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P23204 (PPARA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length468 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Zinc
   Molecular functionActivator
Receptor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbehavioral response to nicotine

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

lipid metabolic process

Traceable author statement PubMed 10377439. Source: MGI

lipoprotein metabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of appetite

Inferred from mutant phenotype Ref.8. Source: UniProtKB

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

negative regulation of cholesterol storage

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron death

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of receptor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of sequestering of triglyceride

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of fatty acid oxidation

Inferred from mutant phenotype PubMed 15639194. Source: BHF-UCL

positive regulation of gluconeogenesis

Inferred from mutant phenotype PubMed 15232616. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16571721PubMed 20385772PubMed 8041794. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.8. Source: UniProtKB

regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of fatty acid metabolic process

Inferred from mutant phenotype PubMed 9488698. Source: MGI

regulation of gene expression

Inferred from mutant phenotype PubMed 15313227. Source: MGI

regulation of glycolysis by positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Traceable author statement PubMed 10377439. Source: MGI

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

wound healing

Inferred from mutant phenotype PubMed 11514592. Source: MGI

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement PubMed 10377439. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 12015306PubMed 15232616PubMed 15237213. Source: MGI

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 15232616. Source: MGI

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: Ensembl

lipid binding

Inferred from direct assay Ref.8. Source: UniProtKB

protein heterodimerization activity

Traceable author statement PubMed 16271724. Source: UniProtKB

receptor activity

Inferred from direct assay PubMed 12802337. Source: MGI

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...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Men1O885592EBI-5273083,EBI-3990176

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 468468Peroxisome proliferator-activated receptor alpha
PRO_0000053482

Regions

DNA binding99 – 17375Nuclear receptor Ref.11
Zinc finger102 – 12221NR C4-type
Zinc finger139 – 16123NR C4-type
Region280 – 468189Ligand-binding By similarity
Region304 – 433130Required for heterodimerization with RXRA By similarity

Sites

Site4331Essential for heterodimerization with RXRA By similarity

Experimental info

Mutagenesis1191C → A: Reduced DNA binding and strongly decreased transcriptional activation; when associated with A-122. Ref.11
Mutagenesis1221C → A: Reduced DNA binding and strongly decreased transcriptional activation; when associated with A-119. Ref.11
Sequence conflict751A → R in CAA40856. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P23204 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 2930A5191C610B6B

FASTA46852,347
        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 

« Hide

References

« Hide '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 expand/collapse EMBL AC list , X75290, X75291, X75292, X75293, X75294 Genomic DNA. Translation: CAA53042.1.
BC016892 mRNA. Translation: AAH16892.1.
X89577 mRNA. Translation: CAA61754.1.
PIRJC2085.
RefSeqNP_001106889.1. NM_001113418.1.
NP_035274.2. NM_011144.6.
XP_006520682.1. XM_006520619.1.
XP_006520683.1. XM_006520620.1.
XP_006520684.1. XM_006520621.1.
XP_006520685.1. XM_006520622.1.
XP_006520686.1. XM_006520623.1.
UniGeneMm.212789.

3D structure databases

ProteinModelPortalP23204.
SMRP23204. Positions 93-468.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202317. 15 interactions.
DIPDIP-5958N.
IntActP23204. 3 interactions.
STRING10090.ENSMUSP00000059719.

Chemistry

BindingDBP23204.
ChEMBLCHEMBL2128.
GuidetoPHARMACOLOGY593.

PTM databases

PhosphoSiteP23204.

Proteomic databases

PRIDEP23204.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000057979; ENSMUSP00000059719; ENSMUSG00000022383.
ENSMUST00000109422; ENSMUSP00000105049; ENSMUSG00000022383.
ENSMUST00000109423; ENSMUSP00000105050; ENSMUSG00000022383.
GeneID19013.
KEGGmmu:19013.
UCSCuc007xdj.2. mouse.

Organism-specific databases

CTD5465.
MGIMGI:104740. Ppara.

Phylogenomic databases

eggNOGNOG266867.
HOGENOMHOG000261626.
HOVERGENHBG106004.
InParanoidP23204.
KOK07294.
OMATESPICP.
OrthoDBEOG7X9G7F.
PhylomeDBP23204.
TreeFamTF316304.

Enzyme and pathway databases

ReactomeREACT_109335. Circadian Clock.
REACT_188937. Metabolism.
REACT_24972. Circadian Clock.

Gene expression databases

BgeeP23204.
CleanExMM_PPARA.
GenevestigatorP23204.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR003074. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01288. PROXISOMEPAR.
PR01289. PROXISOMPAAR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio295428.
PROP23204.
SOURCESearch...

Entry information

Entry namePPARA_MOUSE
AccessionPrimary (citable) accession number: P23204
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot