ID UCP3_MOUSE Reviewed; 308 AA.
AC P56501; O88293;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 27-MAR-2024, entry version 161.
DE RecName: Full=Putative mitochondrial transporter UCP3 {ECO:0000305};
DE AltName: Full=Solute carrier family 25 member 9;
DE AltName: Full=Uncoupling protein 3 {ECO:0000303|PubMed:10748196};
DE Short=UCP 3;
GN Name=Ucp3 {ECO:0000312|MGI:MGI:1099787}; Synonyms=Slc25a9;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Sanchis D., Fleury C., Bouillaud F., Ricquier D.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster; TISSUE=Embryo;
RX PubMed=9666083; DOI=10.1016/s0378-1119(98)00279-0;
RA Yoshitomi H., Yamazaki K., Tanaka I.;
RT "Cloning of mouse uncoupling protein 3 cDNA and 5'-flanking region, and its
RT genetic map.";
RL Gene 215:77-84(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Skeletal muscle;
RA Grujic D., Zhan C.-Y., Sleiker L.J., Lowell B.B.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skeletal muscle;
RA Son C., Hosoda K., Matsuda J., Nakao K.;
RT "Cloning of mouse UCP3 cDNA.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10066417; DOI=10.1006/bbrc.1999.0239;
RA Gong D.W., He Y., Reitman M.L.;
RT "Genomic organization and regulation by dietary fat of the uncoupling
RT protein 3 and 2 genes.";
RL Biochem. Biophys. Res. Commun. 256:27-32(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 84-180.
RC STRAIN=C57BL/6J; TISSUE=Skeletal muscle;
RX PubMed=9600108; DOI=10.1006/bbrc.1998.8600;
RA Shimokawa T., Kato M., Ezaki O., Hashimoto S.;
RT "Transcriptional regulation of muscle-specific genes during myoblast
RT differentiation.";
RL Biochem. Biophys. Res. Commun. 246:287-292(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-252.
RA Yan X., Ramsay T.G.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10748195; DOI=10.1074/jbc.m910177199;
RA Gong D.W., Monemdjou S., Gavrilova O., Leon L.R., Marcus-Samuels B.,
RA Chou C.J., Everett C., Kozak L.P., Li C., Deng C., Harper M.E.,
RA Reitman M.L.;
RT "Lack of obesity and normal response to fasting and thyroid hormone in mice
RT lacking uncoupling protein-3.";
RL J. Biol. Chem. 275:16251-16257(2000).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10748196; DOI=10.1074/jbc.m910179199;
RA Vidal-Puig A.J., Grujic D., Zhang C.Y., Hagen T., Boss O., Ido Y.,
RA Szczepanik A., Wade J., Mootha V., Cortright R., Muoio D.M., Lowell B.B.;
RT "Energy metabolism in uncoupling protein 3 gene knockout mice.";
RL J. Biol. Chem. 275:16258-16266(2000).
RN [10]
RP FUNCTION.
RX PubMed=11707458; DOI=10.1074/jbc.m109736200;
RA Cadenas S., Echtay K.S., Harper J.A., Jekabsons M.B., Buckingham J.A.,
RA Grau E., Abuin A., Chapman H., Clapham J.C., Brand M.D.;
RT "The basal proton conductance of skeletal muscle mitochondria from
RT transgenic mice overexpressing or lacking uncoupling protein-3.";
RL J. Biol. Chem. 277:2773-2778(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION.
RX PubMed=20363757; DOI=10.1074/jbc.m110.102699;
RA Lombardi A., Busiello R.A., Napolitano L., Cioffi F., Moreno M.,
RA de Lange P., Silvestri E., Lanni A., Goglia F.;
RT "UCP3 translocates lipid hydroperoxide and mediates lipid hydroperoxide-
RT dependent mitochondrial uncoupling.";
RL J. Biol. Chem. 285:16599-16605(2010).
RN [13]
RP INTERACTION WITH HAX1, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=26915802; DOI=10.1016/j.bbrc.2016.02.075;
RA Hirasaka K., Mills E.M., Haruna M., Bando A., Ikeda C., Abe T., Kohno S.,
RA Nowinski S.M., Lago C.U., Akagi K., Tochio H., Ohno A., Teshima-Kondo S.,
RA Okumura Y., Nikawa T.;
RT "UCP3 is associated with Hax-1 in mitochondria in the presence of calcium
RT ion.";
RL Biochem. Biophys. Res. Commun. 472:108-113(2016).
