Peroxisome proliferator-activated receptor gamma

PPAR-G dimer bound to DNA. PDB rendering based on 3e00^[1].

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes

1FM6, 1FM9, 1I7I, 1K74, 1KNU, 1NYX, 1PRG, 1RDT, 1WM0, 1ZEO, 1ZGY, 2ATH, 2F4B, 2FVJ, 2G0G, 2G0H, 2GTK, 2HFP, 2HWQ, 2HWR, 2I4J, 2I4P, 2I4Z, 2OM9, 2P4Y, 2POB, 2PRG, 2Q59, 2Q5P, 2Q5S, 2Q61, 2Q6R, 2Q6S, 2Q8S, 2QMV, 2VSR, 2VST, 2VV0, 2VV1, 2VV2, 2VV3, 2VV4, 2XKW, 2YFE, 2ZK0, 2ZK1, 2ZK2, 2ZK3, 2ZK4, 2ZK5, 2ZK6, 2ZNO, 2ZVT, 3ADS, 3ADT, 3ADU, 3ADV, 3ADW, 3ADX, 3AN3, 3AN4, 3B0Q, 3B0R, 3B1M, 3B3K, 3BC5, 3CDP, 3CDS, 3CS8, 3CWD, 3D6D, 3DZU, 3DZY, 3E00, 3ET0, 3ET3, 3FEJ, 3FUR, 3G9E, 3GBK, 3H0A, 3HO0, 3HOD, 3IA6, 3K8S, 3KMG, 3LMP, 3NOA, 3OSI, 3OSW, 3PBA, 3PO9, 3PRG, 3QT0, 3R5N, 3R8A, 3R8I, 3S9S, 3SZ1, 3T03, 3TY0, 3U9Q, 3V9T, 3V9V, 3V9Y, 3VJH, 3VJI, 3VN2, 3VSO, 3VSP, 3WJ4, 3WJ5, 3WMH, 3X1H, 3X1I, 4A4V, 4A4W, 4CI5, 4E4K, 4E4Q, 4EM9, 4EMA, 4F9M, 4FGY, 4HEE, 4JAZ, 4JL4, 4L96, 4L98, 4O8F, 4OJ4, 4PRG, 4PVU, 4PWL

Identifiers

Symbols

PPARG ; CIMT1; GLM1; NR1C3; PPARG1; PPARG2; PPARgamma

External IDs

OMIM: 601487 MGI: 97747 HomoloGene: 7899 IUPHAR: 595 ChEMBL: 235 GeneCards: PPARG Gene

Gene ontology
Molecular function	• RNA polymerase II regulatory region DNA binding • core promoter sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • steroid hormone receptor activity • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • prostaglandin receptor activity • protein binding • drug binding • zinc ion binding • enzyme binding • protein phosphatase binding • estrogen receptor binding • ligand-dependent nuclear receptor transcription coactivator activity • activating transcription factor binding • sequence-specific DNA binding • transcription regulatory region DNA binding • retinoid X receptor binding • arachidonic acid binding • alpha-actinin binding
Cellular component	• nucleus • nucleoplasm • cytosol • perinuclear region of cytoplasm • RNA polymerase II transcription factor complex
Biological process	• negative regulation of transcription from RNA polymerase II promoter • placenta development • diet induced thermogenesis • negative regulation of acute inflammatory response • transcription initiation from RNA polymerase II promoter • lipid metabolic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • signal transduction • G-protein coupled receptor signaling pathway • heart development • response to nutrient • regulation of blood pressure • response to cold • response to mechanical stimulus • gene expression • negative regulation of macrophage derived foam cell differentiation • negative regulation of receptor biosynthetic process • negative regulation of cholesterol storage • negative regulation of sequestering of triglyceride • long-chain fatty acid transport • fatty acid oxidation • monocyte differentiation • negative regulation of cell growth • epithelial cell differentiation • response to caffeine • organ regeneration • response to retinoic acid • cellular response to insulin stimulus • negative regulation of collagen biosynthetic process • response to vitamin A • response to lipid • peroxisome proliferator activated receptor signaling pathway • response to immobilization stress • response to diuretic • glucose homeostasis • response to starvation • regulation of circadian rhythm • lipoprotein transport • steroid hormone mediated signaling pathway • response to estrogen • innate immune response • cell fate commitment • positive regulation of fat cell differentiation • low-density lipoprotein particle receptor biosynthetic process • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • positive regulation of fatty acid oxidation • cell maturation • rhythmic process • negative regulation of smooth muscle cell proliferation • positive regulation of oligodendrocyte differentiation • white fat cell differentiation • brown fat cell differentiation • positive regulation of sequence-specific DNA binding transcription factor activity • negative regulation of telomerase activity • lipid homeostasis • response to low-density lipoprotein particle • positive regulation of phagocytosis, engulfment • negative regulation of interferon-gamma-mediated signaling pathway • regulation of cholesterol transporter activity • regulation of transcription involved in cell fate commitment • cellular response to lithium ion • cellular response to retinoic acid • cellular response to vitamin E • cellular response to prostaglandin E stimulus • cellular response to hyperoxia • response to metformin • negative regulation of pancreatic stellate cell proliferation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 3:
12.29 – 12.43 Mb

