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Estrogen signaling via the classical pathway mediated by the estrogen receptor alpha and beta, Esr1 and Esr2, respectively and via the non-classical (non-genomic) pathway mediated by the G-protein coupled receptor Gper (also known as GPR30) and membrane bound Esr receptors, plays key roles in several important biological processes. Estrogen is essential for female sexual development and reproductive functions; it is also important in bone and cardiovascular systems and in brain functions. The tw

Pathway Diagram:

Ariadne Genomics Inc. ERs coactivators ERs corepressors ERs chaperones G protein mediated signaling pathway via Galphas family membrane tethered ERs - rapid, non-genomic effects Esr1 ---> direct and indirect target gene expression Esr1 ---> direct and indirect target gene expression ERs corepressors ---| Esr2 ERs corepressors ---| Esr1 Src ---> epidermal growth factor/neuregulin signaling pathway Src G protein mediated signaling pathway via Galphas family --+> cAMP ERs coactivators --+> Esr1 ERs coactivators ---- Esr1 Esr2 ---> direct and indirect target gene expression direct and indirect target gene expression Esr2 Esr2 ---> direct and indirect target gene expression Esr1 ERs coactivators ---- Esr2 ERs corepressors ---- Esr2 ERs corepressors ---- Esr1 ERs coactivators --+> Esr2 ERs chaperones ---- Esr2 ERs chaperones ---- Esr1 Esr1 ---- estradiol Esr2 ---- estradiol estradiol ---- Gper cAMP G protein mediated signaling pathway via Galphas family --+> Src mERs estradiol ---- mERs mERs ---- Src Gper epidermal growth factor/neuregulin signaling pathway estradiol biosynthetic pathway estradiol

Genes in Pathway:

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estrogen signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Ascc1 activating signal cointegrator 1 complex subunit 1 JBrowse link 20 29,558,330 29,648,899 RGD:5128512
G Calcoco1 calcium binding and coiled coil domain 1 JBrowse link 7 144,307,562 144,322,253 RGD:5128512
G Carm1 coactivator-associated arginine methyltransferase 1 JBrowse link 8 22,577,723 22,622,555 RGD:5128512
G Crebbp CREB binding protein JBrowse link 10 11,590,994 11,721,039 RGD:5128512
G Ddx5 DEAD-box helicase 5 JBrowse link 10 94,979,759 94,988,461 RGD:5128512
G Dnaja2 DnaJ heat shock protein family (Hsp40) member A2 JBrowse link 19 22,569,999 22,588,143 RGD:4892102
G Ep300 E1A binding protein p300 JBrowse link 7 122,818,194 122,889,055 RGD:5128512
G Esr1 estrogen receptor 1 JBrowse link 1 41,192,029 41,594,799 RGD:1580338
G Esr2 estrogen receptor 2 JBrowse link 6 99,163,953 99,214,711 RGD:1582269
G Fkbp4 FKBP prolyl isomerase 4 JBrowse link 4 161,748,993 161,757,447 RGD:4892102
G Gper1 G protein-coupled estrogen receptor 1 JBrowse link 12 17,309,122 17,315,267 RGD:4892064
G Hsp90aa1 heat shock protein 90 alpha family class A member 1 JBrowse link 6 135,107,262 135,112,793 RGD:4892102
G Hsp90ab1 heat shock protein 90 alpha family class B member 1 JBrowse link 9 17,817,791 17,823,163 RGD:4892102
G Hspa4 heat shock protein family A member 4 JBrowse link 10 38,601,624 38,642,397 RGD:4892102
G Med1 mediator complex subunit 1 JBrowse link 10 86,101,560 86,145,271 RGD:5128512
G Ncoa1 nuclear receptor coactivator 1 JBrowse link 6 28,677,563 28,931,844 RGD:5128512
G Ncoa2 nuclear receptor coactivator 2 JBrowse link 5 5,466,544 5,696,540 RGD:5128512
G Ncoa3 nuclear receptor coactivator 3 JBrowse link 3 162,692,176 162,788,582 RGD:5128512
G Ncoa6 nuclear receptor coactivator 6 JBrowse link 3 150,919,317 150,990,391 RGD:5128512
G Ncor1 nuclear receptor co-repressor 1 JBrowse link 10 48,629,121 48,772,890 RGD:5128512
G Ncor2 nuclear receptor co-repressor 2 JBrowse link 12 36,871,917 37,033,701 RGD:5128512
G Nrip1 nuclear receptor interacting protein 1 JBrowse link 11 14,658,225 14,742,478 RGD:5128512
G Phb2 prohibitin 2 JBrowse link 4 157,230,769 157,235,375 RGD:5128512
G Ppid peptidylprolyl isomerase D JBrowse link 2 178,354,830 178,366,843 RGD:4892102
G Prmt1 protein arginine methyltransferase 1 JBrowse link 1 100,971,132 100,980,411 RGD:5128512
G Ptges3 prostaglandin E synthase 3 JBrowse link 7 2,479,267 2,497,024 RGD:4892102
G Siah2 siah E3 ubiquitin protein ligase 2 JBrowse link 2 148,874,151 148,891,900 RGD:5128512
G Sra1 steroid receptor RNA activator 1 JBrowse link 18 29,494,004 29,497,232 RGD:5128512
G Src SRC proto-oncogene, non-receptor tyrosine kinase JBrowse link 3 153,547,807 153,595,643 RGD:5128669
G Stip1 stress-induced phosphoprotein 1 JBrowse link 1 222,274,133 222,293,139 RGD:4892102

