DDX58/IFIH1-mediated induction of interferon-alpha/beta (Homo sapiens)

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17, 18, 22, 23, 26...60521, 27, 3169, 713, 39, 67731, 45, 46, 7027, 44, 54, 57, 6850, 72685, 43, 5511, 628, 14, 50367048, 56, 7410, 344, 7, 12, 19, 58...323, 39, 676, 74403416, 256042403721, 24, 30, 4713, 20, 33, 6335, 50, 5338591, 5038, 44, 6411, 629, 29, 711551404, 7, 12, 19, 585, 284, 7, 12, 19, 58IRF3-Pdimer:CBP/p300[nucleoplasm]S100A12 dimer[extracellularregion]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi[mitochondrial outermembrane]AGE adducts:Peptide[extracellularregion]RIG-I E3 ubiquitinligases [cytosol]p-IRF3 dimer:PIN1[nucleoplasm]dsRNA:RIG-I/MDA5[cytosol]RNF125:E2 enzyme(UBE2K,UbcH5a-c):K48-polyubiquitin[cytosol]IRF1:Promotors ofIFN alpha, IFN beta[nucleoplasm]p-2S-IRF7:p-2S-IRF7[cytosol]dsRNA:RIG-I/MDA5:IPS-1[mitochondrial outermembrane]IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]TRAF2 and TRAF6[cytosol]dsRNA:MDA5 [cytosol]TAX1BP1:TNFAIP3:TBK1/IKKi[cytosol]Nuclear factorNF-kappa-B [cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5[cytosol]CBP/p300[nucleoplasm]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]dsRNA:MDA5 [cytosol]IPS-1:RIP-1/FADD[mitochondrial outermembrane]dsRNA:MDA5 [cytosol]dsRNA:RIG-I/MDA5:IPS-1[mitochondrial outermembrane]IRF1:Promoter regionof IFN beta[nucleoplasm]dsRNA:MDA5 [cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]ATG5-ATG12 conjugate[cytosol]dsRNA:MDA5 [cytosol]RIG-I E3 ubiquitinligases [cytosol]AGER ligands[extracellularregion]dsRNA:RIG-I/MDA5:IPS-1[mitochondrial outermembrane]ISG15:RIG-Iconjugate [cytosol]MDA5:DAK [cytosol]IRF2:promoters ofINF alpha, INF beta[nucleoplasm]IRF3-P:IRF7-P[nucleoplasm]p-T,4S-IRF3:p-T,4S-IRF3[nucleoplasm]cytosolp-2S-IRF7:p-2S-IRF7[nucleoplasm]NFkB Complex[cytosol]IPS-1:RIP-1/FADD:Casp-8/10prodomain[mitochondrial outermembrane]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10prodomain[mitochondrial outermembrane]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5:NLRC5[cytosol]IRF3/ IRF7 [cytosol]FADD:Casp-8/10prodomain [cytosol]RIG-I E3 ubiquitinligases [cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1[mitochondrial outermembrane]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3[mitochondrial outermembrane]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi[mitochondrial outermembrane]TAX1BP1:TNFAIP3[cytosol]IKK related kinasesTBK1/IKK epsilon[cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]CBP/p300[nucleoplasm]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10[mitochondrial outermembrane]IPS-1:ATG5-ATG12conjugate[mitochondrial outermembrane]RIG-I E3 ubiquitinligases [cytosol]p-2S-IRF7:p-2S-IRF7[nucleoplasm]dsRNA:RIG-I/MDA5[cytosol]nucleoplasmdsRNA:Ub-RIG-I:TRIM25[cytosol]FADD:Casp-8/10prodomain [cytosol]dsRNA:MDA5 [cytosol]IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]TBK1/IKKi:SIKE1[cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]IKKA:IKKB:NEMO[cytosol]CBP/p300[nucleoplasm]IKK related kinasesTBK1/IKK epsilon[cytosol]RIG-I E3 ubiquitinligases [cytosol]dsRNA:RIG-I/MDA5[cytosol]p-T,4S-IRF3:p-T,4S-IRF3[nucleoplasm]NFkB Complex[cytosol]VAF (virus-activatedfactor)[nucleoplasm]p-2S-IRF7:p-2S-IRF7[nucleoplasm]mitochondriondsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]dsRNA:RIG-I/MDA5[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:RIG-I/MDA5:IPS-1[mitochondrial outermembrane]dsRNA:Ub-RIG-I:TRIM25[cytosol]RIG-I E3 ubiquitinligases [cytosol]FADD:procaspase-8/10[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]IPS-1:RIP-1/FADD:procaspase-8/10[mitochondrial outermembrane]RIG-I E3 ubiquitinligases [cytosol]IkBs:NFkB [cytosol]CBP/p300[nucleoplasm]dsRNA:RIG-I/MDA5[cytosol]Casp-8/10 prodomain[cytosol]VAF/pIRF7:CBP/p300bound to type I IFNgene promoter[nucleoplasm]IKK related kinasesTBK1/IKK epsilon[cytosol]RIG-I E3 ubiquitinligases [cytosol]IPS-1:RIP-1/FADD:procaspase-8/10dimer [mitochondrialouter membrane]dsRNA:MDA5 [cytosol]IRF3-P:IRF7-P[nucleoplasm]Casp-8/10 prodomain[cytosol]TRAF2 and TRAF6[cytosol]VAF/pIRF7:CBP/p300[nucleoplasm]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3[mitochondrial outermembrane]NF-kappaB inhibitor[cytosol]dsRNA:RIG-I/MDA5:IPS-1[mitochondrial outermembrane]TRAF2 and TRAF6[cytosol]dsRNA:RIG-I/MDA5[cytosol]IKK related kinasesTBK1/IKK epsilon[cytosol]dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10dimer [mitochondrialouter membrane]ISGylated IRF3[cytosol]E2 enzymesUbcH8/UBE1L[cytosol]IKK related kinasesTBK1/IKK epsilon[cytosol]TRAF2 and TRAF6[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:MDA5 [cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]CBP/p300:pIRF7:pIRF7[nucleoplasm]IPS-1:RIP-1/FADD:Casp-8/10prodomain[mitochondrial outermembrane]RIG-I E3 ubiquitinligases [cytosol]RIG-I E3 ubiquitinligases [cytosol]RIG-I E3 ubiquitinligases [cytosol]IKKA:IKKB:NEMO[cytosol]dsRNA:RIG-I/MDA5:K48Ub-IPS-1[mitochondrial outermembrane]dsRNA:MDA5 [cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:MDA5 [cytosol]IPS-1:ATG5-ATG12conjugate[mitochondrial outermembrane]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7[mitochondrial outermembrane]dsRNA:MDA5 [cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:MDA5 [cytosol]dsRNA:MDA5 [cytosol]FADD:procaspase-8/10dimer [cytosol]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi[mitochondrial outermembrane]IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]VAF/pIRF7:CBP/p300[nucleoplasm]S100B homodimer[extracellularregion]IRF2:Promoter regionof INF alpha[nucleoplasm]dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12[mitochondrial outermembrane]TRAF2 and TRAF6[cytosol]ISG15:UBEIL/UbcH8:CEB1[cytosol]RIG-I E3 ubiquitinligases [cytosol]E2 enzymesUbcH8/UBE1L[cytosol]dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10prodomain[mitochondrial outermembrane]Promoter region oftype-I IFN genes[nucleoplasm]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-1/MDA5:IPS-1:TRAF3[mitochondrial outermembrane]dsRNA:MDA5 [cytosol]RIG-I E3 ubiquitinligases [cytosol]RIG-I E3 ubiquitinligases [cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:MDA5 [cytosol]dsRNA:RIG-I/MDA5:IPS-1[mitochondrial outermembrane]procaspase-8/10[cytosol]ATG5-ATG12 conjugate[cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]IRF3-P:IRF7-P[nucleoplasm]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi[mitochondrial outermembrane]dsRNA:MDA5 [cytosol]dsRNA:MDA5 [cytosol]NFkB Complex[nucleoplasm]RIG-I E3 ubiquitinligases [cytosol]procaspase-8/10dimer [cytosol]CBP/p300[nucleoplasm]CBP/p300:pIRF7:pIRF7[nucleoplasm]RIG-I E3 ubiquitinligases [cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]p-T,4S-IRF3:p-T,4S-IRF3[cytosol]dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD[mitochondrial outermembrane]dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10prodomain:IKKcomplex[mitochondrial outermembrane]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]RIG-I E3 ubiquitinligases [cytosol]RIG-I E3 ubiquitinligases [cytosol]IRF3 bound toIFN-beta promoter[nucleoplasm]dsRNA:Ub-RIG-I:TRIM25[cytosol]dsRNA:MDA5 [cytosol]RIG-I E3 ubiquitinligases [cytosol]p-2S-IRF7:p-2S-IRF7[nucleoplasm]dsRNA:Ub-RIG-I:TRIM25[cytosol]K48polyUb RIG-I/MDA5[cytosol]IRF3-Pdimer:CBP/p300[nucleoplasm]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK[mitochondrial outermembrane]p-IRF3:p-IRF3[nucleoplasm]AGER ligands:AGER[plasma membrane]dsRNA:Ub-RIG-I:TRIM25[cytosol]RIG-I E3 ubiquitinligases [cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7[mitochondrial outermembrane]TAX1BP1:TNFAIP3[cytosol]dsRNA:MDA5 [cytosol]dsRNA:RIG-I/MDA5:K48Ub-IPS-1:PCBP2:AIP4[mitochondrial outermembrane]dsRNA:Ub-RIG-I:TRIM25[cytosol]Nuclear factorNF-kappa-B [cytosol]dsRNA:RIG-I/MDA5:IPS-1:PCBP2[mitochondrial outermembrane]dsRNA bound to RIG-I[cytosol]dsRNA:MDA5 [cytosol]IRF3-P:IRF7-P[nucleoplasm]CBP/p300[nucleoplasm]IRF2:Promoter regionof INF beta[nucleoplasm]dsRNA:Ub-RIG-I:TRIM25[cytosol]IRF-1:IFN-alphapromoter[nucleoplasm]dsRNA:MDA5 [cytosol]dsRNA:RIG-I/MDA5[cytosol]dsRNA:RIG-I/MDA5[cytosol]VAF (virus-activatedfactor)[nucleoplasm]Nuclear factorNF-kappa-B[nucleoplasm]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK[mitochondrial outermembrane]IPS-1:NLRX1[mitochondrial outermembrane]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK[mitochondrial outermembrane]RIG-I E3 ubiquitinligases [cytosol]Activated IKKComplex [cytosol]VAF (virus-activatedfactor)[nucleoplasm]p-IRF3:p-IRF3[nucleoplasm]ISG15:UBEIL/UbcH8:CEB1[cytosol]p-T,4S-IRF3:p-T,4S-IRF3[nucleoplasm]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3[mitochondrial outermembrane]IKKA:IKKB:NEMO[cytosol]IKK related kinasesTBK1/IKK epsilon[cytosol]AGE adducts[extracellularregion]CBP/p300:pIRF7:pIRF7[nucleoplasm]IPS-1:TRAF2/TRAF6[mitochondrial outermembrane]IRF3-P:IRF7-P[cytosol]dsRNA:Ub-RIG-I:TRIM25[cytosol]procaspase-8/10[cytosol]TRIM25 [cytosol]IKK related kinasesTBK1/IKK epsilonCASP8(385-479)ISG15 [cytosol]ATP [cytosol]IKKA:IKKB:NEMOATP [cytosol]HERC5 [cytosol]HMGB1 [extracellularregion]TRIM25 [cytosol]CASP8(1-479)[cytosol]RELA [cytosol]IKKA:IKKB:NEMOK63polyUb-DDX58[cytosol]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7p-S477,S479-IRF7[nucleoplasm]MAVS [mitochondrialouter membrane]ATPATPK63polyUb-DDX58[cytosol]CHUK [cytosol]EP300(1-2414)[nucleoplasm]K63polyUb-DDX58[cytosol]K63polyUb-TRAF3[cytosol]TRAF3 [cytosol]ATP [cytosol]p-S477,S479-IRF7[nucleoplasm]TBK1 [cytosol]APP(672-713)[extracellularregion]IFIH1 [cytosol]p-4S,T404-IRF3[nucleoplasm]UBA7 [cytosol]Promotor region ofinterferon betaCASP8(1-216)[cytosol]K63polyUb-DDX58[cytosol]K63polyUb-TRAF3[cytosol]NLRC5 [cytosol]DDX58 [cytosol]Phospho-NF-kappaBInhibitorPIN1TRIM25 [cytosol]dsRNA:RIG-1/MDA5:IPS-1:TRAF3ATP [cytosol]ADPK63polyUb-DDX58[cytosol]IFNB1Activated IKKComplexEP300(1-2414)[nucleoplasm]K63-UbDDX58K63polyUb-DDX58[cytosol]RIPK1ATG5 [cytosol]MAVS [mitochondrialouter membrane]IFIH1 [cytosol]IKBKE [cytosol]ATP [cytosol]S100B [extracellularregion]HERC5 [cytosol]TRIM25 [cytosol]ATP [cytosol]IFIH1 [cytosol]IFIH1 [cytosol]ATP [cytosol]VAF/pIRF7:CBP/p300bound to type I IFNgene promoterEP300(1-2414)[nucleoplasm]ATP [cytosol]TRAF2 [cytosol]K63polyUb-DDX58[cytosol]MAVS [mitochondrialouter membrane]K63polyUb-DDX58[cytosol]TRIM25 [cytosol]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3ATP [cytosol]K63polyUb-DDX58[cytosol]CREBBP(2-2442)[nucleoplasm]CHUK [cytosol]ADPRNF125:E2 enzyme(UBE2K,UbcH5a-c):K48-polyubiquitinATG12 [cytosol]IFIH1 [cytosol]IFIH1 [cytosol]MAP3K1(2-1512)p-T,4S-IRF3:p-T,4S-IRF3UbMAVS [mitochondrialouter membrane]ATPK63polyUb-DDX58[cytosol]K63polyUb-DDX58RNF135 [cytosol]K63polyUb-DDX58[cytosol]TRIM25 [cytosol]dsRNA bound to RIG-ITRIM25 [cytosol]CBP/p300AGER ligands:AGERIKBKB [cytosol]p-4S,T404-IRF3[nucleoplasm]p-IRF3 dimer:PIN1RNF135 [cytosol]K48polyUb-IFIH1[cytosol]TRIM25 [cytosol]TBK1 [cytosol]TRIM25 [cytosol]TRIM25 [cytosol]MAVSdsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12RNF135 [cytosol]p-S477,S479-IRF7[nucleoplasm]TAX1BP1:TNFAIP3:TBK1/IKKiTBK1 [cytosol]PIN1 [nucleoplasm]DHX58TBK1 [cytosol]RNF135 [cytosol]K48polyUb-RNF125[cytosol]TBK1/IKKi:SIKE1RNF135 [cytosol]FADD [cytosol]RIPK1 [cytosol]RNF135 [cytosol]IRF1:Promotors ofIFN alpha, IFN betaRNF135 [cytosol]MAVS [mitochondrialouter membrane]p-2S-IRF7:p-2S-IRF7IFIH1 [cytosol]ATP [cytosol]ATP [cytosol]K63polyUb-DDX58[cytosol]TANKdsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10TNFAIP3(1-790)[cytosol]IKBKE [cytosol]ATP [cytosol]IFIH1 [cytosol]SIKE1IRF3 [cytosol]IKBKG [cytosol]SAA1(19-122)[extracellularregion]DAK [cytosol]IRF3-P:IRF7-PK48polyUb-TRAF3[cytosol]AGER [plasmamembrane]NFKB1(1-433)[cytosol]IFIH1 [cytosol]EP300(1-2414)[nucleoplasm]RIG-I E3 ubiquitinligasesTRAF2 [cytosol]RELA [nucleoplasm]TRIM25 [cytosol]RIPK1 [cytosol]TBK1 [cytosol]UBE2L6 [cytosol]Promoter region oftype-I IFN genesMAVS [mitochondrialouter membrane]p-S477,S479-IRF7[cytosol]FADD [cytosol]IFIH1 [cytosol]ADPTRAF2 and TRAF6dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10prodomainATP [cytosol]MAVS [mitochondrialouter membrane]MAP3K1(2-1512)[cytosol]CYLDdsRNA:Ub-RIG-I:TRIM25ATP [cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7TANK [cytosol]IFIH1 [cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1IKBKB [cytosol]RNF135 [cytosol]UBE2L6 [cytosol]IRF2 [nucleoplasm]K63polyUb-DDX58[cytosol]IKBKB [cytosol]ATPIFIH1 [cytosol]MAVS [mitochondrialouter membrane]TRIM25 [cytosol]TRIM25 [cytosol]CREBBP(2-2442)[nucleoplasm]IFIH1 [cytosol]TAX1BP1 [cytosol]IFIH1 [cytosol]DDX58 [cytosol]IFIH1 [cytosol]K63polyUb-DDX58[cytosol]TRIM25 [cytosol]DAKCASP8(217-374)MAVS [mitochondrialouter membrane]IRF7p-S477,S479-IRF7[nucleoplasm]IPS-1:ATG5-ATG12conjugateMAVS [mitochondrialouter membrane]TRAF6 [cytosol]CASP10(1-219)[cytosol]K63polyUb-DDX58[cytosol]TRAF6 [cytosol]IRF7 [cytosol]MAVS [mitochondrialouter membrane]N-epsilon-(1-(1-carboxy)ethyl)lysine[extracellularregion]CASP8(1-216)[cytosol]dsRNA:RIG-I/MDA5:IPS-1TRIM25 [cytosol]dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiIFIH1 [cytosol]NFKB2(1-454)[cytosol]RNF125IRF3/ IRF7RNF135 [cytosol]VAF (virus-activatedfactor)FADD [cytosol]NECML [extracellularregion]IKBKG [cytosol]CASP10(1-219)[cytosol]ISG15 [cytosol]TRAF6 [cytosol]RNF135 [cytosol]p-4S,T404-IRF3[nucleoplasm]TRIM25 [cytosol]p-T,4S-IRF3:p-T,4S-IRF3RIPK1 [cytosol]TRAF6 [cytosol]S100A12[extracellularregion]TAX1BP1:TNFAIP3K63polyUb-DDX58[cytosol]IPS-1:NLRX1TNFAIP3(1-790)[cytosol]RNF135 [cytosol]TRAF2 [cytosol]p-S477,S479-IRF7[nucleoplasm]ADPTRIM25 [cytosol]CASP8(1-479)[cytosol]ITCH [cytosol]MAVS [mitochondrialouter membrane]NFkB ComplexFADDp-4S,T404-IRF3[nucleoplasm]VAF/pIRF7:CBP/p300RNF135 [cytosol]CBP/p300:pIRF7:pIRF7CREBBP(2-2442)[nucleoplasm]p-4S,T404-IRF3[nucleoplasm]ATP [cytosol]IKBKE [cytosol]IRF3 bound toIFN-beta promoterIFIH1 [cytosol]MDA5:DAKphosphorylatedIRF3/IRF7NLRX1 [mitochondrialouter membrane]IFIH1 [cytosol]NLRX1K48polyUb-MAVS[mitochondrial outermembrane]dsRNA:RIG-I/MDA5:K48Ub-IPS-1:PCBP2:AIP4E2 enzyme (UBE2K,UbcH5a-c)K63polyUb-DDX58[cytosol]ATP [cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6RNF135 [cytosol]DDX58/IFIH1RNF135 [cytosol]IkBs:NFkBNLRC5ITCHRNF135 [cytosol]IFIH1 [cytosol]CASP10(1-521)[cytosol]PCBP2K48polyUb RIG-I/MDA5ATG5 [cytosol]K63polyUb-TRAF3[cytosol]K48polyUb-DDX58[cytosol]procaspase-8/10ATP [cytosol]MAVS [mitochondrialouter membrane]K63polyUb-DDX58[cytosol]p-S477,S479-IRF7TRIM25 [cytosol]dsRNA:RIG-I/MDA5IFN alpha/beta(IFNA/B)MAVS [mitochondrialouter membrane]PCBP2 [cytosol]NFKB2(1-454)[cytosol]IFIH1 [cytosol]Peptide[extracellularregion]p-S477,S479-IRF7[cytosol]RNF135 [cytosol]MAVS [mitochondrialouter membrane]ATP [cytosol]dsRNA:RIG-I/MDA5:IPS-1:PCBP2IKBKE [cytosol]p-4S,T404-IRF3[nucleoplasm]p-S176,S180-CHUK[cytosol]CREBBP(2-2442)[nucleoplasm]p-5S,T404-IRF3[nucleoplasm]FADD [cytosol]CASP8(375-384)ISG15 [cytosol]ATP [cytosol]TRIM25 [cytosol]TRIM25 [cytosol]APP(672-711)[extracellularregion]dsRNA:MDA5K48polyUbTRAF2 [cytosol]NFKBIB [cytosol]NFKB2(1-454)[nucleoplasm]RIPK1 [cytosol]RIPK1 [cytosol]RNF135 [cytosol]IFIH1 [cytosol]RNF135 [cytosol]ATPK63polyUbCASP10(416-521)MAVS [mitochondrialouter membrane]UBA7 [cytosol]RELA [cytosol]TRAF2 [cytosol]K48polyUb-TRAF3NFKBIA [cytosol]CREBBP(2-2442)[nucleoplasm]p-IRF3:p-IRF3TAX1BP1 [cytosol]CHUK [cytosol]Viral dsRNA (-)StrandedTBK1 [cytosol]K63polyUb-TRAF3IRF3 [cytosol]IRF2:promoters ofINF alpha, INF betaMAVS [mitochondrialouter membrane]IKBKE [cytosol]dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10dimerIRF1 [nucleoplasm]CASP10(1-521)[cytosol]EP300(1-2414)[nucleoplasm]IKBKE [cytosol]TRIM25 [cytosol]p-S477,S479-IRF7[nucleoplasm]MAVS [mitochondrialouter membrane]ATP [cytosol]RNF135 [cytosol]NFKB1(1-433)[nucleoplasm]K63polyUb-TRAF3[cytosol]p-4S,T404-IRF3[cytosol]CREBBP(2-2442)[nucleoplasm]K63polyUb-DDX58[cytosol]EP300(1-2414)[nucleoplasm]ISG15:RIG-IconjugatedsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDCASP10(220-415)TANK [cytosol]IKBKG [cytosol]K63polyUb-DDX58[cytosol]IRF7 [cytosol]p-4S,T404-IRF3[cytosol]ATG12 [cytosol]NFkB Complexp-S177,S181-IKBKB[cytosol]IKBKG [cytosol]FADD [cytosol]RNF135 [cytosol]p-5S,T404-IRF3[nucleoplasm]NFKB1(1-433)[cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKISG15:UBEIL/UbcH8:CEB1K63polyUb-DDX58[cytosol]dsRNA:RIG-I/MDA5:NLRC5OTUD5IRF3-P:IRF7-Pp-2S-IRF7:p-2S-IRF7SIKE1 [cytosol]MAVS [mitochondrialouter membrane]ATP [cytosol]ATP [cytosol]dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiTRAF6 [cytosol]PCBP2 [cytosol]IRF3-Pdimer:CBP/p300p-4S,T404-IRF3[nucleoplasm]IFIH1 [cytosol]ISGylated IRF3dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10prodomain:IKKcomplexK63polyUb-DDX58[cytosol]RNF135 [cytosol]TANK [cytosol]21, 24, 6921, 24, 696621, 24, 6921, 24, 697321, 24, 6921, 24, 696021, 24, 696621, 24, 696621, 24, 696921, 24, 6921, 24, 6921, 24, 6926621, 24, 696641, 49221, 24, 6921, 24, 6921, 24, 69666921, 24, 691121, 24, 6921, 24, 6921, 24, 69221, 24, 69697321, 24, 6921, 24, 69


