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P06211 (ESR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Estrogen receptor

Short name=ER
Alternative name(s):
ER-alpha
Estradiol receptor
Nuclear receptor subfamily 3 group A member 1
Gene names
Name:Esr1
Synonyms:Esr, Estr, Nr3a1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length600 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Subunit structure

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 DYX1C1. 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 ESE1 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. Ref.4 Ref.5 Ref.6

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Golgi apparatus By similarity. Cell membrane By similarity. Note: Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs By similarity. Associated with the plasma membrane when palmitoylated By similarity.

Domain

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.

Post-translational modification

Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-123 by PPP5C inhibits its transactivation activity By similarity.

Ubiquitinated. Deubiquitinated by OTUB1 By similarity.

Dimethylated by PRMT1 at Arg-265. The methylation may favor cytoplasmic localization 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.

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.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell membrane
Cytoplasm
Golgi apparatus
Membrane
Nucleus
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Steroid-binding
Zinc
   Molecular functionActivator
Receptor
   PTMGlycoprotein
Lipoprotein
Methylation
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell development

Inferred from expression pattern PubMed 24056172. Source: RGD

Sertoli cell proliferation

Inferred from mutant phenotype PubMed 17928626. Source: RGD

cellular response to estradiol stimulus

Inferred from direct assay PubMed 15705806. Source: UniProtKB

intracellular steroid hormone receptor signaling pathway

Inferred from direct assay PubMed 15705806. Source: UniProtKB

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron death

Inferred from direct assay PubMed 15126114. Source: RGD

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

osteoblast development

Inferred from expression pattern PubMed 9528993. Source: RGD

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 15705806. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 17928626. Source: RGD

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay PubMed 15705806. Source: UniProtKB

positive regulation of epidermal growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 17928626. Source: RGD

positive regulation of nitric oxide biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of nitric-oxide synthase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phospholipase C activity

Inferred from direct assay PubMed 15705806. Source: UniProtKB

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

Traceable author statement PubMed 11562484. Source: RGD

regulation of neuron apoptotic process

Inferred from direct assay PubMed 15126114. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 9528993. Source: RGD

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

T-tubule

Inferred from direct assay PubMed 16876190. Source: RGD

cytoplasm

Inferred from direct assay PubMed 16122717PubMed 16869728. Source: RGD

mitochondrion

Inferred from direct assay PubMed 15994367. Source: RGD

neuron projection

Inferred from direct assay PubMed 16122717. Source: RGD

nucleus

Inferred from direct assay PubMed 15705806. Source: UniProtKB

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 16876190PubMed 17928626PubMed 18489713. Source: RGD

protein complex

Inferred from direct assay PubMed 18434427. Source: RGD

terminal bouton

Inferred from direct assay PubMed 17314305. Source: RGD

   Molecular_functionDNA binding

Inferred from mutant phenotype PubMed 12372009. Source: RGD

core promoter sequence-specific DNA binding

Inferred from direct assay PubMed 24046281. Source: RGD

enzyme binding

Inferred from physical interaction PubMed 19422801. Source: RGD

estrogen receptor activity

Inferred from direct assay PubMed 15105439. Source: RGD

hormone binding

Inferred from direct assay PubMed 17928626. Source: RGD

protein complex binding

Inferred from direct assay PubMed 18434427. Source: RGD

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

steroid binding

Inferred from direct assay PubMed 15705806. Source: UniProtKB

steroid hormone receptor activity

Inferred from direct assay PubMed 17928626. Source: RGD

type 1 metabotropic glutamate receptor binding

Inferred from physical interaction PubMed 18948402. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 600600Estrogen receptor
PRO_0000053623

Regions

DNA binding190 – 25566Nuclear receptor
Zinc finger190 – 21021NR C4-type
Zinc finger226 – 25025NR C4-type
Region1 – 189189Modulating (transactivation AF-1); mediates interaction with MACROD1 By similarity
Region35 – 179145Interaction with DDX5; self-association By similarity
Region35 – 4713Required for interaction with NCOA1 By similarity
Region190 – 315126Mediates interaction with DNTTIP2 By similarity
Region256 – 31560Hinge
Region267 – 600334Interaction with AKAP13 By similarity
Region269 – 600332Self-association By similarity
Region316 – 600285Transactivation AF-2 By similarity
Region316 – 556241Steroid-binding
Compositional bias64 – 718Poly-Ala
Compositional bias171 – 1744Poly-Ser

