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Protein

Peroxisome proliferator-activated receptor gamma

Gene

Pparg

Organism
Rattus norvegicus (Rat)
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.By similarity

Enzyme regulationi

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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi136 – 21075Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri139 – 15921NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri176 – 19823NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • brown fat cell differentiation Source: Ensembl
  • cell maturation Source: Ensembl
  • cellular response to hyperoxia Source: RGD
  • cellular response to insulin stimulus Source: Ensembl
  • cellular response to lithium ion Source: Ensembl
  • cellular response to prostaglandin E stimulus Source: RGD
  • cellular response to prostaglandin stimulus Source: RGD
  • cellular response to retinoic acid Source: RGD
  • cellular response to vitamin E Source: RGD
  • epithelial cell differentiation Source: Ensembl
  • fatty acid metabolic process Source: RGD
  • fatty acid oxidation Source: RGD
  • glucose homeostasis Source: Ensembl
  • heart development Source: RGD
  • lipoprotein transport Source: Ensembl
  • long-chain fatty acid transport Source: Ensembl
  • low-density lipoprotein particle receptor biosynthetic process Source: Ensembl
  • monocyte differentiation Source: Ensembl
  • negative regulation of acute inflammatory response Source: RGD
  • negative regulation of cell growth Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of cholesterol storage Source: Ensembl
  • negative regulation of collagen biosynthetic process Source: RGD
  • negative regulation of interferon-gamma-mediated signaling pathway Source: Ensembl
  • negative regulation of pancreatic stellate cell proliferation Source: RGD
  • negative regulation of receptor biosynthetic process Source: Ensembl
  • negative regulation of sequestering of triglyceride Source: Ensembl
  • negative regulation of smooth muscle cell proliferation Source: Ensembl
  • negative regulation of telomerase activity Source: RGD
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • organ regeneration Source: RGD
  • peroxisome proliferator activated receptor signaling pathway Source: Ensembl
  • placenta development Source: Ensembl
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of fat cell differentiation Source: HGNC
  • positive regulation of fatty acid oxidation Source: RGD
  • positive regulation of oligodendrocyte differentiation Source: RGD
  • positive regulation of phagocytosis, engulfment Source: RGD
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of blood pressure Source: Ensembl
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of fat cell differentiation Source: RGD
  • regulation of lipid metabolic process Source: RGD
  • regulation of transcription from RNA polymerase II promoter Source: RGD
  • regulation of transcription involved in cell fate commitment Source: UniProtKB
  • response to caffeine Source: RGD
  • response to cold Source: RGD
  • response to diuretic Source: RGD
  • response to drug Source: RGD
  • response to estrogen Source: RGD
  • response to immobilization stress Source: RGD
  • response to lipid Source: RGD
  • response to low-density lipoprotein particle Source: Ensembl
  • response to mechanical stimulus Source: RGD
  • response to metformin Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to retinoic acid Source: UniProtKB
  • response to starvation Source: RGD
  • response to vitamin A Source: RGD
  • rhythmic process Source: UniProtKB-KW
  • 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

ReactomeiREACT_334119. Nuclear Receptor transcription pathway.
REACT_351396. Transcriptional regulation of white adipocyte differentiation.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi3371. Pparg.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation
  • Cytoplasm By similarity

  • Note: Redistributed from the nucleus to the cytosol through a MAP2K1/MEK1-dependent manner. CCRN4L/NOC enhances its nuclear translocation (By similarity).By similarity

GO - Cellular componenti

  • cytosol Source: RGD
  • nucleus Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • RNA polymerase II transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi112 – 1121S → A: Increases adipogenic activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 505505Peroxisome proliferator-activated receptor gammaPRO_0000053497Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi84 – 841O-linked (GlcNAc)By similarity
Modified residuei112 – 1121Phosphoserine; by MAPK1 Publication

Post-translational modificationi

Phosphorylated by MAPK. The phosphorylation inhibits PPAR gamma activity.3 Publications
O-GlcNAcylation at Thr-84 reduces transcriptional activity in adipocytes.By similarity
Phosphorylated at basal conditions and dephosphorylated when treated with the ligand. May be dephosphorylated by PPP5C. The phosphorylated form may be inactive and dephosphorylation at induces adipogenic activity (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiO88275.

PTM databases

PhosphoSiteiO88275.

Expressioni

Tissue specificityi

Highest expression in adipose tissue.

Gene expression databases

GenevisibleiO88275. RN.

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 CCRN4L/NOC. Interacts with FOXO1 (acetylated form). Interacts with ACTN4.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012137.

Structurei

3D structure databases

ProteinModelPortaliO88275.
SMRiO88275. Positions 131-216, 234-505.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni205 – 28076Interaction with FAM120BBy similarityAdd
BLAST
Regioni317 – 505189Ligand-bindingBy similarityAdd
BLAST

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri139 – 15921NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri176 – 19823NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG266867.
GeneTreeiENSGT00780000121834.
HOGENOMiHOG000261626.
HOVERGENiHBG106004.
InParanoidiO88275.
KOiK08530.
OMAiHEEPSNS.
OrthoDBiEOG7X9G7F.
PhylomeDBiO88275.
TreeFamiTF316304.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR003074. 1Cnucl_rcpt.
IPR003077. 1Cnucl_rcpt_G.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR022590. PPARgamma_N.
IPR001723. Str_hrmn_rcpt.
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

Note: Additional isoforms seem to exist.

