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Protein

Peroxisome proliferator-activated receptor gamma

Gene

Pparg

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

Functioni

Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (PubMed:19041764).5 Publications

Enzyme regulationi

PDPK1 activates its transcriptional activity independently of its kinase activity.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi136 – 210Nuclear receptorPROSITE-ProRule annotationAdd BLAST75
Zinc fingeri139 – 159NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri176 – 198NR C4-typePROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

  • activating transcription factor binding Source: MGI
  • alpha-actinin binding Source: MGI
  • arachidonic acid binding Source: BHF-UCL
  • chromatin binding Source: UniProtKB
  • core promoter sequence-specific DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • drug binding Source: MGI
  • enzyme binding Source: MGI
  • ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • retinoid X receptor binding Source: MGI
  • RNA polymerase II regulatory region DNA binding Source: MGI
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: MGI
  • steroid hormone receptor activity Source: InterPro
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: MGI
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: MGI
  • transcription regulatory region DNA binding Source: UniProtKB
  • WW domain binding Source: MGI
  • zinc ion binding Source: InterPro

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • brown fat cell differentiation Source: MGI
  • cell fate commitment Source: MGI
  • cell maturation Source: MGI
  • cellular response to insulin stimulus Source: MGI
  • cellular response to lithium ion Source: MGI
  • cellular response to organic cyclic compound Source: MGI
  • diet induced thermogenesis Source: MGI
  • epithelial cell differentiation Source: MGI
  • fat cell differentiation Source: MGI
  • glucose homeostasis Source: MGI
  • inflammatory response Source: MGI
  • lipoprotein transport Source: MGI
  • long-chain fatty acid transport Source: MGI
  • low-density lipoprotein particle receptor biosynthetic process Source: MGI
  • macrophage derived foam cell differentiation Source: UniProtKB
  • monocyte differentiation Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of cellular response to insulin stimulus Source: BHF-UCL
  • negative regulation of cholesterol storage Source: MGI
  • negative regulation of cytokine production Source: BHF-UCL
  • negative regulation of interferon-gamma-mediated signaling pathway Source: MGI
  • negative regulation of macrophage derived foam cell differentiation Source: MGI
  • negative regulation of peptide hormone secretion Source: BHF-UCL
  • negative regulation of receptor biosynthetic process Source: MGI
  • negative regulation of sequestering of triglyceride Source: MGI
  • negative regulation of smooth muscle cell proliferation Source: MGI
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • peroxisome proliferator activated receptor signaling pathway Source: MGI
  • placenta development Source: MGI
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of blood pressure Source: MGI
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of fat cell differentiation Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription involved in cell fate commitment Source: UniProtKB
  • response to dietary excess Source: MGI
  • response to food Source: UniProtKB
  • response to light stimulus Source: UniProtKB
  • response to lipid Source: BHF-UCL
  • response to low-density lipoprotein particle Source: MGI
  • response to retinoic acid Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
  • signal transduction Source: MGI
  • white fat cell differentiation Source: HGNC
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-381340. Transcriptional regulation of white adipocyte differentiation.
R-MMU-442533. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

Chemistry databases

SwissLipidsiSLP:000001625.

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxisome proliferator-activated receptor gamma
Short name:
PPAR-gamma
Alternative name(s):
Nuclear receptor subfamily 1 group C member 3
Gene namesi
Name:Pparg
Synonyms:Nr1c3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:97747. Pparg.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: MGI
  • Golgi apparatus Source: MGI
  • intracellular membrane-bounded organelle Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • RNA polymerase II transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice develop abnormalities in circadian variations in blood pressure and heart rate, in parallel with a reduction of diurnal variations in the sympathetic nerve activity, and impaired rhythmicity of ARNTL/BMAL1 in the blood vessels.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi112S → A: Increases basal and ligand-induced adipogenic activity. Abolishes repression by PER2 on transactivation activity. 2 Publications1
Mutagenesisi112S → D: No effect on repression by PER2 on transactivation activity. 2 Publications1

