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Protein

Peroxisome proliferator-activated receptor alpha

Gene

Ppara

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. May be required for the propagation of clock information to metabolic pathways regulated by PER2.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei433Essential for heterodimerization with RXRABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi99 – 173Nuclear receptorPROSITE-ProRule annotationAdd BLAST75
Zinc fingeri102 – 122NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri139 – 161NR C4-typePROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. Bmal1:Clock,Npas2 activates circadian gene expression.
R-MMU-1989781. PPARA activates gene expression.
R-MMU-383280. Nuclear Receptor transcription pathway.
R-MMU-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxisome proliferator-activated receptor alpha
Short name:
PPAR-alpha
Alternative name(s):
Nuclear receptor subfamily 1 group C member 1
Gene namesi
Name:Ppara
Synonyms:Nr1c1, Ppar
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:104740. Ppara.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi119C → A: Reduces DNA binding and strongly decreases transcriptional activation; when associated with A-122. 1 Publication1
Mutagenesisi122C → A: Reduces DNA binding and strongly decreases transcriptional activation; when associated with A-119. 1 Publication1
Mutagenesisi292K → A: No effect on interaction with PER2. 1 Publication1
Mutagenesisi459 – 468Missing : Slightly reduces interaction with PER2. 1 Publication10

Chemistry databases

ChEMBLiCHEMBL2128.
GuidetoPHARMACOLOGYi593.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000534821 – 468Peroxisome proliferator-activated receptor alphaAdd BLAST468

Proteomic databases

PaxDbiP23204.
PRIDEiP23204.

PTM databases

iPTMnetiP23204.
PhosphoSitePlusiP23204.

Expressioni

Tissue specificityi

Highly expressed in liver, kidney and heart. Very weakly expressed in brain and testis.

Developmental stagei

It appears first at 13.5 dpc and increases until birth.

Gene expression databases

BgeeiENSMUSG00000022383.
CleanExiMM_PPARA.
ExpressionAtlasiP23204. baseline and differential.
GenevisibleiP23204. MM.

Interactioni

Subunit structurei

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. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the interaction seems to be modulated by NAD+ levels (By similarity).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Men1O885592EBI-5273083,EBI-3990176

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202317. 17 interactors.
DIPiDIP-5958N.
IntActiP23204. 3 interactors.
STRINGi10090.ENSMUSP00000059719.

Chemistry databases

BindingDBiP23204.

Structurei

3D structure databases

ProteinModelPortaliP23204.
SMRiP23204.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni280 – 468Ligand-bindingBy similarityAdd BLAST189
Regioni304 – 433Required for heterodimerization with RXRABy similarityAdd BLAST130

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri102 – 122NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri139 – 161NR C4-typePROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000261626.
HOVERGENiHBG106004.
InParanoidiP23204.
KOiK07294.
OMAiYGSGFIT.
OrthoDBiEOG091G05U8.
PhylomeDBiP23204.
TreeFamiTF316304.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR003074. 1Cnucl_rcpt.
IPR003076. 1Cnucl_rcpt_A.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01288. PROXISOMEPAR.
PR01289. PROXISOMPAAR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P23204-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVDTESPICP LSPLEADDLE SPLSEEFLQE MGNIQEISQS IGEESSGSFG
60 70 80 90 100
FADYQYLGSC PGSEGSVITD TLSPASSPSS VSCPVIPAST DESPGSALNI
110 120 130 140 150
ECRICGDKAS GYHYGVHACE GCKGFFRRTI RLKLVYDKCD RSCKIQKKNR
160 170 180 190 200
NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE KAKLKAEILT CEHDLKDSET
210 220 230 240 250
ADLKSLGKRI HEAYLKNFNM NKVKARVILA GKTSNNPPFV IHDMETLCMA
260 270 280 290 300
EKTLVAKMVA NGVEDKEAEV RFFHCCQCMS VETVTELTEF AKAIPGFANL
310 320 330 340 350
DLNDQVTLLK YGVYEAIFTM LSSLMNKDGM LIAYGNGFIT REFLKNLRKP
360 370 380 390 400
FCDIMEPKFD FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNIGYIEKL
410 420 430 440 450
QEGIVHVLKL HLQSNHPDDT FLFPKLLQKM VDLRQLVTEH AQLVQVIKKT
460
ESDAALHPLL QEIYRDMY
Length:468
Mass (Da):52,347
Last modified:October 1, 1996 - v2
Checksum:i2930A5191C610B6B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75A → R in CAA40856 (PubMed:2129546).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS27721.1.
PIRiJC2085.
RefSeqiNP_001106889.1. NM_001113418.1.
NP_035274.2. NM_011144.6.
XP_006520682.1. XM_006520619.1.
XP_006520683.1. XM_006520620.3.
XP_006520684.1. XM_006520621.3.
XP_006520685.1. XM_006520622.3.
XP_006520686.1. XM_006520623.3.
XP_011243818.1. XM_011245516.2.
XP_011243819.1. XM_011245517.2.
XP_011243821.1. XM_011245519.2.
UniGeneiMm.212789.

