UCP1_HUMAN
ID UCP1_HUMAN Reviewed; 307 AA.
AC P25874; Q13218; Q4KMZ3; Q68G66;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 3.
DT 03-AUG-2022, entry version 182.
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:0000303|PubMed:23266187};
DE AltName: Full=Thermogenin {ECO:0000250|UniProtKB:P04575};
GN Name=UCP1 {ECO:0000312|HGNC:HGNC:12517};
GN Synonyms=SLC25A7 {ECO:0000303|PubMed:23266187},
GN UCP {ECO:0000303|PubMed:2380264};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2380264; DOI=10.1002/jcb.240430306;
RA Cassard A.M., Bouillaud F., Mattei M.-G., Hentz E., Raimbault S.,
RA Thomas M., Ricquier D.;
RT "Human uncoupling protein gene: structure, comparison with rat gene, and
RT assignment to the long arm of chromosome 4.";
RL J. Cell. Biochem. 43:255-264(1990).
RN [2]
RP SEQUENCE REVISION.
RA Bouillaud F.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brown adipose tissue;
RA Bouillaud F., Ricquier D., Raimbault S.;
RT "Sequence of the cDNA coding for the human uncoupling protein UCP.";
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 113-196, AND TISSUE SPECIFICITY.
RC TISSUE=Brown adipose tissue;
RX PubMed=3165741; DOI=10.1042/cs0750021;
RA Bouillaud F., Villarroya F., Hentz E., Raimbault S., Cassard A.M.,
RA Ricquier D.;
RT "Detection of brown adipose tissue uncoupling protein mRNA in adult
RT patients by a human genomic probe.";
RL Clin. Sci. 75:21-27(1988).
RN [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=24196960; DOI=10.1074/jbc.m113.509935;
RA Hoang T., Smith M.D., Jelokhani-Niaraki M.;
RT "Expression, folding, and proton transport activity of human uncoupling
RT protein-1 (UCP1) in lipid membranes: evidence for associated functional
RT forms.";
RL J. Biol. Chem. 288:36244-36258(2013).
RN [8]
RP NOMENCLATURE.
RX PubMed=23266187; DOI=10.1016/j.mam.2012.05.005;
RA Palmieri F.;
RT "The mitochondrial transporter family SLC25: identification, properties and
RT physiopathology.";
RL Mol. Aspects Med. 34:465-484(2013).
RN [9]
RP VARIANT LEU-229.
RX PubMed=11317671; DOI=10.1007/s001250051629;
RA Mori H., Okazawa H., Iwamoto K., Maeda E., Hashiramoto M., Kasuga M.;
RT "A polymorphism in the 5' untranslated region and a Met229-->Leu variant in
RT exon 5 of the human UCP1 gene are associated with susceptibility to type II
RT diabetes mellitus.";
RL Diabetologia 44:373-376(2001).
RN [10]
RP VARIANT THR-64.
RX PubMed=12756473; DOI=10.1007/s00109-003-0431-1;
RA Herrmann S.M., Wang J.G., Staessen J.A., Kertmen E., Schmidt-Petersen K.,
RA Zidek W., Paul M., Brand E.;
RT "Uncoupling protein 1 and 3 polymorphisms are associated with waist-to-hip
RT ratio.";
RL J. Mol. Med. 81:327-332(2003).
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:24196960). 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:24196960}.
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. Activated by noradrenaline and reactive oxygen species.
CC {ECO:0000250|UniProtKB:P12242}.
CC -!- SUBUNIT: Most probably functions as a monomer. Binds one purine
CC nucleotide per monomer (By similarity). However, has also been
CC suggested to function as a homodimer or a homotetramer
CC (PubMed:24196960). Tightly associates with cardiolipin in the
CC mitochondrion inner membrane; may stabilize and regulate its activity
CC (PubMed:24196960). {ECO:0000250|UniProtKB:W5PSH7,
CC ECO:0000269|PubMed:24196960}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P12242}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P04633}.
CC -!- TISSUE SPECIFICITY: Brown adipose tissue. {ECO:0000269|PubMed:3165741}.
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}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A touch of warmth - Issue
CC 195 of September 2017;
CC URL="https://web.expasy.org/spotlight/back_issues/195/";
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DR EMBL; X51952; CAA36214.1; -; Genomic_DNA.
DR EMBL; X51953; CAA36214.1; JOINED; Genomic_DNA.
DR EMBL; X51954; CAA36214.1; JOINED; Genomic_DNA.
DR EMBL; X51955; CAA36214.1; JOINED; Genomic_DNA.
DR EMBL; U28480; AAA85271.1; -; mRNA.
DR EMBL; AC108019; AAY41026.1; -; Genomic_DNA.
DR EMBL; BC069556; AAH69556.1; -; mRNA.
DR EMBL; BC098168; AAH98168.1; -; mRNA.
