InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PPARG

Summary

InnateDB Protein

IDBP-18958.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PPARG

Protein Name

peroxisome proliferator-activated receptor gamma

Synonyms

CIMT1; GLM1; NR1C3; PPARG1; PPARG2; PPARgamma;

Species

Homo sapiens

Ensembl Protein

ENSP00000287820

InnateDB Gene

IDBG-18954 (PPARG)

Protein Structure

UniProt Annotation

Function

Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. {ECO:0000269PubMed:16150867, ECO:0000269PubMed:20829347, ECO:0000269PubMed:23525231, ECO:0000269PubMed:9065481}.

Subcellular Localization

Nucleus. Cytoplasm. Note=Redistributed from the nucleus to the cytosol through a MAP2K1/MEK1-dependent manner. CCRN4L/NOC enhances its nuclear translocation.

Disease Associations

Note=Defects in PPARG can lead to type 2 insulin- resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer.Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269PubMed:9753710}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269PubMed:11788685, ECO:0000269PubMed:12453919}. Note=The disease is caused by mutations affecting the gene represented in this entry.Glioma 1 (GLM1) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

Tissue Specificity

Highest expression in adipose tissue. Lower in skeletal muscle, spleen, heart and liver. Also detectable in placenta, lung and ovary. {ECO:0000269PubMed:9065481}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 149 experimentally validated interaction(s) in this database.
They are also associated with 14 interaction(s) predicted by orthology.

Experimentally validated
Total	149 [view]
Protein-Protein	131 [view]
Protein-DNA	17 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	14 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001012	RNA polymerase II regulatory region DNA binding
GO:0001228	RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003707	steroid hormone receptor activity
GO:0004879	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0004955	prostaglandin receptor activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008144	drug binding
GO:0008270	zinc ion binding
GO:0019899	enzyme binding
GO:0019903	protein phosphatase binding
GO:0030331	estrogen receptor binding
GO:0030374	ligand-dependent nuclear receptor transcription coactivator activity
GO:0033613	activating transcription factor binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding
GO:0046965	retinoid X receptor binding
GO:0050544	arachidonic acid binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001890	placenta development
GO:0002674	negative regulation of acute inflammatory response
GO:0006355	regulation of transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006629	lipid metabolic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007507	heart development
GO:0007584	response to nutrient
GO:0008217	regulation of blood pressure
GO:0008285	negative regulation of cell proliferation
GO:0009409	response to cold
GO:0009612	response to mechanical stimulus
GO:0010033	response to organic substance
GO:0010467	gene expression
GO:0010745	negative regulation of macrophage derived foam cell differentiation
GO:0010871	negative regulation of receptor biosynthetic process
GO:0010887	negative regulation of cholesterol storage
GO:0010891	negative regulation of sequestering of triglyceride
GO:0014070	response to organic cyclic compound
GO:0015909	long-chain fatty acid transport
GO:0019216	regulation of lipid metabolic process
GO:0019395	fatty acid oxidation
GO:0030224	monocyte differentiation
GO:0030308	negative regulation of cell growth
GO:0030522	intracellular receptor signaling pathway
GO:0030855	epithelial cell differentiation
GO:0031000	response to caffeine
GO:0031100	organ regeneration
GO:0032526	response to retinoic acid
GO:0032869	cellular response to insulin stimulus
GO:0032966	negative regulation of collagen biosynthetic process
GO:0033189	response to vitamin A
GO:0033993	response to lipid
GO:0035357	peroxisome proliferator activated receptor signaling pathway
GO:0035902	response to immobilization stress
GO:0036270	response to diuretic
GO:0042493	response to drug
GO:0042593	glucose homeostasis
GO:0042594	response to starvation
GO:0042953	lipoprotein transport
GO:0043065	positive regulation of apoptotic process
GO:0043401	steroid hormone mediated signaling pathway
GO:0043627	response to estrogen
GO:0045087	innate immune response (InnateDB)
GO:0045165	cell fate commitment
GO:0045444	fat cell differentiation
GO:0045598	regulation of fat cell differentiation
GO:0045600	positive regulation of fat cell differentiation
GO:0045713	low-density lipoprotein particle receptor biosynthetic process
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046321	positive regulation of fatty acid oxidation
GO:0048469	cell maturation
GO:0048662	negative regulation of smooth muscle cell proliferation
GO:0048714	positive regulation of oligodendrocyte differentiation
GO:0050872	white fat cell differentiation
GO:0050873	brown fat cell differentiation
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051974	negative regulation of telomerase activity
GO:0055088	lipid homeostasis
GO:0055098	response to low-density lipoprotein particle stimulus
GO:0060100	positive regulation of phagocytosis, engulfment
GO:0060336	negative regulation of interferon-gamma-mediated signaling pathway
GO:0060694	regulation of cholesterol transporter activity
GO:0060850	regulation of transcription involved in cell fate commitment
GO:0071285	cellular response to lithium ion
GO:0071300	cellular response to retinoic acid
GO:0071306	cellular response to vitamin E
GO:0071379	cellular response to prostaglandin stimulus
GO:0071380	cellular response to prostaglandin E stimulus
GO:0071407	cellular response to organic cyclic compound
GO:0071455	cellular response to hyperoxia
GO:1901558	response to metformin
GO:2000230	negative regulation of pancreatic stellate cell proliferation

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005829	cytosol
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001628 Zinc finger, nuclear hormone receptor-type
IPR001723 Steroid hormone receptor
IPR003074 Peroxisome proliferator-activated receptor
IPR003077 Peroxisome proliferator-activated receptor, gamma
IPR008946 Nuclear hormone receptor, ligand-binding
IPR022590 Peroxisome proliferator-activated receptor gamma, N-terminal

PFAM

PF00104
PF00105
PF12577

PRINTS

PR00047
PR00398
PR01288
PR01291

PIRSF

SMART

SM00430
SM00399

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt