m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00514)
Target Name TNF alpha-induced protein 3 (TNFAIP3)
Synonyms
TNF alpha-induced protein 3; OTU domain-containing protein 7C; Putative DNA-binding protein A20; Zinc finger protein A20
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Gene Name TNFAIP3
Chromosomal Location 6q23.3
Family Peptidase C64 family
Function
Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages.
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Gene ID 7128
Uniprot ID
TNAP3_HUMAN
HGNC ID
HGNC:11896
Ensembl Gene ID
ENSG00000118503
KEGG ID
hsa:7128
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
TNFAIP3 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).
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RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line 143B cell line Homo sapiens
Treatment: siALKBH5 transfected 143B cells
Control: siControl 143B cells
 GSE154528
Regulation
logFC: 1.17E+00
p-value: 2.43E-06
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Lower expression TNF alpha-induced protein 3 (TNFAIP3) resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification.
Target Regulation Down regulation
Responsed Disease Diabetic retinopathy ICD-11: 9B71.0
 Disease Info 
In-vitro Model BV-2 Normal Mus musculus CVCL_0182
In-vivo Model The male Sprague-Dawley rats (8 weeks old, 200-220 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. Streptozotocin (Sigma, USA) was given by intraperitoneal injection at a dose of 60 mg/Kg to induce diabetics rats, while the control rats were given by empty citrate buffer. One week after induction, those rats with blood glucose levels > 16.7 mmol/L for three times were considered as successful inducted diabetes. All the rats did not receive insulin during the experiments.In the intraocular injection experiments, rats confirmed as the DM model (blood glucose levels > 16.7 mmol/L for three times) were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/Kg). A total of 10 ul DMEM with 1*109 TU lentiviruses (A20-overexpression, OE-A20 group) or the same volume of DMEM with control lentiviruses (OE-NC group) was injected into the vitreous cavity using a 33-gauge needle. This treatment was performed one time per month, and the rats were sacrificed for further experiments at the 3 months.
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between TNFAIP3 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.94E+00 GSE49339
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of EPHB3 and TNF alpha-induced protein 3 (TNFAIP3).
Target Regulation Down regulation
Responsed Disease Glioblastoma ICD-11: 2A00.00
 Disease Info 
Responsed Drug Temozolomide Approved
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process RNA stability
In-vitro Model T98G Glioblastoma Homo sapiens CVCL_0556
LN-229 Glioblastoma Homo sapiens CVCL_0393
In-vivo Model 5 × 106 infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary miR-19a regulated TNF alpha-induced protein 3 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2). The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-Kappa-B axis and acts as an independent biomarker to help the treatment of SLE patients.
Target Regulation Up regulation
Responsed Disease Lupus erythematosus ICD-11: 4A40
 Disease Info 
Cell Process Immunity
In-vitro Model PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Brain cancer [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of EPHB3 and TNF alpha-induced protein 3 (TNFAIP3).
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Temozolomide Approved
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process RNA stability
In-vitro Model T98G Glioblastoma Homo sapiens CVCL_0556
LN-229 Glioblastoma Homo sapiens CVCL_0393
In-vivo Model 5 × 106 infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
Lupus erythematosus [ICD-11: 4A40]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary miR-19a regulated TNF alpha-induced protein 3 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2). The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-Kappa-B axis and acts as an independent biomarker to help the treatment of SLE patients.
Responsed Disease Lupus erythematosus [ICD-11: 4A40]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process Immunity
In-vitro Model PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Retinopathy [ICD-11: 9B71]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Lower expression TNF alpha-induced protein 3 (TNFAIP3) resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification.
Responsed Disease Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Down regulation
In-vitro Model BV-2 Normal Mus musculus CVCL_0182
In-vivo Model The male Sprague-Dawley rats (8 weeks old, 200-220 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. Streptozotocin (Sigma, USA) was given by intraperitoneal injection at a dose of 60 mg/Kg to induce diabetics rats, while the control rats were given by empty citrate buffer. One week after induction, those rats with blood glucose levels > 16.7 mmol/L for three times were considered as successful inducted diabetes. All the rats did not receive insulin during the experiments.In the intraocular injection experiments, rats confirmed as the DM model (blood glucose levels > 16.7 mmol/L for three times) were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/Kg). A total of 10 ul DMEM with 1*109 TU lentiviruses (A20-overexpression, OE-A20 group) or the same volume of DMEM with control lentiviruses (OE-NC group) was injected into the vitreous cavity using a 33-gauge needle. This treatment was performed one time per month, and the rats were sacrificed for further experiments at the 3 months.
Temozolomide [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of EPHB3 and TNF alpha-induced protein 3 (TNFAIP3).
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Glioblastoma ICD-11: 2A00.00
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process RNA stability
In-vitro Model T98G Glioblastoma Homo sapiens CVCL_0556
LN-229 Glioblastoma Homo sapiens CVCL_0393
In-vivo Model 5 × 106 infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
References
Ref 1 ALKBH5-Mediated m(6)A Modification of A20 Regulates Microglia Polarization in Diabetic Retinopathy. Front Immunol. 2022 Mar 1;13:813979. doi: 10.3389/fimmu.2022.813979. eCollection 2022.
Ref 2 YTHDF2 promotes temozolomide resistance in glioblastoma by activation of the Akt and NF-KappaB signalling pathways via inhibiting EPHB3 and TNFAIP3. Clin Transl Immunology. 2022 May 9;11(5):e1393. doi: 10.1002/cti2.1393. eCollection 2022.
Ref 3 N6-methyladenosine-dependent modification of circGARS acts as a new player that promotes SLE progression through the NF-KappaB/A20 axis. Arthritis Res Ther. 2022 Feb 4;24(1):37. doi: 10.1186/s13075-022-02732-x.