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Protein

Mitochondrial brown fat uncoupling protein 1

Gene

UCP1

Organism
Homo sapiens (Human)
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 (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

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. Activated by noradrenaline and reactive oxygen species.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109424-MONOMER.
ReactomeiR-HSA-167826. The fatty acid cycling model.
R-HSA-167827. The proton buffering model.
SIGNORiP25874.

Protein family/group databases

TCDBi2.A.29.3.2. the mitochondrial carrier (mc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial brown fat uncoupling protein 1Curated
Short name:
UCP 1Curated
Alternative name(s):
Solute carrier family 25 member 71 Publication
ThermogeninBy similarity
Gene namesi
Name:UCP1Imported
Synonyms:SLC25A71 Publication, UCP1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:12517. UCP1.

Subcellular locationi

  • Mitochondrion inner membrane By similarity; Multi-pass membrane protein By similarity

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 inner membrane Source: UniProtKB
  • mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Keywords - Diseasei

Diabetes mellitus, Obesity

Organism-specific databases

DisGeNETi7350.
MalaCardsiUCP1.
OpenTargetsiENSG00000109424.
PharmGKBiPA37164.

Polymorphism and mutation databases

BioMutaiUCP1.
DMDMi71153184.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000906572 – 307Mitochondrial brown fat uncoupling protein 1Add BLAST306

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei254Cysteine sulfenic acid (-SOH)By similarity1

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

Oxidation

Proteomic databases

PaxDbiP25874.
PeptideAtlasiP25874.
PRIDEiP25874.

PTM databases

iPTMnetiP25874.
PhosphoSitePlusiP25874.

Expressioni

Tissue specificityi

Brown adipose tissue.1 Publication

Gene expression databases

BgeeiENSG00000109424.
CleanExiHS_UCP1.
GenevisibleiP25874. HS.

Organism-specific databases

HPAiCAB037199.

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 Publication

Protein-protein interaction databases

BioGridi113197. 3 interactors.
STRINGi9606.ENSP00000262999.

Structurei

3D structure databases

ProteinModelPortaliP25874.
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.
InParanoidiP25874.
KOiK08769.
OMAiKMFTNEG.
OrthoDBiEOG091G0BQ7.
PhylomeDBiP25874.
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.

P25874-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:307
Mass (Da):33,005
Last modified:July 19, 2005 - v3
Checksum:iBCC99AB27171FC67
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21G → P in CAA36214 (PubMed:2380264).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02284064A → T Polymorphism; associated with an increased waist-to-hip ratio. 1 PublicationCorresponds to variant rs45539933dbSNPEnsembl.1
Natural variantiVAR_022841229M → L Polymorphism; associated with susceptibility to type II diabetes mellitus. 1 PublicationCorresponds to variant rs2270565dbSNPEnsembl.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.
CCDSiCCDS3753.1.
PIRiG01858.
RefSeqiNP_068605.1. NM_021833.4.
UniGeneiHs.249211.

Genome annotation databases

EnsembliENST00000262999; ENSP00000262999; ENSG00000109424.
GeneIDi7350.
KEGGihsa:7350.
UCSCiuc011chj.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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.
CCDSiCCDS3753.1.
PIRiG01858.
RefSeqiNP_068605.1. NM_021833.4.
UniGeneiHs.249211.

3D structure databases

ProteinModelPortaliP25874.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113197. 3 interactors.
STRINGi9606.ENSP00000262999.

Protein family/group databases

TCDBi2.A.29.3.2. the mitochondrial carrier (mc) family.

PTM databases

iPTMnetiP25874.
PhosphoSitePlusiP25874.

Polymorphism and mutation databases

BioMutaiUCP1.
DMDMi71153184.

Proteomic databases

PaxDbiP25874.
PeptideAtlasiP25874.
PRIDEiP25874.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262999; ENSP00000262999; ENSG00000109424.
GeneIDi7350.
KEGGihsa:7350.
UCSCiuc011chj.3. human.

Organism-specific databases

CTDi7350.
DisGeNETi7350.
GeneCardsiUCP1.
HGNCiHGNC:12517. UCP1.
HPAiCAB037199.
MalaCardsiUCP1.
MIMi113730. gene.
neXtProtiNX_P25874.
OpenTargetsiENSG00000109424.
PharmGKBiPA37164.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0753. Eukaryota.
ENOG410XRV1. LUCA.
GeneTreeiENSGT00760000119170.
HOGENOMiHOG000165140.
HOVERGENiHBG009528.
InParanoidiP25874.
KOiK08769.
OMAiKMFTNEG.
OrthoDBiEOG091G0BQ7.
PhylomeDBiP25874.
TreeFamiTF323211.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109424-MONOMER.
ReactomeiR-HSA-167826. The fatty acid cycling model.
R-HSA-167827. The proton buffering model.
SIGNORiP25874.

Miscellaneous databases

GeneWikiiThermogenin.
GenomeRNAii7350.
PROiP25874.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109424.
CleanExiHS_UCP1.
GenevisibleiP25874. HS.

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_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 149 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.