Peroxisome proliferator-activated receptor gamma

NamePeroxisome proliferator-activated receptor gamma
Synonyms
  • NR1C3
  • Nuclear receptor subfamily 1 group C member 3
  • PPAR-gamma
Gene NamePPARG
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000429|Peroxisome proliferator-activated receptor gamma
MGETLGDSPIDPESDSFTDTLSANISQEMTMVDTEMPFWPTNFGISSVDLSVMEDHSHSF
DIKPFTTVDFSSISTPHYEDIPFTRTDPVVADYKYDLKLQEYQSAIKVEPASPPYYSEKT
QLYNKPHEEPSNSLMAIECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLIYDRCDLNC
RIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEISSDIDQLNPESADLR
ALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMGEDKIKFKHITPLQE
QSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLLKYGVHEIIYTMLAS
LMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALELDDSDLAIFIAVII
LSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQKMTDLRQIVTEHVQL
LQVIKKTETDMSLHPLLQEIYKDLY
Number of residues505
Molecular Weight57619.58
Theoretical pI5.77
GO Classification
Functions
  • core promoter sequence-specific DNA binding
  • RNA polymerase II regulatory region DNA binding
  • transcription factor activity, sequence-specific DNA binding
  • retinoid X receptor binding
  • drug binding
  • ligand-dependent nuclear receptor transcription coactivator activity
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
  • zinc ion binding
  • alpha-actinin binding
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
  • prostaglandin receptor activity
  • transcription regulatory region DNA binding
  • steroid hormone receptor activity
  • DNA binding
  • activating transcription factor binding
  • chromatin binding
  • arachidonic acid binding
  • enzyme binding
Processes
  • positive regulation of transcription from RNA polymerase II promoter
  • cellular response to hyperoxia
  • fatty acid oxidation
  • negative regulation of smooth muscle cell proliferation
  • regulation of blood pressure
  • lipid metabolic process
  • response to lipid
  • response to vitamin A
  • G-protein coupled receptor signaling pathway
  • gene expression
  • epithelial cell differentiation
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • cellular response to lithium ion
  • low-density lipoprotein particle receptor biosynthetic process
  • transcription initiation from RNA polymerase II promoter
  • cell fate commitment
  • response to estrogen
  • negative regulation of interferon-gamma-mediated signaling pathway
  • placenta development
  • response to caffeine
  • negative regulation of transcription from RNA polymerase II promoter
  • negative regulation of receptor biosynthetic process
  • response to retinoic acid
  • monocyte differentiation
  • response to starvation
  • negative regulation of acute inflammatory response
  • cellular response to insulin stimulus
  • negative regulation of sequestering of triglyceride
  • negative regulation of cholesterol storage
  • white fat cell differentiation
  • glucose homeostasis
  • lipoprotein transport
  • negative regulation of transcription, DNA-templated
  • signal transduction
  • negative regulation of macrophage derived foam cell differentiation
  • brown fat cell differentiation
  • response to low-density lipoprotein particle
  • positive regulation of phagocytosis, engulfment
  • innate immune response
  • positive regulation of sequence-specific DNA binding transcription factor activity
  • diet induced thermogenesis
