ID UCP1_SHEEP Reviewed; 305 AA.
AC W5PSH7;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 27-MAR-2024, entry version 51.
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:0000303|PubMed:26038550};
GN Synonyms=Slc25a7 {ECO:0000250|UniProtKB:P25874};
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20809919; DOI=10.1111/j.1365-2052.2010.02100.x;
RA Archibald A.L., Cockett N.E., Dalrymple B.P., Faraut T., Kijas J.W.,
RA Maddox J.F., McEwan J.C., Hutton Oddy V., Raadsma H.W., Wade C., Wang J.,
RA Wang W., Xun X.;
RT "The sheep genome reference sequence: a work in progress.";
RL Anim. Genet. 41:449-453(2010).
RN [2]
RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBUNIT, GDP-BINDING,
RP AND SUBCELLULAR LOCATION.
RX PubMed=26038550; DOI=10.1073/pnas.1503833112;
RA Lee Y., Willers C., Kunji E.R., Crichton P.G.;
RT "Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by
RT tightly bound cardiolipin.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:6973-6978(2015).
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
CC (PubMed:26038550). However, LCFAs remaining associated with the
CC transporter via their hydrophobic tails, it results in an apparent
CC transport of protons activated by LCFAs. 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:26038550}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000269|PubMed:26038550};
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:26038550). Activated by noradrenaline and reactive
CC oxygen species. Despite lacking canonical translational encoding for
CC selenocysteine, a small pool of the protein has been observed to
CC selectively incorporate selenocysteine at 'Cys-252'. Selenocysteine-
CC modified protein is highly sensitive to redox modification and may
CC constitute a pool of protein highly sensitive to activation by elevated
CC levels of reactive oxygen species (ROS) (By similarity).
CC {ECO:0000250|UniProtKB:P12242}.
CC -!- SUBUNIT: Most probably functions as a monomer (PubMed:26038550). Binds
CC one purine nucleotide per monomer (PubMed:26038550). However, has also
CC been suggested to function as a homodimer or a homotetramer (By
CC similarity). Tightly associates with cardiolipin in the mitochondrion
CC inner membrane; may stabilize and regulate its activity
CC (PubMed:26038550). {ECO:0000250|UniProtKB:P25874,
CC ECO:0000269|PubMed:26038550}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:26038550}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P04633}.
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 -!- PTM: May undergo ubiquitin-mediated proteasomal degradation.
CC {ECO:0000250|UniProtKB:P04633}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AMGL01037664; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; W5PSH7; -.
DR SMR; W5PSH7; -.
DR STRING; 9940.ENSOARP00000013406; -.
DR PaxDb; 9940-ENSOARP00000013406; -.
DR Ensembl; ENSOART00000013603.1; ENSOARP00000013406.1; ENSOARG00000012510.1.
DR Ensembl; ENSOART00020019420; ENSOARP00020016071; ENSOARG00020012680.
DR eggNOG; KOG0753; Eukaryota.
DR HOGENOM; CLU_015166_14_2_1; -.
DR OMA; NCAMKMF; -.
DR OrthoDB; 1832865at2759; -.
DR Proteomes; UP000002356; Chromosome 17.
DR Bgee; ENSOARG00000012510; Expressed in prescapular lymph node and 28 other cell types or tissues.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:1901612; F:cardiolipin binding; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0036041; F:long-chain fatty acid binding; ISS:UniProtKB.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
DR GO; GO:0015078; F:proton transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0022857; F:transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0070417; P:cellular response to cold; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; ISS:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; ISS:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:Ensembl.
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; 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:SF19; MITOCHONDRIAL BROWN FAT UNCOUPLING PROTEIN 1; 1.
DR PANTHER; PTHR45618; MITOCHONDRIAL DICARBOXYLATE CARRIER-RELATED; 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 Ion channel; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidation; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..305
FT /note="Mitochondrial brown fat uncoupling protein 1"
FT /id="PRO_0000438246"
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..114
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 115..131
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..176
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 177..193
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..210
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 211..230
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..264
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT TRANSMEM 265..287
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..305
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P04633"
FT REPEAT 11..102
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 109..199
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 208..293
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT BINDING 56
FT /ligand="fatty acid 16:0"
FT /ligand_id="ChEBI:CHEBI:78123"
FT /evidence="ECO:0000250|UniProtKB:P25874"
FT BINDING 267
FT /ligand="fatty acid 16:0"
FT /ligand_id="ChEBI:CHEBI:78123"
FT /evidence="ECO:0000250|UniProtKB:P25874"
FT MOD_RES 252
FT /note="Cysteine sulfenic acid (-SOH)"
FT /evidence="ECO:0000250|UniProtKB:P12242"
SQ SEQUENCE 305 AA; 32952 MW; 3D4BE09BF08C1E43 CRC64;
MVGHAATDVP PTMAVKIFSA GVAACVADII TFPLDTAKVR LQIQGECLTS SAFRYKGVLG
TIITLAKTEG PVKLYSGLPA GLQRQISFAS LRIGLYDTVQ EFFTTGKEAS LGSKISAGLT
TGGVAVFIGQ PTEVVKVRLQ AQSHLHGPKP RYTGTYNAYR IIATTEGLTG LWKGTTPNLT
RNVIINCTEL VTYDLMKEAL VKNKLLADDV PCHFVSAVVA GFCTTVLSSP VDVVKTRFVN
SSPGQYTSVP NCAMMMLTRE GPSAFFKGFV PSFLRLGSWN IIMFVCFEQL KRELMKSRQA
MDCAT
//
