m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00306)
Target Name Kelch-like ECH-associated protein 1 (KEAP1)
Synonyms
Cytosolic inhibitor of Nrf2; INrf2; Kelch-like protein 19; INRF2; KIAA0132; KLHL19
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Gene Name KEAP1
Chromosomal Location 19p13.2
Family KEAP1 family
Function
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes. In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 . The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation. The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome.
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Gene ID 9817
Uniprot ID
KEAP1_HUMAN
HGNC ID
HGNC:23177
Ensembl Gene ID
ENSG00000079999
KEGG ID
hsa:9817
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
KEAP1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
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Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line HeLa cell line Homo sapiens
Treatment: METTL3 knockdown HeLa cells
Control: HeLa cells
 GSE70061
Regulation
logFC: -1.79E+00
p-value: 1.23E-03
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between KEAP1 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.17E+00 GSE60213
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Kelch-like ECH-associated protein 1 (KEAP1)/Nrf2 signaling pathway.
Target Regulation Down regulation
Responsed Disease Diseases of the urinary system ICD-11: GC2Z
 Disease Info 
Responsed Drug Colistin Approved
 Drug Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1
Cell Line AGS cell line Homo sapiens
Treatment: shYTHDF1 AGS
Control: shControl AGS
 GSE159425
Regulation
logFC: 1.01E+00
p-value: 4.73E-09
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between KEAP1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.61E+00 GSE63591
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Chemical carcinogenesis - reactive oxygen species hsa05208
Cell cycle hsa04110
Cell Process Biological regulation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
GLC-82 Endocervical adenocarcinoma Homo sapiens CVCL_3371
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H838 Lung adenocarcinoma Homo sapiens CVCL_1594
SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
In-vivo Model Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Chemical carcinogenesis - reactive oxygen species hsa05208
Cell cycle hsa04110
Cell Process Biological regulation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
GLC-82 Endocervical adenocarcinoma Homo sapiens CVCL_3371
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H838 Lung adenocarcinoma Homo sapiens CVCL_1594
SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
In-vivo Model Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Diseases of the urinary system [ICD-11: GC2Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Kelch-like ECH-associated protein 1 (KEAP1)/Nrf2 signaling pathway.
Responsed Disease Diseases of the urinary system [ICD-11: GC2Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Colistin Approved
 Drug Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Cisplatin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Chemical carcinogenesis - reactive oxygen species hsa05208
Cell cycle hsa04110
Cell Process Biological regulation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
GLC-82 Endocervical adenocarcinoma Homo sapiens CVCL_3371
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H838 Lung adenocarcinoma Homo sapiens CVCL_1594
SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
In-vivo Model Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Colistin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Kelch-like ECH-associated protein 1 (KEAP1)/Nrf2 signaling pathway.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Diseases of the urinary system ICD-11: GC2Z
 Disease Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
References
Ref 1 METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nrf2 signaling pathway. Toxicology. 2021 Oct;462:152961. doi: 10.1016/j.tox.2021.152961. Epub 2021 Sep 21.
Ref 2 YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat Commun. 2019 Oct 25;10(1):4892. doi: 10.1038/s41467-019-12801-6.