Histo-Blood Group A and B Transferases, Their Gene Structures, and Common O Group Gene Structures

  • Sen-itiroh Hakomori
  • Monica Palcic
Reference work entry


The human ABO antigens are the most important blood groups in transfusion and transplantation medicine (Storry and Olsson 2009; Yamamoto et al. 2012). Histo-blood group A and B antigens are produced by UDP-GalNAc: H-α3GalNAc transferase (GTA; EC and UDP-Gal: H-α3Gal transferase (GTB; EC, respectively (Fig. 44.1). GTA and GTB are retaining enzymes and are members of GT family 6 in the CAZy database. The minimal acceptor is an H-disaccharide (αFuc1→2βGal) on a glycoprotein, glycolipid, or free oligosaccharide. Depending on the structure of the H precursor, four types of A antigen and three types of B antigen have been identified (Fig. 44.2). Type-3 chain A, i.e., repetitive A, is present only as a glycosphingolipid in A1-erythrocytes but not in A2-erythrocytes (see  Chap. 69, “ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 5,6 (ST6GALNAC5,6)”; “Cross-References”). The corresponding “repetitive B” is absent or unknown. Type-4 chain A (globo-A) is also expressed in A1-erythrocytes but not in A2-erythrocytes. Type-4 chain B (globo-B) is not known in erythrocytes; however, both globo-A and globo-B are highly expressed in other organs, particularly the kidney and surogenital epithelia. The distribution patterns of these isotypes of A and B antigens, and their patterns during development, have been reviewed (Hakomori 1981; Oriol et al. 1986; Clausen and Hakomori 1989; Oriol 1995). In this chapter, only allelic structures of A and B transferases, and the allele for the common O blood group gene, are described. Alleles for variants are described in  Chap. 69, “ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 5,6 (ST6GALNAC5,6)” (see “Cross-References”).


Blood Group Critical Amino Acid Covalent Adduct CAZy Database Gastric Cancer Cell Line MKN45 
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  1. Aird I, Bentall HH, Roberts JA (1953) A relationship between cancer of stomach and the ABO blood groups. Br Med J 1:799–801PubMedCentralPubMedCrossRefGoogle Scholar
  2. Aird I, Bentall HH, Mehigan JA, Roberts JA (1954) The blood groups in relation to peptic ulceration and carcinoma of colon, rectum, breast, and bronchus; an association between the ABO groups and peptic ulceration. Br Med J 2:315–321PubMedCentralPubMedCrossRefGoogle Scholar
  3. Alfaro JA, Zheng RB, Persson M, Letts JA, Polakowski R, Bai Y, Borisova SN, Seto NOL, Lowary TL, Palcic MM, Evans SV (2008) ABO(H) Blood group A and B glycosyltransferases recognize substrate via specific conformational changes. J Biol Chem 283:10097–10108PubMedCrossRefGoogle Scholar
  4. Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM et al (2009) Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nature Genet 41:986–990PubMedCentralPubMedCrossRefGoogle Scholar
  5. Aspholm-Hurtig M, Dailide G, Lahmann M et al (2004) Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science 305:519–522PubMedCrossRefGoogle Scholar
  6. Athrerya BH, Coriell LL (1967) Relation of blood groups to infection. I. A survey and review of data suggesting possible relationship between blood group and malaria. Am J Epidemiol 86:292–304Google Scholar
  7. Bennett EP, Steffensen R, Clausen H, Weghuis DO, van Kessel AG (1995) Genomic cloning of the human histo- blood group ABO locus. Biochem Biophys Res Commun 206:318–325PubMedCrossRefGoogle Scholar
  8. Borén T, Falk P, Roth KA, Larson G, Normark S (1993) Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 262:1892–1895PubMedCrossRefGoogle Scholar
  9. Clausen H, Hakomori S (1989) ABH and related histo-blood group antigens: immunochemical differences in carrier isotypes and their distribution. Vox Sang 56:1–20PubMedCrossRefGoogle Scholar
  10. Clausen H, White T, Takio K, Titani K, Stroud MR, Holmes EH, Karkov J, Thim L, Hakomori S (1990) Isolation to homogeneity and partial characterization of a histoblood group A defined Fucα1→2Galαl→3-N-acetyl galactosaminyltransferase from human lung tissue. J Biol Chem 265:1139–1145PubMedGoogle Scholar
  11. Cserti CM, Dzik WH (2007) The ABO blood group system and Plasmodium falciparum malaria. Blood 110:2250–2258PubMedCrossRefGoogle Scholar
  12. Fry AE, Griffiths MJ, Auburn S, Diakite M, Forton JT, Green A et al (2008) Common variation in the ABO glycosyltransferase is associated with susceptibility to severe malaria. Hum Mol Genet 17:567–576PubMedCentralPubMedGoogle Scholar
  13. Fukuda MN, Fukuda M, Hakomori S (1979) Cell surface modification by endo-β-galactosidase: change of blood group activities and release of oligosaccharides from glycoproteins and glycosphingolipids of human erythrocytes. J Biol Chem 254:5458–5465PubMedGoogle Scholar
  14. Hakomori S (1981) Blood group ABH and Ii antigens of human erythrocytes: chemistry, polymorphism, and their developmental change. Semin Hematol 18:39–62PubMedGoogle Scholar
  15. Hakomori S (1984) Blood group glycolipid antigens and their modifications as human cancer antigens. Am J Clin Pathol 82:635–648PubMedGoogle Scholar
  16. Hakomori S (1999) Antigen structure and gnetic basis of histo-blood groups A, B and O: their changes associated with human cancer. Biochim Biophys Acta 1473:247–266PubMedCrossRefGoogle Scholar
  17. Hakomori S, Strycharz GB (1968) Investigations on cellular blood group substance. I. Isolation and chemical composition of blood group ABH and Leb isoantigens of sphingoglycolipid nature. Biochemistry 7:1279–1286PubMedCrossRefGoogle Scholar
  18. Iwamoto S, Withers DA, Handa K, Hakomori S (1999) Deletion of A-antigen in a human cancer cell line is associated with reduced promoter activity of CBF/NF-Y binding region, and possibly with enhanced DNA methylation of A transferase promoter. Glycoconj J 16:659–666PubMedCrossRefGoogle Scholar
  19. Kabat EA (1973) Immunochemical studies on the carbohydrate moiety of water-soluble blood group A, B, H, Lea, and Leb substances and their precursor I antigens. In: Isbell H (ed) Carbohydrates in solution, vol 117, Advance Chemistry Series. American Chemical Society, Washington, pp 334–361CrossRefGoogle Scholar
  20. Kominato Y, Tsuchiya T, Hata N, Takizawa H, Yamamoto F (1997) Transcription of human ABO histo-blood group genes is dependent upon binding of transcription factor CBF/NF-Y to minisatellite sequence. J Biol Chem 272:25890–25898PubMedCrossRefGoogle Scholar
  21. Kominato Y, Hata Y, Takizawa H, Tsuchiya T, Tsukada J, Yamamoto F (1999) Expression of human histo-blood group ABO genes is dependent upon DNA methylation of the promoter region. J Biol Chem 274:37240–37250PubMedCrossRefGoogle Scholar
  22. Koscielak J (1963) Blood-group A-specific glycolipids from human erythrocytes. Biochim Biophys Acta 78:313–328PubMedCrossRefGoogle Scholar
  23. Lairson LL, Henrissat B, Davies GJ, Withers SG (2008) Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem 77:521–555PubMedCrossRefGoogle Scholar
  24. Letts JA, Rose NL, Fang YR, Barry CH et al (2006) Differential recognition of the type I and type II H antigen acceptors by the human ABO(H) blood group A and glycosyltransferases. J Biol Chem 281:3625–3632PubMedCrossRefGoogle Scholar
  25. Marionneau S, Ruvoën N, Le Moullac-Vaidye B, Clement M et al (2002) Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals. Gastroenterology 122:1967–1977PubMedCrossRefGoogle Scholar
  26. Morgan WTJ, Watkins WM (1969) Genetic and biochemical aspects of human blood group A-, B-, H-, Lea- and Leb-specificity. Br Med Bull 25:30–34PubMedGoogle Scholar
  27. Oriol R (1995) ABO, Hh, Lewis, and secretion: serology, genetics, and tissue distribution. In: Cartron JP, Rouger P (eds) Molecular basis of human blood group antigens, vol 6, Blood cell biochemistry. Plenum Press, New York, pp 37–73CrossRefGoogle Scholar
