UCP1

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

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
Inferred from direct assayⁱ
- 24196960

View the complete GO annotation on QuickGO ...

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: Ensembl
mitochondrial transmembrane transport Source: UniProtKB
mitochondrial transport Source: GO_Central
proton transmembrane transport
Source: UniProtKB
Inferred from direct assayⁱ
- 24196960
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

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Ion channel
Biological process	Ion transport, Transport

Enzyme and pathway databases

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

TCDBⁱ

2.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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 4

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000109424.3
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:12517 UCP1
MIMⁱ	113730 gene
neXtProtⁱ	NX_P25874

Topology

Feature key	Position(s)	DescriptionActions	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 membrane

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

Diabetes mellitus, Obesity

Organism-specific databases

DisGeNET More...DisGeNETⁱ	7350
MalaCards human disease database More...MalaCardsⁱ	UCP1
Open Targets More...OpenTargetsⁱ	ENSG00000109424
PharmGKBⁱ	PA37164

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

Oxidation

Proteomic databases

PaxDbⁱ	P25874
PeptideAtlas More...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
CleanExⁱ	HS_UCP1
Genevisibleⁱ	P25874 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

BioGridⁱ	113197, 3 interactors
STRINGⁱ	9606.ENSP00000262999

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P25874
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Repeatⁱ	11 – 102	Solcar 1Add BLAST	92
Repeatⁱ	111 – 201	Solcar 2Add BLAST	91
Repeatⁱ	210 – 295	Solcar 3Add BLAST	86

Sequence similaritiesⁱ

Belongs to the mitochondrial carrier (TC 2.A.29) family. [View classification]Curated

Keywords - Domainⁱ

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG0753 Eukaryota ENOG410XRV1 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119170
HOGENOMⁱ	HOG000165140
HOVERGENⁱ	HBG009528
InParanoidⁱ	P25874
KEGG Orthology (KO) More...KOⁱ	K08769
OMAⁱ	RYTGTYN
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0BQ7
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
Pfam protein domain database More...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

Sequenceⁱ

Sequence statusⁱ: Complete.

P25874-1 [UniParc]FASTA Add 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 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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS3753.1
PIRⁱ	G01858
NCBI Reference Sequences More...RefSeqⁱ	NP_068605.1, NM_021833.4
UniGeneⁱ	Hs.249211

Genome annotation databases

Ensemblⁱ	ENST00000262999; ENSP00000262999; ENSG00000109424
GeneIDⁱ	7350
KEGGⁱ	hsa:7350
UCSC genome browser More...UCSCⁱ	uc011chj.3 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length
P25874	UCP1 isoform 1		PANTR		307
Uncoupling protein 1		PANPA		307
Uncoupling protein 1		MACMU		307
UCP1 isoform 1		PONAB		307
Uncoupling protein 1		SAIBB		307
+20

Protein	Similar proteins		Species	Score	Length
P25874	Mitochondrial brown fat uncoupling protein 1		MOUSE		307
UPI0004ED0ADD		NANGA		307
Mitochondrial brown fat uncoupling protein 1		MESAU		307
Mitochondrial brown fat uncoupling protein 1		PHOSU		307
UPI0001547B20		MUSCR		307
+60

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS3753.1
PIRⁱ	G01858
NCBI Reference Sequences More...RefSeqⁱ	NP_068605.1, NM_021833.4
UniGeneⁱ	Hs.249211

3D structure databases

ProteinModelPortalⁱ	P25874
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	113197, 3 interactors
STRINGⁱ	9606.ENSP00000262999

Protein family/group databases

TCDBⁱ	2.A.29.3.2 the mitochondrial carrier (mc) family

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

PaxDbⁱ	P25874
PeptideAtlas More...PeptideAtlasⁱ	P25874
PRIDEⁱ	P25874
ProteomicsDBⁱ	54299

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000262999; ENSP00000262999; ENSG00000109424
GeneIDⁱ	7350
KEGGⁱ	hsa:7350
UCSC genome browser More...UCSCⁱ	uc011chj.3 human

Organism-specific databases

CTDⁱ	7350
DisGeNET More...DisGeNETⁱ	7350
EuPathDBⁱ	HostDB:ENSG00000109424.3
GeneCardsⁱ	UCP1
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:12517 UCP1
MalaCards human disease database More...MalaCardsⁱ	UCP1
MIMⁱ	113730 gene
neXtProtⁱ	NX_P25874
Open Targets More...OpenTargetsⁱ	ENSG00000109424
PharmGKBⁱ	PA37164
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0753 Eukaryota ENOG410XRV1 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119170
HOGENOMⁱ	HOG000165140
HOVERGENⁱ	HBG009528
InParanoidⁱ	P25874
KEGG Orthology (KO) More...KOⁱ	K08769
OMAⁱ	RYTGTYN
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0BQ7
PhylomeDBⁱ	P25874
TreeFamⁱ	TF323211

Enzyme and pathway databases

Reactomeⁱ	R-HSA-167826 The fatty acid cycling model R-HSA-167827 The proton buffering model
SIGNORⁱ	P25874

Miscellaneous databases

GeneWikiⁱ	Thermogenin
GenomeRNAiⁱ	7350
Protein Ontology More...PROⁱ	PR:P25874
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000109424
CleanExⁱ	HS_UCP1
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
Pfam protein domain database More...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...

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:	June 20, 2018
	This is version 159 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

Complete proteome, Reference proteome

Documents

Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
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
Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
SIMILARITY comments
Index of protein domains and families

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UniParc

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UniRef

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Supporting data

UniProtKB - P25874 (UCP1_HUMAN)

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Mitochondrial brown fat uncoupling protein 1

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the ‘Function’ section describes an enzyme regulatory mechanism and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/enzyme_regulation' target='_top'>More...</a></p>Enzyme regulationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Mitochondrion

Mitochondrion

Other locations

Topology

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Functionⁱ

Enzyme regulationⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