Sialic acid metabolism (Homo sapiens)

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10, 432, 4, 25, 33, 503, 3511, 24, 31, 34, 37...9, 13, 176, 44431, 8, 16, 21, 4222, 28, 3043435329431812, 15, 19, 23, 51...7, 26, 365, 14, 27, 32, 39...5, 14, 27, 32, 39...4320, 45nucleoplasmcytosollysosomal lumenGolgi lumenNeu5Ac-2,6-GalNAc-R CMAS ST6GALNAC4 Neu5Ac-2,8-Neu5Ac-R Neu5Ac-2,3-Gal-R CMP-Neu5AcST6GAL2 Neu5Ac-2,8-Neu5Ac-R NEU3Neu5Ac-2,6-Gal-R H2OH2ONeu5Ac-2,8-Neu5Ac-R Neu5Ac-RPiManNGc H2ONeu5Ac ST8SIA2 Neu5Ac-2,6-GalNAc-RGal-RGalNAc-RATPST6GAL1 Neu5Ac-2,6-GalNAc-R Neu5Ac-9-PST3GAL5 Neu5Ac-2,3-Gal-R Gal-R ST8SIA1 Neu5Ac-R Neu5Ac-2,3-Gal-RST6GALNAC5 Neu5Ac-R CTSA(327-480) Neu5Ac-2,6-Gal-RNeu5Ac-2,3-Gal-R CMPNPL tetramerCTSA(29-326) Gal-R,GalNAc-R,Neu5Ac-RPPiCMAS tetramerglycoconjugatesNANSGLB1 GNE hexamerNeu5Ac-2,8-Neu5Ac-R Neu5AcH2OST3GAL2 ST8SIA6 SLC35A1Neu5Ac-R Neu5Ac-2,6-GalNAc-R ST6GALNAC6 Mg2+ H+ST8SIA3 CMPNeu5Gc GalNAc-R Gal-R NEU1 UDP-GlcNAcPYRNEU1,4 substratesNeu5Ac-2,6-Gal-R GNE NANP:Mg2+Neu5AcNeu5AcH+Neu5Ac-2,6-GalNAc-R SLC17A5ST6GALNAC2 Neu5Ac-2,6-GalNAc-R glycoconjugatesGal-R, Neu5Ac-RST6GALNAC1 NEU4 PiST3GAL4 ST6GALNAC1-6ManNAc-6-PNeu5Ac-2,8-Neu5Ac-R Neu5AcCMP-Neu5AcNeu5Ac-2,3-Gal-R CTPglycoconjugatesCMPNeu5Ac-2,3-Gal-R Neu5AcNPL H2ONEU2ST8SIA1-6H2OST3GAL1 ST3GAL3 NEU2 substratesADPNeu5Ac-2,6-Gal-R Neu5Ac-2,6-GalNAc-R Neu5Ac-2,8-Neu5Ac-R Neu5Ac-2,8-Neu5Ac-RST8SIA4 Neu5Ac-2,8-Neu5Ac-R Neu5Ac-2,3-Gal-R UDPST6GAL1,2Neu5Ac-2,6-Gal-R ST6GALNAC3 ST3GAL1-6ManNAcNANP PEPNeu5Ac-2,6-Gal-R ManNAc GalNAc-R Gal-R glycoconjugatesNeu5Ac-2,6-Gal-R CMPNEU1:GLB1:CTSA,NEU4ST8SIA5 NEU3 substratesCMP-Neu5AcNeu5Ac-2,3-Gal-R Neu5Ac, Neu5GcGal-R,GalNAc-R,Neu5Ac-RManNAc,ManNGcST3GAL6


Description

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. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 4085001
Reactome-version 
Reactome version: 61
Reactome Author 
Reactome Author: Jassal, Bijay

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Bigi A, Morosi L, Pozzi C, Forcella M, Tettamanti G, Venerando B, Monti E, Fusi P.; ''Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively.''; PubMed Europe PMC
  2. Verheijen FW, Verbeek E, Aula N, Beerens CE, Havelaar AC, Joosse M, Peltonen L, Aula P, Galjaard H, van der Spek PJ, Mancini GM.; ''A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases.''; PubMed Europe PMC
  3. Kitagawa H, Paulson JC.; ''Cloning and expression of human Gal beta 1,3(4)GlcNAc alpha 2,3-sialyltransferase.''; PubMed Europe PMC
  4. Lucka L, Krause M, Danker K, Reutter W, Horstkorte R.; ''Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis.''; PubMed Europe PMC
  5. Aula N, Salomäki P, Timonen R, Verheijen F, Mancini G, Månsson JE, Aula P, Peltonen L.; ''The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage diseases indicates some genotype-phenotype correlation.''; PubMed Europe PMC
  6. Maliekal P, Vertommen D, Delpierre G, Van Schaftingen E.; ''Identification of the sequence encoding N-acetylneuraminate-9-phosphate phosphatase.''; PubMed Europe PMC
  7. Seyrantepe V, Landry K, Trudel S, Hassan JA, Morales CR, Pshezhetsky AV.; ''Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells.''; PubMed Europe PMC
  8. Broccolini A, Pescatori M, D'Amico A, Sabino A, Silvestri G, Ricci E, Servidei S, Tonali PA, Mirabella M.; ''An Italian family with autosomal recessive inclusion-body myopathy and mutations in the GNE gene.''; PubMed Europe PMC
  9. Wu M, Gu S, Xu J, Zou X, Zheng H, Jin Z, Xie Y, Ji C, Mao Y.; ''A novel splice variant of human gene NPL, mainly expressed in human liver, kidney and peripheral blood leukocyte.''; PubMed Europe PMC
  10. Monti E, Preti A, Rossi E, Ballabio A, Borsani G.; ''Cloning and characterization of NEU2, a human gene homologous to rodent soluble sialidases.''; PubMed Europe PMC
  11. 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
  12. Martinez-Duncker I, Dupré T, Piller V, Piller F, Candelier JJ, Trichet C, Tchernia G, Oriol R, Mollicone R.; ''Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter.''; PubMed Europe PMC
  13. Basu SS, Basu M, Li Z, Basu S.; ''Characterization of two glycolipid: alpha 2-3sialyltransferases, SAT-3 (CMP-NeuAc:nLcOse4Cer alpha 2-3sialyltransferase) and SAT-4 (CMP-NeuAc:GgOse4Cer alpha 2-3sialyltransferase), from human colon carcinoma (Colo 205) cell line.''; PubMed Europe PMC
