PubMed Europe PMC Scholia
  172. Schaub BE, Berger B, Berger EG, Rohrer J.; ''Transition of galactosyltransferase 1 from trans-Golgi cisterna to the trans-Golgi network is signal mediated.''; PubMed Europe PMC Scholia
  173. Schmid M, Prajczer S, Gruber LN, Bertocchi C, Gandini R, Pfaller W, Jennings P, Joannidis M.; ''Uromodulin facilitates neutrophil migration across renal epithelial monolayers.''; PubMed Europe PMC Scholia
  174. Misago M, Liao YF, Kudo S, Eto S, Mattei MG, Moremen KW, Fukuda MN.; ''Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme.''; PubMed Europe PMC Scholia
  175. Ciccarelli FD, von Mering C, Suyama M, Harrington ED, Izaurralde E, Bork P.; ''Complex genomic rearrangements lead to novel primate gene function.''; PubMed Europe PMC Scholia
  176. Zhou H, Sun L, Li J, Xu C, Yu F, Liu Y, Ji C, He J.; ''The crystal structure of human GDP-L-fucose synthase.''; PubMed Europe PMC Scholia
  177. Pinho SS, Reis CA, Paredes J, Magalhães AM, Ferreira AC, Figueiredo J, Xiaogang W, Carneiro F, Gärtner F, Seruca R.; ''The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin.''; PubMed Europe PMC Scholia
  178. Willems PJ, Seo HC, Coucke P, Tonlorenzi R, O'Brien JS.; ''Spectrum of mutations in fucosidosis.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
115049view16:59, 25 January 2021ReactomeTeamReactome version 75
113493view11:57, 2 November 2020ReactomeTeamReactome version 74
112693view16:08, 9 October 2020ReactomeTeamReactome version 73
101610view11:47, 1 November 2018ReactomeTeamreactome version 66
101147view21:33, 31 October 2018ReactomeTeamreactome version 65
100675view20:07, 31 October 2018ReactomeTeamreactome version 64
100225view16:52, 31 October 2018ReactomeTeamreactome version 63
99776view15:17, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99333view12:47, 31 October 2018ReactomeTeamreactome version 62
93956view13:47, 16 August 2017ReactomeTeamreactome version 61
93552view11:26, 9 August 2017ReactomeTeamreactome version 61
86654view09:23, 11 July 2016ReactomeTeamreactome version 56
83351view10:56, 18 November 2015ReactomeTeamVersion54
81512view13:03, 21 August 2015ReactomeTeamVersion53
78300view14:22, 24 December 2014EgonwGave an unlabeled protein a label matching its identifier ("4836523").
76985view08:27, 17 July 2014ReactomeTeamFixed remaining interactions
76690view12:05, 16 July 2014ReactomeTeamFixed remaining interactions
76016view10:07, 11 June 2014ReactomeTeamRe-fixing comment source
75725view11:19, 10 June 2014ReactomeTeamReactome 48 Update
75075view14:02, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74857view15:15, 2 May 2014EgonwMarked a metabolite as a DataNode type="Metabolite"...
74722view08:48, 30 April 2014ReactomeTeamReactome46
44964view12:49, 6 October 2011MartijnVanIerselOntology Term : 'protein modification pathway' added !
42008view21:49, 4 March 2011MaintBotAutomatic update
39811view05:50, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1MetaboliteCHEBI:59081 (ChEBI)
(Glc)1 (GlcNAc)2 (Man)7bc R-ALL-901056 (Reactome)
(Glc)1 (GlcNAc)2 (Man)8b MetaboliteCHEBI:64046 (ChEBI)
(Glc)1 (GlcNAc)2 (Man)8c R-ALL-901027 (Reactome)
(Glc)1 (GlcNAc)2 (Man)9 MetaboliteCHEBI:59080 (ChEBI)
(Glc)2 (GlcNAc)2 (Man)9 (PP-Dol)1MetaboliteCHEBI:53020 (ChEBI)
(Glc)2 (GlcNAc)2 (Man)9 (Asn)1 MetaboliteCHEBI:59082 (ChEBI)
(Glc)3 (GlcNAc)2 (Man)9 (Asn)1MetaboliteCHEBI:59084 (ChEBI)
(Glc)3 (GlcNAc)2 (Man)9 (PP-Dol)1MetaboliteCHEBI:53019 (ChEBI)
(Glc)3 (GlcNAc)2 (Man)9 (Asn)1 MetaboliteCHEBI:59084 (ChEBI)
(GlcNAc)2 (Man)2 (PP-Dol)1MetaboliteCHEBI:59085 (ChEBI)
(GlcNAc)2 (Man)3 (PP-Dol)1MetaboliteCHEBI:53742 (ChEBI)
(GlcNAc)2 (Man)5 (Asn)1MetaboliteCHEBI:59087 (ChEBI)
(GlcNAc)2 (Man)5 (PP-Dol)1MetaboliteCHEBI:53022 (ChEBI)
(GlcNAc)2 (Man)5 MetaboliteCHEBI:59087 (ChEBI)
(GlcNAc)2 (Man)6 (PP-Dol)1MetaboliteCHEBI:53023 (ChEBI)
(GlcNAc)2 (Man)7 (PP-Dol)1MetaboliteCHEBI:59088 (ChEBI)
(GlcNAc)2 (Man)7aa MetaboliteCHEBI:60640 (ChEBI)
(GlcNAc)2 (Man)7bc R-ALL-901089 (Reactome)
(GlcNAc)2 (Man)7bcMetaboliteCHEBI:60637 (ChEBI)
(GlcNAc)2 (Man)8 (Asn)1MetaboliteCHEBI:59089 (ChEBI)
(GlcNAc)2 (Man)8 (PP-Dol)1MetaboliteCHEBI:59091 (ChEBI)
(GlcNAc)2 (Man)8 glycansComplexR-ALL-964831 (Reactome)
(GlcNAc)2 (Man)8a MetaboliteCHEBI:60627 (ChEBI)
(GlcNAc)2 (Man)8b MetaboliteCHEBI:60628 (ChEBI)
(GlcNAc)2 (Man)8b MetaboliteCHEBI:64048 (ChEBI)
(GlcNAc)2 (Man)8c MetaboliteCHEBI:60629 (ChEBI)
(GlcNAc)2 (Man)8c MetaboliteCHEBI:64052 (ChEBI)
(GlcNAc)2 (Man)9 (PP-Dol)1MetaboliteCHEBI:59093 (ChEBI)
(GlcNAc)2 (Man)9 MetaboliteCHEBI:59092 (ChEBI)
(GlcNAc)2 (Man)9-5ComplexR-ALL-8852852 (Reactome)
(GlcNAc)2 (Man)9MetaboliteCHEBI:59092 (ChEBI)
(GlcNAc)3 (Man)3 (Asn)1MetaboliteCHEBI:60615 (ChEBI)
(GlcNAc)3 (Man)5 (Asn)1MetaboliteCHEBI:60625 (ChEBI)
(GlcNAc)4 (Man)3 (Asn)1MetaboliteCHEBI:60651 (ChEBI)
(un)folded

protein:(GlcNAc)2

(Man)9
ComplexR-HSA-909547 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
ComplexR-HSA-912283 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
ComplexR-HSA-915150 (Reactome)
2xGNPNAT1ComplexR-HSA-771697 (Reactome)
2xUAP1ComplexR-HSA-3558426 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ALG10 ProteinQ5BKT4 (Uniprot-TrEMBL)
ALG10 homologueComplexR-HSA-449652 (Reactome)
ALG10B ProteinQ5I7T1 (Uniprot-TrEMBL)
ALG11ProteinQ2TAA5 (Uniprot-TrEMBL)
ALG12ProteinQ9BV10 (Uniprot-TrEMBL)
ALG13(1-165) ProteinQ9NP73 (Uniprot-TrEMBL)
ALG13:ALG14ComplexR-HSA-449326 (Reactome)
ALG14 ProteinQ96F25 (Uniprot-TrEMBL)
ALG1ProteinQ9BT22 (Uniprot-TrEMBL)
ALG2ProteinQ9H553 (Uniprot-TrEMBL)
ALG3ProteinQ92685 (Uniprot-TrEMBL)
ALG5ProteinQ9Y673 (Uniprot-TrEMBL)
ALG6ProteinQ9Y672 (Uniprot-TrEMBL)
ALG8ProteinQ9BVK2 (Uniprot-TrEMBL)
ALG9ProteinQ9H6U8 (Uniprot-TrEMBL)
AMDHD2ProteinQ9Y303 (Uniprot-TrEMBL)
AMFR ProteinQ9UKV5 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
AcGlcN1PMetaboliteCHEBI:7125 (ChEBI)
AcGlcN6PMetaboliteCHEBI:15784 (ChEBI)
B4GALNT2ProteinQ8NHY0 (Uniprot-TrEMBL)
B4GALT1 ProteinP15291 (Uniprot-TrEMBL)
B4GALT1-6 homodimersComplexR-HSA-975898 (Reactome)
B4GALT2 ProteinO60909 (Uniprot-TrEMBL)
B4GALT3 ProteinO60512 (Uniprot-TrEMBL)
B4GALT4 ProteinO60513 (Uniprot-TrEMBL)
B4GALT5 ProteinO43286 (Uniprot-TrEMBL)
B4GALT6 ProteinQ9UBX8 (Uniprot-TrEMBL)
CALR ProteinP27797 (Uniprot-TrEMBL)
CALR,CANXComplexR-HSA-901048 (Reactome)
CALR:CANXComplexR-HSA-548862 (Reactome)
CANX ProteinP27824 (Uniprot-TrEMBL)
CCAMetaboliteCHEBI:16359 (ChEBI)
CDPMetaboliteCHEBI:17239 (ChEBI)
CGA ProteinP01215 (Uniprot-TrEMBL)
CHST10ProteinO43529 (Uniprot-TrEMBL)
CHST8ProteinQ9H2A9 (Uniprot-TrEMBL)
CO2MetaboliteCHEBI:16526 (ChEBI)
CTPMetaboliteCHEBI:17677 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
DAD1 ProteinP61803 (Uniprot-TrEMBL)
DCHOLMetaboliteCHEBI:16091 (ChEBI)
DDOST ProteinP39656 (Uniprot-TrEMBL)
DERL1 ProteinQ9BUN8 (Uniprot-TrEMBL)
DERL2 ProteinQ9GZP9 (Uniprot-TrEMBL)
DHDDS ProteinQ86SQ9 (Uniprot-TrEMBL)
DHDDS:NUS1ComplexR-HSA-6806947 (Reactome)
DOLDPMetaboliteCHEBI:15750 (ChEBI)
DOLKProteinQ9UPQ8 (Uniprot-TrEMBL)
DOLP-ManMetaboliteCHEBI:15809 (ChEBI)
DOLPMetaboliteCHEBI:16214 (ChEBI)
DOLPP1ProteinQ86YN1 (Uniprot-TrEMBL)
DPAGT1ProteinQ9H3H5 (Uniprot-TrEMBL)
DPM1 ProteinO60762 (Uniprot-TrEMBL)
DPM1:DPM2:DPM3ComplexR-HSA-162692 (Reactome)
DPM2 ProteinO94777 (Uniprot-TrEMBL)
DPM3 ProteinQ9P2X0 (Uniprot-TrEMBL)
DbGPMetaboliteCHEBI:15812 (ChEBI)
Deglycosylation complexComplexR-HSA-8850590 (Reactome)
E,E-FPPMetaboliteCHEBI:17407 (ChEBI)
EDEM1 ProteinQ92611 (Uniprot-TrEMBL)
EDEM1,3ComplexR-HSA-6782691 (Reactome)
EDEM2 ProteinQ9BV94 (Uniprot-TrEMBL)
EDEM3 ProteinQ9BZQ6 (Uniprot-TrEMBL)
ENGASEProteinQ8NFI3 (Uniprot-TrEMBL)
ER to Golgi

