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Gene Review

B3GAT1  -  beta-1,3-glucuronyltransferase 1

Homo sapiens

Synonyms: Beta-1,3-glucuronyltransferase 1, CD57, GLCATP, GLCUATP, Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1, ...
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Disease relevance of B3GAT1

  • We suggest, therefore, that the increase in CD57(+) HIV-specific CD8(+) T cells results from chronic antigen stimulation that is a hallmark of HIV infection [1].
  • We overexpressed and purified the recombinant human GlcAT-P from Escherichia coli [2].
  • Therefore, NCAM isoforms that lack the HNK-1 epitope might play a role in the organ specific metastatic behavior of uveal melanomas [3].
  • In liver metastases HNK-1 immunoreactivity was significantly (P = .005) less frequently expressed than NCAM [3].
  • Furthermore, a significant decrease of CD8+ CD57+ T cells was found in patients with advanced gastric cancer [4].

Psychiatry related information on B3GAT1


High impact information on B3GAT1

  • We report here evidence that a marker for natural killer (NK) cells, anti-Leu-7 (HNK-1), specifically binds to components of human and rodent central nervous tissue as well as peripheral nervous tissue, especially to myelin sheaths [7].
  • Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4(+) T cell maturation [8].
  • However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57 [9].
  • The HNK-1 antibody known to define a subpopulation of human lymphocytes with natural killer and killer cell activities was shown to detect a common neuroectodermal antigen [10].
  • At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells) [11].

Chemical compound and disease context of B3GAT1


Biological context of B3GAT1


Anatomical context of B3GAT1


Associations of B3GAT1 with chemical compounds

  • In addition, Val320, which is located on the C-terminal long loop of the neighboring molecule in the dimer and critical in the recognition of the acceptor sugar molecule by the GlcAT-P dimer, is an alanine in GlcAT-S [19].
  • Phe245, one of the most important GlcAT-P residues for the recognition of acceptors, is a tryptophan in GlcAT-S [19].
  • Interleukin 6 (IL-6) is endowed with a lectin activity for oligosaccharide ligands possessing the HNK-1 epitope (3-sulfated glucuronic acid) found on some mammalian glycoprotein N-glycans (Cebo, C., Dambrouck, T., Maes, E., Laden, C., Strecker, G., Michalski, J. C., and Zanetta, J. P. (2001) J. Biol. Chem. 276, 5685-5691) [24].
  • Expression cloning of a human sulfotransferase that directs the synthesis of the HNK-1 glycan on the neural cell adhesion molecule and glycolipids [25].
  • Subsequently, we determined the first x-ray crystal structures of human GlcAT-P, in the absence and presence of a donor substrate product UDP, catalytic Mn(2+), and an acceptor substrate analogue N-acetyllactosamine (Galbeta1-4GlcNAc) or an asparagine-linked biantennary nonasaccharide [2].

Physical interactions of B3GAT1

  • The monoclonal antibody HNK-1 binds to a carbohydrate determinant in the myelin-associated glycoprotein (MAG) and other glycoproteins of human peripheral nerve [26].
  • Electron microscopic analysis of rotary shadowed complexes of laminin-1 and a HNK-1 neoglycoprotein revealed a major binding site on the G domain that comprises the C-terminal globule of the laminin alpha1 chain [27].

Regulatory relationships of B3GAT1

  • The transfected Lec2-NCAM cells expressing the HNK-1 glycan were enriched by fluorescence-activated cell sorting [25].
  • HGF/NK1 is inefficient at promoting autophosphorylation of the HGF receptor, although some activity was detected at very high concentrations [12].
  • These data support the existence, also in human U373 MG cells, of a septide-sensitive NK1 receptor subtype(s) and/or epitope(s) blocked with high affinity by NK1 antagonist [28].
  • Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies [16].
  • However, there was no change of the local background incidence of epiblastic HNK-1 positivity in the structure of streaks induced by "activin only" grafts [29].

Other interactions of B3GAT1

  • Furthermore, N-CAM 180 did not carry the HNK-1 epitope, whereas the other two isoforms did [30].
  • We further observed that CD8(+) cells expressing CD57, a marker of replicative senescence, also expressed KLRG1; however, a population of CD57(-)KLRG1(+) cells was also identified [21].
  • The results combined together indicate that the cloned HNK-1ST directs the synthesis of the HNK-1 carbohydrate epitope on both glycoproteins and glycolipids in the nervous tissues [25].
  • A comparison of the GlcAT-I with another beta1,3-glucuronyltransferase involved in the HNK-1 epitope biosynthesis revealed that the two beta1,3-glucuronyltransferases exhibited distinct and no overlapping acceptor substrate specificities in vitro [22].
  • Thirty-seven carcinoids of the gastrointestinal tract were studied with immunohistochemical staining for chromogranin A (CgA) and Leu-7 (CD57) [23].

