UniProtKB - P25874 (UCP1_HUMAN)
Protein
Mitochondrial brown fat uncoupling protein 1
Gene
UCP1
Organism
Homo sapiens (Human)
Status
Functioni
Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance (By similarity). Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane (PubMed:24196960). However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria (By similarity).By similarity1 Publication
Activity regulationi
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it. Activated by noradrenaline and reactive oxygen species.By similarity
GO - Molecular functioni
- cardiolipin binding Source: UniProtKB
- long-chain fatty acid binding Source: UniProtKB
- oxidative phosphorylation uncoupler activity Source: UniProtKB
- purine ribonucleotide binding Source: UniProtKB
- transmembrane transporter activity Source: UniProtKB
GO - Biological processi
- adaptive thermogenesis Source: UniProtKB
- brown fat cell differentiation Source: HGNC-UCL
- cellular response to fatty acid Source: UniProtKB
- cellular response to hormone stimulus Source: UniProtKB
- cellular response to reactive oxygen species Source: UniProtKB
- diet induced thermogenesis Source: Ensembl
- mitochondrial transmembrane transport Source: UniProtKB
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- proton transmembrane transport Source: UniProtKB
- regulation of reactive oxygen species biosynthetic process Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: Ensembl
- response to cold Source: GO_Central
- response to nutrient levels Source: UniProtKB
- response to temperature stimulus Source: UniProtKB
Keywordsi
Molecular function | Ion channel |
Biological process | Ion transport, Transport |
Enzyme and pathway databases
PathwayCommonsi | P25874 |
Reactomei | R-HSA-167826, The fatty acid cycling model R-HSA-167827, The proton buffering model |
SIGNORi | P25874 |
Protein family/group databases
TCDBi | 2.A.29.3.2, the mitochondrial carrier (mc) family |
Names & Taxonomyi
Protein namesi | Recommended name: Mitochondrial brown fat uncoupling protein 1CuratedShort name: UCP 1Curated Alternative name(s): Solute carrier family 25 member 71 Publication ThermogeninBy similarity |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000109424.3 |
HGNCi | HGNC:12517, UCP1 |
MIMi | 113730, gene |
neXtProti | NX_P25874 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane By similarity; Multi-pass membrane protein By similarity
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrion Source: MGI
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 10 | Mitochondrial intermembraneBy similarity | 10 | |
Transmembranei | 11 – 32 | Helical; Name=1Sequence analysisAdd BLAST | 22 | |
Topological domaini | 33 – 73 | Mitochondrial matrixBy similarityAdd BLAST | 41 | |
Transmembranei | 74 – 96 | Helical; Name=2Sequence analysisAdd BLAST | 23 | |
Topological domaini | 97 – 116 | Mitochondrial intermembraneBy similarityAdd BLAST | 20 | |
Transmembranei | 117 – 133 | Helical; Name=3Sequence analysisAdd BLAST | 17 | |
Topological domaini | 134 – 178 | Mitochondrial matrixBy similarityAdd BLAST | 45 | |
Transmembranei | 179 – 195 | Helical; Name=4Sequence analysisAdd BLAST | 17 | |
Topological domaini | 196 – 212 | Mitochondrial intermembraneBy similarityAdd BLAST | 17 | |
Transmembranei | 213 – 232 | Helical; Name=5Sequence analysisAdd BLAST | 20 | |
Topological domaini | 233 – 266 | Mitochondrial matrixBy similarityAdd BLAST | 34 | |
Transmembranei | 267 – 289 | Helical; Name=6Sequence analysisAdd BLAST | 23 | |
Topological domaini | 290 – 307 | Mitochondrial intermembraneBy similarityAdd BLAST | 18 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Keywords - Diseasei
Diabetes mellitus, ObesityOrganism-specific databases
DisGeNETi | 7350 |
OpenTargetsi | ENSG00000109424 |
PharmGKBi | PA37164 |
Miscellaneous databases
Pharosi | P25874, Tbio |
Polymorphism and mutation databases
BioMutai | UCP1 |
DMDMi | 71153184 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000090657 | 1 – 307 | Mitochondrial brown fat uncoupling protein 1Add BLAST | 307 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 254 | Cysteine sulfenic acid (-SOH)By similarity | 1 |
Post-translational modificationi
May undergo sulfenylation upon cold exposure. May increase the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects.By similarity
May undergo ubiquitin-mediated proteasomal degradation.By similarity
Keywords - PTMi
OxidationProteomic databases
jPOSTi | P25874 |
MassIVEi | P25874 |
PaxDbi | P25874 |
PeptideAtlasi | P25874 |
PRIDEi | P25874 |
ProteomicsDBi | 54299 |
PTM databases
iPTMneti | P25874 |
PhosphoSitePlusi | P25874 |
Expressioni
Tissue specificityi
Brown adipose tissue.1 Publication
Gene expression databases
Bgeei | ENSG00000109424, Expressed in parietal pleura and 48 other tissues |
Genevisiblei | P25874, HS |
Organism-specific databases
HPAi | ENSG00000109424, Group enriched (adipose tissue, adrenal gland, breast, heart muscle) |
Interactioni
Subunit structurei
Most probably functions as a monomer. Binds one purine nucleotide per monomer (By similarity). However, has also been suggested to function as a homodimer or a homotetramer (PubMed:24196960). Tightly associates with cardiolipin in the mitochondrion inner membrane; may stabilize and regulate its activity (PubMed:24196960).
