Fucosyltransferase 3 (FUT3)

Fucosyltransferase 3 (FUT3) is a key enzyme of the fucosyltransferase family responsible for the biosynthesis of Lewis blood group antigens, by catalyzing the addition of fucose in α1,3- and α1,4-linkages to glycolipid and glycoprotein precursors[1][2][4]. The enzyme is encoded by the *FUT3* gene and acts primarily in exocrine epithelial cells, producing antigens that are critical in cell–cell adhesion, immune modulation, and cell signaling. These fucosylated oligosaccharides are shed into the bloodstream and secondarily absorbed onto the surface of erythrocytes, generating Lewis blood group phenotypes[1][4][5]. FUT3 activity is vital for the expression of clinically relevant glycan motifs—such as Lewis a (Le^a^), Lewis b (Le^b^), sialyl Lewis x (sLe^x^), and others—important in embryogenesis, cancer metastasis, inflammatory responses, and host–microbe interactions. Loss-of-function mutations in FUT3 lead to the Lewis-negative blood group, impacting transfusion compatibility and disease susceptibility[1][2][4][5]. Altered FUT3 expression is implicated in tumor progression (by enhancing selectin-mediated tumor cell adhesion), gastrointestinal cancer development, and response to infection[1][5][8]. Serum CA19-9, whose biosynthesis depends on FUT3, serves as a biomarker in oncology[1][2]. Although currently there are no approved drugs specifically targeting FUT3, experimental downregulation via RNA interference has shown that FUT3 suppression can inhibit proliferation and metastasis in some cancer models[9].

Other names

3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferaseFT3BLELewis fucosyltransferaseFucT-IIICD174blood group Lewis alpha-4-fucosyltransferasefucosyltransferase IIIgalactoside 3(4)-L-fucosyltransferase

(For potential drugs/inhibitors under research) Competitive inhibition of fucosyltransferase activity; RNA interference (miRNA/siRNA)–mediated downregulation of FUT3 gene expression