ESR1
entrez
2099
canonical
uniprot
P03372
canonical
ensembl
ENSG00000091831
resolver
ensp
ENSP00000206249
resolver
ensp
ENSP00000342630
resolver
ensp
ENSP00000387500
resolver
ensp
ENSP00000394721
resolver
ensp
ENSP00000405330
resolver
ensp
ENSP00000528392
resolver
ensp
ENSP00000528393
resolver
ensp
ENSP00000528394
resolver
ensp
ENSP00000617818
resolver
ensp
ENSP00000789872
resolver
ensp
ENSP00000789873
resolver
enst
ENST00000427531
resolver
genesymbol
ESR1
resolver
genesymbol_syn
ESR
resolver
genesymbol_syn
NR3A1
resolver
hgnc
HGNC:3467
resolver
uniprot
A0A125SXW3
resolver
uniprot
A8KAF4
resolver
uniprot
G4XH65
resolver
uniprot
H0Y4W6
resolver
uniprot
Q13511
resolver
uniprot
Q14276
resolver
uniprot
Q5T5H7
resolver
uniprot
Q6MZQ9
resolver
uniprot
Q9NU51
resolver
uniprot
Q9UBT1
resolver
uniprot
Q9UDZ7
resolver
uniprot
Q9UIS7
resolver
uniprot_entry
A0A125SXW3_HUMAN
resolver
uniprot_entry
A8KAF4_HUMAN
resolver
uniprot_entry
ESR1_HUMAN
resolver
uniprot_entry
G4XH65_HUMAN
resolver
uniprot_entry
H0Y4W6_HUMAN
resolver
uniprot_entry
Q9UBT1_HUMAN
resolver
uniprot_sec
Q13511
resolver
uniprot_sec
Q14276
resolver
uniprot_sec
Q5T5H7
resolver
uniprot_sec
Q6MZQ9
resolver
uniprot_sec
Q9NU51
resolver
uniprot_sec
Q9UDZ7
resolver
uniprot_sec
Q9UIS7
resolver
amino_acid_sequence
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:23841731, ECO:0000269|PubMed:27754803}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [Isoform 3]: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). 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 (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}.
uniprot
proteins
mass_dalton
66216
uniprot
proteins
mutagenesis
MUTAGEN 39; /note="L->P: Impairs AF-1 transactivation."; /evidence="ECO:0000269|PubMed:11075817"; MUTAGEN 43; /note="Y->P: Impairs AF-1 transactivation."; /evidence="ECO:0000269|PubMed:11075817"; MUTAGEN 104; /note="S->A: Loss of cyclin A-dependent induction of transcriptional activation."; /evidence="ECO:0000269|PubMed:10428798"; MUTAGEN 106; /note="S->A: Loss of cyclin A-dependent induction of transcriptional activation."; /evidence="ECO:0000269|PubMed:10428798"; MUTAGEN 118; /note="S->A: Decreases phosphorylation and transactivation activity. Abolishes AF-1 transactivation. Insensitive to PPP5C inhibition of transactivation activity."; /evidence="ECO:0000269|PubMed:10409727, ECO:0000269|PubMed:14764652"; MUTAGEN 118; /note="S->E: Enhances transactivation activity. Insensitive to PPP5C inhibition of transactivation activity."; /evidence="ECO:0000269|PubMed:14764652"; MUTAGEN 260; /note="R->A,K: Loss of methylation."; /evidence="ECO:0000269|PubMed:18657504"; MUTAGEN 364; /note="V->E: Has higher transcriptional activity in the absence of wild type ER. Inhibits transcriptional activity when coexpressed with the wild type receptor."; /evidence="ECO:0000269|PubMed:8961262"; MUTAGEN 386; /note="I->C: Loss of transmembrane localization, no effect on peripheral membrane localization. Impairs activation of estrogen-induced activation of NOS3 and production of nitric oxide. No effect on binding to ERES."; /evidence="ECO:0000269|PubMed:21937726"; MUTAGEN 447; /note="C->A: Loss of hormone binding capacity and temperature-sensitive loss in DNA-binding."; /evidence="ECO:0000269|PubMed:1577818"; MUTAGEN 537; /note="Y->A: Reduces PELP1-mediated activation of transcriptional activity."; /evidence="ECO:0000269|PubMed:14963108"; MUTAGEN 539; /note="L->A: Abolishes interaction with NCOA1, NCOA2 and NCOA3."; /evidence="ECO:0000269|PubMed:12554772
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by cyclin A/CDK2. Self-association induces phosphorylation. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity. Phosphorylated by LMTK3 in vitro. {ECO:0000269|PubMed:10428798, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:21602804, ECO:0000269|PubMed:7476978, ECO:0000269|PubMed:7539106, ECO:0000269|PubMed:7838153}.; PTM: Glycosylated; contains N-acetylglucosamine, probably O-linked. {ECO:0000269|PubMed:8999954}.; PTM: Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation (PubMed:21602804, PubMed:28068668). Deubiquitinated by OTUB1 (PubMed:19383985). Ubiquitinated by STUB1/CHIP; in the CA1 hippocampal region following loss of endogenous circulating estradiol (17-beta-estradiol/E2) (By similarity). Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound ESR1 when it is not associated with coactivators (NCOAs) (PubMed:37478846). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (PubMed:37478846). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:19383985, ECO:0000269|PubMed:21602804, ECO:0000269|PubMed:28068668, ECO:0000269|PubMed:37478846}.; PTM: Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (PubMed:18657504, PubMed:24498420). Demethylated by JMJD6 at Arg-260 (PubMed:24498420). {ECO:0000269|PubMed:18657504, ECO:0000269|PubMed:24498420}.; PTM: Palmitoylated (isoform 3). Not biotinylated (isoform 3). {ECO:0000269|PubMed:22031296}.; PTM: Palmitoylated 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. {ECO:0000269|PubMed:22031296}.
