InnateDB Protein
|
IDBP-387833.5
|
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
|
ENSP00000415934
|
InnateDB Gene
|
IDBG-97997 (ESR1)
|
Protein Structure
|
|
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 |
|
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.
|
Predicted by orthology |
Total |
19 [view]
|
|
|
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
|
|
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 |
|
PDB ID |
|
InterPro |
IPR001292
Oestrogen receptor
|
PFAM |
PF02159
|
PRINTS |
PR00543
|
PIRSF |
PIRSF500101
|
SMART |
|
TIGRFAMs |
|
Modification |
|
SwissProt |
P03372
|
PhosphoSite |
PhosphoSite-P03372
|
TrEMBL |
Q9UE35
|
UniProt Splice Variant |
|
Entrez Gene |
2099
|
UniGene |
Hs.630134
|
RefSeq |
|
HUGO |
HGNC:3467
|
OMIM |
133430
|
CCDS |
|
HPRD |
00589
|
IMGT |
|
EMBL |
AB685816
AF258449
AH008151
AL035695
AL049821
AL078582
AL356311
AL590993
AY425004
BC128573
BC128574
BX640939
CH471051
JX524780
JX524781
JX996117
M12674
U47678
U68067
U68068
X03635
X62462
X73067
Z75126
|
GenPept |
AAA52399
AAB00115
AAC51874
AAC51875
AAD52984
AAG41358
AAI28574
AAI28575
AAQ91815
AFV77693
AFV77694
AGC74339
BAM62932
CAA27284
CAA44322
CAA51528
CAA99436
CAE45969
CAI14237
CAI21012
CAI22123
CAI42285
EAW47740
|
|
|