Isoform 2 (identifier: O88275-1) [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
MGETLGDPPV DPEHGAFADA LPMSTSQEIT MVDTEMPFWP TNFGISSVDL
60 70 80 90 100
SVMDDHSHSF 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 LKSLRKPFGD 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):57,567
Last modified:August 1, 1999 - v2
Checksum:iF16E5CAB122EBB32
GO
Isoform 1 (identifier: O88275-2) [UniParc]FASTAAdd to basket

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

Show »
Length:475
Mass (Da):54,471
Checksum:iC761352FDF9C4395
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti111 – 1111A → R in CAA73382 (Ref. 3) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3030Missing in isoform 1. 3 PublicationsVSP_003649Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156666 mRNA. Translation: AAD40119.1.
AF156665 mRNA. Translation: AAD40118.1.
AB019561 mRNA. Translation: BAA36485.1.
Y12882 mRNA. Translation: CAA73382.2.
AB011365 mRNA. Translation: BAA32540.1.
AF246457 mRNA. Translation: AAF63385.1.
AF246458 mRNA. Translation: AAF63386.1.
RefSeqiNP_001138838.1. NM_001145366.1. [O88275-2]
NP_001138839.1. NM_001145367.1. [O88275-2]
NP_037256.1. NM_013124.3. [O88275-1]
XP_006237071.1. XM_006237009.2. [O88275-2]
UniGeneiRn.23443.

Genome annotation databases

EnsembliENSRNOT00000012137; ENSRNOP00000012137; ENSRNOG00000008839. [O88275-1]
ENSRNOT00000051858; ENSRNOP00000045012; ENSRNOG00000008839. [O88275-2]
GeneIDi25664.
KEGGirno:25664.
UCSCiRGD:3371. rat. [O88275-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156666 mRNA. Translation: AAD40119.1.
AF156665 mRNA. Translation: AAD40118.1.
AB019561 mRNA. Translation: BAA36485.1.
Y12882 mRNA. Translation: CAA73382.2.
AB011365 mRNA. Translation: BAA32540.1.
AF246457 mRNA. Translation: AAF63385.1.
AF246458 mRNA. Translation: AAF63386.1.
RefSeqiNP_001138838.1. NM_001145366.1. [O88275-2]
NP_001138839.1. NM_001145367.1. [O88275-2]
NP_037256.1. NM_013124.3. [O88275-1]
XP_006237071.1. XM_006237009.2. [O88275-2]
UniGeneiRn.23443.

3D structure databases

ProteinModelPortaliO88275.
SMRiO88275. Positions 131-216, 234-505.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012137.

Chemistry

BindingDBiO88275.
ChEMBLiCHEMBL4797.

PTM databases

PhosphoSiteiO88275.

Proteomic databases

PRIDEiO88275.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012137; ENSRNOP00000012137; ENSRNOG00000008839. [O88275-1]
ENSRNOT00000051858; ENSRNOP00000045012; ENSRNOG00000008839. [O88275-2]
GeneIDi25664.
KEGGirno:25664.
UCSCiRGD:3371. rat. [O88275-1]

Organism-specific databases

CTDi5468.
RGDi3371. Pparg.

Phylogenomic databases

eggNOGiNOG266867.
GeneTreeiENSGT00780000121834.
HOGENOMiHOG000261626.
HOVERGENiHBG106004.
InParanoidiO88275.
KOiK08530.
OMAiHEEPSNS.
OrthoDBiEOG7X9G7F.
PhylomeDBiO88275.
TreeFamiTF316304.

Enzyme and pathway databases

ReactomeiREACT_334119. Nuclear Receptor transcription pathway.
REACT_351396. Transcriptional regulation of white adipocyte differentiation.

Miscellaneous databases

NextBioi607577.
PROiO88275.

Gene expression databases

GenevisibleiO88275. RN.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR003074. 1Cnucl_rcpt.
IPR003077. 1Cnucl_rcpt_G.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR022590. PPARgamma_N.
IPR001723. Str_hrmn_rcpt.
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...

Publicationsi

  1. "Rat peroxisome proliferator-activated receptors and brown adipose tissue function during cold acclimatization."
    Guardiola-Diaz H.M., Rehnmark S., Usuda N., Albrektsen T., Feltkamp D., Gustafsson J.-A., Alexson S.E.H.
    J. Biol. Chem. 274:23368-23377(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Strain: Sprague-Dawley.
    Tissue: Brown adipose tissue.
  2. "Down-regulation of PPAR gammma."
    Tanaka T., Itoh H.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Strain: Sprague-Dawley.
    Tissue: Adipose tissue.
  3. Escher P.
    Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  4. "Molecular cloning of rat PPAR-gamma gene."
    Miyakita A., Okuno S., Watanabe T.K., Oga K., Tsuji A., Hishigaki H., Suto T., Nakagawa K., Nakahara Y., Higashi K.
    Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Adipocyte.
  5. "Photoreceptor phagocytosis selectively activates PPARgamma expression in retinal pigment epithelial cells."
    Ershov A.V., Bazan N.G.
    J. Neurosci. Res. 60:328-337(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Long Evans.
  6. "Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma."
    Hu E., Kim J.B., Sarraf P., Spiegelman B.M.
    Science 274:2100-2103(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  7. "Transcriptional activation by peroxisome proliferator-activated receptor gamma is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site."
    Adams M., Reginato M.J., Shao D., Lazar M.A., Chatterjee V.K.
    J. Biol. Chem. 272:5128-5132(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112, MUTAGENESIS OF SER-112.
  8. "Insulin- and mitogen-activated protein kinase-mediated phosphorylation and activation of peroxisome proliferator-activated receptor gamma."
    Zhang B., Berger J., Zhou G., Elbrecht A., Biswas S., White-Carrington S., Szalkowski D., Moller D.E.
    J. Biol. Chem. 271:31771-31774(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.

Entry informationi

Entry nameiPPARG_RAT
AccessioniPrimary (citable) accession number: O88275
Secondary accession number(s): Q9QWG0, Q9R197
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 1, 1999
Last modified: June 24, 2015
This is version 153 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.