ID ERR3_MOUSE Reviewed; 458 AA. AC P62509; O75454; O96021; Q8CHC9; Q9R1F3; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2004, sequence version 1. DT 24-JAN-2024, entry version 169. DE RecName: Full=Estrogen-related receptor gamma; DE AltName: Full=Estrogen receptor-related protein 3; DE AltName: Full=Nuclear receptor subfamily 3 group B member 3; GN Name=Esrrg; Synonyms=Err3, Kiaa0832, Nr3b3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH GRIP1, MUTAGENESIS RP OF LEU-449; PHE-450; MET-453 AND LEU-454, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=10428842; DOI=10.1074/jbc.274.32.22618; RA Hong H., Yang L., Stallcup M.R.; RT "Hormone-independent transcriptional activation and coactivator binding by RT novel orphan nuclear receptor ERR3."; RL J. Biol. Chem. 274:22618-22626(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=12465718; DOI=10.1093/dnares/9.5.179; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O., RA Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I. RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 9:179-188(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Kidney; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [6] RP DISRUPTION PHENOTYPE. RX PubMed=28572090; DOI=10.15252/emmm.201707604; RA Wang T., Liu J., McDonald C., Lupino K., Zhai X., Wilkins B.J., RA Hakonarson H., Pei L.; RT "GDF15 is a heart-derived hormone that regulates body growth."; RL EMBO Mol. Med. 9:1150-1164(2017). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 229-458 IN COMPLEXES WITH INVERSE RP AGONISTS, AND SUBUNIT. RX PubMed=15161930; DOI=10.1074/jbc.m402195200; RA Greschik H., Flaig R., Renaud J.-P., Moras D.; RT "Structural basis for the deactivation of the estrogen-related receptor RT gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of RT selectivity."; RL J. Biol. Chem. 279:33639-33646(2004). CC -!- FUNCTION: Orphan receptor that acts as a transcription activator in the CC absence of bound ligand. Binds specifically to an estrogen response CC element and activates reporter genes controlled by estrogen response CC elements. Induces the expression of PERM1 in the skeletal muscle. CC {ECO:0000269|PubMed:10428842}. CC -!- SUBUNIT: Homodimer. Interacts with NRIP1, NCOA1 and NCOR2 (By CC similarity). Binds TLE1, PNRC1 and PNRC2 (By similarity). Binds GRIP1. CC {ECO:0000250, ECO:0000269|PubMed:10428842, CC ECO:0000269|PubMed:15161930}. CC -!- INTERACTION: CC P62509; Q91ZR3: Crebzf; NbExp=3; IntAct=EBI-5274019, EBI-5274001; CC P62509; Q9NS37: CREBZF; Xeno; NbExp=3; IntAct=EBI-5274019, EBI-632965; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Long; CC IsoId=P62509-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P62509-2; Sequence=VSP_010766; CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, brain and kidney and CC low expression in the liver. {ECO:0000269|PubMed:10428842}. CC -!- PTM: Acetylated by PCAF/KAT2 (in vitro). {ECO:0000250}. CC -!- PTM: Sumoylation on Lys-40 is enhanced by phosphorylation at Ser-45 and CC represses transcriptional activity. {ECO:0000250}. CC -!- PTM: Phosphorylation on Ser-45 enhances sumoylation on Lys-40 thus CC repressing transcriptional activity. {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Cardiomyocyte-specific double konckout for ESRRA CC and ESRRG are slower at gaining weight, smaller and shorter from 5 to 7 CC days of age compared to controls. They show decreased absolute weight CC of most internal organs except the heart. They have about 70% decreased CC plasma IGF1 levels but normal plasma growth hormone levels. At 14-15 CC days, mutants develop lethal dilated cardiomyopathy and heart failure. CC {ECO:0000269|PubMed:28572090}. CC -!- MISCELLANEOUS: No physiological activating ligand is known for this CC orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as CC inverse agonists and deactivate ESRRG. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC41450.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF117254; AAD48369.1; -; mRNA. DR EMBL; AB093266; BAC41450.1; ALT_INIT; mRNA. DR EMBL; AK052731; BAC35120.1; -; mRNA. DR EMBL; BC082324; AAH82324.1; -; mRNA. DR CCDS; CCDS15606.1; -. [P62509-1] DR CCDS; CCDS56666.1; -. [P62509-2] DR RefSeq; NP_001230721.1; NM_001243792.1. [P62509-2] DR RefSeq; NP_036065.1; NM_011935.3. [P62509-1] DR RefSeq; XP_006497227.1; XM_006497164.3. DR RefSeq; XP_006497228.1; XM_006497165.3. [P62509-2] DR RefSeq; XP_006497230.1; XM_006497167.3. DR RefSeq; XP_006497233.1; XM_006497170.1. [P62509-2] DR PDB; 1S9P; X-ray; 2.13 A; A/B/C/D=232-458. DR PDB; 1S9Q; X-ray; 2.20 A; A/B=229-456. DR PDBsum; 1S9P; -. DR PDBsum; 1S9Q; -. DR AlphaFoldDB; P62509; -. DR SMR; P62509; -. DR BioGRID; 204939; 4. DR IntAct; P62509; 8. DR STRING; 10090.ENSMUSP00000027906; -. DR ChEMBL; CHEMBL3585238; -. DR GlyGen; P62509; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P62509; -. DR PhosphoSitePlus; P62509; -. DR MaxQB; P62509; -. DR PaxDb; 10090-ENSMUSP00000027906; -. DR PeptideAtlas; P62509; -. DR ProteomicsDB; 275945; -. [P62509-1] DR ProteomicsDB; 275946; -. [P62509-2] DR Antibodypedia; 20728; 573 antibodies from 39 providers. DR DNASU; 26381; -. DR Ensembl; ENSMUST00000027906.13; ENSMUSP00000027906.7; ENSMUSG00000026610.14. [P62509-1] DR Ensembl; ENSMUST00000110938.2; ENSMUSP00000106563.2; ENSMUSG00000026610.14. [P62509-2] DR Ensembl; ENSMUST00000110939.8; ENSMUSP00000106564.2; ENSMUSG00000026610.14. [P62509-2] DR GeneID; 26381; -. DR KEGG; mmu:26381; -. DR UCSC; uc007eaa.2; mouse. [P62509-1] DR AGR; MGI:1347056; -. DR CTD; 2104; -. DR MGI; MGI:1347056; Esrrg. DR VEuPathDB; HostDB:ENSMUSG00000026610; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000153433; -. DR HOGENOM; CLU_007368_11_0_1; -. DR InParanoid; P62509; -. DR OMA; MDPVELC; -. DR OrthoDB; 5387678at2759; -. DR PhylomeDB; P62509; -. DR TreeFam; TF323751; -. DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway. DR BioGRID-ORCS; 26381; 4 hits in 78 CRISPR screens. DR ChiTaRS; Esrrg; mouse. DR PRO; PR:P62509; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; P62509; Protein. DR Bgee; ENSMUSG00000026610; Expressed in pontine nuclear group and 210 other cell types or tissues. DR ExpressionAtlas; P62509; baseline and differential. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; NAS:UniProtKB. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0034056; F:estrogen response element binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central. DR GO; GO:0003707; F:nuclear steroid receptor activity; IEA:InterPro. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0005496; F:steroid binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEA:InterPro. DR CDD; cd07170; NR_DBD_ERR; 1. DR CDD; cd06946; NR_LBD_ERR; 1. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 1. DR InterPro; IPR024178; Est_rcpt/est-rel_rcp. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR027289; Oest-rel_rcp. DR InterPro; IPR003078; Retinoic_acid_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR48092:SF10; ESTROGEN-RELATED RECEPTOR GAMMA; 1. DR PANTHER; PTHR48092; KNIRPS-RELATED PROTEIN-RELATED; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PIRSF; PIRSF002527; ER-like_NR; 1. DR PIRSF; PIRSF500939; ERR1-2-3; 1. DR PRINTS; PR01292; RETNOICACIDR. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; P62509; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; DNA-binding; KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Receptor; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..458 FT /note="Estrogen-related receptor gamma" FT /id="PRO_0000053666" FT DOMAIN 233..457 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 125..200 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 128..148 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 164..188 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 42..85 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 42..80 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0000305" FT CROSSLNK 40 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT VAR_SEQ 1..23 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12465718, FT ECO:0000303|PubMed:16141072" FT /id="VSP_010766" FT MUTAGEN 449 FT /note="L->A: Loss of transcriptional activation; when FT associated with A-450." FT /evidence="ECO:0000269|PubMed:10428842" FT MUTAGEN 450 FT /note="F->A: Loss of transcriptional activation; when FT associated with A-449." FT /evidence="ECO:0000269|PubMed:10428842" FT MUTAGEN 453 FT /note="M->A: Loss of transcriptional activation; when FT associated with A-454." FT /evidence="ECO:0000269|PubMed:10428842" FT MUTAGEN 454 FT /note="L->A: Loss of transcriptional activation; when FT associated with A-453." FT /evidence="ECO:0000269|PubMed:10428842" FT CONFLICT 153 FT /note="K -> N (in Ref. 2; BAC41450)" FT /evidence="ECO:0000305" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 261..283 FT /evidence="ECO:0007829|PDB:1S9P" FT TURN 287..291 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 294..316 FT /evidence="ECO:0007829|PDB:1S9P" FT TURN 317..319 FT /evidence="ECO:0007829|PDB:1S9P" FT STRAND 320..322 FT /evidence="ECO:0007829|PDB:1S9P" FT STRAND 324..327 FT /evidence="ECO:0007829|PDB:1S9P" FT STRAND 330..332 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 334..338 FT /evidence="ECO:0007829|PDB:1S9P" FT TURN 339..341 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 343..359 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 363..375 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 385..406 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 413..418 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 421..440 FT /evidence="ECO:0007829|PDB:1S9P" FT HELIX 448..455 FT /evidence="ECO:0007829|PDB:1S9Q" SQ SEQUENCE 458 AA; 51306 MW; 63D36CFD37573152 CRC64; MDSVELCLPE SFSLHYEEEL LCRMSNKDRH IDSSCSSFIK TEPSSPASLT DSVNHHSPGG SSDASGSYSS TMNGHQNGLD SPPLYPSAPI LGGSGPVRKL YDDCSSTIVE DPQTKCEYML NSMPKRLCLV CGDIASGYHY GVASCEACKA FFKRTIQGNI EYSCPATNEC EITKRRRKSC QACRFMKCLK VGMLKEGVRL DRVRGGRQKY KRRIDAENSP YLNPQLVQPA KKPYNKIVSH LLVAEPEKIY AMPDPTVPDS DIKALTTLCD LADRELVVII GWAKHIPGFS TLSLADQMSL LQSAWMEILI LGVVYRSLSF EDELVYADDY IMDEDQSKLA GLLDLNNAIL QLVKKYKSMK LEKEEFVTLK AIALANSDSM HIEDVEAVQK LQDVLHEALQ DYEAGQHMED PRRAGKMLMT LPLLRQTSTK AVQHFYNIKL EGKVPMHKLF LEMLEAKV //