Anterograde

Transport
PathwayR-HSA-199977 (Reactome) Secretory cargo destined to be secreted or to arrive at the plasma membrane (PM) leaves the ER via distinct exit sites. This cargo is destined for the Golgi apparatus for further processing.
FPGTProteinO14772 (Uniprot-TrEMBL)
FUCA1 ProteinP04066 (Uniprot-TrEMBL)
FUCA1 tetramerComplexR-HSA-5693805 (Reactome)
FUKProteinQ8N0W3 (Uniprot-TrEMBL)
FUOM ProteinA2VDF0 (Uniprot-TrEMBL)
FUOM dimerComplexR-HSA-6787682 (Reactome)
FUT3ProteinP21217 (Uniprot-TrEMBL)
FUT8ProteinQ9BYC5 (Uniprot-TrEMBL)
Fru(6)PMetaboliteCHEBI:15946 (ChEBI)
Fuc1PMetaboliteCHEBI:12387 (ChEBI)
G1PMetaboliteCHEBI:16077 (ChEBI)
GANAB ProteinQ14697 (Uniprot-TrEMBL)
GDP-DHDManMetaboliteCHEBI:16955 (ChEBI)
GDP-FucMetaboliteCHEBI:17009 (ChEBI)
GDP-KDGalMetaboliteCHEBI:86476 (ChEBI)
GDP-ManMetaboliteCHEBI:15820 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GFPT1 ProteinQ06210 (Uniprot-TrEMBL)
GFPT1,2ComplexR-HSA-532205 (Reactome)
GFPT2 ProteinO94808 (Uniprot-TrEMBL)
GMDSProteinO60547 (Uniprot-TrEMBL)
GMPPA ProteinQ96IJ6 (Uniprot-TrEMBL)
GMPPA/BComplexR-HSA-532536 (Reactome)
GMPPB ProteinQ9Y5P6 (Uniprot-TrEMBL)
GNPNAT1 ProteinQ96EK6 (Uniprot-TrEMBL)
GTPMetaboliteCHEBI:15996 (ChEBI)
Gal1,3Fuc1,4GlcNAc groupMetaboliteCHEBI:18914 (ChEBI)
Gal1,3GlcNAc groupMetaboliteCHEBI:18915 (ChEBI)
GlcMetaboliteCHEBI:17925 (ChEBI)
GlcN6PMetaboliteCHEBI:15873 (ChEBI)
GlcNAc (Man)9-5ComplexR-ALL-8853381 (Reactome)
GlcNAc MetaboliteCHEBI:17411 (ChEBI)
GlcNAc, GlcNGcComplexR-ALL-6803785 (Reactome)
GlcNAc-6-P MetaboliteCHEBI:15784 (ChEBI)
GlcNAc-6-P, GlcNGc-6-PComplexR-ALL-6803738 (Reactome)
GlcNAcDOLDPMetaboliteCHEBI:18278 (ChEBI)
GlcNGc MetaboliteCHEBI:27459 (ChEBI)
GlcNGc-6-P MetaboliteCHEBI:88130 (ChEBI)
GlcNGc-6-PMetaboliteCHEBI:88130 (ChEBI)
Glycoprotein with

GlcNAc in position

4
R-ALL-981616 (Reactome)
Glycoprotein with

GlcNAc in position

5
R-ALL-981617 (Reactome)
Glycoprotein with

bifurcating GlcNAc

in position 3
R-ALL-981613 (Reactome)
Glycoprotein with galactoseR-ALL-981618 (Reactome)
Glycoprotein-Neu5AcR-ALL-981615 (Reactome)
Glycoproteins with Man8 N-glycansComplexR-HSA-948002 (Reactome)
Glycoproteins with Man8 N-glycansComplexR-HSA-948022 (Reactome)
Glycosaminoglycan metabolismPathwayR-HSA-1630316 (Reactome) Glycosaminoglycans (GAGs) are long, unbranched polysaccharides containing a repeating disaccharide unit composed of a hexosamine (either N-acetylgalactosamine (GalNAc) or N-acetylglucosamine (GlcNAc)) and a uronic acid (glucuronate or iduronate). They can be heavily sulfated. GAGs are located primarily in the extracellular matrix (ECM) and on cell membranes, acting as a lubricating fluid for joints and as part of signalling processes. They have structural roles in connective tissue, cartilage, bone and blood vessels (Esko et al. 2009). GAGs are degraded in the lysosome as part of their natural turnover. Defects in the lysosomal enzymes responsible for the metabolism of membrane-associated GAGs lead to lysosomal storage diseases called mucopolysaccharidoses (MPS). MPSs are characterised by the accumulation of GAGs in lysosomes resulting in chronic, progressively debilitating disorders that in many instances lead to severe psychomotor retardation and premature death (Cantz & Gehler 1976, Clarke 2008). The biosynthesis and breakdown of the main GAGs (hyaluronate, keratan sulfate, chondroitin sulfate, dermatan sulfate and heparan sulfate) is described here.
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HNK1 carbohydrateMetaboliteCHEBI:86336 (ChEBI)
IPPPMetaboliteCHEBI:16584 (ChEBI)
L-GlnMetaboliteCHEBI:58359 (ChEBI)
L-GluMetaboliteCHEBI:29985 (ChEBI)
L-fucoseMetaboliteCHEBI:2181 (ChEBI)
LHB ProteinP01229 (Uniprot-TrEMBL)
LMAN1 ProteinP49257 (Uniprot-TrEMBL)
LMAN1:MCFD2ComplexR-HSA-1017219 (Reactome)
Lysosomal

oligosaccharide

catabolism
PathwayR-HSA-8853383 (Reactome) N-Glycosylation is one of the most common co- and posttranslational modifications of eukaryotic proteins occurring in the ER lumen. N-glycosylation plays pivotal roles in protein folding and intra- or inter-cellular trafficking of N-glycosylated proteins. Quality control mechanisms in the ER sift out incorrectly-folded proteins from correctly-folded proteins, the former then destined for degradation. Incorrectly-folded N-glycans are exported to the cytosol where the process of degradation begins. Once the unfolded protein is cleaved from the oligosaccharide (forming free oligosaccharides, fOS), step-wise degradation of mannose moieties, both in the cytosol (Suzuki & Harada 2014) and then in the lysosome (Aronson & Kuranda 1989, Winchester 2005), results in complete degradation. Breakdown must be complete to avoid lysosomal storage diseases that occur when fragments as small as dimers are left undigested.
MAGT1 ProteinQ9H0U3 (Uniprot-TrEMBL)
MAN1A1 ProteinP33908 (Uniprot-TrEMBL)
MAN1A1/A2/C1ComplexR-HSA-964764 (Reactome)
MAN1A2 ProteinO60476 (Uniprot-TrEMBL)
MAN1B1 ProteinQ9UKM7 (Uniprot-TrEMBL)
MAN1B1,EDEM2ComplexR-HSA-6782581 (Reactome)
MAN1C1 ProteinQ9NR34 (Uniprot-TrEMBL)
MAN2:Zn2+ComplexR-HSA-975821 (Reactome)
MAN2A1 ProteinQ16706 (Uniprot-TrEMBL)
MAN2A2 ProteinP49641 (Uniprot-TrEMBL)
MANEAProteinQ5SRI9 (Uniprot-TrEMBL)
MARCH6 ProteinO60337 (Uniprot-TrEMBL)
MCFD2 ProteinQ8NI22 (Uniprot-TrEMBL)
MDCDDMetaboliteCHEBI:18396 (ChEBI)
MGAT1ProteinP26572 (Uniprot-TrEMBL)
MGAT2ProteinQ10469 (Uniprot-TrEMBL)
MGAT3ProteinQ09327 (Uniprot-TrEMBL)
MGAT4A(1-535) ProteinQ9UM21 (Uniprot-TrEMBL)
MGAT4B ProteinQ9UQ53 (Uniprot-TrEMBL)
MGAT4C ProteinQ9UBM8 (Uniprot-TrEMBL)
MGAT4sComplexR-HSA-975913 (Reactome)
MGAT5ProteinQ09328 (Uniprot-TrEMBL)
MLEC ProteinQ14165 (Uniprot-TrEMBL)
MLECProteinQ14165 (Uniprot-TrEMBL)
MOGSProteinQ13724 (Uniprot-TrEMBL)
MPDU1ProteinO75352 (Uniprot-TrEMBL)
MPIProteinP34949 (Uniprot-TrEMBL)
MVA5PPMetaboliteCHEBI:15899 (ChEBI)
MVD ProteinP53602 (Uniprot-TrEMBL)
MVD dimerComplexR-HSA-191341 (Reactome)
Man1PMetaboliteCHEBI:35374 (ChEBI)
Man6PMetaboliteCHEBI:17369 (ChEBI)
ManMetaboliteCHEBI:4208 (ChEBI)
ManNAc MetaboliteCHEBI:17122 (ChEBI)
ManNAc, ManNGcComplexR-ALL-6803769 (Reactome)
ManNGc MetaboliteCHEBI:28255 (ChEBI)
N,N'-DCDOLDPMetaboliteCHEBI:18341 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NAGK ProteinQ9UJ70 (Uniprot-TrEMBL)
NAGK dimerComplexR-HSA-6803750 (Reactome)
NGLY1 ProteinQ96IV0 (Uniprot-TrEMBL)
NGP:1,6-GlcNAcR-ALL-1028779 (Reactome)
NGP:1,6-GlcNAcR-ALL-6784247 (Reactome)
NGPMetaboliteCHEBI:59520 (ChEBI)
NUDT14ProteinO95848 (Uniprot-TrEMBL)
NUS1 ProteinQ96E22 (Uniprot-TrEMBL)
Neu5AcMetaboliteCHEBI:17012 (ChEBI)
OS9 ProteinQ13438 (Uniprot-TrEMBL)
OS9:SEL1:ERAD E3 ligases:DERL2ComplexR-HSA-8866892 (Reactome)
OST complexComplexR-HSA-532516 (Reactome)
PALM-C36-ASGR1 ProteinP07306 (Uniprot-TrEMBL)
PALM-C36-ASGR1:PALM-C54,58-ASGR2:proteoglycanComplexR-HSA-8855703 (Reactome)
PALM-C36-ASGR1:PALM-C54,58-ASGR2ComplexR-HSA-8855701 (Reactome)
PALM-C54,58-ASGR2 ProteinP07307 (Uniprot-TrEMBL)
PAPMetaboliteCHEBI:17985 (ChEBI)
PAPSMetaboliteCHEBI:17980 (ChEBI)
PDIA3 ProteinP30101 (Uniprot-TrEMBL)
PDIA3ProteinP30101 (Uniprot-TrEMBL)
PGM3ProteinO95394 (Uniprot-TrEMBL)
PMM1 ProteinQ92871 (Uniprot-TrEMBL)
PMM1,2ComplexR-HSA-532532 (Reactome)
PMM2 ProteinO15305 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKCSH ProteinP14314 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RAD23B ProteinP54727 (Uniprot-TrEMBL)
RENBP ProteinP51606 (Uniprot-TrEMBL)
RENBP dimerComplexR-HSA-6803782 (Reactome)
RFT1ProteinQ96AA3 (Uniprot-TrEMBL)
RNF103 ProteinO00237 (Uniprot-TrEMBL)
RNF139 ProteinQ8WU17 (Uniprot-TrEMBL)
RNF185 ProteinQ96GF1 (Uniprot-TrEMBL)
RNF5 ProteinQ99942 (Uniprot-TrEMBL)
RPN1 ProteinP04843 (Uniprot-TrEMBL)
RPN2 ProteinP04844 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
S-HNK1 carbohydrateMetaboliteCHEBI:86335 (ChEBI)
S-glyco-CGA ProteinP01215 (Uniprot-TrEMBL)
S-glyco-LHB ProteinP01229 (Uniprot-TrEMBL)
S-glyco-LutropinComplexR-HSA-6793931 (Reactome)
SEL1L ProteinQ9UBV2 (Uniprot-TrEMBL)
SLC35C1ProteinQ96A29 (Uniprot-TrEMBL)
SRD5A3ProteinQ9H8P0 (Uniprot-TrEMBL)
ST3GAL4ProteinQ11206 (Uniprot-TrEMBL)
ST6GAL1ProteinP15907 (Uniprot-TrEMBL)
ST8SIA2 ProteinQ92186 (Uniprot-TrEMBL)
ST8SIA2,3,6ComplexR-HSA-1022134 (Reactome)
ST8SIA3 ProteinO43173 (Uniprot-TrEMBL)
ST8SIA6 ProteinP61647 (Uniprot-TrEMBL)
STT3A ProteinP46977 (Uniprot-TrEMBL)
SYVN1(1-617) ProteinQ86TM6 (Uniprot-TrEMBL)
Sda-UMODProteinP07911 (Uniprot-TrEMBL)
Sialic acid metabolismPathwayR-HSA-4085001 (Reactome) Sialic acids are a family of 9 carbon alpha-keto acids that are usually present in the non reducing terminal of glycoconjuates on the cell surface of eukaryotic cells. These sialylated conjugates play important roles in cell recognition and signaling, neuronal development, cancer metastasis and bacterial or viral infection. More than 50 forms of sialic acid are found in nature, the most abundant being N-acetylneuraminic acid (Neu5Ac, N-acetylneuraminate) (Li & Chen 2012, Wickramasinghe & Medrano 2011). The steps below describe the biosynthesis, transport, utilization and degradation of Neu5Ac in humans.
TRIM13 ProteinO60858 (Uniprot-TrEMBL)
TSTA3 ProteinQ13630 (Uniprot-TrEMBL)
TSTA3 dimerComplexR-HSA-6787635 (Reactome)
TUSC3(1-348) ProteinQ13454 (Uniprot-TrEMBL)
UAP1 ProteinQ16222 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UBXN1 ProteinQ04323 (Uniprot-TrEMBL)
UDP-GalMetaboliteCHEBI:18307 (ChEBI)
UDP-GlcMetaboliteCHEBI:18066 (ChEBI)
UDP-GlcNAcMetaboliteCHEBI:16264 (ChEBI)
UDPMetaboliteCHEBI:17659 (ChEBI)
UGGT1 ProteinQ9NYU2 (Uniprot-TrEMBL)
UGGT1,2ComplexR-HSA-548881 (Reactome)
UGGT2 ProteinQ9NYU1 (Uniprot-TrEMBL)
UMODProteinP07911 (Uniprot-TrEMBL)
UMPMetaboliteCHEBI:16695 (ChEBI)
UTPMetaboliteCHEBI:15713 (ChEBI)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
ComplexR-HSA-8866894 (Reactome)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
ComplexR-HSA-8867287 (Reactome)
UbComplexR-HSA-113595 (Reactome)
VCP ProteinP55072 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-MetaboliteCHEBI:91282 (ChEBI)
alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-MetaboliteCHEBI:91283 (ChEBI)
alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-MetaboliteCHEBI:91284 (ChEBI)
alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-MetaboliteCHEBI:91281 (ChEBI)
alpha-D-Man-(1->3)-MetaboliteCHEBI:91280 (ChEBI)
alpha-FucMetaboliteCHEBI:42548 (ChEBI)
beta-FucMetaboliteCHEBI:42589 (ChEBI)
glucosidase IIComplexR-HSA-532671 (Reactome)
glyco-LutropinComplexR-HSA-6793934 (Reactome)
pPNOLMetaboliteCHEBI:67132 (ChEBI)
pPPP phosphataseR-HSA-4420020 (Reactome)
pPPPMetaboliteCHEBI:37531 (ChEBI)
proteoglycan MetaboliteCHEBI:37396 (ChEBI)
proteoglycanMetaboliteCHEBI:37396 (ChEBI)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1:chaperone:ERp57
ComplexR-HSA-909545 (Reactome)
unfolded

protein:(Glc)1

(GlcNAc)2 (Man)8b
ComplexR-HSA-6781883 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1:chaperone
ComplexR-HSA-909542 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1
ComplexR-HSA-532672 (Reactome)
unfolded

protein:(Glc)1

(GlcNAc)2 (Man)9
ComplexR-HSA-912297 (Reactome)
unfolded

protein:(Glc)2 (GlcNAc)2 (Man)9

(Asn)1:malectin
ComplexR-HSA-901051 (Reactome)
unfolded

protein:(Glc)2 (GlcNAc)2 (Man)9

(Asn)1
ComplexR-HSA-532669 (Reactome)
unfolded

protein:(Glc)3 (GlcNAc)2 (Man)9

(Asn)1
ComplexR-HSA-532534 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)5
ComplexR-HSA-6782692 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)7aa
ComplexR-HSA-912280 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8a
ComplexR-HSA-912285 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8b
ComplexR-HSA-912284 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8c
ComplexR-HSA-912295 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)9-5
ComplexR-HSA-8852845 (Reactome)
unfolded protein:GlcNAcR-ALL-8853371 (Reactome)
unfolded

protein:glycan (no

glucose)
ComplexR-HSA-901021 (Reactome)
unfolded protein:glycan:chaperone:ERp57ComplexR-HSA-901040 (Reactome)
unfolded protein R-ALL-1022114 (Reactome)
unfolded protein R-HSA-381130 (Reactome)
unfolded protein R-HSA-912296 (Reactome)
unfolded protein R-HSA-915147 (Reactome)
unfolded proteinR-ALL-1022114 (Reactome)
unfolded proteinR-HSA-381130 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1ArrowR-HSA-446202 (Reactome)
(Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1R-HSA-446189 (Reactome)
(Glc)2 (GlcNAc)2 (Man)9 (PP-Dol)1ArrowR-HSA-446189 (Reactome)
(Glc)2 (GlcNAc)2 (Man)9 (PP-Dol)1R-HSA-446194 (Reactome)
(Glc)3 (GlcNAc)2 (Man)9 (Asn)1R-HSA-964759 (Reactome)
(Glc)3 (GlcNAc)2 (Man)9 (PP-Dol)1ArrowR-HSA-446194 (Reactome)
(Glc)3 (GlcNAc)2 (Man)9 (PP-Dol)1R-HSA-446209 (Reactome)
(GlcNAc)2 (Man)2 (PP-Dol)1ArrowR-HSA-446208 (Reactome)
(GlcNAc)2 (Man)2 (PP-Dol)1R-HSA-449718 (Reactome)
(GlcNAc)2 (Man)3 (PP-Dol)1ArrowR-HSA-449718 (Reactome)
(GlcNAc)2 (Man)3 (PP-Dol)1R-HSA-446187 (Reactome)
(GlcNAc)2 (Man)5 (Asn)1ArrowR-HSA-964737 (Reactome)
(GlcNAc)2 (Man)5 (Asn)1ArrowR-HSA-964825 (Reactome)
(GlcNAc)2 (Man)5 (Asn)1ArrowR-HSA-964830 (Reactome)
(GlcNAc)2 (Man)5 (Asn)1R-HSA-964768 (Reactome)
(GlcNAc)2 (Man)5 (PP-Dol)1ArrowR-HSA-446187 (Reactome)
(GlcNAc)2 (Man)5 (PP-Dol)1ArrowR-HSA-446212 (Reactome)
(GlcNAc)2 (Man)5 (PP-Dol)1R-HSA-446188 (Reactome)
(GlcNAc)2 (Man)5 (PP-Dol)1R-HSA-446212 (Reactome)
(GlcNAc)2 (Man)6 (PP-Dol)1ArrowR-HSA-446188 (Reactome)
(GlcNAc)2 (Man)6 (PP-Dol)1R-HSA-446215 (Reactome)
(GlcNAc)2 (Man)7 (PP-Dol)1ArrowR-HSA-446215 (Reactome)
(GlcNAc)2 (Man)7 (PP-Dol)1R-HSA-446198 (Reactome)
(GlcNAc)2 (Man)7bcR-HSA-964830 (Reactome)
(GlcNAc)2 (Man)8 (Asn)1ArrowR-HSA-964759 (Reactome)
(GlcNAc)2 (Man)8 (PP-Dol)1ArrowR-HSA-446198 (Reactome)
(GlcNAc)2 (Man)8 (PP-Dol)1R-HSA-446216 (Reactome)
(GlcNAc)2 (Man)8 glycansR-HSA-964825 (Reactome)
(GlcNAc)2 (Man)9 (PP-Dol)1ArrowR-HSA-446216 (Reactome)
(GlcNAc)2 (Man)9 (PP-Dol)1R-HSA-446202 (Reactome)
(GlcNAc)2 (Man)9-5ArrowR-HSA-8850594 (Reactome)
(GlcNAc)2 (Man)9R-HSA-964737 (Reactome)
(GlcNAc)3 (Man)3 (Asn)1ArrowR-HSA-975814 (Reactome)
(GlcNAc)3 (Man)3 (Asn)1R-HSA-975829 (Reactome)
(GlcNAc)3 (Man)5 (Asn)1ArrowR-HSA-964768 (Reactome)
(GlcNAc)3 (Man)5 (Asn)1R-HSA-975814 (Reactome)
(GlcNAc)4 (Man)3 (Asn)1ArrowR-HSA-975829 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
ArrowR-HSA-912291 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
ArrowR-HSA-915148 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
R-HSA-901024 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
R-HSA-901039 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
R-HSA-901074 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
R-HSA-912291 (Reactome)
(un)folded

protein:(GlcNAc)2

(Man)9
R-HSA-915148 (Reactome)
2xGNPNAT1mim-catalysisR-HSA-449734 (Reactome)
2xUAP1mim-catalysisR-HSA-446204 (Reactome)
ADPArrowR-HSA-191414 (Reactome)
ADPArrowR-HSA-6787540 (Reactome)
ADPArrowR-HSA-6803771 (Reactome)
ALG10 homologuemim-catalysisR-HSA-446194 (Reactome)
ALG11mim-catalysisR-HSA-446187 (Reactome)
ALG12mim-catalysisR-HSA-446198 (Reactome)
ALG13:ALG14mim-catalysisR-HSA-446207 (Reactome)
ALG1mim-catalysisR-HSA-446218 (Reactome)
ALG2mim-catalysisR-HSA-446208 (Reactome)
ALG2mim-catalysisR-HSA-449718 (Reactome)
ALG3mim-catalysisR-HSA-446188 (Reactome)
ALG5mim-catalysisR-HSA-446214 (Reactome)
ALG6mim-catalysisR-HSA-446202 (Reactome)
ALG8mim-catalysisR-HSA-446189 (Reactome)
ALG9mim-catalysisR-HSA-446215 (Reactome)
ALG9mim-catalysisR-HSA-446216 (Reactome)
AMDHD2mim-catalysisR-HSA-6803789 (Reactome)
ATPR-HSA-191414 (Reactome)
ATPR-HSA-6787540 (Reactome)
ATPR-HSA-6803771 (Reactome)
Ac-CoAR-HSA-449734 (Reactome)
AcGlcN1PArrowR-HSA-446185 (Reactome)
AcGlcN1PR-HSA-446204 (Reactome)
AcGlcN6PArrowR-HSA-449734 (Reactome)
AcGlcN6PR-HSA-446185 (Reactome)
B4GALNT2mim-catalysisR-HSA-8855954 (Reactome)
B4GALT1-6 homodimersmim-catalysisR-HSA-975919 (Reactome)
CALR,CANXR-HSA-535717 (Reactome)
CALR:CANXArrowR-HSA-548890 (Reactome)
CCAArrowR-HSA-6803789 (Reactome)
CDPArrowR-HSA-446195 (Reactome)
CHST10mim-catalysisR-HSA-6786048 (Reactome)
CHST8mim-catalysisR-HSA-6786034 (Reactome)
CO2ArrowR-HSA-191414 (Reactome)
CTPR-HSA-446195 (Reactome)
CoA-SHArrowR-HSA-449734 (Reactome)
DCHOLArrowR-HSA-4419979 (Reactome)
DCHOLR-HSA-446195 (Reactome)
DHDDS:NUS1mim-catalysisR-HSA-4419978 (Reactome)
DOLDPR-HSA-446200 (Reactome)
DOLKmim-catalysisR-HSA-446195 (Reactome)
DOLP-ManArrowR-HSA-162715 (Reactome)
DOLP-ManArrowR-HSA-162721 (Reactome)
DOLP-ManR-HSA-162715 (Reactome)
DOLP-ManR-HSA-446188 (Reactome)
DOLP-ManR-HSA-446198 (Reactome)
DOLP-ManR-HSA-446215 (Reactome)
DOLP-ManR-HSA-446216 (Reactome)
DOLPArrowR-HSA-446188 (Reactome)
DOLPArrowR-HSA-446189 (Reactome)
DOLPArrowR-HSA-446194 (Reactome)
DOLPArrowR-HSA-446195 (Reactome)
DOLPArrowR-HSA-446198 (Reactome)
DOLPArrowR-HSA-446200 (Reactome)
DOLPArrowR-HSA-446202 (Reactome)
DOLPArrowR-HSA-446209 (Reactome)
DOLPArrowR-HSA-446215 (Reactome)
DOLPArrowR-HSA-446216 (Reactome)
DOLPArrowR-HSA-548884 (Reactome)
DOLPP1mim-catalysisR-HSA-446200 (Reactome)
DOLPR-HSA-162721 (Reactome)
DOLPR-HSA-446191 (Reactome)
DOLPR-HSA-446214 (Reactome)
DPAGT1mim-catalysisR-HSA-446191 (Reactome)
DPM1:DPM2:DPM3mim-catalysisR-HSA-162721 (Reactome)
DbGPArrowR-HSA-446211 (Reactome)
DbGPArrowR-HSA-446214 (Reactome)
DbGPR-HSA-446189 (Reactome)
DbGPR-HSA-446194 (Reactome)
DbGPR-HSA-446202 (Reactome)
DbGPR-HSA-446211 (Reactome)
DbGPR-HSA-548884 (Reactome)
Deglycosylation complexmim-catalysisR-HSA-8850594 (Reactome)
E,E-FPPR-HSA-4419978 (Reactome)
EDEM1,3mim-catalysisR-HSA-6782685 (Reactome)
ENGASEmim-catalysisR-HSA-8853379 (Reactome)
FPGTmim-catalysisR-HSA-6787533 (Reactome)
FUCA1 tetramermim-catalysisR-HSA-5693807 (Reactome)
FUKmim-catalysisR-HSA-6787540 (Reactome)
FUOM dimermim-catalysisR-HSA-6787677 (Reactome)
FUT3mim-catalysisR-HSA-5693925 (Reactome)
FUT8mim-catalysisR-HSA-1028788 (Reactome)
Fru(6)PR-HSA-449715 (Reactome)
Fru(6)PR-HSA-532549 (Reactome)
Fuc1PArrowR-HSA-6787540 (Reactome)
Fuc1PR-HSA-6787533 (Reactome)
G1PArrowR-HSA-6810464 (Reactome)
GDP-DHDManArrowR-HSA-6787632 (Reactome)
GDP-DHDManR-HSA-6787623 (Reactome)
GDP-FucArrowR-HSA-6787533 (Reactome)
GDP-FucArrowR-HSA-6787642 (Reactome)
GDP-FucArrowR-HSA-742345 (Reactome)
GDP-FucR-HSA-1028788 (Reactome)
GDP-FucR-HSA-5693925 (Reactome)
GDP-FucR-HSA-742345 (Reactome)
GDP-KDGalArrowR-HSA-6787623 (Reactome)
GDP-KDGalR-HSA-6787642 (Reactome)
GDP-ManArrowR-HSA-446221 (Reactome)
GDP-ManR-HSA-162721 (Reactome)
GDP-ManR-HSA-446187 (Reactome)
GDP-ManR-HSA-446208 (Reactome)
GDP-ManR-HSA-446218 (Reactome)
GDP-ManR-HSA-449718 (Reactome)
GDP-ManR-HSA-6787632 (Reactome)
GDPArrowR-HSA-1028788 (Reactome)
GDPArrowR-HSA-162721 (Reactome)
GDPArrowR-HSA-446187 (Reactome)
GDPArrowR-HSA-446208 (Reactome)
GDPArrowR-HSA-446218 (Reactome)
GDPArrowR-HSA-449718 (Reactome)
GDPArrowR-HSA-5693925 (Reactome)
GFPT1,2mim-catalysisR-HSA-449715 (Reactome)
GMDSmim-catalysisR-HSA-6787632 (Reactome)
GMPPA/Bmim-catalysisR-HSA-446221 (Reactome)
GTPR-HSA-446221 (Reactome)
GTPR-HSA-6787533 (Reactome)
Gal1,3Fuc1,4GlcNAc groupArrowR-HSA-5693925 (Reactome)
Gal1,3GlcNAc groupR-HSA-5693925 (Reactome)
GlcArrowR-HSA-532667 (Reactome)
GlcArrowR-HSA-532678 (Reactome)
GlcArrowR-HSA-548890 (Reactome)
GlcArrowR-HSA-964759 (Reactome)
GlcN6PArrowR-HSA-449715 (Reactome)
GlcN6PArrowR-HSA-6803789 (Reactome)
GlcN6PR-HSA-449734 (Reactome)
GlcNAc (Man)9-5ArrowR-HSA-8853379 (Reactome)
GlcNAc, GlcNGcArrowR-HSA-6803761 (Reactome)
GlcNAc, GlcNGcR-HSA-6803771 (Reactome)
GlcNAc-6-P, GlcNGc-6-PArrowR-HSA-6803771 (Reactome)
GlcNAcDOLDPArrowR-HSA-446191 (Reactome)
GlcNAcDOLDPR-HSA-446207 (Reactome)
GlcNGc-6-PR-HSA-6803789 (Reactome)
Glycoprotein with

