Peroxisome proliferator-activated receptor delta

NamePeroxisome proliferator-activated receptor delta
Synonyms
  • NR1C2
  • NUC1
  • NUCI
  • Nuclear hormone receptor 1
  • Nuclear receptor subfamily 1 group C member 2
  • Peroxisome proliferator-activated receptor beta
  • PPAR-beta
  • PPAR-delta
  • PPARB
Gene NamePPARD
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002005|Peroxisome proliferator-activated receptor delta
MEQPQEEAPEVREEEEKEEVAEAEGAPELNGGPQHALPSSSYTDLSRSSSPPSLLDQLQM
GCDGASCGSLNMECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEKCERSCKIQKK
NRNKCQYCRFQKCLALGMSHNAIRFGRMPEAEKRKLVAGLTANEGSQYNPQVADLKAFSK
HIYNAYLKNFNMTKKKARSILTGKASHTAPFVIHDIETLWQAEKGLVWKQLVNGLPPYKE
ISVHVFYRCQCTTVETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASIVNK
DGLLVANGSGFVTREFLRSLRKPFSDIIEPKFEFAVKFNALELDDSDLALFIAAIILCGD
RPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKMADLRQLVTEHAQMMQRI
KKTETETSLHPLLQEIYKDMY
Number of residues441
Molecular Weight49902.99
Theoretical pI7.65
GO Classification
Functions
  • lipid binding
  • linoleic acid binding
  • sequence-specific DNA binding
  • transcription factor activity, sequence-specific DNA binding
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
  • drug binding
  • zinc ion binding
  • steroid hormone receptor activity
  • DNA binding
Processes
  • cholesterol metabolic process
  • keratinocyte migration
  • positive regulation of fat cell differentiation
  • cell-substrate adhesion
  • axon ensheathment
  • cellular response to hypoxia
  • cell proliferation
  • apoptotic signaling pathway
  • keratinocyte proliferation
  • fatty acid beta-oxidation
  • negative regulation of myoblast differentiation
  • intracellular receptor signaling pathway
  • gene expression
  • positive regulation of myoblast proliferation
  • positive regulation of skeletal muscle tissue regeneration
  • embryo implantation
  • transcription initiation from RNA polymerase II promoter
  • regulation of satellite cell proliferation
  • regulation of transcription from RNA polymerase II promoter
  • glucose metabolic process
  • negative regulation of transcription, DNA-templated
  • cell differentiation
  • positive regulation of transcription, DNA-templated
  • fatty acid transport
  • apoptotic process
  • generation of precursor metabolites and energy
  • decidualization
  • wound healing
  • glucose transport
  • lipid metabolic process
  • negative regulation of epithelial cell proliferation
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • adipose tissue development
  • negative regulation of transcription from RNA polymerase II promoter
  • fatty acid catabolic process
Components
  • nucleoplasm
  • nucleus
General FunctionZinc ion binding
Specific FunctionLigand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID190230
UniProtKB IDQ03181
UniProtKB Entry NamePPARD_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0019047|Peroxisome proliferator-activated receptor delta (PPARD)
ATGGAGCAGCCACAGGAGGAAGCCCCTGAGGTCCGGGAAGAGGAGGAGAAAGAGGAAGTG
GCAGAGGCAGAAGGAGCCCCAGAGCTCAATGGGGGACCACAGCATGCACTTCCTTCCAGC
AGCTACACAGACCTCTCCCGGAGCTCCTCGCCACCCTCACTGCTGGACCAACTGCAGATG
GGCTGTGACGGGGCCTCATGCGGCAGCCTCAACATGGAGTGCCGGGTGTGCGGGGACAAG
GCATCGGGCTTCCACTACGGTGTTCATGCATGTGAGGGGTGCAAGGGCTTCTTCCGTCGT
ACGATCCGCATGAAGCTGGAGTACGAGAAGTGTGAGCGCAGCTGCAAGATTCAGAAGAAG
AACCGCAACAAGTGCCAGTACTGCCGCTTCCAGAAGTGCCTGGCACTGGGCATGTCACAC
AACGCTATCCGTTTTGGTCGGATGCCGGAGGCTGAGAAGAGGAAGCTGGTGGCAGGGCTG
ACTGCAAACGAGGGGAGCCAGTACAACCCACAGGTGGCCGACCTGAAGGCCTTCTCCAAG
CACATCTACAATGCCTACCTGAAAAACTTCAACATGACCAAAAAGAAGGCCCGCAGCATC
CTCACCGGCAAAGCCAGCCACACGGCGCCCTTTGTGATCCACGACATCGAGACATTGTGG
CAGGCAGAGAAGGGGCTGGTGTGGAAGCAGTTGGTGAATGGCCTGCCTCCCTACAAGGAG
ATCAGCGTGCACGTCTTCTACCGCTGCCAGTGCACCACAGTGGAGACCGTGCGGGAGCTC
ACTGAGTTCGCCAAGAGCATCCCCAGCTTCAGCAGCCTCTTCCTCAACGACCAGGTTACC
CTTCTCAAGTATGGCGTGCACGAGGCCATCTTCGCCATGCTGGCCTCTATCGTCAACAAG
GACGGGCTGCTGGTAGCCAACGGCAGTGGCTTTGTCACCCGTGAGTTCCTGCGCAGCCTC
CGCAAACCCTTCAGTGATATCATTGAGCCTAAGTTTGAATTTGCTGTCAAGTTCAACGCC
CTGGAACTTGATGACAGTGACCTGGCCCTATTCATTGCGGCCATCATTCTGTGTGGAGAC
CGGCCAGGCCTCATGAACGTTCCACGGGTGGAGGCTATCCAGGACACCATCCTGCGTGCC
CTCGAATTCCACCTGCAGGCCAACCACCCTGATGCCCAGTACCTCTTCCCCAAGCTGCTG
CAGAAGATGGCTGACCTGCGGCAACTGGTCACCGAGCACGCCCAGATGATGCAGCGGATC
AAGAAGACCGAAACCGAGACCTCGCTGCACCCTCTGCTCCAGGAGATCTACAAGGACATG
TACTAA
GenBank Gene IDL07592
GeneCard IDNot Available
GenAtlas IDPPARD
HGNC IDHGNC:9235
Chromosome Location6
Locus6p21.2-p21.1
References
  1. Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA: Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol. 1992 Oct;6(10):1634-41. 1333051
  2. Skogsberg J, Kannisto K, Roshani L, Gagne E, Hamsten A, Larsson C, Ehrenborg E: Characterization of the human peroxisome proliferator activated receptor delta gene and its expression. Int J Mol Med. 2000 Jul;6(1):73-81. 10851270
  3. Kobayashi T, Kodani Y, Nozawa A, Endo Y, Sawasaki T: DNA-binding profiling of human hormone nuclear receptors via fluorescence correlation spectroscopy in a cell-free system. FEBS Lett. 2008 Aug 6;582(18):2737-44. doi: 10.1016/j.febslet.2008.07.003. Epub 2008 Jul 11. 18619963
  4. 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
  5. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  6. 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
  7. van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F: Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005 Mar;46(3):526-34. Epub 2004 Dec 16. 15604518
  8. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV: Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999 Mar;3(3):397-403. 10198642
  9. Takada I, Yu RT, Xu HE, Lambert MH, Montana VG, Kliewer SA, Evans RM, Umesono K: Alteration of a single amino acid in peroxisome proliferator-activated receptor-alpha (PPAR alpha) generates a PPAR delta phenotype. Mol Endocrinol. 2000 May;14(5):733-40. 10809235
  10. Epple R, Azimioara M, Russo R, Xie Y, Wang X, Cow C, Wityak J, Karanewsky D, Bursulaya B, Kreusch A, Tuntland T, Gerken A, Iskandar M, Saez E, Martin Seidel H, Tian SS: 3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5488-92. Epub 2006 Aug 22. 16931011
  11. Fyffe SA, Alphey MS, Buetow L, Smith TK, Ferguson MA, Sorensen MD, Bjorkling F, Hunter WN: Recombinant human PPAR-beta/delta ligand-binding domain is locked in an activated conformation by endogenous fatty acids. J Mol Biol. 2006 Mar 3;356(4):1005-13. Epub 2006 Jan 4. 16405912
  12. Fyffe SA, Alphey MS, Buetow L, Smith TK, Ferguson MA, Sorensen MD, Bjorkling F, Hunter WN: Reevaluation of the PPAR-beta/delta ligand binding domain model reveals why it exhibits the activated form. Mol Cell. 2006 Jan 6;21(1):1-2. 16387648
  13. Pettersson I, Ebdrup S, Havranek M, Pihera P, Korinek M, Mogensen JP, Jeppesen CB, Johansson E, Sauerberg P: Design of a partial PPARdelta agonist. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4625-9. Epub 2007 May 27. 17560785
  14. Shearer BG, Patel HS, Billin AN, Way JM, Winegar DA, Lambert MH, Xu RX, Leesnitzer LM, Merrihew RV, Huet S, Willson TM: Discovery of a novel class of PPARdelta partial agonists. Bioorg Med Chem Lett. 2008 Sep 15;18(18):5018-22. doi: 10.1016/j.bmcl.2008.08.011. Epub 2008 Aug 9. 18722772
  15. Oyama T, Toyota K, Waku T, Hirakawa Y, Nagasawa N, Kasuga JI, Hashimoto Y, Miyachi H, Morikawa K: Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):786-95. doi: 10.1107/S0907444909015935. Epub 2009 Jul 10. 19622862
  16. Connors RV, Wang Z, Harrison M, Zhang A, Wanska M, Hiscock S, Fox B, Dore M, Labelle M, Sudom A, Johnstone S, Liu J, Walker NP, Chai A, Siegler K, Li Y, Coward P: Identification of a PPARdelta agonist with partial agonistic activity on PPARgamma. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3550-4. doi: 10.1016/j.bmcl.2009.04.151. Epub 2009 May 9. 19464171
  17. Artis DR, Lin JJ, Zhang C, Wang W, Mehra U, Perreault M, Erbe D, Krupka HI, England BP, Arnold J, Plotnikov AN, Marimuthu A, Nguyen H, Will S, Signaevsky M, Kral J, Cantwell J, Settachatgull C, Yan DS, Fong D, Oh A, Shi S, Womack P, Powell B, Habets G, West BL, Zhang KY, Milburn MV, Vlasuk GP, Hirth KP, Nolop K, Bollag G, Ibrahim PN, Tobin JF: Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7. doi: 10.1073/pnas.0811325106. Epub 2008 Dec 30. 19116277