UCP1_MOUSE
ID UCP1_MOUSE Reviewed; 307 AA.
AC P12242;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Mitochondrial brown fat uncoupling protein 1 {ECO:0000305};
DE Short=UCP 1 {ECO:0000305};
DE AltName: Full=Solute carrier family 25 member 7 {ECO:0000250|UniProtKB:P25874};
DE AltName: Full=Thermogenin {ECO:0000250|UniProtKB:P04575};
GN Name=Ucp1 {ECO:0000312|MGI:MGI:98894};
GN Synonyms=Slc25a7 {ECO:0000250|UniProtKB:P25874},
GN Ucp {ECO:0000303|PubMed:3410843};
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 [GENOMIC DNA].
RX PubMed=3410843; DOI=10.1016/s0021-9258(18)37751-2;
RA Kozak L.P., Britton J.H., Kozak U.C., Wells J.M.;
RT "The mitochondrial uncoupling protein gene. Correlation of exon structure
RT to transmembrane domains.";
RL J. Biol. Chem. 263:12274-12277(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE, AND TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=8264627; DOI=10.1128/mcb.14.1.59-67.1994;
RA Kozak U.C., Kopecky J., Teisinger J., Enerbaeck S., Boyer B., Kozak L.P.;
RT "An upstream enhancer regulating brown-fat-specific expression of the
RT mitochondrial uncoupling protein gene.";
RL Mol. Cell. Biol. 14:59-67(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9139827; DOI=10.1038/387090a0;
RA Enerbaeck S., Jacobsson A., Simpson E.M., Guerra C., Yamashita H.,
RA Harper M.E., Kozak L.P.;
RT "Mice lacking mitochondrial uncoupling protein are cold-sensitive but not
RT obese.";
RL Nature 387:90-94(1997).
RN [5]
RP FUNCTION, INDUCTION BY HIGH-FAT DIET, AND DISRUPTION PHENOTYPE.
RX PubMed=19187776; DOI=10.1016/j.cmet.2008.12.014;
RA Feldmann H.M., Golozoubova V., Cannon B., Nedergaard J.;
RT "UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in
RT mice exempt from thermal stress by living at thermoneutrality.";
RL Cell Metab. 9:203-209(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20416274; DOI=10.1016/j.bbabio.2010.04.008;
RA Dlaskova A., Clarke K.J., Porter R.K.;
RT "The role of UCP 1 in production of reactive oxygen species by mitochondria
RT isolated from brown adipose tissue.";
RL Biochim. Biophys. Acta 1797:1470-1476(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen;
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 [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION BY COLD.
RX PubMed=20466728; DOI=10.1074/jbc.m110.122861;
RA Oelkrug R., Kutschke M., Meyer C.W., Heldmaier G., Jastroch M.;
RT "Uncoupling protein 1 decreases superoxide production in brown adipose
RT tissue mitochondria.";
RL J. Biol. Chem. 285:21961-21968(2010).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=23063128; DOI=10.1016/j.cell.2012.09.010;
RA Fedorenko A., Lishko P.V., Kirichok Y.;
RT "Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat
RT mitochondria.";
RL Cell 151:400-413(2012).
RN [10]
RP INDUCTION BY COLD.
RX PubMed=25578880; DOI=10.1016/j.molcel.2014.12.005;
RA Dempersmier J., Sambeat A., Gulyaeva O., Paul S.M., Hudak C.S.,
RA Raposo H.F., Kwan H.Y., Kang C., Wong R.H., Sul H.S.;
RT "Cold-inducible Zfp516 activates UCP1 transcription to promote browning of
RT white fat and development of brown fat.";
RL Mol. Cell 57:235-246(2015).
RN [11]
RP FUNCTION, ACTIVITY REGULATION, OXIDATION AT CYS-254, AND MUTAGENESIS OF
RP CYS-25; CYS-189; CYS-214; CYS-225; CYS-254; CYS-288 AND CYS-305.
RX PubMed=27027295; DOI=10.1038/nature17399;
RA Chouchani E.T., Kazak L., Jedrychowski M.P., Lu G.Z., Erickson B.K.,
RA Szpyt J., Pierce K.A., Laznik-Bogoslavski D., Vetrivelan R., Clish C.B.,
RA Robinson A.J., Gygi S.P., Spiegelman B.M.;
RT "Mitochondrial ROS regulate thermogenic energy expenditure and
RT sulfenylation of UCP1.";
RL Nature 532:112-116(2016).
CC -!- FUNCTION: Mitochondrial protein responsible for thermogenic
CC respiration, a specialized capacity of brown adipose tissue and beige
CC fat that participates in non-shivering adaptive thermogenesis to
CC temperature and diet variations and more generally to the regulation of
CC energy balance (PubMed:9139827, PubMed:19187776, PubMed:23063128,
CC PubMed:27027295). Functions as a long-chain fatty acid/LCFA and proton
CC symporter, simultaneously transporting one LCFA and one proton through
CC the inner mitochondrial membrane. However, LCFAs remaining associated
CC with the transporter via their hydrophobic tails, it results in an
CC apparent transport of protons activated by LCFAs. Thereby, dissipates
CC the mitochondrial proton gradient and converts the energy of substrate
CC oxydation into heat instead of ATP (PubMed:23063128). Regulates the
CC production of reactive oxygen species/ROS by mitochondria
CC (PubMed:20416274, PubMed:20466728). {ECO:0000269|PubMed:19187776,
CC ECO:0000269|PubMed:20416274, ECO:0000269|PubMed:20466728,
CC ECO:0000269|PubMed:23063128, ECO:0000269|PubMed:27027295,
CC ECO:0000269|PubMed:9139827}.
CC -!- ACTIVITY REGULATION: Has no constitutive proton transporter activity
CC and has to be activated by long-chain fatty acids/LCFAs. Inhibited by
CC purine nucleotides. Both purine nucleotides and LCFAs bind the
CC cytosolic side of the transporter and directly compete to activate or
CC inhibit it (PubMed:23063128). Activated by noradrenaline and reactive
CC oxygen species (PubMed:27027295). {ECO:0000269|PubMed:23063128,
CC ECO:0000269|PubMed:27027295}.
CC -!- SUBUNIT: Most probably functions as a monomer. Binds one purine
CC nucleotide per monomer. However, has also been suggested to function as
CC a homodimer or a homotetramer. Tightly associates with cardiolipin in
CC the mitochondrion inner membrane; may stabilize and regulate its
CC activity. {ECO:0000250|UniProtKB:P25874, ECO:0000250|UniProtKB:W5PSH7}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:23063128}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P04633}.
CC -!- TISSUE SPECIFICITY: Expressed in brown adipose tissue.
CC {ECO:0000269|PubMed:8264627}.
CC -!- INDUCTION: Up-regulated in response to cold in brown adipose tissue
CC where it may regulate non-shivering thermogenesis (at protein level)
CC (PubMed:20466728, PubMed:25578880). Up-regulated by high-fat diet (at
CC protein level) (PubMed:19187776). {ECO:0000269|PubMed:19187776,
CC ECO:0000269|PubMed:20466728, ECO:0000269|PubMed:25578880}.
CC -!- PTM: Sulfenylation at Cys-254 is increased upon cold exposure. It
CC increases the sensitivity of UCP1 thermogenic function to the
CC activation by noradrenaline probably through structural effects.
CC {ECO:0000269|PubMed:27027295}.
CC -!- PTM: May undergo ubiquitin-mediated proteasomal degradation.
CC {ECO:0000250|UniProtKB:P04633}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Ucp1 display an absence of adaptive
CC thermogenesis in response to cold. Compared to wild-type mice, they are
CC sensitive to cold and consume less oxygen upon treatment with beta-3-
CC adrenergic-receptor agonists that normally activate thermogenesis
CC (PubMed:9139827, PubMed:19187776). They also display impaired adaptive
CC thermogenesis in response to diet variation (PubMed:19187776). If they
CC display lipid accumulation in adipocytes of brown adipose tissues, no
CC overt obesity is observed when mice are housed under classical
CC conditions, i.e. 18 to 20 degrees Celsius (PubMed:9139827). However,
CC when mice are housed at thermoneutrality, i.e. at 30 degrees Celsius,
CC obesity is clearly observed and exacerbated by high fat diet
CC (PubMed:19187776). The brown adipose tissue of mice lacking Ucp1
CC produce higher levels of reactive oxygen species (PubMed:20416274,
CC PubMed:20466728). {ECO:0000269|PubMed:19187776,
CC ECO:0000269|PubMed:20416274, ECO:0000269|PubMed:20466728,
CC ECO:0000269|PubMed:9139827}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; M21247; AAA40521.1; -; Genomic_DNA.
DR EMBL; M21222; AAA40521.1; JOINED; Genomic_DNA.
DR EMBL; M21244; AAA40521.1; JOINED; Genomic_DNA.
DR EMBL; M21245; AAA40521.1; JOINED; Genomic_DNA.
DR EMBL; M21246; AAA40521.1; JOINED; Genomic_DNA.
DR EMBL; U63419; AAB05870.1; -; mRNA.
DR EMBL; U63418; AAB07367.1; -; Genomic_DNA.
DR EMBL; BC012701; AAH12701.1; -; mRNA.
DR CCDS; CCDS22449.1; -.
DR PIR; A31106; A31106.
DR RefSeq; NP_033489.1; NM_009463.3.
DR AlphaFoldDB; P12242; -.
DR SMR; P12242; -.
DR STRING; 10090.ENSMUSP00000034146; -.
DR iPTMnet; P12242; -.
DR PhosphoSitePlus; P12242; -.
DR MaxQB; P12242; -.
DR PaxDb; P12242; -.
DR PRIDE; P12242; -.
DR ProteomicsDB; 297718; -.
DR Antibodypedia; 16250; 460 antibodies from 38 providers.
DR DNASU; 22227; -.
DR Ensembl; ENSMUST00000034146; ENSMUSP00000034146; ENSMUSG00000031710.
DR GeneID; 22227; -.
DR KEGG; mmu:22227; -.
DR UCSC; uc009mjx.2; mouse.
DR CTD; 7350; -.
DR MGI; MGI:98894; Ucp1.
DR VEuPathDB; HostDB:ENSMUSG00000031710; -.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000160382; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; P12242; -.
DR OMA; YTSVPNC; -.
DR OrthoDB; 984118at2759; -.
DR PhylomeDB; P12242; -.
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; 22227; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Ucp1; mouse.
DR PRO; PR:P12242; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P12242; protein.
DR Bgee; ENSMUSG00000031710; Expressed in intercostal muscle and 56 other tissues.
DR Genevisible; P12242; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005740; C:mitochondrial envelope; IDA:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:1901612; F:cardiolipin binding; ISS:UniProtKB.
DR GO; GO:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0036041; F:long-chain fatty acid binding; IDA:UniProtKB.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; IDA:UniProtKB.
DR GO; GO:0032555; F:purine ribonucleotide binding; IDA:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; ISO:MGI.
DR GO; GO:1990845; P:adaptive thermogenesis; IMP:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR GO; GO:0070417; P:cellular response to cold; IDA:MGI.
DR GO; GO:1903495; P:cellular response to dehydroepiandrosterone; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IMP:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; IMP:UniProtKB.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006839; P:mitochondrial transport; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0009409; P:response to cold; IBA:GO_Central.
DR GO; GO:0031667; P:response to nutrient levels; IMP:UniProtKB.
DR GO; GO:0009266; P:response to temperature stimulus; IMP:UniProtKB.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002030; Mit_uncoupling_UCP-like.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR InterPro; IPR040011; UCP1.
DR PANTHER; PTHR45618:SF19; PTHR45618:SF19; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00784; MTUNCOUPLING.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Ion channel; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidation; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..307
FT /note="Mitochondrial brown fat uncoupling protein 1"
FT /id="PRO_0000090659"
FT TOPO_DOM 1..10
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P04633"
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:0000250|UniProtKB:P04633"
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:0000250|UniProtKB:P04633"
FT TRANSMEM 117..133
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..178
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 179..195
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..212
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 213..232
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..266
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 267..289
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..307
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT REPEAT 11..102
FT /note="Solcar 1"
FT REPEAT 111..201
FT /note="Solcar 2"
FT REPEAT 210..295
FT /note="Solcar 3"
FT MOD_RES 254
FT /note="Cysteine sulfenic acid (-SOH)"
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 25
FT /note="C->A: No effect on UCP1 activity in thermogenic
FT respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 189
FT /note="C->A: No effect on UCP1 activity in thermogenic
FT respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 214
FT /note="C->A: No effect on UCP1 activity in thermogenic
FT respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 225
FT /note="C->A: Decreased UCP1 activity in thermogenic
FT respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 254
FT /note="C->A: Decreased sensitivity to activation by
FT noradrenaline in thermogenic respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 288
FT /note="C->A: No effect on UCP1 activity in thermogenic
FT respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
FT MUTAGEN 305
FT /note="C->A: No effect on UCP1 activity in thermogenic
FT respiration."
FT /evidence="ECO:0000269|PubMed:27027295"
SQ SEQUENCE 307 AA; 33248 MW; 33D107EDF04BD1AF CRC64;
MVNPTTSEVQ PTMGVKIFSA GVSACLADII TFPLDTAKVR LQIQGEGQAS STIRYKGVLG
TITTLAKTEG LPKLYSGLPA GIQRQISFAS LRIGLYDSVQ EYFSSGRETP ASLGNKISAG
LMTGGVAVFI GQPTEVVKVR MQAQSHLHGI KPRYTGTYNA YRVIATTESL STLWKGTTPN
LMRNVIINCT ELVTYDLMKG ALVNNKILAD DVPCHLLSAL VAGFCTTLLA SPVDVVKTRF
INSLPGQYPS VPSCAMSMYT KEGPTAFFKG FVASFLRLGS WNVIMFVCFE QLKKELMKSR
QTVDCTT
