P23204 (PPARA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisome proliferator-activated receptor alpha
Short name=PPAR-alpha

Alternative name(s):
Nuclear receptor subfamily 1 group C member 1

Gene names

Name:	Ppara
Synonyms:	Nr1c1, Ppar

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety By similarity. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2 By similarity. Ref.8 Ref.11
Subunit structure	Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with NCOA3 coactivator. Interacts with CITED2; the interaction stimulates its transcriptional activity By similarity. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 AND ASXL2 By similarity. Ref.5 Ref.6 Ref.7 Ref.9 Ref.10
Subcellular location	Nucleus.
Tissue specificity	Highly expressed in liver, kidney and heart. Very weakly expressed in brain and testis.
Developmental stage	It appears first at 13.5 dpc and increases until birth.
Involvement in disease	Peroxisome proliferators are a diverse group of chemicals that include hypolipidaemic drugs, herbicides and industrial plasticisers. Administration of these chemicals to rodents results in the dramatic proliferation of hepatic peroxisomes as well as liver hyperplasia.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Zinc
Molecular function	Activator Receptor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavioral response to nicotine Inferred from electronic annotation. Source: Compara enamel mineralization Inferred from mutant phenotype PubMed 19320717. Source: MGI epidermis development Inferred from mutant phenotype PubMed 12485431. Source: MGI fatty acid metabolic process Inferred from mutant phenotype PubMed 15007068. Source: MGI glucose metabolic process Traceable author statement PubMed 10377439. Source: MGI heart development Inferred from electronic annotation. Source: Compara lipoprotein metabolic process Inferred from electronic annotation. Source: Compara negative regulation of appetite Inferred from mutant phenotype Ref.8. Source: UniProtKB negative regulation of blood pressure Inferred from electronic annotation. Source: Compara negative regulation of cholesterol storage Inferred from electronic annotation. Source: Compara negative regulation of neuron death Inferred from electronic annotation. Source: Compara negative regulation of protein binding Inferred from electronic annotation. Source: Compara negative regulation of receptor biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of sequestering of triglyceride Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara positive regulation of fatty acid oxidation Inferred from mutant phenotype PubMed 15639194. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20385772PubMed 8041794. Source: MGI regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of glycolysis by positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter 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 wound healing Inferred from mutant phenotype PubMed 11514592. Source: MGI
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	drug binding Inferred from sequence or structural similarity. Source: UniProtKB ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from electronic annotation. Source: Compara lipid binding Inferred from direct assay Ref.8. Source: UniProtKB protein heterodimerization activity Traceable author statement PubMed 16271724. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay PubMed 16271724. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 16271724. Source: UniProtKB steroid hormone receptor activity Traceable author statement PubMed 10377439. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 468	468	Peroxisome proliferator-activated receptor alpha		PRO_0000053482
Regions
	DNA binding	99 – 173	75	Nuclear receptor Ref.11
	Zinc finger	102 – 122	21	NR C4-type
	Zinc finger	139 – 161	23	NR C4-type
	Region	280 – 468	189	Ligand-binding By similarity
	Region	304 – 433	130	Required for heterodimerization with RXRA By similarity
Sites
	Site	433	1	Essential for heterodimerization with RXRA By similarity
Experimental info
	Mutagenesis	119	1	C → A: Reduced DNA binding and strongly decreased transcriptional activation; when associated with A-122. Ref.11
	Mutagenesis	122	1	C → A: Reduced DNA binding and strongly decreased transcriptional activation; when associated with A-119. Ref.11
	Sequence conflict	75	1	A → R in CAA40856. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P23204 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 2930A5191C610B6B	FASTA	468	52,347
	10 20 30 40 50 60 MVDTESPICP LSPLEADDLE SPLSEEFLQE MGNIQEISQS IGEESSGSFG FADYQYLGSC 70 80 90 100 110 120 PGSEGSVITD TLSPASSPSS VSCPVIPAST DESPGSALNI ECRICGDKAS GYHYGVHACE 130 140 150 160 170 180 GCKGFFRRTI RLKLVYDKCD RSCKIQKKNR NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE 190 200 210 220 230 240 KAKLKAEILT CEHDLKDSET ADLKSLGKRI HEAYLKNFNM NKVKARVILA GKTSNNPPFV 250 260 270 280 290 300 IHDMETLCMA EKTLVAKMVA NGVEDKEAEV RFFHCCQCMS VETVTELTEF AKAIPGFANL 310 320 330 340 350 360 DLNDQVTLLK YGVYEAIFTM LSSLMNKDGM LIAYGNGFIT REFLKNLRKP FCDIMEPKFD 370 380 390 400 410 420 FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNIGYIEKL QEGIVHVLKL HLQSNHPDDT 430 440 450 460 FLFPKLLQKM VDLRQLVTEH AQLVQVIKKT ESDAALHPLL QEIYRDMY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators." Issemann I., Green S. Nature 347:645-650(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of the mouse peroxisome proliferator activated receptor alpha gene." Gearing K.L., Crickmore A., Gustafsson J.-A. Biochem. Biophys. Res. Commun. 199:255-263(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Sv.
