PRGC1_RAT
ID PRGC1_RAT Reviewed; 796 AA.
AC Q9QYK2;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Peroxisome proliferator-activated receptor gamma coactivator 1-alpha;
DE Short=PGC-1-alpha;
DE Short=PPAR-gamma coactivator 1-alpha;
DE Short=PPARGC-1-alpha;
GN Name=Ppargc1a; Synonyms=Pgc1, Pgc1a, Ppargc1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC STRAIN=Zucker; TISSUE=Heart;
RX PubMed=11108270; DOI=10.1210/endo.141.12.7804;
RA Kakuma T., Wang Z.-W., Pan W., Unger R.H., Zhou Y.-T.;
RT "Role of leptin in peroxisome proliferator-activated receptor gamma
RT coactivator-1 expression.";
RL Endocrinology 141:4576-4582(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=10913342; DOI=10.1006/bbrc.2000.3134;
RA Goto M., Terada S., Kato M., Katoh M., Yokozeki T., Tabata I.,
RA Shimokawa T.;
RT "cDNA cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in
RT swimming-exercised rats.";
RL Biochem. Biophys. Res. Commun. 274:350-354(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kofman A.V.;
RT "Rattus norvegicus PGC1 mRNA.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcriptional coactivator for steroid receptors and nuclear
CC receptors. Greatly increases the transcriptional activity of PPARG and
CC thyroid hormone receptor on the uncoupling protein promoter. Can
CC regulate key mitochondrial genes that contribute to the program of
CC adaptive thermogenesis. Plays an essential role in metabolic
CC reprogramming in response to dietary availability through coordination
CC of the expression of a wide array of genes involved in glucose and
CC fatty acid metabolism. Acts as a key regulator of gluconeogenesis:
CC stimulates hepatic gluconeogenesis by increasing the expression of
CC gluconeogenic enzymes, and acting together with FOXO1 to promote the
CC fasting gluconeogenic program (By similarity). Induces the expression
CC of PERM1 in the skeletal muscle in an ESRRA-dependent manner. Also
CC involved in the integration of the circadian rhythms and energy
CC metabolism. Required for oscillatory expression of clock genes, such as
CC ARNTL/BMAL1 and NR1D1, through the coactivation of RORA and RORC, and
CC metabolic genes, such as PDK4 and PEPCK (By similarity).
CC {ECO:0000250|UniProtKB:O70343, ECO:0000250|UniProtKB:Q9UBK2}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with MYBBP1A; inhibits
CC MYBBP1A transcriptional activation. Interacts with PRDM16, LPIN1 and
CC PML. Interacts (via LXXLL motif) with RORA and RORC (via AF-2 motif);
CC activates RORA and RORC transcriptional activation (By similarity).
CC Interacts with LRPPRC (By similarity). Interacts with FOXO1 (By
CC similarity). {ECO:0000250|UniProtKB:O70343,
CC ECO:0000250|UniProtKB:Q9UBK2}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O70343}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:O70343}.
CC -!- INDUCTION: Up-regulated in brown adipose tissue of diabetic fatty
CC (fa/fa) rats. Exposure of fa/fa rats to cold resulted in a much smaller
CC increase as compared to lean rats in which a 2.6 fold increase was
CC seen. Leptin is required for normal basal and cold-stimulated
CC expression in brown adipose tissue and hyperleptinemia rapidly up-
CC regulates its expression. It is induced not only by cold exposure but
CC also by prolonged low-intensity physical exercise in epitrochlearis
CC muscle. {ECO:0000269|PubMed:10913342, ECO:0000269|PubMed:11108270}.
CC -!- PTM: Phosphorylation by AMPK in skeletal muscle increases activation of
CC its own promoter. Phosphorylated by CLK2.
CC {ECO:0000250|UniProtKB:O70343}.
CC -!- PTM: Heavily acetylated by KAT2A/GCN5 under conditions of high
CC nutrients, leading to inactivation of PPARGC1A. Deacetylated by SIRT1
CC in low nutrients/high NAD conditions, leading to its activation.
CC {ECO:0000250|UniProtKB:Q9UBK2}.
CC -!- PTM: Ubiquitinated. Ubiquitination by RNF34 induces proteasomal
CC degradation. {ECO:0000250|UniProtKB:Q9UBK2}.
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DR EMBL; AB025784; BAA88982.1; -; mRNA.
DR EMBL; AY237127; AAO89279.1; -; mRNA.
DR PIR; JC7355; JC7355.
DR RefSeq; NP_112637.1; NM_031347.1.
DR AlphaFoldDB; Q9QYK2; -.
DR SMR; Q9QYK2; -.
DR STRING; 10116.ENSRNOP00000006071; -.
DR iPTMnet; Q9QYK2; -.
DR PhosphoSitePlus; Q9QYK2; -.
DR PaxDb; Q9QYK2; -.
DR PRIDE; Q9QYK2; -.
DR GeneID; 83516; -.
DR KEGG; rno:83516; -.
DR CTD; 10891; -.
DR RGD; 620925; Ppargc1a.
DR VEuPathDB; HostDB:ENSRNOG00000004473; -.
DR eggNOG; ENOG502QSXU; Eukaryota.
DR HOGENOM; CLU_020104_0_0_1; -.
DR InParanoid; Q9QYK2; -.
DR OMA; KCPSKKK; -.
DR OrthoDB; 94418at2759; -.
DR PhylomeDB; Q9QYK2; -.
DR TreeFam; TF343068; -.
DR PRO; PR:Q9QYK2; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000004473; Expressed in adult mammalian kidney and 16 other tissues.
DR Genevisible; Q9QYK2; RN.
DR GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0022626; C:cytosolic ribosome; IDA:RGD.
DR GO; GO:0000791; C:euchromatin; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISO:RGD.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IPI:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:1990845; P:adaptive thermogenesis; IEP:RGD.
DR GO; GO:0060612; P:adipose tissue development; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0008209; P:androgen metabolic process; IEP:RGD.
DR GO; GO:0000422; P:autophagy of mitochondrion; IEP:RGD.
DR GO; GO:0071313; P:cellular response to caffeine; IEP:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IDA:RGD.
DR GO; GO:0071332; P:cellular response to fructose stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR GO; GO:1904637; P:cellular response to ionomycin; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071250; P:cellular response to nitrite; IEP:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0035865; P:cellular response to potassium ion; IEP:RGD.
DR GO; GO:1904639; P:cellular response to resveratrol; IEP:RGD.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IDA:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; IEP:RGD.
DR GO; GO:0051552; P:flavone metabolic process; IEP:RGD.
DR GO; GO:0030900; P:forebrain development; IEP:RGD.
DR GO; GO:0006012; P:galactose metabolic process; IEP:RGD.
DR GO; GO:0006094; P:gluconeogenesis; IEP:RGD.
DR GO; GO:0007005; P:mitochondrion organization; IMP:RGD.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IMP:RGD.
DR GO; GO:0090258; P:negative regulation of mitochondrial fission; IMP:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IMP:RGD.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISS:UniProtKB.
DR GO; GO:1901857; P:positive regulation of cellular respiration; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:1901860; P:positive regulation of mitochondrial DNA metabolic process; ISO:RGD.
DR GO; GO:0010822; P:positive regulation of mitochondrion organization; ISS:UniProtKB.
DR GO; GO:1901863; P:positive regulation of muscle tissue development; ISO:RGD.
DR GO; GO:1904635; P:positive regulation of podocyte apoptotic process; IMP:RGD.
DR GO; GO:2000184; P:positive regulation of progesterone biosynthetic process; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; IMP:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0022904; P:respiratory electron transport chain; ISS:UniProtKB.
DR GO; GO:0014823; P:response to activity; IDA:RGD.
DR GO; GO:0009409; P:response to cold; IEP:RGD.
