Glycoprotein Alpha 1,3-Galactosyltransferase 1, Pseudogene (GGTA1P)

  • Shuji Miyagawa
  • Akira Maeda
Reference work entry


UDPgalactose:β-d-galactosyl-1,4-N-acetyl-d-glucosaminide α1,3 galactosyltransferase, α1,3GT catalyzes the synthesis of the α-Gal epitope, one of the most common carbohydrate structures found in mammalian tissues (Galili and Tanemura 1999). This gene is present in the DNA of humans and Old World monkeys, but is not transcribed by evolutionary inactivation (Joziasse et al. 1992).


World Monkey Sialyl LewisX Clinical Xenotransplantation Acceptor Substrate Specificity Nuclear Transplantation Technique 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abdel-Motal UM, Wigglesworth K, Galili U (2009) Intratumoral injection of alpha-gal glycolipids induces a protective anti-tumor T cell response which overcomes Treg activity. Cancer Immunol Immunother 58:1545–1556PubMedCentralPubMedCrossRefGoogle Scholar
  2. Abdel-Motal UM, Wang S, Awad A, Lu S, Wigglesworth K, Galili U (2010) Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing alpha-gal epitopes. Vaccine 28:1758–1765PubMedCentralPubMedCrossRefGoogle Scholar
  3. Blake DA, Goldstein IJ (1981) An alpha-d-galactosyltransferase activity in Ehrlich ascites tumor cells. Biosynthesis and characterization of a trisaccharide (alpha-d-galactose-(1 goes to 3)-N-acetyllactosamine). J Biol Chem 256:5387–5393PubMedGoogle Scholar
  4. Blanken WM, Van den Eijnden DH (1985) Biosynthesis of terminal Gal alpha 1–3Gal beta 1–4GlcNAc-R oligosaccharide sequences on glycoconjugates. Purification and acceptor specificity of a UDP-Gal:N-acetyllactosaminide alpha 1–3-galactosyltransferase from calf thymus. J Biol Chem 260:12927–12934PubMedGoogle Scholar
  5. Cho SK, Yeh JC, Cummings RD (1997) Secretion of alpha1,3-galactosyltransferase by cultured cells and presence of enzyme in animal sera. Glycoconj J 14:809–819PubMedCrossRefGoogle Scholar
  6. Dai Y, Vaught TD, Boone J, Chen SH, Phelps CJ, Ball S, Monahan JA, Jobst PM, McCreath KJ, Lamborn AE, Cowell-Lucero JL, Wells KD, Colman A, Polejaeva IA, Ayares DL (2002) Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20:251–255PubMedCrossRefGoogle Scholar
  7. Diswall M, Angström J, Schuurman HJ, Dor FJ, Rydberg L, Breimer ME (2007) Studies on glycolipid antigens in small intestine and pancreas from alpha1, 3-galactosyltransferase knockout miniature swine. Transplantation 84:1348–1356PubMedCrossRefGoogle Scholar
  8. Diswall M, Angström J, Karlsson H, Phelps CJ, Ayares D, Teneberg S, Breimer ME (2010) Structural characterization of alpha1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies. Xenotransplantation 17:48–60PubMedCrossRefGoogle Scholar
  9. Diswall M, Gustafsson A, Holgersson J, Sandrin MS, Breimer ME (2011) Antigen-binding specificity of anti-αGal reagents determined by solid-phase glycolipid-binding assays. A complete lack of αGal glycolipid reactivity in α1,3GalT-KO pig small intestine. Xenotransplantation 18:28–39PubMedCrossRefGoogle Scholar
  10. Egge H, Kordowicz M, Peter-Katalinic J, Hanfland P (1985) Immunochemistry of I/i-active oligo- and polyglycosylceramides from rabbit erythrocyte membranes. Characterization of linear, di-, and triantennary neolactoglycosphingolipids. J Biol Chem 260:4927–4935PubMedGoogle Scholar
  11. Eto T, Ichikawa Y, Nishimura K, Ando S, Yamakawa T (1968) Chemistry of lipid of the posthemyolytic residue or stroma of erythrocytes. XVI. Occurrence of ceramide pentasaccharide in the membrane of erythrocytes and reticulocytes of rabbit. J Biochem (Tokyo) 64:205–213Google Scholar
