InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ESR1

Summary

InnateDB Protein

IDBP-387828.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ESR1

Protein Name

estrogen receptor 1

Synonyms

ER; Era; ESR; ESRA; ESTRR; NR3A1;

Species

Homo sapiens

Ensembl Protein

ENSP00000387500

InnateDB Gene

IDBG-97997 (ESR1)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:10681512, ECO:0000269PubMed:10816575, ECO:0000269PubMed:11477071, ECO:0000269PubMed:11682626, ECO:0000269PubMed:14764652, ECO:0000269PubMed:15078875, ECO:0000269PubMed:15891768, ECO:0000269PubMed:16043358, ECO:0000269PubMed:16617102, ECO:0000269PubMed:16684779, ECO:0000269PubMed:17922032, ECO:0000269PubMed:17932106, ECO:0000269PubMed:18247370, ECO:0000269PubMed:19350539, ECO:0000269PubMed:20705611, ECO:0000269PubMed:21330404, ECO:0000269PubMed:22083956, ECO:0000269PubMed:7651415, ECO:0000269PubMed:9328340}.

Subcellular Localization

Isoform 1: Nucleus {ECO:0000255PROSITE- ProRule:PRU00407, ECO:0000269PubMed:12682286}. Cytoplasm {ECO:0000269PubMed:12682286}. Cell membrane {ECO:0000269PubMed:12682286}; Peripheral membrane protein {ECO:0000269PubMed:12682286}; Cytoplasmic side {ECO:0000269PubMed:12682286}. Note=A minor fraction is associated with the inner membrane.Isoform 3: Nucleus. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Single-pass type I membrane protein. Note=Associated with the inner membrane via palmitoylation (Probable). At least a subset exists as a transmembrane protein with a N-terminal extracellular domain. {ECO:0000305}.Nucleus. Golgi apparatus. Cell membrane. Note=Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs. Associated with the plasma membrane when palmitoylated.

Disease Associations

Estrogen resistance (ESTRR) [MIM:615363]: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present. {ECO:0000269PubMed:23841731, ECO:0000269PubMed:8961262}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed. Isoform 3 is not expressed in the pituitary gland. {ECO:0000269PubMed:10970861}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 764 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	764 [view]
Protein-Protein	728 [view]
Protein-DNA	27 [view]
Protein-RNA	1 [view]
DNA-DNA	8 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001046	core promoter sequence-specific DNA binding
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003707	steroid hormone receptor activity
GO:0005496	steroid binding
GO:0005515	protein binding
GO:0008013	beta-catenin binding
GO:0008270	zinc ion binding
GO:0019899	enzyme binding
GO:0030235	nitric-oxide synthase regulator activity
GO:0030284	estrogen receptor activity
GO:0034056	estrogen response element binding
GO:0038052	estrogen-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0042802	identical protein binding
GO:0043565	sequence-specific DNA binding

Biological Process

GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0007165	signal transduction
GO:0007200	phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0010467	gene expression
GO:0010629	negative regulation of gene expression
GO:0010863	positive regulation of phospholipase C activity
GO:0030518	intracellular steroid hormone receptor signaling pathway
GO:0030520	intracellular estrogen receptor signaling pathway
GO:0032355	response to estradiol
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043401	steroid hormone mediated signaling pathway
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043627	response to estrogen
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048386	positive regulation of retinoic acid receptor signaling pathway
GO:0051000	positive regulation of nitric-oxide synthase activity
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0071392	cellular response to estradiol stimulus

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001292 Oestrogen receptor
IPR001628 Zinc finger, nuclear hormone receptor-type
IPR001723 Steroid hormone receptor
IPR008946 Nuclear hormone receptor, ligand-binding

PFAM

PF00104
PF02159
PF00105

PRINTS

PR00543
PR00047
PR00398

PIRSF

PIRSF500101

SMART

SM00430
SM00399

TIGRFAMs

Post-translational Modifications

Modification

Cross-References