GlcNAc in position

4
ArrowR-HSA-975903 (Reactome)
Glycoprotein with

GlcNAc in position

5
ArrowR-HSA-975916 (Reactome)
Glycoprotein with

bifurcating GlcNAc

in position 3
ArrowR-HSA-975926 (Reactome)
Glycoprotein with galactoseArrowR-HSA-975919 (Reactome)
Glycoprotein-Neu5AcArrowR-HSA-1022129 (Reactome)
Glycoprotein-Neu5AcArrowR-HSA-1022133 (Reactome)
Glycoprotein-Neu5AcArrowR-HSA-975902 (Reactome)
Glycoproteins with Man8 N-glycansArrowR-HSA-947991 (Reactome)
Glycoproteins with Man8 N-glycansR-HSA-947991 (Reactome)
H+ArrowR-HSA-6803771 (Reactome)
H+R-HSA-6787642 (Reactome)
H2OArrowR-HSA-6787632 (Reactome)
H2OR-HSA-4419986 (Reactome)
H2OR-HSA-446200 (Reactome)
H2OR-HSA-5693807 (Reactome)
H2OR-HSA-6782685 (Reactome)
H2OR-HSA-6803789 (Reactome)
H2OR-HSA-6810464 (Reactome)
H2OR-HSA-8850594 (Reactome)
H2OR-HSA-8853379 (Reactome)
H2OR-HSA-901024 (Reactome)
H2OR-HSA-901036 (Reactome)
H2OR-HSA-901039 (Reactome)
H2OR-HSA-901074 (Reactome)
HNK1 carbohydrateR-HSA-6786048 (Reactome)
IPPPArrowR-HSA-191414 (Reactome)
IPPPR-HSA-4419978 (Reactome)
L-GlnR-HSA-449715 (Reactome)
L-GluArrowR-HSA-449715 (Reactome)
L-fucoseArrowR-HSA-5693807 (Reactome)
LMAN1:MCFD2mim-catalysisR-HSA-947991 (Reactome)
MAN1A1/A2/C1mim-catalysisR-HSA-964737 (Reactome)
MAN1A1/A2/C1mim-catalysisR-HSA-964825 (Reactome)
MAN1A1/A2/C1mim-catalysisR-HSA-964830 (Reactome)
MAN1B1,EDEM2mim-catalysisR-HSA-901024 (Reactome)
MAN1B1,EDEM2mim-catalysisR-HSA-901036 (Reactome)
MAN1B1,EDEM2mim-catalysisR-HSA-901039 (Reactome)
MAN1B1,EDEM2mim-catalysisR-HSA-901074 (Reactome)
MAN2:Zn2+mim-catalysisR-HSA-975814 (Reactome)
MANEAmim-catalysisR-HSA-964759 (Reactome)
MDCDDArrowR-HSA-446218 (Reactome)
MDCDDR-HSA-446208 (Reactome)
MGAT1mim-catalysisR-HSA-964768 (Reactome)
MGAT2mim-catalysisR-HSA-975829 (Reactome)
MGAT3mim-catalysisR-HSA-975926 (Reactome)
MGAT4smim-catalysisR-HSA-975903 (Reactome)
MGAT5mim-catalysisR-HSA-975916 (Reactome)
MLECArrowR-HSA-532667 (Reactome)
MLECR-HSA-901006 (Reactome)
MOGSmim-catalysisR-HSA-532678 (Reactome)
MPDU1ArrowR-HSA-446188 (Reactome)
MPDU1ArrowR-HSA-446198 (Reactome)
MPDU1ArrowR-HSA-446215 (Reactome)
MPDU1ArrowR-HSA-446216 (Reactome)
MPImim-catalysisR-HSA-532549 (Reactome)
MVA5PPR-HSA-191414 (Reactome)
MVD dimermim-catalysisR-HSA-191414 (Reactome)
Man1PArrowR-HSA-446201 (Reactome)
Man1PR-HSA-446221 (Reactome)
Man6PArrowR-HSA-532549 (Reactome)
Man6PR-HSA-446201 (Reactome)
ManArrowR-HSA-6782685 (Reactome)
ManArrowR-HSA-901024 (Reactome)
ManArrowR-HSA-901036 (Reactome)
ManArrowR-HSA-901039 (Reactome)
ManArrowR-HSA-901074 (Reactome)
ManArrowR-HSA-964737 (Reactome)
ManArrowR-HSA-964825 (Reactome)
ManArrowR-HSA-964830 (Reactome)
ManArrowR-HSA-975814 (Reactome)
ManNAc, ManNGcR-HSA-6803761 (Reactome)
N,N'-DCDOLDPArrowR-HSA-446207 (Reactome)
N,N'-DCDOLDPR-HSA-446218 (Reactome)
NADP+ArrowR-HSA-4419979 (Reactome)
NADP+ArrowR-HSA-6787642 (Reactome)
NADPHR-HSA-4419979 (Reactome)
NADPHR-HSA-6787642 (Reactome)
NAGK dimermim-catalysisR-HSA-6803771 (Reactome)
NGP:1,6-GlcNAcArrowR-HSA-1028788 (Reactome)
NGP:1,6-GlcNAcR-HSA-5693807 (Reactome)
NGPArrowR-HSA-5693807 (Reactome)
NGPR-HSA-1022129 (Reactome)
NGPR-HSA-1022133 (Reactome)
NGPR-HSA-1028788 (Reactome)
NGPR-HSA-975902 (Reactome)
NGPR-HSA-975903 (Reactome)
NGPR-HSA-975916 (Reactome)
NGPR-HSA-975919 (Reactome)
NGPR-HSA-975926 (Reactome)
NUDT14mim-catalysisR-HSA-6810464 (Reactome)
Neu5AcR-HSA-1022129 (Reactome)
Neu5AcR-HSA-1022133 (Reactome)
Neu5AcR-HSA-975902 (Reactome)
OS9:SEL1:ERAD E3 ligases:DERL2mim-catalysisR-HSA-1022127 (Reactome)
OS9:SEL1:ERAD E3 ligases:DERL2mim-catalysisR-HSA-8867288 (Reactome)
OST complexmim-catalysisR-HSA-446209 (Reactome)
PALM-C36-ASGR1:PALM-C54,58-ASGR2:proteoglycanArrowR-HSA-8855711 (Reactome)
PALM-C36-ASGR1:PALM-C54,58-ASGR2R-HSA-8855711 (Reactome)
PAPArrowR-HSA-6786034 (Reactome)
PAPArrowR-HSA-6786048 (Reactome)
PAPSR-HSA-6786034 (Reactome)
PAPSR-HSA-6786048 (Reactome)
PDIA3ArrowR-HSA-548890 (Reactome)
PDIA3R-HSA-901047 (Reactome)
PGM3mim-catalysisR-HSA-446185 (Reactome)
PMM1,2mim-catalysisR-HSA-446201 (Reactome)
PPiArrowR-HSA-4419986 (Reactome)
PPiArrowR-HSA-446204 (Reactome)
PPiArrowR-HSA-446221 (Reactome)
PPiArrowR-HSA-6787533 (Reactome)
PiArrowR-HSA-191414 (Reactome)
PiArrowR-HSA-446200 (Reactome)
R-HSA-1017228 (Reactome) Glycoproteins with lesser folding defects get transported back to the ER and the CNX/CRT complex (Lederkremer, 2009).
R-HSA-1022127 (Reactome) Proteins with major folding defects are extracted from futile folding cycles in the calnexin chaperone system and the ER Quality Control Compartment, and are translocated back to the cytosol for ER-associated degradation (ERAD). The N-glycan is used as a signal to distinguish proteins to be degraded, by direct binding to a ubiquitin ligase complex composed of, minimally, an E3 ubiquitin-protein ligase, protein sel-1 homolog 1 (SEL1L), derlin-2 (DERL2) and protein OS-9 (OS9) (Christianson et al. 2008, Bernasconi et al. 2008, Alcock & Swanton 2009; review Olzmann et al. 2013).
R-HSA-1022129 (Reactome) Addition of sialic acid (Neu5Ac) to galactose-containing N-glycan. Neu5Ac is usually found at terminal positions of the N-glycan. This imparts a negative charge at neutral pH which affects the chemico-physical and biological properties of the N-glycans (for a review, see Schauer 2000); moreover, this modification can lead to the addition of extraordinarily long antennae such as polysialic acid (hundreds of sials) or polylactosamine repeats (dozens of disaccharide repeats) (Harduin-Lepers 2001), while the number of modifications on the antennae of N-glycans is usually lower.
There are over 20 sialyltransferases known in humans, 5 of which are known to act on N-glycans. Beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) is the only sialyltransferase known to transfer Neu5Ac to galactose (Gal) on N-Glycans (Dall'Olio 2000). A second beta-Galactoside alpha-2,6-sialyltransferase has been characterized, but this enzyme acts mainly on oligosaccharides (Krzewinski-Recchi et al. 2003). Neu5Ac can also be added via an alpha-2,3-linkage to Gal on N-glycans by CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4) (Ellies et al. 2002). ST8Sia II (ST8SIA2), ST8Sia III (ST8SIA3), and ST8Sia IV (ST8SIA6) have alpha-2,8-activity (Angata et al. 1997, Angata et al. 2000; Angata & Fuduka 2003).
R-HSA-1022133 (Reactome) Addition of sialic acid (Neu5Ac) to galactose-containing N-glycan. Sialic acid is usually found at terminal positions of the N-glycan. This imparts a negative charge at neutral pH which affects the chemico-physical and biological properties of the N-glycans (for a review, see Schauer 2000); moreover, this modification can lead to the addition of extraordinarily long antennae such as polysialic acid (hundreds of sials) or polylactosamine repeats (dozens of disaccharide repeats) (Harduin-Lepers 2001), while the number of modifications on the antennae of N-glycans is usually lower.
There are over 20 sialyltransferases known in humans, 5 of which are known to act on N-glycans. Beta-galactoside alpha-2,6-sialyltransferase 1
(ST6GAL1) is the only sialyltransferase known to transfer Neu5Ac to Gal on N-Glycans (Dall'Olio 2000). A second beta-galactoside alpha-2,6-sialyltransferase has been characterized, but this enzyme acts mainly on oligosaccharides (Krzewinski-Recchi et al. 2003). Neu5Ac can also be added via an alpha-2,3-linkage to Gal on N-glycans by CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4) (Ellies et al. 2002). ST8Sia II (ST8SIA2), ST8Sia III (ST8SIA3), and ST8Sia IV (ST8SIA6) have alpha-2,8-activity (Angata et al. 1997, Angata et al. 2000, Angata & Fuduka 2003).
R-HSA-1028788 (Reactome) Addition of a fucose moiety as an alpha 1-6 linkage to the first GlcNAc residue of the N-glycan (Clarke JL, Watkins WM 1999; Yamaguchi Y et al, 1999; Yamaguchi Y et al 2000).
R-HSA-162715 (Reactome) Dolichyl phosphate D-mannose (DOLPman) is flipped in the endoplasmic reticulum membrane so that its mannose moiety is oriented inwards, towards the endoplasmic reticulum lumen, where it is accessible to transferases catalyzing the synthesis of glycolipids and glycoproteins (Kinoshita & Inoue 2000).
R-HSA-162721 (Reactome) Cytosolic GDP-mannose reacts with dolichyl phosphate in the endoplasmic reticulum membrane to form dolichyl phosphate D-mannose (DOLPman). The reaction is catalysed by dolichyl-phosphate mannosyltransferase, a heterotrimeric protein embedded in the endoplasmic reticulum membrane. The first subunit of the heterotrimer (DPM1) appears to be the actual catalyst, and the other two subunits appear to stabilise it (Maeda et al. 2000).
R-HSA-191414 (Reactome) Mevalonate pyrophosphate decarboxylase (MPD) decarboxylates mevalonate-5-pyrophosphate (MVA5PP) into isopentenyl pyrophosphate (IPPP) while hydrolysing ATP to ADP and orthophosphate (Toth & Huwyler 1996).
R-HSA-4419978 (Reactome) The ER membrane-associated enzyme dehydrodolichyl diphosphate synthase (DHDDS) mediates the sequential head-to-tail cis addition of multiple isopentyl pyrophosphate (IPP) molecules to farnesyl pyrophosphate (E,E-FPP) to produce polyprenol pyrophosphate (pPPP) (Shridas et al. 2003). Dolichol in humans contain homologues ranging from 17-23 isoprene units, the most common homologues contain 19 or 20 isoprene units (Freeman et al. 1980). Dehydrodolichyl diphosphate syntase complex subunit NUS1 (NUS1, aka Nogo-B receptor NgBR) interacts with DHDDS, enhancing its stability and promoting Dol-P production (Harrison et al. 2011).

