ESR1_MACMU
ID ESR1_MACMU Reviewed; 121 AA.
AC P49886;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Estrogen receptor;
DE Short=ER;
DE AltName: Full=ER-alpha;
DE AltName: Full=Estradiol receptor;
DE AltName: Full=Nuclear receptor subfamily 3 group A member 1;
DE Flags: Fragment;
GN Name=ESR1; Synonyms=ESR, NR3A1;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=8013365; DOI=10.1210/endo.135.1.8013365;
RA Chandrasekher Y.A., Melner M.H., Nagalla S.R., Stouffer R.L.;
RT "Progesterone receptor, but not estradiol receptor, messenger ribonucleic
RT acid is expressed in luteinizing granulosa cells and the corpus luteum in
RT rhesus monkeys.";
RL Endocrinology 135:307-314(1994).
CC -!- FUNCTION: Nuclear hormone receptor. The steroid hormones and their
CC receptors are involved in the regulation of eukaryotic gene expression
CC and affect cellular proliferation and differentiation in target
CC tissues. Ligand-dependent nuclear transactivation involves either
CC direct homodimer binding to a palindromic estrogen response element
CC (ERE) sequence or association with other DNA-binding transcription
CC factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-
CC independent signaling. Ligand binding induces a conformational change
CC allowing subsequent or combinatorial association with multiprotein
CC coactivator complexes through LXXLL motifs of their respective
CC components. Mutual transrepression occurs between the estrogen receptor
CC (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-
CC B DNA-binding activity and inhibits NF-kappa-B-mediated transcription
CC from the IL6 promoter and displace RELA/p65 and associated coregulators
CC from the promoter. Recruited to the NF-kappa-B response element of the
CC CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B
CC components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act
CC synergistically with NF-kappa-B to activate transcription involving
CC respective recruitment adjacent response elements; the function
CC involves CREBBP. Can activate the transcriptional activity of TFF1.
CC Also mediates membrane-initiated estrogen signaling involving various
CC kinase cascades. Essential for MTA1-mediated transcriptional regulation
CC of BRCA1 and BCAS3 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds DNA as a homodimer. Can form a heterodimer with ESR2.
CC Interacts with coactivator NCOA5. Interacts with NCOA7; the interaction
CC is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1, KDM5A,
CC MAP1S, PELP1, SMARD1, and UBE1C. Interacts with MUC1; the interaction
CC is stimulated by 7 beta-estradiol (E2) and enhances ERS1-mediated
CC transcription. Interacts with DNTTIP2, and UIMC1. Interacts with
CC KMT2D/MLL2. Interacts with ATAD2; the interaction is enhanced by
CC estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via its
CC C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG.
CC Interacts with SH2D4A; the interaction blocks binding to PLCG and
CC inhibits estrogen-induced cell proliferation. Interacts with DYNLL1.
CC Interacts with CCDC62; the interaction requires estradiol and appears
CC to enhance the transcription of target genes. Interacts with NR2C1; the
CC interaction prevents homodimerization of ESR1 and suppresses its
CC transcriptional activity and cell growth. Interacts with DNAAF4.
CC Interacts with PRMT2. Interacts with PI3KR1 or PIK3R2, SRC and
CC PTK2/FAK1. Interacts with RBFOX2. Interacts with EP300; the interaction
CC is estrogen-dependent and enhanced by CITED1. Interacts with CITED1;
CC the interaction is estrogen-dependent. Interacts with FAM120B, FOXL2,
CC PHB2 and SLC30A9. Interacts with coactivators NCOA3 and NCOA6.
CC Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa.
CC Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-
CC 1 and AF-2 domains simultaneously and mediate their transcriptional
CC synergy. Interacts with DDX5. Interacts with NCOA1; the interaction
CC seems to require a self-association of N-terminal and C-terminal
CC regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3.
CC Interacts with NRIP1. Interacts with GPER1; the interaction occurs in
CC an estrogen-dependent manner. Interacts with CLOCK and the interaction
CC is stimulated by estrogen. Interacts with TRIP4 (ufmylated); estrogen
CC dependent. Interacts with LMTK3; the interaction phosphorylates ESR1
CC (in vitro) and protects it against proteasomal degradation. Interacts
CC with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts
CC with ZFHX3. Interacts with SFR1 in a ligand-dependent and -independent
CC manner. Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1
CC ubiquitination and ubiquitin-mediated proteasomal degradation.
CC Interacts (via DNA-binding domain) with POU4F2 (C-terminus); this
CC interaction increases the estrogen receptor ESR1 transcriptional
CC activity in a DNA- and ligand 17-beta-estradiol-independent manner.
CC Interacts with ESRRB isoform 1. Interacts with UBE3A and WBP2.
CC Interacts with GTF2B. Interacts with RBM39. In the absence of hormonal
CC ligand, interacts with TACC1 (By similarity).
CC {ECO:0000250|UniProtKB:P03372, ECO:0000250|UniProtKB:P19785}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC Cytoplasm {ECO:0000250}. Golgi apparatus {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi
CC apparatus where most probably palmitoylation occurs. Associated with
CC the plasma membrane when palmitoylated. {ECO:0000250}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain. The
CC modulating domain, also known as A/B or AF-1 domain has a ligand-
CC independent transactivation function. The C-terminus contains a ligand-
CC dependent transactivation domain, also known as E/F or AF-2 domain
CC which overlaps with the ligand binding domain. AF-1 and AF-2 activate
CC transcription independently and synergistically and act in a
CC promoter- and cell-specific manner (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1
CC proteasomal degradation. Deubiquitinated by OTUB1.
CC {ECO:0000250|UniProtKB:P03372}.
CC -!- PTM: Palmitoylated at Cys-45 by ZDHHC7 and ZDHHC21. Palmitoylation is
CC required for plasma membrane targeting and for rapid intracellular
CC signaling via ERK and AKT kinases and cAMP generation, but not for
CC signaling mediated by the nuclear hormone receptor (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably
CC enhances transcriptional activity. Dephosphorylation by PPP5C inhibits
CC its transactivation activity (By similarity). Phosphorylated by LMTK3
CC (in vitro) (By similarity). {ECO:0000250|UniProtKB:P03372}.
CC -!- PTM: Dimethylated by PRMT1. Demethylated by JMJD6.
CC {ECO:0000250|UniProtKB:P03372}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; S71040; AAB31102.1; -; mRNA.
DR PIR; I67419; I67419.
DR AlphaFoldDB; P49886; -.
DR SMR; P49886; -.
DR STRING; 9544.ENSMMUP00000025044; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; P49886; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProt.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISS:UniProtKB.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.565.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR Pfam; PF00104; Hormone_recep; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
PE 2: Evidence at transcript level;
KW Activator; Cell membrane; Cytoplasm; DNA-binding; Golgi apparatus;
KW Lipid-binding; Lipoprotein; Membrane; Metal-binding; Nucleus; Palmitate;
KW Receptor; Reference proteome; Steroid-binding; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN <1..>121
FT /note="Estrogen receptor"
FT /id="PRO_0000053619"
FT DOMAIN <1..>121
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT LIPID 45
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT NON_TER 1
FT NON_TER 121
SQ SEQUENCE 121 AA; 13836 MW; E985B0C710DBC402 CRC64;
LFAPNLLLDR NQGKCVEGMV ESFDMLLATS SRFRMMNLQG EEFVCLKSII LLNSGVYTFL
SSTLKSLEEK DHIHRVLDKI TDTLIHLMAK AGLTLQQQHR RLAQLLLILS HIRHMSNKGM
E
