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This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative promoter usage and alternative splicing result in dozens of transcript variants, but the full-length nature of many of these variants has not been determined. [provided by RefSeq, Mar 2014]
ESR1 has been a focus in breast cancer for quite some time, but is also clinically relevant in endometrial, ovarian and other cancer types. The identification of ER-positive breast cancers that are resistant to hormone therapy have inspired clinical sequencing efforts to shed light on the mechanisms of this resistance. A number of mutations in the ligand binding domain of ESR1 have been implicated in hormone resistance and anti-estrogen therapies. These observations have spurred efforts to develop therapeutics that stimulate ESR1 protein degradation (e.g. Fulvestrant), rather than acting as a small molecule antagonist. These agents are currently in clinical trials and have seen some success.
ESR1 (Estrogen Receptor 1) is a Protein Coding gene. Diseases associated with ESR1 include Estrogen Resistance and Breast Cancer. Among its related pathways are Ovarian tumor domain proteases and Proteoglycans in cancer. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and identical protein binding. An important paralog of this gene is ESR2.
Estrogen controls many cellular processes including growth, differentiation and function of the reproductive system. Estrogen is also responsible for the growth and maintenance of the skeleton and the normal function of the cardiovascular and nervous systems.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IDA | 12047722 |
GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | NAS | 19274049 |
GO:0001093 | TFIIB-class transcription factor binding | IPI | 9841876 |
GO:0001223 | transcription coactivator binding | IPI | 21642474 |
GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | IDA | 12047722 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000790 | nuclear chromatin | IDA | 15831516 |
GO:0005634 | nucleus | IDA,IEA | 9841876 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IDA,IEA | 17505058 |
GO:0005794 | Golgi apparatus | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Prolactin Signaling Pathway | ||
2 | Gene Expression |
.48
|
|
3 | Metabolism of proteins | ||
4 | Nuclear Receptor transcription pathway | ||
5 | Signaling by ERBB4 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000122 | negative regulation of transcription by RNA polymerase II | IMP | 20388878 |
GO:0001547 | antral ovarian follicle growth | IEA | -- |
GO:0002064 | epithelial cell development | IEA | -- |
GO:0006338 | chromatin remodeling | NAS | 12351687 |
GO:0006351 | transcription, DNA-templated | TAS | 2040605 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Fulvestrant | Approved, Investigational | Pharma | Antagonist, Target, antagonist, inhibitor | Estrogen receptor antagonist,high affinity, Hormone therapy | 275 | |
Tamoxifen | Approved | Pharma | Antagonist, Target, antagonist, agonist, Biomarker | TGF-β modulatory and PKC inhibitory effects, ER antagonist, Anti-Estrogens | 446 | |
Toremifene | Approved, Investigational | Pharma | Target, modulator | Estrogen-receptor modulator | 30 | |
Diethylstilbestrol | Approved, Investigational | Pharma | Antagonist, Agonist, Target, agonist | 6 | ||
Estrone | Approved | Pharma | Agonist, Target, agonist | Estrogenic hormone | 23 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
17beta-estradiol |
|
Agonist, Activator |
|
|||
4-hydroxy?aetamoxifen |
|
Antagonist |
|
|||
AC 186 |
|
1421854-16-1 |
|
|
||
beta-Estradiol |
|
50-28-2 |
|
|
||
ICI 182,780 |
|
129453-61-8 |
|
|
Compound | Action | Cas Number |
---|---|---|
AC 186 | Potent and selective ERbeta agonist; neuroprotective | 1421854-16-1 |
beta-Estradiol | Endogenous ER agonist | 50-28-2 |
ICI 182,780 | Estrogen receptor antagonist | 129453-61-8 |
PPT | Subtype-selective ERalpha agonist | 263717-53-9 |
Tamoxifen citrate | Estrogen receptor partial agonist/antagonist | 54965-24-1 |
Compound | Action | Cas Number |
---|---|---|
(E)-2-Decenoic acid | Fatty acid identified in royal jelly | 334-49-6 |
(R)-DPN | 524047-78-7 | |
(R,R)-THC | 138090-06-9 | |
(Z)-2-decenoic acid | Unsaturated short chain fatty acid for biofilm dispersion | 15790-91-7 |
(Z)-4-Hydroxytamoxifen | ER modulator, potent and selective | 68047-06-3 |
Altrenogest | 850-52-2 | |
Bazedoxifene | Estrogen receptor modulator | 198481-32-2 |
Bazedoxifene acetate | Estrogen receptor modulator | 198481-33-3 |
Bazedoxifene HCl | 198480-56-7 | |
Chlorotrianisene | Estrogen agonist | 569-57-3 |
Clomiphene citrate | 50-41-9 | |
Cyclofenil | 2624-43-3 | |
Diethylstilbestrol | 56-53-1 | |
DPN | 1428-67-7 | |
Endoxifen | 112093-28-4 | |
Equol | 531-95-3 | |
ERB 041 | 524684-52-4 | |
Erteberel (LY500307) | 533884-09-2 | |
Estradiol | Sex hormone | 50-28-2 |
Estradiol Benzoate | 50-50-0 | |
Estradiol Cypionate | 313-06-4 | |
Estriol | 50-27-1 | |
Estrone | Estrogenic hormone | 53-16-7 |
Estropipate | 7280-37-7 | |
Ethinyl Estradiol | Oral contraceptive | 57-63-6 |
Ethisterone | Progestogen hormone | 434-03-7 |
Ethynodiol diacetate | 297-76-7 | |
Etonogestrel | 54048-10-1 | |
FERb 033 | 1111084-78-6 | |
Fulvestrant | Estrogen receptor antagonist,high affinity | 129453-61-8 |
G-36 | 1392487-51-2 | |
Gestodene | 60282-87-3 | |
GSK 4716 | 101574-65-6 | |
Hexestrol | 84-16-2 | |
Medroxyprogesterone acetate | Steroidal progestin | 71-58-9 |
Megestrol Acetate | Anti-estrogen agent | 595-33-5 |
Mestranol | Estrogen used in contraceptives | 72-33-3 |
MPP dihydrochloride | 911295-24-4 | |
Ospemifene | 128607-22-7 | |
PHTPP | 805239-56-9 | |
PPT | 263717-53-9 | |
Raloxifene HCl | Estrogen receptor (ER) | 82640-04-8 |
RU 58668 | 151555-47-4 | |
Tamoxifen | TGF-β modulatory and PKC inhibitory effects | 10540-29-1 |
Tamoxifen Citrate | Antiestrogen drug | 54965-24-1 |
Toremifene | Estrogen-receptor modulator | 89778-26-7 |
Toremifene Citrate | 89778-27-8 | |
Ulipristal | 159811-51-5 | |
WAY 200070 | 440122-66-7 | |
Y 134 | 849662-80-2 | |
Zearalenone | 17924-92-4 | |
ZK 164015 | 177583-70-9 | |
α-Estradiol | 57-91-0 |
ExUns: | 1a | · | 1b | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | |||||||||||||||||||
SP2: | - | - | - | ||||||||||||||||
SP3: | - | - | - | - |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
chimpanzee (Pan troglodytes) |
Mammalia | ESR1 33 32 |
|
OneToOne | |
cow (Bos Taurus) |
Mammalia | ESR1 33 32 |
|
OneToOne | |
dog (Canis familiaris) |
Mammalia | ESR1 33 32 |
|
OneToOne | |
oppossum (Monodelphis domestica) |
Mammalia | ESR1 33 |
|
OneToOne | |
mouse (Mus musculus) |
Mammalia | Esr1 17 33 32 |
|
||
rat (Rattus norvegicus) |
Mammalia | Esr1 32 |
|
||
platypus (Ornithorhynchus anatinus) |
Mammalia | ESR1 33 |
|
OneToOne | |
chicken (Gallus gallus) |
Aves | ESR1 33 32 |
|
OneToOne | |
lizard (Anolis carolinensis) |
Reptilia | ESR1 33 |
|
OneToOne | |
tropical clawed frog (Silurana tropicalis) |
Amphibia | esr1 32 |
|
||
LOC394461 32 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | LOC398734 32 |
|
||
zebrafish (Danio rerio) |
Actinopterygii | esr1 33 32 |
|
OneToOne | |
fruit fly (Drosophila melanogaster) |
Insecta | ERR 33 |
|
OneToMany |