LipidDB ID

LipidDB-9606-00784

Entry Name

UniProt Accession

P03372; Q13511; Q14276; Q5T5H7; Q6MZQ9; Q9NU51; Q9UDZ7; Q9UIS7;

Theoretical PI

8.3

Molecular Weight

66216.0

Genbank Protein ID

CAA27284.1; AAA52399.1; AAB00115.1; AAQ91815.1; CAE45969.1; CAI21012.1; CAI21012.1; CAI21012.1; CAI21012.1; CAI22123.1; CAI22123.1; CAI22123.1; CAI22123.1; CAI14237.1; CAI14237.1; CAI14237.1; CAI14237.1; CAI42285.1; CAI42285.1; CAI42285.1; EAW47740.1; AAI28574.1; AAI28575.1; AAD52984.1; CAA51528.1; CAA99436.1;

Genbank Nucleotide ID

X03635; M12674; U47678; AY425004; BX640939; AL356311; AL049821; AL078582; AL590993; AL049821; AL078582; AL356311; AL590993; AL590993; AL049821; AL078582; AL356311; AL078582; AL356311; AL590993; CH471051; BC128573; BC128574; AH008151; X73067; Z75126;

Protein Name

Estrogen receptor

Protein Synonyms/Alias

ER; ER-alpha; Estradiol receptor; Nuclear receptor subfamily 3 group A member 1;

Gene Name

ESR1

Gene Synonyms/Alias

ESR; NR3A1;

Created Date

21-JUL-1986

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Acconcia F, Ascenzi P, Bocedi A, Spisni E, Tomasi V, Trentalance A, Visca P,Marino M. Palmitoylation-dependent estrogen receptor alpha membrane localization:regulation by 17beta-estradiol. Mol Biol Cell. 2005 Jan;16(1):231-7. Epub 2004Oct 20.[PMID:15496458]
[2] Pedram A, Razandi M, Sainson RC, Kim JK, Hughes CC, Levin ER. A conservedmechanism for steroid receptor translocation to the plasma membrane. J Biol Chem.2007 Aug 3;282(31):22278-88. Epub 2007 May 29.[PMID:17535799]

Functional Description

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. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.

Sequence Annotation

Region: 1 184 Modulating (transactivation AF-1);mediates interaction with MACROD1.
Region: 35 174 Interaction with DDX5; self-association.
Region: 35 47 Required for interaction with NCOA1.
Region: 185 310 Mediates interaction with DNTTIP2.
Region: 251 310 Hinge.
Region: 262 595 Interaction with AKAP13.
Region: 264 595 Self-association.
Region: 311 595 Transactivation AF-2.
Region: 311 551 Steroid-binding.
Modified residue: 104 104 Phosphoserine; by CDK2.
Modified residue: 106 106 Phosphoserine; by CDK2.
Modified residue: 118 118 Phosphoserine.
Modified residue: 167 167 Phosphoserine; by CK2.
Modified residue: 260 260 Asymmetric dimethylarginine; by PRMT1.
Modified residue: 537 537 Phosphotyrosine; by Tyr-kinases.

Protein Length

595 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0005794; C:Golgi apparatus; IEA:UniProtKB-KW
GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW
GO:0016020; C:membrane; NAS:UniProtKB
GO:0005654; C:nucleoplasm; TAS:Reactome
GO:0005634; C:nucleus; IDA:UniProtKB
GO:0005886; C:plasma membrane; IDA:UniProtKB
GO:0035327; C:transcriptionally active chromatin; IDA:UniProtKB
GO:0008013; F:beta-catenin binding; IPI:BHF-UCL
GO:0003682; F:chromatin binding; IDA:UniProtKB
GO:0001046; F:core promoter sequence-specific DNA binding; IDA:UniProtKB
GO:0019899; F:enzyme binding; IPI:UniProtKB
GO:0030284; F:estrogen receptor activity; NAS:UniProtKB
GO:0034056; F:estrogen response element binding; IDA:UniProtKB
GO:0038052; F:estrogen-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; IGI:MGI
GO:0042802; F:identical protein binding; IPI:IntAct
GO:0030235; F:nitric-oxide synthase regulator activity; NAS:UniProtKB
GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB
GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IDA:NTNU_SB
GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:BHF-UCL
GO:0005496; F:steroid binding; ISS:UniProtKB
GO:0003707; F:steroid hormone receptor activity; TAS:ProtInc
GO:0008134; F:transcription factor binding; IPI:UniProtKB
GO:0008270; F:zinc ion binding; IEA:InterPro
GO:0008209; P:androgen metabolic process; IEA:Ensembl
GO:0001547; P:antral ovarian follicle growth; IEA:Ensembl
GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB
GO:0006338; P:chromatin remodeling; NAS:UniProtKB
GO:0002064; P:epithelial cell development; IEA:Ensembl
GO:0060750; P:epithelial cell proliferation involved in mammary gland duct elongation; IEA:Ensembl
GO:0010467; P:gene expression; TAS:Reactome
GO:0030520; P:intracellular estrogen receptor signaling pathway; NAS:UniProtKB
GO:0030518; P:intracellular steroid hormone receptor signaling pathway; ISS:UniProtKB
GO:0008584; P:male gonad development; IEA:Ensembl
GO:0060749; P:mammary gland alveolus development; IEA:Ensembl
GO:0060745; P:mammary gland branching involved in pregnancy; IEA:Ensembl
GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB
GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB
GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB
GO:0007200; P:phospholipase C-activating G-protein coupled receptor signaling pathway; ISS:UniProtKB
GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB
GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl
GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:UniProtKB
GO:0051000; P:positive regulation of nitric-oxide synthase activity; IDA:UniProtKB
GO:0010863; P:positive regulation of phospholipase C activity; ISS:UniProtKB
GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IDA:BHF-UCL
GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB
GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IEA:Ensembl
GO:0060523; P:prostate epithelial cord elongation; IEA:Ensembl
GO:0042981; P:regulation of apoptotic process; IEA:Ensembl
GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Ensembl
GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB
GO:0032355; P:response to estradiol; IDA:BHF-UCL
GO:0043627; P:response to estrogen; IDA:UniProtKB
GO:0007165; P:signal transduction; TAS:ProtInc
GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome
GO:0006351; P:transcription, DNA-templated; TAS:ProtInc
GO:0060065; P:uterus development; IEA:Ensembl
GO:0060068; P:vagina development; IEA:Ensembl

Interpro

InterPro; IPR008946; Nucl_hormone_rcpt_ligand-bd
InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd_core
InterPro; IPR024178; Oest_rcpt/oest-rel_rcp
InterPro; IPR001292; Oestr_rcpt
InterPro; IPR024736; Oestrogen-typ_rcpt_final_C_dom
InterPro; IPR001723; Str_hrmn_rcpt
InterPro; IPR001628; Znf_hrmn_rcpt
InterPro; IPR013088; Znf_NHR/GATA

Pfam

Pfam; PF12743; ESR1_C;
Pfam; PF00104; Hormone_recep;
Pfam; PF02159; Oest_recep;
Pfam; PF00105; zf-C4;

SMART

SMART; SM00430; HOLI;
SMART; SM00399; ZnF_C4;

PROSITE

PROSITE; PS00031; NUCLEAR_REC_DBD_1;
PROSITE; PS51030; NUCLEAR_REC_DBD_2;

PRINTS

PRINTS; PR00543; OESTROGENR;
PRINTS; PR00398; STRDHORMONER;
PRINTS; PR00047; STROIDFINGER;