N-Acetyllactosaminide Beta-1,6-N-Acetylglucosaminyl-Transferase (GCNT2) (IGnT)

  • Minoru Fukuda
  • Misa Suzuki-Anekoji
Reference work entry


During the development, poly-N-acetyllactosamine in human erythrocytes changes from linear form, N-acetyllactosamine repeats (i-antigen), to branched form (I-antigen). This conversion takes place due to an appearance of N-acetyllactosaminide β-1,6-N-acetylglucosaminyltransferase (I enzyme, also called I-branching enzyme, or GCNT2), transferring N-acetylglucosamine to galactose residue of poly-N-acetyllactosamine. The presence of I-enzyme was assumed based on a structural change, which was described in (Fukuda et al. 1979, Fig. 33.1). These carbohydrate structure i/I antigens and adult patients with antibodies reacting against i antigen were recognized. Antigen in those patients exhibited coagulation of blood cells when exposed to low temperature that caused cold hemolytic anemia. By using these antibodies, Chinese hamster ovary (CHO) cells that was transfected with polyoma large T antigen was used for expression cloning of I enzyme. Upon cloning of I-branching enzyme, the amino acid sequence of I-branching enzyme was found to be highly homologous to β-1,6-N-acetylglucosaminyltransferase (GCNT1) (C2GnT-1), which forms core2 branch of O-glycans. C2GnT-1 enzyme transfers N-acetylglucosamine to GalNAc residue of Galβ1-3GalNAc-Ser/Thr in β-1.6 linkage. These studies established that the carbohydrate structure similar to each other has similar enzyme protein structure; thus, the concept of the gene family in glycosyltransferases was established.


