Peroxisome proliferator-activated receptor delta
Also known as: NR1C2, PPARB, PPARD
Function
Ligand-activated transcription factor key mediator of energy metabolism in adipose tissues. 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.
Classification
- Family (Pfam)
- PF00104 Hormone_recep, PF00105 zf-C4
- InterPro
- 1Cnucl_rcpt, 1Cnucl_rcpt_B, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR1, Nuclear_hrmn_rcpt, Znf_hrmn_rcpt, Znf_NHR/GATA
- Functional cluster
- Zinc-Finger & Chromatin Regulatory Proteins
Experimental structures · PDB · 56
- 1GWX X-ray 2.50A
- 1Y0S X-ray 2.65A
- 2AWH X-ray 2.00A
- 2B50 X-ray 2.00A
- 2BAW X-ray 2.30A
- 2ENV NMR
- 2GWX X-ray 2.30A
- 2J14 X-ray 2.80A
- 2Q5G X-ray 2.70A
- 2XYJ X-ray 2.30A
- 2XYW X-ray 3.14A
- 2XYX X-ray 2.70A
- … and 44 more
A predicted model is available from AlphaFold.
Gene Ontology · 69
- GO:0000785 chromatin
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0090575 RNA polymerase II transcription regulator complex
- GO:0003677 DNA binding
- GO:0003700 DNA-binding transcription factor activity
- GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
- GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
- GO:0070539 linoleic acid binding
- GO:0008289 lipid binding
- GO:0051059 NF-kappaB binding
- GO:0004879 nuclear receptor activity
- GO:0003707 nuclear steroid receptor activity
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:1990837 sequence-specific double-stranded DNA binding
- GO:0001223 transcription coactivator binding
- GO:0008270 zinc ion binding
- GO:0006915 apoptotic process
- GO:0097190 apoptotic signaling pathway
- GO:0008366 axon ensheathment
- GO:0030154 cell differentiation
- GO:0008283 cell population proliferation
- GO:0071222 cellular response to lipopolysaccharide
- GO:0031669 cellular response to nutrient levels
- GO:0008203 cholesterol metabolic process
- GO:1904659 D-glucose transmembrane transport
- GO:0046697 decidualization
- GO:0006351 DNA-templated transcription
- GO:0007566 embryo implantation
- GO:0097009 energy homeostasis
- GO:0006635 fatty acid beta-oxidation
- GO:0009062 fatty acid catabolic process
- GO:0006631 fatty acid metabolic process
- GO:0015908 fatty acid transport
- GO:0006091 generation of precursor metabolites and energy
- GO:0006006 glucose metabolic process
- GO:0007507 heart development
- GO:0009755 hormone-mediated signaling pathway
- GO:0030522 intracellular receptor signaling pathway
- GO:0006629 lipid metabolic process
- GO:0043066 negative regulation of apoptotic process
- GO:0030308 negative regulation of cell growth
- GO:0010887 negative regulation of cholesterol storage
- GO:0032966 negative regulation of collagen biosynthetic process
- GO:0045892 negative regulation of DNA-templated transcription
- GO:0050728 negative regulation of inflammatory response
- GO:1902894 negative regulation of miRNA transcription
- GO:0045662 negative regulation of myoblast differentiation
- GO:0014912 negative regulation of smooth muscle cell migration
- GO:0048662 negative regulation of smooth muscle cell proliferation
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0008654 phospholipid biosynthetic process
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0045684 positive regulation of epidermis development
- GO:0045600 positive regulation of fat cell differentiation
- GO:0045923 positive regulation of fatty acid metabolic process
- GO:0046321 positive regulation of fatty acid oxidation
- GO:0010628 positive regulation of gene expression
- GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
- GO:2000288 positive regulation of myoblast proliferation
- GO:0043415 positive regulation of skeletal muscle tissue regeneration
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0006029 proteoglycan metabolic process
- GO:0014842 regulation of skeletal muscle satellite cell proliferation
- GO:0006357 regulation of transcription by RNA polymerase II
- GO:0014823 response to activity
- GO:0009749 response to glucose
- GO:0033189 response to vitamin A
- GO:0042311 vasodilation
Drugs targeting this protein · 10
- INDEGLITAZAR agonist
- SODELGLITAZAR agonist
- SELADELPAR agonist
- BEZAFIBRATE agonist
- FONADELPAR agonist
- ELAFIBRANOR agonist
- GW501516 agonist
- SELADELPAR LYSINE agonist
- LANIFIBRANOR agonist
- CHIGLITAZAR agonist
Related proteins · sequence + function similarity
- Peroxisome proliferator-activated receptor delta 0.99
- Peroxisome proliferator-activated receptor delta 0.98
- Peroxisome proliferator-activated receptor alpha 0.93
- Peroxisome proliferator-activated receptor alpha 0.91
- Peroxisome proliferator-activated receptor delta 0.90
- Peroxisome proliferator-activated receptor alpha 0.90
- Peroxisome proliferator-activated receptor alpha 0.89
- Peroxisome proliferator-activated receptor alpha 0.89
- Peroxisome proliferator-activated receptor alpha 0.88
- Peroxisome proliferator-activated receptor alpha 0.86
- Retinoic acid receptor RXR-alpha-B 0.86
- Peroxisome proliferator-activated receptor gamma 0.85
Co-cited proteins · studied together in the literature
- Peroxisome proliferator-activated receptor alpha 3 shared papers
- OTU domain-containing protein 3 1 shared papers
- NPC1-like intracellular cholesterol transporter 1 1 shared papers
- NPC1-like intracellular cholesterol transporter 1 1 shared papers
- COUP transcription factor 2 1 shared papers
- OTU domain-containing protein 3 1 shared papers
- Peroxisome proliferator-activated receptor delta 1 shared papers
- Nuclear receptor subfamily 2 group C member 2 1 shared papers
- Retinoic acid receptor RXR-alpha 1 shared papers
- CREB-binding protein 1 shared papers
Literature · 18 cited papers
- Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses. Cell Metab. · 2022
- Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. Acta Crystallogr. D · 2009
- Identification of a PPARdelta agonist with partial agonistic activity on PPARgamma. Bioorg. Med. Chem. Lett. · 2009
- Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc. Natl. Acad. Sci. U.S.A. · 2009
- Discovery of a novel class of PPARdelta partial agonists. Bioorg. Med. Chem. Lett. · 2008
- DNA-binding profiling of human hormone nuclear receptors via fluorescence correlation spectroscopy in a cell-free system. FEBS Lett. · 2008
- Design of a partial PPARdelta agonist. Bioorg. Med. Chem. Lett. · 2007
- 3,4,5-trisubstituted isoxazoles as novel PPARdelta agonists. Part 2. Bioorg. Med. Chem. Lett. · 2006
- Recombinant human PPAR-beta/delta ligand-binding domain is locked in an activated conformation by endogenous fatty acids. J. Mol. Biol. · 2006
- Reevaluation of the PPAR-beta/delta ligand binding domain model reveals why it exhibits the activated form. Mol. Cell · 2006
- Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J. Lipid Res. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- … and 6 more in the literature graph
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