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O88275 (PPARG_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Peroxisome proliferator-activated receptor gamma

Short name=PPAR-gamma
Alternative name(s):
Nuclear receptor subfamily 1 group C member 3
Gene names
Name:Pparg
Synonyms:Nr1c3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length505 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Enzyme regulation

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

Subunit structure

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 (via DNA-binding domain) with HELZ2; the interaction stimulates the transcriptional activity of PPARG. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction enhances the transcriptional activity of PPARG By similarity.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Note: Redistributed from the nucleus to the cytosol through a MAP2K1/MEK1-dependent manner By similarity.

Tissue specificity

Highest expression in adipose tissue.

Post-translational modification

Phosphorylated by MAPK. The phosphorylation inhibits PPAR gamma activity. Ref.6 Ref.7 Ref.8

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. Ref.6 Ref.7 Ref.8

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 componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Receptor
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

cell fate commitment

Inferred from electronic annotation. Source: Ensembl

cell maturation

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to lithium ion

Inferred from electronic annotation. Source: Ensembl

epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

fatty acid metabolic process

Traceable author statement Ref.1. Source: RGD

fatty acid oxidation

Inferred from mutant phenotype PubMed 17003342. Source: RGD

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from expression pattern PubMed 15754086. Source: RGD

lipoprotein transport

Inferred from electronic annotation. Source: Ensembl

long-chain fatty acid transport

Inferred from electronic annotation. Source: Ensembl

low-density lipoprotein particle receptor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

monocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of acute inflammatory response

Inferred from mutant phenotype PubMed 18479673. Source: RGD

negative regulation of cell growth

Inferred from mutant phenotype PubMed 18600431. Source: RGD

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 16556873PubMed 18594976. Source: RGD

negative regulation of cholesterol storage

Inferred from electronic annotation. Source: Ensembl

negative regulation of interferon-gamma-mediated signaling pathway

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 smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of telomerase activity

Inferred from mutant phenotype PubMed 16556873. Source: RGD

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from expression pattern PubMed 18565023. Source: RGD

peroxisome proliferator activated receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from electronic annotation. Source: Ensembl

positive regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of fatty acid oxidation

Inferred from mutant phenotype PubMed 18475159. Source: RGD

positive regulation of oligodendrocyte differentiation

Inferred from mutant phenotype PubMed 18543250. Source: RGD

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19383491. Source: BHF-UCL

regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

regulation of fat cell differentiation

Inferred from direct assay Ref.1. Source: RGD

regulation of lipid metabolic process

Inferred from mutant phenotype PubMed 18621767. Source: RGD

regulation of transcription from RNA polymerase II promoter

Inferred from expression pattern Ref.1. Source: RGD

response to caffeine

Inferred from expression pattern PubMed 18486259. Source: RGD

response to cold

Inferred from expression pattern Ref.1. Source: RGD

response to drug

Inferred from expression pattern PubMed 18846335. Source: RGD

response to estrogen

Inferred from expression pattern PubMed 18769493. Source: RGD

response to low-density lipoprotein particle

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from expression pattern PubMed 18520050. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 18304850. Source: RGD

response to retinoic acid

Inferred from sequence or structural similarity. Source: UniProtKB

response to vitamin A

Inferred from expression pattern PubMed 18384703. Source: RGD

white fat cell differentiation

Inferred from sequence or structural similarity. Source: HGNC

   Cellular_componentcytosol

Inferred from direct assay PubMed 16247333. Source: RGD

nucleus

Inferred from direct assay PubMed 16247333. Source: RGD

   Molecular_functionDNA binding

Inferred from direct assay PubMed 16257923. Source: RGD

RNA polymerase II regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from electronic annotation. Source: Ensembl

drug binding

Inferred from electronic annotation. Source: Ensembl

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from electronic annotation. Source: InterPro

ligand-dependent nuclear receptor transcription coactivator activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 19383491. Source: BHF-UCL

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19383491. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 2 (identifier: O88275-1)

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.
Isoform 1 (identifier: O88275-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 505505Peroxisome proliferator-activated receptor gamma
PRO_0000053497

