Pathway
KEAP1-NFE2L2 pathway
The KEAP1:NFE2L2 (KEAP1-NRF2, Kelch-like ECH-associated protein 1-Nuclear Factor (erythroid-derived 2)-like 2) regulatory pathway plays a central role in protecting cells against multiple homeostatic responses including adaptation to oxidative, inflammatory, metabolic, proteotoxic and xenobiotic stresses. The NFE2L2 transcriptome has been implicated in protection against many chronic diseases including cardiovascular, metabolic, neurodgenerative and respiratory diseases (reviewed in Cuadrado et al, 2018; Baird and Yamamoto, 2020). In cancer, NFE2L2 plays a critical role in the metabolic reprogramming, directing metabolic intermediates into the Warburg and pentose phosphate pathways to support proliferative growth and redox homeostasis (reviewed in He et al, 2020; Ge et al, 2020; Hayes et al, 2020; Kitamura and Hotomashi, 2018)
Continue reading
KEAP1 is a redox sensor that together with CUL3/RBX1 forms part of an E3 ubiquitin ligase, which tightly regulates the activity of the transcription factor NFE2L2 by targeting it for ubiquitination and proteasome-dependent degradation. Oxidative modifications or electrophile adduct formation with redox-sensitive cysteines within KEAP1 renders this protein unable to target bound NFE2L2 for ubiquitination and allows newly translated NFE2L2 to accumulate within the cell and translocate to the nucleus where it can promote its transcriptional program (reviewed in Cuadrado et al, 2019; Baird and Yamamoto, 2020).
What the reference databases state
Statements
112 statements
112 statements · 1 reference database · Subject: KEAP1-NFE2L2 pathway · Sources: Reactome
- ABCC1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- ABCC3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- ABCF2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- ABCG2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- ADRM1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- AKT1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- AKT2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- AKT3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- AMER1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- AREG participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- ATF4 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- BACH1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
Show the remaining 100
- BCL2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- BCL2L1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- BRCA1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- BTRC participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CCL2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CDKN1A participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CDKN2A participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CHD6 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CREBBP participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CSNK2A1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CSNK2A2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CSNK2B participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CUL1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- CUL3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- DPP3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- EGF participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- EIF2AK3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- EP300 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- FBXL17 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- G6PD participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- GCLC participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- GCLM participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- GSK3B participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- GSTA1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- GSTA3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- HMOX1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- IDH1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- KEAP1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- MAFG participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- MAFK participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- MAP1LC3B participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- ME1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- MUL1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- MYC participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- NFE2L2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- NFKB1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- NOTCH1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- NPLOC4 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- NQO1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PALB2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PDGFA participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PGD participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PRDX1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PRKAA2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PRKCD participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PRKCI participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA4 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA5 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA6 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMA7 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB4 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB5 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB6 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMB7 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMC1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMC2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMC3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMC4 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMC5 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMC6 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD11 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD12 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD13 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD14 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD6 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD7 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- PSMD8 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- RBX1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- RELA participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- RPS27A participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SEM1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SESN1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SESN2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SKP1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SKP2 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SLC7A11 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SOD3 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SP1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SQSTM1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- SRXN1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- TALDO1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- TKT participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- TRIM21 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- TXN participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- TXNRD1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- UBA52 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- UBB participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- UBC participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- UBXN7 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- UFD1 participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only
- VCP participates in KEAP1-NFE2L2 pathwayProteinReactome R-HSA-9755511Inferred only