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Protein

Estrogen receptor beta

Gene

Esr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1 (ER-alpha), and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. May play a role in ovarian follicular growth and maturation.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi149 – 214Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri149 – 169NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri185 – 209NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

  • brain development Source: MGI
  • epithelial cell maturation involved in prostate gland development Source: MGI
  • hormone-mediated apoptotic signaling pathway Source: MGI
  • intracellular estrogen receptor signaling pathway Source: MGI
  • negative regulation of androgen receptor signaling pathway Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • neuron migration Source: MGI
  • ovarian follicle development Source: MGI
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • prostate gland epithelium morphogenesis Source: MGI
  • regulation of cell proliferation Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • uterus development Source: MGI
  • vagina development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, Steroid-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Estrogen receptor beta
Short name:
ER-beta
Alternative name(s):
Nuclear receptor subfamily 3 group A member 2
Gene namesi
Name:Esr2
Synonyms:Estrb, Nr3a2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:109392. Esr2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • mitochondrion Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi105S → A: Abolishes stimulatory effect of Ras. 1 Publication1
Mutagenesisi139S → A: No loss of the stimulatory effect of Ras. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2995.
GuidetoPHARMACOLOGYi621.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536441 – 530Estrogen receptor betaAdd BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei61Phosphoserine; alternate1 Publication1
GlycosylationiCAR_00020161O-linked (GlcNAc); alternate1 Publication1
Modified residuei87Phosphoserine; by MAPK1 Publication1
Modified residuei105Phosphoserine; by MAPK1 Publication1

Post-translational modificationi

Phosphorylation at Ser-87 and Ser-105 recruits NCOA1.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO08537.
PRIDEiO08537.

PTM databases

iPTMnetiO08537.
PhosphoSitePlusiO08537.
UniCarbKBiO08537.

Expressioni

Tissue specificityi

Expressed in prostate, ovary, Leydig cells and in epithelium of the efferent ductules and of the initial segment of the epididymis.1 Publication

Inductioni

Isoforms 1 and 2 are down-regulated by 17-beta-estradiol.1 Publication

Gene expression databases

BgeeiENSMUSG00000021055.
CleanExiMM_ESR2.

Interactioni

Subunit structurei

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 DYX1C1. Interacts with PRMT2. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
FosP011012EBI-2526214,EBI-4288185

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199522. 3 interactors.
IntActiO08537. 2 interactors.
STRINGi10090.ENSMUSP00000098849.

Chemistry databases

BindingDBiO08537.

Structurei

3D structure databases

ProteinModelPortaliO08537.
SMRiO08537.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 148ModulatingAdd BLAST148
Regioni215 – 530Steroid-bindingAdd BLAST316

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri149 – 169NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri185 – 209NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000233468.
HOVERGENiHBG108344.
InParanoidiO08537.
KOiK08551.
TreeFamiTF323751.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR028355. ER-beta/gamma.
IPR021064. Estrogen_rcpt_beta_N.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF12497. ERbeta_N. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF500102. ER-b. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O08537-1) [UniParc]FASTAAdd to basket
Also known as: Beta-1

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.

« Hide

        10         20         30         40         50
MEIKNSPSSL TSPASYNCSQ SILPLEHGPI YIPSSYVESR HEYSAMTFYS
60 70 80 90 100
PAVMNYSVPS STGNLEGGPV RQTASPNVLW PTSGHLSPLA THCQSSLLYA
110 120 130 140 150
EPQKSPWCEA RSLEHTLPVN RETLKRKLGG SGCASPVTSP SAKRDAHFCA
160 170 180 190 200
VCSDYASGYH YGVWSCEGCK AFFKRSIQGH NDYICPATNQ CTIDKNRRKS
210 220 230 240 250
CQACRLRKCY EVGMVKCGSR RERCGYRIVR RQRSASEQVH CLNKAKRTSG
260 270 280 290 300
HTPRVKELLL NSLSPEQLVL TLLEAEPPNV LVSRPSMPFT EASMMMSLTK
310 320 330 340 350
LADKELVHMI GWAKKIPGFV ELSLLDQVRL LESCWMEVLM VGLMWRSIDH
360 370 380 390 400
PGKLIFAPDL VLDRDEGKCV EGILEIFDML LATTARFREL KLQHKEYLCV
410 420 430 440 450
KAMILLNSSM YPLATASQEA ESSRKLTHLL NAVTDALVWV ISKSGISSQQ
460 470 480 490 500
QSVRLANLLM LLSHVRHISN KGMEHLLSMK CKNVVPVYDL LLEMLNAHTL
510 520 530
RGYKSSISGS ECCSTEDSKS KEGSQNLQSQ
Length:530
Mass (Da):59,070
Last modified:March 21, 2012 - v3
Checksum:iBEFA25F62650A8D4
GO
Isoform 2 (identifier: O08537-2) [UniParc]FASTAAdd to basket
Also known as: Beta-2

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

Show »
Length:548
Mass (Da):61,084
Checksum:i5A3BFF5FCD158E7C
GO
Isoform 3 (identifier: O08537-4) [UniParc]FASTAAdd to basket
Also known as: Beta-5A

The sequence of this isoform differs from the canonical sequence as follows:
     319-409: Missing.

Note: Corresponds to exons 5 and 6 deletion.1 Publication
Show »
Length:439
Mass (Da):48,550
Checksum:iFCA85E5235E368D2
GO
Isoform 4 (identifier: O08537-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     319-343: FVELSLLDQVRLLESCWMEVLMVGL → MRGSAWKGFWKSLTCSWRRRHGSVS
     344-530: Missing.

Note: Corresponds to exon 5 deletion (PubMed:9685228). May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.1 Publication
Show »
Length:343
Mass (Da):38,185
Checksum:i0073C2E153F493D3
GO
Isoform 5 (identifier: O08537-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     365-377: DEGKCVEGILEIF → YVPLGYRKPGSRE
     378-530: Missing.

Note: Corresponds to exon 6 deletion (PubMed:9685228). May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.1 Publication
Show »
Length:377
Mass (Da):42,107
Checksum:i59314206E084E413
GO

Sequence cautioni

The sequence AAC17919 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAI41076 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAI45330 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAL15175 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAC35719 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAC35770 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti47T → A in CAA03949 (PubMed:9280064).Curated1
Sequence conflicti142A → T in CAA03949 (PubMed:9280064).Curated1
Sequence conflicti200S → N in CAA03949 (PubMed:9280064).Curated1
Sequence conflicti378D → G in AAB51132 (PubMed:16141072).Curated1
Sequence conflicti378D → G in AAL15175 (PubMed:11878304).Curated1
Sequence conflicti412P → H in CAA03949 (PubMed:9280064).Curated1
Sequence conflicti445G → R in CAA03949 (PubMed:9280064).Curated1
Sequence conflicti511E → G in CAA03949 (PubMed:9280064).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003696319 – 409Missing in isoform 3. CuratedAdd BLAST91
Alternative sequenceiVSP_042429319 – 343FVELS…LMVGL → MRGSAWKGFWKSLTCSWRRR HGSVS in isoform 4. CuratedAdd BLAST25
Alternative sequenceiVSP_042430344 – 530Missing in isoform 4. CuratedAdd BLAST187
Alternative sequenceiVSP_003693364R → RSSEDPHWHVAQTKSAVPR in isoform 2. 2 Publications1
Alternative sequenceiVSP_042431365 – 377DEGKC…ILEIF → YVPLGYRKPGSRE in isoform 5. CuratedAdd BLAST13
Alternative sequenceiVSP_042432378 – 530Missing in isoform 5. CuratedAdd BLAST153

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK054290 mRNA. Translation: BAC35719.1. Different initiation.
AK054413 mRNA. Translation: BAC35770.1. Different initiation.
AC164121 Genomic DNA. No translation available.
BC141075 mRNA. Translation: AAI41076.1. Different initiation.
BC145329 mRNA. Translation: AAI45330.1. Different initiation.
U81451 mRNA. Translation: AAB51132.1.
AJ000220 Genomic DNA. Translation: CAA03949.1.
AY054413 mRNA. Translation: AAL15175.1. Different initiation.
AF067422 mRNA. Translation: AAC17919.1. Different initiation.
AF063853 mRNA. Translation: AAC16656.1.
RefSeqiNP_034287.3. NM_010157.3.
NP_997590.1. NM_207707.1.
UniGeneiMm.2561.

Genome annotation databases

GeneIDi13983.
KEGGimmu:13983.
UCSCiuc007nxu.1. mouse. [O08537-2]
uc007nxv.1. mouse. [O08537-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK054290 mRNA. Translation: BAC35719.1. Different initiation.
AK054413 mRNA. Translation: BAC35770.1. Different initiation.
AC164121 Genomic DNA. No translation available.
BC141075 mRNA. Translation: AAI41076.1. Different initiation.
BC145329 mRNA. Translation: AAI45330.1. Different initiation.
U81451 mRNA. Translation: AAB51132.1.
AJ000220 Genomic DNA. Translation: CAA03949.1.
AY054413 mRNA. Translation: AAL15175.1. Different initiation.
AF067422 mRNA. Translation: AAC17919.1. Different initiation.
AF063853 mRNA. Translation: AAC16656.1.
RefSeqiNP_034287.3. NM_010157.3.
NP_997590.1. NM_207707.1.
UniGeneiMm.2561.

3D structure databases

ProteinModelPortaliO08537.
SMRiO08537.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199522. 3 interactors.
IntActiO08537. 2 interactors.
STRINGi10090.ENSMUSP00000098849.

Chemistry databases

BindingDBiO08537.
ChEMBLiCHEMBL2995.
GuidetoPHARMACOLOGYi621.

PTM databases

iPTMnetiO08537.
PhosphoSitePlusiO08537.
UniCarbKBiO08537.

Proteomic databases

PaxDbiO08537.
PRIDEiO08537.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi13983.
KEGGimmu:13983.
UCSCiuc007nxu.1. mouse. [O08537-2]
uc007nxv.1. mouse. [O08537-1]

Organism-specific databases

CTDi2100.
MGIiMGI:109392. Esr2.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000233468.
HOVERGENiHBG108344.
InParanoidiO08537.
KOiK08551.
TreeFamiTF323751.

Miscellaneous databases

PROiO08537.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021055.
CleanExiMM_ESR2.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR028355. ER-beta/gamma.
IPR021064. Estrogen_rcpt_beta_N.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF12497. ERbeta_N. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF500102. ER-b. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiESR2_MOUSE
AccessioniPrimary (citable) accession number: O08537
Secondary accession number(s): B2RUC6
, E9QKX7, O35635, O70519, Q8BG65, Q91Z86
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: March 21, 2012
Last modified: November 2, 2016
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.