[3]	"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]. Strain: FVB/N. Tissue: Kidney.
[4]	"Chromosomal localisation, inducibility, tissue-specific expression and strain differences in three murine peroxisome-proliferator-activated-receptor genes." Jones P.S., Savory R., Barratt P., Bell A.R., Gray T.J.B., Jenkins N.A., Gilbert D.J., Copeland N.G., Bell D.R. Eur. J. Biochem. 233:219-226(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 413-468. Strain: Swiss Webster. Tissue: Liver.
[5]	"Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor." Zhu Y., Qi C., Jain S., Rao M.S., Reddy J.K. J. Biol. Chem. 272:25500-25506(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPARBP.
[6]	"Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action." Rubino D., Driggers P., Arbit D., Kemp L., Miller B., Coso O., Pagliai K., Gray K., Gutkind S., Segars J. Oncogene 16:2513-2526(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AKAP13.
[7]	"Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR." Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K. J. Biol. Chem. 275:13510-13516(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA6.
[8]	"Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha." Fu J., Gaetani S., Oveisi F., Lo Verme J., Serrano A., Rodriguez De Fonseca F., Rosengarth A., Luecke H., Di Giacomo B., Tarzia G., Piomelli D. Nature 425:90-93(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS RECEPTOR FOR OLEYLETHANOLAMIDE, FUNCTION.
[9]	"Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway." Finck B.N., Gropler M.C., Chen Z., Leone T.C., Croce M.A., Harris T.E., Lawrence J.C. Jr., Kelly D.P. Cell Metab. 4:199-210(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LIPN1.
[10]	"PRDM16 controls a brown fat/skeletal muscle switch." Seale P., Bjork B., Yang W., Kajimura S., Chin S., Kuang S., Scime A., Devarakonda S., Conroe H.M., Erdjument-Bromage H., Tempst P., Rudnicki M.A., Beier D.R., Spiegelman B.M. Nature 454:961-967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRDM16.
[11]	"Identification of a physiologically relevant endogenous ligand for PPARalpha in liver." Chakravarthy M.V., Lodhi I.J., Yin L., Malapaka R.R., Xu H.E., Turk J., Semenkovich C.F. Cell 138:476-488(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF 1-PALMITOYL-2-OLEOYL-SN-GLYCEROL-3-PHOSPHOCHOLINE AS A PHYSIOLOGICAL LIGAND, DNA-BINDING, FUNCTION, MUTAGENESIS OF CYS-119 AND CYS-122.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X57638 mRNA. Translation: CAA40856.1. X75289 , X75290, X75291, X75292, X75293, X75294 Genomic DNA. Translation: CAA53042.1. BC016892 mRNA. Translation: AAH16892.1. X89577 mRNA. Translation: CAA61754.1.
IPI	IPI00314804.
PIR	JC2085.
RefSeq	NP_001106889.1. NM_001113418.1. NP_035274.2. NM_011144.6.
UniGene	Mm.212789.
3D structure databases
ProteinModelPortal	P23204.
SMR	P23204. Positions 93-468.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5958N.
IntAct	P23204. 2 interactions.
STRING	10090.ENSMUSP00000059719.
PTM databases
PhosphoSite	P23204.
Proteomic databases
PRIDE	P23204.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000057979; ENSMUSP00000059719; ENSMUSG00000022383. ENSMUST00000109422; ENSMUSP00000105049; ENSMUSG00000022383. ENSMUST00000109423; ENSMUSP00000105050; ENSMUSG00000022383.
GeneID	19013.
KEGG	mmu:19013.
Organism-specific databases
CTD	5465.
MGI	MGI:104740. Ppara.
Phylogenomic databases
eggNOG	NOG266867.
HOGENOM	HOG000261626.
HOVERGEN	HBG106004.
InParanoid	P23204.
KO	K07294.
OMA	ICPLSPL.
OrthoDB	EOG4FFD1Q.
Enzyme and pathway databases
Reactome	REACT_109335. Circadian Clock. REACT_112621. Metabolism. REACT_24972. Circadian Clock (mouse).
Gene expression databases
ArrayExpress	P23204.
Bgee	P23204.
CleanEx	MM_PPARA.
Genevestigator	P23204.
GermOnline	ENSMUSG00000022383. Mus musculus.
Family and domain databases
Gene3D	1.10.565.10. 2 hits. 3.30.50.10. 1 hit.
InterPro	IPR003074. 1Cnucl_rcpt. IPR003076. 1Cnucl_rcpt_A. IPR008946. Nucl_hormone_rcpt_ligand-bd. IPR000536. Nucl_hrmn_rcpt_lig-bd_core. IPR001723. Str_hrmn_rcpt. IPR001628. Znf_hrmn_rcpt. IPR013088. Znf_NHR/GATA. [Graphical view]
Pfam	PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PRINTS	PR01288. PROXISOMEPAR. PR01289. PROXISOMPAAR. PR00398. STRDHORMONER. PR00047. STROIDFINGER.
SMART	SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view]
SUPFAM	SSF48508. Str_ncl_receptor. 1 hit.
PROSITE	PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P23204.
ChEMBL	CHEMBL2128.
NextBio	295428.
SOURCE	Search...

Entry information

Entry name

PPARA_MOUSE

Accession

Primary (citable) accession number: P23204

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 141 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program