ID ERR2_HUMAN Reviewed; 508 AA. AC O95718; A2VDJ2; B6ZGU4; Q5F0P7; Q5F0P8; Q9HCB4; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 25-JAN-2012, sequence version 2. DT 25-JAN-2012, entry version 118. DE RecName: Full=Steroid hormone receptor ERR2; DE AltName: Full=ERR beta-2; DE AltName: Full=Estrogen receptor-like 2; DE AltName: Full=Estrogen-related receptor beta; DE Short=ERR-beta; DE AltName: Full=Nuclear receptor subfamily 3 group B member 2; GN Name=ESRRB; Synonyms=ERRB2, ESRL2, NR3B2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Testis; RX MEDLINE=99173874; PubMed=10072763; DOI=10.1016/S0378-1119(98)00619-2; RA Chen F., Zhang Q., McDonald T., Davidoff M.J., Bailey W., Bai C., RA Liu Q., Caskey C.T.; RT "Identification of two hERR2-related novel nuclear receptors utilizing RT bioinformatics and inverse PCR."; RL Gene 228:101-109(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND ALTERNATIVE RP SPLICING. RC TISSUE=Heart, and Testis; RX PubMed=16332939; DOI=10.1210/jc.2004-1957; RA Zhou W., Liu Z., Wu J., Liu J.H., Hyder S.M., Antoniou E., RA Lubahn D.B.; RT "Identification and characterization of two novel splicing isoforms of RT human estrogen-related receptor beta."; RL J. Clin. Endocrinol. Metab. 91:569-579(2006). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Kobayashi T., Kodani Y., Sawasaki T., Endo Y.; RT "Comprehensive DNA-binding analysis of human hormone nuclear receptors RT by fluorescence correlation spectroscopy based on cell-free system."; RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RA Kaighin V.A., Martin A.L., Aronstam R.S.; RT "Isolation of cDNA coding for multiple human nuclear receptor RT clones."; RL Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22459283; PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-503 (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-395, AND MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [8] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=19755138; DOI=10.1016/j.mce.2009.09.007; RA Bombail V., Collins F., Brown P., Saunders P.T.; RT "Modulation of ER alpha transcriptional activity by the orphan nuclear RT receptor ERR beta and evidence for differential effects of long- and RT short-form splice variants."; RL Mol. Cell. Endocrinol. 314:53-61(2010). RN [9] RP STRUCTURE BY NMR OF 97-194, SUBUNIT, DNA-BINDING, AND MUTAGENESIS OF RP TYR-185. RX PubMed=12654265; DOI=10.1016/S0022-2836(03)00183-9; RA Gearhart M.D., Holmbeck S.M., Evans R.M., Dyson H.J., Wright P.E.; RT "Monomeric complex of human orphan estrogen related receptor-2 with RT DNA: a pseudo-dimer interface mediates extended half-site RT recognition."; RL J. Mol. Biol. 327:819-832(2003). RN [10] RP VARIANTS DFNB35 VAL-110; PRO-320; LEU-342; PRO-347 AND MET-389, AND RP VARIANT SER-386. RX PubMed=18179891; DOI=10.1016/j.ajhg.2007.09.008; RA Collin R.W.J., Kalay E., Tariq M., Peters T., van der Zwaag B., RA Venselaar H., Oostrik J., Lee K., Ahmed Z.M., Caylan R., Li Y., RA Spierenburg H.A., Eyupoglu E., Heister A., Riazuddin S., Bahat E., RA Ansar M., Arslan S., Wollnik B., Brunner H.G., Cremers C.W.R.J., RA Karaguzel A., Ahmad W., Cremers F.P.M., Vriend G., Friedman T.B., RA Riazuddin S., Leal S.M., Kremer H.; RT "Mutations of ESRRB encoding estrogen-related receptor beta cause RT autosomal-recessive nonsyndromic hearing impairment DFNB35."; RL Am. J. Hum. Genet. 82:125-138(2008). CC -!- FUNCTION: Nuclear receptor, may regulate ESR1 transcriptional CC activity. CC -!- SUBUNIT: Binds DNA as a monomer. CC -!- SUBCELLULAR LOCATION: Nucleus (Potential). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=ERRbeta2-delta10; CC IsoId=O95718-1; Sequence=Displayed; CC Name=2; CC IsoId=O95718-2; Sequence=VSP_042211; CC Name=3; Synonyms=ERRbeta-short-form; CC IsoId=O95718-3; Sequence=VSP_042212; CC -!- DISEASE: Defects in ESRRB are the cause of deafness autosomal CC recessive type 35 (DFNB35) [MIM:608565]. DFNB35 is a form of CC sensorineural hearing loss. Sensorineural deafness results from CC damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives CC sound information. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF094517; AAC99409.1; -; mRNA. DR EMBL; AY451389; AAS15571.1; -; mRNA. DR EMBL; AY451390; AAS15572.1; -; mRNA. DR EMBL; AB307714; BAH02305.1; -; mRNA. DR EMBL; HQ692852; ADZ17363.1; -; mRNA. DR EMBL; AC008050; AAG17472.1; -; Genomic_DNA. DR EMBL; AC016543; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC131517; AAI31518.1; -; mRNA. DR IPI; IPI00032812; -. DR UniGene; Hs.435845; -. DR PDB; 1LO1; NMR; -; A=97-192. DR PDBsum; 1LO1; -. DR ProteinModelPortal; O95718; -. DR SMR; O95718; 97-432. DR STRING; O95718; -. DR PhosphoSite; O95718; -. DR PRIDE; O95718; -. DR Ensembl; ENST00000261532; ENSP00000261532; ENSG00000119715. DR UCSC; uc001xso.1; human. DR GeneCards; GC14P076837; -. DR HGNC; HGNC:3473; ESRRB. DR MIM; 602167; gene. DR MIM; 608565; phenotype. DR neXtProt; NX_O95718; -. DR Orphanet; 90636; Autosomal recessive nonsyndromic sensorineural deafness type DFNB. DR HOVERGEN; HBG108344; -. DR OMA; CASGLME; -. DR PhylomeDB; O95718; -. DR Reactome; REACT_71; Gene Expression. DR NextBio; 8507; -. DR ArrayExpress; O95718; -. DR Bgee; O95718; -. DR CleanEx; HS_ESRRB; -. DR Genevestigator; O95718; -. DR GermOnline; ENSG00000119715; Homo sapiens. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; ISS:BHF-UCL. DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro. DR GO; GO:0005496; F:steroid binding; IEA:InterPro. DR GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro. DR GO; GO:0003713; F:transcription coactivator activity; ISS:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; ISS:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL. DR GO; GO:0034339; ?:regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR InterPro; IPR008946; Nucl_hormone_rcpt_ligand-bd. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd_core. DR InterPro; IPR024178; Oestrogen_rcpt-rel. DR InterPro; IPR001723; Str_hrmn_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR Gene3D; G3DSA:1.10.565.10; Nucl_hrmn_rcpt_lig_bd; 1. DR Gene3D; G3DSA:3.30.50.10; Znf_NHR/GATA; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PIRSF; PIRSF002527; ER-like_NR; 1. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF48508; Str_ncl_receptor; 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; Alternative splicing; Complete proteome; Deafness; KW Disease mutation; DNA-binding; Metal-binding; Non-syndromic deafness; KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 508 Steroid hormone receptor ERR2. FT /FTId=PRO_0000053662. FT DNA_BIND 100 186 Nuclear receptor. FT ZN_FING 103 123 NR C4-type. FT ZN_FING 139 163 NR C4-type. FT SITE 185 185 Important for stabilizing DNA-binding. FT MOD_RES 395 395 Phosphothreonine. FT VAR_SEQ 433 508 VGQEQLRGSPKDERMSSHDGKCPFQSAAFTSRDQSNSPGIP FT NPRPSSPTPLNERGRQISPSTRTPGGQGKHLWLTM -> AW FT ARADSLQEWRPLEQVPSPLHRATKRQHVHFLTPLPPPPSVA FT WVGTAQAGYHLEVFLPQRAGWPRAA (in isoform 2). FT /FTId=VSP_042211. FT VAR_SEQ 434 508 Missing (in isoform 3). FT /FTId=VSP_042212. FT VARIANT 110 110 A -> V (in DFNB35). FT /FTId=VAR_043503. FT VARIANT 320 320 L -> P (in DFNB35). FT /FTId=VAR_043504. FT VARIANT 342 342 V -> L (in DFNB35). FT /FTId=VAR_043505. FT VARIANT 347 347 L -> P (in DFNB35). FT /FTId=VAR_043506. FT VARIANT 386 386 P -> S. FT /FTId=VAR_043507. FT VARIANT 389 389 T -> M (in DFNB35; uncertain pathological FT significance). FT /FTId=VAR_043508. FT MUTAGEN 185 185 Y->A: 6-fold decrease in DNA-binding FT affinity. FT CONFLICT 248 248 D -> E (in Ref. 3; BAH02305). FT CONFLICT 429 429 L -> V (in Ref. 6; AAI31518). FT TURN 104 107 FT STRAND 111 119 FT HELIX 121 132 FT HELIX 149 154 FT HELIX 156 166 FT HELIX 170 172 SQ SEQUENCE 508 AA; 56208 MW; 1BF4637DC1D45B13 CRC64; MSSDDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGLALG THANGLDSPP MFAGAGLGGT PCRKSYEDCA SGIMEDSAIK CEYMLNAIPK RLCLVCGDIA SGYHYGVASC EACKAFFKRT IQGNIEYSCP ATNECEITKR RRKSCQACRF MKCLKVGMLK EGVRLDRVRG GRQKYKRRLD SESSPYLSLQ ISPPAKKPLT KIVSYLLVAE PDKLYAMPPP GMPEGDIKAL TTLCDLADRE LVVIIGWAKH IPGFSSLSLG DQMSLLQSAW MEILILGIVY RSLPYDDKLV YAEDYIMDEE HSRLAGLLEL YRAILQLVRR YKKLKVEKEE FVTLKALALA NSDSMYIEDL EAVQKLQDLL HEALQDYELS QRHEEPWRTG KLLLTLPLLR QTAAKAVQHF YSVKLQGKVP MHKLFLEMLE AKVGQEQLRG SPKDERMSSH DGKCPFQSAA FTSRDQSNSP GIPNPRPSSP TPLNERGRQI SPSTRTPGGQ GKHLWLTM //