Tclin ESR1 Estrogen receptor

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• P03372
• Q13511
• Q14276
• Q5T5H7
• Q6MZQ9
• Q9NU51
• Q9UDZ7
• Q9UIS7
• ER

Gene Name

• ESR1

Ensembl ID

• ENST00000206249
• ENSP00000206249
• ENSG00000091831
• ENST00000338799
• ENSP00000342630
• ENST00000440973
• ENSP00000405330
• ENST00000443427
• ENSP00000387500

Symbol

• ESR
• NR3A1
• ER
• ESR
• Era
• ESRA
• ESTRR
• NR3A1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
drug	1
hub protein	1

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Estrogen Receptor

Protein / Receptor / Estrogen Receptor

Protein / Nucleic Acid Binding / Estrogen Receptor

Protein / ... / C4 Zinc Finger Nuclear Receptor / Estrogen Receptor

DTO Classes

Protein / Nuclear Receptor / Estrogen Receptors / Estrogen Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 15920.85   (req: < 5)

Gene RIFs: 2353   (req: <= 3)

Antibodies: 3731   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 15920.85   (req: >= 5)

Gene RIFs: 2353   (req: > 3)

Antibodies: 3731   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 72

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1443

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 27

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (27)

Explore Approved Drugs

1 – 10 of 27

tamoxifen

ESR1Tclin NR

MODULATOR pKi : 7.51

raloxifene

ESR1Tclin NR

MODULATOR pEC50 : 8

estradiol

ESR1Tclin NR

AGONIST pEC50 : 10.3

ethinylestradiol

ESR1Tclin NR

AGONIST pKd : 9.83

fulvestrant

ESR1Tclin NR

ANTAGONIST pKi : 8.74

diethylstilbestrol

ESR1Tclin NR

AGONIST pKi : 9.66

estrone

ESR1Tclin NR

AGONIST pEC50 : 9.15

estrone sulphate

ESR1Tclin NR

AGONIST :

stanozolol

ESR1Tclin NR

AGONIST :

estriol

ESR1Tclin NR

AGONIST pKi : 8.67

Active Ligands (1443)

Explore Active Ligands

1 – 10 of 1443

Clomiphene

ESR1Tclin NR

pKi : 9

4'-Hydroxynorendoxifen

ESR1Tclin NR

pKi : 6.37

(E)-Norendoxifen

ESR1Tclin NR

pKi : 7.12

CHEMBL415621

ESR1Tclin NR

pKi : 8.34

genistein

ESR1Tclin NR

pKi : 7.41

4-hydroxytamoxifen

ESR1Tclin NR

pKi : 8.24

CHEMBL408376

ESR1Tclin NR

pKi : 8.13

CHEMBL407672

ESR1Tclin NR

pKi : 8.05

CHEMBL406027

ESR1Tclin NR

pKi : 7.77

CHEMBL440251

ESR1Tclin NR

pKi : 7.28

Protein-Protein Interactions (861)

