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

Site Information
SREVFDFsQRRkEYE   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 , 13 ) , immunoprecipitation ( 10 , 11 , 14 , 16 , 17 ) , mutation of modification site ( 5 , 6 , 8 , 15 , 16 , 18 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 17 , 18 ) , western blotting ( 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 16 , 17 , 18 )
Disease tissue studied:
bladder cancer ( 17 ) , breast cancer ( 1 ) , colorectal cancer ( 9 ) , colorectal carcinoma ( 9 ) , kidney cancer ( 7 ) , lung cancer ( 12 ) , non-small cell lung cancer ( 12 ) , non-small cell lung adenocarcinoma ( 12 ) , prostate cancer ( 14 ) , cancer, squamous cell carcinoma ( 15 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 4 ) , 293 (epithelial) ( 3 , 6 , 16 ) , A549 (pulmonary) ( 12 ) , ACHN (renal) ( 7 ) , ARPE19 (retinal) ( 8 ) , corneal ( 2 ) , COS7 (fibroblast) ( 18 ) , E.coli (bacterial) ( 15 ) , endometrial ( 5 ) , epithelial-lens ( 8 ) , HBE (epithelial) ( 10 ) , HCT116 (intestinal) ( 9 ) , HEK293T (epithelial) ( 11 , 13 ) , HeLa (cervical) ( 12 ) , HEp-3 ( 15 ) , HESCs (endometrial) ( 5 ) , HMVEC (endothelial) ( 11 , 13 ) , HUVEC (endothelial) ( 11 ) , LNCaP (prostate cell) ( 14 ) , MDA-MB-231 (breast cell) ( 1 ) , NBT-II (bladder cell) ( 17 ) , RT4 (bladder cell) ( 17 ) , WI-38 (fibroblast) ( 18 )

Upstream Regulation
Regulatory protein:
Akt1 (human) ( 8 ) , CENPU (human) ( 11 ) , FILIP1 (human) ( 13 ) , PKCA (human) ( 15 )
Putative in vivo kinases:
PKCD (human) ( 1 ) , PKCI (human) ( 18 ) , PKCZ (human) ( 11 )
Treatments:
17-beta-estradiol ( 7 ) , baicalein ( 9 ) , Bay_11-7082 ( 13 ) , celecoxib ( 11 , 13 ) , CPDT ( 17 ) , DPI ( 13 ) , exercise ( 4 ) , ginsenoside ( 5 ) , H2O2 ( 13 ) , hypoxia ( 4 ) , IL-24 ( 12 ) , ischemia ( 4 ) , LPS ( 10 ) , LXA4 ( 10 ) , LY294002 ( 13 ) , MG132 ( 6 ) , NAC ( 13 ) , patulin ( 3 ) , PDTC ( 13 ) , PEITC ( 1 ) , PGE2 ( 11 , 13 ) , PKC_inhibitor_myristoylated ( 11 ) , PP2 ( 13 ) , rottlerin ( 1 ) , SB203580 ( 12 ) , serum ( 6 ) , sulforaphane ( 17 ) , U0126 ( 12 ) , U73122 ( 13 ) , UV ( 13 ) , virus infection ( 11 , 13 ) , wortmannin ( 11 , 13 )

Downstream Regulation
Effects of modification on NRF2:
activity, induced ( 8 , 11 , 13 ) , intracellular localization ( 2 , 3 , 5 , 10 , 11 , 12 , 13 , 18 ) , molecular association, regulation ( 12 , 13 , 14 , 15 ) , protein stabilization ( 3 , 5 , 13 )
Effects of modification on biological processes:
apoptosis, inhibited ( 12 ) , autophagy, inhibited ( 11 ) , carcinogenesis, induced ( 12 ) , carcinogenesis, inhibited ( 1 ) , cell motility, inhibited ( 1 ) , transcription, induced ( 3 , 5 , 10 , 11 , 12 , 13 , 18 )
Induce interaction with:
DNA ( 13 ) , LANA (herpesvirus) ( 13 ) , SIAH2 (human) ( 15 )
Inhibit interaction with:
HMOX1 (human) ( 14 ) , KEAP1 (human) ( 10 , 12 , 15 )

