Beta-1,3-Galactosyl-O-Glycosyl-Glycoprotein Beta-1,6-N-Acetylglucosaminyltransferase 3 (GCNT3)

  • Jiunn-Chern (Gene) Yeh
  • Minoru Fukuda
Reference work entry


GCNT3 (C2GnT2/M) is a unique glycosyltransferase in having multiple enzymatic activities (Yeh et al. 1999; Schwientek et al. 1999). It was shown to have core2 and core4 branching as well as I branching, mainly dIGnT, enzymatic activities. GCNT3 is the only glycosyltransferase identified up-to-date to possess core4GnT activity. This is in line with the observations that the presence of core4GnT activity is always associated with core2GnT activity (Brockhausen et al. 1986; Ropp et al. 1991; Yang et al. 1994; Vavasseur et al. 1995). GCNT3 is highly expressed in mucin-producing tissues (Yeh et al. 1999; Schwientek et al. 1999), indicating a pivotal role in mucosal functions.


Dextran Sodium Sulfate Mucosal Function Multiple Enzymatic Activity Sole Enzyme Triple Knockout Mouse 
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  1. An G, Wei B, Xia B, McDaniel JM, Ju T, Cummings RD, Braun J, Xia L (2007) Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J Exp Med 204(6):1417–1429PubMedCentralPubMedCrossRefGoogle Scholar
  2. Aoki D, Lee N, Yamaguchi N, Dubois C, Fukuda MN (1992) Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain. Proc Natl Acad Sci 89(10):4319–4323PubMedCrossRefGoogle Scholar
  3. Beum PV, Bastola DR, Cheng PW (2003) Mucin biosynthesis: epidermal growth factor downregulates core 2 enzymes in a human airway adenocarcinoma cell line. Am J Respir Cell Mol Biol 29(1):48–56PubMedCrossRefGoogle Scholar
  4. Beum PV, Basma H, Bastola DR, Cheng PW (2005) Mucin biosynthesis: upregulation of core 2 beta 1,6 N-acetylglucosaminyltransferase by retinoic acid and Th2 cytokines in a human airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol 288(1):L116–L124PubMedCrossRefGoogle Scholar
  5. Bierhuizen MF, Fukuda M (1992) Expression cloning of a cDNA encoding UDP-GlcNAc: Gal beta 1-3-GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase by gene transfer into CHO cells expressing polyoma large tumor antigen. Proc Natl Acad Sci USA 89:9326–9330PubMedCrossRefGoogle Scholar
  6. Bierhuizen MF, Mattei MG, Fukuda M (1993) Expression of the developmental I antigen by a cloned human cDNA encoding a member of a beta-1,6-N-acetylglucosaminyltransferase gene family. Genes Dev 7(3):468–478PubMedCrossRefGoogle Scholar
  7. Brockhausen I, Matta KL, Orr J, Schachter H, Koenderman AH, van den Eijnden DH (1986) Mucin synthesis. Conversion of R1-beta 1-3Gal-R2 to R1-beta 1-3(GlcNAc beta 1-6)Gal-R2 and of R1-beta 1-3GalNAc-R2 to R1-beta 1-3(GlcNAc beta 1-6)GalNAc-R2 by a beta 6-N-acetylglucosaminyltransferase in pig gastric mucosa. Eur J Biochem 157(3):463–474PubMedCrossRefGoogle Scholar
  8. Chen GY, Muramatsu H, Kondo M, Kurosawa N, Miyake Y, Takeda N, Muramatsu T (2005) Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice. Mol Cell Biol 25(17):7828–7838PubMedCentralPubMedCrossRefGoogle Scholar
  9. Cheng PW, Radhakrishnan P (2011) Mucin O-Glycan branching enzymes: structure, function, and gene regulation. Adv Exp Med Biol 705:465–492PubMedCrossRefGoogle Scholar
  10. Choi KH, Osorio FA, Cheng PW (2004) Mucin biosynthesis: bovine C2GnT-M gene, tissue-specific expression, and herpes virus-4-homologue. Am J Respir Cell Mol Biol 30(5):710–719PubMedCrossRefGoogle Scholar
  11. Ellies LG, Tsuboi S, Petryniak B, Lowe JB, Fukuda M, Marth JD (1998) Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation. Immunity 9(6):881–890PubMedCrossRefGoogle Scholar
  12. Gu J, Nishikawa A, Fujii S, Gasa S, Taniguchi N (1992) Biosynthesis of blood group I and i antigens in rat tissues. Identification of a novel beta 1-6-N-acetylglucosaminyltransferase. J Biol Chem 267:2994–2999PubMedGoogle Scholar
  13. Hashimoto M, Tan S, Mori N, Cheng H, Cheng PW (2007) Mucin biosynthesis: molecular cloning and expression of mouse mucus-type core 2 beta1,6 N-acetylglucosaminyltransferase. Glycobiology 17(9):994–1006PubMedCrossRefGoogle Scholar
