ERR1_HUMAN
ID ERR1_HUMAN Reviewed; 423 AA.
AC P11474; Q14514;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Steroid hormone receptor ERR1;
DE AltName: Full=Estrogen receptor-like 1;
DE AltName: Full=Estrogen-related receptor alpha;
DE Short=ERR-alpha;
DE AltName: Full=Nuclear receptor subfamily 3 group B member 1;
GN Name=ESRRA; Synonyms=ERR1, ESRL1, NR3B1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=3267207; DOI=10.1038/331091a0;
RA Giguere V., Yang N., Segui P., Evans R.M.;
RT "Identification of a new class of steroid hormone receptors.";
RL Nature 331:91-94(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=8621448; DOI=10.1074/jbc.271.10.5795;
RA Yang N., Shigeta H., Shi H., Teng C.T.;
RT "Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated
RT response of human lactoferrin gene promoter.";
RL J. Biol. Chem. 271:5795-5804(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP PROTEIN SEQUENCE OF 69-76.
RX PubMed=8224847; DOI=10.1101/gad.7.11.2206;
RA Wiley S.R., Kraus R.J., Zuo F., Murray E.E., Loritz K., Mertz J.E.;
RT "SV40 early-to-late switch involves titration of cellular transcriptional
RT repressors.";
RL Genes Dev. 7:2206-2219(1993).
RN [5]
RP FUNCTION.
RX PubMed=9271417; DOI=10.1128/mcb.17.9.5400;
RA Sladek R., Bader J.-A., Giguere V.;
RT "The orphan nuclear receptor estrogen-related receptor alpha is a
RT transcriptional regulator of the human medium-chain acyl coenzyme A
RT dehydrogenase gene.";
RL Mol. Cell. Biol. 17:5400-5409(1997).
RN [6]
RP INTERACTION WITH PPARGC1A, INDUCTION, AND FUNCTION.
RX PubMed=12522104; DOI=10.1074/jbc.m212923200;
RA Schreiber S.N., Knutti D., Brogli K., Uhlmann T., Kralli A.;
RT "The transcriptional coactivator PGC-1 regulates the expression and
RT activity of the orphan nuclear receptor estrogen-related receptor alpha
RT (ERRalpha).";
RL J. Biol. Chem. 278:9013-9018(2003).
RN [7]
RP DNA-BINDING SPECIFICITY, INTERACTION WITH PPARGC1A, HOMODIMERIZATION,
RP FUNCTION, AND MUTAGENESIS OF SER-118 AND THR-124.
RX PubMed=16150865; DOI=10.1210/me.2005-0313;
RA Barry J.B., Laganiere J., Giguere V.;
RT "A single nucleotide in an estrogen-related receptor alpha site can dictate
RT mode of binding and peroxisome proliferator-activated receptor gamma
RT coactivator 1alpha activation of target promoters.";
RL Mol. Endocrinol. 20:302-310(2006).
RN [8]
RP SUMOYLATION AT LYS-14 AND LYS-403, PHOSPHORYLATION AT SER-19 AND SER-22,
RP FUNCTION, AND MUTAGENESIS OF LYS-14; SER-19; SER-22; LYS-403; LEU-413 AND
RP LEU-418.
RX PubMed=17676930; DOI=10.1021/bi700316g;
RA Vu E.H., Kraus R.J., Mertz J.E.;
RT "Phosphorylation-dependent sumoylation of estrogen-related receptor
RT alpha1.";
RL Biochemistry 46:9795-9804(2007).
RN [9]
RP SUMOYLATION AT LYS-14 AND LYS-403, PHOSPHORYLATION AT SER-19 AND SER-22,
RP INTERACTION WITH PIAS4, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-14; SER-19; SER-22 AND LYS-403.
RX PubMed=18063693; DOI=10.1210/me.2007-0357;
RA Tremblay A.M., Wilson B.J., Yang X.-J., Giguere V.;
RT "Phosphorylation-dependent sumoylation regulates estrogen-related receptor-
RT alpha and -gamma transcriptional activity through a synergy control
RT motif.";
RL Mol. Endocrinol. 22:570-584(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-22, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP ACETYLATION AT LYS-129; LYS-138; LYS-160 AND LYS-162 BY PCAF/KAT2B,
RP MUTAGENESIS OF LYS-129; LYS-138; LYS-160 AND LYS-162, AND DEACETYLATION BY
RP SIRT1 AND HDAC8.
RX PubMed=20484414; DOI=10.1210/me.2009-0441;
RA Wilson B.J., Tremblay A.M., Deblois G., Sylvain-Drolet G., Giguere V.;
RT "An acetylation switch modulates the transcriptional activity of estrogen-
RT related receptor alpha.";
RL Mol. Endocrinol. 24:1349-1358(2010).
RN [12]
RP INTERACTION WITH MAPK15, AND SUBCELLULAR LOCATION.
RX PubMed=21190936; DOI=10.1074/jbc.m110.179523;
RA Rossi M., Colecchia D., Iavarone C., Strambi A., Piccioni F.,
RA Verrotti di Pianella A., Chiariello M.;
RT "Extracellular signal-regulated kinase 8 (ERK8) controls estrogen-related
RT receptor alpha (ERRalpha) cellular localization and inhibits its
RT transcriptional activity.";
RL J. Biol. Chem. 286:8507-8522(2011).
RN [13]
RP FUNCTION.
RX PubMed=23836911; DOI=10.1074/jbc.m113.489674;
RA Cho Y., Hazen B.C., Russell A.P., Kralli A.;
RT "Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-
RT 1)- and estrogen-related receptor (ERR)-induced regulator in muscle 1
RT (Perm1) is a tissue-specific regulator of oxidative capacity in skeletal
RT muscle cells.";
RL J. Biol. Chem. 288:25207-25218(2013).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-189 AND LYS-403, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [15]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-403, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [16]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-189 AND LYS-403, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 193-423 IN COMPLEX WITH THE L3
RP SITE-CONTAINING PEPTIDE OF COACTIVATOR PPARGC1A, HOMODIMERIZATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15337744; DOI=10.1074/jbc.m407999200;
RA Kallen J., Schlaeppi J.-M., Bitsch F., Filipuzzi I., Schilb A., Riou V.,
RA Graham A., Strauss A., Geiser M., Fournier B.;
RT "Evidence for ligand-independent transcriptional activation of the human
RT estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha
RT ligand binding domain in complex with peroxisome proliferator-activated
RT receptor coactivator-1alpha.";
RL J. Biol. Chem. 279:49330-49337(2004).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 180-423 IN COMPLEX WITH THE L3
RP SITE-CONTAINING PEPTIDE OF COACTIVATOR PPARGC1A, INTERACTION WITH PPARGC1A,
RP AND MUTAGENESIS OF 258-MET--GLN-262; SER-259; ARG-315; ASP-338; HIS-341;
RP GLU-343 AND 421-MET--ASP-423.
RX PubMed=18441008; DOI=10.1074/jbc.m801920200;
RA Greschik H., Althage M., Flaig R., Sato Y., Chavant V., Peluso-Iltis C.,
RA Choulier L., Cronet P., Rochel N., Schuele R., Stroemstedt P.E., Moras D.;
RT "Communication between the ERRalpha homodimer interface and the PGC-1alpha
RT binding surface via the helix 8-9 loop.";
RL J. Biol. Chem. 283:20220-20230(2008).
