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Gene Review

ST8SIA4  -  ST8 alpha-N-acetyl-neuraminide alpha-2,8...

Homo sapiens

Synonyms: Alpha-2,8-sialyltransferase 8D, CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase, PST, PST1, Polysialyltransferase-1, ...
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Disease relevance of ST8SIA4


Psychiatry related information on ST8SIA4


High impact information on ST8SIA4


Chemical compound and disease context of ST8SIA4

  • The objective of the present study was to assess the potential predictive value of supine morning plasma aldosterone concentration, a component of the postural stimulation test (PST), in distinguishing aldosterone-producing adenoma (APA) from idiopathic adrenal hyperplasia (IAH) in a series of 61 patients with confirmed primary aldosteronism (PAL) [12].

Biological context of ST8SIA4

  • The cloning and characterization of two polysialyltransferases, termed ST8SiaII (STX) and ST8SiaIV (PST), opened up new perspectives in the search for factors that control this unique cell surface glycosylation [13].
  • We first determined the catalytic domain of ST8Sia IV by deletion mutants [14].
  • To understand the role of autopolysialylation in PST enzymatic activity, we employed a mutagenesis approach [15].
  • METHODS: We performed an association study of single nucleotide polymorphisms (SNPs) within SIAT8B and SIAT8D, using 188 schizophrenics and 156 age and gender matched controls [16].
  • These data are consistent with a model in which Pst1p-Clr6p temporally associate with centromeres to carry out the initial deacetylation necessary for subsequent steps in heterochromatin formation [17].

Anatomical context of ST8SIA4


Associations of ST8SIA4 with chemical compounds


Physical interactions of ST8SIA4

  • Furthermore, ST8Sia IV was able to add polysialic acid to oligosialylated oligosaccharides and unpolysialylated antennas in N-glycans attached to NCAM, even when polysialic acid was attached to at least one of the other antennas [24].

Enzymatic interactions of ST8SIA4


Other interactions of ST8SIA4

  • The polysialyltransferase ST8Sia II/STX: posttranslational processing and role of autopolysialylation in the polysialylation of neural cell adhesion molecule [26].
  • To obtain insight into the structure/function of ST8Sia IV, we expressed human ST8Sia IV in insect cells, Trichoplusia ni, and found that the enzyme produced in the insect cells catalyzes NCAM polysialylation, although it cannot polysialylate itself ("autopolysialylation") [20].
  • However, chimeric enzymes that contain only the carboxyl-terminal segment of ST8Sia IV and the amino-terminal segment of ST8Sia III showed very weak activity toward NCAM, even though they had strong activity in polysialylating themselves [14].
  • The occurrence of novel 9-O-sulfated N-glycolylneuraminic acid-capped alpha2-->5-Oglycolyl-linked oligo/polyNeu5Gc chains in sea urchin egg cell surface glycoprotein. Identification of a new chain termination signal for polysialyltransferase [27].
  • All blood leukocytes expressed ST8Sia IV, implicated in polysialic acid synthesis, and NK cells variably expressed high levels of ST8Sia V mRNA required for GT3 expression [28].

Analytical, diagnostic and therapeutic context of ST8SIA4

  • Polysialyltransferase expression levels analyzed by real-time RT-PCR indicated that ST8SiaII/STX mRNA is markedly down-regulated in vivo, decreasing abruptly at about the first week of postnatal development [1].
  • This review focuses on the molecular cloning of human polysialyltransferase, designated PST [29].
  • Analysis of these high molecular mass forms by glycosidase digestion and serial immunoprecipitation/immunoblot experiments demonstrated that PST and STX are autopolysialylated in vivo [18].
  • Reverse transcription-PCR showed simultaneous expression of the two enzymes, and in situ hybridization demonstrated that the polysialyltransferase mRNA expression parallels immunoreactivity with the PSA-specific monoclonal antibody 735 [30].
  • Site-directed mutagenesis showed that Ile(275), Lys(276) and Arg(277) in the C-terminus of PSTD in ST8Sia IV, which is contiguous with the N-terminus of sialylmotif-S, were essential for polysialylation [23].


