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P55851 (UCP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitochondrial uncoupling protein 2

Short name=UCP 2
Alternative name(s):
Solute carrier family 25 member 8
UCPH
Gene names
Name:UCP2
Synonyms:SLC25A8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length309 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Acts as a dimer forming a proton channel By similarity.

Subcellular location

Mitochondrion inner membrane; Multi-pass membrane protein.

Tissue specificity

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

Polymorphism

Genetic variations in UCP2 define the body mass index quantitative trait locus 4 (BMIQ4) [MIM: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.

Sequence similarities

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

Contains 3 Solcar repeats.

Ontologies

Keywords
   Biological processTransport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Transmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

cellular metabolic process

Traceable author statement. Source: Reactome

cellular response to amino acid starvation

Inferred from electronic annotation. Source: Ensembl

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

liver regeneration

Inferred from electronic annotation. Source: Ensembl

mitochondrial transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell death

Inferred from electronic annotation. Source: Ensembl

proton transport

Traceable author statement. Source: Reactome

respiratory electron transport chain

Traceable author statement. Source: Reactome

response to fatty acid

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to superoxide

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

transport

Non-traceable author statement PubMed 9196039. Source: ProtInc

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial inner membrane

Traceable author statement. Source: Reactome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 309309Mitochondrial uncoupling protein 2
PRO_0000090664

Regions

Topological domain1 – 1010Mitochondrial matrix Potential
Transmembrane11 – 3222Helical; Name=1; Potential
Topological domain33 – 7745Mitochondrial intermembrane Potential
Transmembrane78 – 10023Helical; Name=2; Potential
Topological domain101 – 11919Mitochondrial matrix Potential
Transmembrane120 – 13617Helical; Name=3; Potential
Topological domain137 – 18044Mitochondrial intermembrane Potential
Transmembrane181 – 19717Helical; Name=4; Potential
Topological domain198 – 21417Mitochondrial matrix Potential
Transmembrane215 – 23420Helical; Name=5; Potential
Topological domain235 – 26834Mitochondrial intermembrane Potential
Transmembrane269 – 29123Helical; Name=6; Potential
Topological domain292 – 30918Mitochondrial matrix Potential
Repeat11 – 10696Solcar 1
Repeat114 – 20390Solcar 2
Repeat212 – 29786Solcar 3
Region276 – 29823Purine nucleotide binding By similarity

Natural variations

Natural variant551A → V. Ref.3 Ref.4 Ref.7 Ref.8
Corresponds to variant rs660339 [ dbSNP | Ensembl ].
VAR_016129
Natural variant761R → Q. Ref.8
Corresponds to variant rs45541732 [ dbSNP | Ensembl ].
VAR_023998
Natural variant1541R → Q. Ref.8
Corresponds to variant rs45486692 [ dbSNP | Ensembl ].
VAR_023999
Natural variant2681A → G. Ref.8
Corresponds to variant rs45490393 [ dbSNP | Ensembl ].
VAR_024000
Natural variant2821S → C. Ref.8
Corresponds to variant rs45596837 [ dbSNP | Ensembl ].
VAR_024001

Experimental info

Sequence conflict2191T → I in AAB48411. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P55851 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 2E1741391621E3D9

FASTA30933,229
        10         20         30         40         50         60 
MVGFKATDVP PTATVKFLGA GTAACIADLI TFPLDTAKVR LQIQGESQGP VRATASAQYR 

        70         80         90        100        110        120 
GVMGTILTMV RTEGPRSLYN GLVAGLQRQM SFASVRIGLY DSVKQFYTKG SEHASIGSRL 

       130        140        150        160        170        180 
LAGSTTGALA VAVAQPTDVV KVRFQAQARA GGGRRYQSTV NAYKTIAREE GFRGLWKGTS 

       190        200        210        220        230        240 
PNVARNAIVN CAELVTYDLI KDALLKANLM TDDLPCHFTS AFGAGFCTTV IASPVDVVKT 

       250        260        270        280        290        300 
RYMNSALGQY SSAGHCALTM LQKEGPRAFY KGFMPSFLRL GSWNVVMFVT YEQLKRALMA 


ACTSREAPF 

« Hide

References

« Hide 'large scale' references
[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]"Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia."
Fleury C., Neverova M., Collins S., Raimbault S., Champigny O., Levi-Meyrueis C., Bouillaud F., Seldin M.F., Surwit R.S., Ricquier D., Warden C.H.
Nat. Genet. 15:269-272(1997) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_003346.2. NM_003355.2.
UniGeneHs.80658.

3D structure databases

ProteinModelPortalP55851.
SMRP55851. Positions 14-308.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113198. 5 interactions.
IntActP55851. 1 interaction.
STRING9606.ENSP00000312029.

Protein family/group databases

TCDB2.A.29.3.4. the mitochondrial carrier (mc) family.

PTM databases

PhosphoSiteP55851.

Polymorphism databases

DMDM2497981.

Proteomic databases

PaxDbP55851.
PRIDEP55851.

Protocols and materials databases

DNASU7351.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000310473; ENSP00000312029; ENSG00000175567.
GeneID7351.
KEGGhsa:7351.
UCSCuc001oup.1. human.

Organism-specific databases

CTD7351.
GeneCardsGC11M073685.
H-InvDBHIX0095887.
HGNCHGNC:12518. UCP2.
HPACAB025583.
MIM601693. gene.
607447. phenotype.
neXtProtNX_P55851.
Orphanet276556. Hyperinsulinism due to UCP2 deficiency.
PharmGKBPA37165.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300436.
HOGENOMHOG000165140.
HOVERGENHBG009528.
InParanoidP55851.
KOK15103.
OMASPNIARN.
OrthoDBEOG793B7Z.
PhylomeDBP55851.
TreeFamTF323211.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP55851.
BgeeP55851.
CleanExHS_UCP2.
GenevestigatorP55851.

Family and domain databases

Gene3D1.50.40.10. 1 hit.
InterProIPR002030. Mit_uncoupling.
IPR018108. Mitochondrial_sb/sol_carrier.
IPR023395. Mt_carrier_dom.
[Graphical view]
PfamPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSPR00784. MTUNCOUPLING.
SUPFAMSSF103506. SSF103506. 1 hit.
PROSITEPS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUCP2. human.
GeneWikiUCP2.
GenomeRNAi7351.
NextBio28778.
PROP55851.
SOURCESearch...

Entry information

Entry nameUCP2_HUMAN
AccessionPrimary (citable) accession number: P55851
Secondary accession number(s): Q4PJH8, Q53HM3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM