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{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
{{Infobox_gene}}
'''Mitochondrial uncoupling protein 3''' is a [[protein]] that in humans is encoded by the ''UCP3'' [[gene]].<ref name="pmid9480760">{{cite journal | vauthors = Boss O, Giacobino JP, Muzzin P | title = Genomic structure of uncoupling protein-3 (UCP3) and its assignment to chromosome 11q13 | journal = Genomics | volume = 47 | issue = 3 | pages = 425–6 | date = April 1998 | pmid = 9480760 | pmc = | doi = 10.1006/geno.1997.5135 }}</ref><ref name="pmid9196039">{{cite journal | vauthors = Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB | title = UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue | journal = Biochem Biophys Res Commun | volume = 235 | issue = 1 | pages = 79–82 | date = July 1997 | pmid = 9196039 | pmc = | doi = 10.1006/bbrc.1997.6740 }}</ref>
'''Mitochondrial uncoupling protein 3''' is a [[protein]] that in humans is encoded by the ''UCP3'' [[gene]].<ref name="pmid9480760">{{cite journal | vauthors = Boss O, Giacobino JP, Muzzin P | title = Genomic structure of uncoupling protein-3 (UCP3) and its assignment to chromosome 11q13 | journal = Genomics | volume = 47 | issue = 3 | pages = 425–6 | date = February 1998 | pmid = 9480760 | doi = 10.1006/geno.1997.5135 }}</ref><ref name="pmid9196039">{{cite journal | vauthors = Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB | title = UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue | journal = Biochemical and Biophysical Research Communications | volume = 235 | issue = 1 | pages = 79–82 | date = June 1997 | pmid = 9196039 | doi = 10.1006/bbrc.1997.6740 }}</ref> The gene is located in chromosome (11q13.4) with an exon count of 7 (HGNC et al., 2016) and is expressed on the [[inner mitochondrial membrane]]. Uncoupling proteins transfer anions from the inner mitochondrial membrane to the outer mitochondrial membrane, thereby separating (or uncoupling) [[oxidative phosphorylation]] from [[ATP synthase|synthesis of ATP]], and dissipating energy stored in the mitochondrial membrane potential as heat. Uncoupling proteins also reduce generation of [[reactive oxygen species]].


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 ==
== Function ==
Mitochondrial uncoupling proteins (UCP) are members of the larger family of [[Mitochondrial carrier|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.<ref name="entrez">{{cite web | title = Entrez Gene: UCP3 uncoupling protein 3 (mitochondrial, proton carrier)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7352| accessdate = }}</ref>
Mitochondrial uncoupling protein 3 (UCP3) is a members of the larger family of [[Mitochondrial carrier|mitochondrial anion carrier proteins]] (MACP). UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and transfer of protons from the outer to the inner mitochondrial membrane, reducing the mitochondrial membrane potential in mammalian cells. The exact mechanisms of how UCPs transfer H+/OH− are not known.<ref name="entrez">{{cite web | title = Entrez Gene: UCP3 uncoupling protein 3 (mitochondrial, proton carrier)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7352}}</ref> In addition to UCP1, UCP3 is an important mediator of thermogenesis.

⚫
== 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.


⚫
== Protein expression ==
Uncoupling proteins are transporters in mitochondrial membrane which deplete the proton gradient. UCP1 is highly expressed in brown adipocytes, UCP2 is variably expressed in many different tissues, and UCP3 is expressed primarily in skeletal muscle. At amino acid level human UCP3 is 71% equivalent to UCP2. UCP3 i


== Associated SNPs ==
== 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)
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.
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 ==
== Structure ==
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== Disease association ==
== Disease association ==


