α3-Fucosyltransferase-VI (FUT6)

  • Reiji Kannagi


Fuc-TVI (FUT6) was cloned as a fourth member of the human α1→3/4 fucosyltransferase gene family by Weston et al. in 1992. The enzyme shared 85% and 89% amino acid sequence identity with previously cloned Fuc-TIII (FUT3) and Fuc-TV (FUT5), respectively, and the FUT6 gene encoding the enzyme was shown to be located on chromosome 19, where the genes for FUT3 and FUT5 were known to be located. FUT6 could synthesize Lewis X and sialyl Lewis X, but not Lewis A or sialyl Lewis A. The enzyme turned out to be a “plasma-type” fucosyltransferase, and is known to synthesize the sialyl Lewis X determinant carried by plasma proteins and epithelial cancer cells.


Epithelial Cancer Cell Sialyl Lewisx Altered mRNA Expression Fucosyltransferase Activity Fucosyltransferase Gene 
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  1. Borsig L, Katopodis AG, Bowen BR, Berger EG (1998) Trafficking and localization studies of recombinant α1,3-fucosyltransferase VI stably expressed in CHO cells. Glycobiology 8:259–268PubMedCrossRefGoogle Scholar
  2. Borsig L, Imbach T, Höchli M, Berger EG (1999) α1,3Fucosyltransferase VI is expressed in HepG2 cells and codistributed with β1,4galactosyltransferase I in the Golgi apparatus and monensin-induced swollen vesicles. Glycobiology 9:1273–1280PubMedCrossRefGoogle Scholar
  3. Brinkman-Van der Linden ECM, Mollicone R, Oriol R, Larson G, van den Eijnden DH, Van Dijk W (1996) A missense mutation in the FUT6 gene results in total absence of α3-fucosylation of human α1-acid glycoprotein. J Biol Chem 271:14492–14495PubMedCrossRefGoogle Scholar
  4. Brinkman-Van der Linden EC, de Haan PF, Havenaar EC, Van Dijk W (1998) Inflammation-induced expression of sialyl Lewis X is not restricted to α1-acid glycoprotein, but also occurs to a lesser extent on α1-antichymotrypsin and haptoglobin. Glycoconj J 15:177–182PubMedCrossRefGoogle Scholar
  5. Britten CJ, Bird MI (1997) Chemical modification of an α3-fucosyltransferase: definition of amino acid residues essential for enzyme activity. Biochim Biophys Acta 1334:57–64PubMedCrossRefGoogle Scholar
  6. Cailleau-Thomas A, Coullin P, Candelier JJ, Balanzino L, Mennesson B, Oriol R, Mollicone R (2000) FUT4 and FUT9 genes are expressed early in human embryogenesis. Glycobiology 10:789–802PubMedCrossRefGoogle Scholar
  7. Cameron HS, Szczepaniak D, Weston BW (1995) Expression of human chromosome 19p α(1,3)-fucosyltransferase genes in normal tissues—alternative splicing, polyadenylation, and isoforms. J Biol Chem 270:20112–20122PubMedCrossRefGoogle Scholar
  8. Candelier J-J, Mollicone R, Mennesson B, Bergemer A-M, Henry S, Coullin P, Oriol R (1993) α-3-fucosyltransferases and their glycoconjugate antigen products in the developing human kidney. Lab Invest 69:449–459PubMedGoogle Scholar
  9. Chandrasekaran EV, Rhodes JM, Jain RK, Matta KL (1994) Lactose as affinity eluent and a synthetic sulfated copolymer as inhibitor, in conjunction with synthetic and natural acceptors, differentiate human milk Lewis-type and plasma-type α-1-fucosyltransferases. Biochem Biophys Res Commun 198:350–358PubMedCrossRefGoogle Scholar
  10. Costache M, Apoil PA, Cailleau A, Elmgren A, Larson G, Henry S, Blancher A, Iordachescu D, Oriol R, Mollicone R (1997a) Evolution of fucosyltransferase genes in vertebrates. J Biol Chem 272:29721–29728PubMedCrossRefGoogle Scholar
  11. Costache M, Cailleau A, Fernandez-Mateos P, Oriol R, Mollicone R (1997b) Advances in molecular genetics of α2-and α3/4-fucosyltransferases. Transfus Clin Biol 4:367–382PubMedCrossRefGoogle Scholar
