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 11-NOV-2015, entry version 140. DE RecName: Full=Mitochondrial brown fat uncoupling protein 1; DE Short=UCP 1; DE AltName: Full=Solute carrier family 25 member 7; DE AltName: Full=Thermogenin; GN Name=UCP1; Synonyms=SLC25A7, UCP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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, RT and 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., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA 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., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA 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., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 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 RT project: 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; 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 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 RT variant in exon 5 of the human UCP1 gene are associated with RT susceptibility to type II diabetes mellitus."; RL Diabetologia 44:373-376(2001). RN [8] 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., RA Schmidt-Petersen K., Zidek W., Paul M., Brand E.; RT "Uncoupling protein 1 and 3 polymorphisms are associated with waist- RT to-hip ratio."; RL J. Mol. Med. 81:327-332(2003). CC -!- FUNCTION: UCP are mitochondrial transporter proteins that create CC proton leaks across the inner mitochondrial membrane, thus CC uncoupling oxidative phosphorylation from ATP synthesis. As a CC result, energy is dissipated in the form of heat. CC -!- SUBUNIT: Acts as a dimer forming a proton channel. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass CC membrane protein. CC -!- TISSUE SPECIFICITY: Brown adipose tissue. CC {ECO:0000269|PubMed:3165741}. CC -!- POLYMORPHISM: The Thr-64 polymorphism is associated with an CC increased waist-to-hip ratio. The Leu-229 polymorphism is CC associated with susceptibility to type II diabetes mellitus. CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 3 Solcar repeats. {ECO:0000255|PROSITE- CC ProRule:PRU00282}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 UniGene; Hs.249211; -. DR ProteinModelPortal; P25874; -. DR SMR; P25874; 13-304. DR BioGrid; 113197; 3. DR STRING; 9606.ENSP00000262999; -. DR TCDB; 2.A.29.3.2; the mitochondrial carrier (mc) family. DR PhosphoSite; P25874; -. DR BioMuta; UCP1; -. DR DMDM; 71153184; -. DR PaxDb; P25874; -. DR PRIDE; P25874; -. DR Ensembl; ENST00000262999; ENSP00000262999; ENSG00000109424. DR GeneID; 7350; -. DR KEGG; hsa:7350; -. DR UCSC; uc011chj.2; human. DR CTD; 7350; -. DR GeneCards; UCP1; -. DR HGNC; HGNC:12517; UCP1. DR HPA; CAB037199; -. DR MIM; 113730; gene. DR neXtProt; NX_P25874; -. DR PharmGKB; PA37164; -. DR eggNOG; KOG0753; Eukaryota. DR eggNOG; ENOG410XRV1; LUCA. DR GeneTree; ENSGT00760000119170; -. DR HOGENOM; HOG000165140; -. DR HOVERGEN; HBG009528; -. DR InParanoid; P25874; -. DR KO; K08769; -. DR OMA; KMFTNEG; -. DR OrthoDB; EOG793B7Z; -. DR PhylomeDB; P25874; -. DR TreeFam; TF323211; -. DR Reactome; R-HSA-167826; The fatty acid cycling model. DR Reactome; R-HSA-167827; The proton buffering model. DR GeneWiki; Thermogenin; -. DR GenomeRNAi; 7350; -. DR NextBio; 28774; -. DR PRO; PR:P25874; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; P25874; -. DR CleanEx; HS_UCP1; -. DR Genevisible; P25874; 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:MGI. DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; IEA:Ensembl. DR GO; GO:0050873; P:brown fat cell differentiation; ISS:HGNC. DR GO; GO:0044237; P:cellular metabolic process; TAS:Reactome. DR GO; GO:0006839; P:mitochondrial transport; IEA:InterPro. DR GO; GO:0015992; P:proton transport; TAS:Reactome. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0022904; P:respiratory electron transport chain; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 1.50.40.10; -; 1. DR InterPro; IPR002030; Mit_uncoupling. DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier. DR InterPro; IPR023395; Mt_carrier_dom. DR Pfam; PF00153; Mito_carr; 3. DR PRINTS; PR00784; MTUNCOUPLING. DR SUPFAM; SSF103506; SSF103506; 1. DR PROSITE; PS50920; SOLCAR; 3. PE 2: Evidence at transcript level; KW Complete proteome; Diabetes mellitus; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Obesity; Polymorphism; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; KW Transport. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P04575}. FT CHAIN 2 307 Mitochondrial brown fat uncoupling FT protein 1. FT /FTId=PRO_0000090657. FT TRANSMEM 11 32 Helical; Name=1. {ECO:0000255}. FT TRANSMEM 74 96 Helical; Name=2. {ECO:0000255}. FT TRANSMEM 117 133 Helical; Name=3. {ECO:0000255}. FT TRANSMEM 179 195 Helical; Name=4. {ECO:0000255}. FT TRANSMEM 213 232 Helical; Name=5. {ECO:0000255}. FT TRANSMEM 267 289 Helical; Name=6. {ECO:0000255}. FT REPEAT 11 102 Solcar 1. FT REPEAT 111 201 Solcar 2. FT REPEAT 210 295 Solcar 3. FT REGION 274 296 Purine nucleotide binding. {ECO:0000250}. FT VARIANT 64 64 A -> T (in dbSNP:rs45539933). FT {ECO:0000269|PubMed:12756473}. FT /FTId=VAR_022840. FT VARIANT 229 229 M -> L (in dbSNP:rs2270565). FT {ECO:0000269|PubMed:11317671}. FT /FTId=VAR_022841. FT CONFLICT 21 21 G -> P (in Ref. 1; CAA36214). FT {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 //