By similarity1 PublicationProtein-protein interaction databases
BioGRIDi | 113197, 3 interactors |
IntActi | P25874, 1 interactor |
STRINGi | 9606.ENSP00000262999 |
Miscellaneous databases
RNActi | P25874, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 11 – 102 | Solcar 1Add BLAST | 92 | |
Repeati | 111 – 201 | Solcar 2Add BLAST | 91 | |
Repeati | 210 – 295 | Solcar 3Add BLAST | 86 |
Sequence similaritiesi
Keywords - Domaini
Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0753, Eukaryota |
GeneTreei | ENSGT00940000160382 |
HOGENOMi | CLU_015166_14_2_1 |
InParanoidi | P25874 |
OMAi | NCAMKMF |
OrthoDBi | 984118at2759 |
PhylomeDBi | P25874 |
TreeFami | TF323211 |
Family and domain databases
Gene3Di | 1.50.40.10, 1 hit |
InterProi | View protein in InterPro IPR002030, Mit_uncoupling_UCP-like IPR018108, Mitochondrial_sb/sol_carrier IPR023395, Mt_carrier_dom_sf IPR040011, UCP1 |
PANTHERi | PTHR45618:SF19, PTHR45618:SF19, 1 hit |
Pfami | View protein in Pfam PF00153, Mito_carr, 3 hits |
PRINTSi | PR00784, MTUNCOUPLING |
SUPFAMi | SSF103506, SSF103506, 1 hit |
PROSITEi | View protein in PROSITE PS50920, SOLCAR, 3 hits |
i Sequence
Sequence statusi: Complete.
P25874-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGGLTASDVH PTLGVQLFSA GIAACLADVI TFPLDTAKVR LQVQGECPTS
60 70 80 90 100
SVIRYKGVLG TITAVVKTEG RMKLYSGLPA GLQRQISSAS LRIGLYDTVQ
110 120 130 140 150
EFLTAGKETA PSLGSKILAG LTTGGVAVFI GQPTEVVKVR LQAQSHLHGI
160 170 180 190 200
KPRYTGTYNA YRIIATTEGL TGLWKGTTPN LMRSVIINCT ELVTYDLMKE
210 220 230 240 250
AFVKNNILAD DVPCHLVSAL IAGFCATAMS SPVDVVKTRF INSPPGQYKS
260 270 280 290 300
VPNCAMKVFT NEGPTAFFKG LVPSFLRLGS WNVIMFVCFE QLKRELSKSR
QTMDCAT
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 21 | G → P in CAA36214 (PubMed:2380264).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022840 | 64 | A → T Polymorphism; associated with an increased waist-to-hip ratio. 1 PublicationCorresponds to variant dbSNP:rs45539933Ensembl. | 1 | |
Natural variantiVAR_022841 | 229 | M → L Polymorphism; associated with susceptibility to type II diabetes mellitus. 1 PublicationCorresponds to variant dbSNP:rs2270565Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X51952 , X51953, X51954, X51955 Genomic DNA Translation: CAA36214.1 U28480 mRNA Translation: AAA85271.1 AC108019 Genomic DNA Translation: AAY41026.1 BC069556 mRNA Translation: AAH69556.1 BC098168 mRNA Translation: AAH98168.1 BC098258 mRNA Translation: AAH98258.1 |
CCDSi | CCDS3753.1 |
PIRi | G01858 |
RefSeqi | NP_068605.1, NM_021833.4 |
Genome annotation databases
Ensembli | ENST00000262999; ENSP00000262999; ENSG00000109424 |
GeneIDi | 7350 |
KEGGi | hsa:7350 |
UCSCi | uc011chj.3, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight A touch of warmth - Issue 195 of September 2017 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X51952 , X51953, X51954, X51955 Genomic DNA Translation: CAA36214.1 U28480 mRNA Translation: AAA85271.1 AC108019 Genomic DNA Translation: AAY41026.1 BC069556 mRNA Translation: AAH69556.1 BC098168 mRNA Translation: AAH98168.1 BC098258 mRNA Translation: AAH98258.1 |
CCDSi | CCDS3753.1 |
PIRi | G01858 |
RefSeqi | NP_068605.1, NM_021833.4 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 113197, 3 interactors |
IntActi | P25874, 1 interactor |
STRINGi | 9606.ENSP00000262999 |
Protein family/group databases
TCDBi | 2.A.29.3.2, the mitochondrial carrier (mc) family |
PTM databases
iPTMneti | P25874 |
PhosphoSitePlusi | P25874 |
Polymorphism and mutation databases
BioMutai | UCP1 |
DMDMi | 71153184 |
Proteomic databases
jPOSTi | P25874 |
MassIVEi | P25874 |
PaxDbi | P25874 |
PeptideAtlasi | P25874 |
PRIDEi | P25874 |
ProteomicsDBi | 54299 |
Protocols and materials databases
Antibodypediai | 16250, 433 antibodies |
Genome annotation databases
Ensembli | ENST00000262999; ENSP00000262999; ENSG00000109424 |
GeneIDi | 7350 |
KEGGi | hsa:7350 |
UCSCi | uc011chj.3, human |
Organism-specific databases
CTDi | 7350 |
DisGeNETi | 7350 |
EuPathDBi | HostDB:ENSG00000109424.3 |
GeneCardsi | UCP1 |
HGNCi | HGNC:12517, UCP1 |
HPAi | ENSG00000109424, Group enriched (adipose tissue, adrenal gland, breast, heart muscle) |
MIMi | 113730, gene |
neXtProti | NX_P25874 |
OpenTargetsi | ENSG00000109424 |
PharmGKBi | PA37164 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0753, Eukaryota |
GeneTreei | ENSGT00940000160382 |
HOGENOMi | CLU_015166_14_2_1 |
InParanoidi | P25874 |
OMAi | NCAMKMF |
OrthoDBi | 984118at2759 |
PhylomeDBi | P25874 |
TreeFami | TF323211 |
Enzyme and pathway databases
PathwayCommonsi | P25874 |
Reactomei | R-HSA-167826, The fatty acid cycling model R-HSA-167827, The proton buffering model |
SIGNORi | P25874 |
Miscellaneous databases
BioGRID-ORCSi | 7350, 2 hits in 844 CRISPR screens |
GeneWikii | Thermogenin |
GenomeRNAii | 7350 |
Pharosi | P25874, Tbio |
PROi | PR:P25874 |
RNActi | P25874, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000109424, Expressed in parietal pleura and 48 other tissues |
Genevisiblei | P25874, HS |
Family and domain databases
Gene3Di | 1.50.40.10, 1 hit |
InterProi | View protein in InterPro IPR002030, Mit_uncoupling_UCP-like IPR018108, Mitochondrial_sb/sol_carrier IPR023395, Mt_carrier_dom_sf IPR040011, UCP1 |
PANTHERi | PTHR45618:SF19, PTHR45618:SF19, 1 hit |
Pfami | View protein in Pfam PF00153, Mito_carr, 3 hits |
PRINTSi | PR00784, MTUNCOUPLING |
SUPFAMi | SSF103506, SSF103506, 1 hit |
PROSITEi | View protein in PROSITE PS50920, SOLCAR, 3 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UCP1_HUMAN | |
Accessioni | P25874Primary (citable) accession number: P25874 Secondary accession number(s): Q13218, Q4KMZ3, Q68G66 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 1992 |
Last sequence update: | July 19, 2005 | |
Last modified: | December 2, 2020 | |
This is version 175 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations