Peroxisome proliferator-activated receptor alpha
Also known as: NR1C1, PPAR, PPARA
Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as a transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Classification
- Family (Pfam)
- PF00104 Hormone_recep, PF00105 zf-C4
- InterPro
- 1Cnucl_rcpt, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR1, Nuclear_hrmn_rcpt, PPAR-alpha, Znf_hrmn_rcpt, Znf_NHR/GATA
- Functional cluster
- Zinc-Finger & Chromatin Regulatory Proteins
Experimental structures · PDB · 76
- 1I7G X-ray 2.20A
- 1K7L X-ray 2.50A
- 1KKQ X-ray 3.00A
- 2NPA X-ray 2.30A
- 2P54 X-ray 1.79A
- 2REW X-ray 2.35A
- 2ZNN X-ray 2.01A
- 3ET1 X-ray 2.50A
- 3FEI X-ray 2.40A
- 3G8I X-ray 2.20A
- 3KDT X-ray 2.70A
- 3KDU X-ray 2.07A
- … and 64 more
A predicted model is available from AlphaFold.
Gene Ontology · 72
- GO:0000785 chromatin
- GO:0001650 fibrillar center
- GO:0016604 nuclear body
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0090575 RNA polymerase II transcription regulator complex
- GO:0003677 DNA binding
- GO:0001216 DNA-binding transcription activator activity
- GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
- 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:0008289 lipid binding
- GO:0097371 MDM2/MDM4 family protein binding
- GO:0031435 mitogen-activated protein kinase kinase kinase binding
- GO:0051525 NFAT protein binding
- GO:0004879 nuclear receptor activity
- GO:0003707 nuclear steroid receptor activity
- GO:0019902 phosphatase binding
- GO:0019904 protein domain specific binding
- GO:0044877 protein-containing complex binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
- GO:0043565 sequence-specific DNA binding
- GO:0001223 transcription coactivator binding
- GO:0031624 ubiquitin conjugating enzyme binding
- GO:0008270 zinc ion binding
- GO:0035095 behavioral response to nicotine
- GO:0030154 cell differentiation
- GO:0071332 cellular response to fructose stimulus
- GO:0009267 cellular response to starvation
- GO:0032922 circadian regulation of gene expression
- GO:0051607 defense response to virus
- GO:0006351 DNA-templated transcription
- GO:0006631 fatty acid metabolic process
- GO:0007507 heart development
- GO:0009755 hormone-mediated signaling pathway
- GO:0030522 intracellular receptor signaling pathway
- GO:0007595 lactation
- GO:0042157 lipoprotein metabolic process
- GO:0032099 negative regulation of appetite
- GO:0045776 negative regulation of blood pressure
- GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
- GO:0010887 negative regulation of cholesterol storage
- GO:1900016 negative regulation of cytokine production involved in inflammatory response
- GO:0045820 negative regulation of glycolytic process
- GO:1903944 negative regulation of hepatocyte apoptotic process
- GO:0050728 negative regulation of inflammatory response
- GO:1903038 negative regulation of leukocyte cell-cell adhesion
- GO:0010745 negative regulation of macrophage derived foam cell differentiation
- GO:1902894 negative regulation of miRNA transcription
- GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:1903427 negative regulation of reactive oxygen species biosynthetic process
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
- GO:0046209 nitric oxide metabolic process
- GO:0035357 peroxisome proliferator activated receptor signaling pathway
- GO:2001171 positive regulation of ATP biosynthetic process
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0032000 positive regulation of fatty acid beta-oxidation
- GO:0045923 positive regulation of fatty acid metabolic process
- GO:0046321 positive regulation of fatty acid oxidation
- GO:0046889 positive regulation of lipid biosynthetic process
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0042752 regulation of circadian rhythm
- GO:0019217 regulation of fatty acid metabolic process
- GO:2000191 regulation of fatty acid transport
- GO:0010565 regulation of ketone metabolic process
- GO:0045471 response to ethanol
- GO:0001666 response to hypoxia
- GO:0032868 response to insulin
- GO:0007584 response to nutrient
Disease associations
- OMIM:170998 RAW:OMIM_170998
Drugs targeting this protein · 23
- CHOLINE FENOFIBRATE agonist
- INDEGLITAZAR agonist
- NAVEGLITAZAR agonist
- MURAGLITAZAR agonist
- SODELGLITAZAR agonist
- GW590735 agonist
- PEMAFIBRATE agonist
- BEZAFIBRATE agonist
- TESAGLITAZAR agonist
- ELAFIBRANOR agonist
- LANIFIBRANOR agonist
- LY-518674 agonist
- MK-0767 agonist
- SAROGLITAZAR agonist
- GEMFIBROZIL agonist
- CHIGLITAZAR agonist
- ALEGLITAZAR agonist
- CP-778875 agonist
- CIPROFIBRATE agonist
- CLOFIBRATE agonist
- IMIGLITAZAR agonist
- FENOFIBRATE agonist
- FENOFIBRIC ACID agonist
Related proteins · sequence + function similarity
- Peroxisome proliferator-activated receptor alpha 0.99
- Peroxisome proliferator-activated receptor alpha 0.99
- Peroxisome proliferator-activated receptor alpha 0.98
- Peroxisome proliferator-activated receptor alpha 0.98
- Peroxisome proliferator-activated receptor alpha 0.98
- Peroxisome proliferator-activated receptor alpha 0.97
- Peroxisome proliferator-activated receptor gamma 0.91
- Peroxisome proliferator-activated receptor gamma 0.90
- Peroxisome proliferator-activated receptor gamma 0.90
- Peroxisome proliferator-activated receptor gamma 0.90
- Peroxisome proliferator-activated receptor gamma 0.90
- Peroxisome proliferator-activated receptor gamma 0.90
Co-cited proteins · studied together in the literature
- Peroxisome proliferator-activated receptor delta 3 shared papers
- Peroxisome proliferator-activated receptor gamma 4 shared papers
- Retinoic acid receptor RXR-alpha 5 shared papers
- Peroxisome proliferator-activated receptor alpha 1 shared papers
- Nuclear receptor coactivator 3 1 shared papers
- Nuclear receptor subfamily 2 group C member 2 1 shared papers
- Nuclear receptor subfamily 2 group C member 2 2 shared papers
- Genome polyprotein 1 shared papers
- Putative Polycomb group protein ASXL2 1 shared papers
- COUP transcription factor 2 1 shared papers
- Polycomb group protein ASXL1 1 shared papers
- NAD-dependent protein lipoamidase sirtuin-4, mitochondrial 1 shared papers
Literature · 26 cited papers
- MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases. Proc. Natl. Acad. Sci. U.S.A. · 2017
- SIRT4 represses peroxisome proliferator-activated receptor alpha activity to suppress hepatic fat oxidation. Mol. Cell. Biol. · 2013
- 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
- Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. Acta Crystallogr. D · 2009
- Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. Bioorg. Med. Chem. Lett. · 2009
- Optimization of an enzyme-linked immunosorbent assay to screen ligand of Peroxisome proliferator-activated receptor alpha. Immunopharmacol. Immunotoxicol. · 2009
- Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc. Natl. Acad. Sci. U.S.A. · 2009
- DNA-binding profiling of human hormone nuclear receptors via fluorescence correlation spectroscopy in a cell-free system. FEBS Lett. · 2008
- Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARalpha agonists. 1. Discovery of a novel series of potent HDLc raising agents. J. Med. Chem. · 2007
- Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic acids as PPAR dual agonists. Bioorg. Med. Chem. Lett. · 2007
- A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- … and 14 more in the literature graph
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