ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 3 (ST6GALNAC3)
The members of the ST6GalNAc family transfer sialic acid from CMP-sialic acid (CMP-Sia) to the N-acetylgalactosamine residues of glycoconjugates through an α2,6-linlage. To date, six members of the ST6GalNAc family have been identified in both the mouse and humans. From amino acid sequence similarities, substrate specificities, and gene structures, these members can be classified into two subfamilies. One subfamily consists of two members, ST6GalNAc-I and ST6GalNAc-II. The other subfamily consists of four members, ST6GalNAc-III, ST6GalNAc-IV, ST6GalNAc-V, and ST6GalNAc-VI. These members except ST6GalNAc-IV can efficiently synthesize the ganglioside GD1α from GM1b (Sjoberg et al. 1996; Lee et al. 1999; Okajima et al. 1999, 2000; Ikehara et al. 1999; Tsuchida et al. 2005). GD1α has been implicated as a molecular component of a variety of important biological processes. Each gene has different tissue-specific expression patterns, suggesting that there may be several tissue-specific ST6GalNAc members capable of synthesizing GD1α. ST6GalNAc-III also exhibits sialyltransferase activity toward O-glycans and forms NeuAcα2-3Galβ1-3(NeuAcα2-6)GalNAc structure. ST6GalNAc-III is composed of 305 amino acids in length for human, mouse, and rat enzymes. The overall amino acid sequence identity of mouse ST6GalNAc-III is 94.4 % to rat ST6GalNAc-III, 85.3 % to human ST6GalNAc-III, 43.0 % to mouse ST6GalNAc-IV, 42.6 % to mouse ST6GalNAc-V, and 41.4 % to mouse ST6GalNAc-VI, but ST6GalNAc-III shows no significant similarity to other sialyltransferases except in sialylmotifs. Analysis of the genomic structures of the ST6GalNAc-III, ST6GalNAc-IV, ST6GalNAc-V, and ST6GalNAc-VI genes suggested that these genes arose from a common ancestral gene (Harduin-Lepers et al. 2005; Takashima 2008; Harduin-Lepers 2010).
KeywordsSialic Acid Acceptor Substrate Important Biological Process Common Ancestral Gene Selenious Acid
- Furuya S, Irie F, Hashikawa T, Nakazawa K, Kozakai A, Hasegawa A, Sudo K, Hirabayashi Y (1994) Ganglioside GD1α in cerebellar Purkinje cells. Its specific absence in mouse mutants with Purkinje cell abnormality and altered immunoreactivity in response to conjunctive stimuli causing long-term desensitization. J Biol Chem 269:32418–32425PubMedGoogle Scholar
- Furuya S, Hashikawa T, Hirabayashi Y (1996) Restricted occurrence of an unusual ganglioside GD1α in rat brain and its possible involvement in dendritic growth of cerebellar Purkinje neurons. J Neurosci Res 44:73–83. doi:10.1002/(SICI)1097-4547(19960401)44:1<73::AID-JNR10>3.0.CO;2-9PubMedCrossRefGoogle Scholar
- Lee YC, Kaufmann M, Kitazume-Kawaguchi S, Kono M, Takashima S, Kurosawa N, Liu H, Pircher H, Tsuji S (1999) Molecular cloning and functional expression of two members of mouse NeuAcα2,3Galβ1,3GalNAc GalNAcα2,6-sialyltransferase family, ST6GalNAc III and IV. J Biol Chem 274:11958–11967. doi:10.1074/jbc.274.17.11958PubMedCrossRefGoogle Scholar
- Takashima S, Kurosawa N, Tachida Y, Inoue M, Tsuji S (2000) Comparative analysis of the genomic structures and promoter activities of mouse Siaα2,3Galβ1,3GalNAc GalNAcα2,6-sialyltransferase genes (ST6GalNAc III and IV): characterization of their Sp1 binding sites. J Biochem 127:399–409PubMedCrossRefGoogle Scholar