  • regulation of circadian rhythm
  • positive regulation of fat cell differentiation
  • negative regulation of collagen biosynthetic process
  • cellular response to retinoic acid
  • response to diuretic
  • response to cold
  • organ regeneration
  • response to immobilization stress
  • negative regulation of pancreatic stellate cell proliferation
  • cellular response to vitamin E
  • long-chain fatty acid transport
  • negative regulation of cell growth
  • cellular response to prostaglandin E stimulus
  • positive regulation of oligodendrocyte differentiation
  • negative regulation of telomerase activity
  • positive regulation of transcription, DNA-templated
  • lipid homeostasis
  • response to mechanical stimulus
  • positive regulation of fatty acid oxidation
  • rhythmic process
  • response to nutrient
  • regulation of cholesterol transporter activity
  • heart development
  • regulation of transcription involved in cell fate commitment
  • peroxisome proliferator activated receptor signaling pathway
  • cell maturation
  • response to metformin
Components
  • Golgi apparatus
  • cytosol
  • nucleoplasm
  • perinuclear region of cytoplasm
  • nucleus
  • intracellular membrane-bounded organelle
  • RNA polymerase II transcription factor complex
General FunctionZinc ion binding
Specific FunctionNuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. 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. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1711117
UniProtKB IDP37231
UniProtKB Entry NamePPARG_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0021642|Peroxisome proliferator-activated receptor gamma (PPARG)
ATGACCATGGTTGACACAGAGATGCCATTCTGGCCCACCAACTTTGGGATCAGCTCCGTG
GATCTCTCCGTAATGGAAGACCACTCCCACTCCTTTGATATCAAGCCCTTCACTACTGTT
GACTTCTCCAGCATTTCTACTCCACATTACGAAGACATTCCATTCACAAGAACAGATCCA
GTGGTTGCAGATTACAAGTATGACCTGAAACTTCAAGAGTACCAAAGTGCAATCAAAGTG
GAGCCTGCATCTCCACCTTATTATTCTGAGAAGACTCAGCTCTACAATAAGCCTCATGAA
GAGCCTTCCAACTCCCTCATGGCAATTGAATGTCGTGTCTGTGGAGATAAAGCTTCTGGA
TTTCACTATGGAGTTCATGCTTGTGAAGGATGCAAGGGTTTCTTCCGGAGAACAATCAGA
TTGAAGCTTATCTATGACAGATGTGATCTTAACTGTCGGATCCACAAAAAAAGTAGAAAT
AAATGTCAGTACTGTCGGTTTCAGAAATGCCTTGCAGTGGGGATGTCTCATAATGCCATC
AGGTTTGGGCGGATGCCACAGGCCGAGAAGGAGAAGCTGTTGGCGGAGATCTCCAGTGAT
ATCGACCAGCTGAATCCAGAGTCCGCTGACCTCCGGGCCCTGGCAAAACATTTGTATGAC
TCATACATAAAGTCCTTCCCGCTGACCAAAGCAAAGGCGAGGGCGATCTTGACAGGAAAG
ACAACAGACAAATCACCATTCGTTATCTATGACATGAATTCCTTAATGATGGGAGAAGAT
AAAATCAAGTTCAAACACATCACCCCCCTGCAGGAGCAGAGCAAAGAGGTGGCCATCCGC
ATCTTTCAGGGCTGCCAGTTTCGCTCCGTGGAGGCTGTGCAGGAGATCACAGAGTATGCC
AAAAGCATTCCTGGTTTTGTAAATCTTGACTTGAACGACCAAGTAACTCTCCTCAAATAT
GGAGTCCACGAGATCATTTACACAATGCTGGCCTCCTTGATGAATAAAGATGGGGTTCTC
ATATCCGAGGGCCAAGGCTTCATGACAAGGGAGTTTCTAAAGAGCCTGCGAAAGCCTTTT
GGTGACTTTATGGAGCCCAAGTTTGAGTTTGCTGTGAAGTTCAATGCACTGGAATTAGAT
GACAGCGACTTGGCAATATTTATTGCTGTCATTATTCTCAGTGGAGACCGCCCAGGTTTG
CTGAATGTGAAGCCCATTGAAGACATTCAAGACAACCTGCTACAAGCCCTGGAGCTCCAG
CTGAAGCTGAACCACCCTGAGTCCTCACAGCTGTTTGCCAAGCTGCTCCAGAAAATGACA
GACCTCAGACAGATTGTCACGGAACACGTGCAGCTACTGCAGGTGATCAAGAAGACGGAG
ACAGACATGAGTCTTCACCCGCTCCTGCAGGAGATCTACAAGGACTTGTACTAG
GenBank Gene IDU79012
GeneCard IDNot Available
GenAtlas IDPPARG
HGNC IDHGNC:9236
Chromosome Location3
Locus3p25
References
  1. Mukherjee R, Jow L, Croston GE, Paterniti JR Jr: Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists. J Biol Chem. 1997 Mar 21;272(12):8071-6. 9065481
  2. Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz Md, Moller DE, Berger J: Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun. 1996 Jul 16;224(2):431-7. 8702406
  3. Yanase T, Yashiro T, Takitani K, Kato S, Taniguchi S, Takayanagi R, Nawata H: Differential expression of PPAR gamma1 and gamma2 isoforms in human adipose tissue. Biochem Biophys Res Commun. 1997 Apr 17;233(2):320-4. 9144532
  4. Greene ME, Blumberg B, McBride OW, Yi HF, Kronquist K, Kwan K, Hsieh L, Greene G, Nimer SD: Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr. 1995;4(4-5):281-99. 7787419
  5. Okazawa H, Mori H, Tamori Y, Araki S, Niki T, Masugi J, Kawanishi M, Kubota T, Shinoda H, Kasuga M: No coding mutations are detected in the peroxisome proliferator-activated receptor-gamma gene in Japanese patients with lipoatrophic diabetes. Diabetes. 1997 Nov;46(11):1904-6. 9356045
  6. Lambe KG, Tugwood JD: A human peroxisome-proliferator-activated receptor-gamma is activated by inducers of adipogenesis, including thiazolidinedione drugs. Eur J Biochem. 1996 Jul 1;239(1):1-7. 8706692
  7. Kim HJ, Woo IS, Kang ES, Eun SY, Kim HJ, Lee JH, Chang KC, Kim JH, Seo HG: Identification of a truncated alternative splicing variant of human PPARgamma1 that exhibits dominant negative activity. Biochem Biophys Res Commun. 2006 Sep 1;347(3):698-706. Epub 2006 Jul 5. 16842753
  8. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  9. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. 16641997
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  11. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA: Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem. 2000 Feb 25;275(8):5308-17. 10681503
  12. Zhou XP, Smith WM, Gimm O, Mueller E, Gao X, Sarraf P, Prior TW, Plass C, von Deimling A, Black PM, Yates AJ, Eng C: Over-representation of PPARgamma sequence variants in sporadic cases of glioblastoma multiforme: preliminary evidence for common low penetrance modifiers for brain tumour risk in the general population. J Med Genet. 2000 Jun;37(6):410-4. 10851250
  13. Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ: Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. J Biol Chem. 2002 Aug 9;277(32):28624-30. Epub 2002 May 30. 12039952
  14. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. 11971969
  15. Bu H, Kashireddy P, Chang J, Zhu YT, Zhang Z, Zheng W, Rao SM, Zhu YJ: ERBP, a novel estrogen receptor binding protein enhancing the activity of estrogen receptor. Biochem Biophys Res Commun. 2004 Apr 23;317(1):54-9. 15047147
  16. Drori S, Girnun GD, Tou L, Szwaya JD, Mueller E, Xia K, Shivdasani RA, Spiegelman BM: Hic-5 regulates an epithelial program mediated by PPARgamma. Genes Dev. 2005 Feb 1;19(3):362-75. 15687259
  17. Tomaru T, Satoh T, Yoshino S, Ishizuka T, Hashimoto K, Monden T, Yamada M, Mori M: Isolation and characterization of a transcriptional cofactor and its novel isoform that bind the deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-gamma. Endocrinology. 2006 Jan;147(1):377-88. Epub 2005 Oct 20. 16239304
  18. Yin Y, Yuan H, Wang C, Pattabiraman N, Rao M, Pestell RG, Glazer RI: 3-phosphoinositide-dependent protein kinase-1 activates the peroxisome proliferator-activated receptor-gamma and promotes adipocyte differentiation. Mol Endocrinol. 2006 Feb;20(2):268-78. Epub 2005 Sep 8. 16150867