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Functional ClassErs chaperonesestrogen receptor chaperones
Functional ClassERs coactivatorsestrogen receptor coactivators
Functional ClassErs corepressorsestrogen receptor corepressors

Pathway Gene Annotations

Disease Annotations Associated with Genes in the estrogen signaling pathway
Disease TermsGene Symbols
acute myeloid leukemiaCrebbp , Ncoa2
Acute-Phase ReactionNcor1
adenocarcinomaEsr1 , Esr2 , Ncoa3
adenoid cystic carcinomaCrebbp , Ep300
adult respiratory distress syndromeHspa4
Alzheimer's diseaseCrebbp , Ep300 , Esr1 , Esr2 , Hsp90aa1 , Nrip1
amyotrophic lateral sclerosis type 1Crebbp
anaplastic large cell lymphomaHsp90aa1
androgen insensitivity syndromeFkbp4
Animal Disease ModelsEsr1
Animal Mammary NeoplasmsEsr1 , Esr2
anxiety disorderEsr2 , Ncor1
aortic valve stenosisEsr2
asthmaCarm1 , Esr2 , Prmt1
astrocytomaEsr1 , Esr2 , Ncoa3
atherosclerosisEsr1 , Esr2 , Ptges3
atrial fibrillationEsr2
atrial heart septal defectCrebbp
attention deficit hyperactivity disorderCrebbp
autistic disorderCrebbp
autosomal recessive polycystic kidney diseaseSrc
Autosomal Recessive Spinocerebellar Ataxia 8Esr1
Barrett's esophagusAscc1
bladder urothelial carcinomaCrebbp , Ep300
Blast CrisisEsr2
bone diseaseEsr1
Bone FracturesEsr1
Bone NeoplasmsNcoa3
Brain HypoxiaEp300
Brain InjuriesHspa4 , Phb2
brain ischemiaEsr2 , Ppid , Src
breast cancerEsr1 , Esr2 , Ncoa6
Breast Cancer, FamilialEsr1 , Ncor1
Breast NeoplasmsCarm1 , Ep300 , Esr1 , Esr2 , Gper1 , Hsp90aa1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Nrip1 , Ptges3 , Src
Bronchial HyperreactivityEsr1
campomelic dysplasiaSra1
carcinomaEsr1 , Esr2
cardiac arrestEp300
Cardiac ArrhythmiasEsr2
CardiomegalyEp300 , Src
cataract 33Esr1
Cell Transformation, NeoplasticEsr1
central nervous system diseaseCrebbp
cerebellar ataxiaEsr1
Chagas diseaseHspa4
Chemical and Drug Induced Liver InjuryMed1
chronic obstructive pulmonary diseaseHspa4
Chronic PeriodontitisEsr1
clear cell renal cell carcinomaEp300
Cocaine-Related DisordersEsr2
Cognitive DysfunctionEsr2 , Hsp90aa1
colitisEsr2 , Src
colon cancerNcoa6 , Src
colon carcinomaEp300
Colonic NeoplasmsEsr2 , Src
colorectal cancerEp300 , Src
Colorectal NeoplasmsCrebbp , Ep300 , Esr2 , Src
congenital diaphragmatic herniaEp300
congestive heart failureEp300 , Med1 , Nrip1
contact dermatitisEsr2 , Hsp90aa1
coronary artery diseaseEsr1 , Esr2
Coronary DiseaseEsr2
Craniofacial AbnormalitiesEp300
Crohn's diseaseEsr2
Developmental DisabilitiesCrebbp , Ep300 , Ncor1
Diabetes Mellitus, Experimental Ep300 , Esr1 , Hsp90aa1
Diabetic NephropathiesEp300 , Esr1 , Prmt1
diabetic retinopathyEp300
dilated cardiomyopathyMed1
disease of cellular proliferationSrc
Disease ProgressionEsr1
dry eye syndromeHspa4
ductal carcinoma in situSrc
Emery-Dreifuss muscular dystrophyEsr1
Endometrial NeoplasmsEp300 , Esr1 , Esr2 , Ncoa1 , Ncor2 , Nrip1
Endometrioid CarcinomasEsr1
endometriosisDdx5 , Esr1 , Esr2 , Med1 , Ncoa1 , Ncoa6 , Ncor1
esophageal carcinomaEp300
Estrogen ResistanceEsr1
Experimental ArthritisEsr1 , Esr2 , Ptges3