  14. Nakayama J, Fukuda MN, Hirabayashi Y, Kanamori A, Sasaki K, Nishi T, Fukuda M.; ''Expression cloning of a human GT3 synthase. GD3 AND GT3 are synthesized by a single enzyme.''; PubMed Europe PMC
  15. Ikehara Y, Kojima N, Kurosawa N, Kudo T, Kono M, Nishihara S, Issiki S, Morozumi K, Itzkowitz S, Tsuda T, Nishimura SI, Tsuji S, Narimatsu H.; ''Cloning and expression of a human gene encoding an N-acetylgalactosamine-alpha2,6-sialyltransferase (ST6GalNAc I): a candidate for synthesis of cancer-associated sialyl-Tn antigens.''; PubMed Europe PMC
  16. Monti E, Bassi MT, Papini N, Riboni M, Manzoni M, Venerando B, Croci G, Preti A, Ballabio A, Tettamanti G, Borsani G.; ''Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane.''; PubMed Europe PMC
  17. Li Y, Chen X.; ''Sialic acid metabolism and sialyltransferases: natural functions and applications.''; PubMed Europe PMC
  18. Tomimitsu H, Ishikawa K, Shimizu J, Ohkoshi N, Kanazawa I, Mizusawa H.; ''Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene.''; PubMed Europe PMC
  19. Galjart NJ, Gillemans N, Harris A, van der Horst GT, Verheijen FW, Galjaard H, d'Azzo A.; ''Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases.''; PubMed Europe PMC
  20. Chavas LM, Tringali C, Fusi P, Venerando B, Tettamanti G, Kato R, Monti E, Wakatsuki S.; ''Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition.''; PubMed Europe PMC
  21. Angata K, Yen TY, El-Battari A, Macher BA, Fukuda M.; ''Unique disulfide bond structures found in ST8Sia IV polysialyltransferase are required for its activity.''; PubMed Europe PMC
  22. Nonaka I, Sunohara N, Ishiura S, Satoyoshi E.; ''Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation.''; PubMed Europe PMC
  23. Takashima S, Tsuji S, Tsujimoto M.; ''Characterization of the second type of human beta-galactoside alpha 2,6-sialyltransferase (ST6Gal II), which sialylates Galbeta 1,4GlcNAc structures on oligosaccharides preferentially. Genomic analysis of human sialyltransferase genes.''; PubMed Europe PMC
  24. Samyn-Petit B, Krzewinski-Recchi MA, Steelant WF, Delannoy P, Harduin-Lepers A.; ''Molecular cloning and functional expression of human ST6GalNAc II. Molecular expression in various human cultured cells.''; PubMed Europe PMC
  25. Scheidegger EP, Sternberg LR, Roth J, Lowe JB.; ''A human STX cDNA confers polysialic acid expression in mammalian cells.''; PubMed Europe PMC
  26. Wu ZL, Ethen CM, Prather B, Machacek M, Jiang W.; ''Universal phosphatase-coupled glycosyltransferase assay.''; PubMed Europe PMC
  27. Lawrence SM, Huddleston KA, Pitts LR, Nguyen N, Lee YC, Vann WF, Coleman TA, Betenbaugh MJ.; ''Cloning and expression of the human N-acetylneuraminic acid phosphate synthase gene with 2-keto-3-deoxy-D-glycero- D-galacto-nononic acid biosynthetic ability.''; PubMed Europe PMC
  28. Keppler OT, Hinderlich S, Langner J, Schwartz-Albiez R, Reutter W, Pawlita M.; ''UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation.''; PubMed Europe PMC
  29. Lawrence SM, Huddleston KA, Tomiya N, Nguyen N, Lee YC, Vann WF, Coleman TA, Betenbaugh MJ.; ''Cloning and expression of human sialic acid pathway genes to generate CMP-sialic acids in insect cells.''; PubMed Europe PMC
  30. 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
  31. Rudenko G, Bonten E, d'Azzo A, Hol WG.; ''Three-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism.''; PubMed Europe PMC
  32. Argov Z, Eisenberg I, Grabov-Nardini G, Sadeh M, Wirguin I, Soffer D, Mitrani-Rosenbaum S.; ''Hereditary inclusion body myopathy: the Middle Eastern genetic cluster.''; PubMed Europe PMC
  33. Kim YJ, Kim KS, Kim SH, Kim CH, Ko JH, Choe IS, Tsuji S, Lee YC.; ''Molecular cloning and expression of human Gal beta 1,3GalNAc alpha 2,3-sialytransferase (hST3Gal II).''; PubMed Europe PMC
  34. Seppala R, Lehto VP, Gahl WA.; ''Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme.''; PubMed Europe PMC
  35. Tomimitsu H, Shimizu J, Ishikawa K, Ohkoshi N, Kanazawa I, Mizusawa H.; ''Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant.''; PubMed Europe PMC
  36. Zhou XY, Galjart NJ, Willemsen R, Gillemans N, Galjaard H, d'Azzo A.; ''A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable.''; PubMed Europe PMC
  37. Okajima T, Fukumoto S, Miyazaki H, Ishida H, Kiso M, Furukawa K, Urano T, Furukawa K.; ''Molecular cloning of a novel alpha2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids.''; PubMed Europe PMC
  38. Lee YC, Kim YJ, Lee KY, Kim KS, Kim BU, Kim HN, Kim CH, Do SI.; ''Cloning and expression of cDNA for a human Sia alpha 2,3Gal beta 1, 4GlcNA:alpha 2,8-sialyltransferase (hST8Sia III).''; PubMed Europe PMC
  39. Senda M, Ito A, Tsuchida A, Hagiwara T, Kaneda T, Nakamura Y, Kasama K, Kiso M, Yoshikawa K, Katagiri Y, Ono Y, Ogiso M, Urano T, Furukawa K, Oshima S, Furukawa K.; ''Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers.''; PubMed Europe PMC
  40. Ishii A, Ohta M, Watanabe Y, Matsuda K, Ishiyama K, Sakoe K, Nakamura M, Inokuchi J, Sanai Y, Saito M.; ''Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase.''; PubMed Europe PMC
  41. Bonten E, van der Spoel A, Fornerod M, Grosveld G, d'Azzo A.; ''Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis.''; PubMed Europe PMC
  42. Shang J, Qiu R, Wang J, Liu J, Zhou R, Ding H, Yang S, Zhang S, Jin C.; ''Molecular cloning and expression of Galbeta1,3GalNAc alpha2, 3-sialyltransferase from human fetal liver.''; PubMed Europe PMC
  43. Kim YJ, Kim KS, Do S, Kim CH, Kim SK, Lee YC.; ''Molecular cloning and expression of human alpha2,8-sialyltransferase (hST8Sia V).''; PubMed Europe PMC
  44. Monti E, Bassi MT, Bresciani R, Civini S, Croci GL, Papini N, Riboni M, Zanchetti G, Ballabio A, Preti A, Tettamanti G, Venerando B, Borsani G.; ''Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family.''; PubMed Europe PMC
  45. Ishida N, Miura N, Yoshioka S, Kawakita M.; ''Molecular cloning and characterization of a novel isoform of the human UDP-galactose transporter, and of related complementary DNAs belonging to the nucleotide-sugar transporter gene family.''; PubMed Europe PMC
  46. Kayashima T, Matsuo H, Satoh A, Ohta T, Yoshiura K, Matsumoto N, Nakane Y, Niikawa N, Kishino T.; ''Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE).''; PubMed Europe PMC
  47. Fu C, Bardhan S, Cetateanu ND, Wamil BD, Wang Y, Yan HP, Shi E, Carter C, Venkov C, Yakes FM, Page DL, Lloyd RS, Mernaugh RL, Hellerqvist CG.; ''Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis.''; PubMed Europe PMC
  48. Harduin-Lepers A, Stokes DC, Steelant WF, Samyn-Petit B, Krzewinski-Recchi MA, Vallejo-Ruiz V, Zanetta JP, Augé C, Delannoy P.; ''Cloning, expression and gene organization of a human Neu5Ac alpha 2-3Gal beta 1-3GalNAc alpha 2,6-sialyltransferase: hST6GalNAcIV.''; PubMed Europe PMC
  49. Wada T, Yoshikawa Y, Tokuyama S, Kuwabara M, Akita H, Miyagi T.; ''Cloning, expression, and chromosomal mapping of a human ganglioside sialidase.''; PubMed Europe PMC
  50. Wickramasinghe S, Medrano JF.; ''Primer on genes encoding enzymes in sialic acid metabolism in mammals.''; PubMed Europe PMC
  51. Tsuchida A, Okajima T, Furukawa K, Ando T, Ishida H, Yoshida A, Nakamura Y, Kannagi R, Kiso M, Furukawa K.; ''Synthesis of disialyl Lewis a (Le(a)) structure in colon cancer cell lines by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of alpha-series gangliosides.''; PubMed Europe PMC
  52. Eisenberg I, Avidan N, Potikha T, Hochner H, Chen M, Olender T, Barash M, Shemesh M, Sadeh M, Grabov-Nardini G, Shmilevich I, Friedmann A, Karpati G, Bradley WG, Baumbach L, Lancet D, Asher EB, Beckmann JS, Argov Z, Mitrani-Rosenbaum S.; ''The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.''; PubMed Europe PMC
  53. Miyagi T, Wada T, Yamaguchi K, Hata K, Shiozaki K.; ''Plasma membrane-associated sialidase as a crucial regulator of transmembrane signalling.''; PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
101514view11:37, 1 November 2018ReactomeTeamreactome version 66
101050view21:19, 31 October 2018ReactomeTeamreactome version 65
100581view19:53, 31 October 2018ReactomeTeamreactome version 64
100130view16:38, 31 October 2018ReactomeTeamreactome version 63
99680view15:08, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99273view12:45, 31 October 2018ReactomeTeamreactome version 62
93742view13:33, 16 August 2017ReactomeTeamreactome version 61
93256view11:18, 9 August 2017ReactomeTeamreactome version 61
87197view10:26, 19 July 2016EgonwOntology Term : 'classic metabolic pathway' added !
86334view09:15, 11 July 2016ReactomeTeamreactome version 56
83354view10:56, 18 November 2015ReactomeTeamVersion54
81514view13:03, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
CMAS ProteinQ8NFW8 (Uniprot-TrEMBL)
CMAS tetramerComplexR-HSA-4085413 (Reactome)
CMP-Neu5AcMetaboliteCHEBI:16556 (ChEBI)
CMPMetaboliteCHEBI:17361 (ChEBI)
CTPMetaboliteCHEBI:17677 (ChEBI)
CTSA(29-326) ProteinP10619 (Uniprot-TrEMBL)
CTSA(327-480) ProteinP10619 (Uniprot-TrEMBL)
GLB1 ProteinP16278 (Uniprot-TrEMBL)
GNE ProteinQ9Y223 (Uniprot-TrEMBL)
GNE hexamerComplexR-HSA-3781918 (Reactome)
Gal-R MetaboliteCHEBI:61248 (ChEBI)
Gal-R, Neu5Ac-RComplexR-ALL-4088103 (Reactome)
Gal-R,GalNAc-R,Neu5Ac-RComplexR-ALL-4087987 (Reactome)
Gal-R,GalNAc-R,Neu5Ac-RComplexR-ALL-4088123 (Reactome)
Gal-RMetaboliteCHEBI:61248 (ChEBI)
GalNAc-R MetaboliteCHEBI:21507 (ChEBI)
GalNAc-RMetaboliteCHEBI:21507 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
ManNAc MetaboliteCHEBI:17122 (ChEBI)
ManNAc,ManNGcComplexR-ALL-4088099 (Reactome)
ManNAc-6-PMetaboliteCHEBI:28273 (ChEBI)
ManNAcMetaboliteCHEBI:17122 (ChEBI)
ManNGc MetaboliteCHEBI:28255 (ChEBI)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NANP ProteinQ8TBE9 (Uniprot-TrEMBL)
NANP:Mg2+ComplexR-HSA-4085395 (Reactome)
NANSProteinQ9NR45 (Uniprot-TrEMBL)
NEU1 ProteinQ99519 (Uniprot-TrEMBL)
NEU1,4 substratesComplexR-ALL-4087983 (Reactome)
NEU1:GLB1:CTSA,NEU4ComplexR-HSA-4088186 (Reactome)
NEU2 substratesComplexR-ALL-4088071 (Reactome)
NEU2ProteinQ9Y3R4 (Uniprot-TrEMBL)
NEU3 substratesComplexR-ALL-4088088 (Reactome)
NEU3ProteinQ9UQ49 (Uniprot-TrEMBL)
NEU4 ProteinQ8WWR8 (Uniprot-TrEMBL)
NPL ProteinQ9BXD5 (Uniprot-TrEMBL)
NPL tetramerComplexR-HSA-4088083 (Reactome)
Neu5Ac MetaboliteCHEBI:17012 (ChEBI)
Neu5Ac, Neu5GcComplexR-ALL-4088096 (Reactome)
Neu5Ac-2,3-Gal-R MetaboliteCHEBI:75127 (ChEBI)
Neu5Ac-2,3-Gal-RMetaboliteCHEBI:75127 (ChEBI)
Neu5Ac-2,6-Gal-R MetaboliteCHEBI:75129 (ChEBI)
Neu5Ac-2,6-Gal-RMetaboliteCHEBI:75129 (ChEBI)
Neu5Ac-2,6-GalNAc-R MetaboliteCHEBI:62634 (ChEBI)
Neu5Ac-2,6-GalNAc-RMetaboliteCHEBI:62634 (ChEBI)
Neu5Ac-2,8-Neu5Ac-R MetaboliteCHEBI:75130 (ChEBI)
Neu5Ac-2,8-Neu5Ac-RMetaboliteCHEBI:75130 (ChEBI)
Neu5Ac-9-PMetaboliteCHEBI:27438 (ChEBI)
Neu5Ac-R MetaboliteCHEBI:75133 (ChEBI)
Neu5Ac-RMetaboliteCHEBI:75133 (ChEBI)
Neu5AcMetaboliteCHEBI:17012 (ChEBI)
Neu5Gc MetaboliteCHEBI:29025 (ChEBI)
PEPMetaboliteCHEBI:18021 (ChEBI)
PPiMetaboliteCHEBI:29888 (ChEBI)
PYRMetaboliteCHEBI:32816 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
SLC17A5ProteinQ9NRA2 (Uniprot-TrEMBL)
SLC35A1ProteinP78382 (Uniprot-TrEMBL)
ST3GAL1 ProteinQ11201 (Uniprot-TrEMBL)
ST3GAL1-6ComplexR-HSA-4086290 (Reactome)
ST3GAL2 ProteinQ16842 (Uniprot-TrEMBL)
ST3GAL3 ProteinQ11203 (Uniprot-TrEMBL)
ST3GAL4 ProteinQ11206 (Uniprot-TrEMBL)
ST3GAL5 ProteinQ9UNP4 (Uniprot-TrEMBL)
ST3GAL6 ProteinQ9Y274 (Uniprot-TrEMBL)
ST6GAL1 ProteinP15907 (Uniprot-TrEMBL)
ST6GAL1,2ComplexR-HSA-975904 (Reactome)
ST6GAL2 ProteinQ96JF0 (Uniprot-TrEMBL)
ST6GALNAC1 ProteinQ9NSC7 (Uniprot-TrEMBL)
ST6GALNAC1-6ComplexR-HSA-4086259 (Reactome)
ST6GALNAC2 ProteinQ9UJ37 (Uniprot-TrEMBL)
ST6GALNAC3 ProteinQ8NDV1 (Uniprot-TrEMBL)
ST6GALNAC4 ProteinQ9H4F1 (Uniprot-TrEMBL)
ST6GALNAC5 ProteinQ9BVH7 (Uniprot-TrEMBL)
ST6GALNAC6 ProteinQ969X2 (Uniprot-TrEMBL)
ST8SIA1 ProteinQ92185 (Uniprot-TrEMBL)
ST8SIA1-6ComplexR-HSA-4086295 (Reactome)
ST8SIA2 ProteinQ92186 (Uniprot-TrEMBL)
ST8SIA3 ProteinO43173 (Uniprot-TrEMBL)
ST8SIA4 ProteinQ92187 (Uniprot-TrEMBL)
ST8SIA5 ProteinO15466 (Uniprot-TrEMBL)
ST8SIA6 ProteinP61647 (Uniprot-TrEMBL)
UDP-GlcNAcMetaboliteCHEBI:16264 (ChEBI)
UDPMetaboliteCHEBI:17659 (ChEBI)
glycoconjugatesComplexR-ALL-4088200 (Reactome)
glycoconjugatesComplexR-ALL-4088202 (Reactome)
glycoconjugatesComplexR-ALL-4088208 (Reactome)
glycoconjugatesComplexR-ALL-4088213 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-4085028 (Reactome)
ATPR-HSA-4085028 (Reactome)
CMAS tetramermim-catalysisR-HSA-4084982 (Reactome)
CMP-Neu5AcArrowR-HSA-4084982 (Reactome)
CMP-Neu5AcArrowR-HSA-4084990 (Reactome)
CMP-Neu5AcArrowR-HSA-727807 (Reactome)
CMP-Neu5AcR-HSA-4084978 (Reactome)
CMP-Neu5AcR-HSA-4084980 (Reactome)
CMP-Neu5AcR-HSA-4084984 (Reactome)
CMP-Neu5AcR-HSA-4084990 (Reactome)
CMP-Neu5AcR-HSA-4085033 (Reactome)
CMP-Neu5AcR-HSA-727807 (Reactome)
CMPArrowR-HSA-4084978 (Reactome)
CMPArrowR-HSA-4084980 (Reactome)
CMPArrowR-HSA-4084984 (Reactome)
CMPArrowR-HSA-4085033 (Reactome)
CMPArrowR-HSA-727807 (Reactome)
CMPR-HSA-727807 (Reactome)
CTPR-HSA-4084982 (Reactome)
GNE hexamermim-catalysisR-HSA-4085021 (Reactome)
GNE hexamermim-catalysisR-HSA-4085028 (Reactome)
Gal-R, Neu5Ac-RArrowR-HSA-4084994 (Reactome)
Gal-R,GalNAc-R,Neu5Ac-RArrowR-HSA-4084999 (Reactome)
Gal-R,GalNAc-R,Neu5Ac-RArrowR-HSA-4085029 (Reactome)
Gal-RR-HSA-4084984 (Reactome)
Gal-RR-HSA-4085033 (Reactome)
GalNAc-RR-HSA-4084980 (Reactome)
H+ArrowR-HSA-428585 (Reactome)
H+R-HSA-428585 (Reactome)
H2OR-HSA-4084976 (Reactome)
H2OR-HSA-4084989 (Reactome)
H2OR-HSA-4084994 (Reactome)
H2OR-HSA-4084999 (Reactome)
H2OR-HSA-4085021 (Reactome)
H2OR-HSA-4085029 (Reactome)
ManNAc,ManNGcArrowR-HSA-4085217 (Reactome)
ManNAc-6-PArrowR-HSA-4085028 (Reactome)
ManNAc-6-PR-HSA-4084976 (Reactome)
ManNAcArrowR-HSA-4085021 (Reactome)
ManNAcR-HSA-4085028 (Reactome)
NANP:Mg2+mim-catalysisR-HSA-4084989 (Reactome)
NANSmim-catalysisR-HSA-4084976 (Reactome)
NEU1,4 substratesR-HSA-4084999 (Reactome)
NEU1:GLB1:CTSA,NEU4mim-catalysisR-HSA-4084999 (Reactome)
NEU2 substratesR-HSA-4085029 (Reactome)
NEU2mim-catalysisR-HSA-4085029 (Reactome)
NEU3 substratesR-HSA-4084994 (Reactome)
NEU3mim-catalysisR-HSA-4084994 (Reactome)
NPL tetramermim-catalysisR-HSA-4085217 (Reactome)
Neu5Ac, Neu5GcR-HSA-4085217 (Reactome)
Neu5Ac-2,3-Gal-RArrowR-HSA-4084984 (Reactome)
Neu5Ac-2,6-Gal-RArrowR-HSA-4085033 (Reactome)
Neu5Ac-2,6-GalNAc-RArrowR-HSA-4084980 (Reactome)
Neu5Ac-2,8-Neu5Ac-RArrowR-HSA-4084978 (Reactome)
Neu5Ac-9-PArrowR-HSA-4084976 (Reactome)
Neu5Ac-9-PR-HSA-4084989 (Reactome)
Neu5Ac-RR-HSA-4084978 (Reactome)
Neu5AcArrowR-HSA-4084989 (Reactome)
Neu5AcArrowR-HSA-4084994 (Reactome)
Neu5AcArrowR-HSA-4084999 (Reactome)
Neu5AcArrowR-HSA-4085020 (Reactome)
Neu5AcArrowR-HSA-4085029 (Reactome)
Neu5AcArrowR-HSA-428585 (Reactome)
Neu5AcR-HSA-4084982 (Reactome)
Neu5AcR-HSA-4085020 (Reactome)
Neu5AcR-HSA-428585 (Reactome)
PEPR-HSA-4084976 (Reactome)
PPiArrowR-HSA-4084982 (Reactome)
PYRArrowR-HSA-4085217 (Reactome)
PiArrowR-HSA-4084976 (Reactome)
PiArrowR-HSA-4084989 (Reactome)
R-HSA-4084976 (Reactome) Sialic acid synthase (NANS, SAS) can convert N-acetylmannosamine 6-phosphate (ManNAc-6-P) to N-acetylneuraminate 9-phosphate (Neu5Ac-9-P) (Lawrence et al. 2000). NANS shows lower activity towards ManNAc and can convert it to Neu5Ac (not shown here, Lawrence et al. 2000).
R-HSA-4084978 (Reactome) The alpha-2,8-sialyltransferases 1-6 (ST8SIA1-6) are involved in the production of gangliosides, glycoproteins and glycolipids. They transfer N-acetylneuraminate (Neu5Ac) to terminal Neu5Ac-yl groups of these glycoconjugates (Nakayama et al. 1996, Scheidegger et al. 1995, Lee et al. 1998, Angata et al. 2001, Kim et al. 1997). Once sialylated, glycoconjugates translocate to the plasma membrane by an unknown mechanism. For simplicity, Neu5Ac-R is shown in a generic form where R represents other sugars O-linked to proteins which can result in a large variability in glycoconjugate structures.
R-HSA-4084980 (Reactome) The alpha-2,6-sialyltransferases 1-6 (ST6GALNAC1-6) are able to transfer a sialic acid (Neu5Ac) moiety to the terminal N-acetylgalactosaminyl (GalNAc-R) residue of O-glycosylated proteins, glycoproteins and some gangliosides. Neu5Ac is added to GalNAc-R via an alpha-2,6 linkage (Ikehara et al. 1999, Samyn-Petit et al, 2000, Harduin-Lepers et al. 2000, Tsuchida et al. 2003, Senda et al. 2007). Once sialylated, glycoconjugates translocate to the plasma membrane by an unknown mechanism. For simplicity, GalNAc-R is shown in a generic form where R represents other sugars O-linked to proteins which can result in a large variability in glycoconjugate structures.
R-HSA-4084982 (Reactome) Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase1 (CMAS) transfers cytidine 5-monophosphate from a CTP donor to N-acetylneuraminate (Neu5Ac) to form CMP-Neu5Ac. CMAS is ubiquitously expressed and localizes to the nucleus in mammalian cells. The active form of the enzyme is a homotetramer (a dimer of dimers) (Lawrence et al. 2001, Huizing 2005). CMP-Neu5Ac is the donor substrate for sialyltransferases.
R-HSA-4084984 (Reactome) The alpha-2,3-sialyltransferases 1-6 (ST3GAL1-6) are able to transfer a sialic acid (Neu5Ac) moiety to the terminal galactosyl (Gal-R) residue of O-glycosylated proteins and some gangliosides. Neu5Ac is added to Gal-R via an alpha-2,3 linkage (Shang et al. 1999, Kim et al. 1996, Kitagawa & Paulson 1993, Basu et al. 1993, Ishii et al. 1998, Okajima et al. 1999). Once sialylated, glycoconjugates translocate to the plasma membrane by an unknown mechanism. For simplicity, Gal is shown in a generic form where R represents other sugars O-linked to proteins which can result in a large variability in glycoconjugate structures.
R-HSA-4084989 (Reactome) N-acylneuraminate 9-phosphatase (NANP) dephosphorylates N-acetylneuraminate -9-phosphate (Neu5Ac-9-P) to produce N-acetylneuraminate (Neu5Ac). NANP requires Mg2+ as a cofactor (Maliekal et al. 2006).
R-HSA-4084990 (Reactome) Once CMP-N-acetylneuraminate (CMP-Neu5Ac) is formed, it leaves the nucleus through nuclear pores to be further modified or used in conjugation reactions in the Golgi apparatus (Li & Chen 2012). The mechanism of translocation is unknown.
R-HSA-4084994 (Reactome) Sialidases 1-4 (NEU1-4, neuraminidases, receptor-destroying enzymes, RDEs) hydrolyze sialic acids (N-acetylneuraminic acid, Neu5Ac) to produce asialo compounds, a step in the degradation process of glycoproteins and gangliosides and are expressed in a variety of cellular locations. NEU3 localizes to the plasma membrane and hydrolyses Neu5Ac especially from gangliosides with alpha2,3- or alpha2,8-linkages present in the lipid bilayer (Wada et al. 1999, Monti et al. 2000). By regulating the composition of the lipid bilayer, NEU3 has been identified as an important regulator of trans-membrane signaling (Miyagi et al. 2008).
R-HSA-4084999 (Reactome) Sialidases 1-4 (NEU1-4, neuraminidases, receptor-destroying enzymes, RDEs) hydrolyse sialic acids (N-acetylneuraminic acid, Neu5Ac) to produce asialo compounds, a step in the degradation process of glycoproteins and gangliosides and are expressed in a variety of cellular locations. NEU4 is an extrinsic membrane protein associated with lysosomes, mitochondria and endoplasmic reticulum. It has broad sialidase activity against glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linkages (Bigi et al. 2010, Monti et al. 2004, Seyrantepe et al. 2004). NEU1 (lysosomal sialidase) hydrolyses Neu5Ac from glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linked terminal sialated residues in the lysosomal lumen. NEU1 is active in a multienzyme complex comprising cathepsin A protective protein (CTSA) and beta-galactosidase (Bonten et al. 1996, Rudenko et al. 1995). Defects in NEU1 cause Sialidosis (MIM:256550), a lysosomal storage disorder manifesting as type I (late-onset) or type II (earlier-onset) (Bonten et al. 1996). CTSA is thought to exert a protective function necessary for stability and activity of these enzymes (Galjart et al. 1988). Defects in CTSA are the cause of galactosialidosis (GSL; MIM:256540) (Zhou et al. 1991).
R-HSA-4085020 (Reactome) N-acetylneuraminate (Neu5Ac) translocates to the nucleus through nuclear pores to be converted to CMP-Neu5Ac. The mechanism of translocation is unknown (Li & Chen 2012).
R-HSA-4085021 (Reactome) UDP-N-acetylglucosamine 2-epimerase, N-acetylmannosamine kinase (GNE) is a bifunctional enzyme in the cytosol that is involved in the first two critical, rate-limiting steps of sialic acid (Neu5Ac, N-acetylneuraminic acid) biosynthesis, a main constituent of glycoconjugates. Because Neu5Ac is found at terminal positions of glycoconjugates, this molecule is involved in most cell-cell or cell-extracellular matrix interactions, serving as recognition sites. Thus, Neu5Ac plays critical roles in health and disease. In the first reaction, GNE hydrolyses and epimerises UDP-N-acetylglucosamine (UDP-GlcNAc) to N-acetylmannosamine (ManNAc) (Lucka et al. 1999, Keppler et al. 1999).

There are various disorders associated with defects in the GNE gene. Defects in GNE can cause sialuria (MIM:269921), an inborn error of metabolism characterised by cytoplasmic accumulation and increased urinary excretion of Neu5Ac (Seppala et al. 1999). Mutations causing sialuria are R266W, R266Q and R263L (Seppala et al. 1999). Defects in GNE can also cause hereditary inclusion body myopathy (IBM2; MIM:600737), an autosomal recessive neuromuscular disorder characterised by adult-onset, progressive distal and proximal muscle weakness and wastage. Muscle pathology shows rimmed vacuoles and filamentous inclusions (Eisenberg et al. 2001). The common M712T mutation can cause IBM2, as well as heterozygosity with the mutation M171V (Eisenberg et al. 2001, Argov et al. 2003, Broccolini et al. 2002). Defects in GNE can also cause Nonaka myopathy (NM; MIM:605820), an early adulthood-onset muscular disorder characterised by weakness and wastage of the lower limbs and rimmed vacuoles (Nonaka et al. 1981, Eisenberg et al. 2001). Mutations causing NK include the common V572L, either homozygous or heterozygous with C303V (Tomimitsu et al. 2002, Kayashima et al. 2002) and the heterozygous M712T with A631V indicated that NK and IBM2 are allelic, if not identical, disorders (Tomimitsu et al. 2004).
R-HSA-4085028 (Reactome) UDP N acetylglucosamine 2 epimerase, N acetylmannosamine kinase (GNE) is a bifunctional enzyme in the cytosol that is involved in the first two critical, rate limiting steps of sialic acid (Neu5Ac, N acetylneuraminic acid) biosynthesis. In the second reaction, GNE phosphorylates N-acetylmannosamine (ManNAc) to ManNAc-6-P. There are various disorders associated with defects in the GNE gene. Defects in GNE can cause sialuria (MIM:269921), an inborn error of metabolism characterised by cytoplasmic accumulation and increased urinary excretion of Neu5Ac (Seppala et al. 1999). Mutations causing sialuria are R266W, R266Q and R263L (Seppala et al. 1999). Defects in GNE can also cause hereditary inclusion body myopathy (IBM2; MIM:600737), an autosomal recessive neuromuscular disorder characterised by adult-onset, progressive distal and proximal muscle weakness and wastage. Muscle pathology shows rimmed vacuoles and filamentous inclusions (Eisenberg et al. 2001). The common M712T mutation can cause IBM2, as well as heterozygosity with the mutation M171V (Eisenberg et al. 2001, Argov et al. 2003, Broccolini et al. 2002). Defects in GNE can also cause Nonaka myopathy (NM; MIM:605820), an early adulthood-onset muscular disorder characterised by weakness and wastage of the lower limbs and rimmed vacuoles (Nonaka et al. 1981, Eisenberg et al. 2001). Mutations causing NK include the common V572L, either homozygous or heterozygous with C303V (Tomimitsu et al. 2002, Kayashima et al. 2002) and the heterozygous M712T with A631V indicated that NK and IBM2 are allelic, if not identical, disorders (Tomimitsu et al. 2004).
R-HSA-4085029 (Reactome) Sialidases 1-4 (NEU1-4, neuraminidases, receptor-destroying enzymes, RDEs) hydrolyze sialic acids (N-acetylneuraminic acid, Neu5Ac) to produce asialo compounds, a step in the degradation process of glycoproteins and gangliosides and are expressed in a variety of cellular locations. NEU2 (cytosolic sialidase) hydrolyzes Neu5Ac from glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linked terminal sialated residues in the cytosol (Monti et al. 1999, Chavas et al. 2005).
R-HSA-4085033 (Reactome) The beta-galactoside alpha-2,6-sialyltransferases 1 and 2 (ST6GAL1,2) are able to transfer a sialic acid (Neu5Ac) moiety to the terminal galactosyl (Gal-R) residue of O-glycosylated proteins and some gangliosides. Neu5Ac is added to Gal-R via an alpha-2,6 linkage (Wu et al. 2011, Takashima et al. 2002, Krzewinski-Recchi et al. 2003). Once sialylated, glycoconjugates translocate to the plasma membrane by an unknown mechanism. For simplicity, Gal is shown in a generic form where R represents other sugars O-linked to proteins. Highest activity is observed toward oligosaccharides that have the Gal-beta-1,4-GlcNAc sequence at the non-reducing end of their carbohydrate groups.
R-HSA-4085217 (Reactome) Once in the cytosol, sialic acids are either reutilized or degraded. N-acetylneuraminate lyase (NPL) is a cytosolic, tetrameric enzyme that can cleave the major sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) to form N-acetylmannosamine (ManNAc) and N-glycolylmannosamine (ManNGc) respectively (Wu et al. 2005). Although humans cannot form Neu5Gc due to a non-functional CMAHP enzyme, Neu5Gc can be ingested by dietary means and must therefore be degraded to avoid accumulation of this immunoreactive sialic acid (Bergfeld et al. 2012).
R-HSA-4088205 (Reactome) Glycoconjugates have to translocate to the cytosol for degradation by cytosol-specific sialidase 2 (NEU2). The mechanism of translocation is unknown but could simply be by diffusion (Li & Chen 2012).
R-HSA-4088207 (Reactome) Once glycoconjugates are sialylated, they translocate to the plasma membrane to carry out their various functions. The mechanism of translocation is unknown (Li & Chen 2012).
R-HSA-4088210 (Reactome) Glycoconjugates have to translocate to the lysosomal lumen for degradation by lysosomal-specific sialidases 1 and 4 (NEU1,4). The mechanism of translocation is unknown but could simply be by diffusion (Li & Chen 2012).
R-HSA-428585 (Reactome) SLC17A5 encodes a lysosomal sialic acid transporter, Sialin (AST, membrane glycoprotein HP59) (Verheijen et al. 1999, Fu et al. 2001). SLC17A5 exports sialic acid (N-acetylneuraminic acid, Neu5Ac) which is derived from the degradation of glycoconjugates. This export is dependent on the proton electrochemical gradient across the lysosomal membrane. SLC17A5 is present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. Sialin is not expressed in a variety of normal tissues, but is significantly expressed in human fetal lung. Defects in SLC17A5 cause Salla disease (SD) and infantile sialic acid storage disorder (ISSD aka N-acetylneuraminic acid storage disease, NSD). These belong to the sialic acid storage disease (SASD) group and are autosomal recessive neurodegenerative disorders characterised by hypotonia, cerebellar ataxia and mental retardation in very young infants (Verheijen et al. 1999, Aula et al. 2000).
R-HSA-727807 (Reactome) The human gene SLC35A1 encodes the CMP-sialic acid transporter which mediates the antiport of CMP-sialic acid (CMP-Neu5Ac) into the Golgi lumen in exchange for CMP (Ishida et al. 1996). Defects in SLC35A1 are the cause of congenital disorder of glycosylation type 2F (CDG2F; MIM:603585). CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation (Martinez-Duncker et al. 2005).
SLC17A5mim-catalysisR-HSA-428585 (Reactome)
SLC35A1mim-catalysisR-HSA-727807 (Reactome)
ST3GAL1-6mim-catalysisR-HSA-4084984 (Reactome)
ST6GAL1,2mim-catalysisR-HSA-4085033 (Reactome)
ST6GALNAC1-6mim-catalysisR-HSA-4084980 (Reactome)
ST8SIA1-6mim-catalysisR-HSA-4084978 (Reactome)
UDP-GlcNAcR-HSA-4085021 (Reactome)
UDPArrowR-HSA-4085021 (Reactome)
glycoconjugatesArrowR-HSA-4088205 (Reactome)
glycoconjugatesArrowR-HSA-4088207 (Reactome)
glycoconjugatesArrowR-HSA-4088210 (Reactome)
glycoconjugatesR-HSA-4088205 (Reactome)
glycoconjugatesR-HSA-4088207 (Reactome)
glycoconjugatesR-HSA-4088210 (Reactome)
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