PPARGC1A

The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq]

peroxisome proliferator-activated receptor gamma, coactivator 1 alpha

Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232).
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 ARNTL/BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity).

Adipose tissue developmentIEA:Ensembl
Brown fat cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
Cellular glucose homeostasis1 PublicationNAS:UniProtKB
Cellular respirationManual Assertion Based On ExperimentTAS:UniProtKB
Cellular response to oxidative stressISS:UniProtKB
Circadian regulation of gene expressionISS:UniProtKB
DigestionManual Assertion Based On ExperimentTAS:UniProtKB
Energy homeostasisISS:UniProtKB
Fatty acid oxidation1 PublicationNAS:UniProtKB
GluconeogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrion organization1 PublicationNAS:UniProtKB
mRNA processingManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of neuron apoptotic processISS:UniProtKB
Negative regulation of neuron deathManual Assertion Based On ExperimentIGI:UniProtKB
Negative regulation of smooth muscle cell proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Neuron apoptotic processIEA:Ensembl
Positive regulation of ATP biosynthetic processISS:UniProtKB
Positive regulation of cellular respirationIEA:Ensembl
Positive regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of fatty acid oxidationManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of gene expressionManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of gluconeogenesisManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of histone acetylationManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of mitochondrial DNA metabolic processIEA:Ensembl
Positive regulation of mitochondrion organizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of muscle tissue developmentIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Protein stabilizationManual Assertion Based On ExperimentTAS:UniProtKB
Protein-containing complex assemblyManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of circadian rhythmISS:UniProtKB
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Respiratory electron transport chainISS:UniProtKB
Response to dietary excessIEA:Ensembl
Response to muscle activityISS:BHF-UCL
Response to starvation1 PublicationNAS:UniProtKB
RNA splicingManual Assertion Based On ExperimentTAS:UniProtKB
Temperature homeostasisManual Assertion Based On ExperimentTAS:UniProtKB
Transcription initiation from RNA polymerase II promoterManual Assertion Based On ExperimentTAS:UniProtKB

Isoform 1
Nucleus
Nucleus, PML body
Isoform B4
Nucleus
Isoform B4-8a
Cytoplasm
Nucleus
Isoform B5
Nucleus
Nucleus, PML body
Isoform 9
Nucleus

Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter. Phosphorylated by CLK2.
Heavily acetylated by KAT2A/GCN5 under conditions of high nutrients, leading to inactivation of PPARGC1A (PubMed:16753578, PubMed:20005308, PubMed:23142079).
Deacetylated by SIRT1 in low nutrients/high NAD conditions, leading to its activation (PubMed:20005308).
Ubiquitinated. Ubiquitination by RNF34 induces proteasomal degradation.