P06211 (ESR1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 159. History...
Names and origin
|Protein names||Recommended name:|
Nuclear receptor subfamily 3 group A member 1
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||600 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
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
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.
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.
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.
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.
Contains 1 nuclear receptor DNA-binding domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 600||600||Estrogen receptor||PRO_0000053623|
|DNA binding||190 – 255||66||Nuclear receptor|
|Zinc finger||190 – 210||21||NR C4-type|
|Zinc finger||226 – 250||25||NR C4-type|
|Region||1 – 189||189||Modulating (transactivation AF-1); mediates interaction with MACROD1 By similarity|
|Region||35 – 179||145||Interaction with DDX5; self-association By similarity|
|Region||35 – 47||13||Required for interaction with NCOA1 By similarity|
|Region||190 – 315||126||Mediates interaction with DNTTIP2 By similarity|
|Region||256 – 315||60||Hinge|
|Region||267 – 600||334||Interaction with AKAP13 By similarity|
|Region||269 – 600||332||Self-association By similarity|
|Region||316 – 600||285||Transactivation AF-2 By similarity|
|Region||316 – 556||241||Steroid-binding|
|Compositional bias||64 – 71||8||Poly-Ala|
|Compositional bias||171 – 174||4||Poly-Ser|
Amino acid modifications
|Modified residue||109||1||Phosphoserine; by CDK2 By similarity|
|Modified residue||111||1||Phosphoserine; by CDK2 By similarity|
|Modified residue||123||1||Phosphoserine By similarity|
|Modified residue||172||1||Phosphoserine; by CK2 By similarity|
|Modified residue||265||1||Asymmetric dimethylarginine; by PRMT1 By similarity|
|Modified residue||542||1||Phosphotyrosine; by Tyr-kinases By similarity|
|Lipidation||452||1||S-palmitoyl cysteine By similarity|
|Glycosylation||10||1||O-linked (GlcNAc) By similarity|
|Glycosylation||576||1||O-linked (GlcNAc) By similarity|
|Sequence conflict||488||1||N → T in CAA43411. Ref.3|
Submitted (MAR-1987) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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].
Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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.
|||"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.
|||"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.|
|Y00102 mRNA. Translation: CAA68287.1.|
X61098 mRNA. Translation: CAA43411.1.
|PIR||QRRTE. S07379. |
|RefSeq||NP_036821.1. NM_012689.1. |
3D structure databases
|SMR||P06211. Positions 185-258, 306-555. |
Protein-protein interaction databases
|BioGrid||247000. 9 interactions.|
|IntAct||P06211. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:2581. rat. |
|RGD||2581. Esr1. |
Gene expression databases
Family and domain databases
|Gene3D||1.10.565.10. 2 hits. |
220.127.116.11. 1 hit.
|InterPro||IPR008946. Nucl_hormone_rcpt_ligand-bd. |
|Pfam||PF12743. ESR1_C. 1 hit. |
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
|PIRSF||PIRSF500101. ER-a. 1 hit. |
PIRSF002527. ER-like_NR. 1 hit.
|PRINTS||PR00543. OESTROGENR. |
|SMART||SM00430. HOLI. 1 hit. |
SM00399. ZnF_C4. 1 hit.
|SUPFAM||SSF48508. SSF48508. 2 hits. |
|PROSITE||PS00031. NUCLEAR_REC_DBD_1. 1 hit. |
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
|Accession||Primary (citable) accession number: P06211|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families