  19. Burgermeister E, Chuderland D, Hanoch T, Meyer M, Liscovitch M, Seger R: Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma. Mol Cell Biol. 2007 Feb;27(3):803-17. Epub 2006 Nov 13. 17101779
  20. Park SH, Choi HJ, Yang H, Do KH, Kim J, Lee DW, Moon Y: Endoplasmic reticulum stress-activated C/EBP homologous protein enhances nuclear factor-kappaB signals via repression of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2010 Nov 12;285(46):35330-9. doi: 10.1074/jbc.M110.136259. Epub 2010 Sep 9. 20829347
  21. Park UH, Yoon SK, Park T, Kim EJ, Um SJ: Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in adipogenesis via reciprocal regulation of peroxisome proliferator-activated receptor {gamma}. J Biol Chem. 2011 Jan 14;286(2):1354-63. doi: 10.1074/jbc.M110.177816. Epub 2010 Nov 3. 21047783
  22. Khurana S, Chakraborty S, Lam M, Liu Y, Su YT, Zhao X, Saleem MA, Mathieson PW, Bruggeman LA, Kao HY: Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors. J Biol Chem. 2012 Apr 6;287(15):12027-35. doi: 10.1074/jbc.M112.345421. Epub 2012 Feb 17. 22351778
  23. Katano-Toki A, Satoh T, Tomaru T, Yoshino S, Ishizuka T, Ishii S, Ozawa A, Shibusawa N, Tsuchiya T, Saito T, Shimizu H, Hashimoto K, Okada S, Yamada M, Mori M: THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation. Mol Endocrinol. 2013 May;27(5):769-80. doi: 10.1210/me.2012-1332. Epub 2013 Mar 22. 23525231
  24. Uppenberg J, Svensson C, Jaki M, Bertilsson G, Jendeberg L, Berkenstam A: Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma. J Biol Chem. 1998 Nov 20;273(47):31108-12. 9813012
  25. Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, Rosenfeld MG, Willson TM, Glass CK, Milburn MV: Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature. 1998 Sep 10;395(6698):137-43. 9744270
  26. Gampe RT Jr, Montana VG, Lambert MH, Miller AB, Bledsoe RK, Milburn MV, Kliewer SA, Willson TM, Xu HE: Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol Cell. 2000 Mar;5(3):545-55. 10882139
  27. Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, Collins JL, Oplinger JA, Kliewer SA, Gampe RT Jr, McKee DD, Moore JT, Willson TM: Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13919-24. Epub 2001 Nov 6. 11698662
  28. Cronet P, Petersen JF, Folmer R, Blomberg N, Sjoblom K, Karlsson U, Lindstedt EL, Bamberg K: Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family. Structure. 2001 Aug;9(8):699-706. 11587644
  29. Ebdrup S, Pettersson I, Rasmussen HB, Deussen HJ, Frost Jensen A, Mortensen SB, Fleckner J, Pridal L, Nygaard L, Sauerberg P: Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar. J Med Chem. 2003 Apr 10;46(8):1306-17. 12672231
  30. Ostberg T, Svensson S, Selen G, Uppenberg J, Thor M, Sundbom M, Sydow-Backman M, Gustavsson AL, Jendeberg L: A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects. J Biol Chem. 2004 Sep 24;279(39):41124-30. Epub 2004 Jul 15. 15258145
  31. Haffner CD, Lenhard JM, Miller AB, McDougald DL, Dwornik K, Ittoop OR, Gampe RT Jr, Xu HE, Blanchard S, Montana VG, Consler TG, Bledsoe RK, Ayscue A, Croom D: Structure-based design of potent retinoid X receptor alpha agonists. J Med Chem. 2004 Apr 8;47(8):2010-29. 15056000
  32. Shi GQ, Dropinski JF, McKeever BM, Xu S, Becker JW, Berger JP, MacNaul KL, Elbrecht A, Zhou G, Doebber TW, Wang P, Chao YS, Forrest M, Heck JV, Moller DE, Jones AB: Design and synthesis of alpha-aryloxyphenylacetic acid derivatives: a novel class of PPARalpha/gamma dual agonists with potent antihyperglycemic and lipid modulating activity. J Med Chem. 2005 Jun 30;48(13):4457-68. 15974597
