Beta-1,4 N-Acetylgalactosaminyltransferase 1,2 (B4GALNT1,2)

Abstract

UDP-GalNAc: GM3 beta-1,4 N-acetylgalactosaminyltransferase (B4GALNT1) catalyzes the transfer of N-acetylgalactosamine from UDP-GalNAc to ganglioside GM3 (Nagata et al. 1992) as shown in Fig. 39.1. The product is GM2. However, this gene product could synthesize not only GM2 but also GD2 and asialo-GM2 (GA2) (Yamashiro et al. 1995) as previously predicted (Pohlentz et al. 1988). These structures are molecules locating at the starting point for the synthesis of mature gangliosides enriched in the nervous tissues such as brain and peripheral nerve tissues. Thus, these complex gangliosides were all deleted in the knockout mice of B4GALNT1 (Takamiya et al. 1996). In addition to the first cDNA clones responsible for the synthesis of GM2 and GD2, a similar enzyme with high homology was identified (Smith and Lowe 1994; Montiel et al. 2003). Thereafter, GM2/GD2/GA2 gene was designated B4GALNT1, and the latter has been called as B4GALNT2. Structures of acceptor substrates are very similar to each other (GM3 vs. sialylparagloboside), but the substrate specificities of them are clearly distinct, i.e., B4GALNT2 catalyzes the synthesis of Sda antigen (or Cad antigen), GalNAcβ1,4(α2,3NeuAc)Galβ1,4GlcNAc-R (Yamashiro et al. 1995). Following the cloning of mouse cDNA (Smith and Lowe 1994), human cDNA was isolated (Montiel et al. 2003). In human cDNAs of B4GALNT2, presence of two isoforms with different length in N-terminus (cytoplasmic region) was reported, while the implication of them has not been clarified (Montiel et al. 2003).