UDP-Gal: BetaGlcNAc Beta 1,3-Galactosyltransferase, Polypeptide 1,2 (B3GALT1,2)
The Galβ1-3GlcNAc linkage (type 1 chain) is widely found on glycolipids and N-linked and mucin-type O-linked glycoproteins primarily in cell types derived from the endoderm (Oriol et al. 1986). In contrast, the Galβ1-4GlcNAc linkage (type 2) is widely distributed on glycolipids and glycoproteins derived from the ectoderm and mesoderm. Type 1 chain constitutes cores for the Lewis blood group antigens including structures such as Lea and Leb and the corresponding ABH structures (Clausen and Hakomori 1989). Type 1 chain also carries classical cancer-associated structures such as sialyl-Lea (N19-9) (Magnani et al. 1982) and disialyl-Lea (FH7) (Nudelman et al. 1986). The type 1 chain core is catalyzed by β3galactosyltransferases (β3Gal-T) and distinct β3Gal-T activities with βGlcNAc substrates were first described in the 1980s (Sheares and Carlson 1983; Sheares et al. 1982) and shown to be distinct from β4galactosyltransferase (β4Gal-T) activities (Holmes 1989; Sheares and Carlson 1983). The first β3Gal-T gene cloned, β3Gal-T1, was identified by expression cloning (Sasaki et al. Japanese patent JP1994181759-A/1). Subsequently, this gene sequence was used to probe emerging EST and gene sequences early in the human genome project and unravel the large β3glycosyltransferase gene family assigned to CAZy family GT31. This family includes three β3Gal-Ts (T1, T2, and T5) catalyzing the Galβ1-3GlcNAc linkage as well as a large number of other β3GalNAc-Ts, β3GlcNAc-Ts (for reviews see Amado et al. 1999; Togayachi et al. 2006). This review summarizes the properties of the first two cloned and expressed β3Gal-Ts, β3Gal-T1 and T2.
KeywordsStem Region Japanese Patent Chimeric Fusion Protein Chain Core Lewis Blood Group Antigen
This work was supported by The Danish Research Councils, a program of excellence from the University of Copenhagen, and the Danish National Research Foundation (DNRF107).
- Almeida R, Amado M, David L, Levery SB, Holmes EH, Merkx G, van Kessel AG, Rygaard E, Hassan H, Bennett E et al (1997) A family of human β4-galactosyltransferases. Cloning and expression of two novel UDP-galactose:b-n-acetylglucosamine β1, 4-galactosyltransferases, β4Gal-T2 and β4Gal-T3. J Biol Chem 272:31979–31991PubMedCrossRefGoogle Scholar
- Amado M, Almeida R, Carneiro F, Levery SB, Holmes EH, Nomoto M, Hollingsworth MA, Hassan H, Schwientek T, Nielsen PA et al (1998) A family of human beta3-galactosyltransferases. Characterization of four members of a UDP-galactose:β-N-acetyl-glucosamine/β-N-acetyl-galactosamine β1,3-galactosyltransferase family. J Biol Chem 273:12770–12778PubMedCrossRefGoogle Scholar
- Holmes EH (1989) Characterization and membrane organization of β1-3- and β1-4-galactosyltransferases from human colonic adenocarcinoma cell lines Colo 205 and SW403: basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures. Arch Biochem Biophys 270:630–646PubMedCrossRefGoogle Scholar
- Isshiki S, Togayachi A, Kudo T, Nishihara S, Watanabe M, Kubota T, Kitajima M, Shiraishi N, Sasaki K, Andoh T et al (1999) Cloning, expression, and characterization of a novel UDP-galactose:b-N-acetylglucosamine β1,3-galactosyltransferase (β3Gal-T5) responsible for synthesis of type 1 chain in colorectal and pancreatic epithelia and tumor cells derived therefrom. J Biol Chem 274:12499–12507PubMedCrossRefGoogle Scholar
- Lunetta KL, D’Agostino RB Sr, Karasik D, Benjamin EJ, Guo CY, Govindaraju R, Kiel DP, Kelly-Hayes M, Massaro JM, Pencina MJ et al (2007) Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham study. BMC Med Genet 8(Suppl 1):S13PubMedCentralPubMedCrossRefGoogle Scholar
- Vasan RS, Larson MG, Aragam J, Wang TJ, Mitchell GF, Kathiresan S, Newton-Cheh C, Vita JA, Keyes MJ, O’Donnell CJ et al (2007) Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham heart study. BMC Med Genet 8(Suppl 1):S2PubMedCentralPubMedCrossRefGoogle Scholar
- Wandall HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J et al (1997) Substrate specificities of three members of the human UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem 272:23503–23514PubMedCrossRefGoogle Scholar