P37238 (PPARG_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. 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. Ref.11
Enzyme regulation	PDPK1 activates its transcriptional activity independently of its kinase activity By similarity.
Subunit structure	Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, MAP2K1/MEK1, NR0B2, PDPK1 and PRMT2. Interacts (via DNA-binding domain) with HELZ2; the interaction stimulates the transcriptional activity of PPARG By similarity. 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 FAM120B, PRDM16 and TGFB1I1. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Subcellular location	Nucleus. 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. 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
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.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	brown 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 inflammatory response Traceable author statement PubMed 12163159. Source: MGI 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 placenta development Inferred from mutant phenotype PubMed 17463056. Source: MGI positive regulation of fat cell differentiation Inferred from expression pattern PubMed 16132694. Source: HGNC positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16239304. Source: UniProtKB response to retinoic acid Inferred from direct assay PubMed 16239304. Source: UniProtKB white fat cell differentiation Inferred from expression pattern PubMed 16132694. Source: HGNC
Cellular_component	cytosol Inferred from direct assay PubMed 12163159PubMed 15164767. Source: MGI nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II regulatory region DNA binding Inferred from direct assay PubMed 15175325. Source: MGI arachidonic acid binding Inferred from direct assay PubMed 9568715. Source: BHF-UCL chromatin binding Inferred from direct assay PubMed 19066220. Source: MGI 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 16239304. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SIRT1	Q96EB6	3	EBI-5260705,EBI-1802965	From a different organism.
Sirt1	Q923E4	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 505	505	Peroxisome proliferator-activated receptor gamma		PRO_0000053494
Regions
	DNA binding	136 – 210	75	Nuclear receptor
	Zinc finger	139 – 159	21	NR C4-type
	Zinc finger	176 – 198	23	NR C4-type
	Region	205 – 280	76	Interaction with FAM120B
	Region	317 – 505	189	Ligand-binding By similarity
Amino acid modifications
	Modified residue	112	1	Phosphoserine; by MAPK By similarity
	Glycosylation	84	1	O-linked (GlcNAc...) Ref.12
Natural variations
	Alternative sequence	1 – 30	30	Missing in isoform 1.		VSP_003647
Experimental info
	Sequence conflict	213 – 214	2	MP → DR in AAA62110. Ref.2
	Sequence conflict	281 – 283	3	NSL → SSF in AAA62110. Ref.2
	Sequence conflict	383	1	N → S Ref.2
	Sequence conflict	383	1	N → S Ref.4
	Sequence conflict	497	1	L → F in AAA62110. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified April 27, 2001. Version 3. Checksum: AB8F3F6086E2A10A	FASTA	505	57,598
	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
	Isoform 1 [UniParc]. Checksum: FD80BD50D9197D3F	FASTA	475	54,512
	10 20 30 40 50 60 MVDTEMPFWP TNFGISSVDL SVMEDHSHSF DIKPFTTVDF SSISAPHYED IPFTRADPMV 70 80 90 100 110 120 ADYKYDLKLQ EYQSAIKVEP ASPPYYSEKT QLYNRPHEEP SNSLMAIECR VCGDKASGFH 130 140 150 160 170 180 YGVHACEGCK GFFRRTIRLK LIYDRCDLNC RIHKKSRNKC QYCRFQKCLA VGMSHNAIRF 190 200 210 220 230 240 GRMPQAEKEK LLAEISSDID QLNPESADLR ALAKHLYDSY IKSFPLTKAK ARAILTGKTT 250 260 270 280 290 300 DKSPFVIYDM NSLMMGEDKI KFKHITPLQE QSKEVAIRIF QGCQFRSVEA VQEITEYAKN 310 320 330 340 350 360 IPGFINLDLN DQVTLLKYGV HEIIYTMLAS LMNKDGVLIS EGQGFMTREF LKNLRKPFGD 370 380 390 400 410 420 FMEPKFEFAV KFNALELDDS DLAIFIAVII LSGDRPGLLN VKPIEDIQDN LLQALELQLK 430 440 450 460 470 LNHPESSQLF AKVLQKMTDL RQIVTEHVQL LHVIKKTETD MSLHPLLQEI YKDLY

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]	"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.
+	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.
IPI	IPI00125193. IPI00266075.
PIR	A54101.
RefSeq	NP_001120802.1. NM_001127330.1. NP_035276.2. NM_011146.3.
UniGene	Mm.3020.
3D structure databases
ProteinModelPortal	P37238.
SMR	P37238. Positions 135-505.
ModBase	Search...
Protein-protein interaction databases
IntAct	P37238. 4 interactions.
STRING	10090.ENSMUSP00000000450.
PTM databases
PhosphoSite	P37238.
Proteomic databases
PRIDE	P37238.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000171644; ENSMUSP00000131962; ENSMUSG00000000440.
GeneID	19016.
KEGG	mmu:19016.
UCSC	uc012eqj.1. mouse.
Organism-specific databases
CTD	5468.
MGI	MGI:97747. Pparg.
Phylogenomic databases
eggNOG	NOG266867.
GeneTree	ENSGT00700000104361.
HOGENOM	HOG000261626.
HOVERGEN	HBG106004.
InParanoid	P37238.
KO	K08530.
OrthoDB	EOG41ZF9W.
Enzyme and pathway databases
Reactome	REACT_127416. Developmental Biology. REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
Gene expression databases
ArrayExpress	P37238.
Bgee	P37238.
CleanEx	MM_PPARG.
Genevestigator	P37238.
GermOnline	ENSMUSG00000000440. Mus musculus.
Family and domain databases
Gene3D	1.10.565.10. 2 hits. 3.30.50.10. 1 hit.
InterPro	IPR003074. 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]
Pfam	PF00104. Hormone_recep. 1 hit. PF12577. PPARgamma_N. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PRINTS	PR01288. PROXISOMEPAR. PR01291. PROXISOMPAGR. PR00398. STRDHORMONER. PR00047. STROIDFINGER.
SMART	SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view]
SUPFAM	SSF48508. Str_ncl_receptor. 1 hit.
PROSITE	PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P37238.
ChEMBL	CHEMBL2459.
NextBio	295444.
SOURCE	Search...

Entry information

Entry name

PPARG_MOUSE

Accession

Primary (citable) accession number: P37238

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	April 27, 2001
Last modified:	April 3, 2013
This is version 142 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program