  12. De Graaf TW, Van der Stelt ME, Anbergen MG, Van Dijk W (1993) Inflammation-induced expression of sialyl Lewis X-containing glycan structures on α1-acid glycoprotein (orosomucoid) in human sera. J Exp Med 177:657–666PubMedCrossRefGoogle Scholar
  13. de Vries T, Palcic MP, Schoenmakers PS, van den Eijnden DH, Joziasse DH (1997) Acceptor specificity of GDP-Fuc:Galβ1→4GlcNAc-R α3-fucosyltransferase VI (Fuc-T VI) expressed in insect cells as soluble, secreted enzyme. Glycobiology 7:921–927PubMedCrossRefGoogle Scholar
  14. Dohi T, Hashiguchi M, Yamamoto S, Morita H, Oshima M (1994) Fucosyltransferase-producing sialyl Lea and sialyl Lex carbohydrate antigen in benign and malignant gastrointestinal mucosa. Cancer 73:1552–1561PubMedCrossRefGoogle Scholar
  15. Ikeda N, Eguchi H, Nishihara S, Narimatsu H, Kannagi R, Irimura T, Ohta M, Matsuda H, Taniguchi N, Honke K (2001) A remodeling system of the 3′-sulfo Lewis a and 3′-sulfo Lewis X epitopes. J Biol Chem, in press ([doi] 10.1074/jbc. M107390200)Google Scholar
  16. Hada T, Fukui K, Ohno M, Akamatsu S, Yazawa S, Enomoto K, Yamaguchi K, Matsuda Y, Amuro Y, Yamanaka N (1995) Increased plasma α(1→3)-L-fucosyltransferase activities in patients with hepatocellular carcinoma. Glycoconj J 12:627–631PubMedCrossRefGoogle Scholar
  17. Havenaar EC, Hoff RC, van den Eijnden DH, Van Dijk W (1998) Sialyl Lewisx epitopes do not occur on acute-phase proteins in mice: relationship to the absence of α3-fucosyltransferase in the liver. Glycoconj J 15:389–395PubMedCrossRefGoogle Scholar
  18. Hiller KM, Mayben JP, Bendt KM, Manousos GA, Senger K, Cameron HS, Weston BW (2000) Transfection of α(1,3)fucosyltransferase antisense sequences impairs the proliferative and tumorigenic ability of human colon carcinoma cells. Mol Carcinog 27:280–288PubMedCrossRefGoogle Scholar
  19. Hutchinson WL, Du M-Q, Johnson PJ, Williams R (1991) Fucosyltransferases: differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis. Hepatology 13:683–688PubMedCrossRefGoogle Scholar
  20. Ito H, Hiraiwa N, Sawada-Kasugai M, Akamatsu S, Tachikawa T, Kasai Y, Akiyama S, Ito K, Takagi H, Kannagi R (1997) Altered mRNA expression of specific molecular species of fucosyl-and sialyltransferases in human colorectal cancer tissues. Int J Cancer 71:556–564PubMedCrossRefGoogle Scholar
  21. Izawa M, Kumamoto K, Mitsuoka C, Kanamori A, Ohmori K, Ishida H, Nakamura S, Kurata-Miura K, Sasaki K, Nishi T, Kannagi R (2000) Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewisx expression in human colorectal cancer. Cancer Res 60:1410–1416PubMedGoogle Scholar
  22. Johnson PH, Donald AS, Clarke JL, Watkins WM (1995) Purification, properties and possible gene assignment of an α1,3-fucosyltransferase expressed in human liver. Glycoconj J 12:879–893PubMedCrossRefGoogle Scholar
  23. Kannagi R (1997) Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconj J 14:577–584PubMedCrossRefGoogle Scholar
  24. Kaplan JC, Kahn A, Chelly J (1992) Illegitimate transcription: its use in the study of inherited disease. Hum Mutat 1:357–360PubMedCrossRefGoogle Scholar
  25. Karaivanova V, Mookerjea S, Hunt D, Nagpurkar A (1996) Characterization and purification of fucosyltransferases from the cytosol of rat colon. Int J Biochem Cell Biol 28:165–174PubMedCrossRefGoogle Scholar
  26. Koszdin KL, Bowen BR (1992) The cloning and expression of a human α-1,3-fucosyltransferase capable of forming the E-selectin ligand. Biochem Biophys Res Commun 187:152–157PubMedCrossRefGoogle Scholar
