Protein O-Linked-Mannose Beta-1,2-N-Acetylglucosaminyltransferase 1 (POMGNT1)

  • Hiroshi Manya
  • Tamao Endo
Reference work entry


The O-mannosyl glycan is a type of O-glycan in which the reducing terminal mannose is attached to the hydroxyl group of serine (Ser) and threonine (Thr) residues. We demonstrated that the major glycans of α-dystroglycan (α-DG) include O-mannosyl glycan and determined the main structure of O-mannosyl glycan, Siaα2-3Galβ1-4GlcNAcβ1-2Man (Chiba et al. 1997). Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the transfer of GlcNAc from UDP-GlcNAc to O-mannose of glycoproteins. The human POMGnT1 gene was cloned from a cDNA sequence homologous to human GnT-I (UDP-GlcNAc: α-3-d-mannoside β1,2-N-acetylglucosaminyltransferase I) (Yoshida et al. 2001). POMGnT1 is responsible for muscle-eye-brain disease (MEB), which is a congenital muscular dystrophy with brain malformation caused by abnormal O-mannosylation of α-DG, the so-called α-dystroglycanopathy (Yoshida et al. 2001) (Fig. 38.1).


Muscular Dystrophy Membrane Fraction Acceptor Substrate Brain Malformation Congenital Muscular Dystrophy 
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  1. Akasaka-Manya K, Manya H, Mizuno M, Inazu T, Endo T (2011) Effects of length and amino acid sequence of O-mannosyl peptides on substrate specificity of protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1). Biochem Biophys Res Commun 410:632–636PubMedCrossRefGoogle Scholar
  2. 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
  3. Endo T (2007) Dystroglycan glycosylation and its role in alpha-dystroglycanopathies. Acta Myol 26:165–170PubMedCentralPubMedGoogle Scholar
  4. Endo T, Manya H (2006) Defect in glycosylation that causes muscular dystrophy. Methods Enzymol 417:137–152PubMedCrossRefGoogle Scholar
  5. Endo T, Manya H, Seta N, Guicheney P (2010) POMGnT1, POMT1, and POMT2 mutations in congenital muscular dystrophies. Methods Enzymol 479:343–352PubMedCrossRefGoogle Scholar
  6. Liu J, Ball SL, Yang Y, Mei P, Zhang L, Shi H, Kaminski HJ, Lemmon VP, Hu H (2006) A genetic model for muscle–eye–brain disease in mice lacking protein O-mannose 1,2-Nacetylglucosaminyltransferase (POMGnT1). Mech Dev 123:228–240PubMedCrossRefGoogle Scholar
  7. Manya H, Bouchet C, Yanagisawa A, Vuillaumier-Barrot S, Quijano-Roy S, Suzuki Y, Maugenre S, Richard P, Inazu T, Merlini L, Romero NB, Leturcq F, Bezier I, Topaloglu H, Estournet B, Seta N, Endo T, Guicheney P (2008) Protein O-mannosyltransferase activities in lymphoblasts from patients with alpha-dystroglycanopathies. Neuromuscul Disord 18:45–51PubMedCrossRefGoogle Scholar
  8. Manya H, Sakai K, Kobayashi K, Taniguchi K, Kawakita M, Toda T, Endo T (2003) Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease. Biochem Biophys Res Commun 306:93–97PubMedCrossRefGoogle Scholar
  9. Miyagoe-Suzuki Y, Masubuchi N, Miyamoto K, Wada MR, Yuasa S, Saito F, Matsumura K, Kanesaki H, Kudo A, Manya H, Endo T, Takeda S (2009) Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro. Mech Dev 126:107–116PubMedCrossRefGoogle Scholar
  10. Mizuno M, Osumi K, Hirose Y, Manya H, Endo T (2012) Synthesis of glycopeptide containing 6-O-Phosphorylated mannose for an α-Dystroglycan/Laminin Interaction Study, Pept Sci 2011 (Proceedings of the 48th Japanese peptide Symposium), 127–130Google Scholar
  11. Moore CJ, Goh HT, Hewitt JE (2008) Genes required for functional glycosylation of dystroglycan are conserved in zebrafish. Genomics 92:159–167PubMedCrossRefGoogle Scholar
  12. Tachikawa M, Kanagawa M, Yu CC, Kobayashi K, Toda T (2012) Mislocalization of fukutin protein by disease-causing missense mutations can be rescued with treatments directed at folding amelioration. J Biol Chem 287:8398–8406PubMedCrossRefGoogle Scholar
  13. 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
  14. Xiong H, Kobayashi K, Tachikawa M, Manya H, Takeda S, Chiyonobu T, Fujikake N, Wang F, Nishimoto A, Morris GE, Nagai Y, Kanagawa M, Endo T, Toda T (2006) Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of alpha-dystroglycan. Biochem Biophys Res Commun 350:935–941PubMedCrossRefGoogle Scholar
  15. 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
  16. 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
  17. Zhang W, Vajsar J, Cao P, Breningstall G, Diesen C, Dobyns W, Herrmann R, Lehesjoki AE, Steinbrecher A, Talim B, Toda T, Topaloglu H, Voit T, Schachter H (2003) Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available reagents. Clin Biochem 36:339–344PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Molecular GlycobiologyTokyo Metropolitan Geriatric Hospital and Institute of GerontologyItabashi-kuJapan

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