RN [14]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ARG-84; ARG-184 AND
RP ARG-278.
RX PubMed=29212043; DOI=10.1016/j.bbamem.2017.12.001;
RA Macher G., Koehler M., Rupprecht A., Kreiter J., Hinterdorfer P.,
RA Pohl E.E.;
RT "Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and
RT phosphate.";
RL Biochim. Biophys. Acta 1860:664-672(2018).
CC -!- FUNCTION: Putative transmembrane transporter that plays a role in
CC mitochondrial metabolism via an as yet unclear mechanism
CC (PubMed:10748195, PubMed:10748196). Originally, this mitochondrial
CC protein was thought to act as a proton transmembrane transporter from
CC the mitochondrial intermembrane space into the matrix, causing proton
CC leaks through the inner mitochondrial membrane, thereby uncoupling
CC mitochondrial membrane potential generation from ATP synthesis
CC (PubMed:29212043). However, this function is controversial and
CC uncoupling may not be the function, or at least not the main function,
CC but rather a consequence of more conventional metabolite transporter
CC activity (PubMed:11707458, PubMed:20363757).
CC {ECO:0000269|PubMed:10748195, ECO:0000269|PubMed:10748196,
CC ECO:0000269|PubMed:11707458, ECO:0000269|PubMed:20363757,
CC ECO:0000269|PubMed:29212043}.
CC -!- ACTIVITY REGULATION: Inhibited by purine nucleotides and inorganic
CC phosphate (in vitro). {ECO:0000269|PubMed:29212043}.
CC -!- SUBUNIT: Interacts with HAX1; the interaction is direct and calcium-
CC dependent. {ECO:0000269|PubMed:26915802}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:26915802}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice lacking Ucp3 show no
CC overt phenotype being born at the expected frequency, with no observed
CC signs of abnormality, illness, or increased mortality at up to one year
CC of age. They are not obese and have reduced free fatty acids and
CC glucose serum levels. They show a normal circadian rhythm in body
CC temperature and motor activity and have normal body temperature
CC responses to fasting, stress, thyroid hormone, and cold exposure. The
CC baseline metabolic rate and respiratory exchange ratio are the same in
CC knockout and control mice. However, there is decreased proton leak in
CC the mitochondria over the complete range of metabolic rates studied
CC (PubMed:10748195, PubMed:10748196). Mitochondria are more coupled and
CC the production of reactive oxygen species is increased. No effect on
CC exercise tolerance and fatty acid oxidation is observed
CC (PubMed:10748196). {ECO:0000269|PubMed:10748195,
CC ECO:0000269|PubMed:10748196}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AF032902; AAB87084.1; -; mRNA.
DR EMBL; AB010742; BAA25697.1; -; mRNA.
DR EMBL; AF030164; AAD01892.1; -; mRNA.
DR EMBL; AB008216; BAA33502.1; -; mRNA.
DR EMBL; AF053352; AAC28328.1; -; mRNA.
DR EMBL; AB013132; BAA31989.1; -; mRNA.
DR EMBL; AF019883; AAB71543.1; -; mRNA.
DR CCDS; CCDS21497.1; -.
DR RefSeq; NP_033490.1; NM_009464.3.
DR AlphaFoldDB; P56501; -.
DR SMR; P56501; -.
DR CORUM; P56501; -.
DR STRING; 10090.ENSMUSP00000032958; -.
DR iPTMnet; P56501; -.
DR PhosphoSitePlus; P56501; -.
DR MaxQB; P56501; -.
DR PaxDb; 10090-ENSMUSP00000032958; -.
DR ProteomicsDB; 298428; -.
DR Antibodypedia; 4388; 316 antibodies from 33 providers.
DR DNASU; 22229; -.
DR Ensembl; ENSMUST00000032958.14; ENSMUSP00000032958.8; ENSMUSG00000032942.15.
DR Ensembl; ENSMUST00000107059.2; ENSMUSP00000102674.2; ENSMUSG00000032942.15.
DR GeneID; 22229; -.
DR KEGG; mmu:22229; -.
DR UCSC; uc009ina.1; mouse.
