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Protein

Mitochondrial uncoupling protein 2

Gene

UCP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation from ATP synthesis. As a result, energy is dissipated in the form of heat.

GO - Biological processi

  1. aging Source: Ensembl
  2. cellular metabolic process Source: Reactome
  3. cellular response to amino acid starvation Source: Ensembl
  4. cellular response to glucose stimulus Source: Ensembl
  5. cellular response to insulin stimulus Source: Ensembl
  6. female pregnancy Source: Ensembl
  7. liver regeneration Source: Ensembl
  8. mitochondrial transport Source: Ensembl
  9. negative regulation of apoptotic process Source: Ensembl
  10. negative regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  11. positive regulation of cell death Source: Ensembl
  12. proton transport Source: Reactome
  13. regulation of mitochondrial membrane potential Source: Ensembl
  14. respiratory electron transport chain Source: Reactome
  15. response to fatty acid Source: Ensembl
  16. response to hypoxia Source: CACAO
  17. response to superoxide Source: Ensembl
  18. small molecule metabolic process Source: Reactome
  19. transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiREACT_6196. The proton buffering model.
REACT_6258. The fatty acid cycling model.

Protein family/group databases

TCDBi2.A.29.3.4. the mitochondrial carrier (mc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial uncoupling protein 2
Short name:
UCP 2
Alternative name(s):
Solute carrier family 25 member 8
UCPH
Gene namesi
Name:UCP2
Synonyms:SLC25A8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:12518. UCP2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1010Mitochondrial matrixSequence Analysis
Transmembranei11 – 3222Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini33 – 7745Mitochondrial intermembraneSequence AnalysisAdd
BLAST
Transmembranei78 – 10023Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini101 – 11919Mitochondrial matrixSequence AnalysisAdd
BLAST
Transmembranei120 – 13617Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini137 – 18044Mitochondrial intermembraneSequence AnalysisAdd
BLAST
Transmembranei181 – 19717Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini198 – 21417Mitochondrial matrixSequence AnalysisAdd
BLAST
Transmembranei215 – 23420Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini235 – 26834Mitochondrial intermembraneSequence AnalysisAdd
BLAST
Transmembranei269 – 29123Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini292 – 30918Mitochondrial matrixSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. mitochondrial inner membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Organism-specific databases

MIMi607447. phenotype.
Orphaneti276556. Hyperinsulinism due to UCP2 deficiency.
PharmGKBiPA37165.

Polymorphism and mutation databases

BioMutaiUCP2.
DMDMi2497981.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 309309Mitochondrial uncoupling protein 2PRO_0000090664Add
BLAST

Proteomic databases

PaxDbiP55851.
PRIDEiP55851.

PTM databases

PhosphoSiteiP55851.

Expressioni

Tissue specificityi

Widely expressed in adult human tissues, including tissues rich in macrophages. Most expressed in white adipose tissue and skeletal muscle.

Gene expression databases

BgeeiP55851.
CleanExiHS_UCP2.
ExpressionAtlasiP55851. baseline and differential.
GenevestigatoriP55851.

Organism-specific databases

HPAiCAB025583.

Interactioni

Subunit structurei

Acts as a dimer forming a proton channel.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP10-7P604093EBI-2842077,EBI-10172290

Protein-protein interaction databases

BioGridi113198. 18 interactions.
IntActiP55851. 2 interactions.
STRINGi9606.ENSP00000312029.

Structurei

3D structure databases

ProteinModelPortaliP55851.
SMRiP55851. Positions 14-308.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati11 – 10696Solcar 1Add
BLAST
Repeati114 – 20390Solcar 2Add
BLAST
Repeati212 – 29786Solcar 3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni276 – 29823Purine nucleotide bindingBy similarityAdd
BLAST

Sequence similaritiesi

Contains 3 Solcar repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG300436.
GeneTreeiENSGT00760000119170.
HOGENOMiHOG000165140.
HOVERGENiHBG009528.
InParanoidiP55851.
KOiK15103.
OMAiLLKAHLM.
OrthoDBiEOG793B7Z.
PhylomeDBiP55851.
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.

P55851-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVGFKATDVP PTATVKFLGA GTAACIADLI TFPLDTAKVR LQIQGESQGP
60 70 80 90 100
VRATASAQYR GVMGTILTMV RTEGPRSLYN GLVAGLQRQM SFASVRIGLY
110 120 130 140 150
DSVKQFYTKG SEHASIGSRL LAGSTTGALA VAVAQPTDVV KVRFQAQARA
160 170 180 190 200
GGGRRYQSTV NAYKTIAREE GFRGLWKGTS PNVARNAIVN CAELVTYDLI
210 220 230 240 250
KDALLKANLM TDDLPCHFTS AFGAGFCTTV IASPVDVVKT RYMNSALGQY
260 270 280 290 300
SSAGHCALTM LQKEGPRAFY KGFMPSFLRL GSWNVVMFVT YEQLKRALMA

ACTSREAPF
Length:309
Mass (Da):33,229
Last modified:November 1, 1997 - v1
Checksum:i2E1741391621E3D9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti219 – 2191T → I in AAB48411 (PubMed:9054939).Curated

Polymorphismi

Genetic variations in UCP2 define the body mass index quantitative trait locus 4 (BMIQ4) [MIMi:607447]. A common polymorphism in the promoter of UCP2 has been shown to be associated with a decreased risk of obesity in middle-aged individuals.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551A → V.4 Publications
Corresponds to variant rs660339 [ dbSNP | Ensembl ].
VAR_016129
Natural varianti76 – 761R → Q.1 Publication
Corresponds to variant rs45541732 [ dbSNP | Ensembl ].
VAR_023998
Natural varianti154 – 1541R → Q.1 Publication
Corresponds to variant rs45486692 [ dbSNP | Ensembl ].
VAR_023999
Natural varianti268 – 2681A → G.1 Publication
Corresponds to variant rs45490393 [ dbSNP | Ensembl ].
VAR_024000
Natural varianti282 – 2821S → C.1 Publication
Corresponds to variant rs45596837 [ dbSNP | Ensembl ].
VAR_024001

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82819 mRNA. Translation: AAC51336.1.
U76367 mRNA. Translation: AAB48411.1.
U94592 mRNA. Translation: AAB53091.1.
AJ223477, AJ223478, AJ223479 Genomic DNA. Translation: CAA11402.1.
AF019409 Genomic DNA. Translation: AAC39690.1.
AF096289 Genomic DNA. Translation: AAD21151.1.
AK222540 mRNA. Translation: BAD96260.1.
AK222557 mRNA. Translation: BAD96277.1.
DQ087219 Genomic DNA. Translation: AAY68217.1.
BC011737 mRNA. Translation: AAH11737.1.
CCDSiCCDS8228.1.
RefSeqiNP_003346.2. NM_003355.2.
UniGeneiHs.80658.

Genome annotation databases

EnsembliENST00000310473; ENSP00000312029; ENSG00000175567.
GeneIDi7351.
KEGGihsa:7351.
UCSCiuc001oup.1. human.

Polymorphism and mutation databases

BioMutaiUCP2.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82819 mRNA. Translation: AAC51336.1.
U76367 mRNA. Translation: AAB48411.1.
U94592 mRNA. Translation: AAB53091.1.
AJ223477, AJ223478, AJ223479 Genomic DNA. Translation: CAA11402.1.
AF019409 Genomic DNA. Translation: AAC39690.1.
AF096289 Genomic DNA. Translation: AAD21151.1.
AK222540 mRNA. Translation: BAD96260.1.
AK222557 mRNA. Translation: BAD96277.1.
DQ087219 Genomic DNA. Translation: AAY68217.1.
BC011737 mRNA. Translation: AAH11737.1.
CCDSiCCDS8228.1.
RefSeqiNP_003346.2. NM_003355.2.
UniGeneiHs.80658.

