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Gene Review

UCP3  -  uncoupling protein 3 (mitochondrial,...

Homo sapiens

Synonyms: Mitochondrial uncoupling protein 3, SLC25A9, Solute carrier family 25 member 9, UCP 3
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Disease relevance of UCP3

  • Thus, proton leak and the expression of UCP3 correlate with weight loss success and may be candidates for pharmacological regulation of fat oxidation in obese diet-resistant subjects [1].
  • Because skeletal muscle mitochondrial proton leak may account for a large proportion of resting metabolic rate, we compared proton leak in diet-resistant and diet-responsive overweight women and compared the expression and gene characteristics of uncoupling protein (UCP)2 and UCP3 [1].
  • Also [3H]GTP ([3H]ATP) binding to isolated Escherichia coli (Kd, approximately 5 microm) or yeast-expressed UCP2 (Kd, approximately 1.5 microm) or UCP3 exhibited high affinity, similar to UCP1 [2].
  • We conclude it is unlikely that variants in the coding region of the UCP3 gene contribute to the pathogenesis of juvenile-onset obesity among Danish Caucasians [3].
  • Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes [4].

Psychiatry related information on UCP3


High impact information on UCP3

  • 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 [9].
  • UCP2 and UCP3 are recently identified UCP1 homologues [10].
  • We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle [11].
  • However, this HF diet-induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation [11].
  • Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling [11].

Chemical compound and disease context of UCP3


Biological context of UCP3


Anatomical context of UCP3


Associations of UCP3 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 [2].
  • 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 [15].
  • Furthermore, UCP3 gene expression was found to correlate negatively with body mass index and positively with sleeping metabolic rate in Pima Indians [20].
  • Treatment with thyroid hormone increases expression of the UCP2 and UCP3 genes [20].
  • The association of the UCP2 A55V and UCP3 Rsa I CC genotypes with a greater increase in the TSH response to TRH load could reflect a compensatory mechanism counteracting the effects of overfeeding [18].

Regulatory relationships of UCP3


Other interactions of UCP3

  • Yin yang haplotypes were observed only in PTHR1 and UCP3 [26].
  • Slow component of [V]O(2) kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity [17].
  • Our results suggest that the LEP and UCP2/UCP3 genes are unlikely to have a substantial effect on variation in obesity phenotypes in this particular US Caucasian population [27].
  • Direct interaction between UCP3 and 14.3.3 theta could be demonstrated after in vitro translation by coimmunoprecipitation [28].
  • Exercise induced a significant (P < 0.05) increase (2- to 3-fold) in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) genes in the reduced glycogen leg only [29].

