Nuclear factor, erythroid-derived 2, like 2 signaling pathway (WP2376)

Rattus norvegicus

The transcription factor Nfe2l2 (alias: Nrf2), which acts as an antioxidant, is tightly regulated in the cytosol through proteasomal degradation by Keap1. When appropriate stimuli, such as oxidative stress, cause changes in Keap1, Nfe2l2 is translocated to the nucleus where it binds to antioxidant response elements and activates gene expression. Nfe2l2 plays a critical role in regulating redox homeostasis, differentiation, and maturation by modulating the expression of cytoprotective genes like Hmox1, Nqo1, and glutathione. Nfe2l2 is involved in various cellular functions, including differentiation, proliferation, and inflammation, by promoting antioxidative gene expression, suppressing the production of reactive oxygen species and proinflammatory cytokines, and inhibiting Nfkb signaling. Aberrant function or expression of Nfe2l2 is linked to pathological conditions such as inflammation, autoimmunity, cancer, and neurodegeneration.


Ricardo S. Rodrguez , Daniela Digles , Egon Willighagen , Martina Summer-Kutmon , and Alex Pico


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Rattus norvegicus



Pathway Ontology

nuclear factor, erythroid 2 like 2 signaling pathway


Label Type Compact URI Comment
Trigonelline Metabolite hmdb:HMDB0000875
Glutathione Metabolite hmdb:HMDB0000125
ROS Metabolite chebi:26523
Ugdh GeneProduct rgd:621879
Prkcg GeneProduct ensembl:ENSRNOG00000054371
Actg1 GeneProduct rgd:1304556
Cdkn1a GeneProduct rgd:69328
Aldoa GeneProduct rgd:2089
Psmc6 GeneProduct rgd:1308825
Keap1 GeneProduct rgd:621619
Slc1a4 GeneProduct rgd:735146
Cdc34 GeneProduct rgd:1305411
Gsk3b GeneProduct rgd:70982
Acta1 GeneProduct rgd:2025
Txn1 GeneProduct rgd:621157
Mafg GeneProduct rgd:619953
Mgst2 GeneProduct rgd:1311218
Kras GeneProduct rgd:2981
Actb GeneProduct rgd:628837
Map3k7 GeneProduct rgd:1309438
Nras GeneProduct rgd:3205
Map3k5 GeneProduct rgd:1306431
Sod1 GeneProduct rgd:3731
Mdm2 GeneProduct rgd:1305332
Gstm3 GeneProduct rgd:620381
Slc7a11 GeneProduct rgd:1309275
Prkcz GeneProduct rgd:3399
Psmc2 GeneProduct rgd:3428
Hsp90ab1 GeneProduct rgd:1303075
Pik3r2 GeneProduct rgd:68341
Gstm2 GeneProduct rgd:2756
Gsr GeneProduct rgd:621747
Bach1 GeneProduct rgd:1306693
Gclm GeneProduct rgd:619871
Scarb1 GeneProduct rgd:2302
Mapk3 GeneProduct ensembl:ENSRNOG00000053583
Sod2 GeneProduct rgd:3732
Keap1 GeneProduct rgd:621619
Mapk8 GeneProduct ncbigene:116554
Gsto1 GeneProduct rgd:70952
Prkd1 GeneProduct rgd:620964
Map2k7 GeneProduct rgd:1560043
Pik3r1 GeneProduct ncbigene:25513
Pik3c2b GeneProduct rgd:1306541
Akt1 GeneProduct rgd:2081
Fos GeneProduct rgd:2626
Pmf1 GeneProduct rgd:1584694
Pik3r6 GeneProduct rgd:1560850
Pik3c2a GeneProduct rgd:1310389
Map2k6 GeneProduct rgd:620666
Bach1 GeneProduct rgd:1306693
Dnajb9 GeneProduct rgd:3070
Brca1 GeneProduct rgd:2218
Psmc3 GeneProduct rgd:61905
Fmo1 GeneProduct rgd:2622
Slc2a1 GeneProduct rgd:3704
Atf4 GeneProduct rgd:621863
Prkcb GeneProduct ncbigene:25023
Nfe2l2 GeneProduct rgd:620360
Pik3c3 GeneProduct rgd:620899
Mapk9 GeneProduct rgd:628847
Psmc5 GeneProduct rgd:708376
Prkca GeneProduct rgd:3395
Ftl GeneProduct rgd:61813
Fth1 GeneProduct rgd:2635
Mapk7 GeneProduct rgd:621505
Sqstm1 GeneProduct ncbigene:113894
