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: 31936.78   (req: < 5)

Gene RIFs: 2794   (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: 31936.78   (req: >= 5)

Gene RIFs: 2794   (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: 1606

Tclin

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

Active Drugs: 27