NUCLEAR FACTOR, ERYTHROID 2 LIKE 2 SIGNALING PATHWAY (PW:0000369)

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Description

The nuclear factor, erythroid 2 like 2 (Nfe2l2, known as Nrf2) signaling pathway is one of the most important regulators of antioxidant and electrophilic stress responses. Upon activation, the Nrf2 transcription factor induces the expression of antioxidant, xenobiotic metabolism and cytoprotective genes and also controls the expression of genes involved in intermediary metabolism. Under unstressed conditions, Nrf2 is sequestered in the cytoplasm by the ubiquitin E3 ligase adaptor Keap1, and only

Pathway Diagram:

Elsevier Inc. Gsk3b Kelch-repeat BTB ---> CTR Neh6 Neh2 ---- Neh3 Keap1 Pten Sqstm1 mTorc1 complex electrophiles ---| Pten ROS ---| Pten electrophiles ROS Btrc environmental cues cellular stresses Nfe2l2 target genes Cul3/Rbx1 complex ---| Nfe2l2 Skp1/Cul1/Rbx1 complex ---| Nfe2l2 Cul3/Rbx1 complex ---> Nfe2l2 Keap1 ---- Nfe2l2 small MAFs mTOR signaling pathway <++> phosphatidylinositol 3-kinase-Akt signaling pathway cellular stresses --+> phosphatidylinositol 3-kinase-Akt signaling pathway environmental cues --+> mTOR signaling pathway Skp1/Cul1/Rbx1 complex ---> Nfe2l2 Gsk3b --+> Btrc Crebbp ROS ---| Keap1 electrophiles ---| Keap1 nuclear Nfe2l2 nuclear Nfe2l2 ---- small MAFs Neh1 Gsk3b ---> Nfe2l2 Gsk3a ---> Nfe2l2 Btrc ---- Nfe2l2 phosphatidylinositol 3-kinase-Akt signaling pathway ---> Gsk3b phosphatidylinositol 3-kinase-Akt signaling pathway ---| Gsk3b phosphatidylinositol 3-kinase-Akt signaling pathway ---| Gsk3a phosphatidylinositol 3-kinase-Akt signaling pathway ---> Gsk3a IVR Gsk3a ROS --+> nuclear Nfe2l2 electrophiles --+> nuclear Nfe2l2 nuclear Nfe2l2 ---> Nfe2l2 target genes small MAFs ---> Nfe2l2 target genes Pten --+> Gsk3b Pten ---> Gsk3b Pten --+> Gsk3a Pten ---> Gsk3a C226/C613 preferring C273/C288 preferring C434 preferring CTR Skp1/Cul1/Rbx1 complex Nfe2l2 Nfe2l2 interactors ---> Nfe2l2 Keap1 ---- Keap1 interactors Keap1 interactors ---| Keap1 mTorc1 complex ---> Sqstm1 mTorc1 complex --+> Sqstm1 Neh7 Crebbp ---- Neh5 Crebbp ---- Neh4 Neh4 Neh5 Ncoa3 ---- Neh5 Ncoa3 ---- Neh4 Nfe2l2 ---- Nfe2l2 interactors Ncoa3 Chd6 Neh3 Chd6 ---- Neh3 C151 preferring 3-box BTB Neh2 mTOR signaling pathway phosphatidylinositol 3-kinase-Akt signaling pathway Cul3/Rbx1 complex Keap1 interactors Nfe2l2 interactors
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Genes in Pathway:

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nuclear factor, erythroid 2 like 2 signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Brca1 BRCA1, DNA repair associated JBrowse link 10 89,394,821 89,455,093 RGD:11535066
G Btrc beta-transducin repeat containing E3 ubiquitin protein ligase JBrowse link 1 265,100,094 265,270,263 RGD:11535066
RGD:11535070
G Cdkn1a cyclin-dependent kinase inhibitor 1A JBrowse link 20 6,348,422 6,358,864 RGD:11535066
G Chd6 chromodomain helicase DNA binding protein 6 JBrowse link 3 156,937,746 157,099,328 RGD:11535066
G Crebbp CREB binding protein JBrowse link 10 11,590,994 11,721,039 RGD:11535066
G Cul1 cullin 1 JBrowse link 4 77,211,814 77,283,369 RGD:11535066
G Cul3 cullin 3 JBrowse link 9 86,044,485 86,129,066 RGD:11535066
G Dpp3 dipeptidylpeptidase 3 JBrowse link 1 220,166,124 220,189,762 RGD:11535066
G Gadd45gip1 GADD45G interacting protein 1 JBrowse link 19 25,946,979 25,949,528 RGD:11535066
G Gsk3a glycogen synthase kinase 3 alpha JBrowse link 1 82,097,244 82,108,238 RGD:11535070
G Gsk3b glycogen synthase kinase 3 beta JBrowse link 11 65,060,884 65,208,842 RGD:11535070
G Ikbkb inhibitor of nuclear factor kappa B kinase subunit beta JBrowse link 16 74,177,233 74,230,809 RGD:11535066
G Keap1 Kelch-like ECH-associated protein 1 JBrowse link 8 22,250,518 22,259,868 RGD:727319
RGD:11535066
RGD:11530066
RGD:6902900
G Maff MAF bZIP transcription factor F JBrowse link 7 120,580,743 120,592,095 RGD:11535066
G Mafg MAF bZIP transcription factor G JBrowse link 10 109,802,877 109,811,476 RGD:11535066
G Mafk MAF bZIP transcription factor K JBrowse link 12 16,923,989 16,934,706 RGD:11535066
G Ncoa3 nuclear receptor coactivator 3 JBrowse link 3 162,692,176 162,788,582 RGD:11535066
G Nfe2l2 nuclear factor, erythroid 2-like 2 JBrowse link 3 62,497,568 62,525,146 RGD:11530066
RGD:11535070
RGD:11535066
G Palb2 partner and localizer of BRCA2 JBrowse link 1 192,064,586 192,088,547 RGD:11535066
G Pgam5 PGAM family member 5, mitochondrial serine/threonine protein phosphatase JBrowse link 12 52,467,417 52,474,533 RGD:11535066
G Pten phosphatase and tensin homolog JBrowse link 1 251,421,814 251,487,634 RGD:11535070
G Rbx1 ring-box 1 JBrowse link 7 122,700,849 122,710,907 RGD:11535066
G Rnf4 ring finger protein 4 JBrowse link 14 81,658,400 81,679,756 RGD:11535066
G Siah2 siah E3 ubiquitin protein ligase 2 JBrowse link 2 148,874,151 148,891,900 RGD:11535066
G Skp1 S-phase kinase-associated protein 1 JBrowse link 10 37,594,578 37,609,498 RGD:11535066
G Sqstm1 sequestosome 1 JBrowse link 10 35,704,728 35,716,316 RGD:11535066

Pathway Gene Annotations

Pathway Annotations Associated with Genes in the nuclear factor, erythroid 2 like 2 signaling pathway
Pathway TermsGene Symbols
acute myeloid leukemia pathwayIkbkb
adenosine signaling pathwayIkbkb
aldosterone signaling pathwayCrebbp
altered phosphatidylinositol 3-kinase signaling pathwayPten
altered phosphatidylinositol 3-kinase-Akt signaling pathwayPten
Alzheimer disease pathwayGsk3b
androgen signaling pathwayCrebbp , Ncoa3
apoptotic cell death pathwayIkbkb
ataxia telangiectasia-mutated (ATM) signaling pathwayBrca1 , Rnf4
B cell receptor signaling pathwayGsk3b , Ikbkb
basal cell carcinoma pathwayGsk3b
bladder cancer pathwayCdkn1a
Bone morphogenetic proteins signaling pathwayGsk3b
cell cycle pathway, mitoticCdkn1a , Crebbp , Cul1 , Gsk3b , Rbx1 , Skp1
ceramide signaling pathwayIkbkb
chemokine mediated signaling pathwayGsk3a , Gsk3b , Ikbkb
chronic myeloid leukemia pathwayCdkn1a , Ikbkb
colorectal cancer pathwayGsk3b
cortisol signaling pathwayCrebbp , Ncoa3
endometrial cancer pathwayGsk3b , Pten
Endoplasmic Reticulum-associated degradation pathwayCul1 , Nfe2l2 , Rbx1 , Skp1
epidermal growth factor/neuregulin signaling pathwayCdkn1a , Gsk3b
estrogen signaling pathwayCrebbp , Ncoa3 , Siah2
FasL mediated signaling pathwayIkbkb
forkhead class A signaling pathwayBrca1 , Crebbp , Ncoa3
G1/S transition pathwayCdkn1a
glioma pathwayCdkn1a , Pten
glycogen biosynthetic pathwayGsk3a , Gsk3b
granulocyte-macrophage colony-stimulating factor signaling pathwayIkbkb
Hedgehog signaling pathwayBtrc , Crebbp , Gsk3b
hepatitis C virus infection pathwayCdkn1a , Gsk3b , Ikbkb
histone modification pathwayCrebbp
homologous recombination pathway of double-strand break repairBrca1
Huntington disease pathwayCrebbp
hypoxia inducible factor pathwayCrebbp , Rbx1
influenza A virus infection pathwayCrebbp , Gsk3b , Ikbkb
inositol phosphate metabolic pathwayPten
insulin responsive facilitative sugar transporter mediated glucose transport pathwayGsk3b
insulin signaling pathwayGsk3b , Ikbkb
interleukin-1 signaling pathwayIkbkb , Sqstm1
Jak-Stat signaling pathwayCrebbp
long term depressionGsk3b
long term potentiationCrebbp
measles infection pathwayGsk3b
melanoma pathwayCdkn1a , Pten
mitochondrial autophagy pathwayPgam5 , Sqstm1
mitogen activated protein kinase signaling pathwayIkbkb
mTOR signaling pathwayIkbkb
Mycobacterium tuberculosis infection pathwayCrebbp
neddylation pathwayCul1 , Cul3 , Rbx1
neurotrophic factor signaling pathwayGsk3b , Ikbkb
NOD-like receptor signaling pathwayIkbkb
non-small cell lung cancer pathwayPten
Notch signaling pathwayCdkn1a , Crebbp , Cul1 , Skp1
nuclear factor kappa B signaling pathwayBtrc , Cul1 , Ikbkb , Rbx1 , Skp1
nuclear factor, erythroid 2 like 2 signaling pathwayBrca1 , Btrc , Cdkn1a , Chd6 , Crebbp , Cul1 , Cul3 , Dpp3 , Gadd45gip1 , Gsk3a , Gsk3b , Ikbkb , Keap1 , Maff , Mafg , Mafk , Ncoa3 , Nfe2l2 , Palb2 , Pgam5 , Pten , Rbx1 , Rnf4 , Siah2 , Skp1 , Sqstm1
nucleotide excision repair pathwayRbx1
p53 signaling pathwayBrca1 , Cdkn1a , Crebbp , Gsk3b , Pten
pancreatic cancer pathwayIkbkb , Pten
phosphatidylinositol 3-kinase class I signaling pathwayPten
phosphatidylinositol 3-kinase signaling pathwayPten
phosphatidylinositol 3-kinase-Akt signaling pathwayCdkn1a , Gsk3a , Gsk3b , Pten
phosphoinositide metabolic pathwayPten
platelet-derived growth factor signaling pathwayPten
prostate cancer pathwayCdkn1a , Crebbp , Gsk3b , Ikbkb , Pten
proteasome degradation pathway involving cullin-dependent ubiquitin ligasesCul1 , Cul3 , Rbx1
Reelin signaling pathwayGsk3b
renal cell cancer pathwayCrebbp , Rbx1
retinoic acid signaling pathwayNcoa3
Retinoic acid-inducible gene (RIG) I-like receptor signaling pathwayIkbkb
RNA polymerase I transcription pathwayCrebbp
small cell lung cancer pathwayIkbkb , Pten
T cell receptor signaling pathwayGsk3b , Ikbkb
tamoxifen pharmacodynamics pathwayNcoa3
Toll-like receptor signaling pathwayIkbkb
Toxoplasma gondii infection pathwayIkbkb
Trail mediated signaling pathwayIkbkb
transforming growth factor-beta Smad dependent signaling pathwayCrebbp
transforming growth factor-beta superfamily mediated signaling pathwayCrebbp , Cul1 , Rbx1 , Skp1
Trypanosoma cruzi infection pathwayIkbkb
tumor necrosis factor mediated signaling pathwayIkbkb , Sqstm1
type 2 diabetes mellitus pathwayIkbkb
type II interferon signaling pathwayCrebbp
ubiquitin/proteasome degradation pathwayBrca1 , Btrc , Cul1 , Cul3 , Keap1 , Rbx1 , Skp1
vinblastine pharmacodynamics pathwayCdkn1a
vincristine pharmacodynamics pathwayCdkn1a
vindesine pharmacodynamics pathwayCdkn1a
vinorelbine pharmacodynamics pathwayCdkn1a
Wnt signaling pathwayBtrc , Crebbp , Cul1 , Gsk3b , Rbx1 , Skp1
Wnt signaling, canonical pathwayBtrc , Crebbp , Cul3 , Gsk3a , Gsk3b
Phenotype Annotations Associated with Genes in the nuclear factor, erythroid 2 like 2 signaling pathway

References Associated with the nuclear factor, erythroid 2 like 2 signaling pathway:

Ontology Path Diagram:

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