Chr 6:
115.36 – 115.49 Mb

PubMed search

Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor that in humans is encoded by the PPARG gene.^[2]^[3]^[4]

Tissue distribution

PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine).^[5]

Function

PPARG regulates fatty acid storage and glucose metabolism. The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice fail to generate adipose tissue when fed a high-fat diet.^[6]

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. Alternatively spliced transcript variants that encode different isoforms have been described.^[7]

Many naturally occurring agents directly bind with and activate PPAR gamma. These agents include various polyunsaturated fatty acids like arachidonic acid and arachidonic acid metabolites such as certain members of the 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid family, e.g. 5-oxo-15(S)-HETE and 5-oxo-ETE or 15-Hydroxyicosatetraenoic acid family including 15(S)-HETE, 15(R)-HETE, and 15(S)-HpETE.^[8]^[9]^[10] The activation of PPAR gamma by these and other ligands may be responsible for inhibiting the growth of cultured human breast, gastric, lung, prostate and other cancer cell lines.^[11]

Interactions

Peroxisome proliferator-activated receptor gamma has been shown to interact with:

Clinical relevance

PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancer. PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia.^[22] PPAR-gamma decreases the inflammatory response of many cardiovascular cells, particularly endothelial cells.^[23] PPAR-gamma activates the PON1 gene, increasing synthesis and release of paraoxonase 1 from the liver, reducing atherosclerosis.^[24]

Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes target PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. Different classes of compounds which activate PPARgamma weaker than thiazolidinediones (the so-called “partial agonists of PPARgamma”) are currently studied with the hope that such compounds would be still effective hypoglycaemic agents but with fewer side effects.^[25]^[26]

A fusion protein of PPAR-γ1 and the thyroid transcription factor PAX8 is present in approximately one-third of follicular thyroid carcinomas, to be specific those cancers with a chromosomal translocation of t(2;3)(q13;p25), which permits juxtaposition of portions of both genes.^[27]^[28]

References

↑ Chandra, V.; Huang, P.; Hamuro, Y.; Raghuram, S.; Wang, Y.; Burris, T. P.; Rastinejad, F. (2008). "Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNA". Nature 456 (7220): 350–356. doi:10.1038/nature07413. PMC 2743566. PMID 19043829.
↑ Greene ME, Blumberg B, McBride OW, Yi HF, Kronquist K, Kwan K, Hsieh L, Greene G, Nimer SD (1995). "Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping". Gene Expr. 4 (4–5): 281–99. PMID 7787419.
↑ Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz MD, Moller DE, Berger J (July 1996). "Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2". Biochem. Biophys. Res. Commun. 224 (2): 431–7. doi:10.1006/bbrc.1996.1044. PMID 8702406.
↑ Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, Grimaldi PA, Kadowaki T, Lazar MA, O'Rahilly S, Palmer CN, Plutzky J, Reddy JK, Spiegelman BM, Staels B, Wahli W (December 2006). "International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors". Pharmacol. Rev. 58 (4): 726–41. doi:10.1124/pr.58.4.5. PMID 17132851.
↑ Fajas L, Auboeuf D, Raspé E, Schoonjans K, Lefebvre AM, Saladin R, Najib J, Laville M, Fruchart JC, Deeb S, Vidal-Puig A, Flier J, Briggs MR, Staels B, Vidal H, Auwerx J (July 1997). "The organization, promoter analysis, and expression of the human PPARgamma gene". J. Biol. Chem. 272 (30): 18779–89. doi:10.1074/jbc.272.30.18779. PMID 9228052.
↑ Jones JR, Barrick C, Kim KA, Lindner J, Blondeau B, Fujimoto Y, Shiota M, Kesterson RA, Kahn BB, Magnuson MA (April 2005). "Deletion of PPARγ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance". Proc. Natl. Acad. Sci. U.S.A. 102 (17): 6207–12. Bibcode:2005PNAS..102.6207J. doi:10.1073/pnas.0306743102. PMC 556131. PMID 15833818.
↑ "Entrez Gene: PPARG peroxisome proliferator-activated receptor gamma".
↑ Dreyer C, Keller H, Mahfoudi A, Laudet V, Krey G, Wahli W (1993). "Positive regulation of the peroxisomal beta-oxidation pathway by fatty acids through activation of peroxisome proliferator-activated receptors (PPAR)". Biol. Cell 77 (1): 67–76. doi:10.1016/s0248-4900(05)80176-5. PMID 8390886.
↑ O'Flaherty JT, Rogers LC, Paumi CM, Hantgan RR, Thomas LR, Clay CE, High K, Chen YQ, Willingham MC, Smitherman PK, Kute TE, Rao A, Cramer SD, Morrow CS (2005). "5-Oxo-ETE analogs and the proliferation of cancer cells". Biochim. Biophys. Acta 1736 (3): 228–36. doi:10.1016/j.bbalip.2005.08.009. PMID 16154383.
↑ Naruhn S, Meissner W, Adhikary T, Kaddatz K, Klein T, Watzer B, Müller-Brüsselbach S, Müller R (2010). "15-hydroxyeicosatetraenoic acid is a preferential peroxisome proliferator-activated receptor beta/delta agonist". Mol. Pharmacol. 77 (2): 171–84. doi:10.1124/mol.109.060541. PMID 19903832.
↑ Krishnan A, Nair SA, Pillai MR (2007). "Biology of PPAR gamma in cancer: a critical review on existing lacunae". Curr. Mol. Med. 7 (6): 532–40. doi:10.2174/156652407781695765. PMID 17896990.
↑ Brendel C, Gelman L, Auwerx J (June 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Mol. Endocrinol. 16 (6): 1367–77. doi:10.1210/mend.16.6.0843. PMID 12040021.
↑ Berger J, Patel HV, Woods J, Hayes NS, Parent SA, Clemas J, Leibowitz MD, Elbrecht A, Rachubinski RA, Capone JP, Moller DE (April 2000). "A PPARgamma mutant serves as a dominant negative inhibitor of PPAR signaling and is localized in the nucleus". Mol. Cell. Endocrinol. 162 (1–2): 57–67. doi:10.1016/S0303-7207(00)00211-2. PMID 10854698.
↑ Gampe RT, Montana VG, Lambert MH, Miller AB, Bledsoe RK, Milburn MV, Kliewer SA, Willson TM, Xu HE (March 2000). "Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors". Mol. Cell 5 (3): 545–55. doi:10.1016/S1097-2765(00)80448-7. PMID 10882139.
1 2 3 Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, Debril MB, Miard S, Auwerx J (December 2002). "The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation". Dev. Cell 3 (6): 903–10. doi:10.1016/S1534-5807(02)00360-X. PMID 12479814.
1 2 3 4 Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (October 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. 275 (43): 33201–4. doi:10.1074/jbc.C000517200. PMID 10944516.
↑ Franco PJ, Li G, Wei LN (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Mol. Cell. Endocrinol. 206 (1–2): 1–12. doi:10.1016/S0303-7207(03)00254-5. PMID 12943985.
↑ Heinlein CA, Ting HJ, Yeh S, Chang C (June 1999). "Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma". J. Biol. Chem. 274 (23): 16147–52. doi:10.1074/jbc.274.23.16147. PMID 10347167.
↑ Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y (January 2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation". J. Biol. Chem. 277 (2): 1586–92. doi:10.1074/jbc.M104301200. PMID 11696534.
↑ Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (November 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. PMID 14636573.
↑ Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (November 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science 286 (5443): 1368–71. doi:10.1126/science.286.5443.1368. PMID 10558993.
↑ Li Y, Qi Y, Huang TH, Yamahara J, Roufogalis BD (January 2008). "Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties". Diabetes Obes Metab 10 (1): 10–7. doi:10.1111/j.1463-1326.2007.00708.x. PMID 18095947.
↑ Hamblin M, Chang L, Fan Y, Zhang J, Chen YE (June 2009). "PPARs and the Cardiovascular System". Antioxid. Redox Signal. 11 (6): 1415–52. doi:10.1089/ARS.2008.2280. PMC 2737093. PMID 19061437.
↑ Khateeb J, Gantman A, Kreitenberg AJ, Aviram M, Fuhrman B (January 2010). "Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-gamma pathway". Atherosclerosis 208 (1): 119–25. doi:10.1016/j.atherosclerosis.2009.08.051. PMID 19783251.
↑ Atanasov AG, Wang JN, Gu SP, Bu J, Kramer MP, Baumgartner L, Fakhrudin N, Ladurner A, Malainer C, Vuorinen A, Noha SM, Schwaiger S, Rollinger JM, Schuster D, Stuppner H, Dirsch VM, Heiss EH (2013). "Honokiol: a non-adipogenic PPARγ agonist from nature". Biochim. Biophys. Acta 1830 (10): 4813–9. doi:10.1016/j.bbagen.2013.06.021. PMC 3790966. PMID 23811337.
↑ Atanasov AG, Blunder M, Fakhrudin N, Liu X, Noha SM, Malainer C, Kramer MP, Cocic A, Kunert O, Schinkovitz A, Heiss EH, Schuster D, Dirsch VM, Bauer R (2013). "Polyacetylenes from Notopterygium incisum--new selective partial agonists of peroxisome proliferator-activated receptor-gamma". PLoS ONE 8 (4): e61755. Bibcode:2013PLoSO...861755A. doi:10.1371/journal.pone.0061755. PMC 3632601. PMID 23630612.
↑ Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM, Fletcher JA (August 2000). "PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]". Science 289 (5483): 1357–60. Bibcode:2000Sci...289.1357K. doi:10.1126/science.289.5483.1357. PMID 10958784.
↑ Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "20". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders/Elsevier. ISBN 1-4160-2973-7.

Qi C, Zhu Y, Reddy JK (2001). "Peroxisome proliferator-activated receptors, coactivators, and downstream targets". Cell Biochem. Biophys. 32 Spring: 187–204. PMID 11330046.
Kadowaki T, Hara K, Kubota N, Tobe K, Terauchi Y, Yamauchi T, Eto K, Kadowaki H, Noda M, Hagura R, Akanuma Y (2002). "The role of PPARgamma in high-fat diet-induced obesity and insulin resistance". J. Diabetes Complicat. 16 (1): 41–5. doi:10.1016/S1056-8727(01)00206-9. PMID 11872365.
Wakino S, Law RE, Hsueh WA (2002). "Vascular protective effects by activation of nuclear receptor PPARgamma". J. Diabetes Complicat. 16 (1): 46–9. doi:10.1016/S1056-8727(01)00197-0. PMID 11872366.
Takano H, Komuro I (2002). "Roles of peroxisome proliferator-activated receptor gamma in cardiovascular disease". J. Diabetes Complicat. 16 (1): 108–14. doi:10.1016/S1056-8727(01)00203-3. PMID 11872377.
Stumvoll M, Häring H (2002). "The peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism". Diabetes 51 (8): 2341–7. doi:10.2337/diabetes.51.8.2341. PMID 12145143.
Koeffler HP (2003). "Peroxisome proliferator-activated receptor gamma and cancers". Clin. Cancer Res. 9 (1): 1–9. PMID 12538445.
Puigserver P, Spiegelman BM (2003). "Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator". Endocr. Rev. 24 (1): 78–90. doi:10.1210/er.2002-0012. PMID 12588810.
Takano H, Hasegawa H, Nagai T, Komuro I (2003). "The role of PPARgamma-dependent pathway in the development of cardiac hypertrophy". Drugs Today 39 (5): 347–57. doi:10.1358/dot.2003.39.5.799458. PMID 12861348.
Rangwala SM, Lazar MA (2004). "Peroxisome proliferator-activated receptor gamma in diabetes and metabolism". Trends Pharmacol. Sci. 25 (6): 331–6. doi:10.1016/j.tips.2004.03.012. PMID 15165749.
Cuzzocrea S (2005). "Peroxisome proliferator-activated receptors gamma ligands and ischemia and reperfusion injury". Vascul. Pharmacol. 41 (6): 187–95. doi:10.1016/j.vph.2004.10.004. PMID 15653094.
Savage DB (2007). "PPAR gamma as a metabolic regulator: insights from genomics and pharmacology". Expert Reviews in Molecular Medicine 7 (1): 1–16. doi:10.1017/S1462399405008793. PMID 15673477.
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Gurnell M (2006). "Peroxisome proliferator-activated receptor gamma and the regulation of adipocyte function: lessons from human genetic studies". Best Pract. Res. Clin. Endocrinol. Metab. 19 (4): 501–23. doi:10.1016/j.beem.2005.10.001. PMID 16311214.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery

1fm6: THE 2.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE HETERODIMER OF THE HUMAN RXRALPHA AND PPARGAMMA LIGAND BINDING DOMAINS RESPECTIVELY BOUND WITH 9-CIS RETINOIC ACID AND ROSIGLITAZONE AND CO-ACTIVATOR PEPTIDES.

1fm9: THE 2.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE HETERODIMER OF THE HUMAN RXRALPHA AND PPARGAMMA LIGAND BINDING DOMAINS RESPECTIVELY BOUND WITH 9-CIS RETINOIC ACID AND GI262570 AND CO-ACTIVATOR PEPTIDES.

1i7i: CRYSTAL STRUCTURE OF THE LIGAND BINDING DOMAIN OF HUMAN PPAR-GAMMA IN COMPLEX WITH THE AGONIST AZ 242

1k74: The 2.3 Angstrom resolution crystal structure of the heterodimer of the human PPARgamma and RXRalpha ligand binding domains respectively bound with GW409544 and 9-cis retinoic acid and co-activator peptides.

1knu: LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST

1nyx: Ligand binding domain of the human peroxisome proliferator activated receptor gamma in complex with an agonist

1prg: LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA

1rdt: Crystal Structure of a new rexinoid bound to the RXRalpha ligand binding doamin in the RXRalpha/PPARgamma heterodimer

1wm0: PPARgamma in complex with a 2-BABA compound

1zeo: Crystal Structure of Human PPAR-gamma Ligand Binding Domain Complexed with an Alpha-Aryloxyphenylacetic Acid Agonist

1zgy: Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP

2ath: Crystal structure of the ligand binding domain of human PPAR-gamma im complex with an agonist

2f4b: Crystal structure of the ligand binding domain of human PPAR-gamma in complex with an agonist

2fvj: A novel anti-adipogenic partial agonist of peroxisome proliferator-activated receptor-gamma (PPARG) recruits pparg-coactivator-1 alpha (PGC1A) but potentiates insulin signaling in vitro

2g0g: Structure-based drug design of a novel family of PPAR partial agonists: virtual screening, x-ray crystallography and in vitro/in vivo biological activities

2g0h: Structure-based drug design of a novel family of PPAR partial agonists: virtual screening, x-ray crystallography and in vitro/in vivo biological activities

2gtk: Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists

2hfp: Crystal Structure of PPAR Gamma with N-sulfonyl-2-indole carboxamide ligands

2i4j: Crystal structure of the complex between PPARgamma and the agonist LT160 (ureidofibrate derivative)

2i4p: Crystal structure of the complex between PPARgamma and the partial agonist LT127 (ureidofibrate derivative). Structure obtained from crystals of the apo-form soaked for 30 days.

