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Gene Review

Gne  -  glucosamine (UDP-N-acetyl)-2-epimerase/N...

Mus musculus

Synonyms: 2310066H07Rik, Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, DMRV, GLCNE, Glcne, ...
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Disease relevance of Gne

  • These results show that the Gne((-/-)) hGNEV572L-Tg mouse mimics the clinical, histopathological and biochemical features of DMRV/h-IBM, making it useful for understanding the pathomechanism of this myopathy and for employing different strategies for therapy [1].
  • We conclude that susceptibility of cells to HSV-1 entry depends on (1) presence of heparan sulfate chains to which virus can bind and (2) 3-O-sulfation of specific glucosamine residues in heparan sulfate to generate gD-binding sites or the expression of other previously identified gD-binding receptors [2].
  • In vivo chemotherapy of mice bearing TA3 ascites tumors was most effective with respect to tumor growth inhibition and animal survival when GlcN and FUrd were combined [3].
  • Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG [4].
  • Certain Escherichia coli mutants altered in phosphatidylglycerol metabolism accumulate fatty acyl derivatives of glucosamine 1-phosphate [5].

High impact information on Gne


Chemical compound and disease context of Gne


Biological context of Gne

  • Addition of equimolar amounts of glucose or mannose, but not of fructose, galactose, fucose, or glucosamine, to medium containing 50 mM 2-dG results in substantial reversal of the inhibitory effect of 2-dG on Fc and C3 receptor mediated phagocytosis [16].
  • We conclude that (a) heparin's anti-inflammatory effects are mainly mediated by blocking P- and L-selectin-initiated cell adhesion; (b) the sulfate groups at C6 on the glucosamine residues play a critical role in selectin inhibition; and (c) some non-anticoagulant forms of heparin retain anti-inflammatory activity [17].
  • Insulin resistance induced through the HSP by glucosamine and chronic insulin treatment correlated with increased O-GlcNAc levels on nucleocytoplasmic proteins [18].
  • Both the secreted and the intracellular forms incorporate glucosamine label, indicating that at least a portion of the modification observed here is in the form of glycosylation [19].
  • This protein was present in membrane enriched fractions and could be metabolically labeled with [3H )glucosamine, confirming that the transfected mdr1 gene encodes a membrane glycoprotein [20].

Anatomical context of Gne


Associations of Gne with chemical compounds

  • Among other natural sugars examined, only mannose competed effectively with 2-DG and reversed the inhibition of cytolysis, whereas sodium pyruvate, fructose, galactose, fucose, and glucosamine were without effect [24].
  • Effects of D-glucosamine and 6-azauridine on nucleotide contents, 5-fluorouridine uptake, and cytotoxicity in TA3 mammary tumor cells [3].
  • The amino acid composition of gp 160 is compatible with the linkage of carbohydrates (galactose, glucosamine, and sialic acid) to the protein portion [25].
  • In TA3 mammary carcinoma cells in suspension culture, D-glucosamine X HCl (GlcN) induced a diversion of uridylate from UTP into UDP-N-acetylhexosamines, reducing the intracellular pool of UTP and eliciting an increased rate of de novo uridylate synthesis [3].
  • Treatment of TA3 cells with FUrd after a pretreatment with 6-AzaUrd and GlcN resulted in a 2.5-fold increase in [14C]FUrd uptake and a duplication of 5-fluorouridylate incorporation into the RNA [3].

Physical interactions of Gne

  • Glucosamine did not alter basal glucose transport and insulin stimulation of GLUT-1 translocation and mitogen-activated protein kinase [26].
  • Structural gene products of the murine Ah complex. Differences in ontogenesis and glucosamine incorporation between liver microsomal cytochromes P1-450 and P-448 induced by polycyclic aromatic compounds [27].
  • A high proportion of antithrombin-binding sequence was also indicated by the finding that 3-O-sulfated glucosamine residues accounted for about 10% of the total O-sulfate groups [28].

Enzymatic interactions of Gne

  • HS 3-O-sulfotransferases (3-OST) catalyze the transfer of sulfate groups to the 3-O position of glucosamine residues of HS, a rare, but essential HS chain modification required for HS fine structure [29].

