Ancestral exonic organization of FUT8, the gene encoding the alpha 6-fucosyltransferase, reveals successive peptide domains which suggest a particular three-dimensional core structure for the alpha 6-fucosyltransferase family

Based on PCR strategies and expression studies, we define the genomic organ ization of the FUT8b gene. This gene encodes the only known mammalian enzym e transferring fucose in an (alpha1-->6 linkage on the asparagine-branched GlcNAc residue of the chitobiose unit of complex N-glycans. The intron/exon organization of the bovine coding sequence determines five successive func tional domains. The first exon encodes a domain homologous to cytoskeleton proteins, the second presents a proline-rich region including a motif XPXPP YXP similar to the peptide ligand of the SH3-domain proteins, the third enc odes a gyrase-like domain tan enzyme which can bind nucleotides), and the f ourth encodes a peptide sequence homologous to the catalytic domain of prot eins transferring sugars. Finally, the last exon encodes a domain homologou s to the SH3 conserved motif of the SH2-SH3 protein family. This organizati on suggests that intramolecular interactions might give a tulip-shaped scaf folding, including the catalytic pocket of the enzyme in the Golgi lumen. D educed from the published sequence of chromosome 14 (AL109847), the human g ene organization of FUT8 seems to be similar to that of bovine FUT8b, altho ugh the exon partition is more pronounced (bovine exons 1 and 2 correspond to human exons 1-6). The mosaicism and phylogenetic positions of the alpha6 -fucosyltransferase genes are compared with those of other fucosyltransfera se genes.