Defects in DHDDS cause retinitis pigmentosa 59 (RP59; MIM:613861), a pigment retinopathy, characterised by retinal pigment deposits (visible on fundus examination) and primary loss of rod photoreceptors followed by secondary loss of cone photoreceptors. Sufferers typically have night vision blindness and loss of mid to peripheral vision. As the condition progresses, they lose far peripheral vision and eventually central vision (Zuchner et al. 2011).
R-HSA-4419979 (Reactome) Polyprenol reductase (SRD5A3), resident on the endoplasmic reticulum membrane, mediates the reduction of the alpha-isoprene unit of polyprenol (pPNOL) to form dolichol (DCHOL) in a NADPH-dependent manner (Cantagrel et al. 2010). Defects in SRD5A3 cause congenital disorder of glycosylation 1q (SRD5A3-CDG, CDG1Q; MIM:612379), a neurodevelopmental disorder characterised by under-glycosylated serum glycoproteins resulting in nervous system development, psychomotor retardation, hypotonia, coagulation disorders and immunodeficiency (Cantagrel et al. 2010, Kasapkara et al. 2012). Defects in SRD5A3 can also cause Kahrizi syndrome (KHRZ; MIM:612713), a neurodevelopmental disorder characterised by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features (Kahrizi et al. 2011).
R-HSA-4419986 (Reactome) In mammals, polyprenol pyrophosphate (pPPP) requires dephosphorylation to polyprenol (pPNOL), which can then be reduced. Although pPPP phosphatase activity has been reported (Wolf et al. 1991), no pPPP phosphatase enzyme has yet been identified (Schenk et al. 2001).
R-HSA-446185 (Reactome) Cytosolic PGM3 catalyzes the isomerization of N-acetyl-D-glucosamine 6-phosphate (GlcNAc6P) to form N-acetyl-D-glucosamine 1-phosphate (GlcNAc1P) (Pang H et al, 2002).
R-HSA-446187 (Reactome) A fourth mannose is added to the N-glycan precursor by ALG11. The addition of the fifth mannose, also by ALG11, is the last step occurring on the cytosolic side of the ER membrane (Cipollo JF et al, 2001). Both these reactions are alpha1,2 mannose additions.
R-HSA-446188 (Reactome) The sixth mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps. It has been proposed that ALG3, along with all the mannosyl- and glucosyltransferases in the N-glycan biosynthesis pathway that use dolichyl-phosphate-mannose or dolichyl-phosphate-glucose as donor, derive from duplications of a common ancestral enzyme (Oriol et al. 2002). Defects in ALG3 are associated with Congenital Disorder of Glycosylation 1D (CDG1D) (Sun et al. 2005).
R-HSA-446189 (Reactome) The second glucose (supplied from the donor dolichol-phosphate-glucose) is added to the N-glycan precursor, mediated by ALG8 (Schollen E et al, 2004). Defects in ALG8 are the cause of congenital disorder of glycosylation type 1H (CDG1H) (Schollen E et al, 2004; Sun L et al, 2005).
R-HSA-446191 (Reactome) In the first step of N glycan precursor (LLO) synthesis, N acetylglucosamine is added, via an alpha 1,3 linkage, to a molecule of dolichyl phosphate, producing N acetyl D glucosaminyl diphosphodolichol (Eckert et al. 1998). This reaction is catalyzed by DPAGT1 (ALG7 in yeast), mutations in which are associated with CDG disorder type I J (Wu et al. 2003) and with congenital myasthenic syndrome with tubular aggregates type 2 (Belaya et al. 2012). The dolichyl phosphate acts as an anchor for the LLO, so that subsequent sugar addition reactions take place on a sugar anchored in the ER membrane.
R-HSA-446194 (Reactome) The last glucose is added to the N-glycan precursor. This reaction occurs inside the ER lumen and uses Dol-P-Glc as the glucose donor. In yeast, this reaction is catalyzed by ALG10 (Burda P and Aebi M,1998); however, this gene is duplicated in primates (Ciccarelli FD et al, 2005; Table 1), leading to two homologues, ALG10A and ALG10B, and to date there is no clear evidence to say which of these two paralogues (or both) is responsible for catalyzing this reaction in humans. No Congenital Disorders of Glycosylations are known to be associated with either gene.

R-HSA-446195 (Reactome) Dolichol kinase (DOLK, TMEM15) mediates the phosphorylation of dolichol (DCHOL) to form dolichyl phosphate (DOLP) in the ER membrane (Fernandez et al. 2002). Defects in DOLK cause congenital disorder of glycosylation type 1M (CDG1M aka dolichol kinase deficiency; MIM:610768), a severe multisystem disorder characterised by under-glycosylated serum glycoproteins which results in nervous system under-development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Death occurs in early life (Kranz et al. 2007).
R-HSA-446198 (Reactome) The eighth mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose as a mannose donor. Defects in ALG12 are the cause of congenital disorder of glycosylation type 1G (CDG1G) (Chantret I et al, 2002).
R-HSA-446200 (Reactome) In the last step of the N-glycan precursor biosynthesis pathway, the mature N-glycan (Glc3Man9GlcNAc2) is removed from the dolichyl diphosphate (DOLDP) molecule upon which it has been synthesized and attached to a nascent protein. The released DOLDP molecule is de-phosphorylated by dolichyl diphosphatase 1 (DOLPP1) to dolichyl phosphate (DOLP). DOLP is thus salvaged and be used as substrate for the synthesis of another N-glycan oligosaccharide (Wedgwood & Strominger 1980).
R-HSA-446201 (Reactome) Phosphomannomutases 1 and 2 (PMM1 and PMM2) catalyse the isomerisation of mannose 6-phosphate (Man6P) to mannose 1-phosphate (Man1P) in the cytosol of cells (Wada & Sakamoto 1997, Matthijs et al. 1997). Mutations in the PMM2 gene are one of the causes of Jaeken syndrome. a disease of glycosylation, type CDGIa. (Matthijs et al. 1997b).
R-HSA-446202 (Reactome) The first glucose is added to the N-glycan precursor, mediated by ALG6. Defects in ALG6 are associated with CDG-Ic disorder (Imbach T et al, 1999; Sun L et al, 2005). The donor is a dolichol-phosphate-glucose (synthesized by ALG5).
R-HSA-446204 (Reactome) Cytosolic UAP1 catalyzes the reaction of N-acetyl-D-glucosamine 1-phosphate (GlcNAc1P) and UTP to UDP-N-acetyl-D-glucosamine and pyrophosphate. Structural studies indicate that the active form of the enzyme is a dimer (Peneff C et al, 2001).
R-HSA-446207 (Reactome) A second N-acetylglucosamine is added to the N-glycan precursor via a beta-1,4 linkage. This reaction is catalyzed by the ALG13:ALG14 complex, in which ALG13 functions as the catalyst and ALG14 functions as a membrane anchor which recruits ALG13 to the cytosolic face of ER (Gao XD et al, 2005).
R-HSA-446208 (Reactome) A second mannose is added to the N-glycan precursor via an alpha-1,3 linkage. The reaction is catalyzed by the mannosyltransferase ALG2. This is a bifunctional enzyme with both alpha 1,3- and alpha 1,6-mannosyltransferase activities. In humans, only the alpha 1,3 activity used in this reaction has been elucidated (Thiel et al. 2003). Defects in ALG2 are the cause of ALG2-CDG (CDG-1i; MIM:607906) (Thiel et al. 2003).
R-HSA-446209 (Reactome) The 14-sugar N-glycan precursor (aka lipid-linked oligosaccharide, LLO), synthesized in the previous reactions, is attached in a single step to a nascent protein, releasing the dolichyl phosphate anchor and the as-yet unfolded glycoprotein. The reaction occurs cotranslationally as the growing peptide chain leaves a ribosome associated with the ER membrane and enters the ER lumen. This reaction is catalyzed by the oligosaccharyltransferase (OST) complex, comprising at least seven proteins; DAD1 (Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1), DDOST (OST48 in yeast), RPN1 (ribophorin 1), RPN2 (ribophorin 2), OST4, TUSC3 (N33), MAGT1 (magnesium transporter protein 1) and either STT3A or STT3B (Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A and B), which contain the catalytic domain (Kelleher & Gilmore 2006). A mutation in RPN2 is associated with CDG-Ix (Vleugels et al. 2009). The signal for glycosylation is the consensus sequence Asn - X - Thr/Ser, where the first amino acid is always Asn, the second can be any amino acid except for Pro, and the third position may be Thr, Ser or Cys, with a preference for the first (Breuer et al. 2001). Not all Asn - X - Thr/Ser sites are modified in vivo (Petrescu et al. 2004).
R-HSA-446211 (Reactome) Dolichyl-phosphate-glucose is flipped toward the luminal side of the ER membrane (Imbach T et al, 1999). The exact mechanism and proteins involved in this step are not clear yet, but it is known that it must be carried out by a different flippase than the one that catalyzes the flipping of the N-glycan precursor (Sanyal S et al, 2008).
R-HSA-446212 (Reactome) The precursor of the N-glycan sugar, now in the form of (GlcNAc)2 (Man)5 (PP-Dol), is flipped across the ER membrane, moving it from the cytosolic side into the ER lumen. The exact mechanism of this translocation is not well understood: the protein RFT1 is known to be involved (Helenius et al. 2002), along with an unknown flippase, which is distinct from the one that flips the Dol-P linked precursors (Dol-P-Mannose and Dol-P-glucose) (Sanyal et al. 2008). Defects in RFT1 are associated with Congenital Disorder of Glycosylation 1N (CDG1N) (Haeuptle et al. 2008).
R-HSA-446214 (Reactome) Dolichyl-phosphate beta-glucosyltransferase (ALG5) associated with the endoplasmic reticulum (ER) membrane catalyzes the reaction of cytosolic UDP-glucose with dolichyl phosphate exposed on the cytosolic face of the ER membrane to form Dolichyl-P-glucose with its glucose moiety oriented toward the cytosol (Imbach T et al, 1999).
R-HSA-446215 (Reactome) The seventh mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose as the mannose donor with ALG9 mediating the reaction. Defects in ALG9 are the cause of congenital disorder of glycosylation type 1L (CDG1L) (Frank CG et al, 2004; Weinstein M et al, 2005). For many years ALG9 has been thought to be involved in bipolar affective disorder (Baysal BE et al, 2002), but this hypothesis has been proven wrong (Baysal BE et al, 2006).
R-HSA-446216 (Reactome) The last mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen, uses Dolichyl phosphate D-mannose as the mannose donor, and is catalyzed by ALG9. Defects in ALG9 are the cause of congenital disorder of glycosylation type 1L (CDG1L) (Frank CG et al, 2004; Weinstein M et al, 2005). For many years ALG9 was thought to be involved in bipolar affective disorder (Baysal BE et al, 2002), but this hypothesis has been proven wrong (Baysal BE et al, 2006).
R-HSA-446218 (Reactome) A mannose is added to the N-glycan precursor via a beta-1,4 linkage. The reaction is catalyzed by ALG1 (Takahashi T et al, 2000). Defects in ALG1 lead to congenital disorder of glycosylation type 1K (CDG1K) (Schwarz et al. 2004; Kranz et al. 2004; Grubenmann et al. 2004).
R-HSA-446221 (Reactome) Mannose 1-phosphate is converted to GDP-Mannose by mannose-1-phosphate guanyltransferase alpha and beta forms (GMPPA/B). This enzyme had originally been characterized from rat and bovine sources (Verachtert H et al, 1966) and more recently from pig (Ning B and Elbein AD, 2000).
R-HSA-449715 (Reactome) Glucosamine-fructose 6-phosphate aminotransferases 1 and 2 (GFPT1,2) are the first and rate-limiting enzymes in the hexosamine synthesis pathway, and thus formation of hexosamines like N-acetylglucosamine (GlcNAc). These enzymes probably play a role in limiting the availability of substrates for the N- and O- linked glycosylation of proteins (McKnight et al. 1992, Oki et al. 1999). GFPT1 and 2 are required for normal functioning of neuromuscular synaptic transmission. Defects in GFPT1 lead to altered muscle fibre morphology and impaired neuromuscular junction development (Senderek et al. 2011).
R-HSA-449718 (Reactome) A third mannose is added to the N-glycan precursor by ALG2 using its alpha1,6-mannosyltransferase activity. This has been demonstrated experimentally in yeast (O'Reilly MK et al, 2006; Kämpf M et al, 2009); the human reaction is inferred by homology. Defects in ALG2 are the cause for CDG1I (Thiel C et al, 2003).
R-HSA-449734 (Reactome) Cytosolic GNPNAT1 catalyzes the reaction of glucosamine 6-phosphate and acetyl-CoA to form N-acetyl-glucosamine 6-phosphate (GlcNAc6P) and CoA-SH. Structural studies indicate that the active form of the enzyme is a dimer (Wang J et al, 2008).
R-HSA-532549 (Reactome) Mannose-6-phosphate isomerase (MPI) isomerises fructose 6-phosphate (Fru6P) to mannose 6-phosphate (Man6P) (Proudfoot et al. 1994). Defects in this gene are associated with congenital disorder of glycosylation type 1B (CDG1B). Oral administration of mannose is an efficient therapy against this defect (Schollen et al. 2000).
R-HSA-532667 (Reactome) A second glucose is removed from the N-linked glycan. The removal of an alpha1,3 glucose moiety is catalyzed by glucosidase II, a complex composed of an alpha subunit (GANAB) with catalytic activity and a beta subunit (GLU2B; PRKCSH), probably with regulatory and recruitment function (Pelletier MF et al, 2000). GANAB can exist in two different isoforms, but both are able to catalyze both of the reactions catalyzed by glucosidase II (Pelletier MF et al, 2000). Defects in PRKCSH are a cause of polycystic liver disease (PCLD).
R-HSA-532678 (Reactome) After the glycosylated precursor is attached to the protein, the outer alpha-1,2-linked glucose is removed by by mannosyl-oligosaccharide glucosidase (MOGS, GCS1 in yeast). This is a mandatory step for the protein folding control and glycan extension, and defects in MOGS are associated with congenital disorder of glycosylation type IIb (CDGIIb) (De Praeter et al. 2000, Völker et al. 2002).
R-HSA-535717 (Reactome) Calnexin (membrane protein) and calreticulin (soluble in ER) are two lectins (proteins that can bind a glycan) which recognize the mono-glucosylated form of the N-glycan and mediate the folding of the glycoproteins to which they are attached to (Ou WJ et al, 1993; Nauseef Wm et al, 1995). Calmegin is another chaperone with the same role expressed only in testis (van Lith M et al, 2007). These lectins act as chaperons, providing a protected environment where the unfolded glycoprotein can fold without forming interactions with other proteins or components in the ER. The unfolded protein can loop between these two steps multiple time, therefore this process is called the 'calnexin/calreticulin cycle'. If the protein achieves correct folding, it is modified by Mannosidase I and then moved to the cis-Golgi where the glycan is further processed.
R-HSA-548884 (Reactome) The UDP-glucose:glycoprotein glucosyltransferases 1 and 2 (UGGT1 and 2) are able to distinguish proteins with minor folding defects in the ERQC and reglucosylate them, by transferring a glucose (from dolichyl beta-D-glucosyl phosphate, DbGP) onto the alpha 1,3 mannose of the b (or c, not shown here) branch (Arnold et al. 2000, Arnold et al. 2003). The major affinity of these enzymes for proteins with minor folding defects has been demonstrated, but the exact mechanism that enable them to distinguish proteins with major and minor defects is still unknown (Pearse et al. 2008).
R-HSA-548890 (Reactome) While the protein is bound to the chaperone complex, the glycan is still accessible to glucosidase II, which eventually removes the last remaining glucose residue. This also results in breaking the interaction between the chaperone and the glycoprotein, independently of whether the latter has achieved proper folding (Pelletier MF et al, 2000). This has been interpreted as a 'timing mechanism', in which a protein has only a limited period of time to achieve correct folding when bound to the chaperone, to avoid the scenario where proteins that take too long to fold would block the availability of CNX or CRT. Proteins with folding defects get transported to the Endoplasmic Reticulum Quality Control Compartment, while proteins with correct folding are transported to the cis-Golgi where the glycan is further modified.
R-HSA-5693807 (Reactome) Tissue alpha-L-fucosidase (FUCA1) is a lysosomal enzyme that removes terminal L-fucose residues from the oligosaccharide chains of N-glycoproteins (NGPs). In humans, FUCA1 encodes the tissue enzyme, whilst FUCA2 encodes plasma alpha-L-fucosidase (Intra et al. 2007). Defects in FUCA1 can cause fucosidosis (FUCA1D; MIM:230000), a rare lysosomal storage disorder characterised by progressive psychomotor deterioration, angiokeratoma and growth retardation (Willems et al. 1999).
R-HSA-5693925 (Reactome) Human galactoside 3(4)-L-fucosyltransferase (FUT3) may be involved in Lewis blood group (Le) determination. Le+ individuals have an active enzyme while Le- individuals have an inactive enzyme. FUT3 catalyses alpha-1,3 and alpha-1,4 glycosidic linkages involved in the expression of Le blood groups. The 1,3-galactosyl derivative is shown here (Cameron et al. 1995).
R-HSA-6782685 (Reactome) Proteins with major folding defects are extracted from futile folding cycles in the calnexin chaperone system and the ER Quality Control Compartment, and are translocated back to the cytosol for degradation. The ER degradation-enhancing alpha-mannosidase-like proteins 1 and 3 (EDEM1 and 3) can catalyse the sequential hydrolysis of (GlcNAc)2 (Man)8 to (GlcNAc)2 (Man)7-5. The products are recognised by quality control proteins and become targets for ER-associated degradation (ERAD) (Ninagawa et al. 2014, Hirao et al. 2006).
R-HSA-6786034 (Reactome) Carbohydrate sulfotransferase 8 (CHST8) transfers sulfate (SO4(2-)) from the high energy donor 3'-phospho-5'-adenylyl sulfate (PAPS) to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues of N-glycosylated proteins terminating with the saccharide sequence SO(4)-4-GalNAc-beta1,4-GlcNAc-beta1,2-Man-alpha. This sequence is present on the pituitary hormones lutropin (LH), thyrotropin and pro-opiomelanocortin. The sulfated oligosaccharides on LH are essential for its biologic function (Xia et al. 2000, Hiraoka et al. 2001). LH is required for the production of the sex hormones estradiol, progesterone, and testosterone. The unique saccharide signature is used for clearing LH from blood. Ablation of Chst8 in mice exhibited increased levels of circulating LH resulting in precocious sexual maturation (Mi et al. 2008).
R-HSA-6786048 (Reactome) Carbohydrate sulfotransferase 10 (CHST10) transfers sulfate (SO4(2-)) from the high energy donor 3'-phospho-5'-adenylyl sulfate (PAPS) to position 3 of non-reducing glucuronyl (GlcA) residues of N-glycosylated proteins terminating with the saccharide sequence glucuronyl-lactosaminyl (GlcA-LacN), forming the HNK1 carbohydrate (sulfo-3GlcA-beta1,3Gal-beta1,4-GlcNAc-R). The HNK1 carbohydrate is expressed on various adhesion molecules (neural cells, natural killer cells) in the nervous system and may play a role in cell-cell and cell-substratum interactions (Ong et al. 1998, 1999).
R-HSA-6787533 (Reactome) Fucose-1-phosphate guanylyltransferase (FPGT) functions in a salvage pathway to reutilise L-fucose arising from the turnover of glycoproteins and glycolipids in the liver and other tissues. In the second step of the pathway, FPGT catalyses the transfer a guanylyl group from GTP to fucose-1-phosphate (Fu1P) to form GDP-L-fucose (GDP-Fuc), the high energy donor form used by fucosyltransferases in the Golgi to add fucose moieties to growing glycan chains (Quirk & Seley 2005).
R-HSA-6787540 (Reactome) In the GDP-fucose salvage pathway, beta-L-fucose (beta-Fuc) arising from the turnover of glycoproteins and glycolipids in the liver and other tissues is reutilised via a two-step pathway. The first step is the phosphorylation of L-fucose (L-Fuc) to fucose-1-phosphate (Fuc1P) by L-fucose kinase (FUK) (Hinderlich et al. 2002).
R-HSA-6787623 (Reactome) The de novo synthesis pathway for GDP-L-fucose is a two step pathway starting from GDP-mannose. In the second step, GDP-4-dehydro-6-deoxy-alpha-D-mannose (GDP-DHDMan) is epimerised and reduced to GDP-L-fucose (GDP-Fuc). The cytosolic enzyme GDP-L-fucose synthase (TSTA3, aka FX) appears to have both epimerase and reductase activities and functions as a homodimer (Tonetti et al. 1996, Zhou et al. 2013). In the first stage, the hydroxyl group at C-3 and the methyl group at C-5 of the mannose ring of GDP-DHDMan are epimerised to GDP-4-keto-6-deoxygalactose (GDP-KDGal).
R-HSA-6787632 (Reactome) The de novo synthesis pathway for GDP-L-fucose is a two step pathway starting from GDP-mannose. In the first step, GDP-mannose (GDP-Man) is dehydrated to GDP-4-dehydro-6-deoxy-alpha-D-mannose (GDP-DHDMan) by GDP-mannose 4,6 dehydratase (GMDS) (Sullivan et al. 1998, Ohyama et al. 1998). Fucosylation is one of the most important oligosaccharide modifications in cancer and inflammation. Defects in GMDS are involved in the progression of colorectal cancer (Nakayama et al. 2013).
R-HSA-6787642 (Reactome) The de novo synthesis pathway for GDP-L-fucose is a two step pathway starting from GDP-mannose. In the second step, GDP-4-dehydro-6-deoxy-alpha-D-mannose (GDP-DHDMan) is epimerised and reduced to GDP-L-fucose (GDP-Fuc). The cytosolic enzyme GDP-L-fucose synthase (TSTA3, aka FX) appears to have both epimerase and reductase activities and functions as a homodimer (Tonetti et al. 1996, Zhou et al. 2013). In the second stage, 4-reductase activity of TSTA3 dimer catalyses a hydride transfer from NADPH to the keto group at C-4 of GDP-4-keto-6-deoxygalactose (GDP-KDGal), yielding GDP-fucose (GDP-Fuc) and NADP+.
R-HSA-6787677 (Reactome) L-Fucose (6-deoxy-L-galactose) exists in two different forms, alpha-L-fucose (29.5%) and beta-L-fucose (70.5%). The beta-form is metabolised through the salvage pathway to ultimately form GDP-fucose. Fucose mutarotase (FUOM) is involved in the anomeric conversions of monosaccharides, converting alpha-Fuc to beta-Fuc (Timson & Reece 2003).
R-HSA-6803761 (Reactome) Humans are not able to catalyse the formation of N-glycolylneuraminic acid (Neu5Gc) due to an inactive CMAHP enzyme. Neu5Gc can be obtained from dietary sources and must be degraded to avoid accummulation and resultant chronic inflammation known as xenosialitis (Varki et al. 2011). Degradation of excess Neu5Gc results in the formation of two ubiquitous metabolites involved in asparagine N-linked glycosylation; glycolate and glucosamine 6-phosphate. In the Neu5Gc degradation pathway, N-acylglucosamine 2-epimerase (RENBP) dimer catalyses the reversible isomerisation of N-acetylmannosamine (ManNAc) to N-acetylglucosamine (GlcNAc) and of N-glycolylymannosamine (ManNGc) to N-glycolylglucosamine (GlcNGc) (Takahashi et al. 1999, 2001).
