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Gene Review

NUCB2  -  nucleobindin 2

Homo sapiens

Synonyms: DNA-binding protein NEFA, Gastric cancer antigen Zg4, HEL-S-109, NEFA, Nucleobindin-2, ...
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Disease relevance of NUCB2

  • Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2 [1].
  • However, DNA sequence analysis of the NEFA cDNA from lymphocytes of affected individuals provided no evidence of mutation, making structural mutations in the NEFA protein unlikely as the cellular cause of Acadian Usher syndrome [2].
  • Regression modelling suggested that NEFA concentrations were associated with fatty liver independently of whole-body glucose production and disposal measurements [3].
  • AIMS/HYPOTHESIS: Type 2 diabetes mellitus is characterised by increased plasma NEFA and IL-6 concentrations, and IL-6 increases lipolysis in healthy men [4].
  • The absolute and the percentage plasma NEFA pattern of healthy children, Cystic Fibrosis (C.F.) patients and their parents have been determined (table I, III, V) and compared with those of age and sex matched control subjects (table II, Iv, V) [5].

Psychiatry related information on NUCB2

  • Both the concentration of NEFA and their flux through the circulation vary widely from hour to hour, reflecting nutritional state and physical activity [6].
  • In separate experiments, free and bound tryptophan, tyrosine, free fatty acids (NEFA) and albumine were studied in healthy volunteers and depressives treated by sleep deprivation [7].

High impact information on NUCB2

  • PowerBLAST analysis identified six clusters of expressed sequence tags (ESTs), two known genes (BIR, SUR1) mapped previously to this region, and a previously characterized but unmapped gene NEFA (DNA binding/EF hand/acidic amino-acid-rich) [8].
  • The association between endogenous ARTS-1 and NUCB2 in HUVEC was demonstrated by co-immunoprecipitation experiments, which showed the formation of a calcium-dependent NUCB2.ARTS-1 complex that associated with a subset of total cellular TNFR1 [9].
  • Extracellular TNFR1 release requires the calcium-dependent formation of a nucleobindin 2-ARTS-1 complex [9].
  • A yeast two-hybrid screen of a human placenta cDNA library showed that NUCB2 (nucleobindin 2), via its helix-loop-helix domains, binds the ARTS-1 extracellular domain [9].
  • No statistical differences between the two cell types were observed in NEFA uptake or lipolysis [10].

Chemical compound and disease context of NUCB2

  • There is a striking difference in the percentage plasma NEFA pattern of C.F. patients with pancreatic insufficiency: palmitic, palmitoleic and oleic acid are significantly increased while linoleic, linolenic and stearic acid are decreased (table IV) [5].
  • During the improvement of the alkalemic and hyperglycemic state, lactic acidosis disappeared but a paradoxical rise of plasma NEFA and ketone body concentrations supervened so that the high anion gap metabolic acidosis was virtually unchanged [11].
  • This effect could not be accounted for by suppression of release of the counterregulatory hormones glucagon or cortisol, but may be mediated by the inhibition of NEFA and gluconeogenic-substrate release in response to hypoglycemia [12].
  • Thus, before drugs incorporated in MM can be prescribed to neonates who are at risk for having kernicterus, the impact of intravenous MM on bilirubin binding and NEFA levels must be investigated in that patient population [13].

Biological context of NUCB2

  • In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor [1].
  • Heterologous overexpression of human NEFA and studies on the two EF-hand calcium-binding sites [14].
  • Acceleration in lipid metabolism was seen with an increase of about 90% in NEFA and about 20% in TG [15].
  • This DNA binding protein therefore is characterized by a linked motif "b/HLH/a/HLH/Z". The protein was designated NEFA: DNA binding/EF-hand/acidic amino acid rich region [16].
  • Exon trapping of BAC clones from this region resulted in the recovery of an exon of the nuclear EF-hand acidic (NEFA) gene [2].

Anatomical context of NUCB2

  • ADFP null cells treated with Tip47 siRNA retained the ability to form lipid droplets but to a lesser extent and shunted the utilization of exogenously added NEFA from triglycerides to phospholipids [10].
  • CONCLUSIONS/INTERPRETATION: This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state [17].
  • This suggests that previous observations, showing that a prolonged increase of plasma NEFA impairs pancreatic beta-cell function, also apply to the hyperglycaemic state [18].
  • There was a significant increase in the incorporation of glucose into cellular NEFA (88+/-17% increase, p=0.006), triacylglycerol (44+/-21% increase, p=0.04) and cholesterol ester (89+/-36% increase, p=0.02) in hyperglycaemic myotubes compared with controls [19].
  • However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05) [20].

