Alpha 1,3-Galactosyltransferase 2, Pseudogene (A3GALT2P)

  • Dale Christiansen
  • Effie Mouhtouris
  • Mauro S. Sandrin
Reference work entry


Isoglobotriaosylceramide or isogloboside 3 (iGb3) has been the subject of intense research by numerous laboratories and has provoked lively debate in the literature since it was suggested to be the endogenous ligand involved in thymic selection of a subset of natural killer T cells (iNKT) in both mice and humans. iGb3 is the first member of the isoglobo-series glycosphingolipids and is synthesized by alpha 1,3-galactosyltransferase 2.


iNKT Cell Human Thymus Thymic Selection Transfected Chinese Hamster Ovary Cell Activate iNKT Cell 
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  1. Angstrom J, Breimer ME, Falk KE, Hansson GC, Karlsson KA, Leffler H (1982a) Chemical characterization of penta-, hexa-, hepta-, octa-, and nonaglycosylceramides of rat small intestine having a globoside-like terminus. J Biol Chem 257:682–688PubMedGoogle Scholar
  2. Angstrom J, Breimer ME, Falk KE, Hansson GC, Karlsson KA, Leffler H, Pascher I (1982b) Structural characterization of glycolipids of rat small intestine having one to eight hexoses in a linear sequence. Arch Biochem Biophys 213:708–725. doi:0003-9861(82)90601-4 [pii]PubMedCrossRefGoogle Scholar
  3. Ariga T, Suzuki M, Yu RK, Kuroda Y, Shimada I, Inagaki F, Miyatake T (1989) Accumulation of unique globo-series glycolipids in PC 12 h pheochromocytoma cells. J Biol Chem 264:1516–1521PubMedGoogle Scholar
  4. Breimer ME, Hansson GC, Karlsson KA, Leffler H (1982) Glycosphingolipids of rat tissues. Different composition of epithelial and nonepithelial cells of small intestine. J Biol Chem 257:557–568PubMedGoogle Scholar
  5. Brossay L, Chioda M, Burdin N, Koezuka Y, Casorati G, Dellabona P, Kronenberg M (1998) CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med 188:1521–1528PubMedCentralPubMedCrossRefGoogle Scholar
  6. Christiansen D, Milland J, Mouhtouris E, Vaughan H, Pellicci DG, McConville MJ, Godfrey DI, Sandrin MS (2008) Humans lack iGb3 due to the absence of functional iGb3-synthase: implications for NKT cell development and transplantation. PLoS Biol 6:e172. doi:07-PLBI-RA-3601 [pii] 10.1371/journal.pbio.0060172PubMedCentralPubMedCrossRefGoogle Scholar
  7. Diswall M, Angstrom 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 84:1348–1356. doi:10.1097/ 00007890-200711270-00018 [pii]PubMedCrossRefGoogle Scholar
  8. Hansson GC, Karlsson KA, Thurin J (1980) Glycolipids of rat large intestine. Characterization of a novel blood group B-active tetraglycosylceramide absent from small intestine. Biochim Biophys Acta 620:270–280. doi:0005-2760(80)90208-8 [pii]PubMedCrossRefGoogle Scholar
  9. Hansson GC, Bouhours JF, Angstrom J (1987) Characterization of neutral blood group B-active glycosphingolipids of rat gastric mucosa. A novel type of blood group active glycosphingolipid based on isogloboside. J Biol Chem 262:13135–13141PubMedGoogle Scholar
  10. Karlsson KA (1989) Animal glycosphingolipids as membrane attachment sites for bacteria. Annu Rev Biochem 58:309–350. doi:10.1146/ Scholar
  11. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Koseki H, Taniguchi M (1997) CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278:1626–1629PubMedCrossRefGoogle Scholar
  12. 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 275:25308–25314. doi:10.1074/jbc.M002629200 M002629200 [pii]PubMedCrossRefGoogle Scholar
  13. Laine R, Sweeley CC, Li YT, Kisic A, Rapport MM (1972) On the structure of cytolipin R, a ceramide tetrahexoside hapten from rat lymphosarcoma. J Lipid Res 13:519–524PubMedGoogle Scholar
  14. Li Y, Teneberg S, Thapa P, Bendelac A, Levery SB, Zhou D (2008) Sensitive detection of isoglobo and globo series tetraglycosylceramides in human thymus by ion trap mass spectrometry. Glycobiology 18:158–165. doi:cwm129 [pii] 10.1093/glycob/cwm129PubMedCrossRefGoogle Scholar
  15. Li Y, Thapa P, Hawke D, Kondo Y, Furukawa K, Hsu FF, Adlercreutz D, Weadge J, Palcic MM, Wang PG, Levery SB, Zhou D (2009) Immunologic glycosphingolipidomics and NKT cell development in mouse thymus. J Proteome Res 8:2740–2751. doi:10.1021/pr801040hPubMedCentralPubMedCrossRefGoogle Scholar