R-HSA-6803771 (Reactome) Humans are not able to catalyse the formation of N-glycolylneuraminic acid (Neu5Gc) due to an inactive CMAHP enzyme. Neu5Gc can be obtained from dietary sources and must be degraded to avoid accummulation and resultant chronic inflammation known as xenosialitis (Varki et al. 2011). Degradation of excess Neu5Gc results in the formation of two ubiquitous metabolites involved in asparagine N-linked glycosylation; glycolate and glucosamine 6-phosphate. In the Neu5Gc degradation pathway, a salvage reaction of amino sugar metabolism utilises dimeric GlcNAc kinase (NAGK) to phosphorylate N-acetylglucosamine (GlcNAc) to GlcNAc-6-phosphate and N-glycolylglucosamine (GlcNGc) to GlcNGc-6-P (Hinderlich et al. 2000, Weihofen et al. 2006).
R-HSA-6803789 (Reactome) Humans are not able to catalyse the formation of N-glycolylneuraminic acid (Neu5Gc) due to an inactive CMAHP enzyme. Neu5Gc can be obtained from dietary sources and must be degraded to avoid accummulation and resultant chronic inflammation known as xenosialitis (Varki et al. 2011). In the Neu5Gc degradation pathway, the putative N-acetylglucosamine-6-phosphate deacetylase (AMDHD2) is thought to irreversibly hydrolyse N-glycolylglucosamine 6-phosphate (GlcNGc-6-P), resulting in the ubiquitous metabolites glycolate (CCA) and glucosamine 6-phosphate (GlcN6P) (Bergfeld et al. 2012).
R-HSA-6810464 (Reactome) Uridine diphosphate glucose pyrophosphatase (NUDT14) is a member of the Nudix hydrolase family, a ubiquitously distributed group of nucleotide pyrophosphatases. NUDT14 hydrolyses UDP-glucose (UDP-Glc) to glucose 1-phosphate (G1P) and UMP. UDP-Glc is a sugar donor in many glycosylation reactions and a cytosolic pyrophosphatase such as NUDT14 could play a role in regulating gluconeogenesis (Yagi et al. 2003).
R-HSA-742345 (Reactome) The human gene SLC35C1 encodes the GDP-fucose transporter FUCT1. It resides on the Golgi membrane and mediates the transport of GDP-fucose (GDP-Fuc) formed from a de novo pathway and/or a salvage pathway into the Golgi lumen. Defects in SLC35C1 causes the congenital disorder of glycosylation type 2C, also known as leukocyte adhesion deficiency type II (LAD2) (Lubke et al. 2001).
R-HSA-8850594 (Reactome) Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (NGLY1, aka PNGase) is a cytosolic peptide:N-glycanase which acts on N-glycoproteins generating free, unconjugated N-glycans and deglycosylated peptides in which the N-glycosylated asparagine residues are converted to aspartates. It is involved in the quality control system for misfolded glycoproteins exported to the cytosol that need to be targeted for degradation (Suzuki et al. 2016). NGLY1 is part of a complex that couples retrotranslocation, ubiquitination and deglycosylation. It is probably composed of NGLY1, UBX domain-containing protein 1 (UBXN1 aka SAKS1), E3 ubiquitin-protein ligase (AMFR), transitional endoplasmic reticulum ATPase (VCP), derlin-1 (DERL1), 26S protease regulatory subunit 4 (PSMC1) and UV excision repair protein RAD23 homolog B (RAD23B). NGLY1 interacts with the proteasome components RAD23B and PSMC1, directly with VCP and with DERL1, bringing it close to the endoplasmic reticulum membrane (Katiyar & Lennarz 2004, Song et al. 2005, McNeill et al. 2004, Ye et al. 2004, Katiyar et al. 2005).
R-HSA-8853379 (Reactome) Two cytosolic deglycosylating systems can generate free oligosaccharides from glycoproteins; a deglycosylation complex that hydrolyses the whole glycan from an unfolded protein and cytosolic endo-beta-N-acetylglucosaminidase (ENGASE) that catalyses the endohydrolysis of -(Man(GlcNAc)2)Asn- structures in glycoproteins, leaving one N-acetyl-D-glucosamine (GlcNAc) residue attached to the protein (Suzuki et al. 2002). Glycans with a single GlcNAc at their reducing termini need to be further degraded by a cytosolic alpha-mannosidase, MAN2C1.
R-HSA-8855711 (Reactome) Asialoglycoprotein receptors 1 and 2 (ASGR1 and ASGR2) mediate the endocytosis of plasma glycoproteins whose terminal sialic acid residues on their complex carbohydrate moieties has been removed. They can bind each other to form at least a heterodimeric complex (Bischoff et al. 1988). The resultant ligand:receptor complex is internalised and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then cycles back to the cell membrane surface. Palmitoylation of ASGR1 (Cys36) and ASGR2 (Cys54, 58) is essential for efficient endocytosis of ligand by the clathrin-dependent endocytic pathway and especially for the proper dissociation and delivery of ligand to lysosomes (Saxena et al. 2002, Yik et al. 2002).
R-HSA-8855954 (Reactome) The histo-blood group antigen Sda was discovered to be a dominant character found in more than 90 % of Caucasian red blood cells. In addition to erythrocytes, the Sda antigen is also found in other tissues and body fluids, particularly in urine of humans and other mammals. The Sda antigen shares a common minimal saccharide structure (GalNAc-beta1-4[Neu5Ac-alpha2-3]Gal-beta-) with the Cad antigen. Both antigens contain a pentasaccharide structure, the Sda antigen's structure being GalNAc-beta1-4[Neu5Ac-alpha2-3]Gal-beta1-4GlcNAc-beta1-3Gal. The last step in the biosynthesis of both Sda and Cad antigens is catalysed by beta-1,4 N-acetylgalactosaminyltransferase 2 (B4GALNT2), a Golgi membrane protein that transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to position C4 of the Gal residue of the Neu5Ac-alpha2-3Gal-beta1 sequence (Montiel et al. 2003, Lo Presti et al. 2003, Dall'Olio et al. 2014). Both antigens can be expressed by N- or O-linked chains of glycoproteins. Tamm–Horsfall glycoprotein (THGP, aka UMOD) is a major carrier of the Sda antigen in urine (Soh et al. 1980, Serafini-Cessi & Conte 1982). After proteolytic cleavage, UMOD is secreted into the urine where it may play roles in colloid osmotic pressure, retarding passage of positively charged electrolytes, preventing urinary tract infection and modulateing formation of supersaturated salts and their crystals (Schmid et al. 2010).
R-HSA-8867288 (Reactome) Proteins with major folding defects are extracted from futile folding cycles in the calnexin chaperone system and the ER Quality Control Compartment, and are translocated back to the cytosol for ER-associated degradation (ERAD). The N-glycan is used as a signal to distinguish proteins to be degraded, by direct binding to a ubiquitin ligase complex composed of, minimally, an E3 ubiquitin-protein ligase, protein sel-1 homolog 1 (SEL1L), derlin-2 (DERL2) and protein OS-9 (OS9) (Christianson et al. 2008, Bernasconi et al. 2008, Alcock & Swanton 2009; review Olzmann et al. 2013).
R-HSA-901006 (Reactome) A recently discovered protein called malectin is known to recognize the Glc(2)Man(9)GlcNAc(2) glycan (Schallus T et al, 2008). The exact role of this interaction is not clear but malectin is thought to regulate the availability of this substrate to glucosidase II, or to act as a chaperone to stabilize the unfolded protein.
R-HSA-901024 (Reactome) The enzyme ER Man I can slowly trim up to four of the mannoses on the N-glycan on unfolded proteins accumulated in the ER. This step describes the removal of the mannose in the A position (Hirao et al, 2006; Frenkel et al, 2003).
R-HSA-901036 (Reactome) Removal of the second mannose on the alpha 1,3 branch (Frenzel Z et al, 2003).
R-HSA-901039 (Reactome) The enzyme ER Man I can slowly trim up to four of the mannoses on the N-glycan on unfolded proteins accumulated in the ER. This step describes the removal of the mannose in the C position (Gonzalez et al. 1999, Karaveg et al. 2005, Avezov et al. 2008).
R-HSA-901047 (Reactome) ERp57/ERp27 is a thiol-oxidoreductase that interacts with calnexin and mediates the formation of disulfide bonds in the unfolded glycoprotein (Alanen HI et al, 2006).
R-HSA-901074 (Reactome) The enzyme ER Man I can slowly trim up to four of the mannoses on the N-glycan on unfolded proteins accumulated in the ER. This step describes the removal of the mannose in the B position (Gonzalez et al. 1999, Karaveg et al. 2005, Avezov et al. 2008). The ER degradation-enhancing alpha-mannosidase-like protein 2 (EDEM2) is also able to hydrolyse the alpha-1,2-mannose from (GlcNAc)2 (Man)9 to form (GlcNAc)2 (Man)8b (Ninagawa et al. 2014).
R-HSA-912291 (Reactome) Proteins with folding defects get transported to the Endoplasmic Reticulum Quality Control Compartment (Molinari, 2007).
R-HSA-915148 (Reactome) Correctly folded proteins, after being released from the Calnexin/Calreticulin cycle, are translocated to the Golgi (Hauri H et al, 2000; Hauri HP et al, 2002; Molinari, 2007).
R-HSA-947991 (Reactome) The LMAN1(also known as ERGIC-53)/MCFD2 complex recognizes Man8 and Man9 N-glycans released by the Calnexin/Calreticulin cycle and mediate their transport to the Golgi (Nyefeler B et al, 2003; Zhang B et al, 2003). Man8 glycan transfer is shown here.
R-HSA-964737 (Reactome) In the cis-Golgi, Man7, Man8 or Man9 N-glycans are progressively trimmed to Man5 N-glycans. The reaction can be catalyzed by one of three known mannosidases, expressed in different tissues and with slightly different affinity. These enzymes trim the mannoses in a different order (Tremblay and Herscovics, 2000), but produce the same output with 5 mannoses.
A small confusion on the nomenclature of these genes coding for these enzymes is present in the literature: the standard HGNC symbols are MAN1A1, MAN1A2, MAN1C1, but MAN1A2 is also referred to as MAN1B in certain publications, while MAN1B1 is the enzyme acting in the ERQC compartment on unfolded glycoproteins. Moreover, the names do not correspond to a preference of these enzymes for which of the three mannose branches these trim first.
R-HSA-964759 (Reactome) Cells exposed to castanospermine or 1-deoxynojirimycin (inhibitors of the glucosidase enzymes GCS1 and GANAB), are still able to carry out glycosylation and produce complex glycans. This is due to the existence of an alternative route catalyzed by the enzyme endomannosidase (Moore and Spiro, 1990).
Glycoproteins that pass through this route probably skip or have a reduced interaction with the Calnexin/Calreticulin cycle, and are transported to the cis-golgi through a route that has not been described yet (probably through the general ER to Golgi flow). Here, the Endomannosidase enzyme, which resides on the Golgi membrane (Hardt et al 2005; Hamilton et al 2005) is able to remove the tri-, di-, or mono-glucose substituted mannose on branch A, leading to a deglucosylated N-glycan structure (Lubas and Spiro, 1988).
R-HSA-964768 (Reactome) This is the first committed step in the synthesis of complex and hybrid N-glycans and is specific to multicellular organisms (Kumar et al, 1990; Hull et al, 1991). Hybri N-glycans are important for inter-cellular interactions and therefore during embryonic development of multicellular organisms, and it is probable that these pathways have evolved just before the emergence of multicellular organisms. Support for this hypothesis is provided by the phenomena of CDG and by the effects of null mutations in C.elegans.
R-HSA-964825 (Reactome) In the cis-Golgi, Man7, Man8 or Man9 N-glycans are progressively trimmed to Man5 N-glycans. The reaction can be catalyzed by one of three known mannosidases, expressed in different tissues and with slightly different affinity. These enzymes trim the mannoses in a different order (Tremblay and Herscovics, 2000), but produce the same output with 5 mannoses.
A small confusion on the nomenclature of these genes coding for these enzymes is present in the literature: the standard HGNC symbols are MAN1A1, MAN1A2, MAN1C1, but MAN1A2 is also referred to as MAN1B in certain publications, while MAN1B1 is the enzyme acting in the ERQC compartment on unfolded glycoproteins. Moreover, the names do not correspond to a preference of these enzymes for which of the three mannose branches these trim first.
R-HSA-964830 (Reactome) In the cis-Golgi, Man7, Man8 or Man9 N-glycans are progressively trimmed to Man5 N-glycans. The reaction can be catalyzed by one of three known mannosidases, expressed in different tissues and with slightly different affinity. These enzymes trim the mannoses in a different order (Tremblay and Herscovics, 2000), but produce the same output with 5 mannoses.
A small confusion on the nomenclature of these genes coding for these enzymes is present in the literature: the standard HGNC symbols are MAN1A1, MAN1A2, MAN1C1, but MAN1A2 is also referred to as MAN1B in certain publications, while MAN1B1 is the enzyme acting in the ERQC compartment on unfolded glycoproteins. Moreover, the names do not correspond to a preference of these enzymes for which of the three mannose branches these trim first.
R-HSA-975814 (Reactome) The removal of mannoses on the alpha,1,6 arm by MAN2A1 or MAN2A2 is required for efficient formation of complex-type N-glycans (Misago M et al, 1995; Crispin M et al, 2007). These two enzymes carry out the same function and the disruption of both inhibits the formation of complex N-glycans in vivo (Akama TO et al, 2006).
R-HSA-975829 (Reactome) The addition of a GlcNAc on the alpha-1,6 mannose on the alpha-1,4 branch is required for the synthesis of complex N-glycans (Tan et al. 1995). Defects in this gene are associated with Congenital Disorder of Glycosylation type IIa (Tan et al. 1996, Wang et al. 2002).
R-HSA-975902 (Reactome) Addition of sialic acid to galactose-containing N-glycan. Sialic acid is usually found at terminal positions of the N-glycan. This imparts a negative charge at neutral pH which affects the chemico-physical and biological properties of the N-glycans (for review, see Schauer 2000); moreover, this modification can lead to the addition of extraordinarily long antennae such as polysialic acid (hundreds of sials) or polylactosamine repeats (dozens of disaccharide repeats) (Harduin-Lepers 2001), while the number of modifications on the antennae of N-glycans is usually lower.
There are over 20 sialyltransferases known in humans, 5 of which are known to act on N-glycans. Beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) is the only sialyltransferase known to transfer sialic acid to galactose on N-Glycans (Dall'Olio 2000). A second beta-galactoside alpha-2,6-sialyltransferase has been characterized, but this enzyme acts mainly on oligosaccharides (Krzewinski-Recchi et al. 2003). Neu5Ac can also be added via an alpha-2,3-linkage to galactose on N-glycans by CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4) (Ellies et al. 2002). ST8Sia II (ST8SIA2), ST8Sia III (ST8SIA3), and ST8Sia IV (ST8SIA6) have alpha-2,8-activity (Angata et al. 1997, Angata et al. 2000, Angata & Fuduka 2003).
R-HSA-975903 (Reactome) N-acetylglucosaminyltransferase (GnT)-IV catalyzes the addition of GlcNAc beta,1,4 on the GlcNAc beta1,2 Man,alpha1,3 arm of both complex and hybrid N-glycans (Oguri S et al, 2006). Two human GnT-IV isozymes have been characterized (MGAT4A, MGAT4B) , plus a putative MGAT4C on chromosome 2 (Furukawa T et al, 1999). Aberrant expression of MGAT4A or MGAT4B is associated with pancreatic cancer (Ide Y et al, 2006; Kudo T et al , 2007)
R-HSA-975916 (Reactome) N-acetylglucosaminyltransferase (GnT)-V catalyzes the addition of GlcNAc beta 1,4 on the GlcNAc beta1,2 Man,alpha1,6 arm of complex type N-Glycans (Park C et al, 1999; Granowski M et al, 2000; Wang L et al, 2007). The activity of MGAT5 competes with MGAT3 (Pinho SS et al, 2009) and is associated with gastric cancer (Tian H et al, 2008) and multiple sclerosis (Brynedal B et al, 2010).
R-HSA-975919 (Reactome) Addition of a galactose residue on N-acetylglucosamine. The family of beta 4-galactosyltransferases is composed by at least six known members with different K(m) and acceptor specifities (Guo S et al, 2001) and probably originated by duplication (Lo NW et al, 1998). B4GALT1 is associated with Congenital Disorder of Glycosylation of type IId (Hansske B et al, 2002), and is expressed as two splicing isoforms of which only one is localizated in the Golgi system (Lopez LC et al, 1991; Schaub BE et al, 2006). B4GALT2 is key in the regulation of proteins involved in neuronal development (Sasaki N et
al, 2005).
R-HSA-975926 (Reactome) The addition of a bisecting GlcNAc to a complex N-glycan by MGAT3 is one of the most important regulatory steps in N-glycosylation, directing the pathway toward the synthesis of complex and hybrid N-glycans. This addition changes the structure of the N-glycan and inhibits further modification by MGAT2, MGAT4, MGAT5A/B and FUT8. Defects in MGAT3 have been shown to be associated with predisposition to cancer and several developmental defects (Song et al 2010; Stanley 2002).
RENBP dimermim-catalysisR-HSA-6803761 (Reactome)
RFT1mim-catalysisR-HSA-446212 (Reactome)
S-HNK1 carbohydrateArrowR-HSA-6786048 (Reactome)
S-glyco-LutropinArrowR-HSA-6786034 (Reactome)
SLC35C1mim-catalysisR-HSA-742345 (Reactome)
SRD5A3mim-catalysisR-HSA-4419979 (Reactome)
ST3GAL4mim-catalysisR-HSA-1022129 (Reactome)
ST6GAL1mim-catalysisR-HSA-975902 (Reactome)
ST8SIA2,3,6mim-catalysisR-HSA-1022133 (Reactome)
Sda-UMODArrowR-HSA-8855954 (Reactome)
TSTA3 dimermim-catalysisR-HSA-6787623 (Reactome)
TSTA3 dimermim-catalysisR-HSA-6787642 (Reactome)
UDP-GalR-HSA-8855954 (Reactome)
UDP-GalR-HSA-975919 (Reactome)
UDP-GlcNAcArrowR-HSA-446204 (Reactome)
UDP-GlcNAcR-HSA-446191 (Reactome)
UDP-GlcNAcR-HSA-446207 (Reactome)
UDP-GlcNAcR-HSA-964768 (Reactome)
UDP-GlcNAcR-HSA-975829 (Reactome)
UDP-GlcNAcR-HSA-975903 (Reactome)
UDP-GlcNAcR-HSA-975916 (Reactome)
UDP-GlcNAcR-HSA-975926 (Reactome)
UDP-GlcR-HSA-446214 (Reactome)
UDP-GlcR-HSA-6810464 (Reactome)
UDPArrowR-HSA-446207 (Reactome)
UDPArrowR-HSA-446214 (Reactome)
UDPArrowR-HSA-8855954 (Reactome)
UDPArrowR-HSA-964768 (Reactome)
UDPArrowR-HSA-975829 (Reactome)
UGGT1,2mim-catalysisR-HSA-548884 (Reactome)
UMODR-HSA-8855954 (Reactome)
UMPArrowR-HSA-446191 (Reactome)
UMPArrowR-HSA-6810464 (Reactome)
UTPR-HSA-446204 (Reactome)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
ArrowR-HSA-1022127 (Reactome)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
ArrowR-HSA-8867288 (Reactome)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
R-HSA-1022127 (Reactome)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
R-HSA-8850594 (Reactome)
Ub-unfolded

