Q62986 (ESR2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Estrogen receptor beta
Short name=ER-beta

Alternative name(s):
Nuclear receptor subfamily 3 group A member 2

Gene names

Name:	Esr2
Synonyms:	Erbeta, Nr3a2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	530 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds estrogens with an affinity similar to that of ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform 3 and isoform 4 are unable to bind DNA and activate transcription due to the truncation of the DNA binding domain. Isoform 2 shows loss of ligand binding affinity and suppresses ER-alpha and ER-beta1 mediated transcriptional activation and may act as a dominant negative regulator of estrogen action.
Subunit structure	Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA1, NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with PELP1, UBE1C and AKAP13. Interacts with DNTTIP2 By similarity. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with PRMT2 By similarity. Interacts with DYX1C1. Ref.6 Ref.7
Subcellular location	Nucleus.
Tissue specificity	Expressed in prostate, ovary, lung, liver, kidney, fat, bone, brain, uterus and testis.
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Post-translational modification	Phosphorylation at Ser-87 and Ser-105 recruits NCOA1 By similarity.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence CAA05631.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Steroid-binding Zinc
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell proliferation Inferred from mutant phenotype PubMed 17928626. Source: RGD behavioral fear response Inferred from direct assay PubMed 15514081. Source: RGD cellular response to estradiol stimulus Inferred from direct assay PubMed 17928626. Source: RGD intracellular estrogen receptor signaling pathway Traceable author statement Ref.2. Source: RGD learning or memory Inferred from mutant phenotype PubMed 16904920. Source: RGD negative regulation of behavior Inferred from direct assay PubMed 15514081. Source: RGD negative regulation of epithelial cell proliferation Inferred from direct assay PubMed 12370428. Source: RGD negative regulation of neuron death Inferred from direct assay PubMed 15126114. Source: RGD negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.2. Source: RGD positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 17928626. Source: RGD positive regulation of epidermal growth factor receptor signaling pathway Inferred from mutant phenotype PubMed 17928626. Source: RGD positive regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 15564578. Source: RGD regulation of neuron apoptotic process Inferred from direct assay PubMed 15126114. Source: RGD response to testosterone stimulus Inferred from mutant phenotype PubMed 16904920. Source: RGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrion Inferred from direct assay PubMed 15024130. Source: MGI neuron projection Inferred from direct assay PubMed 16122717. Source: RGD nucleus Inferred from direct assay PubMed 16122717PubMed 17928626. Source: RGD perikaryon Inferred from direct assay PubMed 16122717. Source: RGD perinuclear region of cytoplasm Inferred from direct assay PubMed 17928626. Source: RGD plasma membrane Inferred from direct assay PubMed 17928626PubMed 18489713. Source: RGD
Molecular_function	estrogen receptor activity Inferred from direct assay PubMed 15105439. Source: RGD estrogen response element binding Inferred from direct assay Ref.2. Source: RGD hormone binding Inferred from direct assay PubMed 17928626. Source: RGD sequence-specific DNA binding Inferred from direct assay PubMed 12200235. Source: RGD sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro steroid binding Inferred from direct assay PubMed 17928626. Source: RGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q62986-1)

Also known as: Beta1;

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: Q62986-2)

Also known as: Beta2;

The sequence of this isoform differs from the canonical sequence as follows:
     364-364: R → RSSEDPHWHVAQMKSAAPR

Isoform 3 (identifier: Q62986-3)

Also known as: Beta1-delta3;

The sequence of this isoform differs from the canonical sequence as follows:
     179-217: Missing.

Isoform 4 (identifier: Q62986-4)

Also known as: Beta2-delta3;

The sequence of this isoform differs from the canonical sequence as follows:
     179-217: Missing.
     364-364: R → RSSEDPHWHVAQMKSAAPR

Isoform 5 (identifier: Q62986-5)

Also known as: Beta1-delta4;

The sequence of this isoform differs from the canonical sequence as follows:
     219-318: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 530

530

Estrogen receptor beta

PRO_0000053646

Regions

DNA binding

149 – 214

66

Nuclear receptor

Zinc finger

149 – 169

21

NR C4-type

Zinc finger

185 – 209

25

NR C4-type

Region

1 – 148

148

Modulating

Region

215 – 530

316

Steroid-binding

Amino acid modifications

Modified residue

61

1

Phosphoserine; alternate By similarity

Modified residue

87

1

Phosphoserine; by MAPK By similarity

Modified residue

105

1

Phosphoserine; by MAPK By similarity

Glycosylation

61

1

O-linked (GlcNAc); alternate By similarity

Natural variations

Alternative sequence

179 – 217

39

Missing in isoform 3 and isoform 4.

VSP_003697

Alternative sequence

219 – 318

100

Missing in isoform 5.

VSP_003698

Alternative sequence

364

1

R → RSSEDPHWHVAQMKSAAPR in isoform 2 and isoform 4.

VSP_003699

Experimental info

Sequence conflict

72

1

L → Q Ref.3

Sequence conflict

72

1

L → Q Ref.4

Sequence conflict

150

1

P → A Ref.3

Sequence conflict

150

1

P → A Ref.4

Sequence conflict

165

1

S → P in CAA05631. Ref.3

Sequence conflict

505

1

S → P in CAA05631. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

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.

.

.

.

.

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530

Helix Strand Turn

Details...

Helix

265 – 274

10

Helix

291 – 315

25

Helix

319 – 321

3

Helix

324 – 347

24

Beta strand

353 – 357

5

Beta strand

360 – 363

4

Helix

364 – 369

6

Helix

373 – 390

18

Helix

394 – 405

12

Turn

406 – 409

4

Helix

421 – 443

23

Helix

448 – 481

34

Helix

489 – 496

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta1) [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 36F269D9FD773DA9	FASTA	530	59,152
	10 20 30 40 50 60 MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS PAVMNYSVPG 70 80 90 100 110 120 STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA EPQKSPWCEA RSLEHTLPVN 130 140 150 160 170 180 RETLKRKLSG SSCASPVTSP NAKRDAHFCP VCSDYASGYH YGVWSCEGCK AFFKRSIQGH 190 200 210 220 230 240 NDYICPATNQ CTIDKNRRKS CQACRLRKCY EVGMVKCGSR RERCGYRIVR RQRSSSEQVH 250 260 270 280 290 300 CLSKAKRNGG HAPRVKELLL STLSPEQLVL TLLEAEPPNV LVSRPSMPFT EASMMMSLTK 310 320 330 340 350 360 LADKELVHMI GWAKKIPGFV ELSLLDQVRL LESCWMEVLM VGLMWRSIDH PGKLIFAPDL 370 380 390 400 410 420 VLDRDEGKCV EGILEIFDML LATTSRFREL KLQHKEYLCV KAMILLNSSM YPLASANQEA 430 440 450 460 470 480 ESSRKLTHLL NAVTDALVWV IAKSGISSQQ QSVRLANLLM LLSHVRHISN KGMEHLLSMK 490 500 510 520 530 CKNVVPVYDL LLEMLNAHTL RGYKSSISGS ECSSTEDSKN KESSQNLQSQ
	Isoform 2 (Beta2) [UniParc]. Checksum: E9E636A7E317CB3B	FASTA	548	61,168
	10 20 30 40 50 60 MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS PAVMNYSVPG 70 80 90 100 110 120 STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA EPQKSPWCEA RSLEHTLPVN 130 140 150 160 170 180 RETLKRKLSG SSCASPVTSP NAKRDAHFCP VCSDYASGYH YGVWSCEGCK AFFKRSIQGH 190 200 210 220 230 240 NDYICPATNQ CTIDKNRRKS CQACRLRKCY EVGMVKCGSR RERCGYRIVR RQRSSSEQVH 250 260 270 280 290 300 CLSKAKRNGG HAPRVKELLL STLSPEQLVL TLLEAEPPNV LVSRPSMPFT EASMMMSLTK 310 320 330 340 350 360 LADKELVHMI GWAKKIPGFV ELSLLDQVRL LESCWMEVLM VGLMWRSIDH PGKLIFAPDL 370 380 390 400 410 420 VLDRSSEDPH WHVAQMKSAA PRDEGKCVEG ILEIFDMLLA TTSRFRELKL QHKEYLCVKA 430 440 450 460 470 480 MILLNSSMYP LASANQEAES SRKLTHLLNA VTDALVWVIA KSGISSQQQS VRLANLLMLL 490 500 510 520 530 540 SHVRHISNKG MEHLLSMKCK NVVPVYDLLL EMLNAHTLRG YKSSISGSEC SSTEDSKNKE SSQNLQSQ
	Isoform 3 (Beta1-delta3) [UniParc]. Checksum: 6FA4105E37B02A03	FASTA	491	54,663
	10 20 30 40 50 60 MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS PAVMNYSVPG 70 80 90 100 110 120 STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA EPQKSPWCEA RSLEHTLPVN 130 140 150 160 170 180 RETLKRKLSG SSCASPVTSP NAKRDAHFCP VCSDYASGYH YGVWSCEGCK AFFKRSIQGS 190 200 210 220 230 240 RRERCGYRIV RRQRSSSEQV HCLSKAKRNG GHAPRVKELL LSTLSPEQLV LTLLEAEPPN 250 260 270 280 290 300 VLVSRPSMPF TEASMMMSLT KLADKELVHM IGWAKKIPGF VELSLLDQVR LLESCWMEVL 310 320 330 340 350 360 MVGLMWRSID HPGKLIFAPD LVLDRDEGKC VEGILEIFDM LLATTSRFRE LKLQHKEYLC 370 380 390 400 410 420 VKAMILLNSS MYPLASANQE AESSRKLTHL LNAVTDALVW VIAKSGISSQ QQSVRLANLL 430 440 450 460 470 480 MLLSHVRHIS NKGMEHLLSM KCKNVVPVYD LLLEMLNAHT LRGYKSSISG SECSSTEDSK 490 NKESSQNLQS Q
	Isoform 4 (Beta2-delta3) [UniParc]. Checksum: E5DA93F80B6E6BAC	FASTA	509	56,679
	10 20 30 40 50 60 MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS PAVMNYSVPG 70 80 90 100 110 120 STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA EPQKSPWCEA RSLEHTLPVN 130 140 150 160 170 180 RETLKRKLSG SSCASPVTSP NAKRDAHFCP VCSDYASGYH YGVWSCEGCK AFFKRSIQGS 190 200 210 220 230 240 RRERCGYRIV RRQRSSSEQV HCLSKAKRNG GHAPRVKELL LSTLSPEQLV LTLLEAEPPN 250 260 270 280 290 300 VLVSRPSMPF TEASMMMSLT KLADKELVHM IGWAKKIPGF VELSLLDQVR LLESCWMEVL 310 320 330 340 350 360 MVGLMWRSID HPGKLIFAPD LVLDRSSEDP HWHVAQMKSA APRDEGKCVE GILEIFDMLL 370 380 390 400 410 420 ATTSRFRELK LQHKEYLCVK AMILLNSSMY PLASANQEAE SSRKLTHLLN AVTDALVWVI 430 440 450 460 470 480 AKSGISSQQQ SVRLANLLML LSHVRHISNK GMEHLLSMKC KNVVPVYDLL LEMLNAHTLR 490 500 GYKSSISGSE CSSTEDSKNK ESSQNLQSQ
	Isoform 5 (Beta1-delta4) [UniParc]. Checksum: 3136E9B67BA0E01F	FASTA	430	47,904
	10 20 30 40 50 60 MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS PAVMNYSVPG 70 80 90 100 110 120 STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA EPQKSPWCEA RSLEHTLPVN 130 140 150 160 170 180 RETLKRKLSG SSCASPVTSP NAKRDAHFCP VCSDYASGYH YGVWSCEGCK AFFKRSIQGH 190 200 210 220 230 240 NDYICPATNQ CTIDKNRRKS CQACRLRKCY EVGMVKCGFV ELSLLDQVRL LESCWMEVLM 250 260 270 280 290 300 VGLMWRSIDH PGKLIFAPDL VLDRDEGKCV EGILEIFDML LATTSRFREL KLQHKEYLCV 310 320 330 340 350 360 KAMILLNSSM YPLASANQEA ESSRKLTHLL NAVTDALVWV IAKSGISSQQ QSVRLANLLM 370 380 390 400 410 420 LLSHVRHISN KGMEHLLSMK CKNVVPVYDL LLEMLNAHTL RGYKSSISGS ECSSTEDSKN 430 KESSQNLQSQ