Disease / Diagnostics Relevance
Relevant diseases:
Kaposi's sarcoma ( 11 , 13 ) , KC ( 2 )

References 

1

Biswas S, et al. (2022) PEITC: A resounding molecule averts metastasis in breast cancer cells by regulating PKCδ/Aurora A interplay. Heliyon 8, e11656
36458309   Curated Info

2

Lupasco T, et al. (2022) Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes. PLoS One 17, e0273807
36240204   Curated Info

3

Pillay Y, et al. (2021) Patulin activates the NRF2 pathway by modulation of miR-144 expression in HEK293 cells. Mycotoxin Res 37, 97-103
33403569   Curated Info

4

Gallego-Selles A, et al. (2020) Regulation of Nrf2/Keap1 signalling in human skeletal muscle during exercise to exhaustion in normoxia, severe acute hypoxia and post-exercise ischaemia: Influence of metabolite accumulation and oxygenation. Redox Biol 36, 101627
32863217   Curated Info

5

Wang XM, et al. (2020) Ginsenoside Rh3 activates Nrf2 signaling and protects endometrial cells from oxygen and glucose deprivation-reoxygenation. Aging (Albany NY)
32259797   Curated Info

6

Relic B, et al. (2018) Serum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death. Oncotarget 9, 35830-35843
30533198   Curated Info

7

Wu ST, et al. (2016) Cellular effects induced by 17-β-estradiol to reduce the survival of renal cell carcinoma cells. J Biomed Sci 23, 67
27680214   Curated Info

8

Gong YQ, et al. (2016) SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling. Oncotarget 7, 60123-60132
27517753   Curated Info

9

Havermann S, Chovolou Y, Humpf HU, Wätjen W (2016) Modulation of the Nrf2 signalling pathway in Hct116 colon carcinoma cells by baicalein and its methylated derivative negletein. Pharm Biol 54, 1491-502
27143122   Curated Info

10

Cheng X, et al. (2016) Lipoxin A4 attenuates LPS-induced mouse acute lung injury via Nrf2-mediated E-cadherin expression in airway epithelial cells. Free Radic Biol Med 93, 52-66
26845617   Curated Info

11

Gjyshi O, et al. (2015) Kaposi's Sarcoma-Associated Herpesvirus Induces Nrf2 Activation in Latently Infected Endothelial Cells through SQSTM1 Phosphorylation and Interaction with Polyubiquitinated Keap1. J Virol 89, 2268-86
25505069   Curated Info

12

Tian H, et al. (2014) MDA-7/IL-24 inhibits Nrf2-mediated antioxidant response through activation of p38 pathway and inhibition of ERK pathway involved in cancer cell apoptosis. Cancer Gene Ther 21, 416-26
25236495   Curated Info

13

Gjyshi O, et al. (2014) Kaposi's sarcoma-associated herpesvirus induces Nrf2 during de novo infection of endothelial cells to create a microenvironment conducive to infection. PLoS Pathog 10, e1004460
25340789   Curated Info

14

Biswas C, et al. (2014) Nuclear Heme Oxygenase-1 (HO-1) Modulates Subcellular Distribution and Activation of Nrf2, Impacting Metabolic and Anti-oxidant Defenses. J Biol Chem 289, 26882-94
25107906   Curated Info

15

Baba K, Morimoto H, Imaoka S (2013) Seven in Absentia Homolog 2 (Siah2) Protein Is a Regulator of NF-E2-related Factor 2 (Nrf2). J Biol Chem 288, 18393-405
23645672   Curated Info

16

Kim WD, et al. (2012) E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells. J Cell Sci 125, 1284-95
22302998   Curated Info

17

Li Y, Paonessa JD, Zhang Y (2012) Mechanism of chemical activation of nrf2. PLoS One 7, e35122
22558124   Curated Info

18

Numazawa S, et al. (2003) Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress. Am J Physiol Cell Physiol 285, C334-42
12700136   Curated Info