Description: Homo sapiens peroxisome proliferator-activated receptor gamma (PPARG), transcript variant 2, mRNA. RefSeq Summary (NM_015869): This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr3:12,393,001-12,475,855 Size: 82,855 Total Exon Count: 7 Strand: + Coding Region Position: hg19 chr3:12,393,092-12,475,644 Size: 82,553 Coding Exon Count: 7
ID:PPARG_HUMAN DESCRIPTION: RecName: Full=Peroxisome proliferator-activated receptor gamma; Short=PPAR-gamma; AltName: Full=Nuclear receptor subfamily 1 group C member 3; 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. ENZYME REGULATION: PDPK1 activates its transcriptional activity independently of its kinase activity. 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. Interacts with PDPK1. Interacts with ASXL1 AND ASXL2. INTERACTION: Q00535:CDK5; NbExp=2; IntAct=EBI-781416, EBI-1041567; 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. TISSUE SPECIFICITY: Highest expression in adipose tissue. Lower in skeletal muscle, spleen, heart and liver. Also detectable in placenta, lung and ovary. PTM: O-GlcNAcylation at Thr-84 reduces transcriptional activity in adipocytes (By similarity). 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 CAUTION: 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";
atherosclerosis, generalized Temelkova-Kurktschiev, T. et al. 2004, Ala12Ala Genotype of the Peroxisome Proliferator-Activated Receptor {gamma}2 Protects against Atherosclerosis, The Journal of clinical endocrinology and metabolism. 2004 Sep;89(9):4238-42.
[PubMed 15356014]
In conclusion, our data suggest that the Ala(12)Ala genotype of the PPARgamma2 gene may protect from early atherosclerosis in subjects at risk for diabetes.
birth weight preterm delivery Meirhaeghe, A. et al. 2007, A Possible Role for the PPARG Pro12Ala Polymorphism in Preterm Birth, Diabetes 2007 56(2) 494-8.
[PubMed 17259396]
the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life.
body mass energy metabolism Rosado, E. L. et al. 2006, Effect of diet and PPARgamma2 and beta2-adrenergic receptor genes on energy metabolism and body composition in obese women, Nutr Hosp 2006 21(3) 317-31.
[PubMed 16771114]
Polymorphism in PPARgamma2 gene resulted in increased fat oxidation, regardless of genotype of beta2-adrenergic receptor gene. It is recommended control of the total intake of fats and SFA in Pro12Pro/Gln27Gln and Pro12Pro/Gln27Glu, and complex CHO and MUFA in Pro12Pro/Glu27Glu. In Pro12Ala/Gln27Glu, AGPI intake can result in greater body weight loss.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P37231
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AB565476 - Homo sapiens PPAR gamma mRNA for peroxisome proliferative activated receptor gamma, complete cds. LP895444 - Sequence 308 from Patent EP3253886. X90563 - H.sapiens mRNA for peroxisome proliferactor activated receptor gamma. AK290581 - Homo sapiens cDNA FLJ75648 complete cds, highly similar to Homo sapiens peroxisome proliferative activated receptor, gamma(PPARG), transcript variant 4, mRNA. L40904 - Homo sapiens peroxisome proliferator activated receptor gamma (PPARG) mRNA, complete cds. AB472042 - Homo sapiens PPARG mRNA for peroxisome proliferative activated receptor gamma isoform 6 variant, complete cds. BC006811 - Homo sapiens peroxisome proliferator-activated receptor gamma, mRNA (cDNA clone MGC:5041 IMAGE:3447380), complete cds. AJ698135 - Homo sapiens mRNA for peroxisome proliferative activated receptor gamma (PPARG gene), exon 5 skipping transcript. D83233 - Homo sapiens mRNA for PPAR gamma2, complete cds. U79012 - Human ligand activated transcription factor PPARgamma2 mRNA, complete cds. AB451486 - Homo sapiens PPARG mRNA for peroxisome proliferative activated receptor gamma isoform 2, partial cds, clone: FLJ82517SAAF. AB451337 - Homo sapiens PPARG mRNA for peroxisome proliferative activated receptor gamma isoform 2, complete cds, clone: FLJ82517SAAN. U63415 - Human peroxisome proliferator activated receptor gamma 2 mRNA, complete cds. AK223528 - Homo sapiens mRNA for peroxisome proliferative activated receptor gamma isoform 2 variant, clone: FCC124E05. AY222643 - Homo sapiens CREB3L2-PPARgamma mRNA, complete cds. CU675463 - Synthetic construct Homo sapiens gateway clone IMAGE:100019580 5' read PPARG mRNA. DQ356894 - Homo sapiens peroxisome proliferative acitvated receptor gamma (PPARG) mRNA, complete cds, alternatively spliced. AB528351 - Synthetic construct DNA, clone: pF1KB7770, Homo sapiens PPARG gene for peroxisome proliferator-activated receptor gamma, without stop codon, in Flexi system. KU178267 - Homo sapiens peroxisome proliferator-activated receptor gamma isoform 1 (PPARG) mRNA, partial cds. KU178268 - Homo sapiens peroxisome proliferator-activated receptor gamma isoform 2 (PPARG) mRNA, partial cds, alternatively spliced. KJ891855 - Synthetic construct Homo sapiens clone ccsbBroadEn_01249 PPARG gene, encodes complete protein. KR709631 - Synthetic construct Homo sapiens clone CCSBHm_00004352 PPARG (PPARG) mRNA, encodes complete protein. KR709632 - Synthetic construct Homo sapiens clone CCSBHm_00004356 PPARG (PPARG) mRNA, encodes complete protein. KR709633 - Synthetic construct Homo sapiens clone CCSBHm_00004358 PPARG (PPARG) mRNA, encodes complete protein. KR709634 - Synthetic construct Homo sapiens clone CCSBHm_00004362 PPARG (PPARG) mRNA, encodes complete protein. AB307692 - Homo sapiens NR1C3 mRNA for peroxisome proliferator activated receptor gamma, complete cds. BT007281 - Homo sapiens peroxisome proliferative activated receptor, gamma mRNA, complete cds. DQ891108 - Synthetic construct clone IMAGE:100003738; FLH169397.01X; RZPDo839B1196D peroxisome proliferative activated receptor, gamma (PPARG) gene, encodes complete protein. DQ894289 - Synthetic construct Homo sapiens clone IMAGE:100008749; FLH169393.01L; RZPDo839B1195D peroxisome proliferative activated receptor, gamma (PPARG) gene, encodes complete protein. HQ692866 - Homo sapiens peroxisome proliferator-activated nuclear receptor gamma variant 1 (NR1C3) mRNA, complete cds. LS999978 - Homo sapiens partial mRNA for peroxisome proliferator-activated receptor gamma (PPARG1D5 gene). LS999980 - Homo sapiens partial mRNA for peroxisome proliferator-activated receptor gamma (PPARG3D5 gene). LS999979 - Homo sapiens partial mRNA for peroxisome proliferator-activated receptor gamma (PPARG2D5 gene). AB247365 - Homo sapiens PPARG5 mRNA for peroxisome proliferator-activated receptor-gamma 5, complete cds, tissue_type:adipose tissue. AB247366 - Homo sapiens PPARG mRNA for peroxisome proliferator-activated receptor-gamma splicing variant, complete cds, tissue_type:adipose tissue. AB247367 - Homo sapiens PPARG5 mRNA for peroxisome proliferator-activated receptor-gamma 5, complete cds, tissue_type:liver. AB097931 - Homo sapiens PPARG mRNA for peroxisome proliferator-activated receptor gamma 1, partial cds. AB107271 - Homo sapiens PPARG mRNA for peroxisome proliferator-activated receptor, partial cds. AJ563370 - Homo sapiens mRNA for peroxisome proliferative activated receptor gamma (PPARG gene), alternative transcript 3. JD433359 - Sequence 414383 from Patent EP1572962. JD147235 - Sequence 128259 from Patent EP1572962. AJ563369 - Homo sapiens partial mRNA for peroxisome proliferative activated receptor gamma (PPARG gene), alternative transcript 2. JD134108 - Sequence 115132 from Patent EP1572962. JD402843 - Sequence 383867 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03320 - PPAR signaling pathway hsa05016 - Huntington's disease hsa05200 - Pathways in cancer hsa05216 - Thyroid cancer
BioCarta from NCI Cancer Genome Anatomy Project h_pparPathway - Basic mechanism of action of PPARa, PPARb(d) and PPARg and effects on gene expression h_nuclearRsPathway - Nuclear Receptors in Lipid Metabolism and Toxicity h_vobesityPathway - Visceral Fat Deposits and the Metabolic Syndrome h_ppargPathway - Role of PPAR-gamma Coactivators in Obesity and Thermogenesis
Reactome (by CSHL, EBI, and GO)
Protein P37231 (Reactome details) participates in the following event(s):
R-HSA-381262 Formation of PPARG:RXRA heterodimer (ARF6 complex) R-HSA-381290 PPARG:RXRA heterodimer binds to PPARG corepressors R-HSA-8944099 Activated PPARG binds PTEN gene promoter R-HSA-376419 Formation of NR-MED1 Coactivator Complex R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands R-HSA-381340 Transcriptional regulation of white adipocyte differentiation R-HSA-8943724 Regulation of PTEN gene transcription R-HSA-383280 Nuclear Receptor transcription pathway R-HSA-1266738 Developmental Biology R-HSA-6807070 PTEN Regulation R-HSA-212436 Generic Transcription Pathway R-HSA-1257604 PIP3 activates AKT signaling R-HSA-73857 RNA Polymerase II Transcription R-HSA-9006925 Intracellular signaling by second messengers R-HSA-74160 Gene expression (Transcription) R-HSA-162582 Signal Transduction