Mutations in the UCP3 gene are associated with obesity.<ref name="Argyropoulos_1998">{{cite journal | vauthors = Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT | title = Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes | journal = J. Clin. Invest. | volume = 102 | issue = 7 | pages = 1345–51 | date = October 1998 | pmid = 9769326 | pmc = 508981 | doi = 10.1172/JCI4115 }}</ref><ref name="pmid11238538">{{cite journal | vauthors = Dalgaard LT, Sørensen TI, Drivsholm T, Borch-Johnsen K, Andersen T, Hansen T, Pedersen O | title = 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 | journal = J. Clin. Endocrinol. Metab. | volume = 86 | issue = 3 | pages = 1398–402 | date = March 2001 | pmid = 11238538 | doi = 10.1210/jc.86.3.1398 }}</ref>
Mutations in the UCP3 gene are associated with obesity.<ref name="Argyropoulos_1998">{{cite journal | vauthors = Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT | title = Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes | journal = The Journal of Clinical Investigation | volume = 102 | issue = 7 | pages = 1345–51 | date = October 1998 | pmid = 9769326 | pmc = 508981 | doi = 10.1172/JCI4115 }}</ref><ref name="pmid11238538">{{cite journal | vauthors = Dalgaard LT, Sørensen TI, Drivsholm T, Borch-Johnsen K, Andersen T, Hansen T, Pedersen O | title = 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 | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 3 | pages = 1398–402 | date = March 2001 | doi = 10.1210/jcem.86.3.7301 | pmid = 11238538 | doi-access = free }}</ref>
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.<ref name="Argyropoulos_1998" /> 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.<ref name="Argyropoulos_1998"/> Exon 6–splice donor being heterozygotes, fat oxidation rates was reduced by 50%, initiating a role for UCP3 in metabolic fuel partitioning.<ref name="Argyropoulos_1998"/>
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.<ref name="Argyropoulos_1998" /> 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.<ref name="Argyropoulos_1998"/> Exon 6–splice donor being heterozygotes, fat oxidation rates was reduced by 50%, initiating a role for UCP3 in metabolic fuel partitioning.<ref name="Argyropoulos_1998"/>
UCP3 (uncoupling protein) deliberates the hypoxia resistance to the renal epithelial cells and its upregulation in renal cell carcinoma.<ref name="pmid26304588">{{cite journal | vauthors = Braun N, Klumpp D, Hennenlotter J, Bedke J, Duranton C, Bleif M, Huber SM | title = UCP-3 uncoupling protein confers hypoxia resistance to renal epithelial cells and is upregulated in renal cell carcinoma | journal = Scientific Reports | volume = 5 | issue = | pages = 13450 | year = 2015 | pmid = 26304588 | pmc = 4548255 | doi = 10.1038/srep13450 | bibcode = 2015NatSR...513450B }}</ref>
UCP3 (uncoupling protein) deliberates the hypoxia resistance to the renal epithelial cells and its upregulation in renal cell carcinoma.<ref name="pmid26304588">{{cite journal | vauthors = Braun N, Klumpp D, Hennenlotter J, Bedke J, Duranton C, Bleif M, Huber SM | title = UCP-3 uncoupling protein confers hypoxia resistance to renal epithelial cells and is upregulated in renal cell carcinoma | journal = Scientific Reports | volume = 5 | pages = 13450 | date = August 2015 | pmid = 26304588 | pmc = 4548255 | doi = 10.1038/srep13450 | bibcode = 2015NatSR...513450B }}</ref>
The energy consumption of modulated and the association of -55CT polymorphism of UCP3 with the body weight and in type 2 diabetic patients.<ref name="pmid24026107">{{cite journal | vauthors = Lapice E, Monticelli A, Cocozza S, Pinelli M, Giacco A, Rivellese AA, Cocozza S, Riccardi G, Vaccaro O | title = The energy intake modulates the association of the -55CT polymorphism of UCP3 with body weight in type 2 diabetic patients | journal = International Journal of Obesity (2005) | volume = 38 | issue = 6 | pages = 873–7 | year = 2014 | pmid = 24026107 | doi = 10.1038/ijo.2013.174 }}</ref>
The energy consumption of modulated and the association of -55CT polymorphism of UCP3 with the body weight and in type 2 diabetic patients.<ref name="pmid24026107">{{cite journal | vauthors = Lapice E, Monticelli A, Cocozza S, Pinelli M, Giacco A, Rivellese AA, Cocozza S, Riccardi G, Vaccaro O | title = The energy intake modulates the association of the -55CT polymorphism of UCP3 with body weight in type 2 diabetic patients | journal = International Journal of Obesity | volume = 38 | issue = 6 | pages = 873–7 | date = June 2014 | pmid = 24026107 | doi = 10.1038/ijo.2013.174 | s2cid = 205154594 | doi-access = free }}</ref>


