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P37238 (PPARG_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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. Ref.11 Ref.12 Ref.14 Ref.16

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 (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. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16

Subcellular location

Nucleus. Cytoplasm By similarity. Note: Redistributed from the nucleus to the cytosol through a MAP2K1/MEK1-dependent manner By similarity. CCRN4L/NOC enhances its nuclear translocation. Ref.13 Ref.16

Tissue specificity

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. Ref.6 Ref.12

Developmental stage

It appears first at 13.5 dpc and increases until birth.

Post-translational modification

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. Ref.12 Ref.14

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
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbrown fat cell differentiation

Inferred from direct assay PubMed 18492766. Source: MGI

cell fate commitment

Inferred from genetic interaction Ref.9. Source: MGI

cellular response to lithium ion

Inferred from direct assay PubMed 15673614. Source: MGI

cellular response to organic cyclic compound

Inferred from direct assay PubMed 12055200. Source: MGI

epithelial cell differentiation

Inferred from genetic interaction Ref.9. Source: MGI

fat cell differentiation

Inferred from direct assay PubMed 12037571PubMed 12502791. Source: MGI

inflammatory response

Traceable author statement PubMed 12163159. Source: MGI

intracellular receptor signaling pathway

Traceable author statement PubMed 12163159. Source: GOC

long-chain fatty acid transport

Inferred from mutant phenotype PubMed 17463056. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 12370429. Source: MGI

negative regulation of cellular response to insulin stimulus

Inferred from mutant phenotype PubMed 11387233. Source: BHF-UCL

negative regulation of cytokine production

Inferred from mutant phenotype PubMed 18566389. Source: BHF-UCL

negative regulation of peptide hormone secretion

Inferred from mutant phenotype PubMed 11387233. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16127449. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 16127449. Source: BHF-UCL

placenta development

Inferred from mutant phenotype PubMed 17463056. Source: MGI

positive regulation of fat cell differentiation

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of fat cell differentiation

Inferred from direct assay PubMed 12097321. Source: MGI

regulation of transcription involved in cell fate commitment

Inferred from mutant phenotype PubMed 19324970. Source: UniProtKB

response to lipid

Inferred from direct assay PubMed 9568715. Source: BHF-UCL

response to retinoic acid

Inferred from direct assay PubMed 16239304. Source: UniProtKB

white fat cell differentiation

Inferred from direct assay. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay Ref.13. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 12163159PubMed 15164767. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.13. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay PubMed 16239304. Source: UniProtKB

RNA polymerase II regulatory region DNA binding

Inferred from direct assay PubMed 15175325. Source: MGI

RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 23275342. Source: MGI

arachidonic acid binding

Inferred from direct assay PubMed 9568715. Source: BHF-UCL

chromatin binding

Inferred from direct assay Ref.12. Source: UniProtKB

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

Traceable author statement PubMed 12163159. Source: MGI

ligand-dependent nuclear receptor transcription coactivator activity

Inferred from direct assay PubMed 16239304Ref.12. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 22863012. Source: IntAct

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.12. Source: UniProtKB

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from direct assay Ref.12. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SIRT1Q96EB63EBI-5260705,EBI-1802965From a different organism.
Sirt1Q923E42EBI-5260705,EBI-1802585

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P37238-1)

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: P37238-2)

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_0000053494

Regions

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

Amino acid modifications

Modified residue1121Phosphoserine; by MAPK Ref.12 Ref.14
Glycosylation841O-linked (GlcNAc) Ref.15

Natural variations

Alternative sequence1 – 3030Missing in isoform 1.
VSP_003647

Experimental info

Mutagenesis1121S → A: Increases basal and ligand-induced adipogenic activity. Abolishes repression by PER2 on transactivation activity. Ref.12 Ref.14
Mutagenesis1121S → D: No effect on repression by PER2 on transactivation activity. Ref.12 Ref.14
Sequence conflict213 – 2142MP → DR in AAA62110. Ref.2
Sequence conflict281 – 2833NSL → SSF in AAA62110. Ref.2
Sequence conflict3831N → S in AAA62110. Ref.2
Sequence conflict3831N → S in AAA19971. Ref.4
Sequence conflict4971L → F in AAA62110. Ref.2

Sequences

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

Last modified April 27, 2001. Version 3.
Checksum: AB8F3F6086E2A10A

FASTA50557,598
        10         20         30         40         50         60 
MGETLGDSPV DPEHGAFADA LPMSTSQEIT MVDTEMPFWP TNFGISSVDL SVMEDHSHSF 

        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 LKNLRKPFGD 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: FD80BD50D9197D3F
Show »

