Protein / target
Estrogen receptor
Protein at a glance
Biological role
Sequence-specific double-stranded DNA binding
Primary system
Nervous system
Strongest disease association
breast cancer
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
37 approved · 13 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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)
Subcellular location
Domains and Gene Ontology detail (61)Hide
Domains & features
Gene Ontology
- Cchromatin
- Ccytoplasm
- Ccytosol
- Ceuchromatin
- CGolgi apparatus
- Cmembrane
- Cnucleoplasm
- Cnucleus
- Cplasma membrane
- Cprotein-containing complex
- F14-3-3 protein binding
- FATPase binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Nuclear hormone receptor. The steroid hormones and their receptors are involved in the r…
- ·DNA-binding transcription activator activity, RNA polymerase II-specific
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
Nuclear receptor signalling
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
- ·nuclear receptor activity
- ·nuclear receptor-mediated steroid hormone signaling pathway
G protein-coupled signalling
- ·phospholipase C-activating G protein-coupled receptor signaling pathway
Kinase signalling
- ·protein kinase binding
Immune signalling
- ·Nuclear hormone receptor. The steroid hormones and their receptors are involved in the r…
Proteolysis
- ·Ovarian tumor domain proteases
View underlying pathways (17)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Estrogen receptor alpha agonist
Appears in clinical studies involving menopause, Atrophy, hypogonadism, Premature ovarian insufficiency
Estrogen receptor alpha antagonist
Appears in clinical studies involving breast cancer, breast carcinoma, breast neoplasm, neoplasm
Estrogen receptor alpha agonist
Appears in clinical studies involving neoplasm, prostate cancer
Estrogen receptor alpha agonist
Appears in clinical studies involving premenstrual tension
Estrogen receptor alpha degrader
Appears in clinical studies involving breast cancer, breast neoplasm, neoplasm, Hot flashes
Estrogen receptor modulator
Appears in clinical studies involving osteoporosis, breast cancer, viral infectious disease
Estrogen receptor modulator
Appears in clinical studies involving menopause, Dyspareunia, Atrophy, postmenopausal atrophic vaginitis
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 3,206 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 51 total
contraception
breast cancer · osteoporosis
Atrophy · menopause
prostate cancer
Atrophic Vaginitis · Atrophic Vaginitis · urgency urinary incontinence
menopause · Atrophy
female infertility · hypogonadism · hypogonadotropic hypogonadism
breast cancer · neoplasm · mastodynia
breast cancer · menopause · Atrophy
breast cancer · breast carcinoma · breast neoplasm
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Related literature
Papers indexed under “Receptors, Estrogen” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 7 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Trial status changed
PIKture-01: First-in-Human Study of the PI3KαH1047R Mutant-Selective Inhibitor OKI-219 as Monotherapy in Participants With Advanced Solid Tumors and as Part of Combination Therapy in Participants With Advanced Breast Cancer
- Industry developmentSorption and desorption of 17α−ethinylestradiol (EE2) and β−estradiol (E2) to nylon microparticles
- Label change
Label change: ELACESTRANT (NDA217639)
- Label change
Label change: ESTRADIOL (ANDA075182)
- Label change
Label change: ESTRADIOL (ANDA075182)
- Label change
Label change: ESTRADIOL (ANDA075182)
- New publicationThe association between sex hormones and bone mineral density in US females.
- Label change
Label change: OSPEMIFENE (NDA203505)
- New publicationHormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause : A Systematic Review.
- New publicationMetabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations.
- New publicationSex hormones differently regulate lipid metabolism genes in primary human hepatocytes.
- New publicationTFEB controls syncytiotrophoblast formation and hormone production in placenta.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.