Heterodimeric Alg13/Alg14 UDP-GlcNAc Transferase (ALG13,14)

Reference work entry


Protein N- glycosylation begins with the synthesis of a conserved lipid-linked oligosaccharide (LLO) precursor. After assembly, the oligosaccharide is transferred from the lipid to nascent proteins during their translation in the ER. Synthesis of this oligosaccharide is catalyzed in sequential steps by twelve endoplasmic reticulum (ER) membrane-associated Alg (A sparagine-l inked g lycosylation) glycosyltransferases. Seven sugars are added to dolichyl pyrophosphate on the cytoplasmic face of the ER, using nucleotide-sugar substrates UDP-GlcNAc and GDP-Man. After flipping into the ER lumen, seven more sugars, using dolichol-linked sugar substrates, are used to extend the Man5GlcNAc2-PP-Dol intermediate to produce Glc3Man7GlcNAc2-PP-Dol (reviewed in: Helenius and Aebi 2004; Kelleher and Gilmore 2006; Weerapana and Imperiali 2006). The second step of LLO synthesis adds N-acetylglucosamine (GlcNAc) to GlcNAc-PP-Dol to produce GlcNAc2-PP-Dol. This reaction is catalyzed by a glycosyltransferase (GTase) that consists of two subunits, Alg13 and Alg14 (Fig. 109.1). Most of what we know about this UDP-GlcNAc GTase comes from studies in yeast, in which both subunits are essential for viability. Alg13 and Alg14 are highly conserved in virtually all eukaryotes, from yeast to man, so insights from yeast are likely to be applicable to humans.


Endoplasmic Reticulum Endoplasmic Reticulum Membrane Endoplasmic Reticulum Lumen ALG14 Gene Alg13 Protein 


  1. Averbeck N, Gao XD, Nishimura SI, Dean N (2008) Alg13p, the catalytic subunit of the endoplasmic reticulum UDP-GlcNAc glycosyltransferase, is a target for proteasomal degradation. Mol Biol Cell 19:2169–2178PubMedCentralPubMedCrossRefGoogle Scholar
  2. Bickel T, Lehle L, Schwarz M, Aebi M, Jakob CA (2005) Biosynthesis of lipid-linked oligosaccharides in Saccharomyces cerevisiae. J Biol Chem 280:34500–34506PubMedCrossRefGoogle Scholar
  3. Bourne Y, Henrissat B (2001) Glycoside hydrolases and glycosyltransferases: families and functional modules. Curr Opin Struct Biol 11(5):593–600PubMedCrossRefGoogle Scholar
  4. Chantret I, Dancourt J, Barbat A, Moore SHE (2005) Two proteins homologous to the N- and C-terminal domains of the bacterial glycosyltransferase Murg are required for the second step of dolichyl-linked oligosaccharide synthesis in Saccharomyces cerevisiae. J Biol Chem 280:9236–9242PubMedCrossRefGoogle Scholar
  5. Chen W, Lennarz WJ (1977) Metabolism of lipid-linked N-acetylglucosamine intermediates. J Biol Chem 252:3473–3479PubMedGoogle Scholar
  6. Gao XD, Tachikawa H, Sato T, Jigami Y, Dean N (2005) 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. J Biol Chem 280:36254–36262PubMedCrossRefGoogle Scholar
  7. Gao XD, Moriyama S, Miura N, Dean N, Nishimura SI (2008) Interaction between the C termini of Alg13 and Alg14 mediates formation of the active UDP-N-acetylglucosamine transferase complex. J Biol Chem 283:32534–32541PubMedCrossRefGoogle Scholar
  8. Ha S, Walker D, Shi Y, Walker S (2000) The 1.9 A crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis. Protein Sci 9:1045–1052PubMedCrossRefGoogle Scholar
  9. Hu Y, Chen L, Ha S, Gross B, Falcone B, Walker D, Mokhtarzadeh M, Walker S (2003) Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases. Proc Natl Acad Sci USA 100(3):845–9PubMedCrossRefGoogle Scholar
  10. Heifetz A, Elbein AD (1977) Solubilization and properties of mannose and N-acetylglucosamine transferase involved in formation of polyprenyl-sugar intermediates. J Biol Chem 252:3057–3063PubMedGoogle Scholar
  11. Helenius A, Aebi M (2004) Roles of N- linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73:1019–49, ReviewPubMedCrossRefGoogle Scholar
  12. Kaushal GP, Elbein AD (1986) Purification and properties of UDP-GlcNAc: dolichyl-pyrophosphoryl-GlcNAc GlcNAc transferase from mung bean seedling. Plant Physiol 81:1086–1091PubMedCentralPubMedCrossRefGoogle Scholar
  13. Kelleher DJ, Gilmore R (2006) An evolving view of the eukaryotic oligosaccharyltransferase. Glycobiology 16(4):47R–62R, ReviewPubMedCrossRefGoogle Scholar
  14. Leloir LF, Staneloni RJ, Carminatti H, Behrens NH (1973) The biosynthesis of a N, N’-diaccetylchitobiose containing lipid by liver microsomes. Biochem Biophys Res Commun 52:1285–1292PubMedCrossRefGoogle Scholar
  15. Lu JS, Takahashi T, Ohoka A, Nakajima KI, Hashimot R, Miura N, Tachikawa H, Gao XD (2012) Alg14 organizes the formation of a multiglycosyltransferase complex involved in initiation of lipid-linked oligosaccharide biosynthesis. Glycobiology 22:504–516PubMedCrossRefGoogle Scholar
  16. Mengin-Lecreulx D, Texier L, Rousseau M, van Heijenoort J (1991) The murG gene of Escherichia coli codes for the UDP-N-acetylglucosamine: N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase involved in the membrane steps of peptidoglycan synthesis. J Bacteriol 173(15):4625–36PubMedCentralPubMedGoogle Scholar
  17. McLachlan KR, Krag SS (1994) Three enzymes involved in oligosaccharide-lipid assembly in Chinese hamster ovary cells differ in lipid substrate preference. J Lipid Res 35(10):1861–18168PubMedGoogle Scholar
  18. Noffz C, Keppler-Ross S, Dean N (2009) Hetero-oligomeric interactions between early glycosyltransferases of the dolichol cycle. Glycobiology 19:472–478PubMedCrossRefGoogle Scholar
  19. Sharma CB, Lehle L, Tanner W (1982) Solubilization and characterization of the initial enzymes of the dolichol pathway from yeast. Eur J Biochem 126:319–325PubMedCrossRefGoogle Scholar
  20. Tai VWF, O'Reilly MK, Imperiali B (2001) Substrate specificity of N-acetylglucosaminyl (diphosphodolichol)N-acetylglucosaminyl transferase, a key enzyme in the dolichol pathway. Bioorg Med Chem 9:1133–1140PubMedCrossRefGoogle Scholar
  21. Timal S, Hoischen A, Lehle L, Adamowicz M, Huijben K, Sykut-Cegielska J, Paprocka J, Jamroz E, Spronsen FJV, Körner C, Gilissen C, Rodenburg RJ, Eidhof I, Heuvel LVD, Thiel C, Wevers RA, Morava E, Veltman J, Lefeber DJ (2012) Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing. Hum Mol Genet 21:4151–4161PubMedCrossRefGoogle Scholar
  22. Wang X, Weldeghiorghis T, Zhang GF, Imperiali B, Prestegard JH (2008) Solution structure of Alg13: The sugar donor subunit of a yeast N-acetylglucosamine transferase. Structure 16:965–975PubMedCentralPubMedCrossRefGoogle Scholar
  23. Weerapana E, Imperiali B (2006) Asparagine-linked protein glycosylation: from eukaryotic to prokaryotic systems. Glycobiology 16(6):91R–101R, ReviewPubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of Biochemistry and Cell Biology, Stony Brook UniversityStony BrookUSA
  2. 2.The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of EducationSchool of Biotechnology, Jiangnan UniversityWuxiChina

Personalised recommendations