References

[1]	"Cloning of a novel receptor expressed in rat prostate and ovary." Kuiper G.G.J.M., Enmark E., Pelto-Huikko M., Nilsson S., Gustafsson J.-A. Proc. Natl. Acad. Sci. U.S.A. 93:5925-5930(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-530 (ISOFORM 1). Strain: Sprague-Dawley. Tissue: Prostate.
[2]	"A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the ligand binding domain as a putative dominant negative regular of estrogen action." Maruyama K., Endoh H., Sasaki-Iwaoka H., Kanou H., Shimaya E., Hashimoto S., Kato S., Kawashima H. Biochem. Biophys. Res. Commun. 246:142-147(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-530 (ISOFORM 2). Strain: Wistar. Tissue: Ovary.
[3]	"Tissue specific responses to estrogen: an explanation based on differential activation of multiple estrogen receptors with different estrogen response elements." Aldridge T.C. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2). Strain: Wistar. Tissue: Prostate.
[4]	"Identification of estrogen receptor beta2, a functional variant of estrogen receptor beta expressed in normal rat tissues." Petersen D.N., Tkalcevic G.T., Koza-Taylor P.H., Turi T.G., Brown T.A. Endocrinology 139:1082-1092(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 46-530 (ISOFORMS 1; 3 AND 4). Strain: Sprague-Dawley.
[5]	"A novel splice variant of estrogen receptor beta found in rat brain." Price R., Handa R.J. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM 5). Strain: Sprague-Dawley. Tissue: Brain.
[6]	"The activating enzyme of NEDD8 inhibits steroid receptor function." Fan M., Long X., Bailey J.A., Reed C.A., Osborne E., Gize E.A., Kirk E.A., Bigsby R.M., Nephew K.P. Mol. Endocrinol. 16:315-330(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE1C.
[7]	"Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia." Massinen S., Tammimies K., Tapia-Paez I., Matsson H., Hokkanen M.E., Soederberg O., Landegren U., Castren E., Gustafsson J.A., Treuter E., Kere J. Hum. Mol. Genet. 18:2802-2812(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DYX1C1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U57439 mRNA. Translation: AAC52602.1.
AB012721 mRNA. Translation: BAA25431.1.
AJ002602 Genomic DNA. Translation: CAA05631.1. Different initiation.
AJ002603 Genomic DNA. Translation: CAA05632.1.
AF042058 mRNA. Translation: AAB97424.1.
AF042059 mRNA. Translation: AAB97425.1.
AF042060 mRNA. Translation: AAB97426.1.
AF042061 mRNA. Translation: AAB97427.1.
AF161187 mRNA. Translation: AAD47637.1.

IPI

IPI00231793.
IPI00231794.
IPI00231795.
IPI00231871.
IPI00566569.

PIR

JW0046.

RefSeq

NP_036886.1. NM_012754.1.

UniGene

Rn.37460.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HJ1	X-ray	2.30	A	255-509	[»]
1QKN	X-ray	2.25	A	255-509	[»]
2J7X	X-ray	2.10	A	255-509	[»]
2J7Y	X-ray	1.80	A	255-509	[»]

ProteinModelPortal

Q62986.

SMR

Q62986. Positions 144-216, 262-498.

ModBase

Search...

PTM databases

PhosphoSite

Q62986.

Proteomic databases

PaxDb

Q62986.

PRIDE

Q62986.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

25149.

KEGG

rno:25149.

UCSC

RGD:2582. rat.

Organism-specific databases

CTD

2100.

RGD

2582. Esr2.

Phylogenomic databases

eggNOG

NOG271979.

HOVERGEN

HBG108344.

InParanoid

Q62986.

KO

K08551.

Gene expression databases

ArrayExpress

Q62986.

Genevestigator

Q62986.

GermOnline

ENSRNOG00000005343. Rattus norvegicus.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR021064. Estrogen_rcpt_beta_N.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF12497. ERbeta_N. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PIRSF

PIRSF002527. ER-like_NR. 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

Q62986.

ChEMBL

CHEMBL3021.

EvolutionaryTrace

Q62986.

NextBio

605585.

Entry information

Entry name

ESR2_RAT

Accession

Primary (citable) accession number: Q62986
Secondary accession number(s): O35784 , O35785, O55015, O55016, O70195, Q9R185

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	April 3, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program