Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Estrogen receptor

Gene

Esr1

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

Miscellaneous

In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi190 – 255Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri190 – 210NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri226 – 250NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

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, Nr3a1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2581 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

Chemistry databases

ChEMBLiCHEMBL2724
GuidetoPHARMACOLOGYi620

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536231 – 600Estrogen receptorAdd BLAST600

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10O-linked (GlcNAc) serineBy similarity1
Modified residuei109Phosphoserine; by CDK2By similarity1
Modified residuei111Phosphoserine; by CDK2By similarity1
Modified residuei123PhosphoserineBy similarity1
Modified residuei172Phosphoserine; by CK2By similarity1
Modified residuei265Asymmetric dimethylarginine; by PRMT1By similarity1
Lipidationi452S-palmitoyl cysteineBy similarity1
Modified residuei542Phosphotyrosine; by Tyr-kinasesBy similarity1
Glycosylationi576O-linked (GlcNAc) threonineBy similarity1

Post-translational modificationi

Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-123 by PPP5C inhibits its transactivation activity (By similarity). Phosphorylated by LMTK3 (in vitro) (By similarity).By similarity
Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation. Deubiquitinated by OTUB1.By similarity
Dimethylated by PRMT1 at Arg-265. The methylation may favor cytoplasmic localization (By similarity).By similarity
Palmitoylated at Cys-452 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 (By similarity).By similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiP06211
PRIDEiP06211

PTM databases

iPTMnetiP06211
PhosphoSitePlusiP06211

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 (By similarity). 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. Interacts (via DNA-binding domain) with POU4F2 (C-terminus); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (By similarity). Interacts with ESRRB isoform 1 (By similarity). Interacts with UBE3A and WBP2 (By similarity). Interacts with GTF2B (By similarity). Interacts with RBM39 (By similarity).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi247000, 11 interactors
CORUMiP06211
DIPiDIP-41279N
IntActiP06211, 6 interactors
MINTiP06211
STRINGi10116.ENSRNOP00000026350

Chemistry databases

BindingDBiP06211

Structurei

3D structure databases

ProteinModelPortaliP06211
SMRiP06211
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini316 – 552NR LBDPROSITE-ProRule annotationAdd BLAST237

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 189Modulating (transactivation AF-1); mediates interaction with MACROD1By similarityAdd BLAST189
Regioni35 – 179Interaction with DDX5; self-associationBy similarityAdd BLAST145
Regioni35 – 47Required for interaction with NCOA1By similarityAdd BLAST13
Regioni190 – 315Mediates interaction with DNTTIP2By similarityAdd BLAST126
Regioni256 – 315HingeAdd BLAST60
Regioni267 – 600Interaction with AKAP13By similarityAdd BLAST334
Regioni269 – 600Self-associationBy similarityAdd BLAST332
Regioni316 – 600Transactivation AF-2By similarityAdd BLAST285

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi64 – 71Poly-Ala8
Compositional biasi171 – 174Poly-Ser4

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri190 – 210NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri226 – 250NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
HOGENOMiHOG000233468
HOVERGENiHBG108344
InParanoidiP06211
KOiK08550
PhylomeDBiP06211

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, 1 hit
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 5 potential isoforms that are computationally mapped.Show allAlign All

P06211-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKMPMERALG EVYVDNSKPA
60 70 80 90 100
VFNYPEGAAY EFNAAAAAAA AGASAPVYGQ SSITYGPGSE AAAFGANSLG
110 120 130 140 150
AFPQLNSVSP SPLMLLHPPP HVSPFLHPHG HQVPYYLENE PSAYAVRDTG
160 170 180 190 200
PPAFYRSNSD NRRQNGRERL SSSSEKGNMI MESAKETRYC AVCNDYASGY
210 220 230 240 250
HYGVWSCEGC KAFFKRSIQG HNDYMCPATN QCTIDKNRRK SCQACRLRKC
260 270 280 290 300
YEVGMMKGGI RKDRRGGRML KHKRQRDDLE GRNEMGTSGD MRAANLWPSP
310 320 330 340 350
LVIKHTKKNS PALSLTADQM VSALLDAEPP LIYSEYDPSR PFSEASMMGL
360 370 380 390 400
LTNLADRELV HMINWAKRVP GFGDLNLHDQ VHLLECAWLE ILMIGLVWRS
410 420 430 440 450
MEHPGKLLFA PNLLLDRNQG KCVEGMVEIF DMLLATSSRF RMMNLQGEEF
460 470 480 490 500
VCLKSIILLN SGVYTFLSST LKSLEEKDHI HRVLDKINDT LIHLMAKAGL
510 520 530 540 550
TLQQQHRRLA QLLLILSHIR HMSNKGMEHL YNMKCKNVVP LYDLLLEMLD
560 570 580 590 600
AHRLHAPASR MGVPPEEPSQ SQLTTTSSTS AHSLQTYYIP PEAEGFPNTI
Length:600
Mass (Da):67,030
Last modified:January 1, 1988 - v1
Checksum:iC9C7D8CACE0F57D8
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D0FYH4D0FYH4_RAT
Estrogen receptor
Esr1 rCG_41136
600Annotation score:
A0A0G2K0D4A0A0G2K0D4_RAT
Estrogen receptor
Esr1
632Annotation score:
A0A0G2JZG2A0A0G2JZG2_RAT
Estrogen receptor
Esr1
618Annotation score:
A0A0G2K1T9A0A0G2K1T9_RAT
Estrogen receptor
Esr1
125Annotation score:
A0A0G2JXN1A0A0G2JXN1_RAT
Estrogen receptor
Esr1
41Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti488N → T in CAA43411 (Ref. 3) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00102 mRNA Translation: CAA68287.1
X61098 mRNA Translation: CAA43411.1
PIRiS07379 QRRTE
RefSeqiNP_036821.1, NM_012689.1
UniGeneiRn.10595
Rn.231229

Genome annotation databases

GeneIDi24890
KEGGirno:24890
UCSCiRGD:2581 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00102 mRNA Translation: CAA68287.1
X61098 mRNA Translation: CAA43411.1
PIRiS07379 QRRTE
RefSeqiNP_036821.1, NM_012689.1
UniGeneiRn.10595
Rn.231229

3D structure databases

ProteinModelPortaliP06211
SMRiP06211
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247000, 11 interactors
CORUMiP06211
DIPiDIP-41279N
IntActiP06211, 6 interactors
MINTiP06211
STRINGi10116.ENSRNOP00000026350

Chemistry databases

BindingDBiP06211
ChEMBLiCHEMBL2724
GuidetoPHARMACOLOGYi620

PTM databases

iPTMnetiP06211
PhosphoSitePlusiP06211

Proteomic databases

PaxDbiP06211
PRIDEiP06211

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24890
KEGGirno:24890
UCSCiRGD:2581 rat

Organism-specific databases

CTDi2099
RGDi2581 Esr1

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
HOGENOMiHOG000233468
HOVERGENiHBG108344
InParanoidiP06211
KOiK08550
PhylomeDBiP06211

Miscellaneous databases

PROiPR:P06211

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, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiESR1_RAT
AccessioniPrimary (citable) accession number: P06211
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: November 7, 2018
This is version 196 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again