DegronMD - P03372(ESR1)

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). {ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [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). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}. View more >>

GO - Biological processes (BP): androgen metabolic process [GO:0008209]; antral ovarian follicle growth [GO:0001547]; cellular response to estradiol stimulus [GO:0071392]; cellular response to estrogen stimulus [GO:0071391]; chromatin remodeling [GO:0006338]; epithelial cell development [GO:0002064]; epithelial cell proliferation involved in mammary gland duct elongation [GO:0060750]; intracellular estrogen receptor signaling pathway [GO:0030520]; intracellular steroid hormone receptor signaling pathway [GO:0030518]; male gonad development [GO:0008584]; mammary gland alveolus development [GO:0060749]; mammary gland branching involved in pregnancy [GO:0060745]; negative regulation of DNA-binding transcription factor activity [GO:0043433]; negative regulation of gene expression [GO:0010629]; negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124]; negative regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903799]; negative regulation of transcription by RNA polymerase II [GO:0000122]; phospholipase C-activating G protein-coupled receptor signaling pathway [GO:0007200]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of nitric-oxide synthase activity [GO:0051000]; positive regulation of phospholipase C activity [GO:0010863]; positive regulation of RNA polymerase II transcription preinitiation complex assembly [GO:0045899]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis [GO:0060527]; prostate epithelial cord elongation [GO:0060523]; protein localization to chromatin [GO:0071168]; regulation of apoptotic process [GO:0042981]; regulation of branching involved in prostate gland morphogenesis [GO:0060687]; regulation of inflammatory response [GO:0050727]; regulation of toll-like receptor signaling pathway [GO:0034121]; regulation of transcription, DNA-templated [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to estradiol [GO:0032355]; response to estrogen [GO:0043627]; signal transduction [GO:0007165]; stem cell differentiation [GO:0048863]; uterus development [GO:0060065]; vagina development [GO:0060068] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S576L	TCGA-A5-A0G2	UCEC	TCGA	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation blocking phosphorylation signal	0.75
p.S576L	DO41235	UCEC	ICGC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation blocking phosphorylation signal	0.75
p.T585M	TCGA-AA-A022	COAD	TCGA	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.0556
p.T585M	DO10647	COAD	ICGC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.0556
p.S575L	TCGA-EE-A29M	SKCM	TCGA	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation altering degron motif	0.7667
p.S575L	DO37404	SKCM	ICGC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation altering degron motif	0.7667
p.K581T	TCGA-EO-A22X	UCEC	TCGA	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation substituting flanking lysine	0.2778
p.K581T	DO43907	UCEC	ICGC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation substituting flanking lysine	0.2778
p.T563M	TCGA-KK-A8I6	PRAD	TCGA	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.1111
p.T563M	DO35350	PACA	ICGC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.1111
p.T563M	DO219317	PRAD	ICGC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.1111
p.A569T	SIDM01062	Breast Carcinoma	GDSC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.2778
p.A569T	HDQ-P1	breast	COSMIC	AGSTS	DEG_SPOP_SBC_1	571:575	Mutation rewiring degron network	0.2778

DegronMD: protein-targeted degradation, mutation and drug response to degrons

ESR1

UniProt ID: P03372

Entrez ID: 2099

Protein name: Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1)

External links: UniprotKB HGNC RefSeq COSMIC

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