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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.
11-DEC-2019, entry version 107.
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:0005623; C:cell; IEA:GOC.
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; 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
/note="Estrogen receptor"
/id="PRO_0000226725"
DOMAIN 311..547
/note="NR LBD"
/evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
DNA_BIND 185..250
/note="Nuclear receptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
ZN_FING 185..205
/note="NR C4-type"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
ZN_FING 221..245
/note="NR C4-type"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
REGION 1..184
/note="Modulating (transactivation AF-1); mediates
interaction with MACROD1"
/evidence="ECO:0000250"
REGION 35..174
/note="Interaction with DDX5; self-association"
/evidence="ECO:0000250"
REGION 35..47
/note="Required for interaction with NCOA1"
/evidence="ECO:0000250"
REGION 185..310
/note="Mediates interaction with DNTTIP2"
/evidence="ECO:0000250"
REGION 251..310
/note="Hinge"
REGION 262..595
/note="Interaction with AKAP13"
/evidence="ECO:0000250"
REGION 264..595
/note="Self-association"
/evidence="ECO:0000250"
REGION 311..595
/note="Transactivation AF-2"
/evidence="ECO:0000250"
COMPBIAS 64..70
/note="Poly-Ala"
MOD_RES 104
/note="Phosphoserine; by CDK2"
/evidence="ECO:0000250|UniProtKB:P03372"
MOD_RES 106
/note="Phosphoserine; by CDK2"
/evidence="ECO:0000250|UniProtKB:P03372"
MOD_RES 118
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P03372"
MOD_RES 167
/note="Phosphoserine; by CK2"
/evidence="ECO:0000250|UniProtKB:P03372"
MOD_RES 260
/note="Asymmetric dimethylarginine; by PRMT1"
/evidence="ECO:0000250|UniProtKB:P03372"
MOD_RES 537
/note="Phosphotyrosine; by Tyr-kinases"
/evidence="ECO:0000250|UniProtKB:P03372"
LIPID 447
/note="S-palmitoyl cysteine"
/evidence="ECO:0000250"
CARBOHYD 10
/note="O-linked (GlcNAc) serine"
/evidence="ECO:0000250"
CARBOHYD 571
/note="O-linked (GlcNAc) threonine"
/evidence="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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Related Genes :
[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 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)
[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)
[ESR2 ESTRB NR3A2] Estrogen receptor beta (ER-beta) (Nuclear receptor subfamily 3 group A member 2)
[ESR1 ESR NR3A1] Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) (Fragment)
[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)
[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)
[AR DHTR NR3C4] Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4)
[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)
[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)
[ftz-f1 NR5A3 CG4059] Nuclear hormone receptor FTZ-F1 (FTZ-F1 alpha) (Nuclear receptor subfamily 5 group A member 3)
[Rara Nr1b1] Retinoic acid receptor alpha (RAR-alpha) (Nuclear receptor subfamily 1 group B member 1)

Bibliography :
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