Alternative titles; symbols
HGNC Approved Gene Symbol: ST6GAL1
Cytogenetic location: 3q27.3 Genomic coordinates (GRCh38): 3:186,930,526-187,078,553 (from NCBI)
Much interest in the role and regulation of beta-galactoside alpha-2,6-sialyltransferase (EC 2.4.99.1) in B lymphocytes stemmed from its relation to CDw75, a human leukocyte cell-surface antigen expressed in mature and activated B cells but not in B cells at earlier stages of development or in plasma cells. SiaT-1 is required for the elaboration of the CDw75 cell-surface epitope. Grundmann et al. (1990) reported the complete cDNA sequence corresponding to the SIAT1 gene on the basis of cDNA isolated from a human placenta lambda-gt10 library.
Comparative analysis of the human and rat sequences by Wang et al. (1993) demonstrated precise conservation of the intron/exon boundaries throughout the coding domains. Furthermore, there was extensive interspecies sequence similarity in some of the exons that contained information only for the 5-prime leader regions.
Using Northern blot analysis, Kitagawa and Paulson (1994) evaluated the differential expression of 5 human sialyltransferase genes in adult and fetal tissues. A 4.7-kb ST6N transcript was expressed in nearly all tissues examined, with highest expression in liver, followed by kidney, spleen, thymus, prostate, and peripheral blood leukocytes. Several smaller transcripts were also detected in liver. Little to no expression was detected in pancreas, testis, and colon.
Using RT-PCR, Xu et al. (2003) found that 3 ST6GAL1 mRNAs resulting from alternative splicing in the 5-prime UTR were differentially expressed in several human cell lines.
Xu et al. (2003) stated that the ST6GAL1 gene contains 4 alternatively spliced 5-prime noncoding exons, designated X, Y, Z, and 1.
By Southern analysis of somatic cell hybrids and by in situ hybridization, Wang et al. (1993) demonstrated that the SIAT1 gene is located on 3q21-q28.
Influenza viruses manifest species tropism, with avian viruses rarely infecting and spreading between humans. Shinya et al. (2006) noted that the distribution and prevalence of the influenza virus-binding molecules, sialic acid linked to galactose by an alpha-2,3 linkage (SA-alpha-2,3-Gal) or by an alpha-2,6 linkage (SA-alpha-2,6-Gal), in the human airway were unknown. Using lectins specific for each molecule, they showed that SA-alpha-2,6-Gal was dominant on epithelial cells of the nasal mucosa, pharynx, trachea, and bronchi. In contrast, SA-alpha-2,3-Gal was found on nonciliated cuboidal bronchiolar cells at the junction of bronchioles and alveoli, as well as on alveolar cells, including alveolar type II cells, and cells in the alveolar wall. Shinya et al. (2006) found that human-derived viruses preferentially bound epithelial cells expressing SA-alpha-2,6-Gal, whereas avian viruses preferentially interacted with alveolar cells expressing SA-alpha-2,3-Gal. They noted that an H5N1 influenza virus isolated from a human patient bound to both bronchial and alveolar cells. The results indicated that H5N1 virus strains preferentially recognizing SA-alpha-2,3-Gal can be transmitted from birds to humans, but they can replicate efficiently only in alveolar cells. Thus, transmission via cells in the upper respiratory tract may be inefficient in the absence of an ability to recognize SA-alpha-2,6-Gal. Shinya et al. (2006) concluded that mutations in the viral hemagglutinin molecule would be necessary to confer SA-alpha-2,6-Gal-binding ability on H5N1 avian viruses, and that amino acid substitutions in other viral proteins, including PB2, may also be required to confer potential for a human pandemic.
Nicholls et al. (2007) found that ex vivo cultures of human nasopharyngeal, adenoid, and tonsillar tissues could be infected with influenza A H5N1 viruses in spite of the lack of viral receptors for SA-alpha-2,3-Gal in the upper airway. They concluded that the increased severity of H5N1 influenza cannot be explained purely on the basis of a differential tropism of H5N1 to the lower respiratory tract.
For a discussion of a possible association between drug-induced liver injury due to flucloxacillin in HLA-B*5701 carriers and variation in the ST6GAL1 gene, see 142830.0003.
Grundmann, U., Nerlich, C., Rein, T., Zettlmeissl, G. Complete cDNA sequence encoding human beta-galactoside alpha-2,6-sialyltransferase. Nucleic Acids Res. 18: 667 only, 1990. [PubMed: 2408023] [Full Text: https://doi.org/10.1093/nar/18.3.667]
Kitagawa, H., Paulson, J. C. Differential expression of five sialyltransferase genes in human tissues. J. Biol. Chem. 269: 17872-17878, 1994. [PubMed: 8027041]
Nicholls, J. M., Chan, M. C. W., Chan, W. Y., Wong, H. K., Cheung, C. Y., Kwong, D. L. W., Wong, M. P., Chui, W. H., Poon, L. L. M., Tsao, S. W., Guan, Y., Peiris, J. S. M. Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nature Med. 13: 147-149, 2007. [PubMed: 17206149] [Full Text: https://doi.org/10.1038/nm1529]
Shinya, K., Ebina, M., Yamada, S., Ono, M., Kasai, N., Kawaoka, Y. Influenza virus receptors in the human airway: avian and human flu viruses seem to target different regions of a patient's respiratory tract. Nature 440: 435-436, 2006. [PubMed: 16554799] [Full Text: https://doi.org/10.1038/440435a]
Wang, X., Vertino, A., Eddy, R. L., Byers, M. G., Jani-Sait, S. N., Shows, T. B., Lau, J. T. Y. Chromosome mapping and organization of the human beta-galactoside alpha-2,6-sialyltransferase gene: differential and cell-type specific usage of upstream exon sequences in B-lymphoblastoid cells. J. Biol. Chem. 268: 4355-4361, 1993. [PubMed: 7786324]
Xu, L., Kurusu, Y., Takizawa, K., Tanaka, J., Matsumoto, K., Taniguchi, A. Transcriptional regulation of human beta-galactoside alpha-2,6-sialyltransferase (hST6Gal I) gene in colon adenocarcinoma cell line. Biochem. Biophys. Res. Commun. 307: 1070-1074, 2003. [PubMed: 12878221] [Full Text: https://doi.org/10.1016/s0006-291x(03)01314-7]