Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PPARG (P37231) - Overview - Molecular Target Synopsis

Protein


PPARG, Peroxisome proliferator-activated receptor gamma
UniProt P37231

Also Known as PPARG_HUMAN, PPARG, NR1C3

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. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels., (Microbial infection) Upon treatment with M.tuberculosis or its lipoprotein LpqH, phosphorylation of MAPK p38 and IL-6 production are modulated, probably via this protein. Interacts with FOXO1 (acetylated form) (By similarity). Heterodimer with other nuclear receptors, such as RXRA. The heterodimer with the retinoic acid receptor RXRA is called adipocyte-specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction stimulates the transcriptional activity of PPARG. Interacts with PER2, the interaction is ligand dependent and blocks PPARG recruitment to target promoters. Interacts with NOCT. Interacts with ACTN4. Interacts (when in the liganded conformation) with GPS2.

6IZM
CRYSTAL STRUCTURE OF THE PPARGAMMA-LBD COMPLEXED WITH COMPOUND 1L
RCSB/PDB
Inspect Structure
See all 3D Structures for PPARG

Isoforms / Transcripts (Protein Coding)


Drugs


PPARG is targeted by Approved Drugs Troglitazone, Rosiglitazone, Pioglitazone. (see details)
Troglitazone
Rosiglitazone
Pioglitazone

Sub-cellular localization


UniProt: PPARG is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: PPARG is active in the following subcellular-locations: cytosol, intracellular membrane-bounded organelle, nucleoplasm, nucleus, perinuclear region of cytoplasm, protein-containing complex, RNA polymerase II transcription factor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PPARG has gain in 5 cell-lines, loss in 2 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: KM12, HOP_62, PC_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-45, HM7, OCUM-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HeLa-S3, AG445

(see details)

3D Structures


For PPARG there are:
194 structures (333 chains) solved
188 are solved in complex with at least one small molecule ligand
7 are solved with an approved drug

PPARG is solved in complex with the approved drug(s):

IMN/INDOMETHACIN (3ADS_A, 3ADS_B, 3ADX_A, 3ADX_B, 4XUM_A, 4XUM_B),
DIF/DICLOFENAC (4OJ4_A, 4XTA_A, 4XTA_B),
TLS/TELMISARTAN (3VN2_A),
486/MIFEPRISTONE (3QT0_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PPARG has been screened with 5379 compounds (10545 bioactivities), 1895 compounds have bioactivities that show binding affinity of <= 500nM (3183 bioactivities). (see details)