10         20         30         40         50         60
         |          |          |          |          |          |
MGETLGDSPI DPESDSFTDT LSANISQEMT MVDTEMPFWP TNFGISSVDL SVMEDHSHSF - 60
DIKPFTTVDF SSISTPHYED IPFTRTDPVV ADYKYDLKLQ EYQSAIKVEP ASPPYYSEKT - 120
QLYNKPHEEP SNSLMAIECR VCGDKASGFH YGVHACEGCK GFFRRTIRLK LIYDRCDLNC - 180
RIHKKSRNKC QYCRFQKCLA VGMSHNAIRF GRMPQAEKEK LLAEISSDID QLNPESADLR - 240
ALAKHLYDSY IKSFPLTKAK ARAILTGKTT DKSPFVIYDM NSLMMGEDKI KFKHITPLQE - 300
QSKEVAIRIF QGCQFRSVEA VQEITEYAKS IPGFVNLDLN DQVTLLKYGV HEIIYTMLAS - 360
LMNKDGVLIS EGQGFMTREF LKSLRKPFGD FMEPKFEFAV KFNALELDDS DLAIFIAVII - 420
LSGDRPGLLN VKPIEDIQDN LLQALELQLK LNHPESSQLF AKLLQKMTDL RQIVTEHVQL - 480
LQVIKKTETD MSLHPLLQEI YKDLY

UniProt has selected PPAR-gamma Isoform 2 (DP00718) as the canonical sequence. Isoform 1 (DP00718_A001) differs in that aa 1-28 of canonical Isoform 2 are missing in Isoform 1.

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.
SUBUNIT: Forms a heterodimer with the retinoic acid receptor RXRA 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. Interacts with PRDM16 (By similarity). Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 LXXLL motifs. Interacts with DNTTIP2, MAP2K1/MEK1, PRMT2 and TGFB1I1. P10909:CLU; NbExp=3; IntAct=EBI-781384, EBI-1104674; O60869:EDF1; NbExp=4; IntAct=EBI-781384, EBI-781301; Q6STE5-1:SMARCD3; NbExp=3; IntAct=EBI-781384, EBI-488506; Q6STE5-2:SMARCD3; NbExp=3; IntAct=EBI-781384, EBI-488511;


Subcellular Location: Nucleus. Cytoplasm. Note=Redistributed from the nucleus to the cytosol through a MAP2K1/MEK1-dependent manner. Event=Alternative splicing; Named isoforms=2; Comment=Additional isoforms seem to exist; Name=2; IsoId=P37231-1; Sequence=Displayed; Name=1; IsoId=P37231-2; Sequence=VSP_003645;
TISSUE SPECIFICITY: Highest expression in adipose tissue. Lower in skeletal muscle, spleen, heart and liver. Also detectable in placenta, lung and ovary.
POLYMORPHISM: Genetic variation in PPARG may influence body mass index (BMI) [MIM:606641]. BMI reflects the amount of fat, lean mass, and body build.
POLYMORPHISM: Genetic variations in PPARG influence the carotid intimal medial thickness (CIMT) [MIM:609338]. CIMT is a measure of atherosclerosis that is independently associated with traditional atherosclerotic cardiovascular disease risk factors and coronary atherosclerotic burden. 35 to 45% of the variability in multivariable-adjusted CIMT is explained by genetic factors.
DISEASE: Note=Defects in PPARG can lead to type 2 insulin- resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer.
DISEASE: Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.
DISEASE: Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.
DISEASE: Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. Sequence=AAN38992.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA23354.1; Type=Erroneous gene model prediction; Sequence=BAF83270.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA62153.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL='http://atlasgeneticsoncology.org/Genes/PPARGID383ch3p25.html';
WEB RESOURCE: Name=Wikipedia; Note=Peroxisome proliferator- activated receptor entry; URL='http://en.wikipedia.org/wiki/Peroxisome_proliferator-activated_receptor';
WEB RESOURCE: Name=GeneReviews; URL='http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PPARG';
WEB RESOURCE: Name=SeattleSNPs; URL='http://pga.gs.washington.edu/data/pparg/';
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL='http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PPARG';
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NOTE: See DP00714_A001 (Isoform 1) for disorder information.