CC -!- FUNCTION: Binds to an ERR-alpha response element (ERRE) containing a
CC single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-
CC chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and
CC may act as an important regulator of MCAD promoter. Binds to the C1
CC region of the lactoferrin gene promoter. Requires dimerization and the
CC coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex
CC is a regulator of energy metabolism. Induces the expression of PERM1 in
CC the skeletal muscle. {ECO:0000269|PubMed:12522104,
CC ECO:0000269|PubMed:16150865, ECO:0000269|PubMed:17676930,
CC ECO:0000269|PubMed:18063693, ECO:0000269|PubMed:23836911,
CC ECO:0000269|PubMed:9271417}.
CC -!- SUBUNIT: Binds DNA as a monomer or a homodimer. Interacts (via the AF2
CC domain) with coactivator PPARGC1A (via the L3 motif); the interaction
CC greatly enhances transcriptional activity of genes involved in energy
CC metabolism. Interacts with PIAS4; the interaction enhances sumoylation.
CC Interacts with MAPK15; promotes re-localization of ESRRA to the
CC cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA
CC transcriptional activity. {ECO:0000269|PubMed:12522104,
CC ECO:0000269|PubMed:15337744, ECO:0000269|PubMed:16150865,
CC ECO:0000269|PubMed:18063693, ECO:0000269|PubMed:18441008}.
CC -!- INTERACTION:
CC P11474; P62508-3: ESRRG; NbExp=3; IntAct=EBI-372412, EBI-12001340;
CC P11474; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-372412, EBI-8468186;
CC P11474; Q16665: HIF1A; NbExp=3; IntAct=EBI-372412, EBI-447269;
CC P11474; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-372412, EBI-473160;
CC P11474; Q9UBK2: PPARGC1A; NbExp=20; IntAct=EBI-372412, EBI-765486;
CC P11474; Q04864-2: REL; NbExp=3; IntAct=EBI-372412, EBI-10829018;
CC P11474; P78317: RNF4; NbExp=3; IntAct=EBI-372412, EBI-2340927;
CC P11474; P48788: TNNI2; NbExp=3; IntAct=EBI-372412, EBI-7746394;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:18063693, ECO:0000269|PubMed:21190936}. Cytoplasm
CC {ECO:0000269|PubMed:21190936}. Note=Co-localizes to the cytoplasm only
CC in presence of MAPK15. {ECO:0000269|PubMed:21190936}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11474-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11474-2; Sequence=VSP_035756;
CC -!- INDUCTION: Induced by PGC1alpha in a number of specific cell types
CC including heart, kidney and muscle. {ECO:0000269|PubMed:12522104}.
CC -!- PTM: Phosphorylation on Ser-19 enhances sumoylation on Lys-14
CC increasing repression of transcriptional activity.
CC {ECO:0000269|PubMed:17676930, ECO:0000269|PubMed:18063693}.
CC -!- PTM: Sumoylated with SUMO2. Main site is Lys-14 which is enhanced by
CC phosphorylation on Ser-19, cofactor activation, and by interaction with
CC PIAS4. Sumoylation enhances repression of transcriptional activity, but
CC has no effect on subcellular location nor on DNA binding.
CC {ECO:0000269|PubMed:17676930, ECO:0000269|PubMed:18063693}.
CC -!- PTM: Reversibly acetylated. Acetylation by PCAF/KAT2 at Lys-129, Lys-
CC 138, Lys-160 and Lys-162 and PCAF/KAT2 decreases transcriptional
CC activity probably by inhibiting DNA-binding activity; deacetylation
CC involves SIRT1 and HDAC8 and increases DNA-binding.
CC {ECO:0000269|PubMed:20484414}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB17015.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA35778.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ESRRAID44408ch11q13.html";
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DR EMBL; X51416; CAA35778.1; ALT_FRAME; mRNA.
DR EMBL; L38487; AAB17015.1; ALT_INIT; mRNA.
DR EMBL; AP001453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS41667.1; -. [P11474-1]
DR CCDS; CCDS60830.1; -. [P11474-2]
DR PIR; A29345; A29345.
