ESTROGEN SIGNALING PATHWAY (PW:0000507)

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Description

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
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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
RGD:4892064
RGD:5128669
G Esr2 estrogen receptor 2 JBrowse link 6 99,163,953 99,214,711 RGD:1582269
RGD:4892064
RGD:5128669
G Fkbp4 FK506 binding protein 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
RGD:4892084
RGD:5128698
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:4892084
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
Abnormalities, MultipleCrebbp , Gper1
Acute-Phase ReactionNcor1
AdenocarcinomaEsr1 , Esr2 , Ncoa3
Adenocarcinoma of LungCrebbp , Ep300
ADENOCARCINOMA OF STOMACHCrebbp
AdenomaEsr2
Adenoma, Liver CellCarm1
AlopeciaEsr2
Alzheimer DiseaseCrebbp , Ep300 , Esr1 , Esr2 , Hsp90aa1 , Nrip1
Amyotrophic Lateral Sclerosis 1Crebbp
Anxiety DisordersEsr2 , Ncor1
Aortic Valve StenosisEsr2
Arrhythmias, CardiacEsr2
ArteriosclerosisEsr1
Arthritis, ExperimentalEsr1 , Esr2 , Ptges3
Arthritis, RheumatoidEsr2 , Hsp90aa1 , Hspa4
AsthmaCarm1 , Esr2 , Prmt1
AstrocytomaEsr1 , Esr2 , Ncoa3
AtherosclerosisEsr1 , Esr2 , Ptges3
Attention Deficit Disorder with HyperactivityCrebbp
Barrett EsophagusAscc1
bladder urothelial carcinomaCrebbp
Blast CrisisEsr2
Bone Diseases, MetabolicEsr1
Bone NeoplasmsNcoa3
Brain InjuriesHspa4 , Phb2
Brain IschemiaEsr2 , Ppid , Src
Breast Cancer, FamilialEsr1 , Ncor1
Breast NeoplasmsCarm1 , Ep300 , Esr1 , Esr2 , Gper1 , Hsp90aa1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncoa6 , Ncor1 , Ncor2 , Nrip1 , Ptges3 , Src
Bronchial HyperreactivityEsr1
Campomelic DysplasiaSra1
CarcinomaEsr1 , Esr2
Carcinoma in SituEsr1 , Esr2
Carcinoma, Adenoid CysticCrebbp , Ep300
Carcinoma, EndometrioidEsr1
Carcinoma, HepatocellularCarm1 , Crebbp , Ep300 , Esr1 , Med1
Carcinoma, Intraductal, NoninfiltratingSrc
Carcinoma, Non-Small-Cell LungEsr1 , Ncoa3
Carcinoma, Squamous CellCrebbp , Ep300 , Ncoa3
Carcinoma, Squamous Cell of Head and NeckCrebbp , Ep300
Carcinoma, Transitional CellCrebbp , Ep300 , Esr2 , Ncor1
CardiomegalyEp300 , Src
CardiomyopathiesEp300
Cataract, Cortical, Juvenile-OnsetEsr1
Cell Transformation, NeoplasticEsr1
Chagas DiseaseHspa4
Chronic PeriodontitisEsr1
Clear-Cell Metastatic Renal Cell CarcinomaEp300
Cocaine-Related DisordersEsr2
ColitisSrc
colon cancerEp300
Colonic NeoplasmsEp300 , Esr2 , Ncoa6 , Src
colorectal cancerEp300
Colorectal NeoplasmsCrebbp , Ep300 , Esr2 , Src
Coronary Artery DiseaseEsr1 , Esr2
Coronary DiseaseEsr2
Craniofacial AbnormalitiesEp300
Crohn DiseaseEsr2
CryptorchidismEsr1
Cutaneous Squamous Cell CarcinomaDdx5
CystitisEsr2
Cystitis, InterstitialEsr2
DeafnessEsr2
Depressive DisorderEsr2
Dermatitis, ContactEsr2 , Hsp90aa1
Developmental DisabilitiesNcor1
Diabetes Mellitus, ExperimentalEp300 , Esr1 , Hsp90aa1
Diabetes Mellitus, Type 2Ep300 , Esr1 , Hspa4 , Ncoa6 , Src
Diabetic NephropathiesEp300 , Esr1 , Prmt1
Diabetic RetinopathyEp300
Disease Models, AnimalEsr1
Disease ProgressionEsr1
Drug-Induced Liver InjuryMed1
Dry Eye SyndromesHspa4
Encephalomyelitis, Autoimmune, ExperimentalEsr2
Endometrial NeoplasmsEp300 , Esr1 , Esr2 , Ncoa1 , Ncor2 , Nrip1
EndometriosisDdx5 , Esr1 , Esr2 , Med1 , Ncoa1 , Ncoa6 , Ncor1
EndotoxemiaEp300
Esophageal NeoplasmsEp300
Esophageal Squamous Cell CarcinomaCrebbp , Ep300
Estrogen ResistanceEsr1
Female Urogenital DiseasesEsr1
FeminizationEsr1
Fractures, BoneEsr1
Frontotemporal Lobar DegenerationHsp90aa1
Genetic Diseases, InbornCrebbp
GlaucomaCrebbp
Glaucoma, Primary Open AngleEsr2
GlioblastomaCrebbp , Ncor1
GlomerulonephritisEp300 , Esr1
Glomerulonephritis, MembranoproliferativeEp300
GlomerulosclerosisEsr2
Graves DiseaseEsr2
Hashimoto DiseaseEsr2
Hearing LossEsr2
Heart ArrestEp300
Heart DiseasesEp300
Heart FailureNrip1
Heat StrokeHspa4
Hernias, Diaphragmatic, CongenitalEp300
Hirschsprung Disease 1Crebbp
HirsutismEp300
HIV InfectionsHsp90aa1 , Hsp90ab1
Hot FlashesEsr2
Huntington DiseaseNcor1
HyperalgesiaEp300 , Esr1 , Esr2 , Ptges3
HypertensionEp300 , Esr2 , Src
Hypertension, PortalHsp90aa1
Hypertension, PulmonaryEsr1 , Esr2
Hypertrophy, Left VentricularEsr2
HypospadiasEsr2
HypothyroidismNcoa1 , Ncor1
Hypoxia, BrainEp300
Idiopathic Hypogonadotropic HypogonadismSra1
Infarction, Middle Cerebral ArteryHspa4
InfertilityEsr1
Infertility, FemaleEsr1 , Esr2 , Hsp90ab1
Infertility, MaleEsr1
Inflammatory Bowel Disease 11Esr2 , Hspa4
Inflammatory Bowel DiseasesEsr2
Intellectual DisabilityEp300
Ischemic Attack, TransientEp300 , Esr1 , Esr2
Kidney Reperfusion InjuryEp300 , Src
Lead Poisoning, Nervous SystemEp300
LeiomyomaEsr1
Lens DiseasesSiah2
LeukemiaEsr1 , Ncoa3
Leukemia, MyeloidEsr2
Leukemia, Myeloid, AcuteCrebbp , Ncoa2
Leydig Cell TumorEsr1
LithiasisEsr2
Liver Cirrhosis, ExperimentalNcor2
Liver DiseasesDnaja2
Liver NeoplasmsCrebbp , Esr1 , Hspa4 , Ncor1
Long QT SyndromeNrip1
Lung InjuryEsr2
Lung NeoplasmsEsr1 , Ncoa6
Lupus Erythematosus, SystemicEsr2
LymphangioleiomyomatosisEsr1
Lymphoma, FollicularCrebbp
Lymphoma, Large-Cell, AnaplasticHsp90aa1
Lymphoma, T-CellEp300
Macular DegenerationEsr1
Mammary Neoplasms, AnimalEsr1 , Esr2
Mammary Neoplasms, ExperimentalEsr1 , Esr2 , Ncoa1
MedulloblastomaCrebbp , Ep300 , Esr2
MelanomaCrebbp , Ep300 , Esr1 , Esr2 , Stip1
Melanoma, ExperimentalEsr2
MesotheliomaEsr1
MicrocephalyEp300
MicrognathismEp300
Migraine DisordersEsr1
MIGRAINE WITH OR WITHOUT AURA, SUSCEPTIBILITY TO, 1Esr1
Mild Cognitive ImpairmentEsr2 , Hsp90aa1
Multiple SclerosisHsp90ab1
Muscle HypotoniaEp300
Muscular AtrophyHsp90ab1
Muscular Dystrophy, FacioscapulohumeralHspa4
Musculoskeletal PainEsr1
Myasthenia GravisEsr2
Myocardial InfarctionEsr1 , Nrip1
Myocardial Reperfusion InjuryEsr1 , Esr2
MyopiaEp300
