Reviewed, UniProtKB/Swiss-Prot O95718 (ERR2_HUMAN)

Names and origin

Protein names

Recommended name:
Steroid hormone receptor ERR2

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

Gene names

Name:	ESRRB
Synonyms:	ERRB2, ESRL2, NR3B2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	500 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Nuclear receptor that binds DNA as monomer.
Subunit structure	Monomer. Ref.4
Subcellular location	Nucleus Potential.
Involvement in disease	Defects in ESRRB are the cause of non-syndromic sensorineural deafness autosomal recessive type 35 (DFNB35) [MIM:608565]. DFNB35 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Ref.5
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
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cellular transcription Inferred from electronic annotation. Source: UniProtKB-KW regulation of cellular transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	sequence-specific DNA binding Ref.4 Inferred from direct assay. Source: UniProtKB steroid binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 500

500

Steroid hormone receptor ERR2

PRO_0000053662

Regions

DNA binding

100 – 186

87

Nuclear receptor Ref.4

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

Amino acid modifications

Modified residue

395

1

Phosphothreonine Ref.3

Natural variations

Natural variant

110

1

A → V in DFNB35. Ref.5

VAR_043503

Natural variant

320

1

L → P in DFNB35. Ref.5

VAR_043504

Natural variant

342

1

V → L in DFNB35. Ref.5

VAR_043505

Natural variant

347

1

L → P in DFNB35. Ref.5

VAR_043506

Natural variant

386

1

P → S

VAR_043507

Natural variant

389

1

T → M in DFNB35; uncertain pathological significance. Ref.5

VAR_043508

Experimental info

Mutagenesis

185

1

Y → A: 6-fold decrease in DNA-binding affinity. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

500

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)
	O95718-1 [UniParc]. Last modified May 1, 1999. Version 1. 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

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: 10072763] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"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: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-395, MASS SPECTROMETRY.
[4]	"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: 12654265] [Abstract] Cited for: STRUCTURE BY NMR OF 97-194, SUBUNIT, DNA-BINDING, MUTAGENESIS OF TYR-185.
[5]	"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: 18179891] [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.
AC008050 Genomic DNA. Translation: AAG17472.1.
AC016543 Genomic DNA. No translation available.

IPI

IPI00032812.

UniGene

Hs.435845

3D structure databases

PDBe
RCSB PDB
PDBj

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

SMR

O95718. Positions 207-432.

ModBase

Search...

Protein-protein interaction databases

STRING

O95718.

Proteomic databases

PRIDE

O95718.

Genome annotation databases

Ensembl

ENST00000261532; ENSP00000261532; ENSG00000119715; Homo sapiens. [Genome view]

UCSC

uc001xso.1. human.

Organism-specific databases

GeneCards

GC14P075907.

HGNC

HGNC:3473. ESRRB.

MIM

602167. gene.
608565. phenotype.

Orphanet

90636. Deafness, autosomal recessive, nonsyndromic, sensorineural, type DFNB.

PharmGKB

PA27889.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG108344.

OMA

ALGAHAN.

OrthoDB

EOG9V19M4.

PhylomeDB

O95718.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

O95718.

Bgee

O95718.

CleanEx

HS_ESRRB.

Genevestigator

O95718.

GermOnline

ENSG00000119715. Homo sapiens.

Family and domain databases

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR000003. RtnoidX_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Gene3D

G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.
G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.

Pfam

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

PRINTS

PR00545. RETINOIDXR.
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 Resources

NextBio

8507.

SOURCE

Search...

Entry information

Entry name

ERR2_HUMAN

Accession

Primary (citable) accession number: O95718
Secondary accession number(s): Q9HCB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	May 1, 1999
Last modified:	March 2, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.