FASTA47554,512

References

[1]"mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer."
Tontonoz P., Hu E., Graves R.A., Budavari A.I., Spiegelman B.M.
Genes Dev. 8:1224-1234(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBUNIT.
Tissue: Adipose tissue.
[2]"Identification of two mPPAR related receptors and evidence for the existence of five subfamily members."
Chen F., Law S.W., O'Malley B.W.
Biochem. Biophys. Res. Commun. 196:671-677(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: BALB/c.
Tissue: Heart.
[3]"Cloning of a new member of the peroxisome proliferator-activated receptor gene family from mouse liver."
Zhu Y., Alvares K., Huang Q., Rao M.S., Reddy J.K.
J. Biol. Chem. 268:26817-26820(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: C57BL/6 X CBA.
Tissue: Liver.
[4]"Differential expression and activation of a family of murine peroxisome proliferator-activated receptors."
Kliewer S.A., Forman B.M., Blumberg B., Ong E.S., Borgmeyer U., Mangelsdorf D.J., Umesono K., Evans R.M.
Proc. Natl. Acad. Sci. U.S.A. 91:7355-7359(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[5]"Regulation of PPAR gamma gene expression by nutrition and obesity in rodents."
Vidal-Puig A., Jimenez-Linan M., Lowell B.B., Hamann A., Hu E., Spiegelman B., Flier J.S., Moller D.E.
J. Clin. Invest. 97:2553-2561(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]"Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha."
Tontonoz P., Graves R.A., Budavari A.I., Erdjument-Bromage H., Lui M., Hu E., Tempst P., Spiegelman B.M.
Nucleic Acids Res. 22:5628-5634(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 66-85 AND 146-160, SUBUNIT, TISSUE SPECIFICITY.
Tissue: Adipose tissue.
[7]"Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor."
Zhu Y., Qi C., Jain S., Rao M.S., Reddy J.K.
J. Biol. Chem. 272:25500-25506(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPARBP.
[8]"Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR."
Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K.
J. Biol. Chem. 275:13510-13516(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA6.
[9]"Hic-5 regulates an epithelial program mediated by PPARgamma."
Drori S., Girnun G.D., Tou L., Szwaya J.D., Mueller E., Xia K., Shivdasani R.A., Spiegelman B.M.
Genes Dev. 19:362-375(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[10]"Constitutive coactivator of peroxisome proliferator-activated receptor (PPARgamma), a novel coactivator of PPARgamma that promotes adipogenesis."
Li D., Kang Q., Wang D.-M.
Mol. Endocrinol. 21:2320-2333(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAM120B.
[11]"PRDM16 controls a brown fat/skeletal muscle switch."
Seale P., Bjork B., Yang W., Kajimura S., Chin S., Kuang S., Scime A., Devarakonda S., Conroe H.M., Erdjument-Bromage H., Tempst P., Rudnicki M.A., Beier D.R., Spiegelman B.M.
Nature 454:961-967(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PRDM16.
[12]"PER2 controls lipid metabolism by direct regulation of PPARgamma."
Grimaldi B., Bellet M.M., Katada S., Astarita G., Hirayama J., Amin R.H., Granneman J.G., Piomelli D., Leff T., Sassone-Corsi P.
Cell Metab. 12:509-520(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ADIPOGENESIS, INTERACTION WITH PER2, PHOSPHORYLATION AT SER-112, MUTAGENESIS OF SER-112, TISSUE SPECIFICITY.
[13]"A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation."
Kawai M., Green C.B., Lecka-Czernik B., Douris N., Gilbert M.R., Kojima S., Ackert-Bicknell C., Garg N., Horowitz M.C., Adamo M.L., Clemmons D.R., Rosen C.J.
Proc. Natl. Acad. Sci. U.S.A. 107:10508-10513(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CCRN4L.
[14]"Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor-? (PPAR?)."
Hinds T.D. Jr., Stechschulte L.A., Cash H.A., Whisler D., Banerjee A., Yong W., Khuder S.S., Kaw M.K., Shou W., Najjar S.M., Sanchez E.R.
J. Biol. Chem. 286:42911-42922(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ADIPOGENESIS, INTERACTION WITH PPP5C, PHOSPHORYLATION AT SER-112, DEPHOSPHORYLATION AT SER-112, MUTAGENESIS OF SER-112.
[15]"O-GlcNAc modification of PPARgamma reduces its transcriptional activity."
Ji S., Park S.Y., Roth J., Kim H.S., Cho J.W.
Biochem. Biophys. Res. Commun. 417:1158-1163(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-84.
[16]"THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation."
Katano-Toki A., Satoh T., Tomaru T., Yoshino S., Ishizuka T., Ishii S., Ozawa A., Shibusawa N., Tsuchiya T., Saito T., Shimizu H., Hashimoto K., Okada S., Yamada M., Mori M.
Mol. Endocrinol. 27:769-780(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HELZ2 AND THRAP3, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U09138 mRNA. Translation: AAA62277.1.
U01664 mRNA. Translation: AAA62110.1.
U01841 mRNA. Translation: AAC52134.1.
U10374 mRNA. Translation: AAA19971.1.
CCDSCCDS20439.1. [P37238-1]
CCDS51876.1. [P37238-2]
PIRA54101.
RefSeqNP_001120802.1. NM_001127330.1.
NP_035276.2. NM_011146.3.
XP_006505803.1. XM_006505740.1.
XP_006505804.1. XM_006505741.1.
XP_006505805.1. XM_006505742.1.
XP_006505806.1. XM_006505743.1.
XP_006505807.1. XM_006505744.1.
UniGeneMm.3020.

3D structure databases

ProteinModelPortalP37238.
SMRP37238. Positions 135-505.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202320. 27 interactions.
DIPDIP-60435N.
IntActP37238. 4 interactions.
STRING10090.ENSMUSP00000000450.

Chemistry

BindingDBP37238.
ChEMBLCHEMBL2459.

PTM databases

PhosphoSiteP37238.

Proteomic databases

PRIDEP37238.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID19016.
KEGGmmu:19016.
UCSCuc012eqj.1. mouse. [P37238-2]

Organism-specific databases

CTD5468.
MGIMGI:97747. Pparg.

Phylogenomic databases

eggNOGNOG266867.
HOGENOMHOG000261626.
HOVERGENHBG106004.
InParanoidP37238.
KOK08530.
PhylomeDBP37238.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.
REACT_200794. Mus musculus biological processes.

Gene expression databases

ArrayExpressP37238.
BgeeP37238.
CleanExMM_PPARG.
GenevestigatorP37238.

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

NextBio295444.
PROP37238.
SOURCESearch...

Entry information

Entry namePPARG_MOUSE
AccessionPrimary (citable) accession number: P37238
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: April 27, 2001
Last modified: July 9, 2014
This is version 154 of the entry and version 3 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot