UCP2 explained

Mitochondrial uncoupling protein 2 is a protein that in humans is encoded by the UCP2 gene.^[1]

Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate, or uncouple, oxidative phosphorylation from ATP synthesis by dissipating the mitochondrial membrane potential as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells, which reduces production of reactive oxygen species (ROS).

In contrast to UCP1 and UCP3, which are primarily expressed in adipose and smooth muscle, UCP2 is expressed on many different tissues^[2] including the kidney, liver, GI tract, brain, and skeletal muscle.

The exact mechanisms of anion transfer by UCPs are not known.^[3] UCPs contain the three homologous protein domains of MACPs. Although it was originally thought to play a role in non-shivering thermogenesis, obesity, diabetes and atherosclerosis, it now appears that the main function of UCP2 is the control of mitochondria-derived reactive oxygen species.^[4]

Chromosomal order is 5'-UCP3-UCP2-3'.^[5]

See also

• Uncoupling protein

Further reading

• Ricquier D, Bouillaud F . The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. . Biochem. J. . 345 . 2. 161–79 . 2000 . 10620491 . 10.1042/0264-6021:3450161 . 1220743 .
• Saleh MC, Wheeler MB, Chan CB . Uncoupling protein-2: evidence for its function as a metabolic regulator. . Diabetologia . 45 . 2 . 174–87 . 2002 . 11935148 . 10.1007/s00125-001-0737-x . free .
• Muzzin P . The uncoupling proteins. . Ann. Endocrinol. . 63 . 2 Pt 1 . 106–10 . 2002 . 11994670 .
• Horvath TL, Diano S, Barnstable C . Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector. . Biochem. Pharmacol. . 65 . 12 . 1917–21 . 2003 . 12787871 . 10.1016/S0006-2952(03)00143-6 .
• Paradis E, Clavel S, Bouillaud F, etal . Uncoupling protein 2: a novel player in neuroprotection. . Trends in Molecular Medicine . 9 . 12 . 522–5 . 2004 . 14659466 . 10.1016/j.molmed.2003.10.009 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Fleury C, Neverova M, Collins S, etal . Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. . Nat. Genet. . 15 . 3 . 269–72 . 1997 . 9054939 . 10.1038/ng0397-269 . 13421247 .
• Gimeno RE, Dembski M, Weng X, etal . Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. . Diabetes . 46 . 5 . 900–6 . 1997 . 9133562 . 10.2337/diabetes.46.5.900 .
• Boss O, Samec S, Paoloni-Giacobino A, etal . Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. . FEBS Lett. . 408 . 1 . 39–42 . 1997 . 9180264 . 10.1016/S0014-5793(97)00384-0 . 33808140 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Hodný Z, Kolárová P, Rossmeisl M, etal . High expression of uncoupling protein 2 in foetal liver. . FEBS Lett. . 425 . 2 . 185–90 . 1998 . 9559644 . 10.1016/S0014-5793(98)00230-0 . 35050170 .
• Argyropoulos G, Brown AM, Peterson R, etal . Structure and organization of the human uncoupling protein 2 gene and identification of a common biallelic variant in Caucasian and African-American subjects. . Diabetes . 47 . 4 . 685–7 . 1998 . 9568704 . 10.2337/diabetes.47.4.685 . 38803735 .
• Tu N, Chen H, Winnikes U, etal . Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene. . Life Sci. . 64 . 3 . PL41–50 . 1999 . 10027754 . 10.1016/S0024-3205(98)00555-4 .
• Pecqueur C, Cassard-Doulcier AM, Raimbault S, etal . Functional organization of the human uncoupling protein-2 gene, and juxtaposition to the uncoupling protein-3 gene. . Biochem. Biophys. Res. Commun. . 255 . 1 . 40–6 . 1999 . 10082652 . 10.1006/bbrc.1998.0146 .
• Jezek P, Urbánková E . Specific sequence of motifs of mitochondrial uncoupling proteins. . IUBMB Life . 49 . 1 . 63–70 . 2000 . 10772343 . 10.1080/713803586 . 8541209 . free .
• Pierrat B, Ito M, Hinz W, etal . Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family. . Eur. J. Biochem. . 267 . 9 . 2680–7 . 2000 . 10785390 . 10.1046/j.1432-1327.2000.01285.x .
• Esterbauer H, Schneitler C, Oberkofler H, etal . A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. . Nat. Genet. . 28 . 2 . 178–83 . 2001 . 11381268 . 10.1038/88911 . 29550924 .
• Echtay KS, Roussel D, St-Pierre J, etal . Superoxide activates mitochondrial uncoupling proteins. . Nature . 415 . 6867 . 96–9 . 2002 . 11780125 . 10.1038/415096a . 2002Natur.415...96E . 4349744 .
• Rupprecht A, Sittner D, Smorodchenko A, Hilse KE, Goyn J, Moldzio R, Seiler AE, Bräuer AU, Pohl EE. Uncoupling protein 2 and 4 expression pattern during stem cell differentiation provides new insight into their putative function. PLOS ONE. 9. 2. e88474. 2014. 10.1371/journal.pone.0088474. 24523901. 3921169. 2014PLoSO...988474R. free.
• Rupprecht A, Bräuer AU, Smorodchenko A, Goyn J, Hilse KE, Shabalina IG, Infante-Duarte C, Pohl EE. Quantification of uncoupling protein 2 reveals its main expression in immune cells and selective up-regulation during T-cell proliferation. PLOS ONE. 7. 8. e41406. 2012. 10.1371/journal.pone.0041406. 22870219. 3411681. 2012PLoSO...741406R. free.

Notes and References

1. Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB . UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue . Biochem Biophys Res Commun . 235 . 1 . 79–82 . Jul 1997 . 9196039 . 10.1006/bbrc.1997.6740 .
2. Web site: Tissue expression of UCP2 - Summary - The Human Protein Atlas. 2020-08-20. www.proteinatlas.org.
3. 2000-08-15. How do uncoupling proteins uncouple?. Biochimica et Biophysica Acta (BBA) - Bioenergetics. en. 1459. 2–3. 383–389. 10.1016/S0005-2728(00)00175-4. 0005-2728. Garlid. Keith D.. Jabůrek. Martin. Ježek. Petr. Vařecha. Miroslav. 11004454.
4. Arsenijevic D, Onuma H, Pecqueur C, etal . Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production . Nat. Genet. . 26 . 4 . 435–9 . December 2000 . 11101840 . 10.1038/82565 . 29831657 .
5. Web site: Entrez Gene: UCP2 uncoupling protein 2 (mitochondrial, proton carrier).