O88275 (PPARG_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

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. 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 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.
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 Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara brown fat cell differentiation Inferred from electronic annotation. Source: Compara cell fate commitment Inferred from electronic annotation. Source: Compara cell maturation Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara cellular response to lithium ion Inferred from electronic annotation. Source: Compara epithelial cell differentiation Inferred from electronic annotation. Source: Compara fatty acid oxidation Inferred from mutant phenotype PubMed 17003342. Source: RGD glucose homeostasis Inferred from electronic annotation. Source: Compara heart development Inferred from expression pattern PubMed 15754086. Source: RGD induction of apoptosis Inferred from electronic annotation. Source: Compara lipoprotein transport Inferred from electronic annotation. Source: Compara long-chain fatty acid transport Inferred from electronic annotation. Source: Compara low-density lipoprotein particle receptor biosynthetic process Inferred from electronic annotation. Source: Compara monocyte differentiation Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of interferon-gamma-mediated signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of receptor biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of sequestering of triglyceride Inferred from electronic annotation. Source: Compara negative regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara organ regeneration Inferred from expression pattern PubMed 18565023. Source: RGD peroxisome proliferator activated receptor signaling pathway Inferred from electronic annotation. Source: Compara placenta development Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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 stimulus Inferred from expression pattern PubMed 18769493. Source: RGD response to low-density lipoprotein particle stimulus Inferred from electronic annotation. Source: Compara 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_component	cytosol Inferred from direct assay PubMed 16247333. Source: RGD nucleus Inferred from direct assay PubMed 16247333. Source: RGD
Molecular_function	RNA polymerase II regulatory region DNA binding Inferred from electronic annotation. Source: Compara chromatin binding Inferred from electronic annotation. Source: Compara drug binding Inferred from electronic annotation. Source: Compara 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 505	505	Peroxisome proliferator-activated receptor gamma		PRO_0000053497
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 By similarity
	Region	317 – 505	189	Ligand-binding By similarity
Amino acid modifications
	Modified residue	112	1	Phosphoserine; by MAPK Ref.7
	Glycosylation	84	1	O-linked (GlcNAc...) By similarity
Natural variations
	Alternative sequence	1 – 30	30	Missing in isoform 1.		VSP_003649
Experimental info
	Mutagenesis	112	1	S → A: Increases adipogenic activity. Ref.7
	Sequence conflict	111	1	A → R in CAA73382. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified August 1, 1999. Version 2. Checksum: F16E5CAB122EBB32	FASTA	505	57,567
	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
	Isoform 1 [UniParc]. Checksum: C761352FDF9C4395	FASTA	475	54,471
	10 20 30 40 50 60 MVDTEMPFWP TNFGISSVDL SVMDDHSHSF 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 LKSLRKPFGD 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]	"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.
IPI	IPI00207539. IPI00231890.
RefSeq	NP_001138838.1. NM_001145366.1. NP_001138839.1. NM_001145367.1. NP_037256.1. NM_013124.3.
UniGene	Rn.23443.
3D structure databases
ProteinModelPortal	O88275.
SMR	O88275. Positions 131-216, 234-505.
ModBase	Search...
PTM databases
PhosphoSite	O88275.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000012137; ENSRNOP00000012137; ENSRNOG00000008839. ENSRNOT00000051858; ENSRNOP00000045012; ENSRNOG00000008839.
GeneID	25664.
KEGG	rno:25664.
UCSC	RGD:3371. rat.
Organism-specific databases
CTD	5468.
RGD	3371. Pparg.
Phylogenomic databases
eggNOG	NOG266867.
GeneTree	ENSGT00700000104361.
HOGENOM	HOG000261626.
HOVERGEN	HBG106004.
InParanoid	O88275.
KO	K08530.
OMA	KTTDKSP.
Gene expression databases
Genevestigator	O88275.
GermOnline	ENSRNOG00000008839. Rattus norvegicus.
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	O88275.
ChEMBL	CHEMBL4797.
NextBio	607577.

Entry information

Entry name

PPARG_RAT

Accession

Primary (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 3, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program