ID:PRGC1_HUMAN DESCRIPTION: RecName: Full=Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; Short=PGC-1-alpha; Short=PPAR-gamma coactivator 1-alpha; Short=PPARGC-1-alpha; AltName: Full=Ligand effect modulator 6; FUNCTION: Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. 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. SUBUNIT: Binds MYBBP1A, which inhibits transcriptional activation by this protein (By similarity). Interacts with PRDM16 (By similarity). Interacts with LRPPRC. Homooligomer. Interacts with LPIN1 (By similarity). INTERACTION: P42704:LRPPRC; NbExp=2; IntAct=EBI-765486, EBI-1050853; SUBCELLULAR LOCATION: Nucleus. 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. INDUCTION: Transcription is repressed by ZNF746 which binds to 'insulin response sequences' its promoter. PTM: Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter (By similarity). Phosphorylated by CLK2 (By similarity). PTM: Heavily acetylated by GCN5 and biologically inactive under conditions of high nutrients. Deacetylated by SIRT1 in low nutrients/high NAD conditions. SIMILARITY: Contains 1 RRM (RNA recognition motif) domain. WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ppargc1a/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UBK2
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000302 response to reactive oxygen species GO:0000422 mitophagy GO:0001659 temperature homeostasis GO:0001666 response to hypoxia GO:0001678 cellular glucose homeostasis GO:0001933 negative regulation of protein phosphorylation GO:0002021 response to dietary excess GO:0002931 response to ischemia GO:0006012 galactose metabolic process GO:0006094 gluconeogenesis GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006397 mRNA processing GO:0007005 mitochondrion organization GO:0007568 aging GO:0007586 digestion GO:0007623 circadian rhythm GO:0008209 androgen metabolic process GO:0008380 RNA splicing GO:0009409 response to cold GO:0009750 response to fructose GO:0010822 positive regulation of mitochondrion organization GO:0014070 response to organic cyclic compound GO:0014732 skeletal muscle atrophy GO:0014823 response to activity GO:0014850 response to muscle activity GO:0014878 response to electrical stimulus involved in regulation of muscle adaptation GO:0014912 negative regulation of smooth muscle cell migration GO:0019395 fatty acid oxidation GO:0021549 cerebellum development GO:0022904 respiratory electron transport chain GO:0030521 androgen receptor signaling pathway GO:0030900 forebrain development GO:0031325 positive regulation of cellular metabolic process GO:0031667 response to nutrient levels GO:0032922 circadian regulation of gene expression GO:0034599 cellular response to oxidative stress GO:0035066 positive regulation of histone acetylation GO:0035865 cellular response to potassium ion GO:0042493 response to drug GO:0042594 response to starvation GO:0042752 regulation of circadian rhythm GO:0043201 response to leucine GO:0043524 negative regulation of neuron apoptotic process GO:0045333 cellular respiration GO:0045722 positive regulation of gluconeogenesis GO:0045820 negative regulation of glycolytic process GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046321 positive regulation of fatty acid oxidation GO:0048511 rhythmic process GO:0048661 positive regulation of smooth muscle cell proliferation GO:0048662 negative regulation of smooth muscle cell proliferation GO:0050821 protein stabilization GO:0050873 brown fat cell differentiation GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051552 flavone metabolic process GO:0051602 response to electrical stimulus GO:0060612 adipose tissue development GO:0065003 macromolecular complex assembly GO:0071222 cellular response to lipopolysaccharide GO:0071250 cellular response to nitrite GO:0071313 cellular response to caffeine GO:0071332 cellular response to fructose stimulus GO:0071333 cellular response to glucose stimulus GO:0071354 cellular response to interleukin-6 GO:0071356 cellular response to tumor necrosis factor GO:0071372 cellular response to follicle-stimulating hormone stimulus GO:0071392 cellular response to estradiol stimulus GO:0071398 cellular response to fatty acid GO:0071456 cellular response to hypoxia GO:0071560 cellular response to transforming growth factor beta stimulus GO:0071871 response to epinephrine GO:0071873 response to norepinephrine GO:0090258 negative regulation of mitochondrial fission GO:0097009 energy homeostasis GO:0097066 response to thyroid hormone GO:0097067 cellular response to thyroid hormone stimulus GO:1901215 negative regulation of neuron death GO:1901558 response to metformin GO:1901857 positive regulation of cellular respiration GO:1901860 positive regulation of mitochondrial DNA metabolic process GO:1901863 positive regulation of muscle tissue development GO:1904635 positive regulation of glomerular visceral epithelial cell apoptotic process GO:1904637 cellular response to ionomycin GO:1904639 cellular response to resveratrol GO:1904640 response to methionine GO:1990845 adaptive thermogenesis GO:2000184 positive regulation of progesterone biosynthetic process GO:2000272 negative regulation of receptor activity GO:2000310 regulation of N-methyl-D-aspartate selective glutamate receptor activity GO:2001171 positive regulation of ATP biosynthetic process
JQ772116 - Homo sapiens peroxisome proliferator-activated receptor gamma coactivator 1 alpha transcript variant B4 (PPARGC1A) mRNA, complete cds, alternatively spliced. JQ772117 - Homo sapiens peroxisome proliferator-activated receptor gamma coactivator 1 alpha transcript variant B5 (PPARGC1A) mRNA, complete cds, alternatively spliced. JQ772118 - Homo sapiens peroxisome proliferator-activated receptor gamma coactivator 1 alpha transcript variant B5-NT (PPARGC1A) mRNA, complete cds, alternatively spliced. JQ772119 - Homo sapiens peroxisome proliferator-activated receptor gamma coactivator 1 alpha transcript variant B4-8a (PPARGC1A) mRNA, complete cds, alternatively spliced. JQ772120 - Homo sapiens peroxisome proliferator-activated receptor gamma coactivator 1 alpha transcript variant B4-3ext (PPARGC1A) mRNA, complete cds, alternatively spliced. AF106698 - Homo sapiens PPAR gamma coactivator-1 (PPARGC1) mRNA, complete cds. AF186379 - Homo sapiens ligand effect modulator-6 (LEM6) mRNA, complete cds. HQ695733 - Homo sapiens L-PGC-1alpha (PPARGC1A) mRNA, complete cds. AB061325 - Homo sapiens PGC-1v mRNA for PPAR gamma coactivator variant form, complete cds. AF159714 - Homo sapiens PPAR gamma coactivator-1 mRNA, complete cds. BC157068 - Synthetic construct Homo sapiens clone IMAGE:100063322, MGC:190741 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A) mRNA, encodes complete protein. BC156323 - Synthetic construct Homo sapiens clone IMAGE:100061732, MGC:190086 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A) mRNA, encodes complete protein. AK309261 - Homo sapiens cDNA, FLJ99302. AK301883 - Homo sapiens cDNA FLJ52961 complete cds, highly similar to Peroxisome proliferator-activated receptorgamma coactivator 1-alpha. AK296591 - Homo sapiens cDNA FLJ58997 complete cds, highly similar to Peroxisome proliferator-activated receptor gamma coactivator 1-alpha. AK024990 - Homo sapiens cDNA: FLJ21337 fis, clone COL02556, highly similar to AF106698 Homo sapiens PPAR gamma coactivator-1 (PPARGC1) mRNA. JD428537 - Sequence 409561 from Patent EP1572962. JD565967 - Sequence 546991 from Patent EP1572962. JD039268 - Sequence 20292 from Patent EP1572962. JD565813 - Sequence 546837 from Patent EP1572962. JD156041 - Sequence 