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PPARGC1A

Function

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 BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity).

Post-translational modifications

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.

Tissue Specificity

Heart, skeletal muscle, liver and kidney. Expressed at lower levels in brain and pancreas and at very low levels in the intestine and white adipose tissue. In skeletal muscle, levels were lower in obese than in lean subjects and fasting induced a 2-fold increase in levels in the skeletal muscle in obese subjects.

Cellular localization

Alternative names

peroxisome proliferator-activated receptor gamma coactivator 1 beta, Peroxisome proliferative activated receptor gamma coactivator 1 alpha, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, peroxisome proliferator-activated receptor gamma, coactivator 1 beta, Peroxisome proliferative activated receptor, gamma, coactivator 1 alpha, Peroxisome proliferator activated receptor gamma coactivator 1 alpha transcript variant B4, Peroxisome proliferator activated receptor gamma coactivator 1 alpha transcript variant B5, Peroxisome proliferator activated receptor gamma coactivator 1 alpha transcript variant B4 8a, Peroxisome proliferator activated receptor gamma coactivator 1 alpha transcript variant B5 NT, Peroxisome proliferator activated receptor gamma coactivator 1 alpha transcript variant B4 3ext, LEM6, PERC, PGC1, PGC1A, PGC1v, PGC 1v, PPARGC1, PPARGC1A, Ppargc1b, PGC 1 alpha, PGC-1(beta), PGC-1-alpha, PGC-1-beta, PGC1(alpha), PRGC1_HUMAN, L PGC 1alpha, PRGC2_HUMAN, PGC 1 (alpha), PPARGC 1 alpha, PPARGC-1-alpha, PPARGC-1-beta, PPAR gamma coactivator 1, Ligand effect modulator 6, PPAR gamma coactivator-1beta, PPAR gamma coactivator 1 alpha, PPAR-gamma coactivator 1-alpha, PPAR-gamma coactivator 1-beta, PPAR gamma coactivator variant form, PGC-1-related estrogen receptor alpha coactivator, PPAR gamma coactivator 1 alpha 3 ligand effect modulator 6, Peroxisome proliferative activated receptor gamma coactivator 1, Peroxisome proliferative activated receptor, gamma, coactivator 1, Peroxisome proliferator activated receptor gamma coactivator 1 alpha, Peroxisome proliferator-activated receptor gamma coactivator 1-beta

omim:604517 omim:608886 swissprot:415302 swissprot:O70343 swissprot:Q811R2 swissprot:Q865B6 swissprot:Q865B7 swissprot:Q86YN6 swissprot:Q8VHJ7 swissprot:Q9QYK2 swissprot:Q9UBK2 entrezGene:10891 entrezGene:19017 entrezGene:133522 entrezGene:83516 entrezGene:170826 entrezGene:291567 entrezGene:338446 entrezGene:422815 entrezGene:497232 entrezGene:479127 entrezGene:443270