Neoplasm InvasivenessEsr1 , Src
Neoplasm MetastasisEsr1 , Hsp90aa1 , Ncoa1 , Src
Neoplasm Recurrence, LocalEsr1
NeoplasmsSrc
Neurodegenerative DiseasesHspa4
Neuropathy, PainfulEp300
ObesityEp300 , Esr1 , Esr2 , Ncoa3
OligodendrogliomaPtges3
OligospermiaEsr1
Optic Nerve InjuriesEp300
OsteoarthritisEsr1 , Ncor2
Osteoarthritis, HandEsr1 , Esr2
Osteoarthritis, HipEsr1
Osteoarthritis, KneeEsr1 , Esr2 , Hsp90aa1
OsteoporosisEsr1 , Esr2 , Nrip1
Osteoporosis, PostmenopausalEsr1 , Esr2 , Nrip1
Osteoporotic FracturesEsr1 , Esr2
Ovarian NeoplasmsEsr1
PancreatitisHsp90ab1
Parkinson DiseaseEsr2 , Hspa4
Parkinsonian DisordersEsr1 , Src
PeritonitisEsr1 , Esr2
Pituitary NeoplasmsEsr2
PleurisyEsr1
Polycystic Kidney, Autosomal RecessiveSrc
Polycystic Ovary SyndromeNcor1
Pre-EclampsiaEsr2
Precursor Cell Lymphoblastic Leukemia-LymphomaCrebbp
Pregnancy ComplicationsNcoa2
Prostatic HyperplasiaEsr1 , Esr2
Prostatic Intraepithelial NeoplasiaCarm1 , Esr1 , Esr2
Prostatic NeoplasmsCarm1 , Crebbp , Ep300 , Esr1 , Esr2 , Hsp90ab1 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor2 , Src
PsoriasisCarm1
Psychoses, Substance-InducedEsr1
Pulmonary Disease, Chronic ObstructiveHspa4
Pulmonary FibrosisHsp90ab1
Reperfusion InjuryEp300 , Src
Respiratory Distress Syndrome, AdultHspa4
Retinal DegenerationEsr2
Rubinstein-Taybi SyndromeCrebbp , Ep300
SchizophreniaNrip1
Scleroderma, SystemicEsr1 , Esr2
ScoliosisCrebbp
SepsisEp300 , Esr2
Sezary SyndromeCrebbp
Shock, HemorrhagicEsr1 , Esr2
Small Cell Lung CarcinomaCrebbp , Ep300
Smith-Magenis SyndromeDdx5 , Med1
Spinal Cord CompressionHspa4
Spinal Cord InjuriesEsr1 , Esr2 , Gper1 , Hsp90ab1
Spinal FracturesEsr1
SPINAL MUSCULAR ATROPHY WITH CONGENITAL BONE FRACTURES 2Ascc1
SplenomegalyEsr2
Squamous Cell Carcinoma of the LungCrebbp , Ep300
Status EpilepticusSrc
Stevens-Johnson SyndromeEp300
StrokeEsr2 , Src
Subarachnoid HemorrhageEsr1
THROMBOCYTOPENIA 6Src
Thumb DeformityCrebbp
Urinary Bladder NeoplasmsCrebbp , Ep300 , Esr1 , Esr2 , Ncor1 , Src
Urination DisordersEsr1 , Esr2
Uterine Cervical NeoplasmsCrebbp , Ep300
Varicose UlcerEsr1 , Esr2
VitiligoEsr1
Vulvar Lichen SclerosusEsr1 , Esr2
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 disease pathwayCrebbp , Ep300 , Ppid
hypoxia inducible factor pathwayCrebbp , Ep300 , Ncoa1 , Ncoa2
influenza A virus infection 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
Mycobacterium tuberculosis infection pathwayCrebbp , Ep300 , Src
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 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 diseases pathwayStip1
prostaglandin biosynthetic pathwayPtges3
prostate cancer pathwayCrebbp , Ep300 , Hsp90aa1 , Hsp90ab1 , Ncoa2 , Ncor2
protein kinase C (PKC) signaling pathwayHsp90aa1
Reelin signaling pathwaySrc
renal cell cancer 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
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: