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Protein

Mitochondrial brown fat uncoupling protein 1

Gene

UCP1

Organism
Homo sapiens (Human)
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 (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

GO - Biological processi

Keywordsi

Molecular functionIon channel
Biological processIon transport, Transport

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000109424.3
HGNCiHGNC:12517 UCP1
MIMi113730 gene
neXtProtiNX_P25874

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

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
ChainiPRO_00000906571 – 307Mitochondrial brown fat uncoupling protein 1Add BLAST307

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
ProteomicsDBi54299

PTM databases

iPTMnetiP25874
PhosphoSitePlusiP25874

Expressioni

Tissue specificityi

Brown adipose tissue.1 Publication

Gene expression databases

BgeeiENSG00000109424 Expressed in 26 organ(s), highest expression level in parietal pleura
CleanExiHS_UCP1
GenevisibleiP25874 HS

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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

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 dbSNP:rs45539933Ensembl.1
Natural variantiVAR_022841229M → 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
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

Similar 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
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
ProteomicsDBi54299

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7350
DisGeNETi7350
EuPathDBiHostDB:ENSG00000109424.3
GeneCardsiUCP1
HGNCiHGNC:12517 UCP1
MalaCardsiUCP1
MIMi113730 gene
neXtProtiNX_P25874
OpenTargetsiENSG00000109424
PharmGKBiPA37164
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-167826 The fatty acid cycling model
R-HSA-167827 The proton buffering model
SIGNORiP25874

Miscellaneous databases

GeneWikiiThermogenin
GenomeRNAii7350
PROiPR:P25874
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109424 Expressed in 26 organ(s), highest expression level in parietal pleura
CleanExiHS_UCP1
GenevisibleiP25874 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiUCP1_HUMAN
AccessioniPrimary (citable) accession number: P25874
Secondary accession number(s): Q13218, Q4KMZ3, Q68G66
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: July 19, 2005
Last modified: September 12, 2018
This is version 160 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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