Peroxisome proliferator-activated receptor-β/δ
Target not currently curated in GtoImmuPdb
Target id: 594
Nomenclature: Peroxisome proliferator-activated receptor-β/δ
Systematic Nomenclature: NR1C2
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Selected 3D Structures
- Natural/Endogenous Ligands
- Agonists
- Antagonists
- Immuno Process Associations
- Main Co-regulators
- Main Target Genes
- Tissue Distribution
- Functional Assays
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Gene Expression and Pathophysiology
- References
- How to cite this page
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 441 | 6p21.31 | PPARD | peroxisome proliferator activated receptor delta | 33 |
| Mouse | 440 | 17 14.64 cM | Ppard | peroxisome proliferator activator receptor delta | 20 |
| Rat | 440 | 20p12 | Ppard | peroxisome proliferator-activated receptor delta | 40 |
| Previous and Unofficial Names |
| NUCII | PPARβ/δ | NUC1 | Pparb | Pparb/d | PPARδ |
| Database Links |
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| Alphafold | Q03181 (Hs), P35396 (Mm) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL3979 (Hs), CHEMBL2458 (Mm) |
| DrugBank Target | Q03181 (Hs) |
| Ensembl Gene | ENSG00000112033 (Hs), ENSMUSG00000002250 (Mm), ENSRNOG00000000503 (Rn) |
| Entrez Gene | 5467 (Hs), 19015 (Mm), 25682 (Rn) |
| Human Protein Atlas | ENSG00000112033 (Hs) |
| KEGG Gene | hsa:5467 (Hs), mmu:19015 (Mm), rno:25682 (Rn) |
| OMIM | 600409 (Hs) |
| Pharos | Q03181 (Hs) |
| RefSeq Nucleotide | NM_177435 (Hs), NM_011145 (Mm), NM_013141 (Rn) |
| RefSeq Protein | NP_006229 (Hs), NP_035275 (Mm), NP_037273 (Rn) |
| SynPHARM |
6326 (in complex with GW0742X) 6325 (in complex with GW2433) 6332 (in complex with L-165041) |
| UniProtKB | Q03181 (Hs), P35396 (Mm) |
| Wikipedia | PPARD (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| tretinoin |
| Comments: Fatty acids and eisosanoids are natural ligands |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Endogenous fatty acid full agonists have also been reported with pIC50 values of 5.2 for the human isoform [41]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists |
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| Immuno Process Associations | ||
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| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOA1 | Co-activator | No | No | Yes | 31 | |
| NCOA3 | Co-activator | No | No | Yes | 28 | |
| NCOA6 | Co-activator | No | Yes | Yes | 8 | |
| NCOR2 | Co-repressor | No | No | No | 18,42 | |
| NCOR1 | Co-repressor | No | No | No | 18,21,43 | |
| PPARGC1A | Co-activator | No | No | No | 38 | |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| ANGPTL4 angiopoietin-like 4 (FIAF: fast-induced adipose factor) | Human | Activated | EMSA | 25 | |
| Pdpk1 | Mouse | Activated | EMSA, ChIP | 12 | |
| Ilk | Mouse | Activated | EMSA, ChIP | 12 | |
| Pink1 | Mouse | Repressed | EMSA, ChIP | 12 | |
| Dffa (DFF45) | Mouse | Activated | EMSA | 11 | |
| Tissue Distribution
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| Functional Assays
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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References
1. Akiyama TE, Lambert G, Nicol CJ, Matsusue K, Peters JM, Brewer HB, Gonzalez FJ. (2004) Peroxisome proliferator-activated receptor beta/delta regulates very low density lipoprotein production and catabolism in mice on a Western diet. J Biol Chem, 279 (20): 20874-81. [PMID:15001574]
2. Barak Y, Liao D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R, Evans RM. (2002) Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA, 99 (1): 303-8. [PMID:11756685]
3. Bastie C, Holst D, Gaillard D, Jehl-Pietri C, Grimaldi PA. (1999) Expression of peroxisome proliferator-activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts. J Biol Chem, 274 (31): 21920-5. [PMID:10419513]
4. Berger J, Leibowitz MD, Doebber TW, Elbrecht A, Zhang B, Zhou G, Biswas C, Cullinan CA, Hayes NS, Li Y, Tanen M, Ventre J, Wu MS, Berger GD, Mosley R, Marquis R, Santini C, Sahoo SP, Tolman RL, Smith RG, Moller DE. (1999) Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem, 274 (10): 6718-25. [PMID:10037770]
5. Boubia B, Poupardin O, Barth M, Binet J, Peralba P, Mounier L, Jacquier E, Gauthier E, Lepais V, Chatar M et al.. (2018) Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate. J Med Chem, 61 (6): 2246-2265. [PMID:29446942]
6. Brown PJ, Smith-Oliver TA, Charifson PS, Tomkinson NC, Fivush AM, Sternbach DD, Wade LE, Orband-Miller L, Parks DJ, Blanchard SG, Kliewer SA, Lehmann JM, Willson TM. (1997) Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library. Chem Biol, 4 (12): 909-18. [PMID:9427656]
7. Brown PJ, Stuart LW, Hurley KP, Lewis MC, Winegar DA, Wilson JG, Wilkison WO, Ittoop OR, Willson TM. (2001) Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett, 11 (9): 1225-7. [PMID:11354382]
8. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA. (2000) Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem, 275 (8): 5308-17. [PMID:10681503]
9. Desvergne B, Michalik L, Wahli W. (2004) Be fit or be sick: peroxisome proliferator-activated receptors are down the road. Mol Endocrinol, 18 (6): 1321-32. [PMID:15087471]
10. Desvergne B, Wahli W. (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev, 20 (5): 649-88. [PMID:10529898]
11. Di-Poï N, Michalik L, Tan NS, Desvergne B, Wahli W. (2003) The anti-apoptotic role of PPARbeta contributes to efficient skin wound healing. J Steroid Biochem Mol Biol, 85 (2-5): 257-65. [PMID:12943711]
12. Di-Poï N, Tan NS, Michalik L, Wahli W, Desvergne B. (2002) Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell, 10 (4): 721-33. [PMID:12419217]
13. Graham TL, Mookherjee C, Suckling KE, Palmer CN, Patel L. (2005) The PPARdelta agonist GW0742X reduces atherosclerosis in LDLR(-/-) mice. Atherosclerosis, 181 (1): 29-37. [PMID:15939051]
14. Hanke T, Cheung SY, Kilu W, Heering J, Ni X, Planz V, Schierle S, Faudone G, Friedrich M, Wanior M et al.. (2020) A Selective Modulator of Peroxisome Proliferator-Activated Receptor γ with an Unprecedented Binding Mode. J Med Chem, 63 (9): 4555-4561. [PMID:32267688]
15. Harman FS, Nicol CJ, Marin HE, Ward JM, Gonzalez FJ, Peters JM. (2004) Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med, 10 (5): 481-3. [PMID:15048110]
16. Henke BR. (2004) Peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes. J Med Chem, 47 (17): 4118-27. [PMID:15293980]
17. Holst D, Luquet S, Kristiansen K, Grimaldi PA. (2003) Roles of peroxisome proliferator-activated receptors delta and gamma in myoblast transdifferentiation. Exp Cell Res, 288 (1): 168-76. [PMID:12878168]
18. Jackson TA, Richer JK, Bain DL, Takimoto GS, Tung L, Horwitz KB. (1997) The partial agonist activity of antagonist-occupied steroid receptors is controlled by a novel hinge domain-binding coactivator L7/SPA and the corepressors N-CoR or SMRT. Mol Endocrinol, 11 (6): 693-705. [PMID:9171233]
19. Kim DJ, Bility MT, Billin AN, Willson TM, Gonzalez FJ, Peters JM. (2006) PPARbeta/delta selectively induces differentiation and inhibits cell proliferation. Cell Death Differ, 13 (1): 53-60. [PMID:16021179]
20. Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K, Evans RM. (1994) Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA, 91 (15): 7355-9. [PMID:8041794]
21. Krogsdam AM, Nielsen CA, Neve S, Holst D, Helledie T, Thomsen B, Bendixen C, Mandrup S, Kristiansen K. (2002) Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation. Biochem J, 363 (Pt 1): 157-65. [PMID:11903058]
22. Lee CH, Chawla A, Urbiztondo N, Liao D, Boisvert WA, Evans RM, Curtiss LK. (2003) Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science, 302 (5644): 453-7. [PMID:12970571]
23. Li AC, Binder CJ, Gutierrez A, Brown KK, Plotkin CR, Pattison JW, Valledor AF, Davis RA, Willson TM, Witztum JL, Palinski W, Glass CK. (2004) Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma. J Clin Invest, 114 (11): 1564-76. [PMID:15578089]
24. Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M, Grimaldi PA. (2003) Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB J, 17 (15): 2299-301. [PMID:14525942]
25. Mandard S, Zandbergen F, Tan NS, Escher P, Patsouris D, Koenig W, Kleemann R, Bakker A, Veenman F, Wahli W, Müller M, Kersten S. (2004) The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment. J Biol Chem, 279 (33): 34411-20. [PMID:15190076]
26. Michalik L, Desvergne B, Basu-Modak S, Tan NS, Wahli W. (2000) Nuclear hormone receptors and mouse skin homeostasis: implication of PPARbeta. Horm Res, 54 (5-6): 263-8. [PMID:11595815]
27. Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, Metzger D, Chambon P, Duboule D, Wahli W. (2001) Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J Cell Biol, 154 (4): 799-814. [PMID:11514592]
28. Molnár F, Matilainen M, Carlberg C. (2005) Structural determinants of the agonist-independent association of human peroxisome proliferator-activated receptors with coactivators. J Biol Chem, 280 (28): 26543-56. [PMID:15888456]
29. Oliver WR, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM. (2001) A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci USA, 98 (9): 5306-11. [PMID:11309497]
30. Peters JM, Lee SS, Li W, Ward JM, Gavrilova O, Everett C, Reitman ML, Hudson LD, Gonzalez FJ. (2000) Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol, 20 (14): 5119-28. [PMID:10866668]
31. Qi C, Zhu Y, Reddy JK. (2000) Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell Biochem Biophys, 32 Spring: 187-204. [PMID:11330046]
32. Schierle S, Neumann S, Heitel P, Willems S, Kaiser A, Pollinger J, Merk D. (2020) Design and Structural Optimization of Dual FXR/PPARδ Activators. J Med Chem, 63 (15): 8369-8379. [PMID:32687365]
33. Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA. (1992) Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol, 6 (10): 1634-41. [PMID:1333051]
34. Shaw N, Elholm M, Noy N. (2003) Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J Biol Chem, 278 (43): 41589-92. [PMID:12963727]
35. Shearer BG, Steger DJ, Way JM, Stanley TB, Lobe DC, Grillot DA, Iannone MA, Lazar MA, Willson TM, Billin AN. (2008) Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist. Mol Endocrinol, 22 (2): 523-9. [PMID:17975020]
36. Sznaidman ML, Haffner CD, Maloney PR, Fivush A, Chao E, Goreham D, Sierra ML, LeGrumelec C, Xu HE, Montana VG, Lambert MH, Willson TM, Oliver WR, Sternbach DD. (2003) Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity. Bioorg Med Chem Lett, 13 (9): 1517-21. [PMID:12699745]
37. Tan NS, Michalik L, Desvergne B, Wahli W. (2003) Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound healing drugs: what is possible?. Am J Clin Dermatol, 4 (8): 523-30. [PMID:12862494]
38. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. (2003) Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell, 113 (2): 159-70. [PMID:12705865]
39. Willson TM, Brown PJ, Sternbach DD, Henke BR. (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem, 43 (4): 527-50. [PMID:10691680]
40. Xing G, Zhang L, Zhang L, Heynen T, Yoshikawa T, Smith M, Weiss S, Detera-Wadleigh S. (1995) Rat PPAR delta contains a CGG triplet repeat and is prominently expressed in the thalamic nuclei. Biochem Biophys Res Commun, 217 (3): 1015-25. [PMID:8554552]
41. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV. (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell, 3 (3): 397-403. [PMID:10198642]
42. Yu C, Markan K, Temple KA, Deplewski D, Brady MJ, Cohen RN. (2005) The nuclear receptor corepressors NCoR and SMRT decrease peroxisome proliferator-activated receptor gamma transcriptional activity and repress 3T3-L1 adipogenesis. J Biol Chem, 280 (14): 13600-5. [PMID:15691842]
43. Zamir I, Harding HP, Atkins GB, Hörlein A, Glass CK, Rosenfeld MG, Lazar MA. (1996) A nuclear hormone receptor corepressor mediates transcriptional silencing by receptors with distinct repression domains. Mol Cell Biol, 16 (10): 5458-65. [PMID:8816459]
44. Zhang R, Wang A, DeAngelis A, Pelton P, Xu J, Zhu P, Zhou L, Demarest K, Murray WV, Kuo GH. (2007) Discovery of para-alkylthiophenoxyacetic acids as a novel series of potent and selective PPARdelta agonists. Bioorg Med Chem Lett, 17 (14): 3855-9. [PMID:17524639]
How to cite this page
1C. Peroxisome proliferator-activated receptors: Peroxisome proliferator-activated receptor-β/δ. Last modified on 09/06/2023. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=594.
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