  14. Huang MC, Chen HY, Huang HC, Huang J, Liang JT, Shen TL, Lin NY, Ho CC, Cho IM, Hsu SM (2006) C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells. Oncogene 25(23):3267–3276PubMedCrossRefGoogle Scholar
  15. Ismail MN, Stone EL, Panico M, Lee SH, Luu Y, Ramirez K, Ho SB, Fukuda M, Marth JD, Haslam SM, Dell A (2011) High-sensitivity O-glycomic analysis of mice deficient in core 2 {beta}1,6-N-acetylglucosaminyltransferases. Glycobiology 21(1):82–98PubMedCrossRefGoogle Scholar
  16. Ishibashi Y, Inouye Y, Okano T, Taniguchi A (2005) Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line. Glycoconj J 22:53–62. doi:10.1007/s10719-005-0292-7PubMedCrossRefGoogle Scholar
  17. Korekane H, Taguchi T, Sakamoto Y, Honke K, Dohmae N, Salminen H, Toivonen S, Helin J, Takio K, Renkonen O, Taniguchi N (2003) Purification and cDNA cloning of UDP-GlcNAc: GlcNAcbeta1-3Galbeta1-4Glc(NAc)-R [GlcNAc to Gal]beta1,6N-acetylglucosaminyltransferase from rat small intestine: a major carrier of dIGnT activity in rat small intestine. Glycobiology 13:387–400PubMedCrossRefGoogle Scholar
  18. Lee SH, Yu SY, Nakayama J, Khoo KH, Stone EL, Fukuda MN, Marth JD, Fukuda M (2010) Core2 O-glycan structure is essential for the cell surface expression of sucrase isomaltase and dipeptidyl peptidase-IV during intestinal cell differentiation. J Biol Chem 285(48):37683–37692PubMedCrossRefGoogle Scholar
  19. Markine-Goriaynoff N, Georgin JP, Goltz M, Zimmermann W, Broll H, Wamwayi HM, Pastoret PP, Sharp PM, Vanderplasschen A (2003) The core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin encoded by bovine herpesvirus 4 was acquired from an ancestor of the African buffalo. J Virol 77(3):1784–1792PubMedCentralPubMedCrossRefGoogle Scholar
  20. Markine-Goriaynoff N, Gillet L, Karlsen OA, Haarr L, Minner F, Pastoret PP, Fukuda M, Vanderplasschen A (2004) The core 2 beta-1,6-N-acetylglucosaminyltransferase-M encoded by bovine herpesvirus 4 is not essential for virus replication despite contributing to post-translational modifications of structural proteins. J Gen Virol 85:355–367PubMedCrossRefGoogle Scholar
  21. McBride DS, Brockhausen I, Kan FW (2005) Detection of glycosyltransferases in the golden hamster (Mesocricetus auratus) oviduct and evidence for the regulation of O-glycan biosynthesis during the estrous cycle. Biochim Biophys Acta 1721(1–3):107–115PubMedCrossRefGoogle Scholar
  22. Mullaly SC, Oudhoff MJ, Min PH, Burrows K, Antignano F, Rattray DG, Chenery A, McNagny KM, Ziltener HJ, Zaph C (2013) Requirement for core 2 o-glycans for optimal resistance to helminth infection. PLoS One 8(3):e60124PubMedCentralPubMedCrossRefGoogle Scholar
  23. Pak JE, Arnoux P, Zhou S, Sivarajah P, Satkunarajah M, Xing X, Rini JM (2006) X-ray crystal structure of leukocyte type core 2 beta1,6-N-acetylglucosaminyltransferase. Evidence for a convergence of metal ion-independent glycosyltransferase mechanism. J Biol Chem 281:26693–26701PubMedCrossRefGoogle Scholar
  24. Pak JE, Arnoux P, Zhou S, Sivarajah P, Satkunarajah M, Xing X, Rini JM (2011) Structural and mechanistic characterization of leukocyte-type core 2 β1,6-N-acetylglucosaminyltransferase: a metal-ion-independent GT-A glycosyltransferase. J Mol Biol 414:798–811PubMedCrossRefGoogle Scholar
  25. Radhakrishnan P, Beum PV, Tan S, Cheng PW (2007) Butyrate induces sLex synthesis by stimulation of selective glycosyltransferase genes. Biochem Biophys Res Commun 359(3):457–462PubMedCentralPubMedCrossRefGoogle Scholar
  26. Ropp PA, Little MR, Cheng PW (1991) Mucin biosynthesis: purification and characterization of a mucin β6 N-acetylglucosaminyltransferase. J Biol Chem 266(35):23863–23871PubMedGoogle Scholar
  27. Schachter H, Brockhausen I (1992) Glycoconjugates: composition, structure, and function. In: Allen HJ, Kisailus EC (eds), 1st edn. Marcel New York, pp 263–332Google Scholar
  28. Schwientek T, Nomoto M, Levery SB, Merkx G, van Kessel AG, Bennett EP, Hollingsworth MA, Clausen H (1999) Control of O-glycan branch formation: molecular cloning of human cDNA encoding a novel beta-1,6-N-acetylglucosaminyltransferase forming core 2 and core 4. J Biol Chem 274:4504–4512PubMedCrossRefGoogle Scholar
  29. Schwientek T, Yeh JC, Levery SB, Keck B, Merkx G, van Kessel AG, Fukuda M, Clausen H (2000) Control of O-glycan branch formation. Molecular cloning and characterization of a novel thymus-associated core 2 beta1, 6-n-acetylglucosaminyltransferase. J Biol Chem 275:11106–11113PubMedCrossRefGoogle Scholar
  30. Shafi R, Iyer SP, Ellies LG, O'Donnell N, Marek KW, Chui D, Hart GW, Marth JD (2000) The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. Proc Natl Acad Sci USA 97(11):5735–5739PubMedCrossRefGoogle Scholar
  31. Singh J, Khan GA, Kinarsky L, Cheng H, Wilken J, Choi KH, Bedows E, Sherman S, Cheng PW (2004) Identification of disulfide bonds among the nine core 2 N-acetylglucosaminyltransferase-M cysteines conserved in the mucin beta6-N-acetylglucosaminyltransferase family. J Biol Chem 279:38969–38977PubMedCrossRefGoogle Scholar
  32. Stone EL, Ismail MN, Lee SH, Luu Y, Ramirez K, Haslam SM, Ho SB, Dell A, Fukuda M, Marth JD (2009) Glycosyltransferase function in core 2-type protein O glycosylation. Mol Cell Biol 29:3770–3782PubMedCentralPubMedCrossRefGoogle Scholar
  33. Tan Sand Cheng PW (2007) Mucin biosynthesis: identification of the cis-regulatory elements of human C2GnT-M gene. Am J Respir Cell Mol Biol 36(6):737–745CrossRefGoogle Scholar
  34. Toki D, Sarkar M, Yip B, Reck F, Joziasse D, Fukuda M, Schachter H, Brockhausen I (1997) Expression of stable human O-glycan core 2 beta-1,6-N-acetylglucosaminyltransferase in Sf9 insect cells. Biochem J 325:63–69PubMedGoogle Scholar
  35. Vanderplasschen A, Markine-Goriaynoff N, Lomonte P, Suzuki M, Hiraoka N, Yeh JC, Bureau F, Willems L, Thiry E, Fukuda M, Pastoret PP (2000) A multipotential beta -1,6-N-acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4. Proc Natl Acad Sci USA 97(11):5756–5761PubMedCentralPubMedCrossRefGoogle Scholar
  36. Vavasseur F, Yang JM, Dole K, Paulsen H, Brockhausen I (1995) Synthesis of O-glycan core 3: characterization of UDP-GlcNAc: GalNAc-R beta 3-N-acetyl-glucosaminyltransferase activity from colonic mucosal tissues and lack of the activity in human cancer cell lines. Glycobiology 5(3):351–357PubMedCrossRefGoogle Scholar
  37. Yanagihara K, Seki M, Cheng PW (2001) Lipopolysaccharide induces mucus cell metaplasia in mouse lung. Am J Respir Cell Mol Biol 24(1):66–73PubMedCrossRefGoogle Scholar
  38. Yang JM, Byrd JC, Siddiki BB, Chung YS, Okuno M, Sowa M, Kim YS, Matta KL, Brockhausen I (1994) Alterations of O-glycan biosynthesis in human colon cancer tissues. Glycobiology 4(6):873–884PubMedCrossRefGoogle Scholar
  39. Yeh JC, Ong E, Fukuda M (1999) Molecular cloning and expression of a novel beta-1, 6-N-acetylglucosaminyltransferase that forms core 2, core 4, and I branches. J Biol Chem 274(5):3215–3221PubMedCrossRefGoogle Scholar
  40. Yeh JC, Hiraoka N, Petryniak B, Nakayama J, Ellies LG, Rabuka D, Hindsgaul O, Marth JD, Lowe JB, Fukuda M (2001) Novel sulfated lymphocyte homing receptors and their control by a core 1 extension β1,3-N-acetylglucosaminyltransferase. Cell 105:957–969PubMedCrossRefGoogle Scholar
  41. Yen TY, Macher BA, Bryson S, Chang X, Tvaroska I, Tse R, Takeshita S, Lew AM, Datti A (2003) Highly conserved cysteines of mouse core 2 beta1,6-N-acetylglucosaminyltransferase I form a network of disulfide bonds and include a thiol that affects enzyme activity. J Biol Chem 278(46):45864–45881PubMedCrossRefGoogle Scholar
  42. Yu LC, Twu YC, Chou ML, Reid ME, Gray AR, Moulds JM, Chang CY, Lin M (2003) The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts. Blood 101(6):2081–2088PubMedCrossRefGoogle Scholar
  43. Zerfaoui M, Fukuda M, Langlet C, Mathieu S, Suzuki M, Lombardo D, El-Battari A (2002) The cytosolic and transmembrane domains of the beta 1,6 N-acetylglucosaminyltransferase (C2GnT) function as a cis to medial/Golgi-targeting determinant. Glycobiology 12(1):15–24PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Sanford-Burnham Medical Research InstituteLa JollaUSA
  2. 2.Tumor Microenvironment ProgramSanford-Burnham Medical Research InstituteLa JollaUSA

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