  1. Differential regulation of polysialyltransferase expression during hippocampus development: Implications for neuronal survival. Brocco, M., Pollevick, G.D., Frasch, A.C. J. Neurosci. Res. (2003) [Pubmed]
  2. Prognostic significance of polysialic acid expression in resected non-small cell lung cancer. Tanaka, F., Otake, Y., Nakagawa, T., Kawano, Y., Miyahara, R., Li, M., Yanagihara, K., Inui, K., Oyanagi, H., Yamada, T., Nakayama, J., Fujimoto, I., Ikenaka, K., Wada, H. Cancer Res. (2001) [Pubmed]
  3. Idiopathic pancreatitis related to CFTR: complex inheritance and identification of a modifier gene. Cohn, J.A., Noone, P.G., Jowell, P.S. J. Investig. Med. (2002) [Pubmed]
  4. Expression profiling of glycosyltransferases and related enzymes using in situ hybridization. Nakayama, J., Suzuki, M., Suzuki, M., Fukuda, M. Meth. Enzymol. (2006) [Pubmed]
  5. Polysialic acid engineering: synthesis of polysialylated neoglycosphingolipids by using the polysialyltransferase from neuroinvasive Escherichia coli K1. Cho, J.W., Troy, F.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Preclinical investigation of the topical administration of phenserine: transdermal flux, cholinesterase inhibition, and cognitive efficacy. Utsuki, T., Uchimura, N., Irikura, M., Moriuchi, H., Holloway, H.W., Yu, Q.S., Spangler, E.L., Mamczarz, J., Ingram, D.K., Irie, T., Greig, N.H. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  7. Autocatalytic polysialylation of polysialyltransferase-1. Mühlenhoff, M., Eckhardt, M., Bethe, A., Frosch, M., Gerardy-Schahn, R. EMBO J. (1996) [Pubmed]
  8. Use of polysialic acid in repair of the central nervous system. El Maarouf, A., Petridis, A.K., Rutishauser, U. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Expression cloning of a human polysialyltransferase that forms the polysialylated neural cell adhesion molecule present in embryonic brain. Nakayama, J., Fukuda, M.N., Fredette, B., Ranscht, B., Fukuda, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  10. Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer. Tanaka, F., Otake, Y., Nakagawa, T., Kawano, Y., Miyahara, R., Li, M., Yanagihara, K., Nakayama, J., Fujimoto, I., Ikenaka, K., Wada, H. Cancer Res. (2000) [Pubmed]
  11. NCAM-associated polysialic acid on ciliary ganglion neurons is regulated by polysialytransferase levels and interaction with muscle. Brusés, J.L., Oka, S., Rutishauser, U. J. Neurosci. (1995) [Pubmed]
  12. Morning plasma aldosterone predicts the subtype of primary aldosteronism independant of sodium intake. Plamondon, I., Agharazii, M., Douville, P., Lebel, M. Clin. Exp. Hypertens. (2007) [Pubmed]
  13. Retinoic acid-induced changes in polysialyltransferase mRNA expression and NCAM polysialylation in human neuroblastoma cells. Seidenfaden, R., Hildebrandt, H. J. Neurobiol. (2001) [Pubmed]
  14. Molecular dissection of the ST8Sia IV polysialyltransferase. Distinct domains are required for neural cell adhesion molecule recognition and polysialylation. Angata, K., Chan, D., Thibault, J., Fukuda, M. J. Biol. Chem. (2004) [Pubmed]
  15. Polysialyltransferase-1 autopolysialylation is not requisite for polysialylation of neural cell adhesion molecule. Close, B.E., Tao, K., Colley, K.J. J. Biol. Chem. (2000) [Pubmed]
  16. Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia. Arai, M., Yamada, K., Toyota, T., Obata, N., Haga, S., Yoshida, Y., Nakamura, K., Minabe, Y., Ujike, H., Sora, I., Ikeda, K., Mori, N., Yoshikawa, T., Itokawa, M. Biol. Psychiatry (2006) [Pubmed]
