• FUT3 exhibits broad specificity synthesizing all Lewis antigens, Le^a, Le^b, Le^X, Le^Y, sialyl Le^a (sLe^a), and sLe^X. Le^a and Le^b are histo-blood group antigens which are present not only on erythrocytes but also in gastrointestinal, pancreatic, and other tissues in the body.
• FUT3 α1-4-fucosyltransferase activity creates Lewis-a and Lewis-b on Type I (Galβ3GlcNAc, its preferred substrate) by transferring fucose to GlcNAc on either Type I chain (to make Lewis-a) or on H-antigen formed on Type I chain (to make Lewis-b). It is the only enzyme making Le^a, Le^b, and sLe^a in vivo, since FUT5 is a silent enzyme that is not expressed in any tissue.
• FUT3 can also act on Type II (Galβ4GlcNAc) lactosamine chains to create Lewis^X, Lewis^Y and sialyl Lewis-X type structures.
• FUT3 also forms the stage-specific embryonal antigen-1 (SSEA-1) in humans.
• FUT3, FUT4, FUT5, and FUT6 exhibit similar specificity for preferential fucose transfer to the inner GlcNAc on polylactosamine chains. FUT9 prefers the terminal modifications to create terminal Le^X.
• The sequence of FUT3 is similar to that of FUT5 and FUT6.
• Mouse do not express FUT3 and thus are devoid of Le^a Le^b type structures. Mouse SSEA-1 is created by FUT9 instead of FUT3.
• FUT3 is widely expressed in epithelial cells of the digestive tract, including salivary gland, mammary gland, esophagus, stomach, pancreas, small intestine, colon, and rectum. FUT3 is not expressed in hematopoietic cells. Le^a- and Le^b-active glycolipid antigens on erythrocytes are not synthesized by erythrocytes themselves and are probably synthesized elsewhere in the digestive organs by FUT3; and then absorbed by RBCs.
• CA19-9, tumor biomarker, recognizes the sLe^a epitope on mucins. Individuals who are FUT3 negative will not express this biomarker.
• Similarly, the expression of DU-PAN-2 is also dependent on the activity of genes forming sLe^c.