  27. Larson G, Borjeson C, Elmgren A, Kernholt A, Henry S, Fletcher A, Aziz A, Mollicone R, Oriol R (1996) Identification of a new plasma α(1,3)fucosyltransferase (FUT6) allele requires an extended genotyping strategy. Vox Sang 71:233–241PubMedCrossRefGoogle Scholar
  28. Leppänen A, Mehta P, Ouyang YB, Ju T, Helin J, Moore KL, van Die I, Canfield WM, McEver RP, Cummings RD (1999) A novel glycosulfopeptide binds to P-selectin and inhibits leukocyte adhesion to P-selectin. J Biol Chem 274:24838–24848PubMedCrossRefGoogle Scholar
  29. Lowe JB (1997) Selectin ligands, leukocyte trafficking, and fucosyltransferase genes. Kidney Int 51:1418–1426PubMedCrossRefGoogle Scholar
  30. Malissard M, Zeng S, Berger EG (2000) Expression of functional soluble forms of human β-1,4-galactosyltransferase I, α-2,6-sialyltransferase, and α-1,3-fucosyltransferase VI in the methylotrophic yeast Pichia pastoris. Biochem Biophys Res Commun 267:169–173PubMedCrossRefGoogle Scholar
  31. Mas E, Pasqualini E, Caillol N, El Battari A, Crotte C, Lombardo D, Sadoulet MO (1998) Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines. Glycobiology 8:605–613PubMedCrossRefGoogle Scholar
  32. Matsuura N, Narita T, Hiraiwa N, Hiraiwa M, Murai H, Iwase T, Funahashi H, Imai T, Takagi H, Kannagi R (1998) Gene expression of fucosyl-and sialyltransferases which synthesize sialyl Lewisx, the carbohydrate ligands for E-selectin, in human breast cancer. Int J Oncol 12:1157–1164PubMedGoogle Scholar
  33. McCurley RS, Recinos A, Olsen AS, Gingrich JC, Szczepaniak D, Cameron HS, Krauss R, Weston BW (1995) Physical maps of human α(1,3)fucosyltransferase genes FUT3-FUT6 on chromosomes 19pl3.3 and 11q21. Genomics 26:142–146PubMedCrossRefGoogle Scholar
  34. Mitsuoka C, Sawada-Kasugai M, Ando-Furui K, Izawa M, Nakanishi H, Nakamura S, Ishida H, Kiso M, Kannagi R (1998) Identification of a major carbohydrate capping group of the L-selectin ligand on high-endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis X. J Biol Chem 273:11225–11233PubMedCrossRefGoogle Scholar
  35. Mollicone R, Gibaud A, Francois A, Ratcliffe M, Oriol R (1990) Acceptor specificity and tissue distribution of three human α-3-fucosyltransferases. Eur J Biochem 191:169–176PubMedCrossRefGoogle Scholar
  36. Mollicone R, Reguigne I, Fletcher A, Aziz A, Rustam M, Weston BW, Kelly RJ, Lowe JB, Oriol R (1994) Molecular basis for plasma α(1,3)-fucosyltransferase gene deficiency (FUT6). J Biol Chem 269:12662–12671PubMedGoogle Scholar
  37. Natsuka S, Gersten KM, Zenita K, Kannagi R, Lowe JB (1994) Molecular cloning of a cDNA encoding a novel human leukocyte α-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis X determinant. J Biol Chem 269:16789–16794PubMedGoogle Scholar
  38. Nimtz M, Grabenhorst E, Gambert U, Costa J, Wray V, Morr M, Thiem J, Conradt HS (1998) In vitro α1-3 or α1-4 fucosylation of type I and II oligosaccharides with secreted forms of recombinant human fucosyltransferases III and VI. Glycoconj J 15:873–883PubMedCrossRefGoogle Scholar
  39. Nishihara S, Nakazato M, Kudo T, Kimura H, Ando T, Narimatsu H (1993) Human α-1,3-fucosyltransferase (Fuc-T VI) gene is located at only 13 kb 3′ to the Lewis type fucosyltransferase (Fuc-T III) gene on chromosome 19. Biochem Biophys Res Commun 190:42–46PubMedCrossRefGoogle Scholar
  40. Oriol R, Mollicone R, Cailleau A, Balanzino L, Breton C (1999) Divergent evolution of fucosyltransferase genes from vertebrates, invertebrates, and bacteria. Glycobiology 9:323–334PubMedCrossRefGoogle Scholar
  41. Oulmouden A, Wierinckx A, Petit JM, Costache M, Palcic MM, Mollicone R, Oriol R, Julien R (1997) Molecular cloning and expression of a bovine α(1,3)-fucosyltransferase gene homologous to a putative ancestor gene of the human FUT3-FUT5-FUT6 cluster. J Biol Chem 272:8764–8773PubMedCrossRefGoogle Scholar
  42. Pang H, Koda Y, Soejima M, Schlaphoff T, Du Toit ED, Kimura H (1999) Allelic diversity of the human plasma α(1,3)fucosyltransferase gene (FUT6). Ann Hum Genet 63:277–284PubMedCrossRefGoogle Scholar
  43. Petretti T, Schulze B, Schlag PM, Kemmner W (1999) Altered mRNA expression of glycosyltransferases in human gastric carcinomas. Biochim Biophys Acta 1428:209–218PubMedCrossRefGoogle Scholar
  44. Petretti T, Kemmner W, Schulze B, Schlag PM (2000) Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases. Gut 46:359–366PubMedCrossRefGoogle Scholar
  45. Raychoudhury SS, Millette CF (1995) Glycosidic specificity of fucosyltransferases present in rat epididymal spermatozoa. J Androl 16:448–456PubMedGoogle Scholar
  46. Sasaki K, Kurata K, Funayama K, Nagata M, Watanabe E, Ohta S, Hanai N, Nishi T (1994) Expression cloning of a novel α1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis X carbohydrate determinants in leukocytes. J Biol Chem 269:14730–14737PubMedGoogle Scholar
  47. Sherwood AL, Holmes EH (1999) Analysis of the expression and enzymatic properties of α1→3 fucosyltransferase from human lung carcinoma NCI-H69 and PC9 cells. Glycobiology 9:637–643PubMedCrossRefGoogle Scholar
  48. Schnyder-Candrian S, Borsig L, Moser R, Berger EG (2000) Localization of α1,3-fucosyltransferase VI in Weibel-Palade bodies of human endothelial cells. Proc Natl Acad Sci USA 97:8369–8374PubMedCrossRefGoogle Scholar
  49. Takada A, Ohmori K, Takahashi N, Tsuyuoka K, Yago K, Zenita K, Hasegawa A, Kannagi R (1991) Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun 179:713–719PubMedCrossRefGoogle Scholar
  50. Takada A, Ohmori K, Yoneda T, Tsuyuoka K, Hasegawa A, Kiso M, Kannagi R (1993) Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res 53:354–361PubMedGoogle Scholar
  51. Thompson S, Matta KL, Turner GA (1991) Changes in fucose metabolism associated with heavy drinking and smoking: a preliminary report. Clin Chim Acta 201:59–64PubMedCrossRefGoogle Scholar
  52. Weston BW, Smith PL, Kelly RJ, Lowe JB (1992) Molecular cloning of a fourth member of a human α(1,3)fucosyltransferase gene family. Multiple homologous sequences that determine expression of the Lewis X, sialyl Lewis X, and difucosyl sialyl Lewis X epitopes. J Biol Chem 267:24575–24584PubMedGoogle Scholar
  53. Weston BW, Hiller KM, Mayben JP, Manousos GA, Bendt KM, Liu R, Cusack JC Jr (1999) Expression of human α(1,3)fucosyltransferase antisense sequences inhibits selectinmediated adhesion and liver metastasis of colon carcinoma cells. Cancer Res 59:2127–2135PubMedGoogle Scholar
  54. Yago K, Zenita K, Ginya H, Sawada M, Ohmori K, Okuma M, Kannagi R, Lowe JB (1993) Expression of α(1,3)fucosyltransferases which synthesize sialyl Lex and sialyl Lea, the carbohydrate ligands for E-and P-selectins, in human malignant cell lines. Cancer Res 53:5559–5565PubMedGoogle Scholar
  55. Yazawa S, Tanaka S, Nishimura T, Miyanaga K, Kochibe N (1999) Plasma α1,3-fucosyltransferase deficiency in schizophrenia. Exp Clin Immunogenet 16:125–130PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Reiji Kannagi
    • 1
  1. 1.Department of Molecular PathologyAichi Cancer Center Research InstituteNagoyaJapan

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