  16. Milland J, Sandrin MS (2006) ABO blood group and related antigens, natural antibodies and transplantation. Tissue Antigens 68:459–466. doi:TAN721 [pii] 10.1111/j.1399-0039.2006.00721.xPubMedCrossRefGoogle Scholar
  17. 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 176:2448–2454. doi:176/4/2448 [pii]PubMedGoogle Scholar
  18. Niimura Y (2006) Structural analysis of a unique hybrid-type ganglioside with isoglobo-, neolacto-, and ganglio-core from the gills of the Pacific salmon (Oncorhynchus keta). Carbohydr Res 341:2669–2676. doi:S0008-6215(06)00367-3 [pii] 10.1016/j.carres.2006.07.016PubMedCrossRefGoogle Scholar
  19. Porubsky S, Speak AO, Luckow B, Cerundolo V, Platt FM, Grone HJ (2007) Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency. Proc Natl Acad Sci USA 104:5977–5982. doi:0611139104 [pii] 10.1073/pnas.0611139104PubMedCrossRefGoogle Scholar
  20. Porubsky S, Speak AO, Salio M, Jennemann R, Bonrouhi M, Zafarulla R, Singh Y, Dyson J, Luckow B, Lehuen A, Malle E, Muthing J, Platt FM, Cerundolo V, Grone HJ (2012) Globosides but not isoglobosides can impact the development of invariant NKT cells and their interaction with dendritic cells. J Immunol 189:3007–3017. doi:jimmunol.1201483 [pii] 10.4049/jimmunol.1201483PubMedCentralPubMedCrossRefGoogle Scholar
  21. Puga Yung GL, Li Y, Borsig L, Millard AL, Karpova MB, Zhou D, Seebach JD (2012) Complete absence of the alphaGal xenoantigen and isoglobotrihexosylceramide in alpha1,3galactosyltransferase knock-out pigs. Xenotransplantation 19:196–206. doi:10.1111/j.1399-3089.2012.00705.xPubMedCentralPubMedCrossRefGoogle Scholar
  22. Siddiqui B, Kawanami J, Li YT, Hakomori S (1972) Structures of ceramide tetrasaccharides from various sources: uniqueness of rat kidney ceramide tetrasaccharide. J Lipid Res 13:657–662PubMedGoogle Scholar
  23. Slomiany BL, Slomiany A, Horowitz MI (1974) Characterization of blood-group-H-active ceramide tetrasaccharide from hog-stomach mucosa. Eur J Biochem 43:161–165PubMedCrossRefGoogle Scholar
  24. Speak AO, Salio M, Neville DC, Fontaine J, Priestman DA, Platt N, Heare T, Butters TD, Dwek RA, Trottein F, Exley MA, Cerundolo V, Platt FM (2007) Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals. Proc Natl Acad Sci USA 104:5971–5976. doi:0607285104 [pii] 10.1073/pnas.0607285104PubMedCrossRefGoogle Scholar
  25. Stoffyn P, Stoffyn A, Hauser G (1973a) Structure of trihexosylceramide biosynthesized in vitro. J Biol Chem 248:1920–1923PubMedGoogle Scholar
  26. Stoffyn P, Stoffyn A, Hauser G (1973b) Structure of trihexosylceramide isolated from rat spleen. Biochim Biophys Acta 306:283–286. doi:0005-2760(73)90233-6 [pii]PubMedCrossRefGoogle Scholar
  27. Stoffyn A, Stoffyn P, Hauser G (1974) Structure of trihexosylceramide biosynthesized in vitro by rat kidney galactosyltransferase. Biochim Biophys Acta 360:174–178PubMedCrossRefGoogle Scholar
  28. Sung SS, Sweeley CC (1979) The structure of canine intestinal trihexosylceramide. Biochim Biophys Acta 575:295–298. doi:0005-2760(79)90031-6 [pii]PubMedCrossRefGoogle Scholar
  29. 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 13:327–337. doi:10.1093/glycob/cwg030PubMedCrossRefGoogle Scholar
  30. Teneberg S, Angstrom J, Ljungh A (2004) Carbohydrate recognition by enterohemorrhagic Escherichia coli: characterization of a novel glycosphingolipid from cat small intestine. Glycobiology 14:187–196. doi:10.1093/glycob/cwh015PubMedCrossRefGoogle Scholar
  31. Yamamoto H, Iida-Tanaka N, Kasama T, Ishizuka I, Kushi Y, Handa S (1999) Isolation and characterization of a novel Forssman active acidic glycosphingolipid with branched isoglobo-, ganglio-, and neolacto-series hybrid sugar chains. J Biochem 125:923–930PubMedCrossRefGoogle Scholar
  32. Zhou D, Mattner J, Cantu C 3rd, Schrantz N, Yin N, Gao Y, Sagiv Y, Hudspeth K, Wu YP, Yamashita T, Teneberg S, Wang D, Proia RL, Levery SB, Savage PB, Teyton L, Bendelac A (2004) Lysosomal glycosphingolipid recognition by NKT cells. Science 306:1786–1789. doi:1103440 [pii] 10.1126/science.1103440PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Dale Christiansen
    • 1
  • Effie Mouhtouris
    • 1
  • Mauro S. Sandrin
    • 1
  1. 1.Department of Surgery, Austin Health/Northern HealthThe University of MelbourneHeidelbergAustralia

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