The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

UCP2  -  uncoupling protein 2 (mitochondrial,...

Homo sapiens

Synonyms: BMIQ4, Mitochondrial uncoupling protein 2, SLC25A8, Solute carrier family 25 member 8, UCP 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of UCP2

  • A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans [1].
  • Human UCP2 and 3 expressed in Escherichia coli inclusion bodies are solubilized, and by exchange of sarcosyl against digitonin, nucleotide binding as measured with 2'-O-[5-(dimethylamino)naphthalene-1-sulfonyl]-GTP can be restored [2].
  • The main conclusion is that variation in the UCP1, UCP2 or UCP3 genes is not associated with major alterations of body gain [3].
  • The three uncoupling protein homologue genes UCP1, UCP2, and UCP3 have been investigated for polymorphisms and mutations and their impact on Type II diabetes mellitus, obesity, and body weight gain or BMI [3].
  • Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes [4].
  • Neuroprotection in the thalamus correlated with a high expression of UCP2, which is neuroprotective in a number of models of neurodegenerative diseases [5].

Psychiatry related information on UCP2

  • Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa [6].
  • We have previously found an increased physical activity but a similar 24-h energy expenditure (EE) in subjects with the val/val-55 UCP2 genotype compared to those with the ala/ala genotype which indicates that the val-55 allele is statistically associated with a higher metabolic efficiency [7].
  • The relative liver UCP2 expression of the five major Chinese carps, shows a close relationship with their food habit: benthos and detritus-eating fish (common carp and mud carp) > planktivorious fish (silver carp and bighead carp) > herbivorous fish (grass carp) [8].
  • Fasting-induced T3-mediated UCP2 activation resulted in mitochondrial proliferation in NPY/AgRP neurons, an event that was critical for increased excitability of these orexigenic neurons and consequent rebound feeding following food [9].

High impact information on UCP2

  • Like its close relatives UCP1 and UCP3, UCP2 uncouples proton entry in the mitochondrial matrix from ATP synthesis and is therefore a candidate gene for obesity [1].
  • We show here that a common G/A polymorphism in the UCP2 promoter region is associated with enhanced adipose tissue mRNA expression in vivo and results in increased transcription of a reporter gene in the human adipocyte cell line PAZ-6 [1].
  • The pancreatic beta cell : UCP2 and insulin secretion in diabetes [10].
  • The first report of UCP2-deficient mice reported that they had higher islet ATP levels and increased glucose-stimulated insulin secretion, establishing that UCP2 negatively regulates insulin secretion [11]. However, this has been found to be an artifact of the strain background distribution. Backcrossed animals in three unique strains (A/J, B6 and 129) all show global oxidative stress in various tissues, including pancreatic islets, and signficantly impaired gllucose-stimulated insulin secretion [10]
  • Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli [12].
  • Subsequent work on UCP2 has been unable to demonstrate any significant role in thermoregulation and body weight.

Chemical compound and disease context of UCP2

  • UCP2 message has been shown to be up-regulated in the CNS by stress signals such as kainate administration or ischemia, and overexpression of UCP2 has been reported to be neuroprotective against oxidative stress in vivo and in vitro, although the exact mechanism has not been fully established [13].
  • CONCLUSION: Differential effects of stavudine and zidovudine therapy on mtDNA depletion and expression of adipocyte differentiation markers PPARgamma and UCP2 were observed, consistent with increased adipose tissue toxicity associated with stavudine therapy [14].
  • In conclusion, UCP2 promoter polymorphism -866G/A does not affect obesity in Japanese type 2 diabetic patients but affects its transcription in beta-cells and modulates glucose-induced insulin secretion and eventually insulin requirement in Japanese type 2 diabetic patients [15].
  • CONCLUSIONS/INTERPRETATION: Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians [16].
  • RESULTS: UCP2 mRNA and protein levels were 3- to 4-fold higher in adenocarcinomas, and UCP2 mRNA levels showed significant correlation with increased tumor tissue malondialdehyde contents [17].

Biological context of UCP2


Anatomical context of UCP2

  • Uncoupling protein-2 (UCP2) is a recently identified member of the mitochondrial transporter superfamily that is expressed in many tissues, including adipose tissue [1].
  • It is straightforward to hypothesize that common polymorphisms of UCP1, UCP2 and UCP3 genes lower metabolic rate by a more efficient energy coupling in the mitochondria [3].
  • We also investigated whether the thiazolidinedione, troglitazone, stimulates UCP2 and UCP3 mRNA levels to follow up on the observation that this antidiabetic drug increases the levels of expression in cultured [19].
  • Although it has been postulated that UCP2 could induce type 2 diabetes as developed from obesity due to up-regulated UCP2 transcription by FAs in pancreatic beta-cells [21], the increase in UCP2 is in obesity is perhaps a consequence of ROS and attempts to diminish it.
  • From the three different UCPs identified so far by gene cloning UCP1 is expressed exclusively in brown adipocytes while UCP2 is widely expressed [22].

Associations of UCP2 with chemical compounds

  • Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3 [23].
  • Only nocturnal urinary norepinephrine excretion could explain a significant fraction of the variability in both UCP2 and UCP3 expression in muscle, but not adipose tissue [19].
  • Treatment with thyroid hormone increases expression of the UCP2 and UCP3 genes [20].
  • Also mean plasma TSH concentrations 20, 30 and 45 min after the TRH injection increased more with overfeeding among UCP2 A55V (P<0.005) and UCP3 Rsa I CC (P=0.017) subjects [24].
  • UCP2 mRNA has a ubiquitous distribution in tissue, namely, in skeletal muscle, white and brown adipose tissue, the gastro-intestinal tract, the lung and the spleen [25].

Physical interactions of UCP2

  • We have assessed the expression of the mitochondrial ND2 and ND5 (subunits of the nicotinamide adenine dinucleotide dehydrogenase complex) genes and the nuclear UCP2 (uncoupling protein 2) gene in 22 oxyphilic thyroid tumors and matched controls [26].

Regulatory relationships of UCP2

  • UCP1 and UCP2 were expressed in cultured retinal capillary cells whereas UCP3 was not [27].
  • We show here that the pancreatic transcription factor PAX6 preferentially binds to and more effectively trans activates the variant than the wild-type UCP2 promoter allele in the beta-cell line INS1-E [28].
  • Thus, UCP2 promoter polymorphism may contribute to MS susceptibility by regulating the level of UCP2 protein in the central nervous and/or the immune systems [29].

Other interactions of UCP2

  • These results confirm the regulation of UCP2 and UCP3 by the same factors CoQ, fatty acids, and nucleotides as UCP1 [2].
  • At high levels of glucose, expression of UCP1, UCP2 and MnSOD increased to accommodate ROS production compensatively [27].
  • After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only [30].
  • RESULTS: The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma ( PPARgamma) gene [31].
  • EXPERIMENTAL DESIGN: UCP2 expression was characterized by real-time polymerase chain reaction and Western blotting using paired human colon adenocarcinoma and peritumoral specimens [17].