Analytical, diagnostic and therapeutic context of B3GAT1


  1. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Brenchley, J.M., Karandikar, N.J., Betts, M.R., Ambrozak, D.R., Hill, B.J., Crotty, L.E., Casazza, J.P., Kuruppu, J., Migueles, S.A., Connors, M., Roederer, M., Douek, D.C., Koup, R.A. Blood (2003) [Pubmed]
  2. Structural basis for acceptor substrate recognition of a human glucuronyltransferase, GlcAT-P, an enzyme critical in the biosynthesis of the carbohydrate epitope HNK-1. Kakuda, S., Shiba, T., Ishiguro, M., Tagawa, H., Oka, S., Kajihara, Y., Kawasaki, T., Wakatsuki, S., Kato, R. J. Biol. Chem. (2004) [Pubmed]
  3. Neural cell adhesion molecule distribution in primary and metastatic uveal melanoma. Mooy, C.M., Luyten, G.P., de Jong, P.T., Jensen, O.A., Luider, T.M., van der Ham, F., Bosman, F.T. Hum. Pathol. (1995) [Pubmed]
  4. The increase of CD57+ T cells in the peripheral blood and their impaired immune functions in patients with advanced gastric cancer. Chochi, K., Ichikura, T., Majima, T., Kawabata, T., Matsumoto, A., Sugasawa, H., Kawarabayashi, N., Takayama, E., Hiraide, H., Seki, S., Mochizuki, H. Oncol. Rep. (2003) [Pubmed]
  5. The Leu7Pro polymorphism of preproNPY is associated with decreased insulin secretion, delayed ghrelin suppression, and increased cardiovascular responsiveness to norepinephrine during oral glucose tolerance test. Jaakkola, U., Kuusela, T., Jartti, T., Pesonen, U., Koulu, M., Vahlberg, T., Kallio, J. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  6. Musical hallucinations in patients with Lyme disease. Stricker, R.B., Winger, E.E. South. Med. J. (2003) [Pubmed]
  7. A shared antigenic determinant between natural killer cells and nervous tissue. Schuller-Petrovic, S., Gebhart, W., Lassmann, H., Rumpold, H., Kraft, D. Nature (1983) [Pubmed]
  8. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. Casazza, J.P., Betts, M.R., Price, D.A., Precopio, M.L., Ruff, L.E., Brenchley, J.M., Hill, B.J., Roederer, M., Douek, D.C., Koup, R.A. J. Exp. Med. (2006) [Pubmed]
  9. Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells. Exley, M., Garcia, J., Balk, S.P., Porcelli, S. J. Exp. Med. (1997) [Pubmed]
  10. HNK-1 antibody detects an antigen expressed on neuroectodermal cells. Lipinski, M., Braham, K., Caillaud, J.M., Carlu, C., Tursz, T. J. Exp. Med. (1983) [Pubmed]
  11. Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. Dinges, D.F., Douglas, S.D., Zaugg, L., Campbell, D.E., McMann, J.M., Whitehouse, W.G., Orne, E.C., Kapoor, S.C., Icaza, E., Orne, M.T. J. Clin. Invest. (1994) [Pubmed]
  12. Generation and characterization of a competitive antagonist of human hepatocyte growth factor, HGF/NK1. Lokker, N.A., Godowski, P.J. J. Biol. Chem. (1993) [Pubmed]
  13. Myelin-associated glycoprotein shares an antigenic determinant with a glycoprotein of human melanoma cells. Noronha, A.B., Harper, J.R., Ilyas, A.A., Reisfeld, R.A., Quarles, R.H. J. Neurochem. (1986) [Pubmed]
  14. Substance P activates responses correlated with tumour growth in human glioma cell lines bearing tachykinin NK1 receptors. Palma, C., Nardelli, F., Manzini, S., Maggi, C.A. Br. J. Cancer (1999) [Pubmed]
  15. Cyclosporin A is a substance P (tachykinin NK1) receptor antagonist. Gitter, B.D., Waters, D.C., Threlkeld, P.G., Lovelace, A.M., Matsumoto, K., Bruns, R.F. Eur. J. Pharmacol. (1995) [Pubmed]
  16. The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. Jaques, A.J., Opdenakker, G., Rademacher, T.W., Dwek, R.A., Zamze, S.E. Biochem. J. (1996) [Pubmed]
  17. beta-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation. Jeffries, A.R., Mungall, A.J., Dawson, E., Halls, K., Langford, C.F., Murray, R.M., Dunham, I., Powell, J.F. Mol. Psychiatry (2003) [Pubmed]
  18. Tumor necrosis factor-alpha up-regulates glucuronosyltransferase gene expression in human brain endothelial cells and promotes T-cell adhesion. Dasgupta, S., Yanagisawa, M., Krishnamurthy, K., Liour, S.S., Yu, R.K. J. Neurosci. Res. (2007) [Pubmed]
  19. Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the biosynthesis of the HNK-1 carbohydrate epitope. Shiba, T., Kakuda, S., Ishiguro, M., Morita, I., Oka, S., Kawasaki, T., Wakatsuki, S., Kato, R. Proteins (2006) [Pubmed]
  20. Neural cell adhesion molecule expression and messenger RNA splicing patterns in lung cancer cell lines are correlated with neuroendocrine phenotype and growth morphology. Carbone, D.P., Koros, A.M., Linnoila, R.I., Jewett, P., Gazdar, A.F. Cancer Res. (1991) [Pubmed]
  21. Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57. Ibegbu, C.C., Xu, Y.X., Harris, W., Maggio, D., Miller, J.D., Kourtis, A.P. J. Immunol. (2005) [Pubmed]
  22. Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. Tone, Y., Kitagawa, H., Imiya, K., Oka, S., Kawasaki, T., Sugahara, K. FEBS Lett. (1999) [Pubmed]
  23. Different patterns of chromogranin A and Leu-7 (CD57) expression in gastrointestinal carcinoids: immunohistochemical and confocal laser scanning microscopy study. Jirásek, T., Hozák, P., Mandys, V. Neoplasma (2003) [Pubmed]
  24. Function and molecular modeling of the interaction between human interleukin 6 and its HNK-1 oligosaccharide ligands. Cebo, C., Durier, V., Lagant, P., Maes, E., Florea, D., Lefebvre, T., Strecker, G., Vergoten, G., Zanetta, J.P. J. Biol. Chem. (2002) [Pubmed]
  25. Expression cloning of a human sulfotransferase that directs the synthesis of the HNK-1 glycan on the neural cell adhesion molecule and glycolipids. Ong, E., Yeh, J.C., Ding, Y., Hindsgaul, O., Fukuda, M. J. Biol. Chem. (1998) [Pubmed]
  26. A human lymphocyte antigen is shared with a group of glycoproteins in peripheral nerve. Inuzuka, T., Quarles, R.H., Noronha, A.B., Dobersen, M.J., Brady, R.O. Neurosci. Lett. (1984) [Pubmed]
  27. HNK-1 carbohydrate-mediated cell adhesion to laminin-1 is different from heparin-mediated and sulfatide-mediated cell adhesion. Hall, H., Deutzmann, R., Timpl, R., Vaughan, L., Schmitz, B., Schachner, M. Eur. J. Biochem. (1997) [Pubmed]
  28. Different susceptibility to neurokinin 1 receptor antagonists of substance P and septide-induced interleukin-6 release from U373 MG human astrocytoma cell line. Palma, C., Goso, C., Manzini, S. Neurosci. Lett. (1994) [Pubmed]
  29. Experimental control of axial pattern in the chick blastoderm by local expression of Wnt and activin: the role of HNK-1 positive cells. Cooke, J., Takada, S., McMahon, A. Dev. Biol. (1994) [Pubmed]
  30. Evidence for the presence of N-CAM 180 on astrocytes from rat cerebellum and differences in glycan structures between N-CAM 120 and N-CAM 140. Sasaki, T., Endo, T. Glia (1999) [Pubmed]
  31. Cloning and chromosomal mapping of human glucuronyltransferase involved in biosynthesis of the HNK-1 carbohydrate epitope. Mitsumoto, Y., Oka, S., Sakuma, H., Inazawa, J., Kawasaki, T. Genomics (2000) [Pubmed]
  32. Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxidase stains for CD8, TIA-1, and granzyme B. Morice, W.G., Kurtin, P.J., Tefferi, A., Hanson, C.A. Blood (2002) [Pubmed]
  33. Comparative study of monoclonal antibodies TURP-27 and HNK-1: their relationship to neural cell adhesion molecules and prostate tumor-associated antigens. Lipford, G.B., Wright, G.L. Cancer Res. (1991) [Pubmed]
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