protein:(GlcNAc)2

(Man)9-5
R-HSA-8853379 (Reactome)
UbR-HSA-8867288 (Reactome)
alpha-FucR-HSA-6787677 (Reactome)
beta-FucArrowR-HSA-6787677 (Reactome)
beta-FucR-HSA-6787540 (Reactome)
glucosidase IImim-catalysisR-HSA-532667 (Reactome)
glucosidase IImim-catalysisR-HSA-548890 (Reactome)
glyco-LutropinR-HSA-6786034 (Reactome)
pPNOLArrowR-HSA-4419986 (Reactome)
pPNOLR-HSA-4419979 (Reactome)
pPPP phosphatasemim-catalysisR-HSA-4419986 (Reactome)
pPPPArrowR-HSA-4419978 (Reactome)
pPPPR-HSA-4419986 (Reactome)
proteoglycanR-HSA-8855711 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1:chaperone:ERp57
ArrowR-HSA-901047 (Reactome)
unfolded

protein:(Glc)1

(GlcNAc)2 (Man)8b
ArrowR-HSA-548884 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1:chaperone
ArrowR-HSA-535717 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1:chaperone
R-HSA-901047 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1
ArrowR-HSA-1017228 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1
ArrowR-HSA-532667 (Reactome)
unfolded

protein:(Glc)1 (GlcNAc)2 (Man)9

(Asn)1
R-HSA-535717 (Reactome)
unfolded

protein:(Glc)1

(GlcNAc)2 (Man)9
R-HSA-1017228 (Reactome)
unfolded

protein:(Glc)2 (GlcNAc)2 (Man)9

(Asn)1:malectin
ArrowR-HSA-901006 (Reactome)
unfolded

protein:(Glc)2 (GlcNAc)2 (Man)9

(Asn)1:malectin
R-HSA-532667 (Reactome)
unfolded

protein:(Glc)2 (GlcNAc)2 (Man)9

(Asn)1
ArrowR-HSA-532678 (Reactome)
unfolded

protein:(Glc)2 (GlcNAc)2 (Man)9

(Asn)1
R-HSA-901006 (Reactome)
unfolded

protein:(Glc)3 (GlcNAc)2 (Man)9

(Asn)1
ArrowR-HSA-446209 (Reactome)
unfolded

protein:(Glc)3 (GlcNAc)2 (Man)9

(Asn)1
R-HSA-532678 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)5
ArrowR-HSA-6782685 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)7aa
ArrowR-HSA-901036 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8a
ArrowR-HSA-901024 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8a
R-HSA-901036 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8b
ArrowR-HSA-901074 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8b
R-HSA-548884 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8b
R-HSA-6782685 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)8c
ArrowR-HSA-901039 (Reactome)
unfolded

protein:(GlcNAc)2

(Man)9-5
R-HSA-8867288 (Reactome)
unfolded protein:GlcNAcArrowR-HSA-8853379 (Reactome)
unfolded

protein:glycan (no

glucose)
ArrowR-HSA-548890 (Reactome)
unfolded protein:glycan:chaperone:ERp57R-HSA-548890 (Reactome)
unfolded proteinArrowR-HSA-8850594 (Reactome)
unfolded proteinR-HSA-446209 (Reactome)
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