Biomarker: ERα

Histology type: endometrial carcinoma

Country: Japan

Region: Kyoto

Followed up time :

Subgroup 1 name : ERRFγPositive

Subgroup 1 number: 26

Subgroup 2 name: Negative

Subgroup 2 number: 57

Conclusion: The relationship between ERRF and ER> status could be a predictive marker for the treatment of endometrial cancer, which provides an impetus for the identification of ligands for the ERRF nuclear orphan receptor.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : ERRγ-positive/ERα-negative status

Expression elevation: The ERRF and ER> immunoreactivities were scored in more than 1000 cancer cells, and the percentage of positive cells was indicated as the labeling index.

Statictics: Mean (SD)

Subgroup 1 age: 58.4±1.9

Subgroup 2 age: 56.6 ± 1.6

Funtion Uniprot: 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).20 Publications Isoform 3 Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). 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 (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861).2 Publications

UniProt ID: P03372

UniProt Link: https://www.uniprot.org/uniprotkb/P03372/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Widely expressed (PubMed:10970861). Not expressed in the pituitary gland (PubMed:10970861). Isoform 3 Widely expressed, however not expressed in the pituitary gland.

Subcellular UniProt: #Cell membrane #Cytoplasm #Golgi apparatus #Membrane #Nucleus

Alternative name from UniProt:

Caution: Was reported to be activated by DDX5. However, this study has been retracted due to concerns of image manipulation.

Miscellaneous: Selective estrogen receptor modulators (SERMs), such as tamoxifen, raloxifene, toremifene, lasofoxifene, clomifene, femarelle and ormeloxifene, have tissue selective agonistic and antagonistic effects on the estrogen receptor (ER). They interfere with the ER association with coactivators or corepressors, mainly involving the AF-2 domain.

Recommended name: Estrogen receptor

Gene name from HGNC: ESR1 (ER-alpha, Era, ESR, NR3A1)

HPA class: Cancer-related genes Disease related genes FDA approved drug targets Human disease related genes Nuclear receptors Transcription factors

AlphaFold DB: P03372

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P03372

HPA link: https://www.proteinatlas.org/ENSG00000091831-ESR1

Tissue specificity RNA from HPA: Tissue enhanced (cervix, endometrium, fallopian tube)

Tissue expression from HPA: Selective nuclear expression in female genitalia.

Single cell type specificity Cell type enhanced (Glandular and luminal cells, Breast glandular cells, Endometrial stromal cells, Endometrial ciliated cells, Horizontal cells, Skeletal myocytes, Hepatocytes)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Vesicles

Cancer prognostic summary HPA Prognostic marker in endometrial cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000091831-ESR1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000091831-ESR1/pathology/endometrial+cancer

Phenotype ID: 615363

Disease: Estrogen resistance (ESTRR)

Note1: The disease is caused by variants affecting the gene represented in this entry

OMIM: 133430;615363

OMIM link1: https://www.omim.org/entry/615363

OMIM link2: https://www.omim.org/entry/133430

HGNC ID: HGNC:3467

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3467