General Information of the m6A Target Gene (ID: M6ATAR00605)
Target Name NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
Synonyms
Angiotensin/vasopressin receptor AII/AVP-like; Caterpiller protein 1.1; CLR1.1; Cold-induced autoinflammatory syndrome 1 protein; Cryopyrin; PYRIN-containing APAF1-like protein 1
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Gene Name NLRP3
Chromosomal Location 1q44
Family NLRP family
Function
As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion. The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. Activation upon, at least, K(+) efflux is mediated by the interaction wit NEK7 (By similarity). Activation in presence of cytosolic dsRNA is mediated by DHX33. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity).
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Gene ID 114548
Uniprot ID
NLRP3_HUMAN
HGNC ID
HGNC:16400
Ensembl Gene ID
ENSG00000162711
KEGG ID
hsa:114548
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
NLRP3 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
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
GSE207909
Regulation
logFC: 8.32E-01
p-value: 1.76E-06
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between NLRP3 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 7.81E+00 GSE60213
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) up-regulation, and KLF4 down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.
Target Regulation Up regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
In-vitro Model MAEC Normal Mus musculus CVCL_U411
HUVEC-C Normal Homo sapiens CVCL_2959
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary TFA could ameliorate HG-induced pyroptosis and injury in podocytes by targeting METTL3-dependent m6A modification via the regulation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-inflammasome activation and PTEN/PI3K/Akt signaling. This study provides a better understanding of how TFA can protect podocytes in diabetic kidney disease (DKD).
Target Regulation Down regulation
Responsed Disease Chronic kidney disease ICD-11: GB61.Z
Pathway Response PI3K-Akt signaling pathway hsa04151
In-vitro Model MPC-5 Normal Mus musculus CVCL_AS87
YTH domain-containing family protein 1 (YTHDF1) [READER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary YTHDF1 promotes pro-inflammatory IL-1-Beta production in macrophages during bacterial infections. YTHDF1 overexpression promotes NACHT, LRR and PYD domains-containing protein 3 (NLRP3) translation.YTHDF1 participates in inflammatory responses and subsequent injuries, serving as a new potential therapeutic target in clinical treatment of inflammatory diseases.
Target Regulation Up regulation
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In-vivo Model Female C57BL/6 mice (6-8 weeks) were intraperitoneally injected with 2 ml 3% sterile sodium thioglycolate solution. After 3 days, the cells in the abdominal cavity were collected, centrifugated and maintained in DMEM with 10% (vol/vol) FBS.
Atherosclerosis [ICD-11: BD40]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) up-regulation, and KLF4 down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
In-vitro Model MAEC Normal Mus musculus CVCL_U411
HUVEC-C Normal Homo sapiens CVCL_2959
Chronic kidney disease [ICD-11: GB61]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary TFA could ameliorate HG-induced pyroptosis and injury in podocytes by targeting METTL3-dependent m6A modification via the regulation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-inflammasome activation and PTEN/PI3K/Akt signaling. This study provides a better understanding of how TFA can protect podocytes in diabetic kidney disease (DKD).
Responsed Disease Chronic kidney disease [ICD-11: GB61.Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
In-vitro Model MPC-5 Normal Mus musculus CVCL_AS87
References
Ref 1 METTL3-dependent N(6)-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium. Proc Natl Acad Sci U S A. 2021 Feb 16;118(7):e2025070118. doi: 10.1073/pnas.2025070118.
Ref 2 Total Flavones of Abelmoschus manihot Ameliorates Podocyte Pyroptosis and Injury in High Glucose Conditions by Targeting METTL3-Dependent m(6)A Modification-Mediated NLRP3-Inflammasome Activation and PTEN/PI3K/Akt Signaling. Front Pharmacol. 2021 Jul 15;12:667644. doi: 10.3389/fphar.2021.667644. eCollection 2021.
Ref 3 RNA m6A reader YTHDF1 facilitates inflammation via enhancing NLRP3 translation. Biochem Biophys Res Commun. 2022 Aug 6;616:76-81. doi: 10.1016/j.bbrc.2022.05.076. Epub 2022 May 24.