The structure Siaα2,3(GalNAcβ1,4)Gal- is the
epitope of the Sda
antigen, which is expressed on the erythrocytes and secretions of the vast majority of Caucasians, carried by N- and O-linked chains of
glycoproteins, as well as by
glycolipids. Sda is very similar, but not identical, to
ganglioside GM2 [Siaα2,3(GalNAcβ1,4)Galβ1,4Glc-Cer]. The Sda synthase β1,4 N-acetylgalactosaminyl
transferase 2 (B4GALNT2) exists in a short and a long form, diverging in the aminoterminal domain. The latter has a very long cytoplasmic tail and displays a Golgi- as well as a post-Golgi localization. The biosynthesis of Sda is mutually exclusive with that of the
cancer-associated
sialyl Lewis antigens, whose structure is Siaα2,3Galβ1,3/4(Fucα1,4/3)GlcNAc-. B4GALNT2 is down-regulated in
colon cancer but patients with higher expression survive longer. In experimental systems, B4GALNT2 inhibits
colon cancer progression,not only through inhibition of sialyl Lewis
antigen biosynthesis. By contrast, in
breast cancer B4GALNT2 is associated with
malignancy. In
colon cancer, the B4GALNT2 gene is regulated by multiple mechanisms, which include
miRNA and
transcription factor expression, as well as CpG methylation. In addition, Sda/B4GALNT2 regulates the susceptibility to infectious agents, the protection from muscle dystrophy, the activity of immune system in pregnancy and the immune rejection in
xenotransplantation.