ST6 Beta-Galactoside Alpha-2,6-Sialyltranferase 1 (ST6GAL1)

  • Shinobu Kitazume
Reference work entry


ST6Gal I, β-galactoside α2,6-sialyltransferase, is involved in the formation of NeuAcα2,6-Gal linkages in N-linked glycans. Currently, most glycosyltransferases have been identified by homology searches for known enzymes, but ST6Gal I is one of the few enzymes purified from liver tissues (Weinstein et al. 1982a) to homogeneity for identification of its cDNA (Weinstein et al. 1987). ST6Gal I shows a broad tissue distribution (Kitagawa and Paulson 1994), and its deficiency causes almost complete lack of α2,6-sialylation in N-linked glycans.


Sialic Acid Avian Influenza Virus Acceptor Substrate Human Influenza Virus Platelet Endothelial Cell Adhesion Molecule 
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  1. Amano M, Galvan M, He J, Baum LG (2003) The ST6Gal I sialyltransferase selectively modifies N-glycans on CD45 to negatively regulate galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death. J Biol Chem 278:7469–7475PubMedCrossRefGoogle Scholar
  2. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 105:19571–19578PubMedCrossRefGoogle Scholar
  3. Anthony RM, Kobayashi T, Wermeling F, Ravetch JV (2011) Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 475:110–113PubMedCentralPubMedCrossRefGoogle Scholar
  4. Appenheimer MM, Huang RY, Chandrasekaran EV, Dalziel M, Hu YP, Soloway PD, Wuensch SA, Matta KL, Lau JT (2003) Biologic contribution of P1 promoter-mediated expression of ST6Gal I sialyltransferase. Glycobiology 13:591–600PubMedCrossRefGoogle Scholar
  5. Bateman AC, Karamanska R, Busch MG, Dell A, Olsen CW, Haslam SM (2010) Glycan analysis and influenza A virus infection of primary swine respiratory epithelial cells: the importance of NeuAcα2–6 glycans. J Biol Chem 285:34016–34026PubMedCrossRefGoogle Scholar
  6. Baum LG, Paulson JC (1990) Sialyloligosaccharides of the respiratory epithelium in the selection of human influenza virus receptor specificity. Acta Histochem Suppl 40:35–38PubMedGoogle Scholar
  7. Blasioli J, Paust S, Thomas ML (1999) Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. J Biol Chem 274:2303–2307PubMedCrossRefGoogle Scholar
  8. Chandrasekaran A, Srinivasan A, Raman R, Viswanathan K, Raguram S, Tumpey TM, Sasisekharan V, Sasisekharan R (2008) Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin. Nat Biotechnol 26:107–113PubMedCrossRefGoogle Scholar
  9. Chen WC, Completo GC, Sigal DS, Crocker PR, Saven A, Paulson JC (2010) In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood 115:4778–4786PubMedCrossRefGoogle Scholar
  10. Colley KJ (1997) Golgi localization of glycosyltransferases: more questions than answers. Glycobiology 7:1–13PubMedCrossRefGoogle Scholar
  11. Collins BE, Blixt O, DeSieno AR, Bovin N, Marth JD, Paulson JC (2004) Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact. Proc Natl Acad Sci USA 101:6104–6109PubMedCrossRefGoogle Scholar
  12. Collins BE, Smith BA, Bengtson P, Paulson JC (2006) Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling. Nat Immunol 7:199–206PubMedCrossRefGoogle Scholar
  13. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, Daly MJ, Goldstein DB, John S, Nelson MR, Graham J, Park BK, Dillon JF, Bernal W, Cordell HJ, Pirmohamed M, Aithal GP, Day CP (2009) HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 41:816–819PubMedCrossRefGoogle Scholar
  14. Dalziel M, Huang RY, Dall’Olio F, Morris JR, Taylor-Papadimitriou J, Lau JT (2001) Mouse ST6Gal sialyltransferase gene expression during mammary gland lactation. Glycobiology 11:407–412PubMedCrossRefGoogle Scholar
