Identification of two functionally deficient plasma ?3-fucosyltransferase (FUT6) alleles

Elmgren, Anders; Börjeson, Cecilia; Mollicone, Rosella; Oriol, Rafaël; Fletcher, Anne; Larson, Göran

doi:10.1002/1098-1004(200012)16:6<473::aid-humu4>3.0.co;2-t

Cited by 8 publications

(2 citation statements)

References 37 publications

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“…As none of the known inactivating natural mutations was found in the four complete primate Lewis-like peptide sequences (Mollicone et al 1994a(Mollicone et al , 1994bOrntoft et al 1996;Pang et al 1998aPang et al , 1998bPang et al , 1999Elmgren et al 2000), transient expressions of these enzymes in COS-7 cells were performed in order to determine their ability to transfer fucose in ␣1,3 or in ␣1,4 linkage or in both ( fig. 5).…”

Section: Acceptor Substrate Specificity Of the New Primate ␣3/4-fucosmentioning

confidence: 99%

α1,4-Fucosyltransferase Activity: A Significant Function in the Primate Lineage has Appeared Twice Independently

Dupuy¹,

Germot²,

Marenda³

et al. 2002

Molecular Biology and Evolution

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In the animal kingdom the enzymes that catalyze the formation of alpha1,4 fucosylated-glycoconjugates are known only in apes (chimpanzee) and humans. They are encoded by FUT3 and FUT5 genes, two members of the Lewis FUT5-FUT3-FUT6 gene cluster, which had originated by duplications of an alpha3 ancestor gene. In order to explore more precisely the emergence of the alpha1,4 fucosylation, new Lewis-like fucosyltransferase genes were studied in species belonging to the three main primate groups. Two Lewis-like genes were found in brown and ruffed lemurs (prosimians) as well as in squirrel monkey (New World monkey). In the latter, one gene encodes an enzyme which transfers fucose only in alpha1,3 linkage, whereas the other is a pseudogene. Three genes homologous to chimpanzee and human Lewis genes were identified in rhesus macaque (Old World monkey), and only one encodes an alpha3/4-fucosyltransferase. The ability of new primate enzymes to transfer fucose in alpha1,3 or alpha1,3/4 linkage confirms that the amino acid R or W in the acceptor-binding motif "HH(R/W)(D/E)" is required for the type 1/type 2 acceptor specificity. Expression of rhesus macaque genes proved that fucose transfer in alpha1,4 linkage is not restricted to the hominoid family and may be extended to other Old World monkeys. Moreover, the presence of only one enzyme supporting the alpha1,4 fucosylation in rhesus macaque versus two enzymes in hominoids suggests that this function occurred twice independently during primate evolution.

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Section: Acceptor Substrate Specificity Of the New Primate ␣3/4-fucosmentioning

confidence: 99%

α1,4-Fucosyltransferase Activity: A Significant Function in the Primate Lineage has Appeared Twice Independently

Dupuy¹,

Germot²,

Marenda³

et al. 2002

Molecular Biology and Evolution

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“…Point mutations inactivating or disrupting Fuc-TIII (␣1,3/1,4-fucosyltransferase, Lewis enzyme) give rise to Lewis negative phenotypes (21)(22)(23)(24). Inactivating mutations have also been found in the FUT6 gene coding for the plasma ␣1,3-fucosyltransferase, Fuc-TVI (25)(26)(27)(28). However, there have been no reports on genetic polymorphism in the genes encoding for the ␣1,3-fucosyltransferases expressed in human leukocytes.…”

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confidence: 99%

Identification of a Missense Mutation (G329A; Arg110→ Gln) in the Human FUT7 Gene

Bengtson¹,

Larson²,

Lundblad³

et al. 2001

Journal of Biological Chemistry

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The human FUT7 gene codes for the ␣1,3-fucosyltransferase VII (Fuc-TVII), which is involved in the biosynthesis of the sialyl Lewis x (SLe x ) epitope on human leukocytes. The FUT7 gene has so far been considered to be monomorphic. Neutrophils isolated from patients with ulcerative colitis were examined for apparent alterations in protein glycosylation patterns by Western blot analysis using monoclonal antibodies directed against SLe x and SLe x -related epitopes. One individual showed lower levels of SLe x expression and an elevated expression of CD65s compared to controls. The coding regions of the FUT7 gene from this individual were cloned, and a G329A point mutation (Arg 110 3 Gln) was found in one allele, whereas the other FUT7 allele was wild type. No Fuc-TVII enzyme activity was detected in COS-7 cells transiently transfected with the mutated FUT7 construct. The FUT7 Arg 110 is conserved in all previously cloned vertebrate ␣1,3-fucosyltransferases. Polymerase chain reaction followed by restriction enzyme cleavage was used to screen 364 unselected Caucasians for the G329A mutation, and a frequency of <1% for this mutation was found (3 heterozygotes). Genetic characterization of the family members of one of the additional heterozygotes identified one individual carrying the G329A mutation in both FUT7 alleles. Peripheral blood neutrophils of this homozygously mutated individual showed a lowered expression of SLe x and an elevated expression of CD65s when analyzed by Western blot and flow cytometry. The homozygous individual was diagnosed with ulcer disease, non-insulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjö gren's syndrome but had no history of recurrent bacterial infections or leukocytosis.

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The fucosyltransferase gene family: an amazing summary of the underlying mechanisms of gene evolution

Javaud¹,

Dupuy²,

Maftah³

et al. 2003

Contemporary Issues in Genetics and Evolution

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Identification of two functionally deficient plasma ?3-fucosyltransferase (FUT6) alleles

Cited by 8 publications

References 37 publications

α1,4-Fucosyltransferase Activity: A Significant Function in the Primate Lineage has Appeared Twice Independently

α1,4-Fucosyltransferase Activity: A Significant Function in the Primate Lineage has Appeared Twice Independently

Identification of a Missense Mutation (G329A; Arg110→ Gln) in the Human FUT7 Gene

The fucosyltransferase gene family: an amazing summary of the underlying mechanisms of gene evolution

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