Analytical, diagnostic and therapeutic context of UCP2


  1. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Esterbauer, H., Schneitler, C., Oberkofler, H., Ebenbichler, C., Paulweber, B., Sandhofer, F., Ladurner, G., Hell, E., Strosberg, A.D., Patsch, J.R., Krempler, F., Patsch, W. Nat. Genet. (2001) [Pubmed]
  2. Uncoupling proteins 2 and 3 are highly active H(+) transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone). Echtay, K.S., Winkler, E., Frischmuth, K., Klingenberg, M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes. Dalgaard, L.T., Pedersen, O. Diabetologia (2001) [Pubmed]
  4. Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes. Rudofsky, G., Schroedter, A., Schlotterer, A., Voron'ko, O.E., Schlimme, M., Tafel, J., Isermann, B.H., Humpert, P.M., Morcos, M., Bierhaus, A., Nawroth, P.P., Hamann, A. Diabetes Care (2006) [Pubmed]
  5. Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse. Deierborg, T., Deierborg Olsson, T., Wieloch, T., Diano, S., Warden, C.H., Horvath, T.L., Mattiasson, G. J. Cereb. Blood Flow Metab. (2008) [Pubmed]
  6. Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa. Hu, X., Murphy, F., Karwautz, A., Li, T., Freeman, B., Franklin, D., Giotakis, O., Treasure, J., Collier, D.A. Mol. Psychiatry (2002) [Pubmed]
  7. The association between the val/ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency. Buemann, B., Schierning, B., Toubro, S., Bibby, B.M., Sørensen, T., Dalgaard, L., Pedersen, O., Astrup, A. Int. J. Obes. Relat. Metab. Disord. (2001) [Pubmed]
  8. Structural conservation and food habit-related liver expression of uncoupling protein 2 gene in five major Chinese carps. Liao, W.Q., Liang, X.F., Wang, L., Fang, L., Lin, X., Bai, J., Jian, Q. J. Biochem. Mol. Biol. (2006) [Pubmed]
  9. A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2. Coppola, A., Liu, Z.W., Andrews, Z.B., Paradis, E., Roy, M.C., Friedman, J.M., Ricquier, D., Richard, D., Horvath, T.L., Gao, X.B., Diano, S. Cell metabolism (2007) [Pubmed]
  10. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Pi, J., Bai, Y., Daniel, K.W., Liu, D., Lyght, O., Edelstein, D., Brownlee, M., Corkey, B.E., Collins, S. Endocrinology. (2009) [Pubmed]
  11. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Zhang, C.Y., Baffy, G., Perret, P., Krauss, S., Peroni, O., Grujic, D., Hagen, T., Vidal-Puig, A.J., Boss, O., Kim, Y.B., Zheng, X.X., Wheeler, M.B., Shulman, G.I., Chan, C.B., Lowell, B.B. Cell (2001) [Pubmed]
  12. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi-Meyrueis, C., Bouillaud, F., Seldin, M.F., Surwit, R.S., Ricquier, D., Warden, C.H. Nat. Genet. (1997) [Pubmed]
  13. Mitochondrial uncoupling proteins in the central nervous system. Kim-Han, J.S., Dugan, L.L. Antioxid. Redox Signal. (2005) [Pubmed]
  14. Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Pace, C.S., Martin, A.M., Hammond, E.L., Mamotte, C.D., Nolan, D.A., Mallal, S.A. Antivir. Ther. (Lond.) (2003) [Pubmed]
  15. Uncoupling protein 2 promoter polymorphism -866G/A affects its expression in beta-cells and modulates clinical profiles of Japanese type 2 diabetic patients. Sasahara, M., Nishi, M., Kawashima, H., Ueda, K., Sakagashira, S., Furuta, H., Matsumoto, E., Hanabusa, T., Sasaki, H., Nanjo, K. Diabetes (2004) [Pubmed]
  16. Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians. Kovacs, P., Ma, L., Hanson, R.L., Franks, P., Stumvoll, M., Bogardus, C., Baier, L.J. Diabetologia (2005) [Pubmed]
  17. Expression of uncoupling protein-2 in human colon cancer. Horimoto, M., Resnick, M.B., Konkin, T.A., Routhier, J., Wands, J.R., Baffy, G. Clin. Cancer Res. (2004) [Pubmed]
  18. Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans. Millet, L., Vidal, H., Andreelli, F., Larrouy, D., Riou, J.P., Ricquier, D., Laville, M., Langin, D. J. Clin. Invest. (1997) [Pubmed]
  19. Uncoupling protein-2 and -3 messenger ribonucleic acids in adipose tissue and skeletal muscle of healthy males: variability, factors affecting expression, and relation to measures of metabolic rate. Boivin, M., Camirand, A., Carli, F., Hoffer, L.J., Silva, J.E. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  20. Human uncoupling proteins and obesity. Schrauwen, P., Walder, K., Ravussin, E. Obes. Res. (1999) [Pubmed]
  21. Possible physiological roles of mitochondrial uncoupling proteins--UCPn. Jezek, P. Int. J. Biochem. Cell Biol. (2002) [Pubmed]
  22. Genomic organization and mutational analysis of the human UCP2 gene, a prime candidate gene for human obesity. Lentes, K.U., Tu, N., Chen, H., Winnikes, U., Reinert, I., Marmann, G., Pirke, K.M. J. Recept. Signal Transduct. Res. (1999) [Pubmed]
  23. Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3. Zackova, M., Skobisová, E., Urbánková, E., Jezek, P. J. Biol. Chem. (2003) [Pubmed]
  24. Genetic variation at the uncoupling protein 1, 2 and 3 loci and the response to long-term overfeeding. Ukkola, O., Tremblay, A., Sun, G., Chagnon, Y.C., Bouchard, C. European journal of clinical nutrition. (2001) [Pubmed]
  25. The role of uncoupling proteins in the regulation of metabolism. Erlanson-Albertsson, C. Acta Physiol. Scand. (2003) [Pubmed]
  26. Defective mitochondrial ATP synthesis in oxyphilic thyroid tumors. Savagner, F., Franc, B., Guyetant, S., Rodien, P., Reynier, P., Malthiery, Y. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  27. Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: The role of reactive oxygen species in diabetic retinopathy. Cui, Y., Xu, X., Bi, H., Zhu, Q., Wu, J., Xia, X., Qiushi Ren, n.u.l.l., Ho, P.C. Exp. Eye Res. (2006) [Pubmed]
  28. A functional polymorphism in the promoter of UCP2 enhances obesity risk but reduces type 2 diabetes risk in obese middle-aged humans. Krempler, F., Esterbauer, H., Weitgasser, R., Ebenbichler, C., Patsch, J.R., Miller, K., Xie, M., Linnemayr, V., Oberkofler, H., Patsch, W. Diabetes (2002) [Pubmed]
  29. Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis. Vogler, S., Goedde, R., Miterski, B., Gold, R., Kroner, A., Koczan, D., Zettl, U.K., Rieckmann, P., Epplen, J.T., Ibrahim, S.M. J. Mol. Med. (2005) [Pubmed]
  30. Mitochondrial uncoupling proteins--facts and fantasies. Jezek, P., Zácková, M., Růzicka, M., Skobisová, E., Jabůrek, M. Physiological research / Academia Scientiarum Bohemoslovaca. (2004) [Pubmed]
  31. Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus. Cho, Y.M., Ritchie, M.D., Moore, J.H., Park, J.Y., Lee, K.U., Shin, H.D., Lee, H.K., Park, K.S. Diabetologia (2004) [Pubmed]
  32. Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene. Tu, N., Chen, H., Winnikes, U., Reinert, I., Marmann, G., Pirke, K.M., Lentes, K.U. Life Sci. (1999) [Pubmed]
  33. Systemic inflammation correlates with increased expression of skeletal muscle ubiquitin but not uncoupling proteins in cancer cachexia. DeJong, C.H., Busquets, S., Moses, A.G., Schrauwen, P., Ross, J.A., Argiles, J.M., Fearon, K.C. Oncol. Rep. (2005) [Pubmed]
  34. The -866A/A genotype in the promoter of the human uncoupling protein 2 gene is associated with insulin resistance and increased risk of type 2 diabetes. D'Adamo, M., Perego, L., Cardellini, M., Marini, M.A., Frontoni, S., Andreozzi, F., Sciacqua, A., Lauro, D., Sbraccia, P., Federici, M., Paganelli, M., Pontiroli, A.E., Lauro, R., Perticone, F., Folli, F., Sesti, G. Diabetes (2004) [Pubmed]
WikiGenes - Universities