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Protein

Mitochondrial brown fat uncoupling protein 1

Gene

Ucp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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
  • mitochondrial transport Source: GO_Central
  • proton transmembrane transport Source: UniProtKB
  • regulation of reactive oxygen species biosynthetic process Source: UniProtKB
  • regulation of transcription by RNA polymerase II Source: MGI
  • response to cold Source: GO_Central
  • response to nutrient levels Source: UniProtKB
  • response to temperature stimulus Source: UniProtKB

Keywordsi

Molecular functionIon channel
Biological processIon 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:98894 Ucp1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 10Mitochondrial intermembraneBy similarity10
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

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
ChainiPRO_00000906591 – 307Mitochondrial brown fat uncoupling protein 1Add BLAST307

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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.50.40.10, 1 hit
InterProiView protein in InterPro
IPR002030 Mit_uncoupling_UCP-like
IPR018108 Mitochondrial_sb/sol_carrier
IPR023395 Mt_carrier_dom_sf
PfamiView protein in Pfam
PF00153 Mito_carr, 3 hits
PRINTSiPR00784 MTUNCOUPLING
SUPFAMiSSF103506 SSF103506, 1 hit
PROSITEiView protein in PROSITE
PS50920 SOLCAR, 3 hits

Sequencei

Sequence statusi: Complete.

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

Similar proteinsi

Entry informationi

Entry nameiUCP1_MOUSE
AccessioniPrimary (citable) accession number: P12242
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 153 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health