UCP3

UCP3
Identifiers
AliasesUCP3, uncoupling protein 3 (mitochondrial, proton carrier), SLC25A9, uncoupling protein 3
External IDsMGI: 1099787 HomoloGene: 2517 GeneCards: UCP3
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q13.4Start74,000,281 bp[1]
End74,009,435 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

7352

22229

Ensembl

ENSG00000175564

ENSMUSG00000032942

UniProt

P55916

P56501

RefSeq (mRNA)

NM_022803
NM_003356

NM_009464

RefSeq (protein)

NP_003347
NP_073714

NP_033490

Location (UCSC)Chr 11: 74 – 74.01 MbChr 7: 100.47 – 100.49 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitochondrial uncoupling protein 3 is a protein that in humans is encoded by the UCP3 gene.[5][6]

UCP3 is a mitochondrial uncoupling protein 3, which is encoded by UCP3. The gene is located in chromosome (11q13.4) with an exon count of 7 (HGNC et al., 2016). Uncoupling protein being a supreme family of mitochondrial anion carrier. Its functions is to separate the oxidative phosphorylation from synthesis of ATP as energy which is anticipated as heat. The uncoupling proteins involves in the transferring of anions from inner mitochondrial membrane to outer mitochondrial membrane, its protein is programmed in a way to protect mitochondria from induced oxidative stress.

Function

Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP).UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated 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 there turn transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact method so far how UCPs transfer H+/OH− are not known.[7]

Protein expression

Uncoupling proteins are transporters in mitochondrial membrane which deplete the proton gradient.UCP1 asseverate in brown adipocytes, But UCP2 is widely expressed. Molecular cloning of UCP3 (uncoupling protein homologue). At amino acid level the hUCP3 is 71% equivalent to hUCP2.Uncoupling protein3 is acclaimed from UCP1 and UCP2 because of its ample and preferred expression in skeletal muscle in humans and brown adipose tissue and skeletal muscle in rodents (Antonio et al., 1997). UCP3 is an important mediator of thermogenesis.

Associated SNPs

UCP3 were confirmed containing four single nucleotide polymorphism rs1800849, rs11235972, rs1726745 and rs3781907. There was high impact score of rs11235972 GG genotype thus showing association of UCP3 gene polymorphism and nonalcoholic fatty liver disease in Chinese children (Xu YP et al., 2013) The research of counterfeits in two independent population there was a similarity between the -55CT mutation of UCP3 and lower BMI. This affiliation was being modulated by the energy intake, hence deriving the undefined effect of diet and partly association of inconsistencies of prior related studies.

Structure

UCPs contain the three homologous protein domains of MACPs.[7]

Gene regulation

This gene has tissue-specific transcription initiation with other transcription initiation sites upstream of SM-1 (major skeletal muscle site). Chromosomal order is 5'-UCP3-UCP2-3'. Two splice variants have been found for this gene.[7]

Disease association

Mutations in the UCP3 gene are associated with obesity.[8][9] UCP3 plays an essential role in obesity. A mutation in exon 3 (V102I) was diagnosed in an obese and diabetic. A mutation initializing a stop codon at exon 4 (R143X) and a mutation in the splice donor junction of exon 6 was analyzed in a compound heterozygote which was unnaturally obese and diabetic.[8] Allele frequency of exon 3 and exon 6 splice at an alliance mutation were analyzed to be similar in African American and mende tribe and was absent in Caucasians.[8] Exon 6–splice donor being heterozygotes, fat oxidation rates was reduced by 50%, initiating a role for UCP3 in metabolic fuel partitioning.[8] UCP3 (uncoupling protein) deliberates the hypoxia resistance to the renal epithelial cells and its upregulation in renal cell carcinoma.[10] The energy consumption of modulated and the association of -55CT polymorphism of UCP3 with the body weight and in type 2 diabetic patients.[11]

Inhibitors

Since protein UCP3 is affecting the long chain fatty acid metabolism and preventing cytosolic triglyceride storage. Telmisartan being an inhibitor by proven studies on rat skeletal muscle and improving the mutant protein activity and also its involvement in the dominant negative UCP3 mutants(C V Musa et al., 2012). Hence, novel UCP3 gene variants which associated to childhood obesity and even the effect of fatty acid oxidation prevention in triglyceride storage(C V Musa et al., 2012).

Interactions

UCP3 has been shown to interact with YWHAQ.[12] Uncoupling protein UPC2 and uncoupling protein UPC3 interaction with members of the 14.3.3 family (Benoit pierrat et al., 2000). Uncoupling protein (UCP3) modulating the process of Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) by declining the mitochondrial ATP fabrication (De Marchi U et al., 2011).

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000175564 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032942 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Boss O, Giacobino JP, Muzzin P (February 1998). "Genomic structure of uncoupling protein-3 (UCP3) and its assignment to chromosome 11q13". Genomics. 47 (3): 425–6. doi:10.1006/geno.1997.5135. PMID 9480760.
  6. ↑ Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB (June 1997). "UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue". Biochemical and Biophysical Research Communications. 235 (1): 79–82. doi:10.1006/bbrc.1997.6740. PMID 9196039.
  7. 1 2 3 "Entrez Gene: UCP3 uncoupling protein 3 (mitochondrial, proton carrier)".
  8. 1 2 3 4 Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT (October 1998). "Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes". The Journal of Clinical Investigation. 102 (7): 1345–51. doi:10.1172/JCI4115. PMC 508981. PMID 9769326.
  9. ↑ Dalgaard LT, Sørensen TI, Drivsholm T, Borch-Johnsen K, Andersen T, Hansen T, Pedersen O (March 2001). "A prevalent polymorphism in the promoter of the UCP3 gene and its relationship to body mass index and long term body weight change in the Danish population". The Journal of Clinical Endocrinology and Metabolism. 86 (3): 1398–402. doi:10.1210/jc.86.3.1398. PMID 11238538.
  10. ↑ Braun N, Klumpp D, Hennenlotter J, Bedke J, Duranton C, Bleif M, Huber SM (August 2015). "UCP-3 uncoupling protein confers hypoxia resistance to renal epithelial cells and is upregulated in renal cell carcinoma". Scientific Reports. 5: 13450. Bibcode:2015NatSR...513450B. doi:10.1038/srep13450. PMC 4548255. PMID 26304588.
  11. ↑ Lapice E, Monticelli A, Cocozza S, Pinelli M, Giacco A, Rivellese AA, Cocozza S, Riccardi G, Vaccaro O (June 2014). "The energy intake modulates the association of the -55CT polymorphism of UCP3 with body weight in type 2 diabetic patients". International Journal of Obesity. 38 (6): 873–7. doi:10.1038/ijo.2013.174. PMID 24026107.
  12. ↑ Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J (May 2000). "Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family". European Journal of Biochemistry. 267 (9): 2680–7. doi:10.1046/j.1432-1327.2000.01285.x. PMID 10785390.

Further reading

  • Hilse KE, Kalinovich AV, Rupprecht A, Smorodchenko A, Zeitz U, Staniek K, Erben RG, Pohl EE (January 2016). "The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue". Biochimica et Biophysica Acta. 1857 (1): 72–78. doi:10.1016/j.bbabio.2015.10.011.
  • Muzzin P (April 2002). "The uncoupling proteins". Annales d'Endocrinologie. 63 (2 Pt 1): 106–10. PMID 11994670.
  • Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino JP (May 1997). "Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression". FEBS Letters. 408 (1): 39–42. doi:10.1016/S0014-5793(97)00384-0. PMID 9180264.
  • Gong DW, He Y, Karas M, Reitman M (September 1997). "Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin". The Journal of Biological Chemistry. 272 (39): 24129–32. doi:10.1074/jbc.272.39.24129. PMID 9305858.
  • Solanes G, Vidal-Puig A, Grujic D, Flier JS, Lowell BB (October 1997). "The human uncoupling protein-3 gene. Genomic structure, chromosomal localization, and genetic basis for short and long form transcripts". The Journal of Biological Chemistry. 272 (41): 25433–6. doi:10.1074/jbc.272.41.25433. PMID 9325252.
  • Urhammer SA, Dalgaard LT, Sørensen TI, Tybjaerg-Hansen A, Echwald SM, Andersen T, Clausen JO, Pedersen O (February 1998). "Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity". Diabetologia. 41 (2): 241–4. doi:10.1007/s001250050897. PMID 9498661.
  • Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT (October 1998). "Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes". The Journal of Clinical Investigation. 102 (7): 1345–51. doi:10.1172/JCI4115. PMC 508981. PMID 9769326.
  • Acín A, Rodriguez M, Rique H, Canet E, Boutin JA, Galizzi JP (May 1999). "Cloning and characterization of the 5' flanking region of the human uncoupling protein 3 (UCP3) gene". Biochemical and Biophysical Research Communications. 258 (2): 278–83. doi:10.1006/bbrc.1999.0530. PMID 10329378.
  • Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB (May 2000). "Energy metabolism in uncoupling protein 3 gene knockout mice". The Journal of Biological Chemistry. 275 (21): 16258–66. doi:10.1074/jbc.M910179199. PMID 10748196.
  • Jezek P, Urbánková E (January 2000). "Specific sequence of motifs of mitochondrial uncoupling proteins". IUBMB Life. 49 (1): 63–70. doi:10.1080/713803586. PMID 10772343.
  • Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J (May 2000). "Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family". European Journal of Biochemistry. 267 (9): 2680–7. doi:10.1046/j.1432-1327.2000.01285.x. PMID 10785390.
  • Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, Piercy V, Carter SA, Lehner I, Smith SA, Beeley LJ, Godden RJ, Herrity N, Skehel M, Changani KK, Hockings PD, Reid DG, Squires SM, Hatcher J, Trail B, Latcham J, Rastan S, Harper AJ, Cadenas S, Buckingham JA, Brand MD, Abuin A (July 2000). "Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean". Nature. 406 (6794): 415–8. Bibcode:2000Natur.406..415C. doi:10.1038/35019082. PMID 10935638.
  • Esterbauer H, Oberkofler H, Krempler F, Strosberg AD, Patsch W (November 2000). "The uncoupling protein-3 gene is transcribed from tissue-specific promoters in humans but not in rodents". The Journal of Biological Chemistry. 275 (46): 36394–9. doi:10.1074/jbc.M005713200. PMID 10958796.
  • Lanouette CM, Chagnon YC, Rice T, Pérusse L, Muzzin P, Giacobino JP, Gagnon J, Wilmore JH, Leon AS, Skinner JS, Rao DC, Bouchard C (March 2002). "Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study". Journal of Applied Physiology. 92 (3): 1111–8. doi:10.1152/japplphysiol.00726.2001. PMID 11842047.
  • Collins P, Bing C, McCulloch P, Williams G (February 2002). "Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans". British Journal of Cancer. 86 (3): 372–5. doi:10.1038/sj.bjc.6600074. PMC 2375209. PMID 11875702.
  • Hu X, Murphy F, Karwautz A, Li T, Freeman B, Franklin D, Giotakis O, Treasure J, Collier DA (2002). "Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa". Molecular Psychiatry. 7 (3): 276–7. doi:10.1038/sj.mp.4001044. PMID 11920154.
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