  12. Fang J, Walters A, Hara H, Long C, Yeh P, Ayares D, Cooper DK, Bianchi J (2012) Anti-gal antibodies in α1,3-galactosyltransferase gene-knockout pigs. Xenotransplantation 19:305–310PubMedCentralPubMedCrossRefGoogle Scholar
  13. Galili U, Rachmilewitz EA, Peleg A, Flechner I (1984) A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med 160:1519–1531PubMedCrossRefGoogle Scholar
  14. Galili U, Macher BA, Buehler J, Shohet SB (1985) Human natural anti-alpha-galactosyl IgG. II. The specific recognition of alpha (1–3)-linked galactose residues. J Exp Med 162:573–582PubMedCrossRefGoogle Scholar
  15. Galili U, Clark MR, Shohet SB, Buehler J, Macher BA (1987) Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1–3Gal epitope in primates. Proc Natl Acad Sci U S A 84:1369–1373PubMedCentralPubMedCrossRefGoogle Scholar
  16. Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA (1988) Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem 263:17755–17762PubMedGoogle Scholar
  17. Galili U, Swanson K (1991) Gene sequences suggest inactivation of alpha-1,3-galactosyltransferase in catarrhines after the divergence of apes from monkeys. Proc Natl Acad Sci USA 88:7401–7404PubMedCentralPubMedCrossRefGoogle Scholar
  18. Galili U, Tanemura M (1999) Significance of a-Gal (Gala1-3Galb1-4GlcNAc) Epitopes and a1,3Galactosyltranaferase in Xenotransplantation. Trends Glycosci Glycotechnol 11:317–327CrossRefGoogle Scholar
  19. Gastinel LN, Bignon C, Misra AK, Hindsgaul O, Shaper JH, Joziasse DH (2001) Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases. EMBO J 20:638–649PubMedCrossRefGoogle Scholar
  20. Henion TR, Macher BA, Anaraki F, Galili U (1994) Defining the minimal size of catalytically active primate alpha 1,3 galactosyltransferase: structure-function studies on the recombinant truncated enzyme. Glycobiology 4:193–201PubMedCrossRefGoogle Scholar
  21. Hokke CH, Zervosen A, Elling L, Joziasse DH, van den Eijnden DH (1996) One-pot enzymatic synthesis of the Gal alpha 1–>3Gal beta 1–>4GlcNAc sequence with in situ UDP-Gal regeneration. Glycoconj J 13:687–692PubMedCrossRefGoogle Scholar
  22. Honma K, Manabe H, Tomita M, Hamada A (1981) Isolation and partial structural characterization of macroglycolipid from rabbit erythrocyte membranes. J Biochem (Tokyo) 90:1187–1196Google Scholar
  23. Ikematsu S, Kaname T, Ozawa M, Yonezawa S, Sato E, Uehara F, Obama H, Yamamura K, Muramatsu T (1993) Transgenic mouse lines with ectopic expression of alpha-1,3-galactosyltransferase: production and characteristics. Glycobiology 3:575–580PubMedCrossRefGoogle Scholar
  24. Joziasse DH, Shaper JH, Van den Eijnden DH, Van Tunen AJ, Shaper NL (1989) Bovine alpha 1–3-galactosyltransferase: isolation and characterization of a cDNA clone. Identification of homologous sequences in human genomic DNA. J Biol Chem 264:14290–14297PubMedGoogle Scholar
  25. Joziasse DH, Shaper NL, Salyer LS, Van den Eijnden DH, van der Spoel AC, Shaper JH (1990) Alpha 1–3-galactosyltransferase: the use of recombinant enzyme for the synthesis of alpha-galactosylated glycoconjugates. Eur J Biochem 191:75–83PubMedCrossRefGoogle Scholar
  26. Joziasse DH, Shaper NL, Kim D, Van den Eijnden DH, Shaper JH (1992) Murine alpha 1,3-galactosyltransferase. A single gene locus specifies four isoforms of the enzyme by alternative splicing. J Biol Chem 267:5534–5541PubMedGoogle Scholar
  27. Keusch JJ, Manzella SM, Nyame KA, Cummings RD, Baenziger JU (2000) Expression cloning of a new member of the ABO blood group glycosyltransferases, iGb3 synthase, that directs the synthesis of isoglobo-glycosphingolipids. J Biol Chem 275:25308–25314PubMedCrossRefGoogle Scholar
  28. Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS, Samuel M, Bonk A, Rieke A, Day BN, Murphy CN, Carter DB, Hawley RJ, Prather RS (2002) Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089–1092PubMedCrossRefGoogle Scholar
