P55916 (UCP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial uncoupling protein 3
Short name=UCP 3

Alternative name(s):
Solute carrier family 25 member 9

Gene names

Name:	UCP3
Synonyms:	SLC25A9

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	312 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. As a result, energy is dissipated in the form of heat. May play a role in the modulation of tissue respiratory control. Participates in thermogenesis and energy balance.
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Only in skeletal muscle and heart. Is more expressed in glycolytic than in oxidative skeletal muscles. Ref.3
Involvement in disease	Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.8 Ref.9
Sequence similarities	Belongs to the mitochondrial carrier (TC 2.A.29) family. [View classification] Contains 3 Solcar repeats.
Sequence caution	The sequence AAC51785.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation Obesity
Domain	Repeat Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cellular response to hormone stimulus Inferred from electronic annotation. Source: Compara fatty acid metabolic process Inferred from electronic annotation. Source: Compara lipid metabolic process Traceable author statement PubMed 10935638. Source: ProtInc mitochondrial transport Inferred from electronic annotation. Source: InterPro proton transport Traceable author statement. Source: Reactome respiratory electron transport chain Traceable author statement. Source: Reactome respiratory gaseous exchange Traceable author statement Ref.1. Source: ProtInc response to activity Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara response to nutrient 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
Molecular_function	oxidative phosphorylation uncoupler activity Inferred from electronic annotation. Source: Compara transporter activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform UCP3L (identifier: P55916-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform UCP3S (identifier: P55916-2)

The sequence of this isoform differs from the canonical sequence as follows:
     276-312: Missing.

Isoform 3 (identifier: P55916-3)

The sequence of this isoform differs from the canonical sequence as follows:
     114-216: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 312	312	Mitochondrial uncoupling protein 3		PRO_0000090672
Regions
	Transmembrane	11 – 32	22	Helical; Name=1; Potential
	Transmembrane	77 – 99	23	Helical; Name=2; Potential
	Transmembrane	120 – 136	17	Helical; Name=3; Potential
	Transmembrane	184 – 200	17	Helical; Name=4; Potential
	Transmembrane	218 – 237	20	Helical; Name=5; Potential
	Transmembrane	272 – 294	23	Helical; Name=6; Potential
	Repeat	11 – 105	95	Solcar 1
	Repeat	114 – 206	93	Solcar 2
	Repeat	215 – 300	86	Solcar 3
	Region	279 – 301	23	Purine nucleotide binding By similarity
Natural variations
	Alternative sequence	114 – 216	103	Missing in isoform 3.		VSP_003270
	Alternative sequence	276 – 312	37	Missing in isoform UCP3S.		VSP_003271
	Natural variant	9	1	V → M. Corresponds to variant rs8179180 [ dbSNP | Ensembl ].		VAR_050136
	Natural variant	70	1	R → W in severe obesity with type 2 diabetes. Ref.9 Corresponds to variant rs17848368 [ dbSNP | Ensembl ].		VAR_004407
	Natural variant	102	1	V → I in obesity. Ref.8 Corresponds to variant rs2229707 [ dbSNP | Ensembl ].		VAR_004408
Experimental info
	Sequence conflict	193 – 194	2	NC → KS in AAC18822. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform UCP3L [UniParc]. Last modified November 1, 1997. Version 1. Checksum: D0E04A8DB352B17C	FASTA	312	34,216
	10 20 30 40 50 60 MVGLKPSDVP PTMAVKFLGA GTAACFADLV TFPLDTAKVR LQIQGENQAV QTARLVQYRG 70 80 90 100 110 120 VLGTILTMVR TEGPCSPYNG LVAGLQRQMS FASIRIGLYD SVKQVYTPKG ADNSSLTTRI 130 140 150 160 170 180 LAGCTTGAMA VTCAQPTDVV KVRFQASIHL GPSRSDRKYS GTMDAYRTIA REEGVRGLWK 190 200 210 220 230 240 GTLPNIMRNA IVNCAEVVTY DILKEKLLDY HLLTDNFPCH FVSAFGAGFC ATVVASPVDV 250 260 270 280 290 300 VKTRYMNSPP GQYFSPLDCM IKMVAQEGPT AFYKGFTPSF LRLGSWNVVM FVTYEQLKRA 310 LMKVQMLRES PF
	Isoform UCP3S [UniParc]. Checksum: 4E0FDF29E06A8AD9	FASTA	275	29,783
	10 20 30 40 50 60 MVGLKPSDVP PTMAVKFLGA GTAACFADLV TFPLDTAKVR LQIQGENQAV QTARLVQYRG 70 80 90 100 110 120 VLGTILTMVR TEGPCSPYNG LVAGLQRQMS FASIRIGLYD SVKQVYTPKG ADNSSLTTRI 130 140 150 160 170 180 LAGCTTGAMA VTCAQPTDVV KVRFQASIHL GPSRSDRKYS GTMDAYRTIA REEGVRGLWK 190 200 210 220 230 240 GTLPNIMRNA IVNCAEVVTY DILKEKLLDY HLLTDNFPCH FVSAFGAGFC ATVVASPVDV 250 260 270 VKTRYMNSPP GQYFSPLDCM IKMVAQEGPT AFYKG
	Isoform 3 [UniParc]. Checksum: 4DC46DECA9A50E17	FASTA	209	22,874
	10 20 30 40 50 60 MVGLKPSDVP PTMAVKFLGA GTAACFADLV TFPLDTAKVR LQIQGENQAV QTARLVQYRG 70 80 90 100 110 120 VLGTILTMVR TEGPCSPYNG LVAGLQRQMS FASIRIGLYD SVKQVYTPKG ADNFPCHFVS 130 140 150 160 170 180 AFGAGFCATV VASPVDVVKT RYMNSPPGQY FSPLDCMIKM VAQEGPTAFY KGFTPSFLRL 190 200 GSWNVVMFVT YEQLKRALMK VQMLRESPF

