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Gene Review

FUT3  -  fucosyltransferase 3 (galactoside 3(4)-L...

Homo sapiens

Synonyms: Blood group Lewis alpha-4-fucosyltransferase, CD174, FT3B, FucT-III, Fucosyltransferase 3, ...
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Disease relevance of FUT3


High impact information on FUT3

  • We have generated transgenic mice that express the immunoglobulin (Ig)M heavy chain and kappa light chain genes coding for a human IgM rheumatoid factor (RF), Les. Transgenic B cells expressing human IgM RF show striking similarities to their counterparts in normal humans [5].
  • We isolated the protein-coding region of the Lewis FT cDNA from Le(+) and Le(-) gastric mucosa by polymerase chain reaction (PCR) amplification [6].
  • The metastatic parental cell line, HT-29LMM, expressed high levels of sialyl Lewis x, sialyl Lewis a, alpha(1,3/1,4)fucosyltransferase activity, and FUT3 transcript, but antisense transfectant cell lines did not [1].
  • By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25 LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained the mucus cells of surface gastric epithelium independently of ABO or Lewis status [7].
  • TNF-alpha was shown to increase alpha1,3-fucosyltransferase activity as well as expression of the two alpha1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4 [8].

Chemical compound and disease context of FUT3


Biological context of FUT3


Anatomical context of FUT3

  • Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels [13].
  • COLO-205 cells expressed high levels of sialyl Lewis x/a, alpha(1,3)fucosyltransferase activity, and FUT3/6 transcripts, but COLO</205-derived antisense transfectant cell lines AS5C and AS7A did not [14].
  • Analysis of the expression of Fut genes that encode alpha-1,3-fucosyltransferases, the enzymes that generate the Le(x) determinant, revealed that confluent/contact-inhibited cultures of rabbit corneal epithelium contain markedly elevated levels of Fut4 and Fut3/5/6 gene transcripts compared with sparse cultures [15].
  • We examined effects on the immune system by giving genetically mercury-susceptible Brown Norway (BN) rats and mercury-resistant Lewis (LE) rats silver amalgam restorations in 4 molars of the upper jaw, causing a body burden similar to that described in human amalgam-bearers (from 250 to 375 mg amalgam/kg body weight) [16].
  • Animal studies show that following damage to inner-ear receptors, central representations of intact lesion-edge (LE) frequencies become enlarged (map reorganization) [17].

Associations of FUT3 with chemical compounds

  • These data suggested that the J28 glycotope encompasses structures initiated by Core2GlcNAc-T and further fucosylated by alpha3/4-Fuc-T such as FUT3, likely on GlcNAc residues [18].
  • In contrast to human FUT3, the S. alba alpha4-FucT was insensitive to N-ethylmaleimide (NEM) treatment [19].
  • The in vitro inhibitory activity of UDP-Gal, GDP-Fuc and UDP-GlcNAc analogues towards glycosyltransferases (beta-1,4-GalT, FUT3 and LgtA) was evaluated through a competition fluorescence assay and IC(50) values of 40muM, 2mM and 3.5mM were obtained, respectively [20].
  • Basal expression levels of hST3GalIV, FUT3 and C2/4GnT mRNA, involved in the biosynthesis of sialyl-Lewis x, were higher than those of other glycosyltransferases in NCI-H292 cells [21].
  • In order to determine the potential role(s) of the alpha4-fucosylation during vegetative development, transgenic tobacco plants overexpressing a human Lewis fucosyltransferase (hFUT3), which transfers a fucose residue in a alpha(1,4)-linkage on complex glycans, have been developed [22].

Regulatory relationships of FUT3

  • All Le(a+b-) individuals (nonsecretors) were homozygous for the FUT2 G428A mutation and all Le(a-b-) individuals had inactivating mutations on both FUT3 alleles [23].

Other interactions of FUT3

  • Alternatively spliced transcripts were identified for FUT3 and FUT6 in kidney, liver, and colon [9].
  • Thus, tissue-specific post-transcriptional modifications are associated with expression patterns of FUT3, FUT5, and FUT6 [9].
  • The Lewis (Le) histo-blood group system comprises two major antigens, Le(a) and Le(b) which are determined by alpha (1,2)-fucosyltransferase (FUT2) and alpha (1,3/1,4)-fucosyltransferase (FUT3) [11].
  • For the two remaining loci, FUT9 and FUT3/5/6, the location may correspond to a new small syntenic area or to an insertion [24].
  • These CHO-K1 cells have been previously transfected with the cDNA encoding Core2GlcNAc-T and/or FUT3 and/or FUT7 [18].

Analytical, diagnostic and therapeutic context of FUT3

  • The expression of FUT5 is weaker than FUT3 and FUT6 and the RT-PCR signal is faint and irregular [25].
  • There was no decrease in enzyme activity nor of immunofluorescence staining on cells transfected with the construct containing the isolated C314T mutation compared with cells transfected with a wild type FUT3 allele control [26].
  • Determination of Lewis FUT3 gene mutations by PCR using sequence-specific primers enables efficient genotyping of clinical samples [27].
  • From RT-PCR studies, enzyme specificity of cellular extracts towards a panel of synthetic carbohydrate acceptors and Western blot analysis we concluded that Lea, sLea and Leb were synthesised by FUT3, whereas Lex and Ley were synthesized by FUT4 and FUT9 in both cell lines [28].
  • After 5aza-2'deoxycytidine MKN45 showed increased levels of FUT3 and Le(a), by immunohistochemistry and Real-Time PCR, whereas GP220 showed an increase in FUT3 without increase of Le(a) [4].


  1. Expression of human alpha(1,3)fucosyltransferase antisense sequences inhibits selectin-mediated adhesion and liver metastasis of colon carcinoma cells. Weston, B.W., Hiller, K.M., Mayben, J.P., Manousos, G.A., Bendt, K.M., Liu, R., Cusack, J.C. Cancer Res. (1999) [Pubmed]
  2. Peritoneal colonization by human pancreatic cancer cells is inhibited by antisense FUT3 sequence. Aubert, M., Panicot-Dubois, L., Crotte, C., Sbarra, V., Lombardo, D., Sadoulet, M.O., Mas, E. Int. J. Cancer (2000) [Pubmed]
  3. Influence of the combined ABO, FUT2, and FUT3 polymorphism on susceptibility to Norwalk virus attachment. Marionneau, S., Airaud, F., Bovin, N.V., Le Pendu, J., Ruvoën-Clouet, N. J. Infect. Dis. (2005) [Pubmed]
  4. Expression of Le(a) in gastric cancer cell lines depends on FUT3 expression regulated by promoter methylation. Serpa, J., Mesquita, P., Mendes, N., Oliveira, C., Almeida, R., Santos-Silva, F., Reis, C.A., Lependu, J., David, L. Cancer Lett. (2006) [Pubmed]
  5. Function of B cells expressing a human immunoglobulin M rheumatoid factor autoantibody in transgenic mice. Tighe, H., Chen, P.P., Tucker, R., Kipps, T.J., Roudier, J., Jirik, F.R., Carson, D.A. J. Exp. Med. (1993) [Pubmed]
  6. Analysis of Lewis fucosyltransferase genes from the human gastric mucosa of Lewis-positive and -negative individuals. Koda, Y., Kimura, H., Mekada, E. Blood (1993) [Pubmed]
  7. Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae. Bara, J., Gautier, R., Daher, N., Zaghouani, H., Decaens, C. Cancer Res. (1986) [Pubmed]
  8. Tumor necrosis factor alpha increases the expression of glycosyltransferases and sulfotransferases responsible for the biosynthesis of sialylated and/or sulfated Lewis x epitopes in the human bronchial mucosa. Delmotte, P., Degroote, S., Lafitte, J.J., Lamblin, G., Perini, J.M., Roussel, P. J. Biol. Chem. (2002) [Pubmed]
  9. Expression of human chromosome 19p alpha(1,3)-fucosyltransferase genes in normal tissues. Alternative splicing, polyadenylation, and isoforms. Cameron, H.S., Szczepaniak, D., Weston, B.W. J. Biol. Chem. (1995) [Pubmed]
  10. Relative positions of two clusters of human alpha-L-fucosyltransferases in 19q (FUT1-FUT2) and 19p (FUT6-FUT3-FUT5) within the microsatellite genetic map of chromosome 19. Reguigne-Arnould, I., Couillin, P., Mollicone, R., Fauré, S., Fletcher, A., Kelly, R.J., Lowe, J.B., Oriol, R. Cytogenet. Cell Genet. (1995) [Pubmed]
  11. Molecular basis of Lewis blood type in Taiwanese. Liu, T.C., Lin, S.F., Yang, T.Y., Perng, L.I., Jaung, S.J., Hu, C.Z., Chang, J.G. The Kaohsiung journal of medical sciences. (2000) [Pubmed]
  12. Molecular genetics of alpha-L-fucosyltransferase genes (H, Se, Le, FUT4, FUT5 and FUT6). Mollicone, R., Candelier, J.J., Reguigne, I., Couillin, P., Fletcher, A., Oriol, R. Transfusion clinique et biologique : journal de la Société française de transfusion sanguine. (1994) [Pubmed]
  13. Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. Orntoft, T.F., Vestergaard, E.M., Holmes, E., Jakobsen, J.S., Grunnet, N., Mortensen, M., Johnson, P., Bross, P., Gregersen, N., Skorstengaard, K., Jensen, U.B., Bolund, L., Wolf, H. J. Biol. Chem. (1996) [Pubmed]
  14. Transfection of alpha(1,3)fucosyltransferase antisense sequences impairs the proliferative and tumorigenic ability of human colon carcinoma cells. Hiller, K.M., Mayben, J.P., Bendt, K.M., Manousos, G.A., Senger, K., Cameron, H.S., Weston, B.W. Mol. Carcinog. (2000) [Pubmed]
  15. Role of the Lewis(x) glycan determinant in corneal epithelial cell adhesion and differentiation. Cao, Z., Zhao, Z., Mohan, R., Alroy, J., Stanley, P., Panjwani, N. J. Biol. Chem. (2001) [Pubmed]
  16. Activation of the immune system and systemic immune-complex deposits in Brown Norway rats with dental amalgam restorations. Hultman, P., Lindh, U., Hörsted-Bindslev, P. J. Dent. Res. (1998) [Pubmed]
  17. Neuromagnetic indicators of auditory cortical reorganization of tinnitus. Weisz, N., Wienbruch, C., Dohrmann, K., Elbert, T. Brain (2005) [Pubmed]
  18. The formation of the oncofetal J28 glycotope involves core-2 beta6-N-acetylglucosaminyltransferase and alpha3/4-fucosyltransferase activities. Panicot, L., Mas, E., Pasqualini, E., Zerfaoui, M., Lombardo, D., Sadoulet, M.O., El Battari, A. Glycobiology (1999) [Pubmed]
  19. Biochemical characterization of Silene alba alpha4-fucosyltransferase and Lewis a products. Léonard, R., Lhernould, S., Carlué, M., Fleurat, P., Maftah, A., Costa, G. Glycoconj. J. (2005) [Pubmed]
  20. Non-isosteric C-glycosyl analogues of natural nucleotide diphosphate sugars as glycosyltransferase inhibitors. Vidal, S., Bruyère, I., Malleron, A., Augé, C., Praly, J.P. Bioorg. Med. Chem. (2006) [Pubmed]
  21. Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line. Ishibashi, Y., Inouye, Y., Okano, T., Taniguchi, A. Glycoconj. J. (2005) [Pubmed]
  22. Alteration of gibberellin response in transgenic tobacco plants which express a human Lewis fucosyltransferase. Joly, C., Maftah, A., Riou-Khamlichi, C. Plant Physiol. Biochem. (2004) [Pubmed]
  23. Typing for the human lewis blood group system by quantitative fluorescence-activated flow cytometry: large differences in antigen presentation on erythrocytes between A(1), A(2), B, O phenotypes. Larson, G., Svensson, L., Hynsjö, L., Elmgren, A., Rydberg, L. Vox Sang. (1999) [Pubmed]
  24. Cytogenetics, conserved synteny and evolution of chicken fucosyltransferase genes compared to human. Coullin, P., Crooijmans, R.P., Fillon, V., Mollicone, R., Groenen, M.A., Adrien-Dehais, C., Bernheim, A., Zoorob, R., Oriol, R., Candelier, J.J. Cytogenet. Genome Res. (2003) [Pubmed]
  25. FUT4 and FUT9 genes are expressed early in human embryogenesis. Cailleau-Thomas, A., Coullin, P., Candelier, J.J., Balanzino, L., Mennesson, B., Oriol, R., Mollicone, R. Glycobiology (2000) [Pubmed]
  26. Significance of individual point mutations, T202C and C314T, in the human Lewis (FUT3) gene for expression of Lewis antigens by the human alpha(1,3/1,4)-fucosyltransferase, Fuc-TIII. Elmgren, A., Mollicone, R., Costache, M., Börjeson, C., Oriol, R., Harrington, J., Larson, G. J. Biol. Chem. (1997) [Pubmed]
  27. Determination of Lewis FUT3 gene mutations by PCR using sequence-specific primers enables efficient genotyping of clinical samples. Grahn, A., Elmgren, A., Aberg, L., Svensson, L., Jansson, P.A., Lönnroth, P., Larson, G. Hum. Mutat. (2001) [Pubmed]
  28. Different expression levels of alpha3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines. Escrevente, C., Machado, E., Brito, C., Reis, C.A., Stoeck, A., Runz, S., Marmé, A., Altevogt, P., Costa, J. Int. J. Oncol. (2006) [Pubmed]
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