3D structure databases

ProteinModelPortaliP55851.
SMRiP55851. Positions 14-308.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113198. 18 interactions.
IntActiP55851. 2 interactions.
STRINGi9606.ENSP00000312029.

Protein family/group databases

TCDBi2.A.29.3.4. the mitochondrial carrier (mc) family.

PTM databases

PhosphoSiteiP55851.

Polymorphism and mutation databases

BioMutaiUCP2.
DMDMi2497981.

Proteomic databases

PaxDbiP55851.
PRIDEiP55851.

Protocols and materials databases

DNASUi7351.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310473; ENSP00000312029; ENSG00000175567.
GeneIDi7351.
KEGGihsa:7351.
UCSCiuc001oup.1. human.

Organism-specific databases

CTDi7351.
GeneCardsiGC11M073685.
GeneReviewsiUCP2.
H-InvDBHIX0095887.
HGNCiHGNC:12518. UCP2.
HPAiCAB025583.
MIMi601693. gene.
607447. phenotype.
neXtProtiNX_P55851.
Orphaneti276556. Hyperinsulinism due to UCP2 deficiency.
PharmGKBiPA37165.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG300436.
GeneTreeiENSGT00760000119170.
HOGENOMiHOG000165140.
HOVERGENiHBG009528.
InParanoidiP55851.
KOiK15103.
OMAiLLKAHLM.
OrthoDBiEOG793B7Z.
PhylomeDBiP55851.
TreeFamiTF323211.

Enzyme and pathway databases

ReactomeiREACT_6196. The proton buffering model.
REACT_6258. The fatty acid cycling model.

Miscellaneous databases

ChiTaRSiUCP2. human.
GeneWikiiUCP2.
GenomeRNAii7351.
NextBioi28778.
PROiP55851.
SOURCEiSearch...

Gene expression databases

BgeeiP55851.
CleanExiHS_UCP2.
ExpressionAtlasiP55851. baseline and differential.
GenevestigatoriP55851.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression."
    Boss O., Samec S., Paoloni-Giacobino A., Dulloo A., Seydoux J., Rossier C., Muzzin P., Giacobino J.-P.
    FEBS Lett. 408:39-42(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung and Skeletal muscle.
  3. "Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis."
    Gimeno R.E., Dembski M., Weng X., Deng N., Shyjan A.W., Gimeno C.J., Iris F., Ellis S.J., Woolf E.A., Tartaglia L.A.
    Diabetes 46:900-906(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-55.
    Tissue: Spleen.
  4. Klannemark M., Orho M., Groop L.
    Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-55.
  5. "Structure and organization of the human uncoupling protein 2 gene and identification of a common biallelic variant in Caucasian and African-American subjects."
    Argyropoulos G., Brown A.M., Peterson R., Likes C.E., Watson D.K., Garvey W.T.
    Diabetes 47:685-687(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "Functional organization of the human uncoupling protein-2 gene, and juxtaposition to the uncoupling protein-3 gene."
    Pecqueur C., Cassard-Doulcier A.M., Raimbault S., Miroux B., Fleury C., Gelly C., Bouillaud F., Ricquier D.
    Biochem. Biophys. Res. Commun. 255:40-46(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  7. Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
    Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-55.
    Tissue: Adipose tissue.
  8. NIEHS SNPs program
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-55; GLN-76; GLN-154; GLY-268 AND CYS-282.
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: B-cell.
  10. "A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans."
    Esterbauer H., Schneitler C., Oberkofler H., Ebenbichler C., Paulweber B., Sandhofer F., Ladurner G., Hell E., Strosberg A.D., Patsch J.R., Krempler F., Patsch W.
    Nat. Genet. 28:178-183(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN BMIQ4 AND SUSCEPTIBILITY TO OBESITY.

Entry informationi

Entry nameiUCP2_HUMAN
AccessioniPrimary (citable) accession number: P55851
Secondary accession number(s): Q4PJH8, Q53HM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 29, 2015
This is version 134 of the entry and version 1 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 11
    Human chromosome 11: 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

External Data

Dasty 3

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 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.