ESR1_FELCA
ID ESR1_FELCA Reviewed; 595 AA.
AC Q53AD2;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
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;
GN Name=ESR1; Synonyms=ESR, NR3A1;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15955691; DOI=10.1016/j.jsbmb.2005.02.013;
RA Cardazzo B., Zappulli V., Frassineti F., Patarnello T., Castagnaro M.,
RA Bargelloni L.;
RT "Full-length sequence and expression analysis of estrogen receptor alpha
RT mRNA in feline mammary tumors.";
RL J. Steroid Biochem. Mol. Biol. 96:109-118(2005).
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 PELP1, the interaction
CC is enhanced by 17-beta-estradiol; the interaction increases ESR1
CC transcriptional activity (By similarity). Interacts with NCOA7; the
CC interaction is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1,
CC KDM5A, MAP1S, SMARD1, and UBE1C. Interacts with MUC1; the interaction
CC is stimulated by 7 beta-estradiol (E2) and enhances ESR1-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 RBFOX2. Interacts with EP300; the
CC interaction is estrogen-dependent and enhanced by CITED1. Interacts
CC with CITED1; the interaction is estrogen-dependent. Interacts with
CC FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with coactivators NCOA3 and
CC NCOA6. Interacts with STK3/MST2 only in the presence of SAV1 and vice-
CC versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with
CC ESR1 AF-1 and AF-2 domains simultaneously and mediate their
CC transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the
CC interaction seems to require a self-association of N-terminal and C-
CC terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and
CC SP3. Interacts with NRIP1. Interacts with GPER1; the interaction occurs
CC in an estrogen-dependent manner. Interacts with CLOCK and the
CC interaction is stimulated by estrogen. Interacts with TRIP4
CC (ufmylated); estrogen dependent. Interacts with LMTK3; the interaction
CC phosphorylates ESR1 (in vitro) and protects it against proteasomal
CC degradation. Interacts with CCAR2 (via N-terminus) in a ligand-
CC independent manner. Interacts with ZFHX3. Interacts with SFR1 in a
CC ligand-dependent and -independent manner. Interacts with DCAF13, LATS1
CC and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated
CC proteasomal degradation. Interacts (via DNA-binding domain) with POU4F2
CC (C-terminus); this interaction increases the estrogen receptor ESR1
CC transcriptional activity in a DNA- and ligand 17-beta-estradiol-
CC independent manner. Interacts with ESRRB isoform 1. Interacts with
CC UBE3A and WBP2. Interacts with GTF2B. Interacts with RBM39. In the
CC absence of hormonal ligand, interacts with TACC1 (By similarity).
CC Interacts with PI3KR1 or PI3KR2 and PTK2/FAK1 (By similarity).
CC Interacts with SRC (By similarity). {ECO:0000250|UniProtKB:P03372,
CC 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: Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably
CC enhances transcriptional activity. Dephosphorylation at Ser-118 by
CC PPP5C inhibits its transactivation activity (By similarity).
CC Phosphorylated by LMTK3 (in vitro) (By similarity).
CC {ECO:0000250|UniProtKB:P03372}.
CC -!- PTM: Palmitoylated at Cys-447 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: Dimethylated by PRMT1 at Arg-260. The methylation may favor
CC cytoplasmic localization. Demethylated by JMJD6 at Arg-260.
CC {ECO:0000250|UniProtKB:P03372}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
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DR EMBL; AY605260; AAU11443.1; -; mRNA.
DR RefSeq; NP_001019402.1; NM_001024231.1.
DR AlphaFoldDB; Q53AD2; -.
DR SMR; Q53AD2; -.
DR STRING; 9685.ENSFCAP00000020448; -.
DR GeneID; 552888; -.
DR KEGG; fca:552888; -.
DR CTD; 2099; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q53AD2; -.
DR OrthoDB; 487299at2759; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0030284; F:nuclear estrogen receptor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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 Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR024178; Est_rcpt/est-rel_rcp.
DR InterPro; IPR001292; Estr_rcpt.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR024736; Oestrogen-typ_rcpt_final_C_dom.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF12743; ESR1_C; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF02159; Oest_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PIRSF; PIRSF500101; ER-a; 1.
DR PIRSF; PIRSF002527; ER-like_NR; 1.
DR PRINTS; PR00543; OESTROGENR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Activator; Cell membrane; Cytoplasm; DNA-binding; Glycoprotein;
KW Golgi apparatus; Lipid-binding; Lipoprotein; Membrane; Metal-binding;
KW Methylation; Nucleus; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Steroid-binding; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..595
FT /note="Estrogen receptor"
FT /id="PRO_0000226725"
FT DOMAIN 311..547
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 185..250
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 185..205
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 221..245
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..184
FT /note="Modulating (transactivation AF-1); mediates
FT interaction with MACROD1"
FT /evidence="ECO:0000250"
FT REGION 35..174
FT /note="Interaction with DDX5; self-association"
FT /evidence="ECO:0000250"
FT REGION 35..47
FT /note="Required for interaction with NCOA1"
FT /evidence="ECO:0000250"
FT REGION 149..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..310
FT /note="Mediates interaction with DNTTIP2"
FT /evidence="ECO:0000250"
FT REGION 251..310
FT /note="Hinge"
FT REGION 257..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..595
FT /note="Interaction with AKAP13"
FT /evidence="ECO:0000250"
FT REGION 264..595
FT /note="Self-association"
FT /evidence="ECO:0000250"
FT REGION 311..595
FT /note="Transactivation AF-2"
FT /evidence="ECO:0000250"
FT MOD_RES 104
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 106
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 167
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 260
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 537
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT LIPID 447
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 10
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 571
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 595 AA; 66050 MW; 297D6DE77119787C CRC64;
MTMTLHTKAS GMALLHQIQG NELETLNRPQ LKIPLERPLG EVYVDGSKPA VYNYPEGAAY
DFNAAAAASA PVYGQSGLAY GSGSEAAAFG ANGLGGFPPL NSVSPSPLVL LHPPPQLSPF
LHPHGQQVPY YLENEPSGYA VREAGPPAFY RPTSDNRRQS GRERLASTGD KGSMAMESAK
ETRYCAVCND YASGYHYGVW SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC
RLRKCYEVGM MKGGIRKDRR GGRMLKHKRQ RDEGEGRNEV GSSGDVRASN LWPSPLLIKH
TKKNSPALSL TADQMVSALL EAEPPIIYSD YDPSRPFSEA SMMGLLTNLA DRELVHMINW
AKRVPGFVDL SLHDQVHLLE CAWLEILMIG LVWRSMEHPG KLLFAPNLLL DRNQGKCVEG
MVEIFDMLLA TSSRFRMMNL QGEEFVCLKS IILLNSGVYT FLSSTLKSLE EKDHIHRVLD
KITDTLIHLM AKAGLSLQQQ HRRLAQLLLI LSHIRHMSNK GMEHLYNMKC KNVVPLYDLL
LEMLDAHRLH APANRGGAPM EEMNQSQLAT TGSTSAHSLQ AYYITEEAGA FPTTV
