UCP3_HUMAN
ID UCP3_HUMAN Reviewed; 312 AA.
AC P55916; O60475; Q96HL3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Mitochondrial uncoupling protein 3;
DE Short=UCP 3;
DE AltName: Full=Solute carrier family 25 member 9;
GN Name=UCP3; Synonyms=SLC25A9;
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 [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=9180264; DOI=10.1016/s0014-5793(97)00384-0;
RA Boss O., Samec S., Paoloni-Giacobino A., Dulloo A., Seydoux J., Rossier C.,
RA Muzzin P., Giacobino J.-P.;
RT "Uncoupling protein-3: a new member of the mitochondrial carrier family
RT with tissue-specific expression.";
RL FEBS Lett. 408:39-42(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS UCP3L AND UCP3S).
RX PubMed=9325252; DOI=10.1074/jbc.272.41.25433;
RA Solanes G., Vidal-Puig A., Grujic D., Flier J.S., Lowell B.B.;
RT "The human uncoupling protein-3 gene. Genomic structure, chromosomal
RT localization, and genetic basis for short and long form transcripts.";
RL J. Biol. Chem. 272:25433-25436(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM UCP3L), AND TISSUE SPECIFICITY.
RX PubMed=9196039; DOI=10.1006/bbrc.1997.6740;
RA Vidal-Puig A., Solanes G., Grujic D., Flier J.S., Lowell B.B.;
RT "UCP3: an uncoupling protein homologue expressed preferentially and
RT abundantly in skeletal muscle and brown adipose tissue.";
RL Biochem. Biophys. Res. Commun. 235:79-82(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9305858; DOI=10.1074/jbc.272.39.24129;
RA Gong D.-W., He Y., Karas M., Reitman M.;
RT "Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid
RT hormone, beta3-adrenergic agonists, and leptin.";
RL J. Biol. Chem. 272:24129-24132(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9498661; DOI=10.1007/s001250050897;
RA Urhammer S.A., Dalgaard L.T., Soerensen T.I.A., Tybjaerg-Hansen A.,
RA Echwald S.M., Andersen T., Clausen J.O., Pedersen O.;
RT "Organisation of the coding exons and mutational screening of the
RT uncoupling protein 3 gene in subjects with juvenile-onset obesity.";
RL Diabetologia 41:241-244(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10958796; DOI=10.1074/jbc.m005713200;
RA Esterbauer H., Oberkofler H., Krempler F., Strosberg A.D., Patsch W.;
RT "The uncoupling protein-3 gene is transcribed from tissue-specific
RT promoters in humans but not in rodents.";
RL J. Biol. Chem. 275:36394-36399(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Skeletal muscle;
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 [8]
RP VARIANT OBESITY ILE-102.
RX PubMed=9769326; DOI=10.1172/jci4115;
RA Argyropoulos G., Brown A.M., Willi S.M., Zhu J., He Y., Reitman M.,
RA Gevao S.M., Spruill I., Garvey W.T.;
RT "Effects of mutations in the human uncoupling protein 3 gene on the
RT respiratory quotient and fat oxidation in severe obesity and type 2
RT diabetes.";
RL J. Clin. Invest. 102:1345-1351(1998).
RN [9]
RP VARIANT OBESITY TRP-70.
RA Brown A.M., Willi S.M., Argyropoulos G., Garvey W.T.;
RT "A novel missense mutation, R70W, in the human uncoupling protein 3 gene in
RT a family with type 2 diabetes.";
RL Hum. Mutat. 13:506-506(1999).
CC -!- FUNCTION: UCP are mitochondrial transporter proteins that create proton
CC leaks across the inner mitochondrial membrane, thus uncoupling
CC oxidative phosphorylation. As a result, energy is dissipated in the
CC form of heat. May play a role in the modulation of tissue respiratory
CC control. Participates in thermogenesis and energy balance.
CC -!- INTERACTION:
CC P55916; P03495: NS; Xeno; NbExp=2; IntAct=EBI-9116865, EBI-2548993;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=UCP3L;
CC IsoId=P55916-1; Sequence=Displayed;
CC Name=UCP3S;
CC IsoId=P55916-2; Sequence=VSP_003271;
CC Name=3;
CC IsoId=P55916-3; Sequence=VSP_003270;
CC -!- TISSUE SPECIFICITY: Only in skeletal muscle and heart. Is more
CC expressed in glycolytic than in oxidative skeletal muscles.
CC {ECO:0000269|PubMed:9196039}.
CC -!- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by
CC an increase of body weight beyond the limitation of skeletal and
CC physical requirements, as the result of excessive accumulation of body
CC fat. {ECO:0000269|PubMed:9769326, ECO:0000269|Ref.9}. Note=The gene
CC represented in this entry may be involved in disease pathogenesis.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51785.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U84763; AAC51367.1; -; mRNA.
DR EMBL; U82818; AAC51356.1; -; mRNA.
DR EMBL; AF001787; AAC51369.1; -; mRNA.
DR EMBL; AF011449; AAC51767.1; -; mRNA.
DR EMBL; AF012202; AAC51785.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF012197; AAC51785.1; JOINED; Genomic_DNA.
DR EMBL; AF012198; AAC51785.1; JOINED; Genomic_DNA.
DR EMBL; AF012199; AAC51785.1; JOINED; Genomic_DNA.
DR EMBL; AF012200; AAC51785.1; JOINED; Genomic_DNA.
DR EMBL; AF012201; AAC51785.1; JOINED; Genomic_DNA.
DR EMBL; AF026958; AAC18822.1; -; Genomic_DNA.
DR EMBL; AF026956; AAC18822.1; JOINED; Genomic_DNA.