Regions

DNA binding136 – 21075Nuclear receptor
Zinc finger139 – 15921NR C4-type
Zinc finger176 – 19823NR C4-type
Region205 – 28076Interaction with FAM120B By similarity
Region317 – 505189Ligand-binding By similarity

Amino acid modifications

Modified residue1121Phosphoserine; by MAPK Ref.7
Glycosylation841O-linked (GlcNAc) By similarity

Natural variations

Alternative sequence1 – 3030Missing in isoform 1.
VSP_003649

Experimental info

Mutagenesis1121S → A: Increases adipogenic activity. Ref.7
Sequence conflict1111A → R in CAA73382. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified August 1, 1999. Version 2.
Checksum: F16E5CAB122EBB32

FASTA50557,567
        10         20         30         40         50         60 
MGETLGDPPV DPEHGAFADA LPMSTSQEIT MVDTEMPFWP TNFGISSVDL SVMDDHSHSF 

        70         80         90        100        110        120 
DIKPFTTVDF SSISAPHYED IPFTRADPMV ADYKYDLKLQ EYQSAIKVEP ASPPYYSEKT 

       130        140        150        160        170        180 
QLYNRPHEEP SNSLMAIECR VCGDKASGFH YGVHACEGCK GFFRRTIRLK LIYDRCDLNC 

       190        200        210        220        230        240 
RIHKKSRNKC QYCRFQKCLA VGMSHNAIRF GRMPQAEKEK LLAEISSDID QLNPESADLR 

       250        260        270        280        290        300 
ALAKHLYDSY IKSFPLTKAK ARAILTGKTT DKSPFVIYDM NSLMMGEDKI KFKHITPLQE 

       310        320        330        340        350        360 
QSKEVAIRIF QGCQFRSVEA VQEITEYAKN IPGFINLDLN DQVTLLKYGV HEIIYTMLAS 

       370        380        390        400        410        420 
LMNKDGVLIS EGQGFMTREF LKSLRKPFGD FMEPKFEFAV KFNALELDDS DLAIFIAVII 

       430        440        450        460        470        480 
LSGDRPGLLN VKPIEDIQDN LLQALELQLK LNHPESSQLF AKVLQKMTDL RQIVTEHVQL 

       490        500 
LHVIKKTETD MSLHPLLQEI YKDLY 

« Hide

Isoform 1 [UniParc].

Checksum: C761352FDF9C4395
Show »

FASTA47554,471

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001138838.1. NM_001145366.1.
NP_001138839.1. NM_001145367.1.
NP_037256.1. NM_013124.3.
XP_006237071.1. XM_006237009.1.
UniGeneRn.23443.

3D structure databases

ProteinModelPortalO88275.
SMRO88275. Positions 131-216, 234-505.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBO88275.
ChEMBLCHEMBL4797.

PTM databases

PhosphoSiteO88275.

Proteomic databases

PRIDEO88275.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000012137; ENSRNOP00000012137; ENSRNOG00000008839. [O88275-1]
ENSRNOT00000051858; ENSRNOP00000045012; ENSRNOG00000008839. [O88275-2]
GeneID25664.
KEGGrno:25664.
UCSCRGD:3371. rat. [O88275-1]

Organism-specific databases

CTD5468.
RGD3371. Pparg.

Phylogenomic databases

eggNOGNOG266867.
GeneTreeENSGT00740000115076.
HOGENOMHOG000261626.
HOVERGENHBG106004.
InParanoidO88275.
KOK08530.
OMASTPHYED.
OrthoDBEOG7X9G7F.
PhylomeDBO88275.
TreeFamTF316304.

Gene expression databases

GenevestigatorO88275.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR003074. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF12577. PPARgamma_N. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01288. PROXISOMEPAR.
PR01291. PROXISOMPAGR.
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

NextBio607577.
PROO88275.

Entry information

Entry namePPARG_RAT
AccessionPrimary (citable) accession number: O88275
Secondary accession number(s): Q9QWG0, Q9R197
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 1, 1999
Last modified: April 16, 2014
This is version 140 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