Genome annotation databases

EnsembliENSMUST00000057979; ENSMUSP00000059719; ENSMUSG00000022383.
ENSMUST00000109422; ENSMUSP00000105049; ENSMUSG00000022383.
ENSMUST00000109423; ENSMUSP00000105050; ENSMUSG00000022383.
GeneIDi19013.
KEGGimmu:19013.
UCSCiuc007xdj.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS27721.1.
PIRiJC2085.
RefSeqiNP_001106889.1. NM_001113418.1.
NP_035274.2. NM_011144.6.
XP_006520682.1. XM_006520619.1.
XP_006520683.1. XM_006520620.3.
XP_006520684.1. XM_006520621.3.
XP_006520685.1. XM_006520622.3.
XP_006520686.1. XM_006520623.3.
XP_011243818.1. XM_011245516.2.
XP_011243819.1. XM_011245517.2.
XP_011243821.1. XM_011245519.2.
UniGeneiMm.212789.

3D structure databases

ProteinModelPortaliP23204.
SMRiP23204.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202317. 17 interactors.
DIPiDIP-5958N.
IntActiP23204. 3 interactors.
STRINGi10090.ENSMUSP00000059719.

Chemistry databases

BindingDBiP23204.
ChEMBLiCHEMBL2128.
GuidetoPHARMACOLOGYi593.

PTM databases

iPTMnetiP23204.
PhosphoSitePlusiP23204.

Proteomic databases

PaxDbiP23204.
PRIDEiP23204.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057979; ENSMUSP00000059719; ENSMUSG00000022383.
ENSMUST00000109422; ENSMUSP00000105049; ENSMUSG00000022383.
ENSMUST00000109423; ENSMUSP00000105050; ENSMUSG00000022383.
GeneIDi19013.
KEGGimmu:19013.
UCSCiuc007xdj.2. mouse.

Organism-specific databases

CTDi5465.
MGIiMGI:104740. Ppara.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000261626.
HOVERGENiHBG106004.
InParanoidiP23204.
KOiK07294.
OMAiYGSGFIT.
OrthoDBiEOG091G05U8.
PhylomeDBiP23204.
TreeFamiTF316304.

Enzyme and pathway databases

ReactomeiR-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. Bmal1:Clock,Npas2 activates circadian gene expression.
R-MMU-1989781. PPARA activates gene expression.
R-MMU-383280. Nuclear Receptor transcription pathway.
R-MMU-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).

Miscellaneous databases

PROiP23204.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022383.
CleanExiMM_PPARA.
ExpressionAtlasiP23204. baseline and differential.
GenevisibleiP23204. MM.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR003074. 1Cnucl_rcpt.
IPR003076. 1Cnucl_rcpt_A.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01288. PROXISOMEPAR.
PR01289. PROXISOMPAAR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPPARA_MOUSE
AccessioniPrimary (citable) accession number: P23204
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 176 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.