  33. Li Y, Choi M, Suino K, Kovach A, Daugherty J, Kliewer SA, Xu HE: Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9505-10. Epub 2005 Jun 23. 15976031
  34. Hopkins CR, O'neil SV, Laufersweiler MC, Wang Y, Pokross M, Mekel M, Evdokimov A, Walter R, Kontoyianni M, Petrey ME, Sabatakos G, Roesgen JT, Richardson E, Demuth TP Jr: Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5659-63. Epub 2006 Aug 21. 16919947
  35. Mahindroo N, Wang CC, Liao CC, Huang CF, Lu IL, Lien TW, Peng YH, Huang WJ, Lin YT, Hsu MC, Lin CH, Tsai CH, Hsu JT, Chen X, Lyu PC, Chao YS, Wu SY, Hsieh HP: Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: design, synthesis, structural biology, and molecular docking studies. J Med Chem. 2006 Feb 9;49(3):1212-6. 16451087
  36. Lu IL, Huang CF, Peng YH, Lin YT, Hsieh HP, Chen CT, Lien TW, Lee HJ, Mahindroo N, Prakash E, Yueh A, Chen HY, Goparaju CM, Chen X, Liao CC, Chao YS, Hsu JT, Wu SY: Structure-based drug design of a novel family of PPARgamma partial agonists: virtual screening, X-ray crystallography, and in vitro/in vivo biological activities. J Med Chem. 2006 May 4;49(9):2703-12. 16640330
  37. Yen CJ, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, Burns DK, Roth J, Shuldiner AR: Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun. 1997 Dec 18;241(2):270-4. 9425261
  38. Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR: Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med. 1998 Oct 1;339(14):953-9. 9753710
  39. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998 Nov;20(3):284-7. 9806549
  40. Hamann A, Munzberg H, Buttron P, Busing B, Hinney A, Mayer H, Siegfried W, Hebebrand J, Greten H: Missense variants in the human peroxisome proliferator-activated receptor-gamma2 gene in lean and obese subjects. Eur J Endocrinol. 1999 Jul;141(1):90-2. 10407229
  41. Valve R, Sivenius K, Miettinen R, Pihlajamaki J, Rissanen A, Deeb SS, Auwerx J, Uusitupa M, Laakso M: Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women. J Clin Endocrinol Metab. 1999 Oct;84(10):3708-12. 10523018
  42. Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Spiegelman BM, Eng C: Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol Cell. 1999 Jun;3(6):799-804. 10394368
  43. Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen GL, Williams TD, Lewis H, Schafer AJ, Chatterjee VK, O'Rahilly S: Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999 Dec 23-30;402(6764):880-3. 10622252
  44. Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T: PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes. 2002 Dec;51(12):3586-90. 12453919
  45. Agarwal AK, Garg A: A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002 Jan;87(1):408-11. 11788685
  46. Masud S, Ye S: Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta-analysis. J Med Genet. 2003 Oct;40(10):773-80. 14569127
  47. Temelkova-Kurktschiev T, Hanefeld M, Chinetti G, Zawadzki C, Haulon S, Kubaszek A, Koehler C, Leonhardt W, Staels B, Laakso M: Ala12Ala genotype of the peroxisome proliferator-activated receptor gamma2 protects against atherosclerosis. J Clin Endocrinol Metab. 2004 Sep;89(9):4238-42. 15356014
  48. Kim KS, Choi SM, Shin SU, Yang HS, Yoon Y: Effects of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism on body fat distribution in female Korean subjects. Metabolism. 2004 Dec;53(12):1538-43. 15562396