ST6 Beta-Galactoside Alpha-2,6-Sialyltranferase 2 (ST6GAL2)

  • Shou Takashima
  • Shuichi Tsuji
Reference work entry


Sialic acids are derivatives of the negatively charged acidic sugar neuraminic acid. Over 50 naturally occurring members of the sialic acid family have been discovered to date (Angata and Varki 2002); N-acetylneuraminic acid (NeuAc), N-glycolylneuraminic acid (NeuGc), and deaminoneuraminic acid (KDN) are representative members of this family. The importance of these molecules is demonstrated by the fact that impairment of their biosynthesis is lethal to mice embryos (Schwarzkopf et al. 2002). Sialic acids usually form the terminal ends of the carbohydrate groups of glycoconjugates. Because of their negative charge and their exposed positions on cell-surface molecules, they often function as key determinants of oligosaccharide structures that mediate a variety of biological processes including cell–cell interaction, cell migration, adhesion, metastasis, and pathogen infection. In fact, there are numerous sialic acid recognition molecules such as the sialic acid-binding immunoglobulin-like lectins (siglecs) (Crocker et al. 2007). A superfamily of glycosyltransferases called sialyltransferases catalyzes the synthesis of sialylglycoconjugates by transferring a sialic acid molecule from the donor substrate CMP-Sia to an acceptor carbohydrate. To date, cDNA cloning of 20 mammalian sialyltransferases has been completed, and their enzymatic properties have been analyzed. These enzymes are grouped into four families according to the type of carbohydrate linkage they synthesize: β-galactoside α2,3-sialyltransferases (ST3Gal family), β-galactoside α2,6-sialyltransferases (ST6Gal family), N-acetylgalactosamine (GalNAc) α2,6-sialyltransferases (ST6GalNAc family), and α2,8-sialyltransferases (ST8Sia family). All animal sialyltransferases characterized to date have type II transmembrane topology and are thought to localize to the Golgi body. These sialyltransferases are classified into CAZy (carbohydrate-active enzymes) glycosyltransferase family 29 (Coutinho et al. 2003). All animal sialyltransferases have common structural features composed of a short N-terminal cytoplasmic tail, a transmembrane domain, a stem region, and a catalytic domain, which contains highly conserved motifs called sialylmotifs L (long), S (short), III (third position in the sequence), and VS (very short). The members of the ST6Gal family transfer sialic acid from CMP-sialic acid (CMP-Sia) to the galactose residues at the nonreducing ends of glycoconjugates through an α2,6-linkage. Two members of the ST6Gal family, ST6Gal-I and ST6Gal-II, have been identified in mammals to date. These enzymes commonly utilize the Galβ1–4GlcNAc structure on glycoproteins and oligosaccharides as acceptor substrates (Takashima et al. 2002, 2003; Krzewinski-Recchi et al. 2003); however, ST6Gal-II utilizes the LacdiNAc structure (GalNAcβ1–4GlcNAc) as a preferred acceptor substrate over the Galβ1–4GlcNAc structure (Rohfritsch et al. 2006; Laporte et al. 2009). The ST6Gal-I gene is ubiquitously expressed, whereas the ST6Gal-II gene is expressed in tissue- and stage-specific manner. The overall amino acid sequence identity of human ST6Gal-II is 48.9 % to human ST6Gal-I, 77.1 % to mouse ST6Gal-II, and 73.2 % to bovine ST6Gal-II, respectively. Analysis of the genomic structures of the ST6Gal-I and ST6Gal-II genes suggested that these genes arose from a common ancestral gene (Harduin-Lepers et al. 2005; Takashima 2008; Harduin-Lepers 2010).


Sialic Acid Acceptor Substrate Common Ancestral Gene Entire Open Reading Frame Basic Local Alignment Search Tool Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Angata T, Varki A (2002) Chemical diversity in the sialic acids and related α-keto acids: an evolutionary perspective. Chem Rev 102:439–469. doi:10.1021/cr000407mPubMedCrossRefGoogle Scholar
  2. Coutinho PM, Deleury E, Davies GJ, Henrissat B (2003) An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 328:307–317. doi:10.1016/S0022-2836(03)00307-3PubMedCrossRefGoogle Scholar
  3. Crocker PR, Paulson JC, Varki A (2007) Siglecs and their roles in the immune system. Nat Rev Immunol 7:255–266. doi:10.1038/nri2056PubMedCrossRefGoogle Scholar
  4. Groux-Degroote S, Krzewinski-Recchi MA, Cazet A, Vincent A, Lehoux S, Lafitte JJ, Van Seuningen I, Delannoy P (2008) IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated LewisX epitopes in the human bronchial mucosa. Biochem J 410:213–223. doi:10.1042/BJ20070958PubMedCrossRefGoogle Scholar
  5. Harduin-Lepers A (2010) Comprehensive analysis of sialyltransferases in vertebrate genomes. Glycobiol Insights 2:29–61CrossRefGoogle Scholar
  6. Harduin-Lepers A, Mollicone R, Delannoy P, Oriol R (2005) The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic approach. Glycobiology 15:805–817. doi:10.1093/glycob/cwi063PubMedCrossRefGoogle Scholar
  7. Ikeda M, Tomita Y, Mouri A, Koga M, Okochi T, Yoshimura R, Yamanouchi Y, Kinoshita Y, Hashimoto R, Williams HJ, Takeda M, Nakamura J, Nabeshima T, Owen MJ, O’Donovan MC, Honda H, Arinami T, Ozaki N, Iwata N (2010) Identification of novel candidate genes for treatment response to risperidone and susceptibility for schizophrenia: integrated analysis among pharmacogenomics, mouse expression, and genetic-case control association approaches. Biol Psychiatry 67:263–269. doi:10.1016/j.biopsych.2009.08.030PubMedCrossRefGoogle Scholar
  8. Krzewinski-Recchi MA, Julien S, Juliant S, Teintenier-Lelièvre M, Samyn-Petit B, Montiel MD, Mir AM, Cerutti M, Harduin-Lepers A, Delannoy P (2003) Identification and functional expression of a second human β-galactoside α2,6-sialyltransferase, ST6Gal II. Eur J Biochem 270:950–961. doi:10.1046/j.1432-1033.2003.03458.xPubMedCrossRefGoogle Scholar
  9. Laporte B, Gonzalez-Hilarion S, Maftah A, Petit JM (2009) The second bovine β-galactoside-α2,6-sialyltransferase (ST6Gal II): genomic organization and stimulation of its in vitro expression by IL-6 in bovine mammary epithelial cells. Glycobiology 19:1082–1093. doi:10.1093/glycob/cwp094PubMedCrossRefGoogle Scholar
  10. Lehoux S, Groux-Degroote S, Cazet A, Dhaenens CM, Maurage CA, Caillet-Boudin ML, Delannoy P, Krzewinski-Recchi MA (2010) Transcriptional regulation of the human ST6GAL2 gene in cerebral cortex and neuronal cells. Glycoconj J 27:99–114. doi:10.1007/s10719-009-9260-yPubMedCrossRefGoogle Scholar
  11. Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (2001) Prediction of the coding sequence of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res 8:85–95. doi:10.1093/dnares/8.2.85PubMedCrossRefGoogle Scholar
  12. Rohfritsch PF, Joosten JAF, Krzewinski-Recchi MA, Harduin-Lepers A, Laporte B, Juliant S, Cerutti M, Delannoy P, Vliegenthart JFG, Kamerling JP (2006) Probing the substrate specificity of four different sialyltransferases using synthetic β-D-Galp-(1→4)-β-GlcpNAc-(1→2)-α-D-Manp-(1→O)(CH2)7CH3 analogues. General activating effect of replacing N-acetylglucosamine by N-propionylglucosamine. Biochim Biophys Acta 1760:685–692. doi:10.1016/j.bbagen.2005.12.012PubMedCrossRefGoogle Scholar
  13. Schwarzkopf M, Knobeloch KP, Rohde E, Hinderlich S, Wiechens N, Lucka L, Horak I, Reutter W, Horstkorte R (2002) Sialylation is essential for early development in mice. Proc Natl Acad Sci USA 99:5267–5270. doi:10.1073/pnas.072066199PubMedCrossRefGoogle Scholar
  14. Takashima S (2008) Characterization of mouse sialyltransferase genes: their evolution and diversity. Biosci Biotechnol Biochem 72:1155–1167. doi:10.1271/bbb.80025PubMedCrossRefGoogle Scholar
  15. Takashima S, Tsuji S (2011) Functional diversity of mammalian sialyltransferases. Trends Glycosci Glycotechnol 23:178–193. doi:10.4052/tigg.23.178CrossRefGoogle Scholar
  16. Takashima S, Tsuji S, Tsujimoto M (2002) Characterization of the second type of human β-galactoside α2,6-sialyltransferase (ST6Gal II), which sialylates Galβ1,4GlcNAc structures on oligosaccharides preferentially. J Biol Chem 277:45719–45728. doi:10.1074/jbc.M206808200PubMedCrossRefGoogle Scholar
  17. Takashima S, Tsuji S, Tsujimoto M (2003) Comparison of the enzymatic properties of mouse β-galactoside α2,6-sialyltransferases, ST6Gal I and II. J Biochem 134:287–296. doi:10.1093/jb/mvg142PubMedCrossRefGoogle Scholar
  18. Tsuji S, Datta AK, Paulson JC (1996) Systematic nomenclature for sialyltransferases. Glycobiology 6(7):v–viiPubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Laboratory of GlycobiologyThe Noguchi InstituteItabashi, TokyoJapan
  2. 2.Institute of GlycoscienceTokai UniversityHiratsuka, KanagawaJapan

Personalised recommendations