Analytical, diagnostic and therapeutic context of UCP3


  1. Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women. Harper, M.E., Dent, R., Monemdjou, S., Bézaire, V., Van Wyck, L., Wells, G., Kavaslar, G.N., Gauthier, A., Tesson, F., McPherson, R. Diabetes (2002) [Pubmed]
  2. 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]
  3. Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity. Urhammer, S.A., Dalgaard, L.T., Sørensen, T.I., Tybjaerg-Hansen, A., Echwald, S.M., Andersen, T., Clausen, J.O., Pedersen, O. Diabetologia (1998) [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. 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]
  6. The role of uncoupling protein 3 in fatty acid metabolism: protection against lipotoxicity? Schrauwen, P., Hesselink, M.K. The Proceedings of the Nutrition Society. (2004) [Pubmed]
  7. The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans. Schrauwen, P., Westerterp-Plantenga, M.S., Kornips, E., Schaart, G., van Marken Lichtenbelt, W.D. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  8. A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians. Schrauwen, P., Xia, J., Walder, K., Snitker, S., Ravussin, E. Int. J. Obes. Relat. Metab. Disord. (1999) [Pubmed]
  9. 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]
  10. The mitochondrial uncoupling-protein homologues. Krauss, S., Zhang, C.Y., Lowell, B.B. Nat. Rev. Mol. Cell Biol. (2005) [Pubmed]
  11. Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo. Hesselink, M.K., Greenhaff, P.L., Constantin-Teodosiu, D., Hultman, E., Saris, W.H., Nieuwlaat, R., Schaart, G., Kornips, E., Schrauwen, P. J. Clin. Invest. (2003) [Pubmed]
  12. Roles of norepinephrine, free Fatty acids, thyroid status, and skeletal muscle uncoupling protein 3 expression in sympathomimetic-induced thermogenesis. Sprague, J.E., Yang, X., Sommers, J., Gilman, T.L., Mills, E.M. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  13. Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue. Khalfallah, Y., Fages, S., Laville, M., Langin, D., Vidal, H. Diabetes (2000) [Pubmed]
  14. 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]
  15. 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]
  16. Regulation of UCP1 and UCP3 in arctic ground squirrels and relation with mitochondrial proton leak. Barger, J.L., Barnes, B.M., Boyer, B.B. J. Appl. Physiol. (2006) [Pubmed]
  17. Slow component of [V]O(2) kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity. Russell, A., Wadley, G., Snow, R., Giacobino, J.P., Muzzin, P., Garnham, A., Cameron-Smith, D. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  18. 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]
  19. Expression of UCP3 in CHO cells does not cause uncoupling, but controls mitochondrial activity in the presence of glucose. Mozo, J., Ferry, G., Studeny, A., Pecqueur, C., Rodriguez, M., Boutin, J.A., Bouillaud, F. Biochem. J. (2006) [Pubmed]
  20. Human uncoupling proteins and obesity. Schrauwen, P., Walder, K., Ravussin, E. Obes. Res. (1999) [Pubmed]
  21. 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]
  22. Insulin-like growth factor type 1 prevents hyperglycemia-induced uncoupling protein 3 down-regulation and oxidative stress. Gustafsson, H., Söderdahl, T., Jönsson, G., Bratteng, J.O., Forsby, A. J. Neurosci. Res. (2004) [Pubmed]
  23. Absence of UCP3 in brown adipose tissue does not impair nonshivering thermogenesis. Liebig, M., von Praun, C., Heldmaier, G., Klingenspor, M. Physiol. Biochem. Zool. (2004) [Pubmed]
  24. The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects. Schrauwen, P., Schaart, G., Saris, W.H., Slieker, L.J., Glatz, J.F., Vidal, H., Blaak, E.E. Diabetologia (2000) [Pubmed]
  25. Insulin-like growth factor type 1 upregulates uncoupling protein 3. Gustafsson, H., Adamson, L., Hedander, J., Walum, E., Forsby, A. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  26. Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes. Long, J.R., Zhao, L.J., Liu, P.Y., Lu, Y., Dvornyk, V., Shen, H., Liu, Y.J., Zhang, Y.Y., Xiong, D.H., Xiao, P., Deng, H.W. BMC Genet. (2004) [Pubmed]
  27. Linkage exclusion analysis of two candidate regions on chromosomes 7 and 11: leptin and UCP2/UCP3 are not QTLs for obesity in US Caucasians. Guo, J.J., Liu, Y.J., Li, M.X., Yang, Y.J., Recker, R.R., Deng, H.W. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  28. Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family. Pierrat, B., Ito, M., Hinz, W., Simonen, M., Erdmann, D., Chiesi, M., Heim, J. Eur. J. Biochem. (2000) [Pubmed]
  29. Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes. Pilegaard, H., Keller, C., Steensberg, A., Helge, J.W., Pedersen, B.K., Saltin, B., Neufer, P.D. J. Physiol. (Lond.) (2002) [Pubmed]
  30. UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Vidal-Puig, A., Solanes, G., Grujic, D., Flier, J.S., Lowell, B.B. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  31. 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]
  32. Uncoupling protein-3 (UCP3) mRNA expression in reconstituted human muscle after myoblast transplantation in RAG2-/-/gamma c/C5(-) immunodeficient mice. Guigal, N., Rodriguez, M., Cooper, R.N., Dromaint, S., Di Santo, J.P., Mouly, V., Boutin, J.A., Galizzi, J.P. J. Biol. Chem. (2002) [Pubmed]
  33. Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults. Calsbeek, D.J., Thompson, T.L., Dahl, J.A., Stob, N.R., Brozinick, J.T., Hill, J.O., Hickey, M.S. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
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