Human FUT8 gene is located on chromosome 14q23.3 (Yamaguchi et al., 1999). This gene encompasses approximately 333 kb and contains nine exons with coding regions and three 5-untranslated exons (Yamaguchi et al., 2000; Martinez-Duncker et al., 2004).

Some splicing variants of the 5-untranslated region arise in a developmental stage-specific and tissue-specific manner (Martinez-Duncker et al., 2004). At least three different promoters appear to be functional in regulating the expression of the FUT8 gene. Three transcripts with different 5-untranslated regions have been identified. With respect to coding region, four variants were reported to encode polypeptides containing 575, 446, 308 and 169 amino acid residues. The 575 residue protein is a fully active alpha1,6-fucosyltransferase, which was first of the variants to be identified. The other variants have not yet been examined for enzymatic activity and biological function. The 308 amino acid variant is known to be expressed in the retina (Yamaguchi et al., 2000).

FUT8 was purified and cloned as a cDNA from porcine brain and a human gastric cancer cell line (Uozumi et al., 1996, Yanagidani et al., 1997). Human FUT8 is comprised of 575 amino acids, with a calculated molecular weight of 66516. FUT8 contains no N-glycosylation sites. This enzyme belongs to the GT23 family of the CaZY classification. The structual analysis of a transmembrane domain-truncated form of FUT8 showed that the enzyme consists of a catalytic domain, an N-terminal coiled-coil domain and a C-terminal SH3 domain (Ihara et al., 2007). The catalytic domain was structurally classfied as a member of the GT-B group of glycosylatransferases.

FUT8 gene is widely expressed in human tissues (Martinez-Duncker et al., 2004). The FUT8 gene is expressed at relatively high levels in the brain, placenta, lung, stomach, small intestine and jejunum, while pancreas, uterus, kidney and urinary bladder exhibit moderate expression. The FUT8 gene is weakly expressed in the heart, ileum, colon and spleen. On the other hand, the expression is not detectable in the normal liver (Miyoshi et al., 1997).

FUT8 is a typical type II membrane protein and is localized in the Golgi apparatus.

FUT8 catalyzes the transfer of a fucose residue from GDP-fucose to the reducing terminal GlcNAc of Asn-linked oligosaccharide (N-glycan) via an alpha1.6-linkage (Figure 3). The resulting fucosyl residue is often refered to as a core fucose. The reaction does not require any divalent cations or cofactors. The deletion of the FUT8 gene in mice leads to severe phenotypes that exhibit growth retardation, lung emphysema and death during postnatal development (Wang et al., 2005). As has been clearly shown in studies using knockout mice, the lack of core fucosylation resulted in the biological activities of various proteins to be perturbed (Taniguchi et al., 2006; Takahashi et al., 2009). Examples of this include the TGF-beta1 receptor (Wang et al., 2005), EGF receptor (Wang et al., 2006), VEGF receptor-2 (Wang et al., 2009), LRP-1 (Lee et al., 2006), E-cadherin (Osumi et al., 2009), alpha3beta1 integrin (Zhao et al., 2006), VCAM and alpha4beta1 integrin (Li et al., 2008). The binding affinity of the core fucose-deleted TGF-beta receptor to TGF-beta 1 is diminished in fut8-null mice, resulting in the downregulation of TGF-beta 1 signaling (Wang et al., 2005). The unusual overexpression of matrix metalloproteinases such as MMP-12 and MMP-13 is associated with the impaired receptor function, and has been proposed to cause the lung-destructive phenotypes. The EGF receptor in fut8 null mice is also affected in terms of its binding affinity to EGF and EGF-induced phoshorylation (Wang et al., 2006). These studies strongly suggest that FUT8 and core fucose structures regulate the receptor function.
In addition, core fucosylation was reported to be involved in antibodydependent cellular cytotoxicity (ADCC) (Shields et al., 2002; Shinkawa et al., 2003). The lack of core fucose of N-glycan in the Fc region of the IgG1 molecule enhances ADCC activity up to 50-100-fold. This discorvery promises to be useful in the development of antibody therapy in cancer treatment.

The sequence identities between human FUT8 and other organisms are as follows :
Chimpangee (100%), Dog (97.7%), Cow (97.5%), Pig (95.6%), Rat (96.6%), Mouse (96.5%), Chicken (93.9%), Clawed frog (90.3%), Zebrafish (79.5%), Takifugu (80.2%), Tetraodon (79.8%), Sea squirt (23.2%), Fruit fly (43.7%), C. elegans (34.8%).
Eight cysteine residues in the catalytic domain are conserved among these species, except for ciona (Ihara et al., 2007).
FUT8 contains three short regions that are highly conserved in FUT8, alpha1,2-, bacterial alpha1,6-, and protein O-fucosyltransferases (Oriol et al., 1999; Takahashi et al., 2000a; Chazalet et al., 2001; Martinez-Duncker et al., 2003). The structual analysis has shown that these regions are located adjacent to one another in the Rossmann fold of FUT8 (Ihara et al., 2007). In addition, the C-terminal SH3 domain of FUT8 is structually similar to the typical SH3 domain that is found in many proteins.

One frame-shit mutation and 4 substitution mutants have been identified to date in various SNPs of the FUT8 gene. The frame shift mutant is due to the insertion of a T at position 2 of the codon for Val-85, resulting in 85-VLEEQLVK-92 being change to 85-VFRRAACter-92. The four substitution mutants are K101Q, L153V, E181G and T267K. These mutants are due to A being substituted by C at position 1 of codon 101, C to G at position 1 of codon 153, A to G at position 2 of codon 181, and C to A at posision 2 of codon 267, respectively. Effects of these substitutions on enzymatic activity are not currently known.