Peroxisome proliferator-activated receptor gamma
Also known as: NR1C3, PPARG
Function
Ligand-activated transcription factor that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-oxidation of fatty acids. Activated by lipid ligands: binds peroxisome proliferators, such as hypolipidemic drugs, and fatty acids, such as prostaglandin J2 metabolites. Ligand-binding results in a conformational change in the receptor, promoting dissociation of repressors and recruitment of coactivators, and subsequent activation of target gene expression. Specifically binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase (By similarity). Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity).
Classification
- Family (Pfam)
- PF00104 Hormone_recep, PF12577 PPARgamma_N, PF00105 zf-C4
- InterPro
- 1Cnucl_rcpt, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR1, Nuclear_hrmn_rcpt, PPAR-gamma, PPARgamma_N, Znf_hrmn_rcpt, Znf_NHR/GATA
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 321
- 1FM6 X-ray 2.10A
- 1FM9 X-ray 2.10A
- 1I7I X-ray 2.35A
- 1K74 X-ray 2.30A
- 1KNU X-ray 2.50A
- 1NYX X-ray 2.65A
- 1PRG X-ray 2.20A
- 1RDT X-ray 2.40A
- 1WM0 X-ray 2.90A
- 1ZEO X-ray 2.50A
- 1ZGY X-ray 1.80A
- 2ATH X-ray 2.28A
- … and 309 more
A predicted model is available from AlphaFold.
Gene Ontology · 104
- GO:0000785 chromatin
- GO:0005829 cytosol
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0043235 receptor complex
- GO:0090575 RNA polymerase II transcription regulator complex
- GO:0051393 alpha-actinin binding
- GO:0050544 arachidonate binding
- GO:0003682 chromatin binding
- GO:0003677 DNA binding
- GO:0050692 DNA binding domain binding
- 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:0140297 DNA-binding transcription factor binding
- GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
- GO:0003690 double-stranded DNA binding
- GO:0070888 E-box binding
- GO:0019899 enzyme binding
- GO:0042802 identical protein binding
- GO:0050693 LBD domain binding
- GO:0004879 nuclear receptor activity
- GO:0046965 nuclear retinoid X receptor binding
- GO:0003676 nucleic acid binding
- GO:0042277 peptide binding
- GO:0004955 prostaglandin receptor activity
- GO:0070412 R-SMAD binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0043565 sequence-specific DNA binding
- GO:0097677 STAT family protein binding
- GO:0000976 transcription cis-regulatory region binding
- GO:0001221 transcription coregulator binding
- GO:0050699 WW domain binding
- GO:0008270 zinc ion binding
- GO:0160274 beige fat cell differentiation
- GO:0030509 BMP signaling pathway
- GO:0050873 brown fat cell differentiation
- GO:0030154 cell differentiation
- GO:0045165 cell fate commitment
- GO:0048469 cell maturation
- GO:0071456 cellular response to hypoxia
- GO:0032869 cellular response to insulin stimulus
- GO:0071404 cellular response to low-density lipoprotein particle stimulus
- GO:0030855 epithelial cell differentiation
- GO:0045444 fat cell differentiation
- GO:0006631 fatty acid metabolic process
- GO:0042593 glucose homeostasis
- GO:0009755 hormone-mediated signaling pathway
- GO:0045087 innate immune response
- GO:0030522 intracellular receptor signaling pathway
- GO:0055088 lipid homeostasis
- GO:0015909 long-chain fatty acid transport
- GO:0030224 monocyte differentiation
- GO:0042789 mRNA transcription by RNA polymerase II
- GO:0016525 negative regulation of angiogenesis
- GO:0043537 negative regulation of blood vessel endothelial cell migration
- GO:0030514 negative regulation of BMP signaling pathway
- GO:1903243 negative regulation of cardiac muscle hypertrophy in response to stress
- GO:1903845 negative regulation of cellular response to transforming growth factor beta stimulus
- GO:0010887 negative regulation of cholesterol storage
- GO:1904597 negative regulation of connective tissue replacement involved in inflammatory response wound healing
- GO:0045892 negative regulation of DNA-templated transcription
- GO:1901202 negative regulation of extracellular matrix assembly
- GO:0010629 negative regulation of gene expression
- GO:0050728 negative regulation of inflammatory response
- GO:0010888 negative regulation of lipid storage
- GO:0010745 negative regulation of macrophage derived foam cell differentiation
- GO:0043409 negative regulation of MAPK cascade
- GO:1902894 negative regulation of miRNA transcription
- GO:0090258 negative regulation of mitochondrial fission
- GO:0045668 negative regulation of osteoblast differentiation
- GO:1904893 negative regulation of receptor signaling pathway via STAT
- GO:0060392 negative regulation of SMAD protein signal transduction
- GO:0048662 negative regulation of smooth muscle cell proliferation
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
- GO:0060336 negative regulation of type II interferon-mediated signaling pathway
- GO:1904706 negative regulation of vascular associated smooth muscle cell proliferation
- GO:1905563 negative regulation of vascular endothelial cell proliferation
- GO:0035357 peroxisome proliferator activated receptor signaling pathway
- GO:0001890 placenta development
- GO:0070165 positive regulation of adiponectin secretion
- GO:1904179 positive regulation of adipose tissue development
- GO:2001235 positive regulation of apoptotic signaling pathway
- GO:0010875 positive regulation of cholesterol efflux
- GO:0032376 positive regulation of cholesterol transport
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0045600 positive regulation of fat cell differentiation
- GO:0045923 positive regulation of fatty acid metabolic process
- GO:0010628 positive regulation of gene expression
- GO:0045834 positive regulation of lipid metabolic process
- GO:0140077 positive regulation of lipoprotein transport
- GO:1902895 positive regulation of miRNA transcription
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:1905461 positive regulation of vascular associated smooth muscle cell apoptotic process
- GO:0008217 regulation of blood pressure
- GO:1900076 regulation of cellular response to insulin stimulus
- GO:0042752 regulation of circadian rhythm
- GO:0006357 regulation of transcription by RNA polymerase II
- GO:0033993 response to lipid
- GO:0007584 response to nutrient
- GO:0048384 retinoic acid receptor signaling pathway
- GO:0048511 rhythmic process
- GO:0050872 white fat cell differentiation
Disease associations
- glioma susceptibility 1 MONDO:0024498
- inherited obesity MONDO:0019182
- PPARG-related familial partial lipodystrophy MONDO:0011448
- OMIM:606641 RAW:OMIM_606641
Drugs targeting this protein · 33
- FARGLITAZAR agonist
- BALSALAZIDE DISODIUM agonist
- OLSALAZINE SODIUM agonist
- ROSIGLITAZONE agonist
- INDEGLITAZAR agonist
- INT131 modulator
- LERIGLITAZONE agonist
- PIOGLITAZONE HYDROCHLORIDE agonist
- BARDOXOLONE METHYL antagonist
- NAVEGLITAZAR agonist
- MURAGLITAZAR agonist
- ARHALOFENATE modulator
- BALAGLITAZONE partial agonist
- RIVOGLITAZONE agonist
- SODELGLITAZAR agonist
- BEZAFIBRATE agonist
- TESAGLITAZAR agonist
- ETALOCIB agonist
- ATX08-001 modulator
- EFATUTAZONE HYDROCHLORIDE agonist
- TROGLITAZONE agonist
- LANIFIBRANOR agonist
- MK-0767 agonist
- SAROGLITAZAR agonist
- CHIGLITAZAR agonist
- MK-0533 modulator
- OMS405 agonist
- ALEGLITAZAR agonist
- CLX-0921 agonist
- IMIGLITAZAR agonist
- MESALAMINE agonist
- ROSIGLITAZONE MALEATE agonist
- NETOGLITAZONE modulator
Related proteins · sequence + function similarity
- Peroxisome proliferator-activated receptor gamma 1.00
- Peroxisome proliferator-activated receptor gamma 1.00
- Peroxisome proliferator-activated receptor gamma 1.00
- Peroxisome proliferator-activated receptor gamma 0.99
- Peroxisome proliferator-activated receptor gamma 0.99
- Peroxisome proliferator-activated receptor gamma 0.99
- Peroxisome proliferator-activated receptor gamma 0.98
- Peroxisome proliferator-activated receptor gamma 0.98
- Peroxisome proliferator-activated receptor gamma 0.91
- Peroxisome proliferator-activated receptor alpha 0.90
- Peroxisome proliferator-activated receptor alpha 0.90
- Peroxisome proliferator-activated receptor alpha 0.89
Co-cited proteins · studied together in the literature
- Peroxisome proliferator-activated receptor alpha 4 shared papers
- 3-phosphoinositide-dependent protein kinase 1 1 shared papers
- Tripartite motif-containing protein 55 1 shared papers
- 3'-5' exoribonuclease HELZ2 2 shared papers
- Nuclear receptor subfamily 0 group B member 2 1 shared papers
- 3'-5' exoribonuclease HELZ2 2 shared papers
- Retinoic acid receptor RXR-alpha 5 shared papers
- Nuclear receptor coactivator 1 3 shared papers
- Lipoprotein LpqH 1 shared papers
- Retinoic acid receptor alpha 5 shared papers
- Dual specificity mitogen-activated protein kinase kinase 1 1 shared papers
- Deoxynucleotidyltransferase terminal-interacting protein 2 1 shared papers
Literature · 53 cited papers
- Lysine 222 in PPAR gamma1 functions as the key site of MuRF2-mediated ubiquitination modification. Sci. Rep. · 2023
- Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA activation pathways. J. Steroid Biochem. Mol. Biol. · 2019
- Mycobacterium tuberculosis 19-kDa lipoprotein induces Toll-like receptor 2-dependent peroxisome proliferator-activated receptor gamma expression and promotes inflammatory responses in human macrophages. Mol. Med. Report. · 2015
- THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation. Mol. Endocrinol. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- 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
- 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
- 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
- The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR. BMC Mol. Biol. · 2010
- Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma. Mol. Cell. Biol. · 2007
- 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
- Identification of a truncated alternative splicing variant of human PPARgamma1 that exhibits dominant negative activity. Biochem. Biophys. Res. Commun. · 2006
- … and 41 more in the literature graph