UDP-Xylose and UDP-N-Acetylglucosamine Transporter (SLC35B4)

  • Hans Bakker
  • Angel Ashikov
Reference work entry


Nucleotide sugars that are synthesized in the cytoplasm or nucleus have to be transported over the membrane of the endoplasmic reticulum (ER) or Golgi to be used by glycosyltransferases in the lumen of the secretory pathway. There is one exception; UDP-xylose is made within the lumen of the ER or Golgi (Kearns et al. 1993; Hwang and Horvitz 2002; Moriarity et al. 2002; Bakker et al. 2009), suggesting there is no need for UDP-Xyl transport over the membrane. Still, transport of externally added UDP-Xyl over the Golgi membrane of mammalian cell has been observed (Nuwayhid et al. 1986; Milla et al. 1992; Kearns et al. 1993).


Nucleotide Sugar Golgi Membrane Golgi Vesicle SLC35 Family Hydrophilic Loop 
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  1. Ashikov A, Routier F, Fuhlrott J, Helmus Y, Wild M, Gerardy-Schahn R, Bakker H (2005) The human solute carrier gene SLC35B4 encodes a bifunctional nucleotide sugar transporter with specificity for UDP-xylose and UDP-N-acetylglucosamine. J Biol Chem 280:27230–27235PubMedCrossRefGoogle Scholar
  2. Ashikov A, Buettner FF, Tiemann B, Gerardy-Schahn R, Bakker H (2012) LARGE2 generates the same xylose and glucuronic acid containing glycan structures as LARGE. Glycobiology. doi:10.1093/glycob/cws153PubMedGoogle Scholar
  3. Bakker H, Oka T, Ashikov A, Yadav A, Berger M, Rana NA, Bai X, Jigami Y, Haltiwanger RS, Esko JD, Gerardy-Schahn R (2009) Functional UDP-xylose transport across the endoplasmic reticulum/Golgi membrane in a Chinese hamster ovary cell mutant defective in UDP-xylose synthase. J Biol Chem 284:2576–2583PubMedCrossRefGoogle Scholar
  4. Bossuyt X, Blanckaert N (1997) Carrier-mediated transport of uridine diphosphoglucuronic acid across the endoplasmic reticulum membrane is a prerequisite for UDP-glucuronosyltransferase activity in rat liver. Biochem J 323(Pt 3):645–648PubMedGoogle Scholar
  5. Bossuyt X, Blanckaert N (2001) Differential regulation of UDP-GlcUA transport in endoplasmic reticulum and in Golgi membranes. J Hepatol 34:210–214PubMedCrossRefGoogle Scholar
  6. Capasso JM, Hirschberg CB (1984) Mechanisms of glycosylation and sulfation in the Golgi apparatus: evidence for nucleotide sugar/nucleoside monophosphate and nucleotide sulfate/nucleoside monophosphate antiports in the Golgi apparatus membrane. Proc Natl Acad Sci USA 81:7051–7055PubMedCrossRefGoogle Scholar
  7. Carey DJ, Sommers LW, Hirschberg CB (1980) CMP-N-acetylneuraminic acid: isolation from and penetration into mouse liver microsomes. Cell 19:597–605PubMedCrossRefGoogle Scholar
  8. Eckhardt M, Mühlenhoff M, Bethe A, Gerardy-Schahn R (1996) Expression cloning of the Golgi CMP-sialic acid transporter. Proc Natl Acad Sci USA 93:7572–7576PubMedCrossRefGoogle Scholar
  9. Eckhardt M, Gotza B, Gerardy-Schahn R (1999) Membrane topology of the mammalian CMP-sialic acid transporter. J Biol Chem 274:8779–8787PubMedCrossRefGoogle Scholar
  10. Furuichi T, Kayserili H, Hiraoka S, Nishimura G, Ohashi H, Alanay Y, Lerena JC, Aslanger AD, Koseki H, Cohn DH, Superti-Furga A, Unger S, Ikegawa S (2009) Identification of loss-of-function mutations of SLC35D1 in patients with Schneckenbecken dysplasia, but not with other severe spondylodysplastic dysplasias group diseases. J Med Genet 46:562–568PubMedCrossRefGoogle Scholar
  11. Götting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K (2000) Molecular cloning and expression of human UDP-d-Xylose: proteoglycan core protein beta-d-xylosyltransferase and its first isoform XT-II. J Mol Biol 304:517–528PubMedCrossRefGoogle Scholar
  12. Guillen E, Abeijon C, Hirschberg CB (1998) Mammalian Golgi apparatus UDP-N-acetylglucosamine transporter: molecular cloning by phenotypic correction of a yeast mutant. Proc Natl Acad Sci USA 95:7888–7892PubMedCrossRefGoogle Scholar
  13. Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA (2004) The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins. Introduction. Pflugers Arch 447:465–468PubMedCrossRefGoogle Scholar