Regulatory relationships of Gne


Other interactions of Gne


Analytical, diagnostic and therapeutic context of Gne


  1. A Gne knockout mouse expressing human V572L mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy. Malicdan, M.C., Noguchi, S., Nonaka, I., Hayashi, Y.K., Nishino, I. Hum. Mol. Genet. (2007) [Pubmed]
  2. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Shukla, D., Liu, J., Blaiklock, P., Shworak, N.W., Bai, X., Esko, J.D., Cohen, G.H., Eisenberg, R.J., Rosenberg, R.D., Spear, P.G. Cell (1999) [Pubmed]
  3. Effects of D-glucosamine and 6-azauridine on nucleotide contents, 5-fluorouridine uptake, and cytotoxicity in TA3 mammary tumor cells. Holstege, A., Keppler, D. J. Natl. Cancer Inst. (1986) [Pubmed]
  4. Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice. Ebara, T., Conde, K., Kako, Y., Liu, Y., Xu, Y., Ramakrishnan, R., Goldberg, I.J., Shachter, N.S. J. Clin. Invest. (2000) [Pubmed]
  5. Molecular requirements for B-lymphocyte activation by Escherichia coli lipopolysaccharide. Raetz, C.R., Purcell, S., Takayama, K. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  6. Glycoprotein synthesis and inhibition of glycosylation by tunicamycin in preimplantation mouse embryos: compaction and trophoblast adhesion. Surani, M.A. Cell (1979) [Pubmed]
  7. Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase. Saltiel, A.R., Fox, J.A., Sherline, P., Cuatrecasas, P. Science (1986) [Pubmed]
  8. Inflammatory toxin from Mycoplasma bovis: isolation and characterization. Geary, S.J., Tourtellotte, M.E., Cameron, J.A. Science (1981) [Pubmed]
  9. Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Wang, L., Fuster, M., Sriramarao, P., Esko, J.D. Nat. Immunol. (2005) [Pubmed]
  10. Lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis have components that are immunochemically similar to precursors of human blood group antigens. Carbohydrate sequence specificity of the mouse monoclonal antibodies that recognize crossreacting antigens on LOS and human erythrocytes. Mandrell, R.E., Griffiss, J.M., Macher, B.A. J. Exp. Med. (1988) [Pubmed]
  11. Loss of melanogenic properties in tyrosinases induced by glucosylation inhibitors within malignant melanoma cells. Imokawa, G., Mishima, Y. Cancer Res. (1982) [Pubmed]
  12. Identification of a lipid A binding site in the acute phase reactant lipopolysaccharide binding protein. Tobias, P.S., Soldau, K., Ulevitch, R.J. J. Biol. Chem. (1989) [Pubmed]
  13. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Lin, H.Y., Masso-Welch, P., Di, Y.P., Cai, J.W., Shen, J.W., Subjeck, J.R. Mol. Biol. Cell (1993) [Pubmed]
  14. Deglycosylation of mucin from LS174T colon cancer cells by hydrogen fluoride treatment. Byrd, J.C., Lamport, D.T., Siddiqui, B., Kuan, S.F., Erickson, R., Itzkowitz, S.H., Kim, Y.S. Biochem. J. (1989) [Pubmed]
  15. Chemical structure of lipid A from Porphyromonas (Bacteroides) gingivalis lipopolysaccharide. Ogawa, T. FEBS Lett. (1993) [Pubmed]
  16. 2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect. Michl, J., Ohlbaum, D.J., Silverstein, S.C. J. Exp. Med. (1976) [Pubmed]
  17. Heparin's anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins. Wang, L., Brown, J.R., Varki, A., Esko, J.D. J. Clin. Invest. (2002) [Pubmed]
  18. Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Vosseller, K., Wells, L., Lane, M.D., Hart, G.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  19. Synthesis and glycosylation of the common alpha subunit of human glycoprotein hormones in mouse cells. Ramabhadran, T.V., Reitz, B.A., Tiemeier, D.C. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  20. Characterization of the multidrug resistance protein expressed in cell clones stably transfected with the mouse mdr1 cDNA. Schurr, E., Raymond, M., Bell, J.C., Gros, P. Cancer Res. (1989) [Pubmed]
  21. Size variation of the M protein in group A streptococci. Fischetti, V.A., Jones, K.F., Scott, J.R. J. Exp. Med. (1985) [Pubmed]