2i4z: Crystal structure of the complex between PPARgamma and the partial agonist LT127 (ureidofibrate derivative). This structure has been obtained from crystals soaked for 6 hours.

2om9: Ajulemic acid, a synthetic cannabinoid bound to PPAR gamma

2prg: LIGAND-BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA

3prg: LIGAND BINDING DOMAIN OF HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR

4prg: 0072 PARTIAL AGONIST PPAR GAMMA COCRYSTAL

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

Nuclear receptor ligands

CAR

Agonists	5β-Dihydroprogesterone 6,7-Dimethylesculetin Amiodarone Artemisinin Benfuracarb Carbamazepine Carvedilol Chlorpromazine Chrysin CITCO Clotrimazole Cyclophosphamide Cypermethrin DHEA Efavirenz Ellagic acid Griseofulvin Methoxychlor Mifepristone Nefazodone Nevirapine Nicardipine Octicizer Permethrin Phenobarbital Phenytoin Reserpine TCPOBOP Telmisartan Tolnaftate Troglitazone Valproic acid

Antagonists	3,17β-Estradiol 3α-Androstanol 3α-Androstenol 3β-Androstanol 17-Androstanol AITC Ethinyl estradiol Meclizine Nigramide J Okadaic acid PK-11195 S-07662 T-0901317

ERR

ERRα

Agonists	6,3′,4′-Trihydroxyflavone Biochanin A Cholesterol Daidzein Genistein

Antagonists	XCT-790

ERRβ

Agonists	DY-131 GSK-4716

Antagonists	4-Hydroxytamoxifen (afimoxifene) Diethylstilbestrol

ERRγ

Agonists	Bisphenol A DY-131 GSK-4716

Antagonists	4-Hydroxytamoxifen (afimoxifene) Diethylstilbestrol

FXR

Agonists	Bile acids Cafestol Chenodeoxycholic acid Fexaramine GW-4064 Obeticholic acid

Antagonists	Guggulsterone

LXR

Agonists	22R-Hydroxycholesterol 24S-Hydroxycholesterol 27-Hydroxycholesterol Cholestenoic acid DMHCA GW-3965 Hypocholamide T-0901317

PPAR

PPARα

Agonists	15-HETE 15-HpETE Aleglitazar Aluminium clofibrate Arachidonic acid Bezafibrate Clofibrate CP-775146 Daidzein DHEA Elafibranor Fenofibrate Genistein Gemfibrozil GW-7647 Leukotriene B₄ LG-101506 LG-100754 Lobeglitazone Muraglitazar Oleylethanolamide Palmitoylethanolamide Pemafibrate Perfluorononanoic acid Perfluorooctanoic acid Pioglitazone Saroglitazar Sodelglitazar Tesaglitazar Tetradecylthioacetic acid Troglitazone WY-14643

Antagonists	GW-6471 MK-886

PPARδ

Agonists	15-HETE 15-HpETE Arachidonic acid Bezafibrate Daidzein Elafibranor Genistein GW-0742 GW-501516 L-165,041 LG-101506 MBX-8025 Sodelglitazar Tetradecylthioacetic acid

Antagonists	FH-535 GSK-0660 GSK-3787

PPARγ

Agonists	5-Oxo-ETE 5-Oxo-15-hydroxy-ETE 15-Deoxy-Δ^12,14-prostaglandin J₂ 15-HETE 15-HpETE Aleglitazar Arachidonic acid Berberine Bezafibrate Ciglitazone Daidzein Darglitazone Edaglitazone Etalocib Genistein GW-1929 Ibuprofen LG-100268 LG-100754 LG-101506 Lobeglitazone Muraglitazar nTZDpa Perfluorononanoic acid Pioglitazone Prostaglandin J₂ Rosiglitazone RS5444 Saroglitazar Sodelglitazar Telmisartan Tesaglitazar Troglitazone

SPPARMs	BADGE EPI-001 INT-131 MK-0533 S26948

Antagonists	FH-535 GW-9662 SR-202 T-0070907

Unknown	SR-1664

Unselective

Agonists	Ciprofibrate Clinofibrate Clofibride Englitazone Etofibrate Farglitazar Netoglitazone Ronifibrate Rivoglitazone Simfibrate

PXR

Agonists	5α-Dihydroprogesterone 5β-Dihydroprogesterone 17α-Hydroxypregnenolone 17α-Hydroxyprogesterone Δ⁴-Androstenedione Δ⁵-Androstenediol Δ⁵-Androstenedione AA-861 Allopregnanolone Alpha-Lipoic acid Ambrisentan AMI-193 Amlodipine besylate Antimycotics Artemisinin Aurothioglucose Bile acids Bithionol Bosentan Bumecaine Cafestol Cephaloridine Cephradine Chlorpromazine Ciglitazone Clindamycin Clofenvinfos Chloroxine Clotrimazole Colforsin Corticosterone Cyclophosphamide Cyproterone acetate Demecolcine Dexamethasone DHEA DHEA-S Dibunate sodium Diclazuril Dicloxacillin Dimercaprol Dinaline Docetaxel Docusate calcium Dodecylbenzenesulfonic acid Dronabinol Droxidopa Eburnamonine Ecopipam Enzacamene Epothilone B Erythromycin Famprofazone Febantel Felodipine Fenbendazole Fentanyl Flucloxacillin Fluorometholone Griseofulvin Haloprogin Hetacillin potassium Hyperforin (Hypericum perforatum) Indinavir sulfate Lasalocid sodium Levothyroxine Linolenic acid LOE-908 Loratadine Lovastatin Meclizine Methacycline Methylprednisolone Metyrapone Mevastatin Mifepristone Nafcillin Nicardipine Nicotine Nifedipine Nilvadipine Nisoldipine Norelgestromin Omeprazole Orlistat Oxatomide Paclitaxel Phenobarbital Piperine Plicamycin Prednisolone Pregnanolone Pregnenolone Pregnenolone 16α-carbonitrile Proadifen Progesterone Reserpine Reverse triiodothyronine Rifampicin Rifaximin Rimexolone Riodipine Ritonavir Simvastatin Sirolimus Spironolactone Spiroxatrine SR-12813 Suberoylanilide Sulfisoxazole Suramin Tacrolimus Tenylidone Terconazole Testosterone isocaproate Tetracycline Thiamylal sodium Thiothixene Thonzonium bromide Tianeptine Troglitazone Troleandomycin Tropanyl 3,5-dimethulbenzoate Zafirlukast Zearalanol

Antagonists	Ketoconazole

RAR

Agonists	9CDHRA 9-cis-Retinoic acid (alitretinoin) AC-261066 AC-55649 Acitretin Adapalene all-trans-Retinoic acid (tretinoin) AM-580 BMS-493 BMS-753 BMS-961 CD-1530 CD-2314 CD-437 Ch-55 EC 23 Etretinate Fenretinide Isotretinoin Palovarotene Retinoic acid Retinol (vitamin A) Tamibarotene Tazarotene Tazarotenic acid TTNPB

Antagonists	BMS-195614 BMS-493 CD-2665 ER-50891 LE-135 MM-11253

RXR

Agonists	9CDHRA 9-cis-Retinoic acid (alitretinoin) all-trans-Retinoic acid (tretinoin) Bexarotene CD 3254 Docosahexaenoic acid Fluorobexarotene Isotretinoin LG-100268 LG-101506 LG-100754 Retinoic acid Retinol (vitamin A) SR-11237

Antagonists	HX-531 HX-630 LG-100754 PA-452 UVI-3003

SHR

See here instead.

VDR

Agonists	7-Dehydrocholesterol 22-Oxacalcitriol 25-Hydroxyergocalciferol Alfacalcidol Calcifediol Calciferol Calcipotriol Calcitriol Cholecalciferol (vitamin D₃) Dihydrotachysterol Doxercalciferol EB-1089 Eldecalcitol Ercalcidiol Ercalcitriol Ergocalciferol (vitamin D₂) Lithocholic acid Paricalcitol Tacalcitol

Agonists	Dextrothyroxine GC-1 Levothyroxine Liothyronine Thyroxine Tiratricol Triiodothyronine

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