HGNC Approved Gene Symbol: FUT7
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:137,030,174-137,032,088 (from NCBI)
The sialyl Lewis x oligosaccharide determinant is an essential component of leukocyte counterreceptors for E-selectin (131210)- and P-selectin (173610)-mediated adhesions of leukocytes. This oligosaccharide molecule is displayed on the surfaces of granulocytes, monocytes, and natural killer cells. Formation of leukocyte adhesions to these selectins is an early and important step in the process that ultimately allows leukocytes to leave the vascular tree and become recruited into lymphoid tissues and sites of inflammation. Natsuka et al. (1994) and Sasaki et al. (1994) isolated cDNAs encoding a human leukocyte alpha-1,3-fucosyltransferase, FUT7, capable of synthesizing the sialyl Lewis x determinant. The cDNA predicts a 342-amino acid type II transmembrane protein typical of mammalian glycosyltransferases. By Northern blot analysis, Natsuka et al. (1994) showed that FUT7 was expressed in HL-60 cells, a human promyelocytic cell line, and in YT cells, a natural killer-like cell line. Sequence comparisons indicate that the predicted polypeptide sequence shares approximately 38 to 47% overall identity with other FUTs (e.g., FUT3, 111100; FUT6, 136836).
Natsuka et al. (1994) found when FUT7 was expressed in mammalian cells, the cDNA directed synthesis of cell surface sialyl Lewis x moieties, but not Lewis x, Lewis A, sialyl Lewis a, or VIM-2 determinants. Sasaki et al. (1994) demonstrated in vivo ability of FUT7 to synthesize the sialyl Lewis x moiety that binds to E-selectin and reported the restricted expression of FUT7 in leukocytes.
Mahdavi et al. (2002) identified sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and showed that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin was identified as sabA. Mahdavi et al. (2002) concluded that the ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might contribute to virulence and the extraordinary chronicity of H. pylori infection.
Chen et al. (2006) noted that activated T cells, particularly Th1 cells, express sialyl Lewis x, but resting T cells do not. Using reporter analysis, they showed that TBET (TBX21; 604895) promoted and GATA3 (131320) repressed transcription of FUT7. TBET interfered with GATA3 binding to its target DNA, but GATA3 also interfered with TBET binding to the FUT7 promoter. GATA3 regulated FUT7 transcription by recruiting, in a phosphorylation-dependent manner, histone deacetylase-3 (HDAC3; 605166) and HDAC5 (605315) and by competing with CBP (CREBBP; 600140)/p300 (EP300; 602700) in binding to the N terminus of TBET. Maximal expression of FUT7 and sialyl Lewis x in T cells was obtained by ROG (ZBTB32; 605859)-mediated suppression of GATA3. Chen et al. (2006) concluded that the GATA3/TBET transcription factor complex regulates cell lineage-specific expression of lymphocyte homing receptors and that glycoconjugates are regulated by this complex to attain cell lineage-specific expression in Th1 and Th2 lymphocyte subsets.
Natsuka et al. (1994) mapped the FUT7 gene to chromosome 9 by somatic cell hybrid analysis.
Bengtson et al. (2001) identified 3 individuals who were heterozygous for a 326G-A point mutation (arg110 to gln) in the FUT7 gene. Screening of family members revealed a homozygote for the mutation. Neutrophils isolated from individuals carrying the mutation showed lowered expression of SLeX and elevated expression of CD65 compared to controls. The homozygous individual was found to have ulcer disease, noninsulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjogren syndrome, but the relationship between disease and the mutation was not clear. Bengtson et al. (2001) determined that the mutation causes loss of function. Biochemical analysis of lysates obtained from COS-7 cells transiently transfected with the mutated FUT7 construct revealed no FUT7 activity, and immunocytochemical visualization revealed no SLeX on the surface of these cells.
Pang et al. (2011) used ultrasensitive mass spectrometric analyses to demonstrate that the sialyl-Lewis(X) (SLEX) sequence, composed of NeuAc-alpha2-3Gal-beta1-4(Fuc-alpha1-3)GlcNAc, a well-known selectin ligand, is the most abundant terminal sequence on the N- and O-glycans of human zona pellucida. Sperm-ZP binding was largely inhibited by glycoconjugates terminated with sialyl-Lewis(X) sequences or by antibodies directed against this sequence. Thus, Pang et al. (2011) concluded that the sialyl-Lewis(X) sequence represents the major carbohydrate ligand for human sperm-egg binding.
Bengtson, P., Larson, C., Lundblad, A., Larson, G., Pahlsson, P. Identification of a missense mutation (G329A; arg110-to-gln) in the human FUT7 gene. J. Biol. Chem. 276: 31575-31582, 2001. [PubMed: 11404359] [Full Text: https://doi.org/10.1074/jbc.M104165200]
Chen, G.-Y., Osada, H., Santamaria-Babi, L. F., Kannagi, R. Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. Proc. Nat. Acad. Sci. 103: 16894-16899, 2006. [PubMed: 17075044] [Full Text: https://doi.org/10.1073/pnas.0607926103]
Mahdavi, J., Sonden, B., Hurtig, M., Olfat, F. O., Forsberg, L., Roche, N., Angstrom, J., Larsson, T., Teneberg, S., Karlsson, K.-A., Altraja, S., Wadstrom, T., and 11 others. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297: 573-578, 2002. [PubMed: 12142529] [Full Text: https://doi.org/10.1126/science.1069076]
Natsuka, S., Gersten, K. M., Zenita, K., Kannagi, R., Lowe, J. B. Molecular cloning of a cDNA encoding a novel human leukocyte alpha-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant. J. Biol. Chem. 269: 16789-16794, 1994. Note: Erratum: J. Biol. Chem. 269: 20806 only, 1994. [PubMed: 8207002]
Pang, P.-C., Chiu, P. C. N., Lee, C.-L., Chang, L.-Y., Panico, M., Morris, H. R., Haslam, S. M., Khoo, K.-H., Clark, G. F., Yeung, W. S. B., Dell, A. Human sperm binding is mediated by the sialyl-Lewis(X) oligosaccharide on the zona pellucida. Science 333: 1761-1764, 2011. [PubMed: 21852454] [Full Text: https://doi.org/10.1126/science.1207438]
Sasaki, K., Kurata, K., Funayama, K., Nagata, M., Watanabe, E., Ohta, S., Hannai, N., Nishi, T. Expression cloning of a novel alpha-1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis x carbohydrate determinants in leukocytes. J. Biol. Chem. 269: 14730-14737, 1994. [PubMed: 8182079]