Description

RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. Functionally RIG-I and MDA5 positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. RIG-I is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas MDA5 is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=168928

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
114870view16:37, 25 January 2021ReactomeTeamReactome version 75
113316view11:38, 2 November 2020ReactomeTeamReactome version 74
112527view15:49, 9 October 2020ReactomeTeamReactome version 73
101439view11:31, 1 November 2018ReactomeTeamreactome version 66
100978view21:09, 31 October 2018ReactomeTeamreactome version 65
100514view19:42, 31 October 2018ReactomeTeamreactome version 64
100060view16:26, 31 October 2018ReactomeTeamreactome version 63
99612view15:00, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94503view09:19, 14 September 2017Mkutmonreactome version 61
86432view09:18, 11 July 2016ReactomeTeamreactome version 56
83061view09:50, 18 November 2015ReactomeTeamVersion54
81373view12:54, 21 August 2015ReactomeTeamVersion53
76841view08:06, 17 July 2014ReactomeTeamFixed remaining interactions
76545view11:53, 16 July 2014ReactomeTeamFixed remaining interactions
75878view09:53, 11 June 2014ReactomeTeamRe-fixing comment source
75578view10:41, 10 June 2014ReactomeTeamReactome 48 Update
74933view13:46, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74577view08:37, 30 April 2014ReactomeTeamReactome46
45045view19:04, 6 October 2011ThomasOntology Term : 'signaling pathway' added !
45044view19:02, 6 October 2011ThomasOntology Term : 'Viral Infection' added !
45043view19:02, 6 October 2011ThomasOntology Term : 'influenza' added !
42120view21:58, 4 March 2011MaintBotAutomatic update
39930view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AGER [plasma membrane]ProteinQ15109 (Uniprot-TrEMBL)
AGER ligands:AGERComplexREACT_24620 (Reactome)
APP(672-711)

[extracellular

region]
ProteinP05067 (Uniprot-TrEMBL)
APP(672-713)

[extracellular

region]
ProteinP05067 (Uniprot-TrEMBL)
ATG12 [cytosol]ProteinO94817 (Uniprot-TrEMBL)
ATG5 [cytosol]ProteinQ9H1Y0 (Uniprot-TrEMBL)
ATP [cytosol]MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated IKK ComplexComplexREACT_7826 (Reactome)
CASP10(1-219) [cytosol]ProteinQ92851 (Uniprot-TrEMBL)
CASP10(1-521) [cytosol]ProteinQ92851 (Uniprot-TrEMBL)
CASP10(220-415)ProteinQ92851 (Uniprot-TrEMBL)
CASP10(416-521)ProteinQ92851 (Uniprot-TrEMBL)
CASP8(1-216) [cytosol]ProteinQ14790 (Uniprot-TrEMBL)
CASP8(1-479) [cytosol]ProteinQ14790 (Uniprot-TrEMBL)
CASP8(217-374)ProteinQ14790 (Uniprot-TrEMBL)
CASP8(375-384)ProteinQ14790 (Uniprot-TrEMBL)
CASP8(385-479)ProteinQ14790 (Uniprot-TrEMBL)
CBP/p300:pIRF7:pIRF7ComplexREACT_25574 (Reactome)
CBP/p300ProteinREACT_25880 (Reactome)
CHUK [cytosol]ProteinO15111 (Uniprot-TrEMBL)
CREBBP(2-2442) [nucleoplasm]ProteinQ92793 (Uniprot-TrEMBL)
CYLDProteinQ9NQC7 (Uniprot-TrEMBL)
DAK [cytosol]ProteinQ3LXA3 (Uniprot-TrEMBL)
DAKProteinQ3LXA3 (Uniprot-TrEMBL)
DDX58 [cytosol]ProteinO95786 (Uniprot-TrEMBL)
DDX58/IFIH1ProteinREACT_25428 (Reactome)
DDX58ProteinO95786 (Uniprot-TrEMBL)
DHX58ProteinQ96C10 (Uniprot-TrEMBL)
E2 enzyme (UBE2K, UbcH5a-c)ProteinREACT_26340 (Reactome)
EP300(1-2414) [nucleoplasm]ProteinQ09472 (Uniprot-TrEMBL)
FADD [cytosol]ProteinQ13158 (Uniprot-TrEMBL)
FADDProteinQ13158 (Uniprot-TrEMBL)
HERC5 [cytosol]ProteinQ9UII4 (Uniprot-TrEMBL)
HMGB1 [extracellular region]ProteinP09429 (Uniprot-TrEMBL)
IFIH1 [cytosol]ProteinQ9BYX4 (Uniprot-TrEMBL)
IFN alpha/beta (IFNA/B)ProteinREACT_26595 (Reactome)
IFNB1ProteinP01574 (Uniprot-TrEMBL)
IKBKB [cytosol]ProteinO14920 (Uniprot-TrEMBL)
IKBKE [cytosol]ProteinQ14164 (Uniprot-TrEMBL)
IKBKG [cytosol]ProteinQ9Y6K9 (Uniprot-TrEMBL)
IKK related kinases TBK1/IKK epsilonProteinREACT_21591 (Reactome)
IKKA:IKKB:NEMOComplexREACT_7693 (Reactome)
IPS-1:ATG5-ATG12 conjugateComplexREACT_25931 (Reactome)
IPS-1:NLRX1ComplexREACT_26115 (Reactome)
IRF1 [nucleoplasm]ProteinP10914 (Uniprot-TrEMBL)
IRF1:Promotors of IFN alpha, IFN betaComplexREACT_26239 (Reactome)
IRF2 [nucleoplasm]ProteinP14316 (Uniprot-TrEMBL)
IRF2:promoters of INF alpha, INF betaComplexREACT_26555 (Reactome)
IRF3 [cytosol]ProteinQ14653 (Uniprot-TrEMBL)
IRF3 bound to IFN-beta promoterComplexREACT_25617 (Reactome)
IRF3-P dimer:CBP/p300ComplexREACT_26303 (Reactome)
IRF3-P:IRF7-PComplexREACT_26495 (Reactome)
IRF3-P:IRF7-PComplexREACT_26957 (Reactome)
IRF3/ IRF7ProteinREACT_21735 (Reactome)
IRF7 [cytosol]ProteinQ92985 (Uniprot-TrEMBL)
IRF7ProteinQ92985 (Uniprot-TrEMBL)
ISG15 [cytosol]ProteinP05161 (Uniprot-TrEMBL)
ISG15:RIG-I conjugateComplexREACT_26209 (Reactome)
ISG15:UBEIL/UbcH8:CEB1ComplexREACT_26934 (Reactome)
ISGylated IRF3ComplexREACT_27520 (Reactome)
ITCH [cytosol]ProteinQ96J02 (Uniprot-TrEMBL)
ITCHProteinQ96J02 (Uniprot-TrEMBL)
IkBs:NFkBComplexREACT_7272 (Reactome)
K48polyUb RIG-I/MDA5ComplexREACT_25791 (Reactome)
K48polyUb-DDX58 [cytosol]ProteinO95786 (Uniprot-TrEMBL)
K48polyUb-IFIH1 [cytosol]ProteinQ9BYX4 (Uniprot-TrEMBL)
K48polyUb-MAVS

[mitochondrial outer

membrane]
ProteinQ7Z434 (Uniprot-TrEMBL)
K48polyUb-RNF125 [cytosol]ProteinQ96EQ8 (Uniprot-TrEMBL)
K48polyUb-TRAF3 [cytosol]ProteinQ13114 (Uniprot-TrEMBL)
K48polyUb-TRAF3ComplexQ13114 (Uniprot-TrEMBL)
K48polyUbREACT_24769 (Reactome)
K63-UbProteinREACT_21627 (Reactome)
K63polyUb-DDX58 [cytosol]ProteinO95786 (Uniprot-TrEMBL)
K63polyUb-DDX58ComplexO95786 (Uniprot-TrEMBL)
K63polyUb-TRAF3 [cytosol]ProteinQ13114 (Uniprot-TrEMBL)
K63polyUb-TRAF3ComplexQ13114 (Uniprot-TrEMBL)
K63polyUbREACT_21645 (Reactome)
MAP3K1(2-1512) [cytosol]ProteinQ13233 (Uniprot-TrEMBL)
MAP3K1(2-1512)ProteinQ13233 (Uniprot-TrEMBL)
MAVS [mitochondrial outer membrane]ProteinQ7Z434 (Uniprot-TrEMBL)
MAVSProteinQ7Z434 (Uniprot-TrEMBL)
MDA5:DAKComplexREACT_25465 (Reactome)
N-epsilon-(1-(1-carboxy)ethyl)lysine

