Mannosyl (Alpha-1,6-)-Glycoprotein Beta-1,6-N-Acetyl-Glucosaminyltransferase, Isozyme B (MGAT5B)

  • Kei-ichiro Inamori
  • Michael Pierce
  • Naoyuki Taniguchi
Reference work entry


Protein O-mannosylation is an essential modification in mammals, and the biological significance of the modification has been emerging as it has been linked with muscular dystrophy and other biological processes. In the brain, approximately 30 % of all O-linked glycans are O-mannose-initiated structures. O-Mannosylation is initiated by the addition of α-linked mannose to specific Ser and Thr residues by protein O-mannosyltransferase 1 (POMT1) and POMT 2, and subsequently a GlcNAc residue is added by protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) to form the GlcNAc-β1,2-Man-α-O-Ser/Thr structure. A brain-specific β1,6-N-acetylglucosaminyltransferase IX (GnT-IX, GnT-VB, or MGAT5B) was cloned as a homolog of N-acetylglucosaminyltransferase V (GnT-V). GnT-V is ubiquitously expressed and involved in a variety of biological and pathological processes such as cytokine and growth factor receptor signaling. GnT-IX catalyzes the transfer of GlcNAc to the 6-OH position of α-linked mannose in GlcNAc-β1,2-Man-α sequence which is found in both N-glycans and O-mannosyl glycans. The ability of GnT-IX to transfer GlcNAc in β1,6 linkage to mannose initially identified using agalacto biantennary N-linked oligosaccharide substrate. After that time, GnT-IX was shown to transfer GlcNAc in β1,6 linkage towards the mannose in GlcNAc-β1,2-Man-α-O-Ser, as well to a synthetic peptide bearing the O-mannosyl disaccharide. It is now known that GnT-IX does not act on N-glycans in vivo but is responsible for the formation of β1,6GlcNAc-branch on O-mannosyl glycans in the brain. In addition, lower expression of GnT-IX was also observed in testis in mice and human.


Muscular Dystrophy Acceptor Substrate Polysialic Acid Congenital Muscular Dystrophy GlcNAc Residue 


  1. Abbott KL, Troupe K, Lee I, Pierce M (2006) Integrin-dependent neuroblastoma cell adhesion and migration on laminin is regulated by expression levels of two enzymes in the O-mannosyl-linked glycosylation pathway, PomGnT1 and GnT-Vb. Exp Cell Res 312:2837–2850PubMedCrossRefGoogle Scholar
  2. Abbott KL, Matthews RT, Pierce M (2008) Receptor tyrosine phosphatase beta (RPTPbeta) activity and signaling are attenuated by glycosylation and subsequent cell surface galectin-1 binding. J Biol Chem 283:33026–33035PubMedCrossRefGoogle Scholar
  3. Alvarez-Manilla G, Troupe K, Fleming M, Martinez-Uribe E, Pierce M (2010) Comparison of the substrate specificities and catalytic properties of the sister N-acetylglucosaminyltransferases, GnT-V and GnT-Vb (IX). Glycobiology 20:166–174PubMedCrossRefGoogle Scholar
  4. Barresi R, Campbell KP (2006) Dystroglycan: from biosynthesis to pathogenesis of human disease. J Cell Sci 119:199–207PubMedCrossRefGoogle Scholar
  5. Chai W, Yuen CT, Kogelberg H, Carruthers RA, Margolis RU, Feizi T, Lawson AM (1999) High prevalence of 2-mono- and 2,6-di-substituted manol-terminating sequences among O-glycans released from brain glycopeptides by reductive alkaline hydrolysis. Eur J Biochem 263:879–888PubMedCrossRefGoogle Scholar
  6. Chiba A, Matsumura K, Yamada H, Inazu T, Shimizu T, Kusunoki S, Kanazawa I, Kobata A, Endo T (1997) Structures of sialylated O-linked oligosaccharides of bovine peripheral nerve alpha-dystroglycan. The role of a novel O-mannosyl-type oligosaccharide in the binding of alpha-dystroglycan with laminin. J Biol Chem 272:2156–2162PubMedCrossRefGoogle Scholar
  7. Gu J, Taniguchi N (2008) Potential N-glycan in cell adhesion and migration as either a positive or negative regulator. Cell Adh Migr 2:243–245PubMedCrossRefGoogle Scholar
  8. Guo HB, Lee I, Kamar M, Akiyama SK, Pierce M (2002) Aberrant N-Glycosylation of β1 integrin causes reduced α5β1 integrin clustering and stimulates cell migration. Cancer Res 62:6837PubMedGoogle Scholar
  9. Harroch S, Furtado GC, Brueck W, Rosenbluth J, Lafaille J, Chao M, Buxbaum JD, Schlessinger J (2002) A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions. Nat Genet 32:411–414PubMedCrossRefGoogle Scholar
  10. Inamori K, Endo T, Ide Y, Fujii S, Gu J, Honke K, Taniguchi N (2003) Molecular cloning and characterization of human GnT-IX, a novel beta1,6-N-acetylglucosaminyltransferase that is specifically expressed in the brain. J Biol Chem 278:43102–43109PubMedCrossRefGoogle Scholar
  11. Inamori K, Endo T, Gu J, Matsuo I, Ito Y, Fujii S, Iwasaki H, Narimatsu H, Miyoshi E, Honke K, Taniguchi N (2004) N-Acetylglucosaminyltransferase IX acts on the GlcNAc beta 1,2-Man alpha 1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan. J Biol Chem 279:2337–2340PubMedCrossRefGoogle Scholar
  12. Inamori K, Mita S, Gu J, Mizuno-Horikawa Y, Miyoshi E, Dennis JW, Taniguchi N (2006) Demonstration of the expression and the enzymatic activity of N-acetylglucosaminyltransferase IX in the mouse brain. Biochim Biophys Acta 1760:678–684PubMedCrossRefGoogle Scholar
  13. Kaneko M, Alvarez-Manilla G, Kamar M, Lee I, Lee JK, Troupe K, Zhang W, Osawa M, Pierce M (2003) A novel beta(1,6)-N-acetylglucosaminyltransferase V (GnT-VB)(1). FEBS Lett 554:515–519PubMedCrossRefGoogle Scholar
  14. Kanekiyo K, Inamori K, Kitazume S, Sato K, Maeda J, Higuchi M, Kizuka Y, Korekane H, Matsuo I, Honke K, Taniguchi N (2013) Loss of branched O-mannosyl glycans in astrocytes accelerates remyelination. J Neurosci 33:10037–10047PubMedCrossRefGoogle Scholar
  15. Kizuka Y, Kitazume S, Yoshida M, Taniguchi N (2011) Brain-specific expression of N-acetylglucosaminyltransferase IX (GnT-IX) is regulated by epigenetic histone modifications. J Biol Chem 286:31875–31884PubMedCrossRefGoogle Scholar
  16. Lange T, Ullrich S, Muller I, Nentwich MF, Stubke K, Feldhaus S, Knies C, Hellwinkel OJ, Vessella RL, Abramjuk C, Anders M, Schroder-Schwarz J, Schlomm T, Huland H, Sauter G, Schumacher U (2012) Human prostate cancer in a clinically relevant xenograft mouse model: identification of beta(1,6)-branched oligosaccharides as a marker of tumor progression. Clin Cancer Res 18:1364–1373PubMedCrossRefGoogle Scholar
  17. Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, Demetriou M, Dennis JW (2007) Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129:123–134PubMedCrossRefGoogle Scholar
  18. Lee JK, Matthews RT, Lim JM, Swanier K, Wells L, Pierce JM (2012) Developmental expression of the neuron-specific N-Acetylglucosaminyltransferase Vb (GnT-Vb/IX) and identification of its in vivo glycan products in comparison with those of its paralog, GnT-V. J Biol Chem 287:28526–28536PubMedCrossRefGoogle Scholar
  19. Lommel M, Strahl S (2009) Protein O-mannosylation: conserved from bacteria to humans. Glycobiology 19:816–828PubMedCrossRefGoogle Scholar
  20. Manya H, Chiba A, Yoshida A, Wang X, Chiba Y, Jigami Y, Margolis RU, Endo T (2004) Demonstration of mammalian protein O-mannosyltransferase activity: coexpression of POMT1 and POMT2 required for enzymatic activity. Proc Natl Acad Sci USA 101:500–505PubMedCrossRefGoogle Scholar
  21. Partridge EA, Le Roy C, Di Guglielmo GM, Pawling J, Cheung P, Granovsky M, Nabi IR, Wrana JL, Dennis JW (2004) Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306:120–124PubMedCrossRefGoogle Scholar
  22. Smalheiser NR, Haslam SM, Sutton-Smith M, Morris HR, Dell A (1998) Structural analysis of sequences O-linked to mannose reveals a novel Lewis X structure in cranin (dystroglycan) purified from sheep brain. J Biol Chem 273:23698–23703PubMedCrossRefGoogle Scholar
  23. Stalnaker SH, Aoki K, Lim JM, Porterfield M, Liu M, Satz JS, Buskirk S, Xiong Y, Zhang P, Campbell KP, Hu H, Live D, Tiemeyer M, Wells L (2011a) Glycomic analyses of mouse models of congenital muscular dystrophy. J Biol Chem 286:21180–21190PubMedCrossRefGoogle Scholar
  24. Stalnaker SH, Stuart R, Wells L (2011b) Mammalian O-mannosylation: unsolved questions of structure/function. Curr Opin Struct Biol 21:603–609PubMedCentralPubMedCrossRefGoogle Scholar
  25. Takahashi S, Sasaki T, Manya H, Chiba Y, Yoshida A, Mizuno M, Ishida H, Ito F, Inazu T, Kotani N, Takasaki S, Takeuchi M, Endo T (2001) A new beta-1,2-N-acetylglucosaminyltransferase that may play a role in the biosynthesis of mammalian O-mannosyl glycans. Glycobiology 11:37–45PubMedCrossRefGoogle Scholar
  26. Taniguchi N, Nishikawa A, Fujii S, Gu JG (1989) Glycosyltransferase assays using pyridylaminated acceptors: N-acetylglucosaminyltransferase III, IV, and V. Methods Enzymol 179:397–408PubMedCrossRefGoogle Scholar
  27. Yoshida A, Kobayashi K, Manya H, Taniguchi K, Kano H, Mizuno M, Inazu T, Mitsuhashi H, Takahashi S, Takeuchi M, Herrmann R, Straub V, Talim B, Voit T, Topaloglu H, Toda T, Endo T (2001) Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell 1:717–724PubMedCrossRefGoogle Scholar
  28. Yoshida-Moriguchi T, Yu L, Stalnaker SH, Davis S, Kunz S, Madson M, Oldstone MB, Schachter H, Wells L, Campbell KP (2010) O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding. Science 327:88–92PubMedCentralPubMedCrossRefGoogle Scholar
  29. Yuen CT, Chai W, Loveless RW, Lawson AM, Margolis RU, Feizi T (1997) Brain contains HNK-1 immunoreactive O-glycans of the sulfoglucuronyl lactosamine series that terminate in 2-linked or 2,6-linked hexose (mannose). J Biol Chem 272:8924–8931PubMedCrossRefGoogle Scholar
  30. Zhang W, Betel D, Schachter H (2002) Cloning and expression of a novel UDP-GlcNAc:alpha-D-mannoside beta1,2-N-acetylglucosaminyltransferase homologous to UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I. Biochem J 361:153–162PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Kei-ichiro Inamori
    • 1
  • Michael Pierce
    • 2
  • Naoyuki Taniguchi
    • 3
  1. 1.Division of Glycopathology, Institute of Molecular Biomembrane and GlycobiologyTohoku Pharmaceutical UniversitySendaiJapan
  2. 2.Department of Biochemistry and Molecular Biology, Complex Carbohydrate Research CenterThe University of GeorgiaAthensUSA
  3. 3.Disease Glycomics Team, Systems Glycobiology Research GroupRIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKENWakoJapan

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