  14. Hwang HY, Horvitz HR (2002) The SQV-1 UDP-glucuronic acid decarboxylase and the SQV-7 nucleotide-sugar transporter may act in the Golgi apparatus to affect Caenorhabditis elegans vulval morphogenesis and embryonic development. Proc Natl Acad Sci USA 99:14218–14223PubMedCrossRefGoogle Scholar
  15. Inamori K, Yoshida-Moriguchi T, Hara Y, Anderson ME, Yu L, Campbell KP (2012a) Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science 335:93–96PubMedCentralPubMedCrossRefGoogle Scholar
  16. Inamori KI, Hara Y, Willer T, Anderson ME, Zhu Z, Yoshida-Moriguchi T, Campbell KP (2012b) Xylosyl- and glucuronyltransferase functions of LARGE in alpha-dystroglycan modification are conserved in LARGE2. Glycobiology. doi:10.1093/glycob/cws152PubMedGoogle Scholar
  17. Ishida N, Kawakita M (2004) Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35). Pflugers Arch 447:768–775PubMedCrossRefGoogle Scholar
  18. Ishida N, Kuba T, Aoki K, Miyatake S, Kawakita M, Sanai Y (2005) Identification and characterization of human Golgi nucleotide sugar transporter SLC35D2, a novel member of the SLC35 nucleotide sugar transporter family. Genomics 85:106–116PubMedCrossRefGoogle Scholar
  19. Jack DL, Yang NM, Saier MH Jr (2001) The drug/metabolite transporter superfamily. Eur J Biochem 268:3620–3639PubMedCrossRefGoogle Scholar
  20. Kearns AE, Vertel BM, Schwartz NB (1993) Topography of glycosylation and UDP-xylose production. J Biol Chem 268:11097–11104PubMedGoogle Scholar
  21. Kendler KS, Kalsi G, Holmans PA, Sanders AR, Aggen SH, Dick DM, Aliev F, Shi J, Levinson DF, Gejman PV (2011) Genomewide association analysis of symptoms of alcohol dependence in the molecular genetics of schizophrenia (MGS2) control sample. Alcohol Clin Exp Res 35:963–975PubMedCentralPubMedCrossRefGoogle Scholar
  22. Kobayashi T, Sleeman JE, Coughtrie MW, Burchell B (2006) Molecular and functional characterization of microsomal UDP-glucuronic acid uptake by members of the nucleotide sugar transporter (NST) family. Biochem J 400:281–289PubMedCrossRefGoogle Scholar
  23. Kuhn NJ, White A (1976) Evidence for specific transport of uridine diphosphate galactose across the Golgi membrane of rat mammary gland. Biochem J 154:243–244PubMedGoogle Scholar
  24. Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C (2001) Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet 28:73–76PubMedGoogle Scholar
  25. Lühn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D (2001) The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet 28:69–72PubMedGoogle Scholar
  26. Maszczak-Seneczko D, Olczak T, Olczak M (2011) Subcellular localization of UDP-GlcNAc, UDP-Gal and SLC35B4 transporters. Acta Biochim Pol 58:413–419PubMedGoogle Scholar
  27. Milla ME, Hirschberg CB (1989) Reconstitution of Golgi vesicle CMP-sialic acid and adenosine 3′-phosphate 5′-phosphosulfate transport into proteoliposomes. Proc Natl Acad Sci USA 86:1786–1790PubMedCrossRefGoogle Scholar
  28. Milla ME, Clairmont CA, Hirschberg CB (1992) Reconstitution into proteoliposomes and partial purification of the Golgi apparatus membrane UDP-galactose, UDP-xylose, and UDP-glucuronic acid transport activities. J Biol Chem 267:103–107PubMedGoogle Scholar
  29. Mitchell S, Siegel DH, Shieh JT, Stevenson DA, Grimmer JF, Lewis T, Metry D, Frieden I, Blei F, Kayserili H, Drolet BA, Bayrak-Toydemir P (2012) Candidate locus analysis for PHACE syndrome. Am J Med Genet A 158A:1363–1367PubMedCentralPubMedCrossRefGoogle Scholar
  30. Moriarity JL, Hurt KJ, Resnick AC, Storm PB, Laroy W, Schnaar RL, Snyder SH (2002) UDP-glucuronate decarboxylase, a key enzyme in proteoglycan synthesis: cloning, characterization, and localization. J Biol Chem 277:16968–16975PubMedCrossRefGoogle Scholar
  31. Muraoka M, Kawakita M, Ishida N (2001) Molecular characterization of human UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter, a novel nucleotide sugar transporter with dual substrate specificity. FEBS Lett 495:87–93PubMedCrossRefGoogle Scholar
  32. Muraoka M, Miki T, Ishida N, Hara T, Kawakita M (2007) Variety of nucleotide sugar transporters with respect to the interaction with nucleoside mono- and diphosphates. J Biol Chem 282:24615–24622PubMedCrossRefGoogle Scholar
  33. Nishimura M, Suzuki S, Satoh T, Naito S (2009) Tissue-specific mRNA expression profiles of human solute carrier 35 transporters. Drug Metab Pharmacokinet 24:91–99PubMedCrossRefGoogle Scholar
  34. Nuwayhid N, Glaser JH, Johnson JC, Conrad HE, Hauser SC, Hirschberg CB (1986) Xylosylation and glucuronosylation reactions in rat liver Golgi apparatus and endoplasmic reticulum. J Biol Chem 261:12936–12941PubMedGoogle Scholar
  35. Perez M, Hirschberg CB (1985) Translocation of UDP-N-acetylglucosamine into vesicles derived from rat liver rough endoplasmic reticulum and Golgi apparatus. J Biol Chem 260:4671–4678PubMedGoogle Scholar
  36. Puglielli L, Hirschberg CB (1999) Reconstitution, identification, and purification of the rat liver Golgi membrane GDP-fucose transporter. J Biol Chem 274:35596–35600PubMedCrossRefGoogle Scholar
  37. Roy SK, Chiba Y, Takeuchi M, Jigami Y (2000) Characterization of yeast Yea4p, a uridine diphosphate-N-acetylglucosamine transporter localized in the endoplasmic reticulum and required for chitin synthesis. J Biol Chem 275:13580–13587PubMedCrossRefGoogle Scholar
  38. Seal RL, Gordon SM, Lush MJ, Wright MW, Bruford EA (2011) the HGNC resources in 2011. Nucleic Acids Res 39:D514–D519PubMedCentralPubMedCrossRefGoogle Scholar
  39. Segawa H, Kawakita M, Ishida N (2002) Human and drosophila UDP-galactose transporters transport UDP-N-acetylgalactosamine in addition to UDP-galactose. Eur J Biochem 269:128–138PubMedCrossRefGoogle Scholar
  40. Sethi MK, Buettner FF, Krylov VB, Takeuchi H, Nifantiev NE, Haltiwanger RS, Gerardy-Schahn R, Bakker H (2010) Identification of glycosyltransferase 8 family members as xylosyltransferases acting on O-glucosylated notch epidermal growth factor repeats. J Biol Chem 285:1582–1586PubMedCrossRefGoogle Scholar
  41. Sethi MK, Buettner FF, Ashikov A, Krylov VB, Takeuchi H, Nifantiev NE, Haltiwanger RS, Gerardy-Schahn R, Bakker H (2012) Molecular cloning of a xylosyltransferase that transfers the second xylose to O-glucosylated epidermal growth factor repeats of notch. J Biol Chem 287:2739–2748PubMedCrossRefGoogle Scholar
  42. Sommers LW, Hirschberg CB (1982) Transport of sugar nucleotides into rat liver Golgi. A new Golgi marker activity. J Biol Chem 257:10811–10817PubMedGoogle Scholar
  43. Suda T, Kamiyama S, Suzuki M, Kikuchi N, Nakayama K, Narimatsu H, Jigami Y, Aoki T, Nishihara S (2004) Molecular cloning and characterization of a human multisubstrate specific nucleotide-sugar transporter homologous to Drosophila fringe connection. J Biol Chem 279:26469–26474PubMedCrossRefGoogle Scholar
  44. Sun-Wada GH, Yoshioka S, Ishida N, Kawakita M (1998) Functional expression of the human UDP-galactose transporters in the yeast Saccharomyces cerevisiae. J Biochem 123:912–917PubMedCrossRefGoogle Scholar
  45. Tiralongo J, Ashikov A, Routier F, Eckhardt M, Bakker H, Gerardy-Schahn R, von Itzstein M (2006) Functional expression of the CMP-sialic acid transporter in Escherichia coli and its identification as a simple mobile carrier. Glycobiology 16:73–81PubMedCrossRefGoogle Scholar
  46. Vastermark A, Almen MS, Simmen MW, Fredriksson R, Schioth HB (2011) Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae. BMC Evol Biol 11:123PubMedCentralPubMedCrossRefGoogle Scholar
  47. Yazbek SN, Buchner DA, Geisinger JM, Burrage LC, Spiezio SH, Zentner GE, Hsieh CW, Scacheri PC, Croniger CM, Nadeau JH (2011) Deep congenic analysis identifies many strong, context-dependent QTLs, one of which, Slc35b4, regulates obesity and glucose homeostasis. Genome Res 21:1065–1073PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Institute for Cellular ChemistryHannover Medical SchoolHannoverGermany

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