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Protein

Peroxisome proliferator-activated receptor alpha

Gene

PPARA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 PER2.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei280Synthetic agonist5 Publications1
Binding sitei314Synthetic agonist5 Publications1
Sitei433Essential for heterodimerization with RXRA1
Binding sitei440Synthetic agonist5 Publications1
Binding sitei464Synthetic agonist5 Publications1

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

  • DNA binding Source: ProtInc
  • DNA binding transcription factor activity Source: BHF-UCL
  • drug binding Source: UniProtKB
  • lipid binding Source: UniProtKB
  • MDM2/MDM4 family protein binding Source: Ensembl
  • NFAT protein binding Source: Ensembl
  • nuclear receptor activity Source: UniProtKB
  • phosphatase binding Source: Ensembl
  • protein-containing complex binding Source: Ensembl
  • protein domain specific binding Source: Ensembl
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: BHF-UCL
  • steroid hormone receptor activity Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: Ensembl
  • transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcription coactivator binding Source: Ensembl
  • transcription factor binding Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: BHF-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Receptor
Biological processBiological rhythms, Transcription, Transcription regulation
LigandLipid-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1368082 RORA activates gene expression
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-1989781 PPARA activates gene expression
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-400253 Circadian Clock
SignaLinkiQ07869
SIGNORiQ07869

Chemistry databases

SwissLipidsiSLP:000001644

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000186951.16
HGNCiHGNC:9232 PPARA
MIMi170998 gene+phenotype
neXtProtiNX_Q07869

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi122C → G: Prevents DNA binding but no effect on heterodimerization with RXRA. 1 Publication1
Mutagenesisi304D → A: Reduced heterodimerization with RXRA. Reduced DNA binding. 1 Publication1
Mutagenesisi370L → R: Abolishes heterodimerization with RXRA. No DNA binding. 1 Publication1
Mutagenesisi391L → R: Abolishes heterodimerization with RXRA. No DNA binding. 1 Publication1
Mutagenesisi422L → R: No effect on heterodimerization with RXRA nor on DNA binding and transactivation activity. 1 Publication1
Mutagenesisi431A → T: No effect on heterodimerization with RXRA nor on DNA binding. 1 Publication1
Mutagenesisi433L → R: Abolishes heterodimerization with RXRA, DNA binding and transactivation activity. 1 Publication1

Organism-specific databases

DisGeNETi5465
MIMi170998 gene+phenotype
OpenTargetsiENSG00000186951
PharmGKBiPA280

Chemistry databases

ChEMBLiCHEMBL239
DrugBankiDB07724 3-{5-methoxy-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}propanoic acid
DB08915 Aleglitazar
DB01393 Bezafibrate
DB00636 Clofibrate
DB01039 Fenofibrate
DB01241 Gemfibrozil
DB05187 GFT505
DB00328 Indomethacin
DB01708 Prasterone
DB04971 Reglixane
GuidetoPHARMACOLOGYi593

Polymorphism and mutation databases

BioMutaiPPARA
DMDMi3041727

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000534811 – 468Peroxisome proliferator-activated receptor alphaAdd BLAST468

Proteomic databases

PaxDbiQ07869
PeptideAtlasiQ07869
PRIDEiQ07869
ProteomicsDBi58553

PTM databases

iPTMnetiQ07869
PhosphoSitePlusiQ07869

Expressioni

Tissue specificityi

Skeletal muscle, liver, heart and kidney.2 Publications

Gene expression databases

BgeeiENSG00000186951
CleanExiHS_PPARA
ExpressionAtlasiQ07869 baseline and differential
GenevisibleiQ07869 HS

Organism-specific databases

HPAiCAB075701
HPA058901
HPA067049

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 (PubMed:24043310).By similarity12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111461, 44 interactors
DIPiDIP-241N
IntActiQ07869, 18 interactors
MINTiQ07869
STRINGi9606.ENSP00000262735

Chemistry databases

BindingDBiQ07869

Structurei

Secondary structure

1468
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi203 – 217Combined sources15
Helixi222 – 229Combined sources8
Beta strandi233 – 235Combined sources3
Beta strandi239 – 241Combined sources3
Helixi244 – 254Combined sources11
Helixi256 – 259Combined sources4
Helixi263 – 265Combined sources3
Helixi268 – 290Combined sources23
Helixi291 – 293Combined sources3
Turni295 – 299Combined sources5
Helixi302 – 321Combined sources20
Helixi322 – 324Combined sources3
Beta strandi329 – 332Combined sources4
Turni333 – 336Combined sources4
Beta strandi337 – 340Combined sources4
Helixi341 – 346Combined sources6
Turni349 – 351Combined sources3
Helixi352 – 366Combined sources15
Helixi372 – 383Combined sources12
Helixi394 – 415Combined sources22
Helixi422 – 450Combined sources29
Beta strandi453 – 456Combined sources4
Helixi458 – 464Combined sources7
Turni465 – 467Combined sources3

3D structure databases

ProteinModelPortaliQ07869
SMRiQ07869
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ07869

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini239 – 466NR LBDPROSITE-ProRule annotationAdd BLAST228

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni304 – 433Required for heterodimerization with RXRAAdd BLAST130

Sequence similaritiesi

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
GeneTreeiENSGT00870000136388
HOGENOMiHOG000261626
HOVERGENiHBG106004
InParanoidiQ07869
KOiK07294
OMAiFSFTEYQ
OrthoDBiEOG091G05U8
PhylomeDBiQ07869
TreeFamiTF316304

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR003074 1Cnucl_rcpt
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR003076 PPAR-alpha
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01288 PROXISOMEPAR
PR01289 PROXISOMPAAR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q07869-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVDTESPLCP LSPLEAGDLE SPLSEEFLQE MGNIQEISQS IGEDSSGSFG
60 70 80 90 100
FTEYQYLGSC PGSDGSVITD TLSPASSPSS VTYPVVPGSV DESPSGALNI
110 120 130 140 150
ECRICGDKAS GYHYGVHACE GCKGFFRRTI RLKLVYDKCD RSCKIQKKNR
160 170 180 190 200
NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE KAKLKAEILT CEHDIEDSET
210 220 230 240 250
ADLKSLAKRI YEAYLKNFNM NKVKARVILS GKASNNPPFV IHDMETLCMA
260 270 280 290 300
EKTLVAKLVA NGIQNKEAEV RIFHCCQCTS VETVTELTEF AKAIPGFANL
310 320 330 340 350
DLNDQVTLLK YGVYEAIFAM LSSVMNKDGM LVAYGNGFIT REFLKSLRKP
360 370 380 390 400
FCDIMEPKFD FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNVGHIEKM
410 420 430 440 450
QEGIVHVLRL HLQSNHPDDI FLFPKLLQKM ADLRQLVTEH AQLVQIIKKT
460
ESDAALHPLL QEIYRDMY
Length:468
Mass (Da):52,225
Last modified:July 15, 1998 - v2
Checksum:i850846FD51ADA883
GO
Isoform 2 (identifier: Q07869-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     171-174: IRFG → FCHT
     175-468: Missing.

Show »
Length:174
Mass (Da):18,942
Checksum:i8587321146D06A03
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71T → M in CAA68898 (PubMed:8993548).Curated1
Sequence conflicti123K → M in CAA68898 (PubMed:8993548).Curated1
Sequence conflicti296G → A in AAA36468 (PubMed:7684926).Curated1
Sequence conflicti444V → A in CAA68898 (PubMed:8993548).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016110127R → Q. Corresponds to variant dbSNP:rs1800204Ensembl.1
Natural variantiVAR_016111162L → V1 PublicationCorresponds to variant dbSNP:rs1800206EnsemblClinVar.1
Natural variantiVAR_016112227V → A. Corresponds to variant dbSNP:rs1800234Ensembl.1
Natural variantiVAR_016113268A → V1 PublicationCorresponds to variant dbSNP:rs1042311Ensembl.1
Natural variantiVAR_016114304D → N. Corresponds to variant dbSNP:rs1800242Ensembl.1
Natural variantiVAR_050578395G → R. Corresponds to variant dbSNP:rs2229245Ensembl.1
Natural variantiVAR_016115409R → T. Corresponds to variant dbSNP:rs1800243Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047571171 – 174IRFG → FCHT in isoform 2. 1 Publication4
Alternative sequenceiVSP_047572175 – 468Missing in isoform 2. 1 PublicationAdd BLAST294

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L02932 mRNA Translation: AAA36468.1
S74349 mRNA Translation: AAB32649.1
Y07619 mRNA Translation: CAA68898.1
AB307690 mRNA Translation: BAH02281.1
EU650667 mRNA Translation: ACD12656.1
EU395809 mRNA Translation: ABY73535.1
CR456547 mRNA Translation: CAG30433.1
AK289821 mRNA Translation: BAF82510.1
CR457435 mRNA Translation: CAG33716.1
AY206718 Genomic DNA Translation: AAO13489.1
AL049856, AL078611 Genomic DNA Translation: CAI22450.1
Z94161 Genomic DNA No translation available.
CH471138 Genomic DNA Translation: EAW73402.1
CCDSiCCDS33669.1 [Q07869-1]
PIRiA49289
I56603
RefSeqiNP_001001928.1, NM_001001928.2 [Q07869-1]
NP_005027.2, NM_005036.4 [Q07869-1]
XP_005261712.1, XM_005261655.3 [Q07869-1]
XP_005261713.1, XM_005261656.3 [Q07869-1]
XP_006724332.1, XM_006724269.3 [Q07869-1]
XP_006724333.1, XM_006724270.3 [Q07869-1]
XP_011528541.1, XM_011530239.2 [Q07869-1]
XP_011528542.1, XM_011530240.2 [Q07869-1]
XP_011528543.1, XM_011530241.2 [Q07869-1]
XP_011528544.1, XM_011530242.2 [Q07869-1]
XP_011528545.1, XM_011530243.2 [Q07869-1]
UniGeneiHs.103110
Hs.710044

Genome annotation databases

EnsembliENST00000262735; ENSP00000262735; ENSG00000186951 [Q07869-1]
ENST00000402126; ENSP00000385246; ENSG00000186951 [Q07869-1]
ENST00000407236; ENSP00000385523; ENSG00000186951 [Q07869-1]
GeneIDi5465
KEGGihsa:5465
UCSCiuc003bgx.1 human [Q07869-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Entry informationi

Entry nameiPPARA_HUMAN
AccessioniPrimary (citable) accession number: Q07869
Secondary accession number(s): B0G0X3
, Q16241, Q6I9S0, Q92486, Q92689, Q9Y3N1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: July 15, 1998
Last modified: July 18, 2018
This is version 216 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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