  15. Datta AK, Chammas R, Paulson JC (2001) Conserved cysteines in the sialyltransferase sialylmotifs form an essential disulfide bond. J Biol Chem 276:15200–15207PubMedCrossRefGoogle Scholar
  16. Doody GM, Justement LB, Delibrias CC, Matthews RJ, Lin J, Thomas ML, Fearon DT (1995) A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 269:242–244PubMedCrossRefGoogle Scholar
  17. Futakawa S, Kitazume S, Oka R, Ogawa K, Hagiwara Y, Kinoshita A, Miyashita K, Hashimoto Y (2009) Development of sandwich enzyme-linked immunosorbent assay systems for plasma beta-galactoside α2,6-sialyltransferase, a possible hepatic disease biomarker. Anal Chim Acta 631:116–120PubMedCrossRefGoogle Scholar
  18. Grewal PK, Boton M, Ramirez K, Collins BE, Saito A, Green RS, Ohtsubo K, Chui D, Marth JD (2006) ST6Gal-I restrains CD22-dependent antigen receptor endocytosis and Shp-1 recruitment in normal and pathogenic immune signaling. Mol Cell Biol 26:4970–4981PubMedCentralPubMedCrossRefGoogle Scholar
  19. Han S, Collins BE, Bengtson P, Paulson JC (2005) Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking. Nat Chem Biol 1:93–97PubMedCrossRefGoogle Scholar
  20. Harduin-Lepers A, Mollicone R, Delannoy P, Oriol R (2005) The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic approach. Glycobiology 15:805–817PubMedCrossRefGoogle Scholar
  21. Hennet T, Chui D, Paulson JC, Marth JD (1998) Immune regulation by the ST6Gal sialyltransferase. Proc Natl Acad Sci USA 95:4504–4509PubMedCrossRefGoogle Scholar
  22. Hirabayashi J, Hashidate T, Arata Y, Nishi N, Nakamura T, Hirashima M, Urashima T, Oka T, Futai M, Muller WE, Yagi F, Kasai K (2002) Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochim Biophys Acta 1572:232–254PubMedCrossRefGoogle Scholar
  23. Jones MB, Nasirikenari M, Feng L, Migliore MT, Choi KS, Kazim L, Lau JT (2010) Role for hepatic and circulatory ST6Gal-1 sialyltransferase in regulating myelopoiesis. J Biol Chem 285:25009–25017PubMedCrossRefGoogle Scholar
  24. Jones MB, Nasirikenari M, Lugade AA, Thanavala Y, Lau JT (2012) Anti-inflammatory IgG production requires functional P1 promoter in β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) gene. J Biol Chem 287:15365–15370PubMedCrossRefGoogle Scholar
  25. Joziasse DH, Schiphorst WE, van den Eijnden DH, van Kuik JA, van Halbeek H, Vliegenthart JF (1985) Branch specificity of bovine colostrum CMP-sialic acid: N-acetyllactosaminide α2–6-sialyltransferase. Interaction with biantennary oligosaccharides and glycopeptides of N-glycosylproteins. J Biol Chem 260:714–719PubMedGoogle Scholar
  26. Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313:670–673PubMedCrossRefGoogle Scholar
  27. Kitagawa H, Paulson JC (1994) Differential expression of five sialyltransferase genes in human tissues. J Biol Chem 269:17872–17878PubMedGoogle Scholar
  28. Kitazume S, Tachida Y, Oka R, Shirotani K, Saido TC, Hashimoto Y (2001) Alzheimer’s β-secretase, β-site amyloid precursor protein-cleaving enzyme, is responsible for cleavage secretion of a Golgi-resident sialyltransferase. Proc Natl Acad Sci USA 98:13554–13559PubMedCrossRefGoogle Scholar
  29. Kitazume S, Imamaki R, Ogawa K, Komi Y, Futakawa S, Kojima S, Hashimoto Y, Marth JD, Paulson JC, Taniguchi N (2010) α2,6-sialic acid on platelet endothelial cell adhesion molecule (PECAM) regulates its homophilic interactions and downstream antiapoptotic signaling. J Biol Chem 285:6515–6521PubMedCrossRefGoogle Scholar
  30. Kitazume S, Oka R, Ogawa K, Futakawa S, Hagiwara Y, Takikawa H, Kato M, Kasahara A, Miyoshi E, Taniguchi N, Hashimoto Y (2009) Molecular insights into β-galactoside α2,6-sialyltransferase secretion in vivo. Glycobiology 19:479–487PubMedCrossRefGoogle Scholar
  31. Kitazume-Kawaguchi S, Dohmae N, Takio K, Tsuji S, Colley KJ (1999) The relationship between ST6Gal I Golgi retention and its cleavage-secretion. Glycobiology 9:1397–1406PubMedCrossRefGoogle Scholar
  32. Kleene R, Schachner M (2004) Glycans and neural cell interactions. Nat Rev Neurosci 5:195–208PubMedCrossRefGoogle Scholar
  33. Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia KS, Dimas AS, Hassanali N, Jafar T, Jowett JB, Li X, Radha V, Rees SD, Takeuchi F, Young R, Aung T, Basit A, Chidambaram M, Das D, Grundberg E, Hedman AK, Hydrie ZI, Islam M, Khor CC, Kowlessur S, Kristensen MM, Liju S, Lim WY, Matthews DR, Liu J, Morris AP, Nica AC, Pinidiyapathirage JM, Prokopenko I, Rasheed A, Samuel M, Shah N, Shera AS, Small KS, Suo C, Wickremasinghe AR, Wong TY, Yang M, Zhang F, Abecasis GR, Barnett AH, Caulfield M, Deloukas P, Frayling TM, Froguel P, Kato N, Katulanda P, Kelly MA, Liang J, Mohan V, Sanghera DK, Scott J, Seielstad M, Zimmet PZ, Elliott P, Teo YY, McCarthy MI, Danesh J, Tai ES, Chambers JC (2011) Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet 43:984–989PubMedCentralPubMedCrossRefGoogle Scholar
  34. Legaigneur P, Breton C, El Battari A, Guillemot JC, Auge C, Malissard M, Berger EG, Ronin C (2001) Exploring the acceptor substrate recognition of the human beta-galactoside α2,6-sialyltransferase. J Biol Chem 276:21608–21617PubMedCrossRefGoogle Scholar
  35. Leppanen A, Stowell S, Blixt O, Cummings RD (2005) Dimeric galectin-1 binds with high affinity to α2,3-sialylated and non-sialylated terminal N-acetyllactosamine units on surface-bound extended glycans. J Biol Chem 280:5549–5562PubMedCrossRefGoogle Scholar
  36. Maines TR, Jayaraman A, Belser JA, Wadford DA, Pappas C, Zeng H, Gustin KM, Pearce MB, Viswanathan K, Shriver ZH, Raman R, Cox NJ, Sasisekharan R, Katz JM, Tumpey TM (2009) Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 325:484–487PubMedCentralPubMedGoogle Scholar
  37. Marino JH, Tan C, Davis B, Han ES, Hickey M, Naukam R, Taylor A, Miller KS, Van De Wiele CJ, Teague TK (2008) Disruption of thymopoiesis in ST6Gal I-deficient mice. Glycobiology 18:719–726PubMedCrossRefGoogle Scholar
  38. Marth JD, Grewal PK (2008) Mammalian glycosylation in immunity. Nat Rev Immunol 8:874–887PubMedCentralPubMedCrossRefGoogle Scholar
  39. Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y (2000) Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 74:8502–8512PubMedCentralPubMedCrossRefGoogle Scholar
  40. Naito Y, Takematsu H, Koyama S, Miyake S, Yamamoto H, Fujinawa R, Sugai M, Okuno Y, Tsujimoto G, Yamaji T, Hashimoto Y, Itohara S, Kawasaki T, Suzuki A, Kozutsumi Y (2007) Germinal center marker GL7 probes activation-dependent repression of N-glycolylneuraminic acid, a sialic acid species involved in the negative modulation of B-cell activation. Mol Cell Biol 27:3008–3022PubMedCentralPubMedCrossRefGoogle Scholar
  41. Nycholat CM, McBride R, Ekiert DC, Xu R, Rangarajan J, Peng W, Razi N, Gilbert M, Wakarchuk W, Wilson IA, Paulson JC (2012) Recognition of sialylated poly-N-acetyllactosamine chains on N- and O-linked glycans by human and avian influenza A virus hemagglutinins. Angew Chem Int Ed Engl 51:4860–4863PubMedCentralPubMedCrossRefGoogle Scholar
  42. O’Hanlon TP, Lau KM, Wang XC, Lau JT (1989) Tissue-specific expression of beta-galactoside alpha-2,6-sialyltransferase. Transcript heterogeneity predicts a divergent polypeptide. J Biol Chem 264:17389–17394PubMedGoogle Scholar
  43. Paulson JC, Rademacher C (2009) Glycan terminator. Nat Struct Mol Biol 16:1121–1122PubMedCentralPubMedCrossRefGoogle Scholar
  44. Powell LD, Sgroi D, Sjoberg ER, Stamenkovic I, Varki A (1993) Natural ligands of the B cell adhesion molecule CD22 beta carry N-linked oligosaccharides with alpha-2,6-linked sialic acids that are required for recognition. J Biol Chem 268:7019–7027PubMedGoogle Scholar
  45. Razi N, Varki A (1998) Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes. Proc Natl Acad Sci USA 95:7469–7474PubMedCrossRefGoogle Scholar
  46. Schweizer A, Wohner M, Prescher H, Brossmer R, Nitschke L (2012) Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues. Eur J Immunol 42:2792–2802PubMedCrossRefGoogle Scholar
  47. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y (2006) Avian flu: influenza virus receptors in the human airway. Nature 440:435–436PubMedCrossRefGoogle Scholar
  48. Sugimoto I, Futakawa S, Oka R, Ogawa K, Marth JD, Miyoshi E, Taniguchi N, Hashimoto Y, Kitazume S (2007) ST6Gal I cleavage by BACE1 enhances the sialylation of soluble glycoproteins: a novel regulatory mechanism for α2,6-sialylation. J Biol Chem 282(48):34896–34903PubMedCrossRefGoogle Scholar
  49. Svensson EC, Conley PB, Paulson JC (1992) Regulated expression of alpha 2,6-sialyltransferase by the liver-enriched transcription factors HNF-1, DBP, and LAP. J Biol Chem 267:3466–3472PubMedGoogle Scholar
  50. Takashima S, Tsuji S, Tsujimoto M (2002) 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. J Biol Chem 277:45719–45728PubMedCrossRefGoogle Scholar
  51. Toscano MA, Bianco GA, Ilarregui JM, Croci DO, Correale J, Hernandez JD, Zwirner NW, Poirier F, Riley EM, Baum LG, Rabinovich GA (2007) Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8:825–834PubMedCrossRefGoogle Scholar
  52. van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T (2006) H5N1 Virus attachment to lower respiratory tract. Science 312:399PubMedCrossRefGoogle Scholar
  53. Varki A, Angata T (2006) Siglecs–the major subfamily of I-type lectins. Glycobiology 16:1R–27RPubMedCrossRefGoogle Scholar
  54. Vasta GR (2009) Roles of galectins in infection. Nat Rev Microbiol 7:424–438PubMedCentralPubMedCrossRefGoogle Scholar
  55. Weinstein J, de Souza-e-Silva U, Paulson JC (1982a) Purification of a Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase and a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase to homogeneity from rat liver. J Biol Chem 257:13835–13844PubMedGoogle Scholar
  56. Weinstein J, de Souza-e-Silva U, Paulson JC (1982b) Sialylation of glycoprotein oligosaccharides N-linked to asparagine. Enzymatic characterization of a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase and a Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase from rat liver. J Biol Chem 257:13845–13853PubMedGoogle Scholar
  57. Weinstein J, Lee EU, McEntee K, Lai PH, Paulson JC (1987) Primary structure of beta-galactoside alpha 2,6-sialyltransferase. Conversion of membrane-bound enzyme to soluble forms by cleavage of the NH2-terminal signal anchor. J Biol Chem 262:17735–17743PubMedGoogle Scholar
  58. Woodard-Grice AV, McBrayer AC, Wakefield JK, Zhuo Y, Bellis SL (2008) Proteolytic shedding of ST6Gal-I by BACE1 regulates the glycosylation and function of alpha4beta1 integrins. J Biol Chem 283:26364–26373PubMedCrossRefGoogle Scholar
  59. Zeng J, Joo HM, Rajini B, Wrammert JP, Sangster MY, Onami TM (2009) The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice. J Immunol 182:4721–4727PubMedCentralPubMedCrossRefGoogle Scholar
  60. Zhuo Y, Bellis SL (2011) Emerging role of alpha2,6-sialic acid as a negative regulator of galectin binding and function. J Biol Chem 286:5935–5941PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Disease Glycomics Team, Systems Glycobiology Research GroupRIKENSaitamaJapan

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