  28. Oriol R, Le Pendu J, Mollicone R (1986) Genetics of ABO, H, Lewis, X and related antigens. Vox Sang 51:161–171PubMedCrossRefGoogle Scholar
  29. Patenude SI, Seto NOL, Borisova SN, Szpacenko A, Marcus SL, Palcic MM, Evans S (2002) The structural basis for specificity in human ABO(H) blood group biosynthesis. Nature Struct Biol 9:685–690CrossRefGoogle Scholar
  30. Pesnot T, Jørgensen R, Palcic MM, Wagner GK (2010) Structural and mechanistic basis for a new mode of glycosyltransferase inhibition. Nature Chem Biol 6:321–323CrossRefGoogle Scholar
  31. Reed R, Maniatis T (1986) A role for exon sequences and splice-site proximity in splice-site selection. Cell 46:681–690PubMedCrossRefGoogle Scholar
  32. Rydell GE, Kindberg E, Larson G, Svensson L (2011) Susceptibility to winter vomiting disease: a sweet matter. Rev Med Virol 21:370–382PubMedCrossRefGoogle Scholar
  33. Seto NOL, Palcic MM, Hindsgaul O, Bundle DR, Narang SA (1995) Expression of a recombinant human glycosyltransferase from a synthetic gene and its utilization for synthesis of the human blood group B trisaccharide. Eur J Biochem 234:323–328PubMedCrossRefGoogle Scholar
  34. Seto NOL, Palcic MM, Compston CA, Li H, Bundle DR, Narang SA (1997) Sequential interchange of four amino acids from blood group B to blood group A glycosyltransferase boosts catalytic activity and progressively modifies substrate recognition in human recombinant enzymes. J Biol Chem 272:14133–14138PubMedCrossRefGoogle Scholar
  35. Soya N, Fang Y, Palcic MM, Klassen JS (2011) Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases. Glycobiology 21:547–547PubMedCrossRefGoogle Scholar
  36. Storry JR, Olsson ML (2009) The ABO blood group system revisited: a review and update. Immunohematology 25:48–59PubMedGoogle Scholar
  37. Szulman AE (1971) The histological distribution of the blood group substances in man as disclosed by immunofluorescence. IV. The ABH antigens in embryos at the fifth week post-fertilization. Hum Pathol 2:575–585PubMedCrossRefGoogle Scholar
  38. Watkins WM (1966) Blood-group substances. Science 152:172–181PubMedCrossRefGoogle Scholar
  39. Watkins WM (1980) Biochemistry and genetics of the ABO, Lewis, and P blood group systems. In: Harris H, Hirschhorn K (eds) Advances in human genetics, vol 10. Plenum Press, New York, pp 1–136Google Scholar
  40. Yamakawa T, Iida T (1953) Immunochemical study on the red blood cells. I. Globoside, as the agglutinogen of the ABO system on erythrocytes. Jpn J Exp Med 23:327–331PubMedGoogle Scholar
  41. Yamamoto F, Hakomori S (1990) Sugar-nucleotide donor specificity of histo-blood group A and B transferases is based on amino acid substitutions. J Biol Chem 265:19257–19262PubMedGoogle Scholar
  42. Yamamoto F, Clausen H, White T, Marken J, Hakomori S (1990a) Molecular and genetic basis of the histo-blood group ABO system. Nature 345:229–233PubMedCrossRefGoogle Scholar
  43. Yamamoto F, Marken J, Tsuji T, White T, Clausen H, Hakomori S (1990b) Cloning and characterization of DNA complementary to human UDP-GalNAc: Fucα→2 Galα→3GalNAc transferase (histo-blood group A transferase) mRNA. J Biol Chem 265:1146–1151PubMedGoogle Scholar
  44. Yamamoto F, McNeill PD, Hakomori S (1995) Genomic organization of human histo-blood group ABO genes. Glycobiology 5:51–58PubMedCrossRefGoogle Scholar
  45. Yamamoto F, Cid E, Yamamoto M, Blancher A (2012) ABO research in the modern era of genomics. Transfus Med Rev 26:103–118PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Division of Biomembrane Research, Pacific Northwest Research Institute, Departments of Microbiology and PathobiologyUniversity of WashingtonSeattleUSA
  2. 2.Carlsberg LaboratoryCopenhagen VDenmark

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