O95718 (ERR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Steroid hormone receptor ERR2

Alternative name(s):
ERR beta-2
Estrogen receptor-like 2
Estrogen-related receptor beta
Short name=ERR-beta
Nuclear receptor subfamily 3 group B member 2

Gene names

Name:	ESRRB
Synonyms:	ERRB2, ESRL2, NR3B2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Nuclear receptor, may regulate ESR1 transcriptional activity. Ref.7
Subunit structure	Binds DNA as a monomer. Ref.8
Subcellular location	Nucleus Potential.
Involvement in disease	Deafness, autosomal recessive, 35 (DFNB35) [MIM:608565]: A form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL stem cell maintenance Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome trophectodermal cell proliferation Inferred from electronic annotation. Source: Compara trophectodermal cellular morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement PubMed 9344655. Source: ProtInc steroid binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Inferred from sequence or structural similarity. Source: BHF-UCL transcription factor binding Inferred from sequence or structural similarity. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95718-1)

Also known as: ERRbeta2-delta10;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95718-2)

The sequence of this isoform differs from the canonical sequence as follows:
     433-508: VGQEQLRGSP...GQGKHLWLTM → AWARADSLQE...PQRAGWPRAA

Isoform 3 (identifier: O95718-3)

Also known as: ERRbeta-short-form;

The sequence of this isoform differs from the canonical sequence as follows:
     434-508: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 508

508

Steroid hormone receptor ERR2

PRO_0000053662

Regions

DNA binding

100 – 186

87

Nuclear receptor Ref.8

Zinc finger

103 – 123

21

NR C4-type

Zinc finger

139 – 163

25

NR C4-type

Sites

Site

185

1

Important for stabilizing DNA-binding

Natural variations

Alternative sequence

433 – 508

76

VGQEQ…LWLTM → AWARADSLQEWRPLEQVPSP LHRATKRQHVHFLTPLPPPP SVAWVGTAQAGYHLEVFLPQ RAGWPRAA in isoform 2.

VSP_042211

Alternative sequence

434 – 508

75

Missing in isoform 3.

VSP_042212

Natural variant

110

1

A → V in DFNB35. Ref.9

VAR_043503

Natural variant

320

1

L → P in DFNB35. Ref.9

VAR_043504

Natural variant

342

1

V → L in DFNB35. Ref.9

VAR_043505

Natural variant

347

1

L → P in DFNB35. Ref.9

VAR_043506

Natural variant

386

1

P → S. Ref.9

VAR_043507

Natural variant

389

1

T → M in DFNB35; uncertain pathological significance. Ref.9

VAR_043508

Experimental info

Mutagenesis

185

1

Y → A: 6-fold decrease in DNA-binding affinity. Ref.8

Sequence conflict

248

1

D → E in BAH02305. Ref.3

Sequence conflict

429

1

L → V in AAI31518. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

508

Helix Strand Turn

Details...

Turn

104 – 107

4

Beta strand

111 – 119

9

Helix

121 – 132

12

Helix

149 – 154

6

Helix

156 – 166

11

Helix

170 – 172

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ERRbeta2-delta10) [UniParc]. Last modified January 25, 2012. Version 2. Checksum: 1BF4637DC1D45B13	FASTA	508	56,208
	10 20 30 40 50 60 MSSDDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGLALG THANGLDSPP 70 80 90 100 110 120 MFAGAGLGGT PCRKSYEDCA SGIMEDSAIK CEYMLNAIPK RLCLVCGDIA SGYHYGVASC 130 140 150 160 170 180 EACKAFFKRT IQGNIEYSCP ATNECEITKR RRKSCQACRF MKCLKVGMLK EGVRLDRVRG 190 200 210 220 230 240 GRQKYKRRLD SESSPYLSLQ ISPPAKKPLT KIVSYLLVAE PDKLYAMPPP GMPEGDIKAL 250 260 270 280 290 300 TTLCDLADRE LVVIIGWAKH IPGFSSLSLG DQMSLLQSAW MEILILGIVY RSLPYDDKLV 310 320 330 340 350 360 YAEDYIMDEE HSRLAGLLEL YRAILQLVRR YKKLKVEKEE FVTLKALALA NSDSMYIEDL 370 380 390 400 410 420 EAVQKLQDLL HEALQDYELS QRHEEPWRTG KLLLTLPLLR QTAAKAVQHF YSVKLQGKVP 430 440 450 460 470 480 MHKLFLEMLE AKVGQEQLRG SPKDERMSSH DGKCPFQSAA FTSRDQSNSP GIPNPRPSSP 490 500 TPLNERGRQI SPSTRTPGGQ GKHLWLTM
	Isoform 2 [UniParc]. Checksum: C219C84D914DF1C6	FASTA	500	55,619
	10 20 30 40 50 60 MSSDDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGLALG THANGLDSPP 70 80 90 100 110 120 MFAGAGLGGT PCRKSYEDCA SGIMEDSAIK CEYMLNAIPK RLCLVCGDIA SGYHYGVASC 130 140 150 160 170 180 EACKAFFKRT IQGNIEYSCP ATNECEITKR RRKSCQACRF MKCLKVGMLK EGVRLDRVRG 190 200 210 220 230 240 GRQKYKRRLD SESSPYLSLQ ISPPAKKPLT KIVSYLLVAE PDKLYAMPPP GMPEGDIKAL 250 260 270 280 290 300 TTLCDLADRE LVVIIGWAKH IPGFSSLSLG DQMSLLQSAW MEILILGIVY RSLPYDDKLV 310 320 330 340 350 360 YAEDYIMDEE HSRLAGLLEL YRAILQLVRR YKKLKVEKEE FVTLKALALA NSDSMYIEDL 370 380 390 400 410 420 EAVQKLQDLL HEALQDYELS QRHEEPWRTG KLLLTLPLLR QTAAKAVQHF YSVKLQGKVP 430 440 450 460 470 480 MHKLFLEMLE AKAWARADSL QEWRPLEQVP SPLHRATKRQ HVHFLTPLPP PPSVAWVGTA 490 500 QAGYHLEVFL PQRAGWPRAA
	Isoform 3 (ERRbeta-short-form) [UniParc]. Checksum: ED1D3F87E2798DD1	FASTA	433	48,054
	10 20 30 40 50 60 MSSDDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGLALG THANGLDSPP 70 80 90 100 110 120 MFAGAGLGGT PCRKSYEDCA SGIMEDSAIK CEYMLNAIPK RLCLVCGDIA SGYHYGVASC 130 140 150 160 170 180 EACKAFFKRT IQGNIEYSCP ATNECEITKR RRKSCQACRF MKCLKVGMLK EGVRLDRVRG 190 200 210 220 230 240 GRQKYKRRLD SESSPYLSLQ ISPPAKKPLT KIVSYLLVAE PDKLYAMPPP GMPEGDIKAL 250 260 270 280 290 300 TTLCDLADRE LVVIIGWAKH IPGFSSLSLG DQMSLLQSAW MEILILGIVY RSLPYDDKLV 310 320 330 340 350 360 YAEDYIMDEE HSRLAGLLEL YRAILQLVRR YKKLKVEKEE FVTLKALALA NSDSMYIEDL 370 380 390 400 410 420 EAVQKLQDLL HEALQDYELS QRHEEPWRTG KLLLTLPLLR QTAAKAVQHF YSVKLQGKVP 430 MHKLFLEMLE AKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR." Chen F., Zhang Q., McDonald T., Davidoff M.J., Bailey W., Bai C., Liu Q., Caskey C.T. Gene 228:101-109(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Testis.
[2]	"Identification and characterization of two novel splicing isoforms of human estrogen-related receptor beta." Zhou W., Liu Z., Wu J., Liu J.H., Hyder S.M., Antoniou E., Lubahn D.B. J. Clin. Endocrinol. Metab. 91:569-579(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), ALTERNATIVE SPLICING. Tissue: Heart and Testis.
[3]	"Comprehensive DNA-binding analysis of human hormone nuclear receptors by fluorescence correlation spectroscopy based on cell-free system." Kobayashi T., Kodani Y., Sawasaki T., Endo Y. Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]	"Isolation of cDNA coding for multiple human nuclear receptor clones." Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[5]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-503 (ISOFORM 1).
[7]	"Modulation of ER alpha transcriptional activity by the orphan nuclear receptor ERR beta and evidence for differential effects of long- and short-form splice variants." Bombail V., Collins F., Brown P., Saunders P.T. Mol. Cell. Endocrinol. 314:53-61(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING.
[8]	"Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition." Gearhart M.D., Holmbeck S.M., Evans R.M., Dyson H.J., Wright P.E. J. Mol. Biol. 327:819-832(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 97-194, SUBUNIT, DNA-BINDING, MUTAGENESIS OF TYR-185.
[9]	"Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35." Collin R.W.J., Kalay E., Tariq M., Peters T., van der Zwaag B., Venselaar H., Oostrik J., Lee K., Ahmed Z.M., Caylan R., Li Y., Spierenburg H.A., Eyupoglu E., Heister A., Riazuddin S., Bahat E., Ansar M., Arslan S. , Wollnik B., Brunner H.G., Cremers C.W.R.J., Karaguzel A., Ahmad W., Cremers F.P.M., Vriend G., Friedman T.B., Riazuddin S., Leal S.M., Kremer H. Am. J. Hum. Genet. 82:125-138(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DFNB35 VAL-110; PRO-320; LEU-342; PRO-347 AND MET-389, VARIANT SER-386.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF094517 mRNA. Translation: AAC99409.1.
AY451389 mRNA. Translation: AAS15571.1.
AY451390 mRNA. Translation: AAS15572.1.
AB307714 mRNA. Translation: BAH02305.1.
HQ692852 mRNA. Translation: ADZ17363.1.
AC008050 Genomic DNA. Translation: AAG17472.1.
AC016543 Genomic DNA. No translation available.
BC131517 mRNA. Translation: AAI31518.1.