Explore Interacting Targets

1 – 10 of 861

• See Interactions on String-DB

PPP1R14C

Tbio

Family:  Enzyme

Novelty:  0.04635786

p_int:  0.999521064

p_ni:  0.000469328

p_wrong:  0.000009608

Score:  0.379

Data Source:  BioPlex,STRINGDB

GBP1

Tbio

Novelty:  0.00634662

p_int:  0.999302822

p_ni:  0.000697103

p_wrong:  7.5e-8

Score:  0.284

Data Source:  BioPlex,STRINGDB

PGK2

Tbio

Family:  Kinase

Novelty:  0.00832045

p_int:  0.997760062

p_ni:  0.002239523

p_wrong:  4.15e-7

Score:  0.163

Data Source:  BioPlex,STRINGDB

SIGLEC10

Tbio

Novelty:  0.02858542

p_int:  0.993513533

p_ni:  0.006486467

Score:  0.345

Data Source:  BioPlex,STRINGDB

PNMT

Tchem

Family:  Enzyme

Novelty:  0.00178141

p_int:  0.929202421

p_ni:  0.042326228

p_wrong:  0.028471351

Score:  0.555

Data Source:  BioPlex,STRINGDB

CNDP1

Tbio

Family:  Enzyme

Novelty:  0.0102642

p_int:  0.901555575

p_ni:  0.098441636

p_wrong:  0.00000279

Score:  0.194

Data Source:  BioPlex,STRINGDB

NCOA1

Tchem

Family:  Epigenetic

Novelty:  0.00344663

Score:  0.997

Data Source:  Reactome,STRINGDB

NCOA2

Tbio

Novelty:  0.00510052

Score:  0.995

Data Source:  STRINGDB

PELP1

Tbio

Novelty:  0.00817675

Score:  0.995

Data Source:  STRINGDB

AKT1

Tchem

Family:  Kinase

Novelty:  0.00003185

Score:  0.991

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (69)

Reactome (34)

KEGG (8)

PathwayCommons (16)

WikiPathways (11)

Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Constitutive Signaling by Aberrant PI3K in Cancer	75 targets	R-HSA-2219530
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of signal transduction	387 targets	R-HSA-5663202
Reactome	ESR-mediated signaling	189 targets	R-HSA-8939211

Name	Explore in Pharos	Explore in Source
Constitutive Signaling by Aberrant PI3K in Cancer	75 targets	R-HSA-2219530
Deubiquitination	278 targets	R-HSA-5688426
Disease	1105 targets	R-HSA-1643685
Diseases of signal transduction	387 targets	R-HSA-5663202
ESR-mediated signaling	189 targets	R-HSA-8939211

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (84)

Functions (23)

Components (12)

Processes (49)

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1 – 10 of 23

GO Term	Evidence	Assigned by
ATPase binding	Inferred from Direct Assay (IDA)	MGI
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
estrogen receptor activity	Inferred from Direct Assay (IDA)	CAFA
estrogen response element binding	Inferred from Direct Assay (IDA)	UniProtKB
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	NTNU_SB
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II transcription factor activity, estrogen-activated sequence-specific DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
beta-catenin binding	Inferred from Physical Interaction (IPI)	BHF-UCL
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
estrogen receptor binding	Inferred from Physical Interaction (IPI)	CAFA

Disease Associations (null)

No disease associations found

GWAS Traits (39)

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1 – 5 of 39

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	3	18	35		99.9
bone density	EFO_0003923	12	13	20		97.2
body height	EFO_0004339	5	4	6		96.6
estrogen-receptor negative breast cancer	EFO_1000650	2	5	0	1.2	96.2
breast carcinoma	EFO_0000305	13	11	0	1.2	95.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	35		99.9
bone density	EFO_0003923	20		97.2
body height	EFO_0004339	6		96.6
estrogen-receptor negative breast cancer	EFO_1000650	0	1.2	96.2
breast carcinoma	EFO_0000305	0	1.2	95.3

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UniProt Keyword Find Similar Targets

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3D-structure
Activator
Alternative promoter usage
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
DNA-binding

GWAS Trait Find Similar Targets

No Header	No Header
age at first birth measurement
age at first sexual intercourse measurement
alkaline phosphatase measurement
anthropometric measurement
birth weight
blood protein measurement
BMI-adjusted hip circumference
BMI-adjusted waist-hip ratio
body fat distribution
body height

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	estrogen receptor 1	VGNC:2781	463079
Macaque	estrogen receptor 1		613025
Mouse	estrogen receptor 1 (alpha)	MGI:1352467	13982
Rat	estrogen receptor 1	RGD:2581	24890
Dog	estrogen receptor 1	VGNC:40476	403640

Species	Name	OMA	EggNOG	Inparanoid
Chimp	estrogen receptor 1
Macaque	estrogen receptor 1
Mouse	estrogen receptor 1 (alpha)
Rat	estrogen receptor 1
Dog	estrogen receptor 1

Publication Statistics

PubMed Score 15920.85

PubMed score by year

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PubTator Score 12162.96

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Patents

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Related Publications

Text Mined References (2853)

GeneRif Annotations (2353)

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PMID	Year	Title