Amino acid modifications

Modified residue1091Phosphoserine; by CDK2 By similarity
Modified residue1111Phosphoserine; by CDK2 By similarity
Modified residue1231Phosphoserine By similarity
Modified residue1721Phosphoserine; by CK2 By similarity
Modified residue2651Asymmetric dimethylarginine; by PRMT1 By similarity
Modified residue5421Phosphotyrosine; by Tyr-kinases By similarity
Lipidation4521S-palmitoyl cysteine By similarity
Glycosylation101O-linked (GlcNAc) By similarity
Glycosylation5761O-linked (GlcNAc) By similarity

Experimental info

Sequence conflict4881N → T in CAA43411. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P06211 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: C9C7D8CACE0F57D8

FASTA60067,030
        10         20         30         40         50         60 
MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKMPMERALG EVYVDNSKPA VFNYPEGAAY 

        70         80         90        100        110        120 
EFNAAAAAAA AGASAPVYGQ SSITYGPGSE AAAFGANSLG AFPQLNSVSP SPLMLLHPPP 

       130        140        150        160        170        180 
HVSPFLHPHG HQVPYYLENE PSAYAVRDTG PPAFYRSNSD NRRQNGRERL SSSSEKGNMI 

       190        200        210        220        230        240 
MESAKETRYC AVCNDYASGY HYGVWSCEGC KAFFKRSIQG HNDYMCPATN QCTIDKNRRK 

       250        260        270        280        290        300 
SCQACRLRKC YEVGMMKGGI RKDRRGGRML KHKRQRDDLE GRNEMGTSGD MRAANLWPSP 

       310        320        330        340        350        360 
LVIKHTKKNS PALSLTADQM VSALLDAEPP LIYSEYDPSR PFSEASMMGL LTNLADRELV 

       370        380        390        400        410        420 
HMINWAKRVP GFGDLNLHDQ VHLLECAWLE ILMIGLVWRS MEHPGKLLFA PNLLLDRNQG 

       430        440        450        460        470        480 
KCVEGMVEIF DMLLATSSRF RMMNLQGEEF VCLKSIILLN SGVYTFLSST LKSLEEKDHI 

       490        500        510        520        530        540 
HRVLDKINDT LIHLMAKAGL TLQQQHRRLA QLLLILSHIR HMSNKGMEHL YNMKCKNVVP 

       550        560        570        580        590        600 
LYDLLLEMLD AHRLHAPASR MGVPPEEPSQ SQLTTTSSTS AHSLQTYYIP PEAEGFPNTI 

« Hide

References

[1]Muramatsu M.
Submitted (MAR-1987) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar.
[2]"Molecular cloning and characterization of rat estrogen receptor cDNA."
Koike S., Sakai M.
Nucleic Acids Res. 15:2499-2513(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]Maggi A.M.A.
Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Uterus.
[4]"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.
[5]"The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain."
Eriksson M., Samuelsson H., Samuelsson E.-B., Liu L., McKeehan W.L., Benedikz E., Sundstroem E.
Biochem. Biophys. Res. Commun. 361:127-132(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP1S.
[6]"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
Y00102 mRNA. Translation: CAA68287.1.
X61098 mRNA. Translation: CAA43411.1.
PIRQRRTE. S07379.
RefSeqNP_036821.1. NM_012689.1.
UniGeneRn.10595.
Rn.231229.

3D structure databases

ProteinModelPortalP06211.
SMRP06211. Positions 185-258, 306-555.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247000. 9 interactions.
DIPDIP-41279N.
IntActP06211. 2 interactions.
MINTMINT-234578.
STRING10116.ENSRNOP00000026350.

Chemistry

BindingDBP06211.
ChEMBLCHEMBL2094114.
GuidetoPHARMACOLOGY620.

PTM databases

PhosphoSiteP06211.

Proteomic databases

PaxDbP06211.
PRIDEP06211.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24890.
KEGGrno:24890.
UCSCRGD:2581. rat.

Organism-specific databases

CTD2099.
RGD2581. Esr1.

Phylogenomic databases

eggNOGNOG320746.
HOGENOMHOG000233468.
HOVERGENHBG108344.
InParanoidP06211.
KOK08550.
PhylomeDBP06211.

Gene expression databases

GenevestigatorP06211.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001292. Oestr_rcpt.
IPR024736. Oestrogen-typ_rcpt_final_C_dom.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFPIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSPR00543. OESTROGENR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 2 hits.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio604756.
PROP06211.

Entry information

Entry nameESR1_RAT
AccessionPrimary (citable) accession number: P06211
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: April 16, 2014
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families