137065 from Patent EP1572962. JD174945 - Sequence 155969 from Patent EP1572962. JD499734 - Sequence 480758 from Patent EP1572962. JD239032 - Sequence 220056 from Patent EP1572962. JD548757 - Sequence 529781 from Patent EP1572962. JD313504 - Sequence 294528 from Patent EP1572962. JD182129 - Sequence 163153 from Patent EP1572962. JD236937 - Sequence 217961 from Patent EP1572962. JD491007 - Sequence 472031 from Patent EP1572962. JD295267 - Sequence 276291 from Patent EP1572962. JD262320 - Sequence 243344 from Patent EP1572962. JD037015 - Sequence 18039 from Patent EP1572962. JD495404 - Sequence 476428 from Patent EP1572962. JD168474 - Sequence 149498 from Patent EP1572962. JD378871 - Sequence 359895 from Patent EP1572962. JD531233 - Sequence 512257 from Patent EP1572962. JD146770 - Sequence 127794 from Patent EP1572962. JD290812 - Sequence 271836 from Patent EP1572962. JD385996 - Sequence 367020 from Patent EP1572962. JD185696 - Sequence 166720 from Patent EP1572962. JD505019 - Sequence 486043 from Patent EP1572962. JD232143 - Sequence 213167 from Patent EP1572962. JD381536 - Sequence 362560 from Patent EP1572962. JD250770 - Sequence 231794 from Patent EP1572962. JD300159 - Sequence 281183 from Patent EP1572962. JD133699 - Sequence 114723 from Patent EP1572962. JD511391 - Sequence 492415 from Patent EP1572962. JD350735 - Sequence 331759 from Patent EP1572962. JD042056 - Sequence 23080 from Patent EP1572962. JD053515 - Sequence 34539 from Patent EP1572962. JD053514 - Sequence 34538 from Patent EP1572962. JD040704 - Sequence 21728 from Patent EP1572962. JD303720 - Sequence 284744 from Patent EP1572962. JD039275 - Sequence 20299 from Patent EP1572962. JD503324 - Sequence 484348 from Patent EP1572962. JD410417 - Sequence 391441 from Patent EP1572962. JD307686 - Sequence 288710 from Patent EP1572962. JD316036 - Sequence 297060 from Patent EP1572962. JD301858 - Sequence 282882 from Patent EP1572962. JD037657 - Sequence 18681 from Patent EP1572962. JD233116 - Sequence 214140 from Patent EP1572962. JD090692 - Sequence 71716 from Patent EP1572962. JD355293 - Sequence 336317 from Patent EP1572962. JD063288 - Sequence 44312 from Patent EP1572962. JD198941 - Sequence 179965 from Patent EP1572962. JD112924 - Sequence 93948 from Patent EP1572962. BC029800 - Homo sapiens peroxisome proliferator-activated receptor gamma, coactivator 1 alpha, mRNA (cDNA clone IMAGE:5187727), with apparent retained intron. JD134845 - Sequence 115869 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ppargPathway - Role of PPAR-gamma Coactivators in Obesity and Thermogenesis h_carm-erPathway - CARM1 and Regulation of the Estrogen Receptor h_pgc1aPathway - Regulation of PGC-1a h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)
Reactome (by CSHL, EBI, and GO)
Protein Q9UBK2 (Reactome details) participates in the following event(s):
R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands R-HSA-1368087 RORA, EP300, PPARGC1A, NRIP1 bind ARNTL (BMAL1) gene R-HSA-1592233 p38 MAPK phosphorylates PPARGC1A R-HSA-1592244 AMPK phosphorylates PPARGC1A R-HSA-5663273 RORA, EP300, PPARGC1A bind NR1D1 gene R-HSA-8939929 ESRRA:PPARG1CA binds the RUNX2 gene promoter R-HSA-1592236 NRF1:p-PPARGC1A, NRF2 bind the TFB1M promoter R-HSA-2466391 NRF1:p-PPARGC1A, NRF2 bind the TFAM promoter R-HSA-2466392 NRF1:p-PPARGC1A, NRF2 bind the TFB2M promoter R-HSA-381340 Transcriptional regulation of white adipocyte differentiation R-HSA-400253 Circadian Clock R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis R-HSA-8939902 Regulation of RUNX2 expression and activity R-HSA-1266738 Developmental Biology R-HSA-1592230 Mitochondrial biogenesis R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-1852241 Organelle biogenesis and maintenance R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)