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Protein

Estrogen receptor beta

Gene

Esr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • behavioral fear response Source: MGI
  • brain development Source: MGI
  • cellular response to estradiol stimulus Source: MGI
  • epithelial cell maturation involved in prostate gland development Source: MGI
  • estrous cycle Source: MGI
  • hormone-mediated apoptotic signaling pathway Source: MGI
  • intracellular estrogen receptor signaling pathway Source: MGI
  • intracellular steroid hormone receptor signaling pathway Source: MGI
  • learning or memory Source: MGI
  • negative regulation of androgen receptor signaling pathway Source: MGI
  • negative regulation of behavior Source: MGI
  • negative regulation of cell death Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of feeding behavior Source: MGI
  • negative regulation of neuron death Source: MGI
  • negative regulation of reactive oxygen species metabolic process Source: MGI
  • negative regulation of smooth muscle cell proliferation Source: MGI
  • negative regulation of transcription by RNA polymerase II Source: MGI
  • neuron migration Source: MGI
  • ovarian follicle development Source: MGI
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of blood vessel diameter Source: MGI
  • positive regulation of DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of epidermal growth factor receptor signaling pathway Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • prostate gland epithelium morphogenesis Source: MGI
  • regulation of cell proliferation Source: MGI
  • regulation of neuron apoptotic process Source: MGI
  • response to testosterone Source: MGI
  • Sertoli cell proliferation Source: MGI
  • uterus development Source: MGI
  • vagina development Source: MGI

Keywordsi

Molecular functionActivator, DNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandLipid-binding, Metal-binding, Steroid-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1257604 PIP3 activates AKT signaling
R-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8939211 ESR-mediated signaling

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:109392 Esr2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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) serine; 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

GlyConnecti146
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

CleanExiMM_ESR2
ExpressionAtlasiO08537 baseline and differential

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 DNAAF4. 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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini264 – 498NR LBDPROSITE-ProRule annotationAdd BLAST235

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 148ModulatingAdd BLAST148

Domaini

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

Sequence similaritiesi

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
GeneTreeiENSGT00760000118887
HOGENOMiHOG000233468
HOVERGENiHBG108344
InParanoidiO08537
KOiK08551
TreeFamiTF323751

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR028355 ER-beta/gamma
IPR021064 Estrogen_rcpt_beta_N
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR024178 Oest_rcpt/oest-rel_rcp
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF12497 ERbeta_N, 1 hit
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PIRSFiPIRSF500102 ER-b, 1 hit
PIRSF002527 ER-like_NR, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 2 hits
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

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

EnsembliENSMUST00000101291; ENSMUSP00000098849; ENSMUSG00000021055 [O08537-2]
ENSMUST00000110421; ENSMUSP00000106051; ENSMUSG00000021055 [O08537-1]
ENSMUST00000133564; ENSMUSP00000138637; ENSMUSG00000021055 [O08537-6]
GeneIDi13983
KEGGimmu:13983
UCSCiuc007nxu.1 mouse [O08537-2]
uc007nxv.1 mouse [O08537-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiESR2_MOUSE
AccessioniPrimary (citable) accession number: O08537
Secondary accession number(s): B2RUC6
, E9QKX7, O35635, O70519, Q8BG65, Q91Z86
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: March 21, 2012
Last modified: June 20, 2018
This is version 182 of the entry and version 3 of the sequence. See 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

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