DR GO; GO:0002021; P:response to dietary excess; ISO:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0014878; P:response to electrical stimulus involved in regulation of muscle adaptation; IEP:RGD.
DR GO; GO:0071871; P:response to epinephrine; IEP:RGD.
DR GO; GO:0009750; P:response to fructose; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0002931; P:response to ischemia; IEP:RGD.
DR GO; GO:0043201; P:response to leucine; IEP:RGD.
DR GO; GO:1901558; P:response to metformin; IEP:RGD.
DR GO; GO:1904640; P:response to methionine; IEP:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0071873; P:response to norepinephrine; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0000302; P:response to reactive oxygen species; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0014732; P:skeletal muscle atrophy; IEP:RGD.
DR CDD; cd12623; RRM_PPARGC1A; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR034605; PGC-1.
DR InterPro; IPR034625; PGC-1alpha.
DR InterPro; IPR034833; PPARGC1A_RRM.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR15528; PTHR15528; 1.
DR PANTHER; PTHR15528:SF10; PTHR15528:SF10; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Biological rhythms; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..796
FT /note="Peroxisome proliferator-activated receptor gamma
FT coactivator 1-alpha"
FT /id="PRO_0000081735"
FT DOMAIN 675..751
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 98..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 288..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 291..337
FT /note="Interaction with PPARG"
FT /evidence="ECO:0000250|UniProtKB:Q9UBK2"
FT REGION 348..796
FT /note="Mediates interaction with RNF34"
FT /evidence="ECO:0000250|UniProtKB:Q9UBK2"
FT REGION 541..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 611..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 142..146
FT /note="LXXLL motif"
FT COMPBIAS 220..239
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..275
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..304
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..350
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..564
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..597
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..669
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 77
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 144
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 176
FT /note="Phosphothreonine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 182
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 269
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 276
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 319
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 345
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 411
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 440
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 449
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 537
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 756
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT MOD_RES 777
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O70343"
FT CONFLICT 427
FT /note="S -> L (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="R -> H (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 796 AA; 90622 MW; CF30A35F95088240 CRC64;
MAWDMCSQDS VWSDIECAAL VGEDQPLCPD LPELDLSELD VNDLDTDSFL GGLKWCSDQS
EIISNQYNNE PANIFEKIDE ENEANLLAVL TETLDSLPVD EDGLPSFDAL TDGDVTTDNE
ASPSSMPDGT PPPQEAEEPS LLKKLLLAPA NTQLSYNECS GLSTQNHANH THRIRTNPAI
VKTENSWSNK AKSICQQQKP QRRPCSELLK YLTTNDDPPH TKPTENRNSS RDKCASKKKS
HTQPQSQHAQ AKPTTLSLPL TPESPNDPKG SPFENKTIER TLSVELSGTA GLTPPTTPPH
KANQDNPFKA SPKLKPSCKT VVPPPTKRAR YSECSGTQGS HSTKKGPEQS ELYAQLSKSS
VLSRGHEERK TKRPSLRLFG DHDYCQSVNS KTDILINISQ ELQDSRQLDF KDASCDWQGH
ICSSTDSSQC YLRETLEASK QVSPCSTRKQ LQDQEIRAEL NKHFGHPSQA VFDDKVDKTS
ELRDGNFSNE QFSKLPVFIN SGLAMDGLFD DSEDENDKLS YPWDGTQSYS LFDVSPSCSS
FNSPCRDSVS PPKSLFSQRP QRMRSRSRSF SRHRSCSRSP YSRSRSRSPG SRSSSRSCYY
YESSHYRHRT HRNSPLYVRS RSRSPYSRRP RYDSYEANEH ERLKRDEYRR EYEKRESERA
KQRERQKQKA IEERRVIYVG KIRPDTTRTE LRDRFEVFGE IEECTVNLRD DGDSYGFITY
RYTCDAFAAL ENGYTLRRSN ETDFELYFCG RKQFFKSNYA DLDSNSDDFD PASTKSKYDS
LDFDSLLKEA QRSLRR