DR AGR; MGI:1099787; -.
DR CTD; 7352; -.
DR MGI; MGI:1099787; Ucp3.
DR VEuPathDB; HostDB:ENSMUSG00000032942; -.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000161030; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; P56501; -.
DR OMA; RYMNAGP; -.
DR OrthoDB; 1832865at2759; -.
DR PhylomeDB; P56501; -.
DR TreeFam; TF323211; -.
DR Reactome; R-MMU-167826; The fatty acid cycling model.
DR Reactome; R-MMU-167827; The proton buffering model.
DR BioGRID-ORCS; 22229; 5 hits in 78 CRISPR screens.
DR ChiTaRS; Ucp3; mouse.
DR PRO; PR:P56501; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P56501; Protein.
DR Bgee; ENSMUSG00000032942; Expressed in hindlimb stylopod muscle and 93 other cell types or tissues.
DR ExpressionAtlas; P56501; baseline and differential.
DR Genevisible; P56501; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IMP:MGI.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; IMP:MGI.
DR GO; GO:0015078; F:proton transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:1990845; P:adaptive thermogenesis; IBA:GO_Central.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:MGI.
DR GO; GO:1901373; P:lipid hydroperoxide transport; IMP:UniProtKB.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IBA:GO_Central.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IBA:GO_Central.
DR GO; GO:1901557; P:response to fenofibrate; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0000303; P:response to superoxide; IMP:MGI.
DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 1.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR PANTHER; PTHR45618; MITOCHONDRIAL DICARBOXYLATE CARRIER-RELATED; 1.
DR PANTHER; PTHR45618:SF2; MITOCHONDRIAL UNCOUPLING PROTEIN 3; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00784; MTUNCOUPLING.
DR SUPFAM; SSF103506; Mitochondrial carrier; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..308
FT /note="Putative mitochondrial transporter UCP3"
FT /id="PRO_0000090673"
FT TOPO_DOM 1..10
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:26915802"
FT TRANSMEM 11..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..73
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:26915802"
FT TRANSMEM 74..96
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..116
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:26915802"
FT TRANSMEM 117..133
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..179
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:26915802"
FT TRANSMEM 180..196
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..213
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:26915802"
FT TRANSMEM 214..233
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..267
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:26915802"
FT TRANSMEM 268..290
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..308
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:26915802"
FT REPEAT 11..102
FT /note="Solcar 1"
FT REPEAT 111..202
FT /note="Solcar 2"
FT REPEAT 211..296
FT /note="Solcar 3"
FT REGION 275..297
FT /note="Purine nucleotide binding"
FT /evidence="ECO:0000250"
FT MUTAGEN 84
FT /note="R->Q: Changed proton transmembrane transport.
FT Decreased inhibition by ATP and ADP. No effect on AMP-
FT mediated inhibition."
FT /evidence="ECO:0000269|PubMed:29212043"
FT MUTAGEN 184
FT /note="R->T: Changed proton transmembrane transport. Loss
FT of inhibition by the purine nucleotides ATP, ADP and AMP."
FT /evidence="ECO:0000269|PubMed:29212043"
FT MUTAGEN 278
FT /note="R->L: No effect on proton transmembrane transport.
FT No effect on inhibition by ATP, ADP and AMP."
FT /evidence="ECO:0000269|PubMed:29212043"
FT CONFLICT 179
FT /note="W -> L (in Ref. 6; BAA31989)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 308 AA; 33911 MW; 12CAD7674DF7D0C3 CRC64;
MVGLQPSEVP PTTVVKFLGA GTAACFADLL TFPLDTAKVR LQIQGENPGA QSVQYRGVLG
TILTMVRTEG PRSPYSGLVA GLHRQMSFAS IRIGLYDSVK QFYTPKGADH SSVAIRILAG
CTTGAMAVTC AQPTDVVKVR FQAMIRLGTG GERKYRGTMD AYRTIAREEG VRGLWKGTWP
NITRNAIVNC AEMVTYDIIK EKLLESHLFT DNFPCHFVSA FGAGFCATVV ASPVDVVKTR
YMNAPLGRYR SPLHCMLKMV AQEGPTAFYK GFVPSFLRLG AWNVMMFVTY EQLKRALMKV
QVLRESPF
//
