P55851 (UCP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara mitochondrial transport Inferred from electronic annotation. Source: Compara 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: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to superoxide Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 309	309	Mitochondrial uncoupling protein 2		PRO_0000090664
Regions
	Topological domain	1 – 10	10	Mitochondrial matrix Potential
	Transmembrane	11 – 32	22	Helical; Name=1; Potential
	Topological domain	33 – 77	45	Mitochondrial intermembrane Potential
	Transmembrane	78 – 100	23	Helical; Name=2; Potential
	Topological domain	101 – 119	19	Mitochondrial matrix Potential
	Transmembrane	120 – 136	17	Helical; Name=3; Potential
	Topological domain	137 – 180	44	Mitochondrial intermembrane Potential
	Transmembrane	181 – 197	17	Helical; Name=4; Potential
	Topological domain	198 – 214	17	Mitochondrial matrix Potential
	Transmembrane	215 – 234	20	Helical; Name=5; Potential
	Topological domain	235 – 268	34	Mitochondrial intermembrane Potential
	Transmembrane	269 – 291	23	Helical; Name=6; Potential
	Topological domain	292 – 309	18	Mitochondrial matrix Potential
	Repeat	11 – 106	96	Solcar 1
	Repeat	114 – 203	90	Solcar 2
	Repeat	212 – 297	86	Solcar 3
	Region	276 – 298	23	Purine nucleotide binding By similarity
Natural variations
	Natural variant	55	1	A → V. Ref.3 Ref.4 Ref.7 Ref.8 Corresponds to variant rs660339 [ dbSNP | Ensembl ].		VAR_016129
	Natural variant	76	1	R → Q. Ref.8 Corresponds to variant rs45541732 [ dbSNP | Ensembl ].		VAR_023998
	Natural variant	154	1	R → Q. Ref.8 Corresponds to variant rs45486692 [ dbSNP | Ensembl ].		VAR_023999
	Natural variant	268	1	A → G. Ref.8 Corresponds to variant rs45490393 [ dbSNP | Ensembl ].		VAR_024000
	Natural variant	282	1	S → C. Ref.8 Corresponds to variant rs45596837 [ dbSNP | Ensembl ].		VAR_024001
Experimental info
	Sequence conflict	219	1	T → I in AAB48411. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P55851 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 2E1741391621E3D9	FASTA	309	33,229
	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

References

	« Hide 'large scale' referencesShow '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

NIEHS-SNPs

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.
IPI	IPI00026573.
RefSeq	NP_003346.2. NM_003355.2.
UniGene	Hs.80658.
3D structure databases
ProteinModelPortal	P55851.
ModBase	Search...
Protein-protein interaction databases
IntAct	P55851. 1 interaction.
STRING	9606.ENSP00000312029.
Protein family/group databases
TCDB	2.A.29.3.4. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	P55851.
Polymorphism databases
DMDM	2497981.
Proteomic databases
PaxDb	P55851.
PRIDE	P55851.
Protocols and materials databases
DNASU	7351.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310473; ENSP00000312029; ENSG00000175567.
GeneID	7351.
KEGG	hsa:7351.
UCSC	uc001oup.1. human.
Organism-specific databases
CTD	7351.
GeneCards	GC11M073685.
H-InvDB	HIX0095887.
HGNC	HGNC:12518. UCP2.
HPA	CAB025583.
MIM	601693. gene. 607447. phenotype.
neXtProt	NX_P55851.
Orphanet	276556. Hyperinsulinism due to UCP2 deficiency.
PharmGKB	PA37165.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300436.
HOGENOM	HOG000165140.
HOVERGEN	HBG009528.
InParanoid	P55851.
KO	K15103.
OMA	PCSLYNG.
OrthoDB	EOG4V6ZH7.
PhylomeDB	P55851.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P55851.
Bgee	P55851.
CleanEx	HS_UCP2.
Genevestigator	P55851.
GermOnline	ENSG00000175567. Homo sapiens.
Family and domain databases
Gene3D	1.50.40.10. 1 hit.
InterPro	IPR002030. Mit_uncoupling. IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00784. MTUNCOUPLING.
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UCP2. human.
GenomeRNAi	7351.
NextBio	28778.
SOURCE	Search...

Entry information

Entry name

UCP2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.