UCP2_HUMAN
ID UCP2_HUMAN Reviewed; 309 AA.
AC P55851; Q4PJH8; Q53HM3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Mitochondrial uncoupling protein 2;
DE Short=UCP 2;
DE AltName: Full=Solute carrier family 25 member 8;
DE AltName: Full=UCPH;
GN Name=UCP2; Synonyms=SLC25A8;
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 [MRNA].
RC TISSUE=Lung, and Skeletal muscle;
RX PubMed=9054939; DOI=10.1038/ng0397-269;
RA Fleury C., Neverova M., Collins S., Raimbault S., Champigny O.,
RA Levi-Meyrueis C., Bouillaud F., Seldin M.F., Surwit R.S., Ricquier D.,
RA Warden C.H.;
RT "Uncoupling protein-2: a novel gene linked to obesity and
RT hyperinsulinemia.";
RL Nat. Genet. 15:269-272(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-55.
RC TISSUE=Spleen;
RX PubMed=9133562; DOI=10.2337/diab.46.5.900;
RA Gimeno R.E., Dembski M., Weng X., Deng N., Shyjan A.W., Gimeno C.J.,
RA Iris F., Ellis S.J., Woolf E.A., Tartaglia L.A.;
RT "Cloning and characterization of an uncoupling protein homolog: a potential
RT molecular mediator of human thermogenesis.";
RL Diabetes 46:900-906(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-55.
RA Klannemark M., Orho M., Groop L.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9568704; DOI=10.2337/diabetes.47.4.685;
RA Argyropoulos G., Brown A.M., Peterson R., Likes C.E., Watson D.K.,
RA Garvey W.T.;
RT "Structure and organization of the human uncoupling protein 2 gene and
RT identification of a common biallelic variant in Caucasian and African-
RT American subjects.";
RL Diabetes 47:685-687(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=10082652; DOI=10.1006/bbrc.1998.0146;
RA Pecqueur C., Cassard-Doulcier A.M., Raimbault S., Miroux B., Fleury C.,
RA Gelly C., Bouillaud F., Ricquier D.;
RT "Functional organization of the human uncoupling protein-2 gene, and
RT juxtaposition to the uncoupling protein-3 gene.";
RL Biochem. Biophys. Res. Commun. 255:40-46(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-55.
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-55; GLN-76; GLN-154;
RP GLY-268 AND CYS-282.
RG NIEHS SNPs program;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
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 [10]
RP INVOLVEMENT IN BMIQ4 AND SUSCEPTIBILITY TO OBESITY.
RX PubMed=11381268; DOI=10.1038/88911;
RA Esterbauer H., Schneitler C., Oberkofler H., Ebenbichler C., Paulweber B.,
RA Sandhofer F., Ladurner G., Hell E., Strosberg A.D., Patsch J.R.,
RA Krempler F., Patsch W.;
RT "A common polymorphism in the promoter of UCP2 is associated with decreased
RT risk of obesity in middle-aged humans.";
RL Nat. Genet. 28:178-183(2001).
CC -!- FUNCTION: UCP are mitochondrial transporter proteins that create proton
CC leaks across the inner mitochondrial membrane, thus uncoupling
CC oxidative phosphorylation from ATP synthesis. As a result, energy is
CC dissipated in the form of heat.
CC -!- SUBUNIT: Acts as a dimer forming a proton channel. {ECO:0000250}.
CC -!- INTERACTION:
CC P55851; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-2842077, EBI-10172290;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane
CC protein.
CC -!- TISSUE SPECIFICITY: Widely expressed in adult human tissues, including
CC tissues rich in macrophages. Most expressed in white adipose tissue and
CC skeletal muscle.
CC -!- POLYMORPHISM: Genetic variations in UCP2 define the body mass index
CC quantitative trait locus 4 (BMIQ4) [MIM:607447]. A common polymorphism
CC in the promoter of UCP2 has been shown to be associated with a
CC decreased risk of obesity in middle-aged individuals.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ucp2/";
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DR EMBL; U82819; AAC51336.1; -; mRNA.
DR EMBL; U76367; AAB48411.1; -; mRNA.
DR EMBL; U94592; AAB53091.1; -; mRNA.
DR EMBL; AJ223477; CAA11402.1; -; Genomic_DNA.
DR EMBL; AJ223478; CAA11402.1; JOINED; Genomic_DNA.
DR EMBL; AJ223479; CAA11402.1; JOINED; Genomic_DNA.
DR EMBL; AF019409; AAC39690.1; -; Genomic_DNA.
DR EMBL; AF096289; AAD21151.1; -; Genomic_DNA.
DR EMBL; AK222540; BAD96260.1; -; mRNA.
DR EMBL; AK222557; BAD96277.1; -; mRNA.
DR EMBL; DQ087219; AAY68217.1; -; Genomic_DNA.
DR EMBL; BC011737; AAH11737.1; -; mRNA.
DR CCDS; CCDS8228.1; -.
DR RefSeq; NP_003346.2; NM_003355.2.
DR AlphaFoldDB; P55851; -.
DR BioGRID; 113198; 25.
DR IntAct; P55851; 14.
DR STRING; 9606.ENSP00000312029; -.
DR TCDB; 2.A.29.3.4; the mitochondrial carrier (mc) family.
DR iPTMnet; P55851; -.
DR PhosphoSitePlus; P55851; -.
DR BioMuta; UCP2; -.
DR DMDM; 2497981; -.
DR MassIVE; P55851; -.
DR PaxDb; P55851; -.
DR PeptideAtlas; P55851; -.
DR PRIDE; P55851; -.
DR ProteomicsDB; 56873; -.
DR Antibodypedia; 31003; 415 antibodies from 40 providers.
DR DNASU; 7351; -.
DR Ensembl; ENST00000310473.9; ENSP00000312029.3; ENSG00000175567.11.
DR Ensembl; ENST00000663595.2; ENSP00000499695.1; ENSG00000175567.11.
DR GeneID; 7351; -.
DR KEGG; hsa:7351; -.
DR MANE-Select; ENST00000663595.2; ENSP00000499695.1; NM_003355.3; NP_003346.2.
DR UCSC; uc001oup.2; human.
DR CTD; 7351; -.
DR DisGeNET; 7351; -.
DR GeneCards; UCP2; -.
DR GeneReviews; UCP2; -.
DR HGNC; HGNC:12518; UCP2.
DR HPA; ENSG00000175567; Tissue enhanced (lymphoid).
DR MalaCards; UCP2; -.
DR MIM; 601693; gene.
DR MIM; 607447; phenotype.
DR neXtProt; NX_P55851; -.
DR OpenTargets; ENSG00000175567; -.
DR Orphanet; 276556; Hyperinsulinism due to UCP2 deficiency.
DR PharmGKB; PA37165; -.
DR VEuPathDB; HostDB:ENSG00000175567; -.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000159524; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; P55851; -.
DR OMA; MMAANHS; -.
DR OrthoDB; 1126848at2759; -.
DR PhylomeDB; P55851; -.
DR TreeFam; TF323211; -.
DR PathwayCommons; P55851; -.
DR Reactome; R-HSA-167826; The fatty acid cycling model.
DR Reactome; R-HSA-167827; The proton buffering model.
DR SignaLink; P55851; -.
DR BioGRID-ORCS; 7351; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; UCP2; human.
DR GeneWiki; UCP2; -.
DR GenomeRNAi; 7351; -.
DR Pharos; P55851; Tbio.
DR PRO; PR:P55851; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P55851; protein.
DR Bgee; ENSG00000175567; Expressed in granulocyte and 201 other tissues.
DR ExpressionAtlas; P55851; baseline and differential.
DR Genevisible; P55851; 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; IDA:HPA.
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:0034198; P:cellular response to amino acid starvation; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IBA:GO_Central.
DR GO; GO:0006839; P:mitochondrial transport; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:1902600; P:proton transmembrane transport; TAS:ProtInc.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IBA:GO_Central.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IDA:CACAO.
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 Membrane; Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..309
FT /note="Mitochondrial uncoupling protein 2"
FT /id="PRO_0000090664"
FT TOPO_DOM 1..10
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..77
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..100
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..119
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..136
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..180
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..197
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..214
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..234
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 235..268
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..291
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..309
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT REPEAT 11..106
FT /note="Solcar 1"
FT REPEAT 114..203
FT /note="Solcar 2"
FT REPEAT 212..297
FT /note="Solcar 3"
FT REGION 276..298
FT /note="Purine nucleotide binding"
FT /evidence="ECO:0000250"
FT VARIANT 55
FT /note="A -> V (in dbSNP:rs660339)"
FT /evidence="ECO:0000269|PubMed:9133562, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.7, ECO:0000269|Ref.8"
FT /id="VAR_016129"
FT VARIANT 76
FT /note="R -> Q (in dbSNP:rs45541732)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_023998"
FT VARIANT 154
FT /note="R -> Q (in dbSNP:rs45486692)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_023999"
FT VARIANT 268
FT /note="A -> G (in dbSNP:rs45490393)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_024000"
FT VARIANT 282
FT /note="S -> C (in dbSNP:rs45596837)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_024001"
FT CONFLICT 219
FT /note="T -> I (in Ref. 2; AAB48411)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 309 AA; 33229 MW; 2E1741391621E3D9 CRC64;
MVGFKATDVP PTATVKFLGA GTAACIADLI TFPLDTAKVR LQIQGESQGP VRATASAQYR
GVMGTILTMV RTEGPRSLYN GLVAGLQRQM SFASVRIGLY DSVKQFYTKG SEHASIGSRL
LAGSTTGALA VAVAQPTDVV KVRFQAQARA GGGRRYQSTV NAYKTIAREE GFRGLWKGTS
PNVARNAIVN CAELVTYDLI KDALLKANLM TDDLPCHFTS AFGAGFCTTV IASPVDVVKT
RYMNSALGQY SSAGHCALTM LQKEGPRAFY KGFMPSFLRL GSWNVVMFVT YEQLKRALMA
ACTSREAPF
