UCP4_HUMAN
ID UCP4_HUMAN Reviewed; 323 AA.
AC O95847; F5GWR4; Q5VTS9; Q8N518;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Mitochondrial uncoupling protein 4;
DE Short=UCP 4;
DE AltName: Full=Solute carrier family 25 member 27;
GN Name=SLC25A27; Synonyms=UCP4; ORFNames=UNQ772/PRO1566;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10025957; DOI=10.1016/s0014-5793(98)01713-x;
RA Mao W., Yu X.X., Zhong A., Li W., Brush J., Sherwood S.W., Adams S.H.,
RA Pan G.;
RT "UCP4, a novel brain-specific mitochondrial protein that reduces membrane
RT potential in mammalian cells.";
RL FEBS Lett. 443:326-330(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-145.
RC TISSUE=Prostate;
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).
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. May play a role in thermoregulatory
CC heat production and metabolism in brain.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95847-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95847-2; Sequence=VSP_045916;
CC -!- TISSUE SPECIFICITY: Found in adult and fetal brain. Present in most of
CC the brain tissues, with low levels in spinal chord, corpus callosum and
CC substantia nigra.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AF110532; AAD16995.1; -; mRNA.
DR EMBL; AY358711; AAQ89951.1; -; mRNA.
DR EMBL; AK291427; BAF84116.1; -; mRNA.
DR EMBL; AL591242; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04299.1; -; Genomic_DNA.
DR EMBL; BC033091; AAH33091.1; -; mRNA.
DR CCDS; CCDS43470.1; -. [O95847-1]
DR CCDS; CCDS56431.1; -. [O95847-2]
DR RefSeq; NP_001190980.1; NM_001204051.1.
DR RefSeq; NP_001190981.1; NM_001204052.1. [O95847-2]
DR RefSeq; NP_004268.3; NM_004277.4. [O95847-1]
DR AlphaFoldDB; O95847; -.
DR SMR; O95847; -.
DR BioGRID; 114866; 1.
DR IntAct; O95847; 3.
DR STRING; 9606.ENSP00000360398; -.
DR TCDB; 2.A.29.24.3; the mitochondrial carrier (mc) family.
DR iPTMnet; O95847; -.
DR PhosphoSitePlus; O95847; -.
DR BioMuta; SLC25A27; -.
DR jPOST; O95847; -.
DR MassIVE; O95847; -.
DR PaxDb; O95847; -.
DR PeptideAtlas; O95847; -.
DR PRIDE; O95847; -.
DR ProteomicsDB; 24193; -.
DR ProteomicsDB; 51088; -. [O95847-1]
DR Antibodypedia; 4016; 86 antibodies from 23 providers.
DR DNASU; 9481; -.
DR Ensembl; ENST00000371347.10; ENSP00000360398.3; ENSG00000153291.16. [O95847-1]
DR Ensembl; ENST00000411689.6; ENSP00000412024.2; ENSG00000153291.16. [O95847-2]
DR GeneID; 9481; -.
DR KEGG; hsa:9481; -.
DR MANE-Select; ENST00000371347.10; ENSP00000360398.3; NM_004277.5; NP_004268.3.
DR UCSC; uc003oyg.3; human. [O95847-1]
DR CTD; 9481; -.
DR DisGeNET; 9481; -.
DR GeneCards; SLC25A27; -.
DR HGNC; HGNC:21065; SLC25A27.
DR HPA; ENSG00000153291; Low tissue specificity.
DR MIM; 613725; gene.
DR neXtProt; NX_O95847; -.
DR OpenTargets; ENSG00000153291; -.
DR PharmGKB; PA134970102; -.
DR VEuPathDB; HostDB:ENSG00000153291; -.
DR eggNOG; KOG0753; Eukaryota.
DR GeneTree; ENSGT00940000160098; -.
DR HOGENOM; CLU_015166_14_2_1; -.
DR InParanoid; O95847; -.
DR OMA; QLRPVKY; -.
DR OrthoDB; 1013743at2759; -.
DR PhylomeDB; O95847; -.
DR TreeFam; TF354328; -.
DR PathwayCommons; O95847; -.
DR Reactome; R-HSA-167826; The fatty acid cycling model.
DR Reactome; R-HSA-167827; The proton buffering model.
DR SignaLink; O95847; -.
DR BioGRID-ORCS; 9481; 11 hits in 1073 CRISPR screens.
DR ChiTaRS; SLC25A27; human.
DR GeneWiki; SLC25A27; -.
DR GenomeRNAi; 9481; -.
DR Pharos; O95847; Tbio.
DR PRO; PR:O95847; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95847; protein.
DR Bgee; ENSG00000153291; Expressed in mucosa of stomach and 170 other tissues.
DR ExpressionAtlas; O95847; baseline and differential.
DR Genevisible; O95847; 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:0031966; C:mitochondrial membrane; IDA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0009409; P:response to cold; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 2: Evidence at transcript level;
KW Alternative splicing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..323
FT /note="Mitochondrial uncoupling protein 4"
FT /id="PRO_0000090676"
FT TRANSMEM 23..40
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..109
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..144
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..212
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..248
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..311
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 21..115
FT /note="Solcar 1"
FT REPEAT 125..217
FT /note="Solcar 2"
FT REPEAT 226..317
FT /note="Solcar 3"
FT VAR_SEQ 236..323
FT /note="LCSGLVASILGTPADVIKSRIMNQPRDKQGRGLLYKSSTDCLIQAVQGEGFM
FT SLYKGFLPSWLRMTPWSMVFWLTYEKIREMSGVSPF -> DLVGSHKAIQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045916"
FT VARIANT 145
FT /note="A -> V (in dbSNP:rs17853162)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_069101"
FT VARIANT 197
FT /note="I -> T (in dbSNP:rs35884480)"
FT /id="VAR_050137"
SQ SEQUENCE 323 AA; 36064 MW; 4C54A56BB10333ED CRC64;
MSVPEEEERL LPLTQRWPRA SKFLLSGCAA TVAELATFPL DLTKTRLQMQ GEAALARLGD
GARESAPYRG MVRTALGIIE EEGFLKLWQG VTPAIYRHVV YSGGRMVTYE HLREVVFGKS
EDEHYPLWKS VIGGMMAGVI GQFLANPTDL VKVQMQMEGK RKLEGKPLRF RGVHHAFAKI
LAEGGIRGLW AGWVPNIQRA ALVNMGDLTT YDTVKHYLVL NTPLEDNIMT HGLSSLCSGL
VASILGTPAD VIKSRIMNQP RDKQGRGLLY KSSTDCLIQA VQGEGFMSLY KGFLPSWLRM
TPWSMVFWLT YEKIREMSGV SPF