DR EMBL; AF026957; AAC18822.1; JOINED; Genomic_DNA.
DR EMBL; AF050113; AAG02284.1; -; Genomic_DNA.
DR EMBL; BC008392; AAH08392.1; -; mRNA.
DR CCDS; CCDS44677.1; -. [P55916-2]
DR CCDS; CCDS8229.1; -. [P55916-1]
DR PIR; JC5522; JC5522.
DR RefSeq; NP_003347.1; NM_003356.3. [P55916-1]
DR RefSeq; NP_073714.1; NM_022803.2. [P55916-2]
DR AlphaFoldDB; P55916; -.
DR BioGRID; 113199; 14.
DR IntAct; P55916; 1.
DR MINT; P55916; -.
DR STRING; 9606.ENSP00000323740; -.
DR TCDB; 2.A.29.3.5; the mitochondrial carrier (mc) family.
DR iPTMnet; P55916; -.
DR PhosphoSitePlus; P55916; -.
DR BioMuta; UCP3; -.
DR EPD; P55916; -.
DR PaxDb; P55916; -.
DR PeptideAtlas; P55916; -.
DR PRIDE; P55916; -.
DR Antibodypedia; 4388; 285 antibodies from 33 providers.
DR DNASU; 7352; -.
DR Ensembl; ENST00000314032.9; ENSP00000323740.4; ENSG00000175564.13. [P55916-1]
DR Ensembl; ENST00000426995.2; ENSP00000392143.2; ENSG00000175564.13. [P55916-2]
DR GeneID; 7352; -.
DR KEGG; hsa:7352; -.
DR MANE-Select; ENST00000314032.9; ENSP00000323740.4; NM_003356.4; NP_003347.1.
DR UCSC; uc001our.4; human. [P55916-1]
DR CTD; 7352; -.
DR DisGeNET; 7352; -.
DR GeneCards; UCP3; -.
DR HGNC; HGNC:12519; UCP3.
DR HPA; ENSG00000175564; Group enriched (skeletal muscle, tongue).
DR MalaCards; UCP3; -.
DR MIM; 601665; phenotype.
DR MIM; 602044; gene.
DR neXtProt; NX_P55916; -.
DR OpenTargets; ENSG00000175564; -.
DR PharmGKB; PA37166; -.
DR VEuPathDB; HostDB:ENSG00000175564; -.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000161030; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; P55916; -.
DR OMA; DCMLKLV; -.
DR PhylomeDB; P55916; -.
DR TreeFam; TF323211; -.
DR PathwayCommons; P55916; -.
DR Reactome; R-HSA-167826; The fatty acid cycling model.
DR Reactome; R-HSA-167827; The proton buffering model.
DR SignaLink; P55916; -.
DR SIGNOR; P55916; -.
DR BioGRID-ORCS; 7352; 14 hits in 1068 CRISPR screens.
DR GeneWiki; UCP3; -.
DR GenomeRNAi; 7352; -.
DR Pharos; P55916; Tbio.
DR PRO; PR:P55916; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P55916; protein.
DR Bgee; ENSG00000175564; Expressed in gastrocnemius and 179 other tissues.
DR ExpressionAtlas; P55916; baseline and differential.
DR Genevisible; P55916; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:1990845; P:adaptive thermogenesis; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IBA:GO_Central.
DR GO; GO:0006839; P:mitochondrial transport; IEA:InterPro.
DR GO; GO:1902600; P:proton transmembrane transport; TAS:ProtInc.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; TAS:ProtInc.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IBA:GO_Central.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
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; IEA:Ensembl.
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 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 Alternative splicing; Diabetes mellitus; Disease variant; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Obesity; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..312
FT /note="Mitochondrial uncoupling protein 3"
FT /id="PRO_0000090672"
FT TRANSMEM 11..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..99
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..136
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..200
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..237
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..294
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 11..105
FT /note="Solcar 1"
FT REPEAT 114..206
FT /note="Solcar 2"
FT REPEAT 215..300
FT /note="Solcar 3"
FT REGION 279..301
FT /note="Purine nucleotide binding"
FT /evidence="ECO:0000250"
FT VAR_SEQ 114..216
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003270"
FT VAR_SEQ 276..312
FT /note="Missing (in isoform UCP3S)"
FT /evidence="ECO:0000305"
FT /id="VSP_003271"
FT VARIANT 9
FT /note="V -> M (in dbSNP:rs8179180)"
FT /id="VAR_050136"
FT VARIANT 70
FT /note="R -> W (in severe obesity with type 2 diabetes;
FT dbSNP:rs17848368)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_004407"
FT VARIANT 102
FT /note="V -> I (in obesity; dbSNP:rs2229707)"
FT /evidence="ECO:0000269|PubMed:9769326"
FT /id="VAR_004408"
FT CONFLICT 193..194
FT /note="NC -> KS (in Ref. 5; AAC18822)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 34216 MW; D0E04A8DB352B17C CRC64;
MVGLKPSDVP PTMAVKFLGA GTAACFADLV TFPLDTAKVR LQIQGENQAV QTARLVQYRG
VLGTILTMVR TEGPCSPYNG LVAGLQRQMS FASIRIGLYD SVKQVYTPKG ADNSSLTTRI
LAGCTTGAMA VTCAQPTDVV KVRFQASIHL GPSRSDRKYS GTMDAYRTIA REEGVRGLWK
GTLPNIMRNA IVNCAEVVTY DILKEKLLDY HLLTDNFPCH FVSAFGAGFC ATVVASPVDV
VKTRYMNSPP GQYFSPLDCM IKMVAQEGPT AFYKGFTPSF LRLGSWNVVM FVTYEQLKRA
LMKVQMLRES PF
