0/0pig palmitoyl-proteome article0orthologues in palmitoyl-proteomes0targeted study2orthologue in targeted studies0sitePredicted1cysteines in main isoform
Protein general information
UniProt names and subcellular location Protein identifiers Protein names Subcellular locations Estrogen receptor
Nuclear receptor subfamily 3 group A member 1
Source Identifiers UniProt gene names ESR1, ESR, NR3A1 Refseq protein ID NP_999385.1 UniProt AC Q29040 UniProt ID ESR1_PIG Protein length Isoform 1 (main): 595 aa Known functions (from UniProt) 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). 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 (By similarity). Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs. Associated with the plasma membrane when palmitoylated. 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-118 by PPP5C inhibits its transactivation activity (By similarity). Phosphorylated by LMTK3 (in vitro) (By similarity). Ubiquitinated. Deubiquitinated by OTUB1 (By similarity). Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (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). Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Cysteine summary and predictions
Pos in alignment 185 188 202 205 221 227 237 240 245 381 417 447 530 Topology U U U U U U U U U U U U U Disulfide no no no no no no no no no no no no no SS prediction NA NA NA NA NA NA NA NA NA NA NA NA NA SS UniProt NA NA NA NA NA NA NA NA NA NA NA NA NA Isoform 1
Topology U Undefined E Extracellular/Lumenal T Transmembrane C Cytosolic/Nuclear Prediction scores From top to bottom: Cysteine position, CSS-Palm 4.0 score, PalmPred score
Color code for cysteine position: Predicted (high confidence prediction with CSS-Palm or/and PalmPred) / Predicted but not validated (in terms of disulfide bond and cellular location) / Not predicted
Color code for CSS-Palm 4.0: High confidence, Medium confidence, Low confidence, Not predicted.
Color code for PalmPred: High confidence (score > 0.4), Medium confidence (0.1 > score > 0.4), Low confidence (score < 0.1), Not predicted.
UniProt AC UniProt ID Orthology source Organism Gene names Description Isoforms # palmitome articles # targeted studies # of distinct techniques # of known sites Predicted P19785 ESR1_MOUSE MetaPhors Mouse Esr1, Esr, Estr, Estra, Nr3a1 Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) 1 0/8 1 0 1 Yes P03372 ESR1_HUMAN MetaPhors Human ESR1, ESR, NR3A1 Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) 4 0/15 3 0 1 Yes