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UniProtKB - P19785 (ESR1_MOUSE)

Protein

Estrogen receptor

Gene

Esr1

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

Functioni

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi189 – 254Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri189 – 209NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri225 – 249NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-1251985 Nuclear signaling by ERBB4
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors
R-MMU-5689896 Ovarian tumor domain proteases
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-MMU-8931987 RUNX1 regulates estrogen receptor mediated transcription
R-MMU-8939211 ESR-mediated signaling
R-MMU-9018519 Estrogen-dependent gene expression

Names & Taxonomyi

Protein namesi
Recommended name:
Estrogen receptor
Short name:
ER
Alternative name(s):
ER-alpha
Estradiol receptor
Nuclear receptor subfamily 3 group A member 1
Gene namesi
Name:Esr1
Synonyms:Esr, Estr, Estra, Nr3a1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1352467 Esr1

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

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi362I → A: No effect on transcriptional activity and estrogen-induced interaction with NCOA1. Abolishes estrogen-induced interaction with NCOA1; when associated with A-376 and A-380. 1 Publication1
Mutagenesisi362I → D: Abolishes transcriptional activity and estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi366K → A: Greatly reduces transcriptional activity and estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi366K → D: Abolishes transcriptional activity and estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi366K → L: Reduces transcriptional activity and estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi371F → A: Abolishes estrogen-dependent NF-kappa B transcriptional repression, impairs transcriptional activity, abolishes estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi376L → A: Reduces transcriptional activity, no effect on estrogen-induced interaction with NCOA1. Abolishes estrogen-induced interaction with NCOA1; when associated with A-362 and A-380. 1 Publication1
Mutagenesisi376L → D: Reduces transcriptional activity and estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi380V → A: No effect on transcriptional activity and estrogen-induced interaction with NCOA1. Abolishes estrogen-induced interaction with NCOA1; when associated with A-362 and A-376. 1 Publication1
Mutagenesisi380V → D: Abolishes transcriptional activity and estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi451C → A: Loss of ZDHHC7 and ZDHHC21 binding. Loss of palmitoylation. 1 Publication1
Mutagenesisi508L → A: Reduces DNA-binding, attenuates transcriptional activity, does not effect estrogen-dependent NF-kappa B transcriptional repression; when associated with E-512 and E-515. 1 Publication1
Mutagenesisi508L → E: Abolishes DNA-binding, abolishes transcriptional activity and estrogen-dependent NF-kappa B transcriptional repression; when associated with E-512 and E-515. 1 Publication1
Mutagenesisi509A → E: Reduces DNA-binding,, attenuates transcriptional activity, does not effect estrogen-dependent NF-kappa B transcriptional repression. 1 Publication1
Mutagenesisi512L → A: Reduces DNA-binding, attenuates transcriptional activity, does not effect estrogen-dependent NF-kappa B transcriptional repression; when associated with E-508 and E-515. 1 Publication1
Mutagenesisi512L → E: Abolishes DNA-binding, abolishes transcriptional activity and estrogen-dependent NF-kappa B transcriptional repression; when associated with E-508 and E-515. 1 Publication1
Mutagenesisi515L → A: Reduces DNA-binding, attenuates transcriptional activity, does not effect estrogen-dependent NF-kappa B transcriptional repression; when associated with E-508 and E-512. 1 Publication1
Mutagenesisi515L → E: Abolishes DNA-binding, abolishes transcriptional activity and estrogen-dependent NF-kappa B transcriptional repression; when associated with E-508 and E-512. 1 Publication1
Mutagenesisi525G → R: Abolishes estrogen binding; impairs repression of NF-kappa activity. 1 Publication1
Mutagenesisi542D → N: Abolishes estrogen-dependent NF-kappa B transcriptional repression, impairs transcriptional activity, impairs estrogen-induced interaction with NCOA1; when associated with Q-546 and N-548. 1 Publication1
Mutagenesisi543 – 544LL → AA: Abolishes estrogen-dependent NF-kappa B transcriptional repression, abolishes estrogen-induced interaction with NCOA1. 1 Publication2
Mutagenesisi543L → A: Abolishes estrogen-induced interaction with NCOA1. 1 Publication1
Mutagenesisi546E → Q: Abolishes estrogen-dependent NF-kappa B transcriptional repression, impairs transcriptional activity, impairs estrogen-induced interaction with NCOA1; when associated with N-542 and N-548. 1 Publication1
Mutagenesisi547 – 548ML → AA: No effect on estrogen-dependent NF-kappa B transcriptional repression, greatly impairs transcriptional activity, abolishes estrogen-induced interaction with NCOA1. 1 Publication2
Mutagenesisi549D → N: Abolishes estrogen-dependent NF-kappa B transcriptional repression, impairs transcriptional activity, impairs estrogen-induced interaction with NCOA1; when associated with N-542 and Q-546. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3065
GuidetoPHARMACOLOGYi620

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536211 – 599Estrogen receptorAdd BLAST599

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10O-linked (GlcNAc) serine1 Publication1
Glycosylationi50O-linked (GlcNAc) threonine1 Publication1
Modified residuei108Phosphoserine; by CDK2By similarity1
Modified residuei110Phosphoserine; by CDK2By similarity1
Modified residuei122PhosphoserineBy similarity1
Modified residuei171Phosphoserine; by CK2By similarity1
Modified residuei264Asymmetric dimethylarginine; by PRMT1By similarity1
Lipidationi451S-palmitoyl cysteine1 Publication1
Modified residuei541Phosphotyrosine; by Tyr-kinasesBy similarity1
GlycosylationiCAR_000137575O-linked (GlcNAc) threonine2 Publications1

Post-translational modificationi

Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-122 by PPP5C inhibits its transactivation activity (By similarity). Phosphorylated by LMTK3 (in vitro) (By similarity).By similarity
Ubiquitinated. Deubiquitinated by OTUB1 (By similarity).By similarity
Dimethylated by PRMT1 at Arg-264. The methylation may favor cytoplasmic localization (By similarity).By similarity
Palmitoylated at Cys-451 by ZDHHC7 and ZDHHC21. This modification is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor.1 Publication
Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation. Deubiquitinated by OTUB1.By similarity

Keywords - PTMi

Glycoprotein, Lipoprotein, Methylation, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP19785
PRIDEiP19785

PTM databases

GlyConnecti145
iPTMnetiP19785
PhosphoSitePlusiP19785
SwissPalmiP19785
UniCarbKBiP19785

Expressioni

Gene expression databases

BgeeiENSMUSG00000019768 Expressed in 219 organ(s), highest expression level in uterus
CleanExiMM_ESR1
ExpressionAtlasiP19785 baseline and differential
GenevisibleiP19785 MM

Interactioni

Subunit structurei

Interacts with BCAS3. Binds DNA as a homodimer (By similarity). Can form a heterodimer with ESR2 (By similarity). Interacts with coactivator NCOA5. Interacts with NCOA7; the interaction is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1, KDM5A, MAP1S, PELP1, SMARD1, and UBE1C. Interacts with MUC1; the interaction is stimulated by 7 beta-estradiol (E2) and enhances ERS1-mediated transcription. Interacts with DNTTIP2, and UIMC1. Interacts with KMT2D/MLL2. Interacts with ATAD2; the interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via its C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interacts with SH2D4A; the interaction blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62; the interaction requires estradiol and appears to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DNAAF4. Interacts with PRMT2. Interacts with PI3KR1 or PIK3R2, SRC and PTK2/FAK1. Interacts with RBFOX2. Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent (By similarity). Interacts with FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with coactivators NCOA3 and NCOA6. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3. Interacts with NRIP1 (By similarity). Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts with CLOCK and the interaction is stimulated by estrogen (By similarity). Interacts with BCAS3. Interacts with TRIP4 (ufmylated); estrogen dependent (By similarity). Interacts with LMTK3; the interaction phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with ZFHX3 (By similarity). Interacts with SFR1 in a ligand-dependent and -independent manner (By similarity). Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (By similarity). Interacts (via DNA-binding domain) with POU4F2 isoform 2 (C-terminus); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (PubMed:9448000). Interacts with ESRRB isoform 1 (By similarity). Interacts with UBE3A nad WBP2 (By similarity). Interacts with GTF2B (By similarity).By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi199521, 25 interactors
IntActiP19785, 8 interactors
MINTiP19785
STRINGi10090.ENSMUSP00000070070

Chemistry databases

BindingDBiP19785

Structurei

3D structure databases

ProteinModelPortaliP19785
SMRiP19785
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini315 – 551NR LBDPROSITE-ProRule annotationAdd BLAST237

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 188Modulating (transactivation AF-1); mediates interaction with MACROD1By similarityAdd BLAST188
Regioni35 – 178Interaction with DDX5; self-associationBy similarityAdd BLAST144
Regioni35 – 47Required for interaction with NCOA1By similarityAdd BLAST13
Regioni189 – 314Mediates interaction with DNTTIP2By similarityAdd BLAST126
Regioni255 – 314HingeAdd BLAST60
Regioni266 – 599Interaction with AKAP13By similarityAdd BLAST334
Regioni268 – 599Self-associationBy similarityAdd BLAST332
Regioni315 – 599Transactivation AF-2By similarityAdd BLAST285

