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Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)

 ESR1_FELCA              Reviewed;         595 AA.
Q53AD2;
07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
24-MAY-2005, sequence version 1.
03-JUL-2019, entry version 105.
RecName: Full=Estrogen receptor;
Short=ER;
AltName: Full=ER-alpha;
AltName: Full=Estradiol receptor;
AltName: Full=Nuclear receptor subfamily 3 group A member 1;
Name=ESR1; Synonyms=ESR, NR3A1;
Felis catus (Cat) (Felis silvestris catus).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae;
Felinae; Felis.
NCBI_TaxID=9685;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=15955691; DOI=10.1016/j.jsbmb.2005.02.013;
Cardazzo B., Zappulli V., Frassineti F., Patarnello T., Castagnaro M.,
Bargelloni L.;
"Full-length sequence and expression analysis of estrogen receptor
alpha mRNA in feline mammary tumors.";
J. Steroid Biochem. Mol. Biol. 96:109-118(2005).
-!- FUNCTION: 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). {ECO:0000250}.
-!- SUBUNIT: Binds DNA as a homodimer. Can form a heterodimer with
ESR2. 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 DNAAF4.
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.
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. Interacts with TRIP4
(ufmylated); estrogen dependent. 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. Interacts with ZFHX3. Interacts with
SFR1 in a ligand-dependent and -independent manner. Interacts with
DCAF13, LATS1 and DCAF1; regulates ESR1 ubiquitination and
ubiquitin-mediated proteasomal degradation. Interacts (via DNA-
binding domain) with POU4F2 (C-terminus); this interaction
increases the estrogen receptor ESR1 transcriptional activity in a
DNA- and ligand 17-beta-estradiol-independent manner. Interacts
with ESRRB isoform 1. Interacts with UBE3A and WBP2. Interacts
with GTF2B. Interacts with RBM39. In the absence of hormonal
ligand, interacts with TACC1 (By similarity).
{ECO:0000250|UniProtKB:P03372, ECO:0000250|UniProtKB:P19785}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00407}. Cytoplasm {ECO:0000250}. Golgi apparatus
{ECO:0000250}. Cell membrane {ECO:0000250}. Note=Colocalizes with
ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably
palmitoylation occurs. Associated with the plasma membrane when
palmitoylated. {ECO:0000250}.
-!- DOMAIN: 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).
{ECO:0000250}.
-!- PTM: Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1
proteasomal degradation. Deubiquitinated by OTUB1.
{ECO:0000250|UniProtKB:P03372}.
-!- PTM: 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).
{ECO:0000250|UniProtKB:P03372}.
-!- PTM: 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). {ECO:0000250}.
-!- PTM: Dimethylated by PRMT1 at Arg-260. The methylation may favor
cytoplasmic localization. Demethylated by JMJD6 at Arg-260.
{ECO:0000250|UniProtKB:P03372}.
-!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AY605260; AAU11443.1; -; mRNA.
RefSeq; NP_001019402.1; NM_001024231.1.
SMR; Q53AD2; -.
STRING; 9685.ENSFCAP00000020448; -.
GeneID; 552888; -.
KEGG; fca:552888; -.
CTD; 2099; -.
eggNOG; KOG3575; Eukaryota.
eggNOG; ENOG410XRZC; LUCA.
InParanoid; Q53AD2; -.
KO; K08550; -.
OrthoDB; 487299at2759; -.
Proteomes; UP000011712; Unplaced.
GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
GO; GO:0005634; C:nucleus; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
GO; GO:0030284; F:estrogen receptor activity; IEA:InterPro.
GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB.
GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; ISS:UniProtKB.
GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISS:UniProtKB.
GO; GO:0010863; P:positive regulation of phospholipase C activity; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
Gene3D; 1.10.565.10; -; 1.
Gene3D; 3.30.50.10; -; 1.
InterPro; IPR035500; NHR-like_dom_sf.
InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
InterPro; IPR001723; Nuclear_hrmn_rcpt.
InterPro; IPR024178; Oest_rcpt/oest-rel_rcp.
InterPro; IPR001292; Oestr_rcpt.
InterPro; IPR024736; Oestrogen-typ_rcpt_final_C_dom.
InterPro; IPR001628; Znf_hrmn_rcpt.
InterPro; IPR013088; Znf_NHR/GATA.
Pfam; PF12743; ESR1_C; 1.
Pfam; PF00104; Hormone_recep; 1.
Pfam; PF02159; Oest_recep; 1.
Pfam; PF00105; zf-C4; 1.
PIRSF; PIRSF500101; ER-a; 1.
PIRSF; PIRSF002527; ER-like_NR; 1.
PRINTS; PR00543; OESTROGENR.
PRINTS; PR00398; STRDHORMONER.
PRINTS; PR00047; STROIDFINGER.
SMART; SM00430; HOLI; 1.
SMART; SM00399; ZnF_C4; 1.
SUPFAM; SSF48508; SSF48508; 1.
PROSITE; PS51843; NR_LBD; 1.
PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
2: Evidence at transcript level;
Activator; Cell membrane; Complete proteome; Cytoplasm; DNA-binding;
Glycoprotein; Golgi apparatus; Lipid-binding; Lipoprotein; Membrane;
Metal-binding; Methylation; Nucleus; Palmitate; Phosphoprotein;
Receptor; Reference proteome; Steroid-binding; Transcription;
Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
CHAIN 1 595 Estrogen receptor.
/FTId=PRO_0000226725.
DOMAIN 311 547 NR LBD. {ECO:0000255|PROSITE-
ProRule:PRU01189}.
DNA_BIND 185 250 Nuclear receptor. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 185 205 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 221 245 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
REGION 1 184 Modulating (transactivation AF-1);
mediates interaction with MACROD1.
{ECO:0000250}.
REGION 35 174 Interaction with DDX5; self-association.
{ECO:0000250}.
REGION 35 47 Required for interaction with NCOA1.
{ECO:0000250}.
REGION 185 310 Mediates interaction with DNTTIP2.
{ECO:0000250}.
REGION 251 310 Hinge.
REGION 262 595 Interaction with AKAP13. {ECO:0000250}.
REGION 264 595 Self-association. {ECO:0000250}.
REGION 311 595 Transactivation AF-2. {ECO:0000250}.
COMPBIAS 64 70 Poly-Ala.
MOD_RES 104 104 Phosphoserine; by CDK2.
{ECO:0000250|UniProtKB:P03372}.
MOD_RES 106 106 Phosphoserine; by CDK2.
{ECO:0000250|UniProtKB:P03372}.
MOD_RES 118 118 Phosphoserine.
{ECO:0000250|UniProtKB:P03372}.
MOD_RES 167 167 Phosphoserine; by CK2.
{ECO:0000250|UniProtKB:P03372}.
MOD_RES 260 260 Asymmetric dimethylarginine; by PRMT1.
{ECO:0000250|UniProtKB:P03372}.
MOD_RES 537 537 Phosphotyrosine; by Tyr-kinases.
{ECO:0000250|UniProtKB:P03372}.
LIPID 447 447 S-palmitoyl cysteine. {ECO:0000250}.
CARBOHYD 10 10 O-linked (GlcNAc) serine. {ECO:0000250}.
CARBOHYD 571 571 O-linked (GlcNAc) threonine.
{ECO:0000250}.
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


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[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[Esr1 Esr Estr Estra Nr3a1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[Esr1 Esr Estr Nr3a1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) (Fragment)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
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[Esr2 Erbeta Nr3a2] Estrogen receptor beta (ER-beta) (Nuclear receptor subfamily 3 group A member 2)
[Esr2 Estrb Nr3a2] Estrogen receptor beta (ER-beta) (Nuclear receptor subfamily 3 group A member 2)
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[ESRRA ERR1 ESRL1 NR3B1] Steroid hormone receptor ERR1 (Estrogen receptor-like 1) (Estrogen-related receptor alpha) (ERR-alpha) (Nuclear receptor subfamily 3 group B member 1)
[Esrra Err1 Estrra Nr3b1] Steroid hormone receptor ERR1 (Estrogen receptor-like 1) (Estrogen-related receptor alpha) (ERR-alpha) (Nuclear receptor subfamily 3 group B member 1)
[Esrra Nr3b1] Steroid hormone receptor ERR1 (Estrogen-related receptor alpha) (ERR-alpha) (Nuclear receptor subfamily 3 group B member 1)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)
[Esrrb Err-2 Err2 Nr3b2] Steroid hormone receptor ERR2 (Estrogen receptor-like 2) (Estrogen-related receptor beta) (ERR-beta) (Nuclear receptor subfamily 3 group B member 2)
[ESRRB ERRB2 ESRL2 NR3B2] Steroid hormone receptor ERR2 (ERR beta-2) (Estrogen receptor-like 2) (Estrogen-related receptor beta) (ERR-beta) (Nuclear receptor subfamily 3 group B member 2)
[Esrrg Err3 Kiaa0832 Nr3b3] Estrogen-related receptor gamma (Estrogen receptor-related protein 3) (Nuclear receptor subfamily 3 group B member 3)
[Esrrb Err2 Esrl2 Nr3b2] Steroid hormone receptor ERR2 (Estrogen receptor-like 2) (Estrogen-related receptor beta) (ERR-beta) (Nuclear receptor subfamily 3 group B member 2)
[NR5A2 B1F CPF FTF] Nuclear receptor subfamily 5 group A member 2 (Alpha-1-fetoprotein transcription factor) (B1-binding factor) (hB1F) (CYP7A promoter-binding factor) (Hepatocytic transcription factor) (Liver receptor homolog 1) (LRH-1)
[NR1D2] Nuclear receptor subfamily 1 group D member 2 (Orphan nuclear hormone receptor BD73) (Rev-erb alpha-related receptor) (RVR) (Rev-erb-beta) (V-erbA-related protein 1-related) (EAR-1R)
[THRA EAR7 ERBA1 NR1A1 THRA1 THRA2] Thyroid hormone receptor alpha (Nuclear receptor subfamily 1 group A member 1) (V-erbA-related protein 7) (EAR-7) (c-erbA-1) (c-erbA-alpha)
[AR DHTR NR3C4] Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4)
[RARA NR1B1] Retinoic acid receptor alpha (RAR-alpha) (Nuclear receptor subfamily 1 group B member 1)
[NR3C1 GRL] Glucocorticoid receptor (GR) (Nuclear receptor subfamily 3 group C member 1)
[Rara Nr1b1] Retinoic acid receptor alpha (RAR-alpha) (Nuclear receptor subfamily 1 group B member 1)
[ftz-f1 NR5A3 CG4059] Nuclear hormone receptor FTZ-F1 (FTZ-F1 alpha) (Nuclear receptor subfamily 5 group A member 3)

Bibliography :
[28087261] DNA aptamer probes for detection of estrogen receptor α positive carcinomas.
[26573009] Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands.
[25943116] Estrogen-Induced Cholestasis Leads to Repressed CYP2D6 Expression in CYP2D6-Humanized Mice.
[25769926] Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter.
[25675114] Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump.
[23592396] Estrogen receptor α induction by mitoxantrone increases Abcg2 expression in placental trophoblast cells.
[23064813] Expression of MAGE-A11 in breast cancer tissues and its effects on the proliferation of breast cancer cells.
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