[extracellular

region]
MetaboliteCHEBI:60125 (ChEBI)
NECML [extracellular region]MetaboliteCHEBI:53014 (ChEBI)
NFKB1(1-433) [cytosol]ProteinP19838 (Uniprot-TrEMBL)
NFKB1(1-433) [nucleoplasm]ProteinP19838 (Uniprot-TrEMBL)
NFKB2(1-454) [cytosol]ProteinQ00653 (Uniprot-TrEMBL)
NFKB2(1-454) [nucleoplasm]ProteinQ00653 (Uniprot-TrEMBL)
NFKBIA [cytosol]ProteinP25963 (Uniprot-TrEMBL)
NFKBIB [cytosol]ProteinQ15653 (Uniprot-TrEMBL)
NFkB ComplexComplexREACT_7108 (Reactome)
NFkB ComplexComplexREACT_7143 (Reactome)
NLRC5 [cytosol]ProteinQ86WI3 (Uniprot-TrEMBL)
NLRC5ProteinQ86WI3 (Uniprot-TrEMBL)
NLRX1 [mitochondrial outer membrane]ProteinQ86UT6 (Uniprot-TrEMBL)
NLRX1ProteinQ86UT6 (Uniprot-TrEMBL)
OTUD5ProteinQ96G74 (Uniprot-TrEMBL)
PCBP2 [cytosol]ProteinQ15366 (Uniprot-TrEMBL)
PCBP2ProteinQ15366 (Uniprot-TrEMBL)
PIN1 [nucleoplasm]ProteinQ13526 (Uniprot-TrEMBL)
PIN1ProteinQ13526 (Uniprot-TrEMBL)
Peptide

[extracellular

region]
MetaboliteCHEBI:16670 (ChEBI)
Phospho-NF-kappaB InhibitorProteinREACT_7645 (Reactome)
Promoter region of type-I IFN genesREACT_25653 (Reactome)
Promotor region of interferon betaREACT_25836 (Reactome)
RELA [cytosol]ProteinQ04206 (Uniprot-TrEMBL)
RELA [nucleoplasm]ProteinQ04206 (Uniprot-TrEMBL)
RIG-I E3 ubiquitin ligasesProteinREACT_25644 (Reactome)
RIPK1 [cytosol]ProteinQ13546 (Uniprot-TrEMBL)
RIPK1ProteinQ13546 (Uniprot-TrEMBL)
RNF125:E2 enzyme

(UBE2K,

UbcH5a-c):K48-polyubiquitin
ComplexREACT_25756 (Reactome)
RNF125ProteinQ96EQ8 (Uniprot-TrEMBL)
RNF135 [cytosol]ProteinQ8IUD6 (Uniprot-TrEMBL)
S100A12

[extracellular

region]
ProteinP80511 (Uniprot-TrEMBL)
S100B [extracellular region]ProteinP04271 (Uniprot-TrEMBL)
SAA1(19-122)

[extracellular

region]
ProteinP0DJI8 (Uniprot-TrEMBL)
SIKE1 [cytosol]ProteinQ9BRV8 (Uniprot-TrEMBL)
SIKE1ProteinQ9BRV8 (Uniprot-TrEMBL)
TANK [cytosol]ProteinQ92844 (Uniprot-TrEMBL)
TANKProteinQ92844 (Uniprot-TrEMBL)
TAX1BP1 [cytosol]ProteinQ86VP1 (Uniprot-TrEMBL)
TAX1BP1:TNFAIP3:TBK1/IKKiComplexREACT_25569 (Reactome)
TAX1BP1:TNFAIP3ComplexREACT_26309 (Reactome)
TBK1 [cytosol]ProteinQ9UHD2 (Uniprot-TrEMBL)
TBK1/IKKi:SIKE1ComplexREACT_25799 (Reactome)
TNFAIP3(1-790) [cytosol]ProteinP21580 (Uniprot-TrEMBL)
TRAF2 [cytosol]ProteinQ12933 (Uniprot-TrEMBL)
TRAF2 and TRAF6ProteinREACT_26063 (Reactome)
TRAF3 [cytosol]ProteinQ13114 (Uniprot-TrEMBL)
TRAF6 [cytosol]ProteinQ9Y4K3 (Uniprot-TrEMBL)
TRIM25 [cytosol]ProteinQ14258 (Uniprot-TrEMBL)
UBA7 [cytosol]ProteinP41226 (Uniprot-TrEMBL)
UBE2L6 [cytosol]ProteinO14933 (Uniprot-TrEMBL)
UbProteinREACT_3316 (Reactome)
VAF (virus-activated factor)ComplexREACT_25426 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN

gene promoter
ComplexREACT_26244 (Reactome)
VAF/pIRF7:CBP/p300ComplexREACT_25775 (Reactome)
Viral dsRNA (-) StrandedREACT_6589 (Reactome)
dsRNA bound to RIG-IComplexREACT_25966 (Reactome)
dsRNA:MDA5ComplexREACT_26245 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:TRAF3ComplexREACT_25597 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7ComplexREACT_25519 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiComplexREACT_26022 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3ComplexREACT_26564 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12ComplexREACT_26782 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:PCBP2ComplexREACT_25961 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10ComplexREACT_26650 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerComplexREACT_26858 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDComplexREACT_26077 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1ComplexREACT_26122 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7ComplexREACT_26674 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiComplexREACT_25493 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKComplexREACT_27050 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6ComplexREACT_26067 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1ComplexREACT_26220 (Reactome)
dsRNA:RIG-I/MDA5:K48 Ub-IPS-1:PCBP2:AIP4ComplexREACT_26024 (Reactome)
dsRNA:RIG-I/MDA5:NLRC5ComplexREACT_26732 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10

prodomain:IKK

complex
ComplexREACT_27017 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainComplexREACT_26324 (Reactome)
dsRNA:RIG-I/MDA5ComplexREACT_25628 (Reactome)
dsRNA:Ub-RIG-I:TRIM25ComplexREACT_26009 (Reactome)
p-2S-IRF7:p-2S-IRF7ComplexREACT_21640 (Reactome)
p-2S-IRF7:p-2S-IRF7ComplexREACT_21965 (Reactome)
p-4S,T404-IRF3 [cytosol]ProteinQ14653 (Uniprot-TrEMBL)
p-4S,T404-IRF3 [nucleoplasm]ProteinQ14653 (Uniprot-TrEMBL)
p-5S,T404-IRF3 [nucleoplasm]ProteinQ14653 (Uniprot-TrEMBL)
p-IRF3 dimer:PIN1ComplexREACT_26699 (Reactome)
p-IRF3:p-IRF3ComplexREACT_26064 (Reactome)
p-S176,S180-CHUK [cytosol]ProteinO15111 (Uniprot-TrEMBL)
p-S177,S181-IKBKB [cytosol]ProteinO14920 (Uniprot-TrEMBL)
p-S477,S479-IRF7 [cytosol]ProteinQ92985 (Uniprot-TrEMBL)
p-S477,S479-IRF7 [nucleoplasm]ProteinQ92985 (Uniprot-TrEMBL)
p-S477,S479-IRF7ProteinQ92985 (Uniprot-TrEMBL)
p-T,4S-IRF3:p-T,4S-IRF3ComplexREACT_7146 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ComplexREACT_7444 (Reactome)
phosphorylated IRF3/IRF7ProteinREACT_21760 (Reactome)
procaspase-8/10ProteinREACT_26572 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_24935 (Reactome)
ADPArrowREACT_25327 (Reactome)
ADPArrowREACT_25368 (Reactome)
ADPArrowREACT_6848 (Reactome)
AGER ligands:AGERArrowREACT_6906 (Reactome)
ATPREACT_24935 (Reactome)
ATPREACT_25327 (Reactome)
ATPREACT_25357 (Reactome)
ATPREACT_25368 (Reactome)
ATPREACT_6848 (Reactome)
Activated IKK ComplexArrowREACT_24935 (Reactome)
Activated IKK Complexmim-catalysisREACT_6848 (Reactome)
ArrowREACT_25209 (Reactome)
CASP10(220-415)ArrowREACT_24999 (Reactome)
CASP10(416-521)ArrowREACT_24999 (Reactome)
CASP8(217-374)ArrowREACT_24999 (Reactome)
CASP8(375-384)ArrowREACT_24999 (Reactome)
CASP8(385-479)ArrowREACT_24999 (Reactome)
CBP/p300:pIRF7:pIRF7ArrowREACT_25099 (Reactome)
CBP/p300REACT_25099 (Reactome)
CBP/p300REACT_25196 (Reactome)
CBP/p300REACT_25275 (Reactome)
CYLDmim-catalysisREACT_25235 (Reactome)
DAKArrowREACT_25160 (Reactome)
DDX58/IFIH1REACT_25252 (Reactome)
DDX58ArrowREACT_25235 (Reactome)
DDX58REACT_25191 (Reactome)
DDX58REACT_25357 (Reactome)
DHX58TBarREACT_25357 (Reactome)
E2 enzyme (UBE2K, UbcH5a-c)ArrowREACT_25252 (Reactome)
FADDREACT_25147 (Reactome)
IFN alpha/beta (IFNA/B)ArrowREACT_25209 (Reactome)
IFNB1ArrowREACT_25400 (Reactome)
IKK related kinases TBK1/IKK epsilonREACT_25179 (Reactome)
IKKA:IKKB:NEMOREACT_24935 (Reactome)
IKKA:IKKB:NEMOREACT_25134 (Reactome)
IPS-1:ATG5-ATG12 conjugateREACT_24982 (Reactome)
IPS-1:NLRX1ArrowREACT_25223 (Reactome)
IPS-1:NLRX1TBarREACT_24957 (Reactome)
IRF2:promoters of INF alpha, INF betaTBarREACT_25209 (Reactome)
IRF3 bound to IFN-beta promoterArrowREACT_25153 (Reactome)
IRF3 bound to IFN-beta promoterArrowREACT_25400 (Reactome)
IRF3-P dimer:CBP/p300ArrowREACT_25275 (Reactome)
IRF3-P dimer:CBP/p300REACT_25153 (Reactome)
IRF3-P:IRF7-PArrowREACT_24983 (Reactome)
IRF3-P:IRF7-PArrowREACT_25352 (Reactome)
IRF3-P:IRF7-PREACT_25196 (Reactome)
IRF3-P:IRF7-PREACT_25352 (Reactome)
IRF3/ IRF7REACT_25170 (Reactome)
IRF7REACT_25308 (Reactome)
ISG15:RIG-I conjugateArrowREACT_25191 (Reactome)
ISG15:RIG-I conjugateTBarREACT_25357 (Reactome)
ISG15:UBEIL/UbcH8:CEB1REACT_25191 (Reactome)
ISGylated IRF3TBarREACT_24932 (Reactome)
ITCHREACT_25398 (Reactome)
ITCHmim-catalysisREACT_25398 (Reactome)
IkBs:NFkBREACT_6848 (Reactome)
K48polyUb RIG-I/MDA5ArrowREACT_25252 (Reactome)
K48polyUb-TRAF3ArrowREACT_24974 (Reactome)
K48polyUbREACT_24974 (Reactome)
K48polyUbREACT_25398 (Reactome)
K63-UbArrowREACT_25055 (Reactome)
K63polyUb-DDX58REACT_25235 (Reactome)
K63polyUb-TRAF3REACT_25364 (Reactome)
K63polyUbREACT_25220 (Reactome)
MAP3K1(2-1512)REACT_25003 (Reactome)
MAVSREACT_24957 (Reactome)
MAVSREACT_25223 (Reactome)
MDA5:DAKREACT_25160 (Reactome)
NFkB ComplexArrowREACT_6848 (Reactome)
NFkB ComplexArrowREACT_6906 (Reactome)
NFkB ComplexREACT_6906 (Reactome)
NLRC5REACT_25113 (Reactome)
NLRX1REACT_25223 (Reactome)
OTUD5mim-catalysisREACT_25055 (Reactome)
PCBP2REACT_24967 (Reactome)
PIN1ArrowREACT_24932 (Reactome)
PIN1REACT_25077 (Reactome)
Phospho-NF-kappaB InhibitorArrowREACT_6848 (Reactome)
Promoter region of type-I IFN genesREACT_24975 (Reactome)
Promotor region of interferon betaREACT_25153 (Reactome)
REACT_24920 (Reactome) p-IRF7 dimers are then transported into the nucleus and assemble with the coactivator CBP/p300 to activate transcription of type I interferons and other target genes.
REACT_24932 (Reactome) PIN1 acts as a negative regulator of IFN induction. Its association with IRF3 leads to ubiquitin-mediated proteosomal degradation of IRF3. PIN1 on its own does not have ubiquitin activation, transfer or ligase activities. Exactly how this IRF3 degradation is achieved is unclear at present. Immunoprecipitation of ubiquitin followed by immunoblot analysis for IRF3 demonstrated that polyubiquitination of IRF3 was induced by RNA stimulation and that polyubiquitination was augmented by PIN1 expression and abrogated by expression of PIN1-specific shRNA.
REACT_24935 (Reactome) In Human, IKKs - IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kB by various stimuli. It contains two catalytic subunits, IKK alpha and IKK beta, and a regulatory subunit, IKKgamma/NEMO. The activation of IKK complex and NFkB mediated antiviral responce are dependent on the phosphorylation of IKK alpha/beta at its activation loop and the ubiquitination of NEMO.[Solt et al 2009]; [Li et al 2002]. NEMO ubiquitination by TRAF6 is required for optimal activation of IKKalpha/beta; it's remained unclear if NEMO subunit undergoes K63-linked or linear ubiquitination.

This basic trimolecular complex is referred to as the IKK complex. Each catalytic IKK subunit has a N-term kinase domain a leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-ter NEMO binding domain (NBD). IKK catalytic subunits are dimerized through their LZ motifs.

