Protein / target
Peroxisome proliferator-activated receptor gamma
Protein at a glance
Biological role
Transcription cis-regulatory region binding
Primary system
Endocrine & metabolic
Strongest disease association
Abnormality of the skeletal system
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
12 approved · 28 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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 (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Activated by lipid ligands: binds peroxisome proliferators, such as hypolipidemic drugs, and fatty acids, such as prostaglandin J2 metabolites (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). 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 (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). 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 (PubMed:20829347). Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)
Subcellular location
Domains and Gene Ontology detail (105)Hide
Domains & features
Gene Ontology
- Cchromatin
- Ccytosol
- Cnucleoplasm
- Cnucleus
- Creceptor complex
- CRNA polymerase II transcription regulator complex
- Falpha-actinin binding
- Farachidonate binding
- Fchromatin binding
- FDNA binding
- FDNA binding domain binding
- FDNA-binding transcription activator activity, RNA polymerase II-specific
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Ligand-activated transcription factor that forms obligate heterodimers with the retinoic…
- ·RNA polymerase II transcription regulator complex
- ·DNA-binding transcription activator activity, RNA polymerase II-specific
- ·DNA-binding transcription factor activity
Nuclear receptor signalling
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
- ·nuclear receptor activity
- ·Nuclear Receptor transcription pathway
Immune signalling
- ·Ligand-activated transcription factor that forms obligate heterodimers with the retinoic…
- ·beige fat cell differentiation
- ·brown fat cell differentiation
- ·fat cell differentiation
Metabolic enzyme activity
- ·fatty acid metabolic process
- ·positive regulation of fatty acid metabolic process
- ·positive regulation of lipid metabolic process
Cell adhesion
- ·negative regulation of extracellular matrix assembly
Apoptosis & cell death
- ·positive regulation of vascular associated smooth muscle cell apoptotic process
View underlying pathways (8)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Peroxisome proliferator-activated receptor gamma agonist
Appears in clinical studies involving diabetes mellitus, type 2 diabetes mellitus, type 2 diabetes mellitus, Alzheimer disease
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,867 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 40 total
type 2 diabetes mellitus · type 2 diabetes mellitus · Hyperglycemia
Alzheimer disease · Alzheimer disease
type 2 diabetes mellitus
X-linked cerebral adrenoleukodystrophy · adrenomyeloneuropathy · Friedreich ataxia
type 2 diabetes mellitus · type 2 diabetes mellitus
malignant pancreatic neoplasm · exocrine pancreatic carcinoma · non-small cell lung carcinoma
type 2 diabetes mellitus · type 2 diabetes mellitus · postherpetic neuralgia
Hepatic fibrosis · metabolic dysfunction-associated steatohepatitis · systemic sclerosis
type 1 diabetes mellitus · Hepatic fibrosis
ulcerative colitis · inflammatory bowel disease
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Related literature
Papers indexed under “PPAR gamma” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationRisk of Pancreatitis With Incretin Therapies Versus Thiazolidinediones in the Veterans Health Administration.
- Safety communication
Drug Safety Update: Rosiglitazone: recommended withdrawal from clinical use
- New publicationRecombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.
- New publicationDrospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.
- New publicationRandomized comparison of the effects of rosiglitazone vs. placebo on peak integrated cardiovascular performance, cardiac structure, and function.
- New publicationRosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.
- New publicationChronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.