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Protein

Mitochondrial brown fat uncoupling protein 1

Gene

Ucp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates to non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance (PubMed:9139827, PubMed:19187776, PubMed:23063128, PubMed:27027295). Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. 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 (PubMed:23063128). Regulates the production of reactive oxygen species/ROS by mitochondria (PubMed:20416274, PubMed:20466728).6 Publications

Enzyme 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 (PubMed:23063128). Activated by noradrenaline and reactive oxygen species (PubMed:27027295).2 Publications

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: MGI

GO - Biological processi

  • adaptive thermogenesis Source: UniProtKB
  • brown fat cell differentiation Source: HGNC
  • 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: UniProtKB
  • mitochondrial transmembrane transport Source: UniProtKB
  • proton transport Source: UniProtKB
  • regulation of reactive oxygen species biosynthetic process Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to nutrient levels Source: UniProtKB
  • response to temperature stimulus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-MMU-167826. The fatty acid cycling model.
R-MMU-167827. The proton buffering model.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial brown fat uncoupling protein 1Curated
Short name:
UCP 1Curated
Alternative name(s):
Solute carrier family 25 member 7By similarity
ThermogeninBy similarity
Gene namesi
Name:Ucp1Imported
Synonyms:Slc25a7By similarity, Ucp1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:98894. Ucp1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 10Mitochondrial intermembraneBy similarity9
Transmembranei11 – 32Helical; Name=1Sequence analysisAdd BLAST22
Topological domaini33 – 73Mitochondrial matrixBy similarityAdd BLAST41
Transmembranei74 – 96Helical; Name=2Sequence analysisAdd BLAST23
Topological domaini97 – 116Mitochondrial intermembraneBy similarityAdd BLAST20
Transmembranei117 – 133Helical; Name=3Sequence analysisAdd BLAST17
Topological domaini134 – 178Mitochondrial matrixBy similarityAdd BLAST45
Transmembranei179 – 195Helical; Name=4Sequence analysisAdd BLAST17
Topological domaini196 – 212Mitochondrial intermembraneBy similarityAdd BLAST17
Transmembranei213 – 232Helical; Name=5Sequence analysisAdd BLAST20
Topological domaini233 – 266Mitochondrial matrixBy similarityAdd BLAST34
Transmembranei267 – 289Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini290 – 307Mitochondrial intermembraneBy similarityAdd BLAST18

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial envelope Source: MGI
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Disruption phenotypei

Mice lacking Ucp1 display an absence of adaptive thermogenesis in response to cold. Compared to wild-type mice, they are sensitive to cold and consume less oxygen upon treatment with beta-3-adrenergic-receptor agonists that normally activate thermogenesis (PubMed:9139827, PubMed:19187776). They also display impaired adaptive thermogenesis in response to diet variation (PubMed:19187776). If they display lipid accumulation in adipocytes of brown adipose tissues, no overt obesity is observed when mice are housed under classical conditions, i.e. 18 to 20 degrees Celsius (PubMed:9139827). However, when mice are housed at thermoneutrality, i.e. at 30 degrees Celsius, obesity is clearly observed and exacerbated by high fat diet (PubMed:19187776). The brown adipose tissue of mice lacking Ucp1 produce higher levels of reactive oxygen species (PubMed:20416274, PubMed:20466728).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25C → A: No effect on UCP1 activity in thermogenic respiration. 1 Publication1
Mutagenesisi189C → A: No effect on UCP1 activity in thermogenic respiration. 1 Publication1
Mutagenesisi214C → A: No effect on UCP1 activity in thermogenic respiration. 1 Publication1
Mutagenesisi225C → A: Decreased UCP1 activity in thermogenic respiration. 1 Publication1
Mutagenesisi254C → A: Decreased sensitivity to activation by noradrenaline in thermogenic respiration. 1 Publication1
Mutagenesisi288C → A: No effect on UCP1 activity in thermogenic respiration. 1 Publication1
Mutagenesisi305C → A: No effect on UCP1 activity in thermogenic respiration. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000906592 – 307Mitochondrial brown fat uncoupling protein 1Add BLAST306

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei254Cysteine sulfenic acid (-SOH)1 Publication1

Post-translational modificationi

Sulfenylation at Cys-254 is increased upon cold exposure. It increases the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects.1 Publication
May undergo ubiquitin-mediated proteasomal degradation.By similarity

Keywords - PTMi

Oxidation

Proteomic databases

MaxQBiP12242.
PaxDbiP12242.
PRIDEiP12242.

PTM databases

iPTMnetiP12242.
PhosphoSitePlusiP12242.

Expressioni

Tissue specificityi

Expressed in brown adipose tissue.1 Publication

Inductioni

Up-regulated in response to cold in brown adipose tissue where it may regulate non-shivering thermogenesis (at protein level) (PubMed:20466728, PubMed:25578880). Up-regulated by high-fat diet (at protein level) (PubMed:19187776).3 Publications

Gene expression databases

BgeeiENSMUSG00000031710.
GenevisibleiP12242. MM.

Interactioni

Subunit structurei

Most probably functions as a monomer. Binds one purine nucleotide per monomer. However, has also been suggested to function as a homodimer or a homotetramer. Tightly associates with cardiolipin in the mitochondrion inner membrane; may stabilize and regulate its activity.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034146.

Structurei

3D structure databases

ProteinModelPortaliP12242.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati11 – 102Solcar 1Add BLAST92
Repeati111 – 201Solcar 2Add BLAST91
Repeati210 – 295Solcar 3Add BLAST86

Sequence similaritiesi

Contains 3 Solcar repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0753. Eukaryota.
ENOG410XRV1. LUCA.
GeneTreeiENSGT00760000119170.
HOGENOMiHOG000165140.
HOVERGENiHBG009528.
InParanoidiP12242.
KOiK08769.
OMAiQGECQTS.
OrthoDBiEOG091G0BQ7.
PhylomeDBiP12242.
TreeFamiTF323211.

Family and domain databases

Gene3Di1.50.40.10. 1 hit.
InterProiIPR002030. Mit_uncoupling.
IPR018108. Mitochondrial_sb/sol_carrier.
IPR023395. Mt_carrier_dom.
[Graphical view]
PfamiPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSiPR00784. MTUNCOUPLING.
SUPFAMiSSF103506. SSF103506. 1 hit.
PROSITEiPS50920. SOLCAR. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P12242-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVNPTTSEVQ PTMGVKIFSA GVSACLADII TFPLDTAKVR LQIQGEGQAS
60 70 80 90 100
STIRYKGVLG TITTLAKTEG LPKLYSGLPA GIQRQISFAS LRIGLYDSVQ
110 120 130 140 150
EYFSSGRETP ASLGNKISAG LMTGGVAVFI GQPTEVVKVR MQAQSHLHGI
160 170 180 190 200
KPRYTGTYNA YRVIATTESL STLWKGTTPN LMRNVIINCT ELVTYDLMKG
210 220 230 240 250
ALVNNKILAD DVPCHLLSAL VAGFCTTLLA SPVDVVKTRF INSLPGQYPS
260 270 280 290 300
VPSCAMSMYT KEGPTAFFKG FVASFLRLGS WNVIMFVCFE QLKKELMKSR

QTVDCTT
Length:307
Mass (Da):33,248
Last modified:January 23, 2007 - v2
Checksum:i33D107EDF04BD1AF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21247
, M21222, M21244, M21245, M21246 Genomic DNA. Translation: AAA40521.1.
U63419 mRNA. Translation: AAB05870.1.
U63418 Genomic DNA. Translation: AAB07367.1.
BC012701 mRNA. Translation: AAH12701.1.
CCDSiCCDS22449.1.
PIRiA31106.
RefSeqiNP_033489.1. NM_009463.3.
UniGeneiMm.4177.

Genome annotation databases

EnsembliENSMUST00000034146; ENSMUSP00000034146; ENSMUSG00000031710.
GeneIDi22227.
KEGGimmu:22227.
UCSCiuc009mjx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21247
, M21222, M21244, M21245, M21246 Genomic DNA. Translation: AAA40521.1.
U63419 mRNA. Translation: AAB05870.1.
U63418 Genomic DNA. Translation: AAB07367.1.
BC012701 mRNA. Translation: AAH12701.1.
CCDSiCCDS22449.1.
PIRiA31106.
RefSeqiNP_033489.1. NM_009463.3.
UniGeneiMm.4177.

3D structure databases

ProteinModelPortaliP12242.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034146.

PTM databases

iPTMnetiP12242.
PhosphoSitePlusiP12242.

Proteomic databases

MaxQBiP12242.
PaxDbiP12242.
PRIDEiP12242.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034146; ENSMUSP00000034146; ENSMUSG00000031710.
GeneIDi22227.
KEGGimmu:22227.
UCSCiuc009mjx.2. mouse.

Organism-specific databases

CTDi7350.
MGIiMGI:98894. Ucp1.

Phylogenomic databases

eggNOGiKOG0753. Eukaryota.
ENOG410XRV1. LUCA.
GeneTreeiENSGT00760000119170.
HOGENOMiHOG000165140.
HOVERGENiHBG009528.
InParanoidiP12242.
KOiK08769.
OMAiQGECQTS.
OrthoDBiEOG091G0BQ7.
PhylomeDBiP12242.
TreeFamiTF323211.

Enzyme and pathway databases

ReactomeiR-MMU-167826. The fatty acid cycling model.
R-MMU-167827. The proton buffering model.

Miscellaneous databases

ChiTaRSiUcp1. mouse.
PROiP12242.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031710.
GenevisibleiP12242. MM.

Family and domain databases

Gene3Di1.50.40.10. 1 hit.
InterProiIPR002030. Mit_uncoupling.
IPR018108. Mitochondrial_sb/sol_carrier.
IPR023395. Mt_carrier_dom.
[Graphical view]
PfamiPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSiPR00784. MTUNCOUPLING.
SUPFAMiSSF103506. SSF103506. 1 hit.
PROSITEiPS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUCP1_MOUSE
AccessioniPrimary (citable) accession number: P12242
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.