  22. Alterations in surface glycoproteins and level of sialyltransferase of cells transformed by a temperature-sensitive mutant of simian virus 40. Onodera, K., Yamaguchi, N., Kuchino, T., Aoi, Y. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  23. Receptor-mediated endocytosis of carcinoembryonic antigen by rat liver Kupffer cells. Toth, C.A., Thomas, P., Broitman, S.A., Zamcheck, N. Cancer Res. (1985) [Pubmed]
  24. Energy metabolism and T-cell-mediated cytolysis. II. Selective inhibition of cytolysis by 2-deoxy-D-glucose. MacDonald, H.R. J. Exp. Med. (1977) [Pubmed]
  25. Isolation, purification, and characterization of a mouse plasmacytoma cell surface glycoprotein involved in the resistance of the tumor cells to immune destruction. Rosenstein, Y., Theelen, M., Sánchez, I., Celis, E. J. Natl. Cancer Inst. (1985) [Pubmed]
  26. Glucosamine-induced insulin resistance in 3T3-L1 adipocytes. Heart, E., Choi, W.S., Sung, C.K. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  27. Structural gene products of the murine Ah complex. Differences in ontogenesis and glucosamine incorporation between liver microsomal cytochromes P1-450 and P-448 induced by polycyclic aromatic compounds. Negishi, M., Jensen, N.M., Garcia, G.S., Nebert, D.W. Eur. J. Biochem. (1981) [Pubmed]
  28. Structure and affinity for antithrombin of heparan sulfate chains derived from basement membrane proteoglycans. Pejler, G., Bäckström, G., Lindahl, U., Paulsson, M., Dziadek, M., Fujiwara, S., Timpl, R. J. Biol. Chem. (1987) [Pubmed]
  29. Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: I. The 3-O-sulfotransferase family. Cadwallader, A.B., Yost, H.J. Dev. Dyn. (2006) [Pubmed]
  30. Glucosamine-induced insulin resistance is coupled to O-linked glycosylation of Munc18c. Chen, G., Liu, P., Thurmond, D.C., Elmendorf, J.S. FEBS Lett. (2003) [Pubmed]
  31. Hexosamines stimulate leptin production in transgenic mice. McClain, D.A., Alexander, T., Cooksey, R.C., Considine, R.V. Endocrinology (2000) [Pubmed]
  32. Enhanced synthesis and extracellular accumulation of hyaluronic acid during stimulation of quiescent human fibroblasts by mouse epidermal growth factor. Lembach, K.J. J. Cell. Physiol. (1976) [Pubmed]
  33. Heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 is 6-O-sulfated but contains no N-sulfate groups. Holmborn, K., Ledin, J., Smeds, E., Eriksson, I., Kusche-Gullberg, M., Kjellén, L. J. Biol. Chem. (2004) [Pubmed]
  34. Role of glucosamine synthesis in the stimulation of TGF-alpha gene transcription by glucose and EGF. Roos, M.D., Han, I.O., Paterson, A.J., Kudlow, J.E. Am. J. Physiol. (1996) [Pubmed]
  35. Cloning and partial characterization of the mouse glutamine:fructose-6-phosphate amidotransferase (GFAT) gene promoter. Sayeski, P.P., Wang, D., Su, K., Han, I.O., Kudlow, J.E. Nucleic Acids Res. (1997) [Pubmed]
  36. Defective Akt activation is associated with glucose- but not glucosamine-induced insulin resistance. Nelson, B.A., Robinson, K.A., Buse, M.G. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  37. Immunosuppressive effects of glucosamine. Ma, L., Rudert, W.A., Harnaha, J., Wright, M., Machen, J., Lakomy, R., Qian, S., Lu, L., Robbins, P.D., Trucco, M., Giannoukakis, N. J. Biol. Chem. (2002) [Pubmed]
  38. Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response. Zhang, G.X., Yu, S., Gran, B., Rostami, A. J. Immunol. (2005) [Pubmed]
  39. Characterization of a sustained-release delivery system for combined cytokine/peptide vaccination using a poly-N-acetyl glucosamine-based polymer matrix. Cole, D.J., Gattoni-Celli, S., McClay, E.F., Metcalf, J.S., Brown, J.M., Nabavi, N., Newton, D.A., Woolhiser, C.B., Wilson, M.C., Vournakis, J.N. Clin. Cancer Res. (1997) [Pubmed]
  40. Glycoconjugates of murine tumor lines with different metastatic capacities. II. Diversity of glycolipid composition. Schwartz, R., Kniep, B., Müthing, J., Mühlradt, P.F. Int. J. Cancer (1985) [Pubmed]
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