Protein / target
Estrogen receptor
Protein at a glance
Biological role
Sequence-specific double-stranded DNA binding
Strongest disease association
Estrogen resistance syndrome
Therapeutic position
Established drug target
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Nuclear hormone receptor.
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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.
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Nuclear receptor signalling
- ·nuclear receptor activity
- ·nuclear receptor-mediated steroid hormone signaling pathway
- ·steroid hormone receptor signaling pathway
- ·Nuclear Receptor transcription pathway
Cell proliferation & survival
- ·PIP3 activates AKT signaling
- ·PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
Receptor tyrosine kinase signalling
- ·Nuclear signaling by ERBB4
Oncogenic signalling
- ·Constitutive Signaling by Aberrant PI3K in Cancer
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
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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
37 medicines meet Open Targets' target-level approved-medicine definition; the 4 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Estrogen receptor alpha agonist
Indicated for Atrophy, Breast Neoplasms, Dyspareunia, Hypogonadism
Estrogen receptor alpha antagonist
Indicated for Breast Neoplasms, Neoplasms
Estrogen receptor alpha agonist
Indicated for Neoplasms
Estrogen receptor alpha agonist
Estrogen receptor alpha degrader
Estrogen receptor modulator
View all 8 targeting drugsHide
Estrogen receptor modulator
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene ESR1
Gene-level evidence surfaced through the gene ESR1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
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 per-type scores above show the calculation.
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Drug development
51 compounds recorded · 37 approved · 13 in clinical development · 1 earlier-stage
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Strong
Other modalities — Strong
View underlying tractability evidence (14)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Label change
Label change: ESTRADIOL (ANDA218507)
- Trial status changed
A Phase Ib/III, Open-label, Randomised Study of Capivasertib Plus CDK4/6 Inhibitors and Fulvestrant Versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)
- Trial status changed
A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)
- Trial status changed
A Randomized, Open-label, Phase III Study of SIM0270 Combined With Everolimus Versus Treatment of Physician's Choice in Patients With CDK4/6 Inhibitors Previously Treated , ER+/HER2- Locally Advanced or Metastatic Breast Cancer
- Trial status changed
An Open-Label, Multicenter, First-in-Human, Phase 1 Study of BBI-940 in Advanced or Metastatic Breast Cancer: Kinesin Oral Molecular Degrader for Oncology (KOMODO-1)
- Label change
Label change: ELACESTRANT (NDA217639)
- Label change
Label change: ESTRADIOL (ANDA075182)
- Label change
Label change: ESTRADIOL (ANDA075182)
- New publicationHormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause : A Systematic Review.
- New publicationTFEB controls syncytiotrophoblast formation and hormone production in placenta.
- New publicationInhibition of lysine acetyltransferase KAT6 in ER<sup>+</sup>HER2<sup>-</sup> metastatic breast cancer: a phase 1 trial.
- New publicationAssociations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.
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.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Related family literature
Papers about “Receptors, Estrogen” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.
via Receptors, Estrogen
via Receptors, Estrogen
via Receptors, Estrogen
via Receptors, Estrogen
via Receptors, Estrogen
via Receptors, Estrogen
via Receptors, Estrogen
Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.
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.