Mgst3 GeneProduct rgd:1306373
Eif2ak3 GeneProduct rgd:70884
Map2k2 GeneProduct rgd:61888
Cebpa GeneProduct rgd:2326
Gstm4 GeneProduct rgd:1565825
Rbx1 GeneProduct rgd:1308453
Mras GeneProduct rgd:3111
Mgst1 GeneProduct rgd:70927
Sod3 GeneProduct rgd:3733
Gsta4 GeneProduct rgd:1309970
Gsto2 GeneProduct rgd:1310764
Prkcq GeneProduct rgd:620968
Slc35b1 GeneProduct rgd:727783
Mafk GeneProduct rgd:628633
Gpx2 GeneProduct rgd:727780
Map2k1 GeneProduct rgd:70495
Prkci GeneProduct rgd:620961
Ep300 GeneProduct ncbigene:170915
Taldo1 GeneProduct rgd:620674
Ran GeneProduct rgd:620367
Gclc GeneProduct rgd:619868
Ldhb GeneProduct rgd:2997
Rras GeneProduct rgd:1311443
Prdx1 GeneProduct rgd:620039
Gsta1 GeneProduct rgd:2753
Atf4 GeneProduct rgd:621863
Ubb GeneProduct rgd:621562
Gstm5 GeneProduct rgd:61964
Mapk1 GeneProduct rgd:70500
Fos GeneProduct rgd:2626
Herpud1 GeneProduct rgd:620818
Aox1 GeneProduct ncbigene:54349
Nfe2l2 GeneProduct rgd:620360
Dnajc5 GeneProduct rgd:620516
Atm GeneProduct rgd:1593265
Smarca4 GeneProduct rgd:621728
Pik3c2g GeneProduct rgd:620231
Aldh3a1 GeneProduct rgd:2088
Gsta3 GeneProduct ncbigene:24421
Jun GeneProduct rgd:2943
Pik3r5 GeneProduct rgd:1563261
Cacng6 GeneProduct ensembl:ENSRNOG00000057852
Prkd3 GeneProduct rgd:1310236
Gstt1 GeneProduct rgd:2765
Hras GeneProduct ncbigene:293621
Crebbp GeneProduct rgd:2401
Hmox1 GeneProduct rgd:2806
Dhcr7 GeneProduct rgd:621769
Nqo2 GeneProduct rgd:1303320
Yy1 GeneProduct rgd:3982
Prkcd GeneProduct rgd:67383
Pik3cg GeneProduct rgd:1306468
Mapk14 GeneProduct rgd:70496
Abcc3 GeneProduct rgd:71101
Abcc4 GeneProduct rgd:620266
Maff GeneProduct rgd:1309531
Vcp GeneProduct rgd:621595
Gstm1 GeneProduct rgd:2755
Map2k3 GeneProduct ensembl:ENSRNOG00000006612
Rras2 GeneProduct rgd:1310793
Pik3ca GeneProduct ncbigene:170911
Sqstm1 GeneProduct ncbigene:113894
Akr7a2 GeneProduct rgd:620311
Psmc4 GeneProduct rgd:621102
Tp53 GeneProduct rgd:3889
Akr7a3 GeneProduct rgd:628635
Abcc1 GeneProduct ensembl:ENSRNOG00000022305
Map3k1 GeneProduct rgd:620966
Pik3r4 GeneProduct ncbigene:363131
Akr1b10 GeneProduct rgd:1308277
Cbr1 GeneProduct rgd:2286
Me1 GeneProduct rgd:3074
G6pd GeneProduct ensembl:ENSRNOG00000056728
Map2k5 GeneProduct ncbigene:29568
Txnrd1 GeneProduct rgd:61959
Prkce GeneProduct rgd:61925
Xpo1 GeneProduct rgd:620517
Actc1 GeneProduct rgd:2026
Actg2 GeneProduct rgd:2027
Dnajb4 GeneProduct rgd:1305826
Gstp1 GeneProduct rgd:2758
Gss GeneProduct rgd:2752
Usp14 GeneProduct rgd:1311825
Slc35a2 GeneProduct rgd:2293497
Fyn GeneProduct rgd:2641
Pik3cd GeneProduct rgd:1310990
Ube2k GeneProduct rgd:1311626
Prkch GeneProduct rgd:621888
Pik3r3 GeneProduct rgd:621042
Gstk1 GeneProduct rgd:735188
Psmc1 GeneProduct rgd:621097
Akr1a1 GeneProduct rgd:68346
Nqo1 GeneProduct rgd:2503
Pgd GeneProduct ensembl:ENSRNOG00000023562
Gstt2 GeneProduct ncbigene:29487
Ephx1 GeneProduct rgd:2557
Raf1 GeneProduct rgd:3531
Acta2 GeneProduct ncbigene:81633
Cul3 GeneProduct rgd:1308190
Fosl1 GeneProduct rgd:2627
Bard1 GeneProduct rgd:621072
Gsta2 GeneProduct rgd:2754
Pik3cb GeneProduct rgd:620917
Keap1 GeneProduct rgd:621619
Actc1 GeneProduct rgd:2026
Acta2 GeneProduct ncbigene:81633
Actb GeneProduct rgd:628837
Acta1 GeneProduct rgd:2025
Actg1 GeneProduct rgd:1304556
Actg2 GeneProduct rgd:2027
Nfe2l2 GeneProduct rgd:620360
Nfe2l2 GeneProduct rgd:620360