IPI

IPI00032812.

RefSeq

NP_004443.3. NM_004452.3.

UniGene

Hs.435845.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LO1	NMR	-	A	97-192	[»]

ProteinModelPortal

O95718.

SMR

O95718. Positions 97-433.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000261532.

PTM databases

PhosphoSite

O95718.

Proteomic databases

PaxDb

O95718.

PRIDE

O95718.

Protocols and materials databases

DNASU

2103.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261532; ENSP00000261532; ENSG00000119715.
ENST00000380887; ENSP00000370270; ENSG00000119715.
ENST00000505752; ENSP00000423004; ENSG00000119715.
ENST00000509242; ENSP00000422488; ENSG00000119715.
ENST00000556177; ENSP00000451658; ENSG00000119715.

GeneID

2103.

KEGG

hsa:2103.

UCSC

uc001xsq.1. human.
uc001xsr.3. human.

Organism-specific databases

CTD

2103.

GeneCards

GC14P076837.

HGNC

HGNC:3473. ESRRB.

MIM

602167. gene.
608565. phenotype.

neXtProt

NX_O95718.

Orphanet

90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.

PharmGKB

PA27889.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG282629.

HOGENOM

HOG000233467.

HOVERGEN

HBG108344.

KO

K08553.

OMA

EDRHLGS.

OrthoDB

EOG479F71.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

SignaLink

O95718.

Gene expression databases

ArrayExpress

O95718.

Bgee

O95718.

CleanEx

HS_ESRRB.

Genevestigator

O95718.

GermOnline

ENSG00000119715. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR027289. Oest-rel_rcp.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PIRSF

PIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.

PRINTS

PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O95718.

ChEMBL

CHEMBL3751.

ChiTaRS

ESRRB. human.

EvolutionaryTrace

O95718.

GenomeRNAi

2103.

NextBio

8507.

SOURCE

Search...

Entry information

Entry name

ERR2_HUMAN

Accession

Primary (citable) accession number: O95718
Secondary accession number(s): A2VDJ2 , B6ZGU4, Q5F0P7, Q5F0P8, Q9HCB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	January 25, 2012
Last modified:	May 29, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.