Experimental Autoimmune EncephalomyelitisEsr2
Experimental Liver CirrhosisNcor2
Experimental MelanomaEsr2
facioscapulohumeral muscular dystrophyHspa4
Female InfertilityEsr1 , Esr2 , Hsp90ab1
Female Urogenital DiseasesEsr1
follicular lymphomaCrebbp
Frontotemporal Lobar DegenerationHsp90aa1
gastric adenocarcinomaCrebbp
genetic diseaseCrebbp , Ep300
glioblastoma multiformeCrebbp , Ncor1
glomerulonephritisEp300 , Esr1
Graves' diseaseEsr2
Hashimoto DiseaseEsr2
head and neck squamous cell carcinomaCrebbp , Ep300
Hearing LossEsr2
heart diseaseEp300
Heat StrokeHspa4
hepatocellular adenomaCarm1
hepatocellular carcinomaCarm1 , Crebbp , Ep300 , Esr1 , Med1
Hereditary Neoplastic SyndromesHspa4 , Sra1
Hirschsprung Disease 1Crebbp
Hot FlashesEsr2
human immunodeficiency virus infectious diseaseHsp90aa1 , Hsp90ab1
Huntington's diseaseCrebbp , Ep300 , Ncor1
HyperalgesiaEp300 , Esr1 , Esr2 , Ptges3
hyperkalemic periodic paralysisDdx5
hypertensionEp300 , Esr2 , Src
hypogonadotropic hypogonadism 7 with or without anosmiaSra1
hypothyroidismNcoa1 , Ncor1
in situ carcinomaEsr1 , Esr2
inflammatory bowel diseaseEsr2
intellectual disabilityEp300
interstitial cystitisEsr2
Kidney Reperfusion InjuryEp300 , Src
Knee OsteoarthritisEsr1 , Esr2 , Hsp90aa1
Lead Poisoning, Nervous SystemEp300
Left Ventricular HypertrophyEsr2
lens diseaseSiah2
leukemiaEsr1 , Ncoa3
Leydig cell tumorEsr1
liver benign neoplasmEsr1 , Hspa4 , Ncor1
liver cancerCrebbp
liver diseaseDnaja2
long QT syndromeNcoa6 , Nrip1
lung cancerNcoa6
Lung InjuryEsr2
Lung NeoplasmsEsr1
lung small cell carcinomaCrebbp , Ep300
lung squamous cell carcinomaCrebbp , Ep300
macular degenerationEsr1
male infertilityEsr1
Mammary Neoplasms, ExperimentalEsr1 , Esr2 , Ncoa1
medulloblastomaCrebbp , Ep300 , Esr2
melanomaCrebbp , Ep300 , Esr1 , Esr2 , Stip1
membranoproliferative glomerulonephritisEp300
mental depressionEsr2
Metabolic Bone DiseasesEsr1
middle cerebral artery infarctionHspa4
Multiple AbnormalitiesCrebbp , Ep300 , Gper1
multiple sclerosisHsp90ab1
Muscle HypotoniaEp300
Muscle SpasticityCrebbp
muscular atrophyHsp90ab1
Musculoskeletal PainEsr1
myasthenia gravisEsr2
myelodysplastic syndromeCrebbp
myeloid leukemiaEsr2
myocardial infarctionEsr1 , Nrip1
Myocardial Reperfusion InjuryEsr1 , Esr2
Neonatal HyperbilirubinemiaNcor1
Neoplasm InvasivenessEsr1 , Src
Neoplasm MetastasisEsr1 , Hsp90aa1 , Ncoa1 , Src
Neoplasm Recurrence, LocalEsr1
nephronophthisis-like nephropathy 1Ep300
neurodegenerative diseaseHspa4
non-small cell lung carcinomaEsr1 , Ncoa3
obesityEp300 , Esr1 , Esr2 , Ncoa1 , Ncoa3
Optic Nerve InjuriesEp300
osteoarthritisEsr1 , Ncor2
Osteoarthritis, HandEsr1 , Esr2
Osteoarthritis, HipEsr1
osteoporosisEsr1 , Esr2 , Nrip1
Osteoporotic FracturesEsr1 , Esr2
Ovarian NeoplasmsEsr1
Painful NeuropathyEp300
Parkinson's diseaseEsr2 , Hspa4
Parkinsonian DisordersEsr1 , Src
peritonitisEsr1 , Esr2
Pituitary NeoplasmsEsr2
polycystic ovary syndromeNcor1
portal hypertensionHsp90aa1
Postmenopausal OsteoporosisEsr1 , Esr2 , Nrip1
precursor lymphoblastic lymphoma/leukemiaCrebbp
Pregnancy ComplicationsNcoa2
primary open angle glaucomaEsr2
prostate cancerEsr2 , Med1
prostate carcinoma in situCarm1 , Esr1 , Esr2
prostatic hypertrophyEsr1 , Esr2
Prostatic NeoplasmsCarm1 , Crebbp , Ep300 , Esr1 , Esr2 , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Src
pulmonary fibrosisHsp90ab1
pulmonary hypertensionEsr1 , Esr2
Reperfusion InjuryEp300 , Src
retinal degenerationEsr2
rheumatoid arthritisEsr2 , Hsp90aa1 , Hspa4
Rubinstein-Taybi syndromeCrebbp , Ep300
SepsisEp300 , Esr2
Sezary's diseaseCrebbp
Shock, HemorrhagicEsr1 , Esr2
skin squamous cell carcinomaDdx5
Smith-Magenis syndromeDdx5 , Med1
spina bifidaCrebbp
Spinal Cord CompressionHspa4
Spinal Cord InjuriesEsr1 , Esr2 , Gper1 , Hsp90ab1
Spinal FracturesEsr1
squamous cell carcinomaCrebbp , Ep300 , Ncoa3
status epilepticusSrc
Stevens-Johnson syndromeEp300
StrokeEsr2 , Src
Subarachnoid HemorrhageEsr1
substance-induced psychosisEsr1
systemic lupus erythematosusEp300 , Esr2
systemic sclerodermaEsr1 , Esr2
T-Cell LymphomaEp300
Thumb DeformityCrebbp , Ep300
thyroid hormone resistance syndromeNcoa1
toxic encephalopathyPtges3
transient cerebral ischemiaEp300 , Esr1 , Esr2
transitional cell carcinomaCrebbp , Ep300 , Esr2 , Ncor1
type 2 diabetes mellitusEp300 , Esr1 , Hspa4 , Ncoa6 , Src
ulcerative colitisEsr2 , Hspa4
urinary bladder cancerCrebbp , Ep300 , Esr1 , Esr2 , Ncor1 , Src
Urination DisordersEsr1 , Esr2
Uterine Cervical NeoplasmsCrebbp , Ep300
Varicose UlcerEsr1 , Esr2
Vulvar Lichen SclerosusEsr1 , Esr2
Williams-Beuren syndromeSrc
Pathway Annotations Associated with Genes in the estrogen signaling pathway
Pathway TermsGene Symbols
aldosterone signaling pathwayCrebbp , Fkbp4 , Hsp90aa1 , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncor1 , Ncor2 , Ptges3
altered androgen signaling pathwayNcoa2 , Ncor2
altered Reelin signaling pathwaySrc
androgen signaling pathwayCarm1 , Crebbp , Dnaja2 , Ep300 , Hsp90aa1 , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Prmt1 , Stip1
antigen processing and presentation pathwayHsp90aa1 , Hsp90ab1 , Hspa4
bisphenol A response pathwayEsr1 , Esr2 , Gper1
calcium/calcium-mediated signaling pathwayPpid
cell cycle pathway, mitoticCrebbp , Ep300
chaperone mediated autophagy pathwayHsp90aa1 , Stip1
cortisol signaling pathwayCrebbp , Dnaja2 , Ep300 , Fkbp4 , Hsp90aa1 , Hsp90ab1 , Hspa4 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Ptges3 , Stip1
dopamine signaling pathwaySrc
E-cadherin signaling pathwaySrc
eicosanoid signaling pathwaySrc
endocytosis pathwaySrc
Endoplasmic Reticulum-associated degradation pathwayDnaja2 , Hsp90aa1 , Hsp90ab1
endothelin signaling pathwaySrc
ephrin - ephrin receptor bidirectional signaling axisSrc
epidermal growth factor/neuregulin signaling pathwayHsp90aa1 , Src
estrogen signaling pathwayAscc1 , Calcoco1 , Carm1 , Crebbp , Ddx5 , Dnaja2 , Ep300 , Esr1 , Esr2 , Fkbp4 , Gper1 , Hsp90aa1 , Hsp90ab1 , Hspa4 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncoa6 , Ncor1 , Ncor2 , Nrip1 , Phb2 , Ppid , Prmt1 , Ptges3 , Siah2 , Sra1 , Src , Stip1
FasL mediated signaling pathwaySrc
fibroblast growth factor signaling pathwaySrc
follicle-stimulating hormone signaling pathwayEsr1
forkhead class A signaling pathwayCrebbp , Ep300 , Esr1 , Ncoa3 , Nrip1
G protein mediated signaling pathway via Galphas familyGper1
glypican signaling pathwaySrc
gonadotropin-releasing hormone signaling pathwaySrc
Hedgehog signaling pathwayCrebbp
histamine signaling pathway, immunologicalEsr1
histone modification pathwayCarm1 , Crebbp , Ep300 , Ncoa6 , Prmt1
homocysteine metabolic pathwayCarm1 , Prmt1
Huntington's disease pathwayCrebbp , Ep300 , Ppid
hypoxia inducible factor pathwayCrebbp , Ep300 , Ncoa1 , Ncoa2
influenza A pathwayCrebbp , Ep300
insulin-like growth factor signaling pathwayEsr1
Jak-Stat signaling pathwayCrebbp , Ep300
long term potentiationCrebbp , Ep300
luteinizing hormone signaling pathwayEsr1
methionine cycle/metabolic pathwayCarm1 , Prmt1
mitochondria fusion pathwayPhb2
mitochondrial autophagy pathwaySrc
nerve growth factor signaling pathwaySrc
NOD-like receptor signaling pathwayHsp90aa1 , Hsp90ab1
Notch signaling pathwayCrebbp , Ep300 , Ncor1 , Ncor2
nuclear factor kappa B signaling pathwaySrc
nuclear factor, erythroid 2 like 2 signaling pathwayCrebbp , Ncoa3 , Siah2
p53 signaling pathwayCrebbp , Ep300
Parkinson's disease pathwayPpid
phosphatidylinositol 3-kinase class I signaling pathwayHsp90aa1 , Src
phosphatidylinositol 3-kinase-Akt signaling pathwayHsp90aa1 , Src
platelet-derived growth factor signaling pathwaySrc
prednisolone pharmacodynamics pathwayHsp90aa1
prednisolone pharmacokinetics pathwayHsp90aa1
prion disease pathwayStip1
prostaglandin biosynthetic pathwayPtges3
prostate cancer pathwayCrebbp , Ep300 , Hsp90aa1 , Hsp90ab1 , Ncoa2 , Ncor2
protein kinase C (PKC) signaling pathwayHsp90aa1
Reelin signaling pathwaySrc
renal cell carcinoma pathwayCrebbp , Ep300
retinoic acid signaling pathwayNcoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Nrip1
RNA polymerase I transcription pathwayCrebbp
RNA polymerase II transcription pathwayMed1
scatter factor/hepatocyte growth factor signaling pathwaySrc
serotonin signaling pathway via receptors engaging G alphas protein familyEsr1
signaling pathway pertinent to the brain and nervous systemSrc
somatostatin signaling pathwaySrc
sphingosine 1-phosphate signaling pathwaySrc
spliceosome pathwayDdx5
syndecan signaling pathwaySrc
tamoxifen pharmacodynamics pathwayEsr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Phb2
tamoxifen pharmacokinetics pathwayEsr1
transforming growth factor-beta Smad dependent signaling pathwayCrebbp
transforming growth factor-beta superfamily mediated signaling pathwayCrebbp , Ep300
tuberculosis pathwayCrebbp , Ep300 , Src
type II interferon signaling pathwayCrebbp , Ep300
ubiquitin/proteasome degradation pathwaySrc
vascular endothelial growth factor signaling pathwayHsp90aa1 , Hsp90ab1 , Src
Wnt signaling pathwayCrebbp , Ep300
Wnt signaling, canonical pathwayCrebbp
Phenotype Annotations Associated with Genes in the estrogen signaling pathway

References Associated with the estrogen signaling pathway:

Ontology Path Diagram:

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Import into Pathway Studio: