ERR3_MOUSE
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 03-AUG-2022, entry version 161.
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 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};
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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 iPTMnet; P62509; -.
DR PhosphoSitePlus; P62509; -.
DR MaxQB; P62509; -.
DR PaxDb; P62509; -.
DR PeptideAtlas; P62509; -.
DR PRIDE; P62509; -.
DR ProteomicsDB; 275945; -. [P62509-1]
DR ProteomicsDB; 275946; -. [P62509-2]
DR Antibodypedia; 20728; 525 antibodies from 39 providers.
DR DNASU; 26381; -.
DR Ensembl; ENSMUST00000027906; ENSMUSP00000027906; ENSMUSG00000026610. [P62509-1]
DR Ensembl; ENSMUST00000110938; ENSMUSP00000106563; ENSMUSG00000026610. [P62509-2]
DR Ensembl; ENSMUST00000110939; ENSMUSP00000106564; ENSMUSG00000026610. [P62509-2]
DR GeneID; 26381; -.
DR KEGG; mmu:26381; -.
DR UCSC; uc007eaa.2; mouse. [P62509-1]
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; 669799at2759; -.
DR PhylomeDB; P62509; -.
DR TreeFam; TF323751; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 26381; 4 hits in 73 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 208 other tissues.
DR ExpressionAtlas; P62509; baseline and differential.
DR Genevisible; P62509; MM.
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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEA:InterPro.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
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
