Ser40
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Home > Phosphorylation Site Page: > Ser40  -  NRF2 (mouse)

Site Information
SREVFDFsQRQKDYE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 450082

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 2 , 3 ) , immunoprecipitation ( 9 ) , mutation of modification site ( 8 , 9 , 10 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 9 , 10 ) , western blotting ( 1 , 4 , 5 , 6 , 7 , 9 )
Disease tissue studied:
breast cancer ( 9 ) , leukemia ( 2 ) , liver cancer ( 9 )
Relevant cell line - cell type - tissue:
'neuron, substantia nigra'-brain ( 3 ) , BT-549 (breast cell) ( 9 ) , D2 ( 2 ) , E.coli (bacterial) ( 8 ) , Hepa-1 (hepatic) ( 9 , 10 ) , HT-22 (neuron) ( 1 ) , MCF-7 (breast cell) ( 9 ) , MCF10A1 (epithelial) ( 2 ) , MEF (fibroblast) ( 6 ) , myocyte-heart ( 4 ) , testis ( 7 )

Upstream Regulation
Regulatory protein:
ALKBH8 (mouse) ( 6 ) , EGFR (mouse) ( 5 ) , PKCA (mouse) ( 4 ) , PKCE (mouse) ( 4 ) , PKCH (mouse) ( 4 ) , SHANK3 (human) ( 1 )
Putative in vivo kinases:
PKCA (mouse) ( 10 ) , PKCD (human) ( 4 , 9 )
Kinases, in vitro:
PKCA (mouse) ( 10 )
Treatments:
AG1478 ( 5 ) , astragaloside_IV ( 5 ) , Dihydrotanshinone ( 4 ) , Go_6850 ( 9 ) , Go_6976 ( 9 ) , Go_6983 ( 4 , 9 ) , H2O2 ( 6 ) , MK-2206 ( 4 ) , phorbol_ester ( 4 ) , rotenone ( 6 ) , rottlerin ( 9 ) , siRNA ( 4 ) , staurosporine ( 9 ) , stiff ECM substrate ( 2 ) , sulforaphane ( 7 ) , tBHQ ( 9 )

Downstream Regulation
Effects of modification on NRF2:
activity, induced ( 2 ) , intracellular localization ( 1 , 4 , 9 ) , molecular association, regulation ( 9 , 10 ) , protein stabilization ( 4 , 9 ) , ubiquitination ( 4 )
Effects of modification on biological processes:
carcinogenesis, induced ( 2 ) , transcription, induced ( 1 , 2 , 4 )
Inhibit interaction with:
KEAP1 (human) ( 9 ) , KEAP1 (mouse) ( 10 )

Disease / Diagnostics Relevance
Relevant diseases:
diabetes mellitus ( 7 )

References 

1

Zhang H, et al. (2023) Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation. Redox Biol 69, 102983
38064762   Curated Info

2

Romani P, et al. (2022) Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance. Nat Cell Biol 24, 168-180
35165418   Curated Info

3

Delaidelli A, et al. (2021) α-Synuclein pathology in Parkinson disease activates homeostatic NRF2 anti-oxidant response. Acta Neuropathol Commun 9, 105
34092244   Curated Info

4

Zeng H, et al. (2021) Activated PKB/GSK-3 synergizes with PKC- signaling in attenuating myocardial ischemia/reperfusion injury potentiation of NRF2 activity: Therapeutic efficacy of dihydrotanshinone-I. Acta Pharm Sin B 11, 71-88
33532181   Curated Info

5

Gu DM, et al. (2015) EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages. Biochem Biophys Res Commun 457, 391-7
25582778   Curated Info

6

Endres L, et al. (2015) Alkbh8 Regulates Selenocysteine-Protein Expression to Protect against Reactive Oxygen Species Damage. PLoS One 10, e0131335
26147969   Curated Info

7

Jiang X, et al. (2014) Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function. Toxicol Appl Pharmacol 279, 198-210
24967692   Curated Info

8

Fukutomi T, et al. (2014) Kinetic, Thermodynamic, and Structural Characterizations of the Association between Nrf2-DLGex Degron and Keap1. Mol Cell Biol 34, 832-46
24366543   Curated Info

9

Niture SK, Jain AK, Jaiswal AK (2009) Antioxidant-induced modification of INrf2 cysteine 151 and PKC-delta-mediated phosphorylation of Nrf2 serine 40 are both required for stabilization and nuclear translocation of Nrf2 and increased drug resistance. J Cell Sci 122, 4452-64
19920073   Curated Info

10

Bloom DA, Jaiswal AK (2003) Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression. J Biol Chem 278, 44675-82
12947090   Curated Info

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