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]	"The human uncoupling protein-3 gene. Genomic structure, chromosomal localization, and genetic basis for short and long form transcripts." Solanes G., Vidal-Puig A., Grujic D., Flier J.S., Lowell B.B. J. Biol. Chem. 272:25433-25436(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS UCP3L AND UCP3S).
[3]	"UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue." Vidal-Puig A., Solanes G., Grujic D., Flier J.S., Lowell B.B. Biochem. Biophys. Res. Commun. 235:79-82(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM UCP3L), TISSUE SPECIFICITY.
[4]	"Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin." Gong D.-W., He Y., Karas M., Reitman M. J. Biol. Chem. 272:24129-24132(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity." Urhammer S.A., Dalgaard L.T., Soerensen T.I.A., Tybjaerg-Hansen A., Echwald S.M., Andersen T., Clausen J.O., Pedersen O. Diabetologia 41:241-244(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The uncoupling protein-3 gene is transcribed from tissue-specific promoters in humans but not in rodents." Esterbauer H., Oberkofler H., Krempler F., Strosberg A.D., Patsch W. J. Biol. Chem. 275:36394-36399(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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] (ISOFORM 3). Tissue: Skeletal muscle.
[8]	"Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes." Argyropoulos G., Brown A.M., Willi S.M., Zhu J., He Y., Reitman M., Gevao S.M., Spruill I., Garvey W.T. J. Clin. Invest. 102:1345-1351(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OBESITY ILE-102.
[9]	"A novel missense mutation, R70W, in the human uncoupling protein 3 gene in a family with type 2 diabetes." Brown A.M., Willi S.M., Argyropoulos G., Garvey W.T. Hum. Mutat. 13:506-506(1999) Cited for: VARIANT OBESITY TRP-70.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U84763 mRNA. Translation: AAC51367.1. U82818 mRNA. Translation: AAC51356.1. AF001787 mRNA. Translation: AAC51369.1. AF011449 mRNA. Translation: AAC51767.1. AF012202 , AF012197, AF012198, AF012199, AF012200, AF012201 Genomic DNA. Translation: AAC51785.1. Different initiation. AF026958, AF026956, AF026957 Genomic DNA. Translation: AAC18822.1. AF050113 Genomic DNA. Translation: AAG02284.1. BC008392 mRNA. Translation: AAH08392.1.
IPI	IPI00026815. IPI00221047. IPI01018886.
PIR	JC5522.
RefSeq	NP_003347.1. NM_003356.3. NP_073714.1. NM_022803.2.
UniGene	Hs.101337. Hs.621879.
3D structure databases
ProteinModelPortal	P55916.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000323740.
Protein family/group databases
TCDB	2.A.29.3.5. mitochondrial carrier (MC) family.
Polymorphism databases
DMDM	2497983.
Proteomic databases
PaxDb	P55916.
PRIDE	P55916.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000314032; ENSP00000323740; ENSG00000175564. ENST00000426995; ENSP00000392143; ENSG00000175564.
GeneID	7352.
KEGG	hsa:7352.
UCSC	uc001our.3. human.
Organism-specific databases
CTD	7352.
GeneCards	GC11M073711.
HGNC	HGNC:12519. UCP3.
HPA	CAB010771.
MIM	601665. phenotype. 602044. gene.
neXtProt	NX_P55916.
PharmGKB	PA37166.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300436.
HOGENOM	HOG000165140.
HOVERGEN	HBG009528.
InParanoid	P55916.
KO	K15103.
OMA	YHLLTDN.
OrthoDB	EOG4V6ZH7.
PhylomeDB	P55916.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P55916.
Bgee	P55916.
CleanEx	HS_UCP3.
Genevestigator	P55916.
GermOnline	ENSG00000175564. 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
GenomeRNAi	7352.
NextBio	28782.
SOURCE	Search...

Entry information

Entry name

UCP3_HUMAN

Accession

Primary (citable) accession number: P55916
Secondary accession number(s): O60475, Q96HL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 119 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.