ESR1 - Estrogen receptor - human protein (Function)
 
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ESR1 »  Estrogen receptor  (ER)
 
Protein also known as:  Nuclear receptor subfamily 3 group A member 1.
Gene name:  ESR1
Family name: Nuclear hormone receptor » NR3
Entry whose protein(s) existence is based on evidence at protein level
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1 1619 4
GENE REF ISO

Function

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Overview 
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.  
19
  • CuratedUniProtKB
Isoform  Iso 3   Can bind to ERE and inhibit isoform 1.  
19
  • CuratedUniProtKB
Isoform  Iso 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.  
19
  • CuratedUniProtKB
GO molecular function 
Beta-catenin bindingdefinition[GO:0008013]  
1
  • IPIBHF-UCL
Chromatin bindingdefinition[GO:0003682] silver  
  • IEAOrtholog Compara
Core promoter sequence-specific DNA bindingdefinition[GO:0001046]  
1
  • IDAUniProtKB
Enzyme bindingdefinition[GO:0019899]  
2
  • IPIUniProtKB
Estrogen receptor activitydefinition[GO:0030284]  
1
  • NASUniProtKB
Estrogen response element bindingdefinition[GO:0034056]  
2
  • IDAUniProtKB
Estrogen-activated sequence-specific DNA binding RNA polymerase II transcription factor activitydefinition[GO:0038052]  
1
  • IGIMGI
Identical protein bindingdefinition[GO:0042802]  
4
  • IPIIntAct
Nitric-oxide synthase regulator activitydefinition[GO:0030235]  
1
  • NASUniProtKB
Protein bindingdefinition[GO:0005515]  
62
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
RNA polymerase II core promoter proximal region sequence-specific DNA bindingdefinition[GO:0000978]  
1
  • IDANTNU_SB
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcriptiondefinition[GO:0001077]  
1
  • IDANTNU_SB
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
1
  • NASBHF-UCL
Steroid bindingdefinition[GO:0005496]  
  • ISSOrtholog Curator
Steroid hormone receptor activitydefinition[GO:0003707]  
1
  • TASPINC
Transcription factor bindingdefinition[GO:0008134] silver  
  • IEAOrtholog Compara
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Androgen metabolic processdefinition[GO:0008209] silver  
  • IEAOrtholog Compara
Antral ovarian follicle growthdefinition[GO:0001547] silver  
  • IEAOrtholog Compara
Cellular response to estradiol stimulusdefinition[GO:0071392]  
  • ISSOrtholog Curator
Chromatin remodelingdefinition[GO:0006338]  
1
  • NASUniProtKB
Epithelial cell developmentdefinition[GO:0002064] silver  
  • IEAOrtholog Compara
Epithelial cell proliferation involved in mammary gland duct elongationdefinition[GO:0060750] silver  
  • IEAOrtholog Compara
Intracellular estrogen receptor signaling pathwaydefinition[GO:0030520]  
1
  • NASUniProtKB
Intracellular steroid hormone receptor signaling pathwaydefinition[GO:0030518]  
  • ISSOrtholog Curator
Male gonad developmentdefinition[GO:0008584] silver  
  • IEAOrtholog Compara
Mammary gland alveolus developmentdefinition[GO:0060749] silver  
  • IEAOrtholog Compara
Mammary gland branching involved in pregnancydefinition[GO:0060745] silver  
  • IEAOrtholog Compara
Negative regulation of gene expressiondefinition[GO:0010629]  
1
  • IDAUniProtKB
Negative regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043124]  
2
  • IDAUniProtKB
Negative regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0043433]  
1
  • IDAUniProtKB
Phospholipase C-activating G-protein coupled receptor signaling pathwaydefinition[GO:0007200]  
  • ISSOrtholog Curator
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204]  
  • ISSOrtholog Curator
Positive regulation of fibroblast proliferationdefinition[GO:0048146] silver  
  • IEAOrtholog Compara
Isoform  Iso 3   Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429]  
1
  • IDAUniProtKB
Isoform  Iso 3   Positive regulation of nitric-oxide synthase activitydefinition[GO:0051000]  
1
  • IDAUniProtKB
Positive regulation of phospholipase C activitydefinition[GO:0010863]  
  • ISSOrtholog Curator
Positive regulation of retinoic acid receptor signaling pathwaydefinition[GO:0048386]  
1
  • IDABHF-UCL
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
2
  • IDAUniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
2
  • IDAUniProtKB
  • IDANTNU_SB
Prostate epithelial cord arborization involved in prostate glandular acinus morphogenesisdefinition[GO:0060527] silver  
  • IEAOrtholog Compara
Prostate epithelial cord elongationdefinition[GO:0060523] silver  
  • IEAOrtholog Compara
Regulation of apoptotic processdefinition[GO:0042981] silver  
  • IEAOrtholog Compara
Regulation of branching involved in prostate gland morphogenesisdefinition[GO:0060687] silver  
  • IEAOrtholog Compara
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • NASUniProtKB
Response to estradioldefinition[GO:0032355]  
1
  • IDABHF-UCL
Response to estrogendefinition[GO:0043627]  
1
  • IDAUniProtKB
Signal transductiondefinition[GO:0007165]  
2
  • TASPINC
Steroid hormone mediated signaling pathwaydefinition[GO:0043401] silver  
  • IEAInterPro 2 GO
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • TASPINC
Uterus developmentdefinition[GO:0060065] silver  
  • IEAOrtholog Compara
Vagina developmentdefinition[GO:0060068] silver  
  • IEAOrtholog Compara
Pathways 
According to KEGG, this protein belongs to the following pathway:
Endocrine and other factor-regulated calcium reabsorption  hsa04961+2099  
According to Reactome, this protein belongs to the following pathways:
Nuclear Receptor transcription pathway  REACT_15525  
Nuclear signaling by ERBB4  REACT_116022  
Note 
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.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Receptor  definition   [KW-0675]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Estrogen_receptor_alpha
GenomeRNAi: 2099
PRO: PR:P03372
Chemistry
GuidetoPHARMACOLOGY: 620