A missense mutation in the FUT6 gene results in total absence of alpha 3-fucosylation of human alpha(1)-acid glycoprotein

被引:58
作者
BrinkmanVanderLinden, ECM
Mollicone, R
Oriol, R
Larson, G
VandenEijnden, DH
VanDijk, W
机构
[1] FREE UNIV AMSTERDAM, FAC MED, DEPT MED CHEM, 1081 BT AMSTERDAM, NETHERLANDS
[2] INSERM U178, F-94807 VILLEJUIF, FRANCE
[3] GOTHENBURG UNIV, SAHLGRENS HOSP, DEPT CLIN CHEM & TRANSFUS MED, S-41345 GOTHENBURG, SWEDEN
关键词
D O I
10.1074/jbc.271.24.14492
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The major alpha 3-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 alpha 3-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 FUTG gene(s) but with a functional FUT5 gene. alpha(1)-Acid glycoprotein was used as the principal reporter protein for liver alpha 3-fucosyltransferase activity, because of its high fucose content. In all individuals with the FUTG missense mutation Gly-739-->Ala in double dose, no fucosylation of alpha(1)-acid glycoprotein was found. This alpha(1)-acid glycoprotein was not intrinsically resistant to fucosylation, since it was susceptible to in vitro fucosylation using an alpha 3/4-fucosyltransferase isolated from human milk. The same result was found for alpha(1)-antichymotrypsin and alpha(1)-protease inhibitor. On the other hand in all individuals with alpha 3-fucosyltransferase activity in plasma, alpha 3-fucosylated glycoforms of the glycoproteins studied were found. The degree of fucosylation of alpha(1)-acid glycoprotein was correlated with alpha 3-fucosyltransferase activity (Rs = 0.82). These data indicate that the product of FUTG, but not of FUT3 or of FUT5, is responsible for the alpha 3-fucosylation of glycoproteins produced in liver and suggest that this organ is a major source of alpha 3-fucosyltransferase activity in plasma.
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页码:14492 / 14495
页数:4
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