Chemistry databases

ChEMBLiCHEMBL2459.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000534941 – 505Peroxisome proliferator-activated receptor gammaAdd BLAST505

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi84O-linked (GlcNAc)1 Publication1
Modified residuei112Phosphoserine; by MAPK2 Publications1

Post-translational modificationi

O-GlcNAcylation at Thr-84 reduces transcriptional activity in adipocytes.
Phosphorylated in basal conditions and dephosphorylated when treated with the ligand. May be dephosphorylated by PPP5C. The phosphorylated Ser-112 form is recognized by PER2 and repressed, dephosphorylation at Ser-112 induces adipogenic activity. Ser-112 phosphorylation levels are reduced by 65% in brown adipose tissue compared to white adipose tissue.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP37238.
PRIDEiP37238.

PTM databases

iPTMnetiP37238.
PhosphoSitePlusiP37238.

Expressioni

Tissue specificityi

Highest expression in white and brown adipose tissue. Also found in liver, skeletal muscle, heart, adrenal gland, spleen, kidney and intestine. Isoform 2 is more abundant than isoform 1 in adipose tissue.2 Publications

Developmental stagei

It appears first at 13.5 dpc and increases until birth.

Inductioni

Expressed in a circadian manner in the aorta.1 Publication

Gene expression databases

CleanExiMM_PPARG.

Interactioni

Subunit structurei

Heterodimer with other nuclear receptors, such as RXRA. The heterodimer with the retinoic acid receptor RXRA is called adipocyte-specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction stimulates the transcriptional activity of PPARG. Interacts with PER2, the interaction is ligand dependent and blocks PPARG recruitment to target promoters. Interacts with NOCT. Interacts with FOXO1 (acetylated form). Interacts with ACTN4 (By similarity).By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SIRT1Q96EB63EBI-5260705,EBI-1802965From a different organism.
Sirt1Q923E42EBI-5260705,EBI-1802585

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202320. 35 interactors.
DIPiDIP-60435N.
IntActiP37238. 4 interactors.
STRINGi10090.ENSMUSP00000000450.

Chemistry databases

BindingDBiP37238.

Structurei

3D structure databases

ProteinModelPortaliP37238.
SMRiP37238.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni205 – 280Interaction with FAM120B1 PublicationAdd BLAST76
Regioni317 – 505Ligand-bindingBy similarityAdd BLAST189

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri139 – 159NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri176 – 198NR C4-typePROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000261626.
HOVERGENiHBG106004.
InParanoidiP37238.
KOiK08530.
PhylomeDBiP37238.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR003074. 1Cnucl_rcpt.
IPR003077. 1Cnucl_rcpt_G.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR022590. PPARgamma_N.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF12577. PPARgamma_N. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01288. PROXISOMEPAR.
PR01291. PROXISOMPAGR.
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]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 2 (identifier: P37238-1) [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
MGETLGDSPV DPEHGAFADA LPMSTSQEIT MVDTEMPFWP TNFGISSVDL
60 70 80 90 100
SVMEDHSHSF DIKPFTTVDF SSISAPHYED IPFTRADPMV ADYKYDLKLQ
110 120 130 140 150
EYQSAIKVEP ASPPYYSEKT QLYNRPHEEP SNSLMAIECR VCGDKASGFH
160 170 180 190 200
YGVHACEGCK GFFRRTIRLK LIYDRCDLNC RIHKKSRNKC QYCRFQKCLA
210 220 230 240 250
VGMSHNAIRF GRMPQAEKEK LLAEISSDID QLNPESADLR ALAKHLYDSY
260 270 280 290 300
IKSFPLTKAK ARAILTGKTT DKSPFVIYDM NSLMMGEDKI KFKHITPLQE
310 320 330 340 350
QSKEVAIRIF QGCQFRSVEA VQEITEYAKN IPGFINLDLN DQVTLLKYGV
360 370 380 390 400
HEIIYTMLAS LMNKDGVLIS EGQGFMTREF LKNLRKPFGD FMEPKFEFAV
410 420 430 440 450
KFNALELDDS DLAIFIAVII LSGDRPGLLN VKPIEDIQDN LLQALELQLK
460 470 480 490 500
LNHPESSQLF AKVLQKMTDL RQIVTEHVQL LHVIKKTETD MSLHPLLQEI

YKDLY
Length:505
Mass (Da):57,598
Last modified:April 27, 2001 - v3
Checksum:iAB8F3F6086E2A10A
GO
Isoform 1 (identifier: P37238-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: Missing.

Show »
Length:475
Mass (Da):54,512
Checksum:iFD80BD50D9197D3F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213 – 214MP → DR in AAA62110 (PubMed:8240342).Curated2
Sequence conflicti281 – 283NSL → SSF in AAA62110 (PubMed:8240342).Curated3
Sequence conflicti383N → S in AAA62110 (PubMed:8240342).Curated1
Sequence conflicti383N → S in AAA19971 (PubMed:8041794).Curated1
Sequence conflicti497L → F in AAA62110 (PubMed:8240342).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0036471 – 30Missing in isoform 1. 3 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09138 mRNA. Translation: AAA62277.1.
U01664 mRNA. Translation: AAA62110.1.
U01841 mRNA. Translation: AAC52134.1.
U10374 mRNA. Translation: AAA19971.1.
CCDSiCCDS20439.1. [P37238-1]
CCDS51876.1. [P37238-2]
PIRiA54101.
RefSeqiNP_001120802.1. NM_001127330.2.
NP_001295281.1. NM_001308352.1.
NP_001295283.1. NM_001308354.1.
NP_035276.2. NM_011146.3.
XP_006505806.1. XM_006505743.3.
XP_011239554.1. XM_011241252.1.
XP_017176944.1. XM_017321455.1.
UniGeneiMm.3020.

Genome annotation databases

GeneIDi19016.
KEGGimmu:19016.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09138 mRNA. Translation: AAA62277.1.
U01664 mRNA. Translation: AAA62110.1.
U01841 mRNA. Translation: AAC52134.1.
U10374 mRNA. Translation: AAA19971.1.
CCDSiCCDS20439.1. [P37238-1]
CCDS51876.1. [P37238-2]
PIRiA54101.
RefSeqiNP_001120802.1. NM_001127330.2.
NP_001295281.1. NM_001308352.1.
NP_001295283.1. NM_001308354.1.
NP_035276.2. NM_011146.3.
XP_006505806.1. XM_006505743.3.
XP_011239554.1. XM_011241252.1.
XP_017176944.1. XM_017321455.1.
UniGeneiMm.3020.

3D structure databases

ProteinModelPortaliP37238.
SMRiP37238.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202320. 35 interactors.
DIPiDIP-60435N.
IntActiP37238. 4 interactors.
STRINGi10090.ENSMUSP00000000450.

Chemistry databases

BindingDBiP37238.
ChEMBLiCHEMBL2459.
SwissLipidsiSLP:000001625.

PTM databases

iPTMnetiP37238.
PhosphoSitePlusiP37238.

Proteomic databases

PaxDbiP37238.
PRIDEiP37238.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi19016.
KEGGimmu:19016.

Organism-specific databases

CTDi5468.
MGIiMGI:97747. Pparg.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000261626.
HOVERGENiHBG106004.
InParanoidiP37238.
KOiK08530.
PhylomeDBiP37238.

Enzyme and pathway databases

ReactomeiR-MMU-381340. Transcriptional regulation of white adipocyte differentiation.
R-MMU-442533. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

Miscellaneous databases

PROiP37238.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PPARG.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR003074. 1Cnucl_rcpt.
IPR003077. 1Cnucl_rcpt_G.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR022590. PPARgamma_N.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF12577. PPARgamma_N. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01288. PROXISOMEPAR.
PR01291. PROXISOMPAGR.
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 nameiPPARG_MOUSE
AccessioniPrimary (citable) accession number: P37238
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: April 27, 2001
Last modified: November 30, 2016
This is version 180 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, 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.