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P06211

- ESR1_RAT

UniProt

P06211 - ESR1_RAT

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Protein

Estrogen receptor

Gene

Esr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- 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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi190 – 25566Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri190 – 21021NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri226 – 25025NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: UniProtKB
  2. core promoter sequence-specific DNA binding Source: RGD
  3. DNA binding Source: RGD
  4. enzyme binding Source: RGD
  5. estrogen receptor activity Source: RGD
  6. hormone binding Source: RGD
  7. protein complex binding Source: RGD
  8. sequence-specific DNA binding transcription factor activity Source: InterPro
  9. steroid binding Source: UniProtKB
  10. steroid hormone receptor activity Source: RGD
  11. type 1 metabotropic glutamate receptor binding Source: RGD
  12. zinc ion binding Source: InterPro

GO - Biological processi

  1. baculum development Source: RGD
  2. cellular response to estradiol stimulus Source: UniProtKB
  3. decidualization Source: RGD
  4. intracellular steroid hormone receptor signaling pathway Source: UniProtKB
  5. male gonad development Source: RGD
  6. negative regulation of glucose import Source: RGD
  7. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  8. negative regulation of neuron death Source: RGD
  9. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  10. negative regulation of smooth muscle cell proliferation Source: RGD
  11. negative regulation of triglyceride metabolic process Source: RGD
  12. osteoblast development Source: RGD
  13. phospholipase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  14. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  15. positive regulation of epidermal growth factor receptor signaling pathway Source: RGD
  16. positive regulation of ERK1 and ERK2 cascade Source: RGD
  17. positive regulation of nitric oxide biosynthetic process Source: UniProtKB
  18. positive regulation of nitric-oxide synthase activity Source: UniProtKB
  19. positive regulation of phospholipase C activity Source: UniProtKB
  20. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  21. positive regulation of transcription from RNA polymerase II promoter Source: RGD
  22. regulation of neuron apoptotic process Source: RGD
  23. response to estradiol Source: RGD
  24. Sertoli cell development Source: RGD
  25. Sertoli cell proliferation Source: RGD
  26. transcription, DNA-templated Source: UniProtKB-KW
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, Estr, Nr3a1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2581. Esr1.

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

  1. cytoplasm Source: RGD
  2. Golgi apparatus Source: UniProtKB-KW
  3. mitochondrion Source: RGD
  4. neuron projection Source: RGD
  5. nucleus Source: UniProtKB
  6. perikaryon Source: RGD
  7. perinuclear region of cytoplasm Source: RGD
  8. plasma membrane Source: RGD
  9. protein complex Source: RGD
  10. terminal bouton Source: RGD
  11. T-tubule Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 600600Estrogen receptorPRO_0000053623Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi10 – 101O-linked (GlcNAc)By similarity
Modified residuei109 – 1091Phosphoserine; by CDK2By similarity
Modified residuei111 – 1111Phosphoserine; by CDK2By similarity
Modified residuei123 – 1231PhosphoserineBy similarity
Modified residuei172 – 1721Phosphoserine; by CK2By similarity
Modified residuei265 – 2651Asymmetric dimethylarginine; by PRMT1By similarity
Lipidationi452 – 4521S-palmitoyl cysteineBy similarity
Modified residuei542 – 5421Phosphotyrosine; by Tyr-kinasesBy similarity
Glycosylationi576 – 5761O-linked (GlcNAc)By similarity

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).By similarity
Ubiquitinated. Deubiquitinated by OTUB1 (By similarity).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

PhosphoSiteiP06211.

Expressioni

Gene expression databases

GenevestigatoriP06211.

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 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 (By similarity). Interacts with GPER1; the interaction occurs in an estrogen-dependent manner (By similarity).By similarity

Protein-protein interaction databases

BioGridi247000. 9 interactions.
DIPiDIP-41279N.
IntActiP06211. 2 interactions.
MINTiMINT-234578.
STRINGi10116.ENSRNOP00000026350.

Structurei

3D structure databases

ProteinModelPortaliP06211.
SMRiP06211. Positions 185-258, 306-555.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 189189Modulating (transactivation AF-1); mediates interaction with MACROD1By similarityAdd
BLAST
Regioni35 – 179145Interaction with DDX5; self-associationBy similarityAdd
BLAST
Regioni35 – 4713Required for interaction with NCOA1By similarityAdd
BLAST
Regioni190 – 315126Mediates interaction with DNTTIP2By similarityAdd
BLAST
Regioni256 – 31560HingeAdd
BLAST
Regioni267 – 600334Interaction with AKAP13By similarityAdd
BLAST
Regioni269 – 600332Self-associationBy similarityAdd
BLAST
Regioni316 – 600285Transactivation AF-2By similarityAdd
BLAST
Regioni316 – 556241Steroid-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi64 – 718Poly-Ala
Compositional biasi171 – 1744Poly-Ser

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri190 – 21021NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri226 – 25025NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG320746.
HOGENOMiHOG000233468.
HOVERGENiHBG108344.
InParanoidiP06211.
KOiK08550.
PhylomeDBiP06211.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR008946. 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]
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.

P06211-1 [UniParc]FASTAAdd to Basket

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        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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti488 – 4881N → T in CAA43411. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00102 mRNA. Translation: CAA68287.1 .
X61098 mRNA. Translation: CAA43411.1 .
PIRi S07379. QRRTE.
RefSeqi NP_036821.1. NM_012689.1.
UniGenei Rn.10595.
Rn.231229.

3D structure databases

ProteinModelPortali P06211.
SMRi P06211. Positions 185-258, 306-555.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247000. 9 interactions.
DIPi DIP-41279N.
IntActi P06211. 2 interactions.
MINTi MINT-234578.
STRINGi 10116.ENSRNOP00000026350.

Chemistry

BindingDBi P06211.
ChEMBLi CHEMBL2094114.
GuidetoPHARMACOLOGYi 620.

PTM databases

PhosphoSitei P06211.

Proteomic databases

PaxDbi P06211.
PRIDEi P06211.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 24890.
KEGGi rno:24890.
UCSCi RGD:2581. rat.

Organism-specific databases

CTDi 2099.
RGDi 2581. Esr1.

Phylogenomic databases

eggNOGi NOG320746.
HOGENOMi HOG000233468.
HOVERGENi HBG108344.
InParanoidi P06211.
KOi K08550.
PhylomeDBi P06211.

Miscellaneous databases

NextBioi 604756.
PROi P06211.

Gene expression databases

Genevestigatori P06211.

Family and domain databases

Gene3Di 1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProi IPR008946. 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 ]
Pfami PF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PIRSFi PIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSi PR00543. OESTROGENR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 2 hits.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiESR1_RAT
AccessioniPrimary (citable) accession number: P06211
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: October 29, 2014
This is version 163 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3