Protein / target

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

Encoded byPPARGC1AQ9UBK2Homo sapiensSwiss-Prot

UniProt: Q9UBK2 Ensembl: ENSG00000109819 HGNC: HGNC:9237 NCBI Gene: 10891

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

DNA-binding transcription factor binding

Strongest disease association

Smoking initiation

Via encoding gene PPARGC1A · Genetic evidence · score 0.63

Research activity

Emerging research

5 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Transcriptional coactivator for steroid receptors and nuclear receptors.

View complete UniProt function annotation

Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:10713165, PubMed:20005308, PubMed:21376232). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:10713165, PubMed:20005308, PubMed:21376232). Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism (PubMed:10713165, PubMed:20005308, PubMed:21376232). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:16753578, PubMed:23142079). Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner (PubMed:23836911). Also involved in the integration of the circadian rhythms and energy metabolism (By similarity). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity)

Subcellular location

NucleusNucleus, PML bodyCytoplasm

Domains and Gene Ontology detail (47)

Domains & features

RRM

Gene Ontology

Cchromatin
Ccytosol
Cnucleoplasm
Cnucleus
CPML body
Fchromatin DNA binding
FDNA binding
FDNA-binding transcription factor binding
FlncRNA binding
Fnuclear receptor binding
FRNA binding
FRNA polymerase II-specific DNA-binding transcription factor binding

798 aa · 91 kDa · 10 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GONuclear receptor signallingUniProt · GOTranscriptional regulationUniProt · GO

View supporting evidence

Lipid & lipoprotein metabolism

·Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165…
·fatty acid oxidation
·positive regulation of fatty acid oxidation

Nuclear receptor signalling

·Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165…
·nuclear receptor binding

Transcriptional regulation

·Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165…
·DNA-binding transcription factor binding
·RNA polymerase II-specific DNA-binding transcription factor binding
·transcription coactivator activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PPARGC1A

Gene-level evidence surfaced through the gene PPARGC1Athat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Amyotrophic Lateral Sclerosis

0.70Moderately supported

Genetic evidence dominant · Open Targets 0.39

Smoking initiation

0.63Moderately supported

Genetic evidence dominant · Open Targets 0.38

Bundle-Branch Block

0.63Moderately supported

Genetic evidence dominant · Open Targets 0.38

Renal Insufficiency

0.61Moderately supported

Genetic evidence dominant · Open Targets 0.37

Neurodegenerative Diseases

0.26Preliminary

Pathway evidence dominant · Open Targets 0.36 · no direct causal or clinical evidence

View evidence synthesis (5)

Amyotrophic Lateral SclerosisModerately supported

0.70

agreement 0.58–0.82

Genetic70%Animal model20%Literature10%

Open Targets aggregate 0.39 · 3 independent evidence families

Smoking initiationModerately supported

0.63

agreement 0.51–0.75

Genetic100%

Open Targets aggregate 0.38 · 1 independent evidence family

Bundle-Branch BlockModerately supported

0.63

agreement 0.51–0.75

Genetic100%

Open Targets aggregate 0.38 · 1 independent evidence family

Renal InsufficiencyModerately supported

0.61

agreement 0.47–0.75

Genetic99%Literature1%

Open Targets aggregate 0.37 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary

0.26

agreement 0.08–0.43

Pathway87%Literature13%

Open Targets aggregate 0.36 · 2 independent evidence families · no direct causal or clinical evidence

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 per-type scores above show the calculation.

Show all associations

Amyotrophic Lateral Sclerosis0.39

Smoking initiation0.38

Bundle-Branch Block0.38

Renal Insufficiency0.37

Neurodegenerative Diseases0.36

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)