uniprot
proteins
protein_family
NR3 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
10359819
uniprot
proteins
pubmed
10409727
uniprot
proteins
pubmed
10428798
uniprot
proteins
pubmed
10567404
uniprot
proteins
pubmed
10619354
uniprot
proteins
pubmed
10681512
uniprot
proteins
pubmed
10816575
uniprot
proteins
pubmed
10942433
uniprot
proteins
pubmed
10970861
uniprot
proteins
pubmed
11075817
uniprot
proteins
pubmed
11113208
uniprot
proteins
pubmed
11265755
uniprot
proteins
pubmed
11358960
uniprot
proteins
pubmed
11477071
uniprot
proteins
pubmed
11481323
uniprot
proteins
pubmed
11581164
uniprot
proteins
pubmed
11682626
uniprot
proteins
pubmed
11875103
uniprot
proteins
pubmed
11971969
uniprot
proteins
pubmed
12039952
uniprot
proteins
pubmed
12093804
uniprot
proteins
pubmed
12415108
uniprot
proteins
pubmed
12554772
uniprot
proteins
pubmed
12682286
uniprot
proteins
pubmed
12917342
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14764652
uniprot
proteins
pubmed
14963108
uniprot
proteins
pubmed
15047147
uniprot
proteins
pubmed
15078875
uniprot
proteins
pubmed
1517211
uniprot
proteins
pubmed
15199063
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1577818
uniprot
proteins
pubmed
15891768
uniprot
proteins
pubmed
15940264
uniprot
proteins
pubmed
16043358
uniprot
proteins
pubmed
16165085
uniprot
proteins
pubmed
16427018
uniprot
proteins
pubmed
16603732
uniprot
proteins
pubmed
16617102
uniprot
proteins
pubmed
16684779
uniprot
proteins
pubmed
16772533
uniprot
proteins
pubmed
17006958
uniprot
proteins
pubmed
17043237
uniprot
proteins
pubmed
17085477
uniprot
proteins
pubmed
17224074
uniprot
proteins
pubmed
17311814
uniprot
proteins
pubmed
17347654
uniprot
proteins
pubmed
17505058
uniprot
proteins
pubmed
17587566
uniprot
proteins
pubmed
17658481
uniprot
proteins
pubmed
17914104
uniprot
proteins
pubmed
17922032
uniprot
proteins
pubmed
17932106
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
17998543
uniprot
proteins
pubmed
18247370
uniprot
proteins
pubmed
18563714
uniprot
proteins
pubmed
18657504
uniprot
proteins
pubmed
19117995
uniprot
proteins
pubmed
19339517
uniprot
proteins
pubmed
19350539
uniprot
proteins
pubmed
19383985
uniprot
proteins
pubmed
19423554
uniprot
proteins
pubmed
19636373
uniprot
proteins
pubmed
19666546
uniprot
proteins
pubmed
19712589
uniprot
proteins
pubmed
19718048
uniprot
proteins
pubmed
19749156
uniprot
proteins
pubmed
19755138
uniprot
proteins
pubmed
20074560
uniprot
proteins
pubmed
20078863
uniprot
proteins
pubmed
20705611
uniprot
proteins
pubmed
20720010
uniprot
proteins
pubmed
21104395
uniprot
proteins
pubmed
21330404
uniprot
proteins
pubmed
21602804
uniprot
proteins
pubmed
21937726
uniprot
proteins
pubmed
22031296
uniprot
proteins
pubmed
22083956
uniprot
proteins
pubmed
2247153
uniprot
proteins
pubmed
23160374
uniprot
proteins
pubmed
23841731
uniprot
proteins
pubmed
23874500
uniprot
proteins
pubmed
24498420
uniprot
proteins
pubmed
24509260
uniprot
proteins
pubmed
25219498
uniprot
proteins
pubmed
27754803
uniprot
proteins
pubmed
2792078
uniprot
proteins
pubmed
28068668
uniprot
proteins
pubmed
34718754
uniprot
proteins
pubmed
37478846
uniprot
proteins
pubmed
3753802
uniprot
proteins
pubmed
3754034
uniprot
proteins
pubmed
7476978
uniprot
proteins
pubmed
7539106
uniprot
proteins
pubmed
7651415
uniprot
proteins
pubmed
7838153
uniprot
proteins
pubmed
7916651
uniprot
proteins
pubmed
8221895
uniprot
proteins
pubmed
8600466
uniprot
proteins
pubmed
8961262
uniprot
proteins
pubmed
8999954
uniprot
proteins
pubmed
9195227
uniprot
proteins
pubmed
9328340
uniprot
proteins
pubmed
9338790
uniprot
proteins
pubmed
9600906
uniprot
proteins
pubmed
9619507
uniprot
proteins
pubmed
9627117
uniprot
proteins
pubmed
9875847
uniprot
proteins
sequence_length
595
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, ECO:0000269|PubMed:12682286, ECO:0000269|PubMed:20074560}. Cytoplasm {ECO:0000269|PubMed:12682286, ECO:0000269|PubMed:24498420}. Cell membrane {ECO:0000269|PubMed:12682286}; Peripheral membrane protein {ECO:0000269|PubMed:12682286}; Cytoplasmic side {ECO:0000269|PubMed:12682286}. Note=A minor fraction is associated with the inner membrane.; SUBCELLULAR LOCATION: [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}.; SUBCELLULAR LOCATION: 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.
uniprot
proteins