Associations of NUCB2 with chemical compounds

  • We therefore measured HGO and fuel use (by indirect calorimetry) both in the basal state and during the last 30 min of a hyperinsulinemic clamp ( in 8 obese NIDDM patients (BMI 34.8 +/- 1.0 kg/m2) after complete overnight suppression of plasma NEFA levels with acipimox, a new nicotinic acid analogue [21].
  • There was an inverse relationship between proportional glucose disappearance and proportional NEFA disappearance (p smaller than 0.001) [22].
  • Similarly, plasma NEFA, glycerol, and beta-OH-butyrate were more suppressed after MI than HI (p < 0.05), whereas plasma lactate increased only after MI, but not after HI [23].
  • CONCLUSIONS/INTERPRETATION: Our study reveals a drop in insulin sensitivity during postprandial lipaemia and strongly suggests that decreased insulin sensitivity is brought about by elevated plasma levels of triglyceride-rich lipoproteins independently of plasma NEFA levels [24].
  • Elevations in serum ketone body, plasma NEFA, and whole-blood branched-chain amino acid concentrations on the loose control day during the basal period persisted throughout the post-exercise recovery period [25].

Other interactions of NUCB2


Analytical, diagnostic and therapeutic context of NUCB2


  1. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Oh-I, S., Shimizu, H., Satoh, T., Okada, S., Adachi, S., Inoue, K., Eguchi, H., Yamamoto, M., Imaki, T., Hashimoto, K., Tsuchiya, T., Monden, T., Horiguchi, K., Yamada, M., Mori, M. Nature (2006) [Pubmed]
  2. Assembly of a high-resolution map of the Acadian Usher syndrome region and localization of the nuclear EF-hand acidic gene. DeAngelis, M.M., Doucet, J.P., Drury, S., Sherry, S.T., Robichaux, M.B., Den, Z., Pelias, M.Z., Ditta, G.M., Keats, B.J., Deininger, P.L., Batzer, M.A. Biochim. Biophys. Acta (1998) [Pubmed]
  3. Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects. Holt, H.B., Wild, S.H., Wood, P.J., Zhang, J., Darekar, A.A., Dewbury, K., Poole, R.B., Holt, R.I., Phillips, D.I., Byrne, C.D. Diabetologia (2006) [Pubmed]
  4. Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion. Watt, M.J., Carey, A.L., Wolsk-Petersen, E., Kraemer, F.B., Pedersen, B.K., Febbraio, M.A. Diabetologia (2005) [Pubmed]
  5. Long chain non-esterified fatty acid pattern in plasma of cystic fibrosis patients and their parents. Rogiers, V., Dab, I., Crokaert, R., Vis, H.L. Pediatr. Res. (1980) [Pubmed]
  6. Non-esterified fatty acid metabolism and postprandial lipaemia. Frayn, K.N. Atherosclerosis (1998) [Pubmed]
  7. Free and bound tryptophan in the blood of depressives. Baumann, P., Schmocker, M., Reyero, F., Heimann, H. Acta Vitaminol. Enzymol. (1975) [Pubmed]
  8. Contig maps and genomic sequencing identify candidate genes in the usher 1C locus. Higgins, M.J., Day, C.D., Smilinich, N.J., Ni, L., Cooper, P.R., Nowak, N.J., Davies, C., de Jong, P.J., Hejtmancik, F., Evans, G.A., Smith, R.J., Shows, T.B. Genome Res. (1998) [Pubmed]
  9. Extracellular TNFR1 release requires the calcium-dependent formation of a nucleobindin 2-ARTS-1 complex. Islam, A., Adamik, B., Hawari, F.I., Ma, G., Rouhani, F.N., Zhang, J., Levine, S.J. J. Biol. Chem. (2006) [Pubmed]
  10. Functional Compensation for Adipose Differentiation-related Protein (ADFP) by Tip47 in an ADFP Null Embryonic Cell Line. Sztalryd, C., Bell, M., Lu, X., Mertz, P., Hickenbottom, S., Chang, B.H., Chan, L., Kimmel, A.R., Londos, C. J. Biol. Chem. (2006) [Pubmed]
  11. Metabolic alkalosis in diabetic ketosis: a case report. Prando, R., Odetti, P., Deferrari, G. Diabète & métabolisme. (1984) [Pubmed]
  12. Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in normal subjects. Viberti, G.C., Keen, H., Bloom, S.R. Metab. Clin. Exp. (1980) [Pubmed]
  13. Increase of plasma nonesterified fatty acid concentration and decrease of albumin binding affinity after intravenous injection of glycocholate-lecithin mixed micelles. Guentert, T.W., Frey, B.M., Luedin, E., Heinzl, S., Brodersen, R. J. Lab. Clin. Med. (1990) [Pubmed]
  14. Heterologous overexpression of human NEFA and studies on the two EF-hand calcium-binding sites. Kroll, K.A., Otte, S., Hirschfeld, G., Barnikol-Watanabe, S., Götz, H., Sternbach, H., Kratzin, H.D., Barnikol, H.U., Hilschmann, N. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  15. Effect of short-term fasting treatment on liver and renal function. Horiuchi, T., Tsuchida, M., Kondo, Y., Sasaki, T. Kitasato Arch. Exp. Med. (1992) [Pubmed]
  16. Human protein NEFA, a novel DNA binding/EF-hand/leucine zipper protein. Molecular cloning and sequence analysis of the cDNA, isolation and characterization of the protein. Barnikol-Watanabe, S., Gross, N.A., Götz, H., Henkel, T., Karabinos, A., Kratzin, H., Barnikol, H.U., Hilschmann, N. Biol. Chem. Hoppe-Seyler (1994) [Pubmed]
  17. Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients. van Loon, L.J., Manders, R.J., Koopman, R., Kaastra, B., Stegen, J.H., Gijsen, A.P., Saris, W.H., Keizer, H.A. Diabetologia (2005) [Pubmed]
  18. Prolonged increase of plasma non-esterified fatty acids fully abolishes the stimulatory effect of 24 hours of moderate hyperglycaemia on insulin sensitivity and pancreatic beta-cell function in obese men. Leung, N., Sakaue, T., Carpentier, A., Uffelman, K., Giacca, A., Lewis, G.F. Diabetologia (2004) [Pubmed]
  19. Chronic hyperglycaemia promotes lipogenesis and triacylglycerol accumulation in human skeletal muscle cells. Aas, V., Kase, E.T., Solberg, R., Jensen, J., Rustan, A.C. Diabetologia (2004) [Pubmed]
  20. Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue. Samra, J.S., Clark, M.L., Humphreys, S.M., MacDonald, I.A., Bannister, P.A., Frayn, K.N. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  21. Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects. Fulcher, G.R., Walker, M., Catalano, C., Agius, L., Alberti, K.G. Diabetes (1992) [Pubmed]
  22. Diurnal variation in the effects of insulin on blood glucose, plasma non-esterified fatty acids and growth hormone. Gibson, T., Stimmler, L., Jarrett, R.J., Rutland, P., Shiu, M. Diabetologia (1975) [Pubmed]
  23. Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. Torlone, E., Fanelli, C., Rambotti, A.M., Kassi, G., Modarelli, F., Di Vincenzo, A., Epifano, L., Ciofetta, M., Pampanelli, S., Brunetti, P. Diabetologia (1994) [Pubmed]
  24. Postprandial lipaemia induces an acute decrease of insulin sensitivity in healthy men independently of plasma NEFA levels. Pedrini, M.T., Niederwanger, A., Kranebitter, M., Tautermann, C., Ciardi, C., Tatarczyk, T., Patsch, J.R. Diabetologia (2006) [Pubmed]
  25. Decreased protein catabolism after exercise in subjects with IDDM. Devlin, J.T., Scrimgeour, A., Brodsky, I., Fuller, S. Diabetologia (1994) [Pubmed]
  26. Partial recovery of insulin secretion and action after combined insulin-sulfonylurea treatment in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral agents. Del Prato, S., Vigili de Kreutzenberg, S., Riccio, A., Maifreni, L., Duner, E., Lisato, G., Iavicoli, M., Tiengo, A. Diabetologia (1990) [Pubmed]
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