DR EMBL; BC098258; AAH98258.1; -; mRNA.
DR CCDS; CCDS3753.1; -.
DR PIR; G01858; G01858.
DR RefSeq; NP_068605.1; NM_021833.4.
DR AlphaFoldDB; P25874; -.
DR SMR; P25874; -.
DR BioGRID; 113197; 4.
DR IntAct; P25874; 1.
DR STRING; 9606.ENSP00000262999; -.
DR TCDB; 2.A.29.3.2; the mitochondrial carrier (mc) family.
DR iPTMnet; P25874; -.
DR PhosphoSitePlus; P25874; -.
DR BioMuta; UCP1; -.
DR DMDM; 71153184; -.
DR jPOST; P25874; -.
DR MassIVE; P25874; -.
DR PaxDb; P25874; -.
DR PeptideAtlas; P25874; -.
DR PRIDE; P25874; -.
DR ProteomicsDB; 54299; -.
DR Antibodypedia; 16250; 460 antibodies from 38 providers.
DR DNASU; 7350; -.
DR Ensembl; ENST00000262999.4; ENSP00000262999.3; ENSG00000109424.4.
DR GeneID; 7350; -.
DR KEGG; hsa:7350; -.
DR MANE-Select; ENST00000262999.4; ENSP00000262999.3; NM_021833.5; NP_068605.1.
DR UCSC; uc011chj.3; human.
DR CTD; 7350; -.
DR DisGeNET; 7350; -.
DR GeneCards; UCP1; -.
DR HGNC; HGNC:12517; UCP1.
DR HPA; ENSG00000109424; Tissue enhanced (adrenal gland, brain).
DR MIM; 113730; gene.
DR neXtProt; NX_P25874; -.
DR OpenTargets; ENSG00000109424; -.
DR PharmGKB; PA37164; -.
DR VEuPathDB; HostDB:ENSG00000109424; -.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000160382; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; P25874; -.
DR OMA; YTSVPNC; -.
DR OrthoDB; 984118at2759; -.
DR PhylomeDB; P25874; -.
DR TreeFam; TF323211; -.
DR PathwayCommons; P25874; -.
DR Reactome; R-HSA-167826; The fatty acid cycling model.
DR Reactome; R-HSA-167827; The proton buffering model.
DR SignaLink; P25874; -.
DR SIGNOR; P25874; -.
DR BioGRID-ORCS; 7350; 12 hits in 1071 CRISPR screens.
DR GeneWiki; Thermogenin; -.
DR GenomeRNAi; 7350; -.
DR Pharos; P25874; Tbio.
DR PRO; PR:P25874; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P25874; protein.
DR Bgee; ENSG00000109424; Expressed in parietal pleura and 51 other tissues.
DR Genevisible; P25874; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:1901612; F:cardiolipin binding; ISS:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
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:0032555; F:purine ribonucleotide binding; ISS:UniProtKB.
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; ISS:HGNC-UCL.
DR GO; GO:0070417; P:cellular response to cold; IEA:Ensembl.
DR GO; GO:1903495; P:cellular response to dehydroepiandrosterone; 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; ISS:UniProtKB.
DR GO; GO:0006839; P:mitochondrial transport; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
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: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 Diabetes mellitus; Ion channel; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Obesity; Oxidation; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..307
FT /note="Mitochondrial brown fat uncoupling protein 1"
FT /id="PRO_0000090657"
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:0000250|UniProtKB:P12242"
FT VARIANT 64
FT /note="A -> T (associated with an increased waist-to-hip
FT ratio; dbSNP:rs45539933)"
FT /evidence="ECO:0000269|PubMed:12756473"
FT /id="VAR_022840"
FT VARIANT 229
FT /note="M -> L (associated with susceptibility to type II
FT diabetes mellitus; dbSNP:rs2270565)"
FT /evidence="ECO:0000269|PubMed:11317671"
FT /id="VAR_022841"
FT CONFLICT 21
FT /note="G -> P (in Ref. 1; CAA36214)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 307 AA; 33005 MW; BCC99AB27171FC67 CRC64;
MGGLTASDVH PTLGVQLFSA GIAACLADVI TFPLDTAKVR LQVQGECPTS SVIRYKGVLG
TITAVVKTEG RMKLYSGLPA GLQRQISSAS LRIGLYDTVQ EFLTAGKETA PSLGSKILAG
LTTGGVAVFI GQPTEVVKVR LQAQSHLHGI KPRYTGTYNA YRIIATTEGL TGLWKGTTPN
LMRSVIINCT ELVTYDLMKE AFVKNNILAD DVPCHLVSAL IAGFCATAMS SPVDVVKTRF
INSPPGQYKS VPNCAMKVFT NEGPTAFFKG LVPSFLRLGS WNVIMFVCFE QLKRELSKSR
QTMDCAT