IKK beta is the major IKK catalytic subunit for NF-kB activation. MEKK1 can activate both IKK-alpha (IKKA) and IKK-beta (IKKB) in vivo. MEKK1 phosphorylates Ser-176 and Ser-180 in IKKA and Ser-177 and Ser-181 in IKKB activation loop and thus activate the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.
REACT_24946 (Reactome) Procaspase-8/10 undergo dimerization and the subsequent conformational changes at the receptor complex results in the formation of catalytic active caspase dimers.
REACT_24957 (Reactome) Upon binding the dsRNA, RIG-I and MDA5 recruit downstream signal transducer, a mitochondria-bound protein: IPS-1/VISA/MAVS/CARDIF. This mitochondria-bound adaptor has been given four different names according to the various groups who identified it: MAVS, mitochondrial antiviral signaling; IPS-1, interferonbeta promoter stimulator 1; VISA, virus-induced signaling adaptor; CARDIF, CARD adaptor inducing IFNbeta. IPS-1 is an adaptor protein with an N-terminal CARD-like domain (CLD) and with this it associates with the CARD regions of RIG-I and MDA5 and mediate the induction of interferons.
REACT_24967 (Reactome) Poly(rC) binding protein 2 (PCB2), is one of the negative regulators of RIG-I/MDA5 signaling. It interacts with MAVS/IPS-1 and mediates its ubiquitin/proteasomal degradation by recruiting E3 ligase AIP4/ITCHY.
REACT_24974 (Reactome) TRAF3 is dual regulated by DUBA and TRIAD3A. TRAF3 K63-polyubiquitin is removed by DUBA to disrupt TRAF3-TBK1/IKKi interactions. TRAF3 then undergoes a late phase K48-linked polyubiquitination by TRIAD3A, leading to TRAF3 proteasomal degradation. Thus TRIAD3A acts as a E3- ubiquitin ligase that negatively regulates RLR pathway.
REACT_24975 (Reactome) IRF7 and VAF transcription factors binds to IFN-alpha and IFN-beta promoter regions and induce the IFN-alpha and beta mRNA.
REACT_24982 (Reactome) Autophagy protein 5 (ATG5) and autophagy-related protein 12 (ATG12) conjugate negatively regulates the type I IFN production pathway by directly associating with RIG-I/MDA5 and IPS-1 through the caspase recruitment domains (CARDs). The ATG5-ATG12 conjugate intercalates between the CARDs of RIG-I/MDA5 and IPS-1 and inhibits signal transmission, resulting in suppression of type I IFN production and innate antiviral immune responses.
REACT_24983 (Reactome) Phosphorylation of these transcription factors IRF3 and IRF7 results in a conformational change that allows their dimerization to form homo- or hetero dimers. Each of the three different combinations of dimers (IRF3:IRF3, IRF7:IRF7 and IRF3:IRF7) may selectively effect the transcription of IFN-alpha gene subfamilies and IFN-beta genes.
REACT_24986 (Reactome) TRAF family member-associated NF-kB activator (TANK also known as I-TRAF) plays an important role in IFN induction through both RIG-I and Toll-like receptor-dependent pathways. TANK has been identified as a TRAF6 binding protein. Transient transfection experiments in 293T cells revealed that TRAF6 associates with IPS-1, TBK1, IKKi, and TANK (Konno H et al).
REACT_24999 (Reactome) Processing of caspases is required for activation of downstream signaling and dsRNA stimulation inducese the processing of these caspases. The nonapoptotic caspase function of both caspase-8 and -10 does not require the protease activity and the DED-containing prodomains are sufficient for NF-kB activation.
REACT_25003 (Reactome) TRAF6 requires MEKK1 to activate NF-kB and MEKK1 may interact with TRAF6, which in turn contribute to the activation of IKK and MAPKK, leading to the activation of NF-kB and AP-1. (Yoshida et al)
REACT_25051 (Reactome) TRAF3 binds with both IPS-1 and downstream interferon regulatory factor 3/7 (IRF3/7) kinases TBK1 and IKK-epsilon (IKKi) and thus serves as a critical link between RIG-I/MDA5 adaptors and downstream regulatory kinases important for interferon regulatory factor (IRF) activation (Oganesyan et al).
SIKE (for Suppressor of IKKepsilon) interacts with IKKepsilon and TBK1. SIKE is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection. Overexpression of SIKE disrupted the interactions of IKKepsilon or TBK1 with RIG-I.
REACT_25055 (Reactome) Deubiquitinating enzyme A (DUBA), an ovarian tumor (OTU) domain-containing deubiquitinating enzyme, is a negative regulator of type I IFN production. TRAF3 is one of the DUBA interacting protein and expression of DUBA increases the cleavage of K63-linked ubiquitin chains of TRAF3. TRAF3 ubiquitination facilitates the recruitment of downstream signaling components and DUBA mediated removal of ubiquitin chains reduce the TRAF3-TBK1 interaction and subsequent blockade of IRF3 and IRF7 phosphorylation.
REACT_25077 (Reactome) Two cluster of serine residues in the C-terminus of IRF3 are essential for its activation. Cluster 1, comprising Ser385 and Ser386, is essential for the formation of IRF3 dimers. The second cluster include a series of serine and threonine residues between Ser396 and Ser405. Phosphorylation of residues in both clusters has been noted in response to virus infection and dsRNA treatment, and the IKKi/TBK1 kinase complex has been shown to phosphorylate both clusters.
Yamaoka et al has shown that IRF3 is also phosphorylated on Ser339 after dsRNA stimulation, however this phosphorylation is associated with destabilization rather than activation of IRF3. This Ser339 precedes a proline residue 340 (Pro340) and this serine-proline motif acts as a binding site for the protein PIN1, a peptidyl-prolyl-isomerase. PIN1 consist of two distinct domains, a short N-terminal WW domain and a C-terminal catalytic domain. The WW domain of PIN1 is involved in binding the ser339-pro340 region. Yamaoka et al showed that exogenous expression of PIN1 suppresses IRF3 activation and type I interferon production and, conversely, that siRNA silencing of PIN1 leads to enhancement of IRF3 activation and IFNB production.
REACT_25079 (Reactome) TANK acts as an adapter protein and regulates the assembly of TBK1/IKK epsilon complex with upstream signaling molecules. SIKE (for Suppressor of IKKepsilon) interacts with IKKepsilon and TBK1. SIKE is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection. Overexpression of SIKE disrupted the interactions of IKKepsilon or TBK1 with RIG-1.
REACT_25099 (Reactome) p-IRF7 dimers after translocation into nucleus interact with the coactivators p300 and CBP (CREB-binding protein) to form a stable complex. This interaction further increases the transcriptional activity of IRF7.
REACT_25113 (Reactome) NLRC5 competes with IPS-1 for binding to the CARD domain of RIG-I/MDA5. NLRC5 specifically recognize the CARD domains of RIG-I/MDA5 when the CARD domains become accessible after viral infection, leading to dampened activation of IRF3.
REACT_25134 (Reactome) The molecular mechanisms by which caspase-8/10 attribute to NF-kB signaling is unclear. Caspase-8 might act as a scaffolding protein by bringing the IKK-complex in close proximity to its activator TAK1. The prodomain of Caspase-8 could interact with IKK2 in the IKK complex whereas the protease homology domain failed to do so. These results indicate that the interaction of the DEDs-containing prodomain of caspase-8 with the IKKs may be crucial for the NF-kB induction by caspase-8.
REACT_25147 (Reactome) Receptor-interacting protein 1 (RIP1) and Fas-Associated Death Domain (FADD) are death domain (DD)-containing proteins. These proteins interact with IPS-1 and activate NF-kB through interaction and activation of caspase-8 and caspase-10.
REACT_25153 (Reactome) IRF3:CBP/p300 complex binds specifically to IFN-beta promoter region and induces IFN-beta mRNA expression.
REACT_25160 (Reactome) MDA5 is the closest relative of RIG-I and contains two CARD-like regions, a DExD/H helicase domain, and a C-terminal region similar to the RD of RIG-I. MDA5 with its C-terminal domain (CTD) preferentially binds dsRNA with blunt ends, but does not associate with dsRNA with either 5' or 3' overhangs. Upon binding dsRNA, MDA5 is presumed to undergo structural alteration and, thereby unmask the CARDs enabling them to recruit downstream signal transducer proteins. Dihydroxyacetone kinase (DAK) binds to the CARD domains of MDA5 and acts as a negative regulator of MAD5. It is released upon the conformational change induced by viral RNA binding, allowing the MDA5 CARD domains to bind to IPS-1 CARD.
REACT_25167 (Reactome) Caspase-8 (casp-8) and caspase-10 (casp-10) are involved in RIG-I/MDA5-dependent antiviral immune responses. Caspase-8/10 activation contributes to NF-kB activation in response to viral dsRNA.
