A missense mutation in the FUT6 gene results in total absence of alpha3-fucosylation of human alpha1-acid glycoprotein.
The major alpha3-fucosyltransferase activity in human plasma is encoded by the gene for fucosyltransferase VI (FUT6). A missense mutation (Gly-739 --> Ala) in this gene is responsible for deficiency of enzyme activity in plasma. To examine whether this fucosyltransferase is the sole enzyme responsible for the alpha3-fucosylation of serum glycoproteins in the liver, we studied the fucosylation of three glycoproteins in sera of individuals with or without inactivated FUT3 and/or FUT6 gene(s) but with a functional FUT5 gene. alpha1-Acid glycoprotein was used as the principal reporter protein for liver alpha3-fucosyltransferase activity, because of its high fucose content. In all individuals with the FUT6 missense mutation Gly-739 --> Ala in double dose, no fucosylation of alpha1-acid glycoprotein was found. This alpha1-acid glycoprotein was not intrinsically resistant to fucosylation, since it was susceptible to in vitro fucosylation using an alpha3/4-fucosyltransferase isolated from human milk. The same result was found for alpha1-antichymotrypsin and alpha1-protease inhibitor. On the other hand in all individuals with alpha3-fucosyltransferase activity in plasma, alpha3-fucosylated glycoforms of the glycoproteins studied were found. The degree of fucosylation of alpha1-acid glycoprotein was correlated with alpha3-fucosyltransferase activity (Rs = 0.82). These data indicate that the product of FUT6, but not of FUT3 or of FUT5, is responsible for the alpha3-fucosylation of glycoproteins produced in liver and suggest that this organ is a major source of alpha3-fucosyltransferase activity in plasma.
Brinkman-Van der Linden
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EC
Department of Medical Chemistry, Faculty of Medicine, Van der Boechorststraat 7, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands.
Mollicone
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Oriol
R
R
Larson
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Van den Eijnden
D H
DH
Van Dijk
W
W
D000409:Alanine; D004912:Erythrocytes / Q000276:immunology; D005060:Europe / Q000208:ethnology; D005260:Female; D005643:Fucose / Q000032:analysis; D005647:Fucosyltransferases / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D005838:Genotype; D005998:Glycine; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007214:Indonesia / Q000208:ethnology; D007700:Kinetics; D007983:Lewis Blood Group Antigens / Q000097:blood / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008895:Milk, Human / Q000276:immunology; D009961:Orosomucoid / Q000096:biosynthesis* / Q000737:chemistry; D017354:Point Mutation; D012016:Reference Values; D012463:Saliva / Q000276:immunology
D007983:Lewis Blood Group Antigens; D009961:Orosomucoid; D005643:Fucose; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D000409:Alanine; D005998:Glycine