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi64 – 72Poly-Ala9

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner (By similarity).By similarity

Sequence similaritiesi

Belongs to the nuclear hormone receptor family. NR3 subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri189 – 209NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri225 – 249NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000233468
HOVERGENiHBG108344
InParanoidiP19785
KOiK08550
OMAiEAGPPAF
OrthoDBiEOG091G03V4
PhylomeDBiP19785
TreeFamiTF323751

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR024178 Oest_rcpt/oest-rel_rcp
IPR001292 Oestr_rcpt
IPR024736 Oestrogen-typ_rcpt_final_C_dom
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF12743 ESR1_C, 1 hit
PF00104 Hormone_recep, 1 hit
PF02159 Oest_recep, 1 hit
PF00105 zf-C4, 1 hit
PIRSFiPIRSF500101 ER-a, 1 hit
PIRSF002527 ER-like_NR, 1 hit
PRINTSiPR00543 OESTROGENR
PR00398 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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

P19785-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKMPMERALG EVYVDNSKPT 
        60         70         80         90        100
VFNYPEGAAY EFNAAAAAAA AASAPVYGQS GIAYGPGSEA AAFSANSLGA 
       110        120        130        140        150
FPQLNSVSPS PLMLLHPPPQ LSPFLHPHGQ QVPYYLENEP SAYAVRDTGP 
       160        170        180        190        200
PAFYRSNSDN RRQNGRERLS SSNEKGNMIM ESAKETRYCA VCNDYASGYH 
       210        220        230        240        250
YGVWSCEGCK AFFKRSIQGH NDYMCPATNQ CTIDKNRRKS CQACRLRKCY 
       260        270        280        290        300
EVGMMKGGIR KDRRGGRMLK HKRQRDDLEG RNEMGASGDM RAANLWPSPL 
       310        320        330        340        350
VIKHTKKNSP ALSLTADQMV SALLDAEPPM IYSEYDPSRP FSEASMMGLL 
       360        370        380        390        400
TNLADRELVH MINWAKRVPG FGDLNLHDQV HLLECAWLEI LMIGLVWRSM 
       410        420        430        440        450
EHPGKLLFAP NLLLDRNQGK CVEGMVEIFD MLLATSSRFR MMNLQGEEFV 
       460        470        480        490        500
CLKSIILLNS GVYTFLSSTL KSLEEKDHIH RVLDKITDTL IHLMAKAGLT 
       510        520        530        540        550
LQQQHRRLAQ LLLILSHIRH MSNKGMEHLY NMKCKNVVPL YDLLLEMLDA 
       560        570        580        590 
HRLHAPASRM GVPPEEPSQT QLATTSSTSA HSLQTYYIPP EAEGFPNTI
Length:599
Mass (Da):66,955
Last modified:February 1, 1991 - v1
Checksum:i05F5E2FC21CC0A8B
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z6V3D3Z6V3_MOUSE
Estrogen receptor
Esr1
499Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti269L → M in AAF22561 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti591E → Q in strain: SJL/J. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M38651 mRNA Translation: AAA37580.1
AK036627 mRNA Translation: BAC29510.1
AK041525 mRNA Translation: BAC30973.1
AJ276597 Genomic DNA Translation: CAB85618.1
AF128221 mRNA Translation: AAF22562.1
AF128220 mRNA Translation: AAF22561.1
CCDSiCCDS56678.1
PIRiA40061 QRMSE
RefSeqiNP_001289460.1, NM_001302531.1
NP_001289461.1, NM_001302532.1
NP_031982.1, NM_007956.5
XP_006512496.1, XM_006512433.3
XP_006512497.1, XM_006512434.3
XP_006512498.1, XM_006512435.2
XP_011241368.1, XM_011243066.2
XP_011241369.1, XM_011243067.2
XP_011241370.1, XM_011243068.2
UniGeneiMm.463262
Mm.489063
Mm.9213

Genome annotation databases

EnsembliENSMUST00000067086; ENSMUSP00000070070; ENSMUSG00000019768
ENSMUST00000105589; ENSMUSP00000101214; ENSMUSG00000019768
ENSMUST00000105590; ENSMUSP00000101215; ENSMUSG00000019768
GeneIDi13982
KEGGimmu:13982
UCSCiuc007egu.3 mouse

Similar proteinsi

Entry informationi

Entry nameiESR1_MOUSE
AccessioniPrimary (citable) accession number: P19785
Secondary accession number(s): Q9JJT5, Q9QY51, Q9QY52
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: September 12, 2018
This is version 215 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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