== Inhibitors ==
== Inhibitors ==
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== Interactions ==
== Interactions ==


UCP3 has been shown to [[Protein-protein interaction|interact]] with [[YWHAQ]].<ref name=pmid10785390>{{cite journal | vauthors = Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J | title = Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family | journal = Eur. J. Biochem. | volume = 267 | issue = 9 | pages = 2680–7 | date = May 2000 | pmid = 10785390 | doi = 10.1046/j.1432-1327.2000.01285.x }}</ref>
UCP3 has been shown to [[Protein-protein interaction|interact]] with [[YWHAQ]].<ref name=pmid10785390>{{cite journal | vauthors = Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J | title = Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family | journal = European Journal of Biochemistry | volume = 267 | issue = 9 | pages = 2680–7 | date = May 2000 | pmid = 10785390 | doi = 10.1046/j.1432-1327.2000.01285.x }}</ref>
Uncoupling protein UPC2 and uncoupling protein UPC3 interaction with members of the 14.3.3 family (Benoit pierrat et al., 2000).
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).
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 ==
== See also ==
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== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin|2}}
* {{cite journal |last1=Hilse |first1=Karolina E. |last2=Rupprecht |first2=Anne |last3=Egerbacher |first3=Monika |last4=Bardakji |first4=Sarah |last5=Zimmermann |first5=Lars |last6=Wulczyn |first6=Andrea E. M. Seiler |last7=Pohl |first7=Elena E. |title=The Expression of Uncoupling Protein 3 Coincides With the Fatty Acid Oxidation Type of Metabolism in Adult Murine Heart |journal=Frontiers in Physiology |date=22 June 2018 |volume=9 |page=747 |doi=10.3389/fphys.2018.00747|pmid=29988383 |pmc=6024016 |doi-access=free }}
* {{cite journal | vauthors = Ricquier D, Bouillaud F | title = The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP | journal = Biochem. J. | volume = 345 | issue = 2 | pages = 161–79 | year = 2000 | pmid = 10620491 | pmc = 1220743 | doi = 10.1042/0264-6021:3450161 }}
* {{cite journal |last1=Macher |first1=Gabriel |last2=Koehler |first2=Melanie |last3=Rupprecht |first3=Anne |last4=Kreiter |first4=Jürgen |last5=Hinterdorfer |first5=Peter |last6=Pohl |first6=Elena E. |title=Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and phosphate |journal=Biochimica et Biophysica Acta (BBA) - Biomembranes |date=March 2018 |volume=1860 |issue=3 |pages=664–672 |doi=10.1016/j.bbamem.2017.12.001|pmid=29212043 |pmc=6118327 }}
* {{cite journal | vauthors = Muzzin P | title = The uncoupling proteins | journal = Ann. Endocrinol. | location = Paris | volume = 63 | issue = 2 Pt 1 | pages = 106–10 | year = 2002 | pmid = 11994670 | doi = }}
* {{cite journal | vauthors = Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino JP | title = Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression | journal = FEBS Lett. | volume = 408 | issue = 1 | pages = 39–42 | year = 1997 | pmid = 9180264 | doi = 10.1016/S0014-5793(97)00384-0 }}
* {{cite journal | vauthors = Hilse KE, Kalinovich AV, Rupprecht A, Smorodchenko A, Zeitz U, Staniek K, Erben RG, Pohl EE | title = The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1857 | issue = 1 | pages = 72–78 | date = January 2016 | pmid = 26518386| pmc = 7115856| doi = 10.1016/j.bbabio.2015.10.011 | doi-access = free }}
* {{cite journal | vauthors = Gong DW, He Y, Karas M, Reitman M | title = Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin | journal = J. Biol. Chem. | volume = 272 | issue = 39 | pages = 24129–32 | year = 1997 | pmid = 9305858 | doi = 10.1074/jbc.272.39.24129 }}
* {{cite journal | vauthors = Muzzin P | title = The uncoupling proteins | journal = Annales d'Endocrinologie | volume = 63 | issue = 2 Pt 1 | pages = 106–10 | date = April 2002 | pmid = 11994670 }}
* {{cite journal | vauthors = Solanes G, Vidal-Puig A, Grujic D, Flier JS, Lowell BB | title = The human uncoupling protein-3 gene. Genomic structure, chromosomal localization, and genetic basis for short and long form transcripts | journal = J. Biol. Chem. | volume = 272 | issue = 41 | pages = 25433–6 | year = 1997 | pmid = 9325252 | doi = 10.1074/jbc.272.41.25433 }}
* {{cite journal | vauthors = Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino JP | title = Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression | journal = FEBS Letters | volume = 408 | issue = 1 | pages = 39–42 | date = May 1997 | pmid = 9180264 | doi = 10.1016/S0014-5793(97)00384-0 | s2cid = 33808140 | doi-access = }}
* {{cite journal | vauthors = Urhammer SA, Dalgaard LT, Sørensen TI, Tybjaerg-Hansen A, Echwald SM, Andersen T, Clausen JO, Pedersen O | title = Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity | journal = Diabetologia | volume = 41 | issue = 2 | pages = 241–4 | year = 1998 | pmid = 9498661 | doi = 10.1007/s001250050897 }}
* {{cite journal | vauthors = Gong DW, He Y, Karas M, Reitman M | title = Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin | journal = The Journal of Biological Chemistry | volume = 272 | issue = 39 | pages = 24129–32 | date = September 1997 | pmid = 9305858 | doi = 10.1074/jbc.272.39.24129 | doi-access = free }}
* {{cite journal | vauthors = Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT | title = Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes | journal = J. Clin. Invest. | volume = 102 | issue = 7 | pages = 1345–51 | year = 1998 | pmid = 9769326 | pmc = 508981 | doi = 10.1172/JCI4115 }}
* {{cite journal | vauthors = Solanes G, Vidal-Puig A, Grujic D, Flier JS, Lowell BB | title = The human uncoupling protein-3 gene. Genomic structure, chromosomal localization, and genetic basis for short and long form transcripts | journal = The Journal of Biological Chemistry | volume = 272 | issue = 41 | pages = 25433–6 | date = October 1997 | pmid = 9325252 | doi = 10.1074/jbc.272.41.25433 | doi-access = free }}
* {{cite journal | vauthors = Acín A, Rodriguez M, Rique H, Canet E, Boutin JA, Galizzi JP | title = Cloning and characterization of the 5' flanking region of the human uncoupling protein 3 (UCP3) gene | journal = Biochem. Biophys. Res. Commun. | volume = 258 | issue = 2 | pages = 278–83 | year = 1999 | pmid = 10329378 | doi = 10.1006/bbrc.1999.0530 }}
* {{cite journal | vauthors = Urhammer SA, Dalgaard LT, Sørensen TI, Tybjaerg-Hansen A, Echwald SM, Andersen T, Clausen JO, Pedersen O | title = Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity | journal = Diabetologia | volume = 41 | issue = 2 | pages = 241–4 | date = February 1998 | pmid = 9498661 | doi = 10.1007/s001250050897 | doi-access = free }}
* {{cite journal | vauthors = 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 | title = Energy metabolism in uncoupling protein 3 gene knockout mice | journal = J. Biol. Chem. | volume = 275 | issue = 21 | pages = 16258–66 | year = 2000 | pmid = 10748196 | doi = 10.1074/jbc.M910179199 }}
* {{cite journal | vauthors = Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT | title = Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes | journal = The Journal of Clinical Investigation | volume = 102 | issue = 7 | pages = 1345–51 | date = October 1998 | pmid = 9769326 | pmc = 508981 | doi = 10.1172/JCI4115 }}
* {{cite journal | vauthors = Jezek P, Urbánková E | title = Specific sequence of motifs of mitochondrial uncoupling proteins | journal = IUBMB Life | volume = 49 | issue = 1 | pages = 63–70 | year = 2000 | pmid = 10772343 | doi = 10.1080/713803586 }}
* {{cite journal | vauthors = Acín A, Rodriguez M, Rique H, Canet E, Boutin JA, Galizzi JP | title = Cloning and characterization of the 5' flanking region of the human uncoupling protein 3 (UCP3) gene | journal = Biochemical and Biophysical Research Communications | volume = 258 | issue = 2 | pages = 278–83 | date = May 1999 | pmid = 10329378 | doi = 10.1006/bbrc.1999.0530 }}
* {{cite journal | vauthors = Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J | title = Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family | journal = Eur. J. Biochem. | volume = 267 | issue = 9 | pages = 2680–7 | year = 2000 | pmid = 10785390 | doi = 10.1046/j.1432-1327.2000.01285.x }}
* {{cite journal | vauthors = 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 | title = Energy metabolism in uncoupling protein 3 gene knockout mice |author-link11=Deborah Muoio| journal = The Journal of Biological Chemistry | volume = 275 | issue = 21 | pages = 16258–66 | date = May 2000 | pmid = 10748196 | doi = 10.1074/jbc.M910179199 | doi-access = free }}
* {{cite journal | vauthors = 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 | title = Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean | journal = Nature | volume = 406 | issue = 6794 | pages = 415–8 | year = 2000 | pmid = 10935638 | doi = 10.1038/35019082 | bibcode = 2000Natur.406..415C }}
* {{cite journal | vauthors = Jezek P, Urbánková E | title = Specific sequence of motifs of mitochondrial uncoupling proteins | journal = IUBMB Life | volume = 49 | issue = 1 | pages = 63–70 | date = January 2000 | pmid = 10772343 | doi = 10.1080/713803586 | s2cid = 8541209 | doi-access = free }}
* {{cite journal | vauthors = Esterbauer H, Oberkofler H, Krempler F, Strosberg AD, Patsch W | title = The uncoupling protein-3 gene is transcribed from tissue-specific promoters in humans but not in rodents | journal = J. Biol. Chem. | volume = 275 | issue = 46 | pages = 36394–9 | year = 2000 | pmid = 10958796 | doi = 10.1074/jbc.M005713200 }}
* {{cite journal | vauthors = Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J | title = Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family | journal = European Journal of Biochemistry | volume = 267 | issue = 9 | pages = 2680–7 | date = May 2000 | pmid = 10785390 | doi = 10.1046/j.1432-1327.2000.01285.x }}
* {{cite journal | vauthors = Lanouette CM, Chagnon YC, Rice T, Pérusse L, Muzzin P, Giacobino JP, Gagnon J, Wilmore JH, Leon AS, Skinner JS, Rao DC, Bouchard C | title = Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study | journal = J. Appl. Physiol. | volume = 92 | issue = 3 | pages = 1111–8 | year = 2002 | pmid = 11842047 | doi = 10.1152/japplphysiol.00726.2001 }}
* {{cite journal | vauthors = 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 | title = Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean | journal = Nature | volume = 406 | issue = 6794 | pages = 415–8 | date = July 2000 | pmid = 10935638 | doi = 10.1038/35019082 | bibcode = 2000Natur.406..415C | s2cid = 4397638 }}
* {{cite journal | vauthors = Collins P, Bing C, McCulloch P, Williams G | title = Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans | journal = Br. J. Cancer | volume = 86 | issue = 3 | pages = 372–5 | year = 2002 | pmid = 11875702 | pmc = 2375209 | doi = 10.1038/sj.bjc.6600074 }}
* {{cite journal | vauthors = Esterbauer H, Oberkofler H, Krempler F, Strosberg AD, Patsch W | title = The uncoupling protein-3 gene is transcribed from tissue-specific promoters in humans but not in rodents | journal = The Journal of Biological Chemistry | volume = 275 | issue = 46 | pages = 36394–9 | date = November 2000 | pmid = 10958796 | doi = 10.1074/jbc.M005713200 | doi-access = free }}
* {{cite journal | vauthors = Hu X, Murphy F, Karwautz A, Li T, Freeman B, Franklin D, Giotakis O, Treasure J, Collier DA | title = Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa | journal = Mol. Psychiatry | volume = 7 | issue = 3 | pages = 276–7 | year = 2002 | pmid = 11920154 | doi = 10.1038/sj.mp.4001044 }}
* {{cite journal | vauthors = Lanouette CM, Chagnon YC, Rice T, Pérusse L, Muzzin P, Giacobino JP, Gagnon J, Wilmore JH, Leon AS, Skinner JS, Rao DC, Bouchard C | title = Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study | journal = Journal of Applied Physiology | volume = 92 | issue = 3 | pages = 1111–8 | date = March 2002 | pmid = 11842047 | doi = 10.1152/japplphysiol.00726.2001 }}
* {{cite journal | vauthors = Collins P, Bing C, McCulloch P, Williams G | title = Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans | journal = British Journal of Cancer | volume = 86 | issue = 3 | pages = 372–5 | date = February 2002 | pmid = 11875702 | pmc = 2375209 | doi = 10.1038/sj.bjc.6600074 }}
* {{cite journal | vauthors = Hu X, Murphy F, Karwautz A, Li T, Freeman B, Franklin D, Giotakis O, Treasure J, Collier DA | title = Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa | journal = Molecular Psychiatry | volume = 7 | issue = 3 | pages = 276–7 | year = 2002 | pmid = 11920154 | doi = 10.1038/sj.mp.4001044 | s2cid = 9405576 | doi-access = }}


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Latest revision as of 11:46, 4 January 2024

UCP3
Identifiers
AliasesUCP3, uncoupling protein 3 (mitochondrial, proton carrier), SLC25A9, uncoupling protein 3
External IDsOMIM: 602044; MGI: 1099787; HomoloGene: 2517; GeneCards: UCP3; OMA:UCP3 - orthologs
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: 100.12 – 100.14 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] The gene is located in chromosome (11q13.4) with an exon count of 7 (HGNC et al., 2016) and is expressed on the inner mitochondrial membrane. Uncoupling proteins transfer anions from the inner mitochondrial membrane to the outer mitochondrial membrane, thereby separating (or uncoupling) oxidative phosphorylation from synthesis of ATP, and dissipating energy stored in the mitochondrial membrane potential as heat. Uncoupling proteins also reduce generation of reactive oxygen species.

Function[edit]

Mitochondrial uncoupling protein 3 (UCP3) is a members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and transfer of protons from the outer to the inner mitochondrial membrane, reducing the mitochondrial membrane potential in mammalian cells. The exact mechanisms of how UCPs transfer H+/OH− are not known.[7] In addition to UCP1, UCP3 is an important mediator of thermogenesis.

Protein expression[edit]

Uncoupling proteins are transporters in mitochondrial membrane which deplete the proton gradient. UCP1 is highly expressed in brown adipocytes, UCP2 is variably expressed in many different tissues, and UCP3 is expressed primarily in skeletal muscle. At amino acid level human UCP3 is 71% equivalent to UCP2. UCP3 i

Associated SNPs[edit]

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[edit]

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

Gene regulation[edit]

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[edit]

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[edit]

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[edit]

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[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175564 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032942 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. ^ a b c "Entrez Gene: UCP3 uncoupling protein 3 (mitochondrial, proton carrier)".
  8. ^ a b c d 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/jcem.86.3.7301. 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. S2CID 205154594.
  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[edit]

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