  17. A new role for the transcriptional corepressor SIN3; regulation of centromeres. Silverstein, R.A., Richardson, W., Levin, H., Allshire, R., Ekwall, K. Curr. Biol. (2003) [Pubmed]
  18. In vivo autopolysialylation and localization of the polysialyltransferases PST and STX. Close, B.E., Colley, K.J. J. Biol. Chem. (1998) [Pubmed]
  19. Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neuronal behavior. Charter, N.W., Mahal, L.K., Koshland, D.E., Bertozzi, C.R. J. Biol. Chem. (2002) [Pubmed]
  20. Unique disulfide bond structures found in ST8Sia IV polysialyltransferase are required for its activity. Angata, K., Yen, T.Y., El-Battari, A., Macher, B.A., Fukuda, M. J. Biol. Chem. (2001) [Pubmed]
  21. Differential and cooperative polysialylation of the neural cell adhesion molecule by two polysialyltransferases, PST and STX. Angata, K., Suzuki, M., Fukuda, M. J. Biol. Chem. (1998) [Pubmed]
  22. Selective inhibition of polysialyltransferase ST8SiaII by unnatural sialic acids. Horstkorte, R., Mühlenhoff, M., Reutter, W., Nöhring, S., Zimmermann-Kordmann, M., Gerardy-Schahn, R. Exp. Cell Res. (2004) [Pubmed]
  23. Molecular basis for polysialylation: A novel polybasic polysialyltransferase domain (PSTD) of 32 amino acids unique to the alpha2,8-polysialyltransferases is essential for polysialylation. Nakata, D., Zhang, L., Troy, F.A. Glycoconj. J. (2006) [Pubmed]
  24. ST8Sia II and ST8Sia IV polysialyltransferases exhibit marked differences in utilizing various acceptors containing oligosialic acid and short polysialic acid. The basis for cooperative polysialylation by two enzymes. Angata, K., Suzuki, M., Fukuda, M. J. Biol. Chem. (2002) [Pubmed]
  25. Screening a series of sialyltransferases for possible BACE1 substrates. Kitazume, S., Tachida, Y., Oka, R., Nakagawa, K., Takashima, S., Lee, Y.C., Hashimoto, Y. Glycoconj. J. (2006) [Pubmed]
  26. The polysialyltransferase ST8Sia II/STX: posttranslational processing and role of autopolysialylation in the polysialylation of neural cell adhesion molecule. Close, B.E., Wilkinson, J.M., Bohrer, T.J., Goodwin, C.P., Broom, L.J., Colley, K.J. Glycobiology (2001) [Pubmed]
  27. The occurrence of novel 9-O-sulfated N-glycolylneuraminic acid-capped alpha2-->5-Oglycolyl-linked oligo/polyNeu5Gc chains in sea urchin egg cell surface glycoprotein. Identification of a new chain termination signal for polysialyltransferase. Kitazume, S., Kitajima, K., Inoue, S., Haslam, S.M., Morris, H.R., Dell, A., Lennarz, W.J., Inoue, Y. J. Biol. Chem. (1996) [Pubmed]
  28. Probing the cis interactions of the inhibitory receptor Siglec-7 with {alpha}2,8-disialylated ligands on natural killer cells and other leukocytes using glycan-specific antibodies and by analysis of {alpha}2,8-sialyltransferase gene expression. Avril, T., North, S.J., Haslam, S.M., Willison, H.J., Crocker, P.R. J. Leukoc. Biol. (2006) [Pubmed]
  29. Polysialic acid, a unique glycan that is developmentally regulated by two polysialyltransferases, PST and STX, in the central nervous system: from biosynthesis to function. Nakayama, J., Angata, K., Ong, E., Katsuyama, T., Fukuda, M. Pathol. Int. (1998) [Pubmed]
  30. Polysialic acid on the neural cell adhesion molecule correlates with expression of polysialyltransferases and promotes neuroblastoma cell growth. Hildebrandt, H., Becker, C., Glüer, S., Rösner, H., Gerardy-Schahn, R., Rahmann, H. Cancer Res. (1998) [Pubmed]
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