DR RefSeq; NP_001269379.1; NM_001282450.1. [P11474-1]
DR RefSeq; NP_001269380.1; NM_001282451.1. [P11474-2]
DR RefSeq; NP_004442.3; NM_004451.4. [P11474-1]
DR PDB; 1XB7; X-ray; 2.50 A; A=194-423.
DR PDB; 2PJL; X-ray; 2.30 A; A/B=193-423.
DR PDB; 3D24; X-ray; 2.11 A; A/C=192-423.
DR PDB; 3K6P; X-ray; 2.00 A; A=193-423.
DR PDB; 7E2E; X-ray; 2.70 A; A/B=194-423.
DR PDBsum; 1XB7; -.
DR PDBsum; 2PJL; -.
DR PDBsum; 3D24; -.
DR PDBsum; 3K6P; -.
DR PDBsum; 7E2E; -.
DR AlphaFoldDB; P11474; -.
DR SMR; P11474; -.
DR BioGRID; 108405; 59.
DR DIP; DIP-35053N; -.
DR IntAct; P11474; 33.
DR MINT; P11474; -.
DR STRING; 9606.ENSP00000384851; -.
DR BindingDB; P11474; -.
DR ChEMBL; CHEMBL3429; -.
DR DrugBank; DB06833; 1-CYCLOHEXYL-N-{[1-(4-METHYLPHENYL)-1H-INDOL-3-YL]METHYL}METHANAMINE.
DR DrugBank; DB04468; Afimoxifene.
DR DrugBank; DB06732; beta-Naphthoflavone.
DR DrugBank; DB00255; Diethylstilbestrol.
DR DrugBank; DB07776; Flavone.
DR DrugBank; DB01645; Genistein.
DR DrugBank; DB00197; Troglitazone.
DR DrugCentral; P11474; -.
DR GuidetoPHARMACOLOGY; 622; -.
DR iPTMnet; P11474; -.
DR PhosphoSitePlus; P11474; -.
DR BioMuta; ESRRA; -.
DR DMDM; 215274146; -.
DR EPD; P11474; -.
DR jPOST; P11474; -.
DR MassIVE; P11474; -.
DR MaxQB; P11474; -.
DR PaxDb; P11474; -.
DR PeptideAtlas; P11474; -.
DR PRIDE; P11474; -.
DR ProteomicsDB; 52781; -. [P11474-1]
DR ProteomicsDB; 52782; -. [P11474-2]
DR ABCD; P11474; 6 sequenced antibodies.
DR Antibodypedia; 7260; 580 antibodies from 40 providers.
DR DNASU; 2101; -.
DR Ensembl; ENST00000000442.11; ENSP00000000442.6; ENSG00000173153.17. [P11474-1]
DR Ensembl; ENST00000405666.5; ENSP00000384851.1; ENSG00000173153.17. [P11474-1]
DR Ensembl; ENST00000677967.1; ENSP00000503245.1; ENSG00000173153.17. [P11474-2]
DR GeneID; 2101; -.
DR KEGG; hsa:2101; -.
DR MANE-Select; ENST00000000442.11; ENSP00000000442.6; NM_004451.5; NP_004442.3.
DR UCSC; uc001nzr.3; human. [P11474-1]
DR CTD; 2101; -.
DR DisGeNET; 2101; -.
DR GeneCards; ESRRA; -.
DR HGNC; HGNC:3471; ESRRA.
DR HPA; ENSG00000173153; Tissue enhanced (skeletal).
DR MIM; 601998; gene.
DR neXtProt; NX_P11474; -.
DR OpenTargets; ENSG00000173153; -.
DR PharmGKB; PA27887; -.
DR VEuPathDB; HostDB:ENSG00000173153; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000160341; -.
DR HOGENOM; CLU_007368_11_0_1; -.
DR InParanoid; P11474; -.
DR OMA; CHSGHKE; -.
DR OrthoDB; 1390068at2759; -.
DR PhylomeDB; P11474; -.
DR TreeFam; TF323751; -.
DR PathwayCommons; P11474; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR SignaLink; P11474; -.
DR SIGNOR; P11474; -.
DR BioGRID-ORCS; 2101; 58 hits in 1101 CRISPR screens.
DR ChiTaRS; ESRRA; human.
DR EvolutionaryTrace; P11474; -.
DR GeneWiki; Estrogen-related_receptor_alpha; -.
DR GenomeRNAi; 2101; -.
DR Pharos; P11474; Tchem.
DR PRO; PR:P11474; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P11474; protein.
DR Bgee; ENSG00000173153; Expressed in apex of heart and 180 other tissues.
DR ExpressionAtlas; P11474; baseline and differential.
DR Genevisible; P11474; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
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:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0005496; F:steroid binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:1900078; P:positive regulation of cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID00021; -.
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; 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; 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; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..423
FT /note="Steroid hormone receptor ERR1"
FT /id="PRO_0000053660"
FT DOMAIN 193..421
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 76..151
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 79..99
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 115..134
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..76
FT /note="Repressor domain"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..423
FT /note="AF-2 domain"
FT SITE 124
FT /note="Required for DNA-dependent dimerization"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693, ECO:0007744|PubMed:18669648"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693, ECO:0007744|PubMed:18669648"
FT MOD_RES 129
FT /note="N6-acetyllysine; by PCAF/KAT2B"
FT /evidence="ECO:0000269|PubMed:20484414"
FT MOD_RES 138
FT /note="N6-acetyllysine; by PCAF/KAT2B"
FT /evidence="ECO:0000269|PubMed:20484414"
FT MOD_RES 160
FT /note="N6-acetyllysine; by PCAF/KAT2B"
FT /evidence="ECO:0000269|PubMed:20484414"
FT MOD_RES 162
FT /note="N6-acetyllysine; by PCAF/KAT2B"
FT /evidence="ECO:0000269|PubMed:20484414"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT CROSSLNK 189
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT VAR_SEQ 191
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8621448"
FT /id="VSP_035756"
FT MUTAGEN 14
FT /note="K->R: Some loss of sumoylation. Complete loss of
FT sumoylation; when associated with R-403."
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT MUTAGEN 19
FT /note="S->A: 50% loss of phosphorylation but represses
FT transactivation activity in the absence of coactivator.
FT Almost complete loss of phosphorylation and 2-fold loss of
FT repression of transactivation activity in response to
FT coactivator; when associated with A-22."
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT MUTAGEN 19
FT /note="S->D: Represses transactivation activity in response
FT to coactivator as for wild type; when associated with D-
FT 22."
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT MUTAGEN 22
FT /note="S->A: 15% loss of phosphorylation but little
FT transactivating activity. Almost complete loss of
FT phosphorylation and 2-fold loss of repression of
FT transactivation activity in the presence of coactivator;
FT when associated with A-19."
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT MUTAGEN 22
FT /note="S->D: Represses transactivation activity in response
FT to coactivator as for wild type; when associated with D-
FT 19."
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT MUTAGEN 118
FT /note="S->A: Binds DNA as a monomer or as a dimer as for
FT wild type. No effect on interaction with PPARGC1A."
FT /evidence="ECO:0000269|PubMed:16150865"
FT MUTAGEN 124
FT /note="T->A: Binds DNA predominantly as a monomer. Loss of
FT interaction with PPARGC1A."
FT /evidence="ECO:0000269|PubMed:16150865"
FT MUTAGEN 129
FT /note="K->R: Abolishes acetylation by PCAF/KAT2B; when
FT associated with R-138, R-160 and R-162."
FT /evidence="ECO:0000269|PubMed:20484414"
FT MUTAGEN 138
FT /note="K->R: Abolishes acetylation by PCAF/KAT2B; when
FT associated with R-129, R-160 and R-162."
FT /evidence="ECO:0000269|PubMed:20484414"
FT MUTAGEN 160
FT /note="K->R: Abolishes acetylation by PCAF/KAT2B; when
FT associated with R-129, R-138 and R-162."
FT /evidence="ECO:0000269|PubMed:20484414"
FT MUTAGEN 162
FT /note="K->R: Abolishes acetylation by PCAF/KAT2B; when
FT associated with R-129, R-138 and R-160."
FT /evidence="ECO:0000269|PubMed:20484414"
FT MUTAGEN 258..262
FT /note="MSVLQ->VSVLE: Almost complete loss of interaction to
FT L2 or to L3 of PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 259
FT /note="S->H: Little effect on binding L2 of PPARGC1A.
FT Greatly reduced binding to L3 of PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 315
FT /note="R->A: Almost complete loss of interaction to L2 or
FT to L3 of PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 338
FT /note="D->A: Almost complete loss of interaction to L2 or
FT to L3 of PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 341
FT /note="H->A: Little effect on binding L3 of PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 343
FT /note="E->A: No effect on binding L3 of PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 403
FT /note="K->R: Decrease in sumoylation. No effect on
FT transcriptional activity. Complete loss of sumoylation;
FT when associated with R-14."
FT /evidence="ECO:0000269|PubMed:17676930,
FT ECO:0000269|PubMed:18063693"
FT MUTAGEN 413
FT /note="L->A: Loss of coactivation activity; when associated
FT with A-418. Loss of increased response to coactivator; when
FT associated with A-19 and A-418."
FT /evidence="ECO:0000269|PubMed:17676930"
FT MUTAGEN 418
FT /note="L->A: Loss of coactivation activity; when associated
FT with A-413. Loss of increased response to coactivator
FT activity; when associated with A-19 and A-413."
FT /evidence="ECO:0000269|PubMed:17676930"
FT MUTAGEN 421..423
FT /note="Missing: Greatly reduced interaction with L3 motif
FT of PPARGC1A. Less effect on binding to L2 motif of
FT PPARGC1A."
FT /evidence="ECO:0000269|PubMed:18441008"
FT MUTAGEN 423
FT /note="D->A: Little effect on binding L3 of PPARGC1A."
FT HELIX 195..204
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 224..244
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 254..277
FT /evidence="ECO:0007829|PDB:3K6P"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:3K6P"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:3K6P"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 294..299
FT /evidence="ECO:0007829|PDB:3K6P"
FT TURN 300..304
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 305..317
FT /evidence="ECO:0007829|PDB:3K6P"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 323..335
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 345..364
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 377..382
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 385..400
FT /evidence="ECO:0007829|PDB:3K6P"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:2PJL"
FT HELIX 410..421
FT /evidence="ECO:0007829|PDB:3K6P"
SQ SEQUENCE 423 AA; 45510 MW; BAE62DAF0BE6BA96 CRC64;
MSSQVVGIEP LYIKAEPASP DSPKGSSETE TEPPVALAPG PAPTRCLPGH KEEEDGEGAG
PGEQGGGKLV LSSLPKRLCL VCGDVASGYH YGVASCEACK AFFKRTIQGS IEYSCPASNE
CEITKRRRKA CQACRFTKCL RVGMLKEGVR LDRVRGGRQK YKRRPEVDPL PFPGPFPAGP
LAVAGGPRKT AAPVNALVSH LLVVEPEKLY AMPDPAGPDG HLPAVATLCD LFDREIVVTI
SWAKSIPGFS SLSLSDQMSV LQSVWMEVLV LGVAQRSLPL QDELAFAEDL VLDEEGARAA
GLGELGAALL QLVRRLQALR LEREEYVLLK ALALANSDSV HIEDAEAVEQ LREALHEALL
EYEAGRAGPG GGAERRRAGR LLLTLPLLRQ TAGKVLAHFY GVKLEGKVPM HKLFLEMLEA
MMD