Chinese Hamster Ovary Carbohydrate Structure Congenital Cataract Expression Cloning Breast Tumor Sample 
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  1. Bierhuizen MFA, Mattei M-G, Fukuda M (1993) Expression of the developmental I antigen by a cloned human cDNA encoding a member of a β-1.6-N-acetylglucosaminyltransferase gene family. Genes Dev 7:468–478PubMedCrossRefGoogle Scholar
  2. Borck G, Kakar N, Hoch J, Friedrich K, Freudenberg J, Nurnberg G, Yilmaz R, Daud S, Baloch DM, Nurnberg P, Oldenburg J, Ahmad J, Kubisch C (2012) An Alu repeat-mediated genomic GCNT2 deletion underlies congenital cataracts and adult I blood group. Hum Genet 131:209–216PubMedCrossRefGoogle Scholar
  3. Chen G-Y, Kurosawa N, Muramatsu T (2000) A novel variant form of murine β-1,6-N-acetylglucosaminyltransferase forming branches in poly-N-acetyllactosamines. Glycobiology 10:1001–1011PubMedCrossRefGoogle Scholar
  4. Chen G-Y, Muramatsu H, Kondo M, Kurosawa N, Miyake Y, Takeda N, Muramatsu T (2005) Abnormalities caused by carbohydrate alterations in Iβ6-N-acetylglucosaminyltransferase-deficient mice. Mol Cell Biol 25:7828–7838PubMedCentralPubMedCrossRefGoogle Scholar
  5. Fukuda M, Fukuda MN, Hakomori S (1979) Developmental change and genetic defect in the carbohydrate structure of band 3 glycoprotein of human erythrocyte membrane. J Biol Chem 254:3700–3703PubMedGoogle Scholar
  6. Fukuda M, Dell A, Oates JE, Fukuda MN (1984) Structure of branched lactosaminoglycan, the carbohydrate moiety of band 3 isolated from adult human erythrocytes. J Biol Chem 259:8260–8273PubMedGoogle Scholar
  7. Fukuda MN, Dell A, Oates JE, Fukuda M (1985) Embryonal lactosaminoglycan. The structure of branched lactosaminoglycans with novel disialosyl (sialyl α2,9 sialyl) terminals isolated from PA1 human embryonal carcinoma cells. J Biol Chem 260:6623–6631PubMedGoogle Scholar
  8. 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 β-1,6-N-acetylglucosaminyltransferase. J Biol Chem 267:2994–2999PubMedGoogle Scholar
  9. Leppanen A, Zhu Y, Maaheimo H, Helin J, Lehtonen E, Renkonen O (1998) Biosynthesis of branched polylactosaminoglycans. Embryonal carcinoma cells express midchain β1,6-N-acetylglucosaminyltransferase activity that generates branches to preformed linear backbones. J Biol Chem 273:17399–17405PubMedCrossRefGoogle Scholar
  10. Lin-Chu M, Broadberry RE, Okubo Y, Tanaka M (1991) The i phenotype and congenital cataracts among Chinese in Taiwan (Letter). Transfusion 31:676–677PubMedCrossRefGoogle Scholar
  11. Mattila P, Salminen H, Hirvas L, Niittymaki J, Salo H, Niemela R, Fukuda M, Renkonen O, Renkonen R (1998) The centrally acting b1,6N-acetylglucosaminyltransferase (GlcNAc to gal). Functional expression, purification, and acceptor specificity of a human enzyme involved in midchain branching of linear poly-N-acetyllactosamines. J Biol Chem 273:27633–27639PubMedCrossRefGoogle Scholar
  12. Marsh WL (1961) Anti-i: a cold antibody defining the Ii relationship in human red cells. Br J Haematol 7:200–209PubMedCrossRefGoogle Scholar
  13. Ogata H, Okubo Y, Akabane T (1979) Phenotype i associated with congenital cataract in Japanese. Transfusion 19:166–168PubMedCrossRefGoogle Scholar
  14. Piller F, Cartron JP, Maranduba A, Veyrieres A, Leroy Y, Fournet B (1984) Biosynthesis of blood group I antigens. Identification of a UDP-GlcNAc: GlcNAc b1-3Gal(-R) b1-6(GlcNAc to Gal) N-acetylglucosaminyltransferase in hog gastric mucosa. J Biol Chem 259:13385–13390PubMedGoogle Scholar
  15. Romans DG et al (1980) Monogamous bivalency of IgG antibodies. I. Deficiency of branched ABHI-active oligosaccharide chains on red cells of infants causes the weak antiglobulin reactions in hemolytic disease of the newborn due to ABO incompatibility. J Immunol 124(6):2807–2811PubMedGoogle Scholar
  16. Ropp PA, Little MR, Cheng PW (1991) Mucin biosynthesis: purification and characterization of a mucin b6 N-acetylglucosaminyltransferase. J Biol Chem 266:23863–23871PubMedGoogle Scholar
  17. Sakamoto Y, Taguchi T, Tano Y, Ogawa T, Leppanen A, Kinnunen M, Aitio O, Parmanne P, Renkonen O, Taniguchi N (1998) Purification and characterization of UDP-GlcNAc:Galβ1–4GlcNAcβ1–3*Galβ1–4Glc(NAc)-R(GlcNAc to *Gal) β1,6N-acetylglucosaminyltransferase from hog small intestine. J Bio Chem 273:27625–27632CrossRefGoogle Scholar
  18. 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 β1,6-N-acetylglucosaminyltransferase forming core 2 and core 4. J Biol Chem 274:4504–4512PubMedCrossRefGoogle Scholar
  19. Ujita M, McAuliffe J, Suzuki M, Hindsgaul O, Clausen H, Fkuda MN, Fukuda M (1999) Regulation of I-branched poly-N-acetyllactosamine synthesis. – Concerted actions by i-extension enzyme, I-branching enzyme, and b1,4-galactosyltransferase I. J Biol Chem 274:9296–9304PubMedCrossRefGoogle Scholar
  20. Watanabe K, Hakomori SI, Childs RA, Feizi T (1979) Characterization of a blood group I-active ganglioside. Structural requirements for I and i specificities. J Biol Chem 254:3221–3228PubMedGoogle Scholar
  21. Wiener AS et al (1956) Type-specific cold auto-antibodies as a cause of acquired hemolytic anemia and hemolytic transfusion reactions: biologic test with bovine red cells. Ann Intern Med 44(2):221–240PubMedCrossRefGoogle Scholar
  22. Yeh J-C, Ong E, Fukuda M (1999) Molecular cloning and expression of a novel b-1,6-N-acetylglucosaminyltransferase that forms core 2, core 4, and I branches. J Biol Chem 274:3215–3221PubMedCrossRefGoogle Scholar
  23. Yu L-C, Twu Y-C, Chou M-L, Reid ME, Gray AR, Moulds JM, Chang C-Y, 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 101:2081–2088PubMedCrossRefGoogle Scholar
  24. Zhang H, Meng F, Wu S, Kreike B, Sethi S, Chen W, Miller FR, Wo G (2011) Engagement of I-branching β-1,6-N-acetylglucosaminyltransferase 2 in breast cancer metastasis and TGF-β signaling. Cancer Res 71:4846–4856PubMedCentralPubMedCrossRefGoogle 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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