Functions (from Uniprot)

Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.

Catalytic activity (from Uniprot)

GDP-beta-L-fucose + N(4)-(N-acetyl-beta-D-glucosaminyl-(1->2)-alpha-D-mannosyl-(1->3)-(N-acetyl-beta-D-glucosaminyl-(1->2)-alpha-D-mannosyl-(1->6))-beta-D-mannosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->4)-N-acetyl-beta-D-glucosaminyl)asparagine = GDP + N(4)-(N-acetyl-beta-D-glucosaminyl-(1->2)-alpha-D-mannosyl-(1->3)-(N-acetyl-beta-D-glucosaminyl-(1->2)-alpha-D-mannosyl-(1->6))-beta-D-mannosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->4)-(alpha-L-fucosyl-(1->6))-N-acetyl-beta-D-glucosaminyl)asparagine.

Disease relevance of FUT8

• Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation [1].
• Herein, we investigated the expression of alpha1,6-fucosyltransferase (FUT8) in 133 cases of thyroid carcinomas using an immunohistochemical approach [1].
• In cases of human liver diseases, alpha1-6FucT is expressed in both hepatoma tissues and their surrounding tissues with chronic liver disease, but not in the case of normal liver [2].
• This enzyme was purified from a human fibroblast cell line, porcine brain, a human gastric cancer cell line and human blood platelets. cDNA cloning of porcine and human alpha1-6FucT was performed from a porcine brain and gastric cancer cell cDNA libraries, respectively [2].

High impact information on FUT8

• To understand the biological meaning of the alpha1-6FucT in hepatoma, especially in terms of metastasis, we established human hepatoma cell lines, which express high levels of alpha1-6FucT by transfection of the alpha1-6FucT gene and investigated intrahepatic metastasis after splenic injection to athymic mice [3].
• Alpha1-6 fucosyltransferase (alpha1-6FucT) catalyzes the transfer of fucose to the innermost GlcNAc in N-glycans [3].
• Attachment of alpha1-6FucT transfectants to a fibronectin-coated dish was decreased compared to controls because alpha5beta1 integrin was more strongly alpha1-6 fucosylated in the alpha1-6FucT transfectants [3].
• The role of core fucosylation in alpha3beta1 integrin-mediated events has been studied by using Fut8(+/+) and Fut8(-/-) embryonic fibroblasts, respectively [4].
• Overexpression of FUT8 mRNA in YB2/0 cells led to an increase of fucosylated oligosaccharides and decrease of ADCC of the IgG1 [5].

Biological context of FUT8

• The phylogeny of fucosyltransferase genes was completed by the addition of the FUT8 family of alpha(1,6)fucosyltransferase genes, which are the oldest genes of the fucosyltransferase family [6].
• The data suggest an expression of FUT8 regulated by three different promoters, starting transcription in exons A, B, or C [7].
• After transfection with these cDNA constructs the transcripts with 5'UT-exons A or C have higher expression of FUT8 transcripts and higher alpha6-fucosyltransferase activity, whereas the activity of the B series is about two-thirds lower for both parameters, suggesting that exon B reduces the expression of the transcripts [7].
• Cultivation of an alpha-1,6-fucosyltransferase (FUT8) knockout Chinese hamster ovary cell line in the presence or absence of a glycosidase inhibitor (either swainsonine or kifunensine) yielded antibody production of each of the three types without contamination by the others [8].
• In this study, we isolated a genomic clone for the human alpha1,6FucT gene (FUT8) and mapped it by fluorescence in situ hybridization to chromosome 14q24 [9].

Anatomical context of FUT8

• The most strongly expressed fucosyltransferase in the COS cells is the alpha1,6-enzyme transferring fucose to the innermost N -acetylglucosamine unit in N -glycan chains; this enzyme is similar in its properties to the product of the human FUT8 gene [10].
• Expression and activity of alpha1,6-fucosyltransferase (FUT8) in control and LAD II fibroblasts were comparable, thus excluding the possibility of a decreased activity of the transferase [11].
• Quantitative PCR analysis indicated that YB2/0 cells had lower expression level of FUT8 mRNA, which codes alpha1,6-fucosyltransferase, than CHO cells [5].
• Northern-blot analysis indicated high expression levels of alpha1-6FucT in brain and gastrointestinal-tract tissues of normal rats, as well as for a number of lung-cancer, gastric-cancer and colon-cancer cell lines [12].

Associations of FUT8 with chemical compounds

• GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1,6-fucosyltransferase (alpha1,6FucT) catalyzes the transfer of a fucosyl moiety from GDP-fucose to the asparagine-linked GlcNAc residue of complex N-glycans via alpha1,6-linkage [13].
• Kinetic analyses and inhibition studies using derivatives of GDP-beta-L-fucose revealed that FUT8 catalyzes the reaction which depends on a rapid equilibrium random mechanism and strongly recognizes the base portion and diphosphoryl group of GDP-beta-L-fucose [14].
• FUT8 encodes an alpha-1,6-fucosyltransferase that catalyzes the transfer of fucose from GDP-fucose to N-acetylglucosamine (GlcNAc) in an alpha-1,6 linkage [15].
• The increase in fucosylation was due to remaining synthesis of GDP-fucose via de novo pathway for the CHO line and the elevation of FUT8 expression by the YB2/0 cells [16].

Other interactions of FUT8

• The enzymes resembling the human FUT4 and FUT8 gene products both had pH optima of 7.0 and were resistant to 10 mM NEM [10].
• FUT8 is a typical type II membrane protein, which is localized in the Golgi apparatus [14].
• Identification of target proteins of N-acetylglucosaminyl-transferase V and fucosyltransferase 8 in human gastric tissues by glycomic approach [17].

References