PPARGC1A (PPARG coactivator 1 alpha)

Gene

• Entrez ID: 10891
• Gene name: PPARG coactivator 1 alpha
• Gene symbol: PPARGC1A
• Synonyms: LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A, PPARGC1
• Chromosome: 4
• Chromosome location: 4p15.2
• Summary: 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, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006280	hsa-miR-23a-3p	Luciferase reporter assay	22318941
MIRT017345	hsa-miR-335-5p	Microarray	18185580
MIRT027602	hsa-miR-98-5p	Microarray	19088304
MIRT039358	hsa-miR-421	CLASH	23622248
MIRT042423	hsa-miR-425-3p	CLASH	23622248
MIRT043961	hsa-miR-378a-5p	CLASH	23622248
MIRT051970	hsa-let-7b-5p	CLASH	23622248
MIRT438552	hsa-miR-130b-3p	Luciferase reporter assay, qRT-PCR, Western blot	23868745
MIRT521783	hsa-miR-1277-5p	PAR-CLIP	23446348
MIRT521783	hsa-miR-1277-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT521783	hsa-miR-1277-5p	HITS-CLIP	23824327
MIRT521783	hsa-miR-1277-5p	HITS-CLIP	23313552
MIRT521783	hsa-miR-1277-5p	HITS-CLIP	22927820
MIRT521784	hsa-miR-6083	PAR-CLIP	23446348
MIRT521784	hsa-miR-6083	PAR-CLIP, HITS-CLIP	21572407
MIRT521784	hsa-miR-6083	HITS-CLIP	23313552
MIRT521784	hsa-miR-6083	HITS-CLIP	22927820
MIRT521785	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT521785	hsa-miR-190a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521785	hsa-miR-190a-3p	HITS-CLIP	23824327
MIRT521785	hsa-miR-190a-3p	HITS-CLIP	23313552
MIRT521785	hsa-miR-190a-3p	HITS-CLIP	22927820
MIRT521786	hsa-miR-4775	PAR-CLIP	23446348
MIRT521786	hsa-miR-4775	HITS-CLIP	22927820
MIRT521787	hsa-miR-3124-3p	PAR-CLIP	23446348
MIRT521788	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT521788	hsa-miR-5011-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT521788	hsa-miR-5011-5p	HITS-CLIP	23824327
MIRT521788	hsa-miR-5011-5p	HITS-CLIP	23313552
MIRT521788	hsa-miR-5011-5p	HITS-CLIP	22927820
MIRT521789	hsa-miR-32-3p	PAR-CLIP	23446348
MIRT521789	hsa-miR-32-3p	HITS-CLIP	22927820
MIRT622631	hsa-miR-5585-3p	HITS-CLIP	23824327
MIRT725208	hsa-miR-3941	HITS-CLIP	19536157
MIRT725209	hsa-miR-8064	HITS-CLIP	19536157
MIRT725210	hsa-miR-4789-3p	HITS-CLIP	19536157
MIRT725211	hsa-miR-603	HITS-CLIP	19536157
MIRT725212	hsa-miR-362-3p	HITS-CLIP	19536157
MIRT725213	hsa-miR-329-3p	HITS-CLIP	19536157
MIRT725214	hsa-miR-8485	HITS-CLIP	19536157
MIRT731334	hsa-miR-485-3p	Luciferase reporter assay	27010860
MIRT731335	hsa-miR-485-5p	Luciferase reporter assay	27010860
MIRT733075	hsa-miR-130a-3p	Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	25595716
MIRT785712	hsa-miR-4311	HITS-CLIP	27418678
MIRT786130	hsa-miR-4524a-3p	HITS-CLIP	27418678
MIRT786154	hsa-miR-4524b-3p	HITS-CLIP	27418678
MIRT786368	hsa-miR-4668-5p	HITS-CLIP	27418678

Transcription factors

Transcription factor	Regulation	Reference
CRTC1	Activation	10893434
MEF2A	Unknown	18222924
MITF	Activation	23416000
TP53	Unknown	19139068

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000302	Process	Response to reactive oxygen species	IEA
GO:0000422	Process	Autophagy of mitochondrion	IEA
GO:0000785	Component	Chromatin	IC	27471003
GO:0001659	Process	Temperature homeostasis	TAS	1258810
GO:0001678	Process	Cellular glucose homeostasis	NAS	11854298
GO:0001933	Process	Negative regulation of protein phosphorylation	IEA
GO:0002021	Process	Response to dietary excess	IEA
GO:0002931	Process	Response to ischemia	IEA
GO:0003677	Function	DNA binding	ISS
GO:0003677	Function	DNA binding	TAS	10713165
GO:0003712	Function	Transcription coregulator activity	TAS	14636573
GO:0003713	Function	Transcription coactivator activity	IDA	19651776, 21376232, 27471003
GO:0003723	Function	RNA binding	TAS	12588810
GO:0005515	Function	Protein binding	IPI	12522104, 15337744, 17050673, 18063693, 18441008, 19171140, 19846556, 19914244, 32296183
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	23836911
GO:0005634	Component	Nucleus	ISS
GO:0005634	Component	Nucleus	TAS	12588810
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0006012	Process	Galactose metabolic process	IEA
GO:0006094	Process	Gluconeogenesis	NAS	11854298
GO:0006355	Process	Regulation of transcription, DNA-templated	IDA	23836911, 27471003
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS	14636573
GO:0006397	Process	MRNA processing	TAS	12588810
GO:0007005	Process	Mitochondrion organization	NAS	11854298
GO:0007005	Process	Mitochondrion organization	TAS
GO:0007568	Process	Aging	IEA
GO:0007586	Process	Digestion	TAS	10585775
GO:0007623	Process	Circadian rhythm	TAS
GO:0008134	Function	Transcription factor binding	IBA	21873635
GO:0008134	Function	Transcription factor binding	TAS	12588810
GO:0008209	Process	Androgen metabolic process	IEA
GO:0008380	Process	RNA splicing	TAS	12588810
GO:0009409	Process	Response to cold	IEA
GO:0010628	Process	Positive regulation of gene expression	IDA	23525105
GO:0010822	Process	Positive regulation of mitochondrion organization	IMP	25118933
GO:0010822	Process	Positive regulation of mitochondrion organization	ISS
GO:0014732	Process	Skeletal muscle atrophy	IEA
GO:0014850	Process	Response to muscle activity	ISS
GO:0014878	Process	Response to electrical stimulus involved in regulation of muscle adaptation	IEA
GO:0014912	Process	Negative regulation of smooth muscle cell migration	IEA
GO:0016605	Component	PML body	IEA
GO:0016922	Function	Nuclear receptor binding	IPI	18798693
GO:0019395	Process	Fatty acid oxidation	NAS	11854298
GO:0021549	Process	Cerebellum development	IEA
GO:0022626	Component	Cytosolic ribosome	IEA
GO:0022904	Process	Respiratory electron transport chain	ISS
GO:0030331	Function	Estrogen receptor binding	IEA
GO:0030374	Function	Nuclear receptor coactivator activity	IBA	21873635
GO:0030374	Function	Nuclear receptor coactivator activity	IDA	16488887
GO:0030900	Process	Forebrain development	IEA
GO:0031490	Function	Chromatin DNA binding	ISS
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	22064484
GO:0032922	Process	Circadian regulation of gene expression	ISS
GO:0034599	Process	Cellular response to oxidative stress	ISS
GO:0035066	Process	Positive regulation of histone acetylation	TAS	14636573
GO:0035865	Process	Cellular response to potassium ion	IEA
GO:0042493	Process	Response to drug	IEA
GO:0042594	Process	Response to starvation	NAS	11854298
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0042975	Function	Peroxisome proliferator activated receptor binding	IEA
GO:0043014	Function	Alpha-tubulin binding	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0043201	Process	Response to leucine	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0043524	Process	Negative regulation of neuron apoptotic process	ISS
GO:0043565	Function	Sequence-specific DNA binding	IDA	23836911
GO:0045333	Process	Cellular respiration	TAS	11551810
GO:0045722	Process	Positive regulation of gluconeogenesis	TAS	12588810
GO:0045820	Process	Negative regulation of glycolytic process	IEA
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	16488887, 19651776
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	21376232
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046321	Process	Positive regulation of fatty acid oxidation	TAS	12588810
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0048662	Process	Negative regulation of smooth muscle cell proliferation	IEA
GO:0050821	Process	Protein stabilization	TAS	14636573
GO:0050873	Process	Brown fat cell differentiation	TAS	12588810
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IBA	21873635
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	19651776
GO:0051552	Process	Flavone metabolic process	IEA
GO:0060612	Process	Adipose tissue development	IEA
GO:0065003	Process	Protein-containing complex assembly	TAS	14636573
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071250	Process	Cellular response to nitrite	IEA
GO:0071313	Process	Cellular response to caffeine	IEA
GO:0071332	Process	Cellular response to fructose stimulus	IEA
GO:0071333	Process	Cellular response to glucose stimulus	IEA
GO:0071354	Process	Cellular response to interleukin-6	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071372	Process	Cellular response to follicle-stimulating hormone stimulus	IEA
GO:0071392	Process	Cellular response to estradiol stimulus	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0071560	Process	Cellular response to transforming growth factor beta stimulus	IEA
GO:0071871	Process	Response to epinephrine	IEA
GO:0071873	Process	Response to norepinephrine	IEA
GO:0090258	Process	Negative regulation of mitochondrial fission	IEA
GO:0097009	Process	Energy homeostasis	ISS
GO:0097067	Process	Cellular response to thyroid hormone stimulus	IEA
GO:0097440	Component	Apical dendrite	IEA
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	15454086
GO:1901215	Process	Negative regulation of neuron death	IGI	21376232
GO:1901558	Process	Response to metformin	IEA
GO:1901857	Process	Positive regulation of cellular respiration	IEA
GO:1901860	Process	Positive regulation of mitochondrial DNA metabolic process	IEA
GO:1901863	Process	Positive regulation of muscle tissue development	IEA
GO:1904635	Process	Positive regulation of glomerular visceral epithelial cell apoptotic process	IEA
GO:1904637	Process	Cellular response to ionomycin	IEA
GO:1904639	Process	Cellular response to resveratrol	IEA
GO:1904640	Process	Response to methionine	IEA
GO:1990841	Function	Promoter-specific chromatin binding	IEA
GO:1990843	Component	Subsarcolemmal mitochondrion	IEA
GO:1990844	Component	Interfibrillar mitochondrion	IEA
GO:1990845	Process	Adaptive thermogenesis	IEA
GO:2000184	Process	Positive regulation of progesterone biosynthetic process	IEA
GO:2000272	Process	Negative regulation of signaling receptor activity	IEA
GO:2000310	Process	Regulation of NMDA receptor activity	IEA
GO:2001171	Process	Positive regulation of ATP biosynthetic process	ISS

Other IDs

• MIM: 604517
• HGNC: 9237
• e!Ensembl: ENSG00000109819

Protein

• UniProt ID: Q9UBK2
• Protein name: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1-alpha) (PPAR-gamma coactivator 1-alpha) (PPARGC-1-alpha) (Ligand effect modulator 6)
• Protein 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. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. Also involved in the integration of the circadian rhythms and energy metabolism. 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.
• PDB: 1XB7, 3B1M, 3CS8, 3D24, 3U9Q, 3V9T, 3V9V, 4QJR, 4QK4, 5Q0I, 5TWO, 5UNJ, 5Z5S, 5Z6S, 6AD9, 6FZF, 6FZP, 6IZM, 6IZN, 6K0T, 6KXX, 6KXY, 6LN4, 6MS7, 6NWK, 6NWL, 6W9K, 6W9L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00076	RRM_1	679 → 742	RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain)	Domain

• Sequence:

  MAWDMCNQDSESVWSDIECAALVGEDQPLCPDLPELDLSELDVNDLDTDSFLGGLKWCSD
  QSEIISNQYNNEPSNIFEKIDEENEANLLAVLTETLDSLPVDEDGLPSFDALTDGDVTTD
  NEASPSSMPDGTPPPQEAEEPSLLKKLLLAPANTQLSYNECSGLSTQNHANHNHRIRTNP
  AIVKTENSWSNKAKSICQQQKPQRRPCSELLKYLTTNDDPPHTKPTENRNSSRDKCTSKK
  KSHTQSQSQHLQAKPTTLSLPLTPESPNDPKGSPFENKTIERTLSVELSGTAGLTPPTTP
  PHKANQDNPFRASPKLKSSCKTVVPPPSKKPRYSESSGTQGNNSTKKGPEQSELYAQLSK
  SSVLTGGHEERKTKRPSLRLFGDHDYCQSINSKTEILINISQELQDSRQLENKDVSSDWQ
  GQICSSTDSDQCYLRETLEASKQVSPCSTRKQLQDQEIRAELNKHFGHPSQAVFDDEADK
  TGELRDSDFSNEQFSKLPMFINSGLAMDGLFDDSEDESDKLSYPWDGTQSYSLFNVSPSC
  SSFNSPCRDSVSPPKSLFSQRPQRMRSRSRSFSRHRSCSRSPYSRSRSRSPGSRSSSRSC
  YYYESSHYRHRTHRNSPLYVRSRSRSPYSRRPRYDSYEEYQHERLKREEYRREYEKRESE
  RAKQRERQRQKAIEERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNLRDDGDSYGFI
  TYRYTCDAFAALENGYTLRRSNETDFELYFCGRKQFFKSNYADLDSNSDDFDPASTKSKY
  DSLDFDSLLKEAQRSLRR

• Sequence length: 798