  29. Larsen RD, Rajan VP, Ruff MM, Kukowska-Latallo J, Cummings RD, Lowe JB (1989) Isolation of a cDNA encoding a murine UDPgalactose:beta-d-galactosyl- 1,4-N-acetyl-d-glucosaminide alpha-1,3-galactosyltransferase: expression cloning by gene transfer. Proc Natl Acad Sci U S A 86:8227–8231PubMedCentralPubMedCrossRefGoogle Scholar
  30. Larsen RD, Rivera-Marrero CA, Ernst LK, Cummings RD, Lowe JB (1990) Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:beta-d-Gal(1,4)-d-GlcNAc alpha(1,3)-galactosyltransferase cDNA. J Biol Chem 265:7055–7061PubMedGoogle Scholar
  31. Lazarus BD, Milland J, Ramsland PA, Mouhtouris E, Sandrin MS (2002) Histidine 271 has a functional role in pig alpha-1,3galactosyltransferase enzyme activity. Glycobiology 12:793–802PubMedCrossRefGoogle Scholar
  32. Milland J, Christiansen D, Sandrin MS (2005) Alpha1,3-galactosyltransferase knockout pigs are available for xenotransplantation: are glycosyltransferases still relevant? Immunol Cell Biol 83:687–693PubMedCrossRefGoogle Scholar
  33. Milland J, Christiansen D, Lazarus BD, Taylor SG, Xing PX, Sandrin MS (2006) The molecular basis for galalpha(1,3)gal expression in animals with a deletion of the alpha1,3galactosyltransferase gene. J Immunol 176:2448–2454PubMedGoogle Scholar
  34. Miyagawa S, Maeda A, Takeishi S, Ueno T, Usui N, Matsumoto S, Teru Okitsu T, Goto M, Nagashima H (2013) A Lectin array analysis for wild-type and alpha-Gal-knockout pig islets, compared with humans. Surg TodayGoogle Scholar
  35. Molina P, Knegtel RM, Macher BA (2007) Site-directed mutagenesis of glutamate 317 of bovine alpha-1,3Galactosyltransferase and its effect on enzyme activity: implications for reaction mechanism. Biochim Biophys Acta 1770:1266–1273PubMedCentralPubMedCrossRefGoogle Scholar
  36. Nottle MB, Beebe LF, Harrison SJ, McIlfatrick SM, Ashman RJ, O’Connell PJ, Salvaris EJ, Fisicaro N, Pommey S, Cowan PJ, d’Apice AJ (2007) Production of homozygous alpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer. Xenotransplantation 14:339–344PubMedCrossRefGoogle Scholar
  37. Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry AC (2000) Pig cloning by microinjection of fetal fibroblast nuclei. Science 289:1188–1190PubMedCrossRefGoogle Scholar
  38. Puga Yung GL, Li Y, Borsig L, Millard AL, Karpova MB, Zhou D, Seebach JD (2012) Complete absence of the αGal xenoantigen and isoglobotrihexosylceramide in α1,3galactosyltransferase knock-out pigs. Xenotransplantation 19:196–206PubMedCentralPubMedCrossRefGoogle Scholar
  39. Ramsoondar JJ, Macháty Z, Costa C, Williams BL, Fodor WL, Bondioli KR (2003) Production of alpha 1,3-galactosyltransferase-knockout cloned pigs expressing human alpha 1,2-fucosylosyltransferase. Biol Reprod 69:437–445PubMedCrossRefGoogle Scholar
  40. Rayat GR, Rajotte RV, Hering BJ, Binette TM, Korbutt GS (2003) In vitro and in vivo expression of Galalpha-(1,3)Gal on porcine islet cells is age dependent. J Endocrinol 177:127–135PubMedCrossRefGoogle Scholar
  41. Sandrin MS, Dabkowski PL, Henning MM, Mouhtouris HE, McKenzie IFC (1994) Characterization of cDNA clones for porcine α(1,3)galactosyl transferase: the enzyme generating the Galα(1,3)Gal epitope. Xenotransplantation 1:81–88CrossRefGoogle Scholar
  42. Sepp A, Skacel P, Lindstedt R, Lechler RI (1997) Expression of alpha-1,3-galactose and other type 2 oligosaccharide structures in a porcine endothelial cell line transfected with human alpha-1,2-fucosyltransferase cDNA. J Biol Chem 272:23104–23110PubMedCrossRefGoogle Scholar
  43. Shah PS, Bizik F, Dukor RK, Qasba PK (2000) Active site studies of bovine alpha1–>3-galactosyltransferase and its secondary structure prediction. Biochim Biophys Acta 1480:222–234PubMedCrossRefGoogle Scholar
  44. Stellner K, Saito H, Hakomori S (1973) Determination of aminosugar linkages in glycolipids by methylation. Aminosugar linkages of ceramide pentasaccharides of rabbit erythrocytes and of Forssman antigen. Arch Biochem Biophys 155:464–472PubMedCrossRefGoogle Scholar
  45. Strahan KM, Gu F, Preece AF, Gustavsson I, Andersson L, Gustafsson K (1995) cDNA sequence and chromosome localization of pig alpha 1,3 galactosyltransferase. Immunogenetics 41:101–105PubMedCrossRefGoogle Scholar
  46. Sujino K, Malet C, Hindsgaul O, Palcic MM (1997) Acceptor hydroxyl group mapping for calf thymus alpha-(1–>3)-galactosyltransferase and enzymatic synthesis of alpha-d-Galp-(1–>3)-beta-d-Galp-(1–>4)-beta d-GlcpNAc analogs. Carbohydr Res 305:483–489PubMedCrossRefGoogle Scholar
  47. Takahagi Y, Fujimura T, Miyagawa S, Nagashima H, Shigehisa T, Shirakura R, Murakami H (2005) Production of alpha 1,3-galactosyltransferase gene knockout pigs expressing both human decay-accelerating factor and N-acetylglucosaminyltransferase III. Mol Reprod Dev 71:331–338PubMedCrossRefGoogle Scholar
  48. Taylor SG, McKenzie IF, Sandrin MS (2003) Characterization of the rat alpha(1,3)galactosyltransferase: evidence for two independent genes encoding glycosyltransferases that synthesize Galalpha(1,3)Gal by two separate glycosylation pathways. Glycobiology 13:327–337PubMedCrossRefGoogle Scholar
  49. Tearle RG, Tange MJ, Zannettino ZL, Katerelos M, Shinkel TA, Van Denderen BJ, Lonie AJ, Lyons I, Nottle MB, Cox T, Becker C, Peura AM, Wigley PL, Crawford RJ, Robins AJ, Pearse MJ, d’Apice AJ (1996) The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation. Transplantation 61:13–19PubMedCrossRefGoogle Scholar
  50. Thall AD, Malý P, Lowe JB (1995) Oocyte Gal alpha 1,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse. J Biol Chem 270:21437–21440PubMedCrossRefGoogle Scholar
  51. Tumbale P, Jamaluddin H, Thiyagarajan N, Brew K, Acharya KR (2008) Structural basis of UDP-galactose binding by alpha-1,3-galactosyltransferase (alpha3GT): role of negative charge on aspartic acid 316 in structure and activity. Biochemistry 47:8711–8718PubMedCrossRefGoogle Scholar
  52. Van den Eijnden DH (2000) On the origin of oligosaccharide species. Glycosyltransferases in action. In: Ernst B, Hart G, Sinay P (eds) Oligosaccharides in chemistry and biology Part I, vol 2. Wiley/VCH, Weinheim, pp 589–624Google Scholar
  53. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813PubMedCrossRefGoogle Scholar
  54. Yung GP, Schneider MK, Seebach JD (2009) Immune responses to alpha1,3galactosyltransferase knockout pigs. Curr Opin Organ Transplant 14:154–160CrossRefGoogle Scholar
  55. Zhang Y, Wang PG, Brew K (2001) Specificity and mechanism of metal ion activation in UDP-galactose:beta -galactoside-alpha-1,3-galactosyltransferase. J Biol Chem 276:11567–11574PubMedCrossRefGoogle Scholar
  56. Zhang Y, Swaminathan GJ, Deshpande A, Boix E, Natesh R, Xie Z, Acharya KR, Brew K (2003) Roles of individual enzyme-substrate interactions by alpha-1,3-galactosyltransferase in catalysis and specificity. Biochemistry 42:13512–13521PubMedCrossRefGoogle Scholar
  57. Zhang Y, Deshpande A, Xie Z, Natesh R, Acharya KR, Brew K (2004) Roles of active site tryptophans in substrate binding and catalysis by alpha-1,3 galactosyltransferase. Glycobiology 14:1295–1302PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Division of Organ Transplantation, Department of SurgeryOsaka University Graduate School of MedicineOsakaJapan

Personalised recommendations