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   27-MAR-2024, entry version 174.
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       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   GlyGen; Q9QYK2; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9QYK2; -.
DR   PhosphoSitePlus; Q9QYK2; -.
DR   PaxDb; 10116-ENSRNOP00000006071; -.
DR   GeneID; 83516; -.
DR   KEGG; rno:83516; -.
DR   AGR; RGD:620925; -.
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   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 cell types or tissues.
DR   GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR   GO; GO:0022626; C:cytosolic ribosome; IDA:RGD.
DR   GO; GO:0000791; C:euchromatin; IDA:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; ISO: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:0106222; F:lncRNA binding; ISO:RGD.
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: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:0003712; F:transcription coregulator activity; ISO: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:0008209; P:androgen metabolic process; 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:0001933; P:negative regulation of protein phosphorylation; 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:0051402; P:neuron apoptotic process; ISO: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:0045893; P:positive regulation of DNA-templated transcription; IMP:RGD.
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: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:0006355; P:regulation of DNA-templated transcription; 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:1903494; P:response to dehydroepiandrosterone; 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:1990910; P:response to hypobaric hypoxia; 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: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:0007584; P:response to nutrient; 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; IPR034833; PPARGC1A_RRM.
DR   InterPro; IPR035979; RBD_domain_sf.
DR   InterPro; IPR000504; RRM_dom.
DR   PANTHER; PTHR15528; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1 PGC-1 -RELATED; 1.
DR   PANTHER; PTHR15528:SF10; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA COACTIVATOR 1-ALPHA; 1.
DR   Pfam; PF00076; RRM_1; 1.
DR   SMART; SM00360; RRM; 1.
DR   SUPFAM; SSF54928; RNA-binding domain, RBD; 1.
DR   PROSITE; PS50102; RRM; 1.
DR   Genevisible; Q9QYK2; RN.
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
//