Globoside Alpha-1,3-N-Acetylgalactosaminyltransferase 1 (GBGT1)

Abstract

Forssman heterophilic glycolipid antigen (GalNAcαl-3GalNAcβl-3Galαl-4Galβ1-4G1c-Cer) is a member of the globo series glycosphingolipid family and is formed by the addition of GalNAc in αl,3-linkage to the terminal GalNAc residue of globoside (globotetraosylceramide). This reaction is catalyzed by globoside α-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1). This enzyme is also called Forssman glycolipid synthase (FS). The canine FS cDNA was cloned from an MDCK-cell cDNA library using an expression cloning method (Haslam and Baenziger 1996). The isolated FS shows 42 % identity in the amino acid sequence to the histo-blood group A and B transferases (Yamamoto et al. 1990) and 35 % identity to the α1,3-galactosyltransferase (Joziasse et al. 1989). The A or B transferases transfer GalNAc or Gal in αl,3-linkage to the histo-H acceptor, respectively, and the α3 galactosyltransferase transfers Gal to the terminal Galβ1-4GlcNAc structure on glycoproteins as well as glycolipids. The close sequence identity and the similar enzyme reaction suggested that these glycosyltransferase genes have the same evolutionary origin (Haslam and Baenziger 1996). Furthermore, in humans, all these related glycosyltransferase genes are located on chromosome 9q34, supporting the hypothesis that they arose by gene duplication and subsequent divergence (Joziasse et al. 1992; Yamamoto et al. 1995; Xu et al. 1999), although the human FS gene encodes nonfunctional FS protein (Xu et al. 1999).