UCP1_RAT
ID UCP1_RAT Reviewed; 307 AA.
AC P04633;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 157.
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|RGD:3931};
GN Synonyms=Slc25a7 {ECO:0000250|UniProtKB:P25874},
GN Ucp {ECO:0000303|PubMed:3753702};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3753702; DOI=10.1016/s0021-9258(17)35962-8;
RA Bouillaud F., Weissenbach J., Ricquier D.;
RT "Complete cDNA-derived amino acid sequence of rat brown fat uncoupling
RT protein.";
RL J. Biol. Chem. 261:1487-1490(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3012461; DOI=10.1093/nar/14.10.4025;
RA Ridley R.G., Patel H.V., Gerber G.E., Morton R.C., Freeman K.B.;
RT "Complete nucleotide and derived amino acid sequence of cDNA encoding the
RT mitochondrial uncoupling protein of rat brown adipose tissue: lack of a
RT mitochondrial targeting presequence.";
RL Nucleic Acids Res. 14:4025-4035(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar;
RX PubMed=3202878; DOI=10.1016/s0006-291x(88)80318-8;
RA Bouillaud F., Raimbault S., Ricquier D.;
RT "The gene for rat uncoupling protein: complete sequence, structure of
RT primary transcript and evolutionary relationship between exons.";
RL Biochem. Biophys. Res. Commun. 157:783-792(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 254-307.
RX PubMed=2421800; DOI=10.1007/bf01145183;
RA Ridley R.G., Patel H.V., Parfett C.L., Olynyk K.A., Reichling S.,
RA Freeman K.B.;
RT "Immunological detection of cDNA clones encoding the uncoupling protein of
RT brown adipose tissue: evidence for an antigenic determinant within the C-
RT terminal eleven amino acids.";
RL Biosci. Rep. 6:87-94(1986).
RN [6]
RP TOPOLOGY.
RX PubMed=7691596; DOI=10.1002/j.1460-2075.1993.tb06051.x;
RA Miroux B., Frossard V., Raimbault S., Ricquier D., Bouillaud F.;
RT "The topology of the brown adipose tissue mitochondrial uncoupling protein
RT determined with antibodies against its antigenic sites revealed by a
RT library of fusion proteins.";
RL EMBO J. 12:3739-3745(1993).
RN [7]
RP FUNCTION, GTP-BINDING, AND MUTAGENESIS OF CYS-25; ASP-28; THR-31; HIS-146;
RP HIS-148 AND ARG-153.
RX PubMed=12479871; DOI=10.1016/s1357-2725(02)00131-0;
RA Urbankova E., Hanak P., Skobisova E., Ruzicka M., Jezek P.;
RT "Substitutional mutations in the uncoupling protein-specific sequences of
RT mitochondrial uncoupling protein UCP1 lead to the reduction of fatty acid-
RT induced H+ uniport.";
RL Int. J. Biochem. Cell Biol. 35:212-220(2003).
RN [8]
RP FUNCTION.
RX PubMed=16814247; DOI=10.1016/j.bbabio.2006.05.027;
RA Jimenez-Jimenez J., Ledesma A., Zaragoza P., Gonzalez-Barroso M.M.,
RA Rial E.;
RT "Fatty acid activation of the uncoupling proteins requires the presence of
RT the central matrix loop from UCP1.";
RL Biochim. Biophys. Acta 1757:1292-1296(2006).
RN [9]
RP UBIQUITIN-MEDIATED PROTEASOMAL DEGRADATION.
RX PubMed=22531154; DOI=10.1016/j.bbabio.2012.03.035;
RA Clarke K.J., Adams A.E., Manzke L.H., Pearson T.W., Borchers C.H.,
RA Porter R.K.;
RT "A role for ubiquitinylation and the cytosolic proteasome in turnover of
RT mitochondrial uncoupling protein 1 (UCP1).";
RL Biochim. Biophys. Acta 1817:1759-1767(2012).
RN [10]
RP ACTIVITY REGULATION, AND PURINE NUCLEOTIDE-BINDING.
RX PubMed=22952235; DOI=10.1074/jbc.m112.381780;
RA Divakaruni A.S., Humphrey D.M., Brand M.D.;
RT "Fatty acids change the conformation of uncoupling protein 1 (UCP1).";
RL J. Biol. Chem. 287:36845-36853(2012).
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 (By similarity). Functions as a long-chain fatty
CC acid/LCFA and proton symporter, simultaneously transporting one LCFA
CC and one proton through the inner mitochondrial membrane. However, LCFAs
CC remaining associated with the transporter via their hydrophobic tails,
CC it results in an apparent transport of protons activated by LCFAs
CC (PubMed:12479871, PubMed:16814247). Thereby, dissipates the
CC mitochondrial proton gradient and converts the energy of substrate
CC oxydation into heat instead of ATP. Regulates the production of
CC reactive oxygen species/ROS by mitochondria (By similarity).
CC {ECO:0000250|UniProtKB:P12242, ECO:0000269|PubMed:12479871,
CC ECO:0000269|PubMed:16814247}.
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:22952235). Activated by noradrenaline and reactive
CC oxygen species (By similarity). {ECO:0000250|UniProtKB:P12242,
CC ECO:0000269|PubMed:22952235}.
CC -!- SUBUNIT: Most probably functions as a monomer (By similarity). Binds
CC one purine nucleotide per monomer (PubMed:12479871, PubMed:22952235).
CC However, has also been suggested to function as a homodimer or a
CC homotetramer (By similarity). Tightly associates with cardiolipin in
CC the mitochondrion inner membrane; may stabilize and regulate its
CC activity (By similarity). {ECO:0000250|UniProtKB:P25874,
CC ECO:0000250|UniProtKB:W5PSH7, ECO:0000269|PubMed:12479871,
CC ECO:0000269|PubMed:22952235}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P12242}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:7691596}.
CC -!- TISSUE SPECIFICITY: Brown adipose tissue. {ECO:0000269|PubMed:3753702}.
CC -!- PTM: May undergo ubiquitin-mediated proteasomal degradation.
CC {ECO:0000269|PubMed:22531154}.
CC -!- PTM: May undergo sulfenylation upon cold exposure. May increase the
CC sensitivity of UCP1 thermogenic function to the activation by
CC noradrenaline probably through structural effects.
CC {ECO:0000250|UniProtKB:P12242}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; M11814; AAA19671.1; -; mRNA.
DR EMBL; X03894; CAA27531.1; -; mRNA.
DR EMBL; BC088156; AAH88156.1; -; mRNA.
DR EMBL; X12925; CAA31392.1; -; Genomic_DNA.
DR PIR; A26294; A26294.
DR RefSeq; NP_036814.1; NM_012682.2.
DR AlphaFoldDB; P04633; -.
DR BioGRID; 246975; 1.
DR STRING; 10116.ENSRNOP00000004900; -.
DR iPTMnet; P04633; -.
DR PhosphoSitePlus; P04633; -.
DR PaxDb; P04633; -.
DR Ensembl; ENSRNOT00000004900; ENSRNOP00000004900; ENSRNOG00000003580.
DR GeneID; 24860; -.
DR KEGG; rno:24860; -.
DR CTD; 7350; -.
DR RGD; 3931; Ucp1.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000160382; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; P04633; -.
DR OMA; YTSVPNC; -.
DR OrthoDB; 984118at2759; -.
DR PhylomeDB; P04633; -.
DR TreeFam; TF323211; -.
DR Reactome; R-RNO-167826; The fatty acid cycling model.
DR Reactome; R-RNO-167827; The proton buffering model.
DR PRO; PR:P04633; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000003580; Expressed in thymus and 4 other tissues.
DR Genevisible; P04633; RN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005740; C:mitochondrial envelope; ISO:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS: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; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0036041; F:long-chain fatty acid binding; ISS:UniProtKB.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; IDA:UniProtKB.
DR GO; GO:0032555; F:purine ribonucleotide binding; ISO:RGD.
DR GO; GO:0022857; F:transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; ISO:RGD.
DR GO; GO:0070417; P:cellular response to cold; ISO:RGD.
DR GO; GO:1903495; P:cellular response to dehydroepiandrosterone; IEP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; ISO:RGD.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:RGD.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006839; P:mitochondrial transport; IDA:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0009893; P:positive regulation of metabolic process; TAS:RGD.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0009409; P:response to cold; IBA:GO_Central.
DR GO; GO:0031667; P:response to nutrient levels; ISS:UniProtKB.
DR GO; GO:0009266; P:response to temperature stimulus; ISS: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_0000090662"
FT TOPO_DOM 1..10
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:7691596"
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:7691596"
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:7691596"
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:0000269|PubMed:7691596"
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:0000303|PubMed:7691596"
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:0000303|PubMed:7691596"
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:0000303|PubMed:7691596"
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:0000250|UniProtKB:P12242"
FT MUTAGEN 25
FT /note="C->A: No effect on GTP-binding. Loss of fatty acid-
FT induced proton transport; when associated with V-28 and A-
FT 31."
FT /evidence="ECO:0000269|PubMed:12479871"
FT MUTAGEN 28
FT /note="D->V: No effect on GTP-binding. Decreased fatty
FT acid-induced proton transport. Loss of fatty acid-induced
FT proton transport; when associated with A-25 and A-31."
FT /evidence="ECO:0000269|PubMed:12479871"
FT MUTAGEN 31
FT /note="T->A: No effect on GTP-binding. No effect on fatty
FT acid-induced proton transport. Loss of fatty acid-induced
FT proton transport; when associated with A-25 and V-28."
FT /evidence="ECO:0000269|PubMed:12479871"
FT MUTAGEN 146
FT /note="H->L: No effect on GTP-binding. Decreased fatty
FT acid-induced proton transport; when associated with L-148."
FT /evidence="ECO:0000269|PubMed:12479871"
FT MUTAGEN 148
FT /note="H->L: No effect on GTP-binding. Decreased fatty
FT acid-induced proton transport; when associated with L-146."
FT /evidence="ECO:0000269|PubMed:12479871"
FT MUTAGEN 153
FT /note="R->L: No effect on GTP-binding. Decreased fatty
FT acid-induced proton transport."
FT /evidence="ECO:0000269|PubMed:12479871"
SQ SEQUENCE 307 AA; 33212 MW; 0B69CEFD3BE6F543 CRC64;
MVSSTTSEVQ PTMGVKIFSA GVSACLADII TFPLDTAKVR LQIQGEGQAS STIRYKGVLG
TITTLAKTEG LPKLYSGLPA GIQRQISFAS LRIGLYDTVQ EYFSSGRETP ASLGSKISAG
LMTGGVAVFI GQPTEVVKVR MQAQSHLHGI KPRYTGTYNA YRVIATTESL STLWKGTTPN
LMRNVIINCT ELVTYDLMKG ALVNHHILAD DVPCHLLSAL VAGFCTTLLA SPVDVVKTRF
INSLPGQYPS VPSCAMTMYT KEGPAAFFKG FAPSFLRLGS WNVIMFVCFE QLKKELMKSR
QTVDCTT
