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Protein

Estrogen receptor

Gene

ESR1

Organism
Mesocricetus auratus (Golden hamster)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi185 – 250Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri185 – 205NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri221 – 245NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

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
Short name:
ER
Alternative name(s):
ER-alpha
Estradiol receptor
Nuclear receptor subfamily 3 group A member 1
Gene namesi
Name:ESR1
Synonyms:ESR, NR3A1
OrganismiMesocricetus auratus (Golden hamster)
Taxonomic identifieri10036 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeMesocricetus

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation
  • 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. Associated with the plasma membrane when palmitoylated.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536201 – 595Estrogen receptorAdd BLAST595

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10O-linked (GlcNAc)By similarity1
Modified residuei103Phosphoserine; by CDK2By similarity1
Modified residuei105Phosphoserine; by CDK2By similarity1
Modified residuei118PhosphoserineBy similarity1
Modified residuei167Phosphoserine; by CK2By similarity1
Modified residuei260Asymmetric dimethylarginine; by PRMT1By similarity1
Lipidationi447S-palmitoyl cysteineBy similarity1
Modified residuei537Phosphotyrosine; by Tyr-kinasesBy similarity1
Glycosylationi571O-linked (GlcNAc)By similarity1

Post-translational modificationi

Ubiquitinated. Deubiquitinated by OTUB1 (By similarity).By similarity
Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (By similarity).By similarity
Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity (By similarity). Phosphorylated by LMTK3 (in vitro) (By similarity).By similarity
Palmitoylated at Cys-447 by ZDHHC7 and ZDHHC21. Palmitoylation 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

Interactioni

Subunit structurei

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 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. 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 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).By similarity

Protein-protein interaction databases

MINTiMINT-4998393.

Structurei

3D structure databases

ProteinModelPortaliQ9QZJ5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 184Modulating(transactivation AF-1); mediates interaction with MACROD1By similarityAdd BLAST184
Regioni35 – 174Interaction with DDX5; self-associationBy similarityAdd BLAST140
Regioni35 – 47Required for interaction with NCOA1By similarityAdd BLAST13
Regioni185 – 310Mediates interaction with DNTTIP2By similarityAdd BLAST126
Regioni251 – 310HingeAdd BLAST60
Regioni262 – 595Interaction with AKAP13By similarityAdd BLAST334
Regioni264 – 595Self-associationBy similarityAdd BLAST332
Regioni311 – 595Transactivation AF-2By similarityAdd BLAST285
Regioni311 – 551Steroid-bindingAdd BLAST241

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi112 – 115Poly-Pro4
Compositional biasi166 – 169Poly-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

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri185 – 205NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri221 – 245NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

HOVERGENiHBG108344.
OrthoDBiEOG091G03V4.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. 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.
[Graphical view]
PfamiPF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSiPR00543. OESTROGENR.
PR00398. 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]

Sequencei

Sequence statusi: Complete.

Q9QZJ5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTMTLHTKAS GMALLHQIQG NELEPLSRPQ LKMPLERALS EVYVDSSKPA
60 70 80 90 100
MFNYPEGAAY EFNAATAPAP VYGQTGIAYG SGSEATAFGS NSLGLFPQLN
110 120 130 140 150
SVSPSPLMLL HPPPPQLSPF LHPHGQQVPY YLENEPSAYA VRDSGPPAFY
160 170 180 190 200
RSNSDNRRQS GRERLSSSSE KGSMAMESVK ETRYCAVCND YASGYHYGVW
210 220 230 240 250
SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC RLRKCYEVGM
260 270 280 290 300
MKGGIRKDRR GGRMLKHKRQ RDDLEGRNDM GPSGDMRATN LWPSPLVIKH
310 320 330 340 350
TKKNSPALSL TADQMVSALL DAEPPLIYSE YDPSRPFSEA SMMGLLTNLA
360 370 380 390 400
DRELVHMINW AKRVPGFGDL NLHDQVHLLE CAWLEILMIG LIWRSMEHPG
410 420 430 440 450
KLLFAPNLLL DRNQGKCVEG MVEIFDMLLA TSARFRMMDL QGEEFVCLKS
460 470 480 490 500
IILLNSGVYT FLSSTLKSLE EKDHIHRVLD KITDTLIHLM AKAGLTLQQQ
510 520 530 540 550
HRRLAQLLLI LSHIRHMSNK GMEHLYNMKC KNVVPFYDLL LEMLDAHRLH
560 570 580 590
TPVSRMGVSP EEPSQSQLTT TNSTSSHSLQ TYYIPSEAES FPNTI
Length:595
Mass (Da):66,834
Last modified:May 1, 2000 - v1
Checksum:iE4D803B4FFDB257E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti98 – 99QL → PF in AAF02721 (Ref. 2) Curated2
Sequence conflicti144S → T in AAF02721 (Ref. 2) Curated1
Sequence conflicti198 – 199GV → EVEQI in AAF02721 (Ref. 2) Curated2
Sequence conflicti290 – 291NL → KG in AAF02721 (Ref. 2) Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF181077 mRNA. Translation: AAD53956.1.
AF184276 mRNA. Translation: AAF02721.1.
RefSeqiNP_001268254.1. NM_001281325.1.

Genome annotation databases

GeneIDi101825539.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF181077 mRNA. Translation: AAD53956.1.
AF184276 mRNA. Translation: AAF02721.1.
RefSeqiNP_001268254.1. NM_001281325.1.

3D structure databases

ProteinModelPortaliQ9QZJ5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4998393.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi101825539.

Organism-specific databases

CTDi2099.

Phylogenomic databases

HOVERGENiHBG108344.
OrthoDBiEOG091G03V4.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. 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.
[Graphical view]
PfamiPF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSiPR00543. OESTROGENR.
PR00398. 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 nameiESR1_MESAU
AccessioniPrimary (citable) accession number: Q9QZJ5
Secondary accession number(s): Q9QZG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 2000
Last modified: October 5, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. 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.