Caspase-8/10 are synthesized as zymogens (procaspases), containing a large N-terminal prodomain with two death effector domains (DED), and a C-terminal catalytic subunit composed of small and a large domain separated by a smaller linker region. FADD plays a crucial role in the recruitment and activation of procaspase-8/10. The two DED domains of procaspase-8/10 interacts with DED domain of FADD.
REACT_25170 (Reactome) IRF3 and IRF7 (IRF3/IRF7) are the two major members of the interferon regulatory factor (IRF) family, involved in modulating the IFN gene expression. However, their roles are different in these processes. In the early phase of viral infection, preexisting IRF-3 is activated and induces expression of IFN beta and IFN alpha4. These early produced IFNs transcriptionally induce IRF-7, and upon viral infection, the induced high-level IRF-7 is activated and transactivates multiple IFN genes, leading to robust production of IFNs in response to viral infection. IPS-1 interacts with both IRF3 and IRF7 and recruits them to RIG-1. TBK1/IKKi kinases phosphorylate and activate IRF3/IRF7.
REACT_25179 (Reactome) TAX1BP1 functions as an adaptor molecule for A20 to terminate antiviral signaling. TAX1BP1 and A20 blocked antiviral signaling by disrupting K63-linked polyubiquitination of TBK1-IKKi.
REACT_25191 (Reactome) ISG15 is a ubiquitin (Ub)-like protein which is conjugated to intracellular proteins via an isopeptide bond. Similar to ubiquitination, the conjugation of ISG15 (ISGylation) requires a three-step process, involving an E1 activating enzyme (UBE1L), an E2 conjugating enzyme (UbcM8/H8), and HERC5/Ceb1 an IFN-inducible ISG15-specific E3 ligase. ISG15 conjugation may play an important regulatory role in IFN-mediated antiviral responses. IFN induces ISG15 conjugation to RIG-I protein and lowers cellular levels of unconjugated RIG-I protein and, thus, negatively regulates RIG-I-mediated antiviral signaling. ISGylated RIG-I protein becomes subject to an irreversible biochemical process, such as proteolysis or proteasomeal degradation.
REACT_25196 (Reactome) IRF3 and IRF7 associate with each other and they further interact with the coactivators CBP and p300 to form a more potent transcription factor complex called VAF (virus-activated factor).
REACT_25209 (Reactome) The Interferon alpha and beta genes are transcribed and translated yielding IFNA and IFNB which are secreted. This process is positively regulated by Interferon Regulatory Factor 1 and negatively regulated by Interferon Regulatory Factor 2, which compete for binding to the same regulatory element (Harada et al. 1989).
REACT_25220 (Reactome) On viral infection RIG-I undergoes robust ubiquitination at its N-terminal CARD region. TRIM25 a member of tripartite motif (TRIM) protein family and Riplet/RNF135/REUL are the ubiquitin E3 ligases involved in K-63-linked polyubiquitination of RIG-I. TRIM25 contains a cluster of domains including a RING-finger domain, a B box/coiled-coil domain and a SPRY domain. The interaction is mediated by the SPRY domain of TRIM25 and the N-terminal CARDs of RIG-I. The polyubiquitin chains added by TRIM25 are unanchored Lys-172 (K-172) residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for IPS-1 binding, as well as the ability of RIG-I to induce antiviral signal transduction. RING-finger protein, RNF135 specifically associate with RIG-I through its PRY and SPRY domains. The Lys 154, 164, and 172 residues of the RIG-I CARD domain were determined to be critical for efficient RNF135-mediated ubiquitination and for the ability of RIG-I to induce antiviral signal transduction. (Michaela et al, Goa et al)
REACT_25223 (Reactome) NLRX1 is a member of nucleotide-binding domain and leucine-rich repeat containing (NLR) protein family. NLRX1 competes with RIG-I for IPS-1 interaction and has been identified as a negative regulator of RLR signaling. NLRX1 resides at the outer mitochondrial membrane where IPS-1 is located and this interaction is mediated by the CARD region of IPS-1 and a putative nucleotide-binding domain (NBD) of NLRX1. This interaction between NLRX1 and IPS-1 prevents the association between RIG-1/MDA5 and IPS-1.
REACT_25235 (Reactome) CYLD is an ovarian tumor (OTU) domain-containing deubiquitinating enzyme (DUB) and has been identified as a negative regulator of RIG-I mediated antiviral signaling. CYLD associates with the CARD domain of RIG-I and removes K63-linked ubiquitin from the RIG-I CARDs that are conjugated by the E3 ubiquitin ligase, TRIM25 and RNF135.
REACT_25252 (Reactome) RNF125 acts as an E3-ubiquitin ligase that conjugates with RIG-I, MDA5 and IPS-1 and mediate their proteosomal degradation. UbcH1, UbcH5a, UbcH5b, and UbcH5c function as an E2 enzyme and conjugate ubiquitin to RNF125 and RIG-1 via K48. Among these enzymes UbcH5c is the major E2 enzyme showing enhanced ubiquitin conjugation to RIG-I. RNF125 mediated ubiquitination of RIG-I/MDA5 and IPS1 inhibits RIG-I signaling by shunting these proteins toward proteasomal degradation.
REACT_25262 (Reactome) IPS-1 interacts with TRAF2 and TRAF6 through its consensus TRAF-interaction motif (TIM) (TRAF2 143-PVGET-147 and TRAF6 153-PGENSE-158 & 455-PEENEY-460). Although IPS-1 can bind to both TRAF6 and TRAF2, TRAF2 binding is not required for IPS-1 activation of NF-kB.
REACT_25275 (Reactome) Phosphorylated IRF3 dimer translocated to the nucleus interacts with the coactivator CBP/p300. This interaction prevents the export of activated IRF3 dimer from nucleus and it may also alter the conformation of the DNA binding domain of IRF3, and induce specific DNA binding of IRF3.
REACT_25292 (Reactome) Phosphorylation stimulates the C-terminal autoinhibitory domain of IRF7 to attain a highly extended conformation triggering dimerization through extensive contacts to a second IRF7 subunit.
REACT_25308 (Reactome) TRAF6 associates with and activates IRF7 but not IRF3.
REACT_25327 (Reactome) IRF7 is activated through phosphorylation of residues Ser477 and Ser479 by TBK1/IKKi kinase complex.
REACT_25352 (Reactome) Phosphorylated IRF dimers after dimerization translocates into the nucleus and associate with general coactivators like CBP/p300 and bind to type-I IFN promoter region.
REACT_25357 (Reactome) RIG-I has two copies of caspase recruitment domain (CARD) in its N-terminus, DExD/H helicase domain with an ATP binding motif in the middle and a repressor domain (RD) in the C-terminus. In the absence of appropriate stimulation, RIG-I is in a 'closed' conformation in which the repressor domain phyically interacts with the helicase domain masking CARD. Upon viral infection the free triphosphate structure at the 5' end of the viral RNAs activate RIG-I by binding to its RNA helicase domain. This provokes change in RIG-I conformation exposing the CARD leading to RIG-I dimerization and allowing it to interact with the mitochondria-bound interferon beta promoter stimulator-1 (IPS-1).
REACT_25364 (Reactome) TRAF3 a E3 ligase for K63-linked polyubiquitination, is one of the critical molecules required for mediating IPS-1 dependent type I IFN production. TRAF3 interacts directly with IPS-1 through the TRAF domain of TRAF3 and a TRAF-interaction motif (TIM) with in IPS-1.
REACT_25368 (Reactome) Human IRF3 is activated through a two-step phosphorylation in the C-terminal domain mediated by TBK1 and/or IKKi, requiring Ser386 and/or Ser385- site 1; and a cluster of serine/threonine residues between Ser396 and Ser405- site 2 [Panne et al 2007]. Phosphorylated residues at site 2 (Ser396—Ser405) alleviate autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitate phosphorylation at site 1 (Ser385 or Ser386). Phosphorylation at site 1 is required for IRF3 dimerization.
IRF3 and IRF7 transcription factors possess distinct structural characteristics; IRF7 is phosphorylated on Ser477 and Ser479 residues [Lin R et al 2000].
Since the number of serine residues involved into IRF activation remains unclear this reaction represents a minimum stoichiometry to achieve the phosphorylation of at least 3 Ser residues per each IRF transcription factor. [Lin et al 2000, Ning et al 2008]
REACT_25398 (Reactome) On viral infection PCB2 binds MAVS/IPS-1 and recruits the HECT domain-containing E3 ligase AIP4/ITCHY. AIP4 catalyses K48-polyubiquitination and degradation of MAVS. PCBP2 overexpression enhanced the interaction between MAVS and AIP4 and led to more degradation of MAVS. MAVS/IPS-1 regulation is very important in preventing excessive harmful immune responses.
REACT_25400 (Reactome) The IFN-beta genes are transcribed and translated yielding IFNB proteins which are secreted. This process is positively regulated by IRF3:CBP/p300 transcription factor complex.
REACT_6848 (Reactome) In human, IkB is an inhibitory protein that sequesters NF-kB in the cytoplasm, by masking a nuclear localization signal, located just at the C-terminal end in each of the NF-kB subunits.

A key event in NF-kB activation involves phosphorylation of IkB by an IkB kinase (IKK). The phosphorylation and ubiquitination of IkB kinase complex is mediated by two distinct pathways, either the classical or alternative pathway. In the classical NF-kB signaling pathway, the activated IKK (IkB kinase) complex, predominantly acting through IKK beta in an IKK gamma-dependent manner, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of human IkB-alpha or Ser19 and Ser22 of human IkB-beta); Once phosphorylated, IkB undergoes ubiquitin-mediated degradation, releasing NF-kB.

REACT_6906 (Reactome) NFkB is a family of transcription factors that play pivotal roles in immune, inflammatory, and antiapoptotic responses. There are five NF-kB/Rel family members, p65 (RelA), RelB, c-Rel, p50/p105 (NF-kappa-B1) and p52/p100 (NFkappa-B2), All members of the NFkB family contain a highly conserved DNA-binding and dimerization domain called Rel-homology region (RHR). The RHR is responsible for homo- or heterodimerization. Therefor, NF-kappa-B exists in unstimulated cells as homo or heterodimers; the most common heterodimer is p65/p50. NF-kappa-B is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins called IkBs, which mask the nuclear localization signal of NF-kB and prevent its nuclear translocation. Various stimuli induce the activation of the IkB kinase (IKK) complex, which then phosphorylates IkBs. The phosphorylated IkBs are ubiquitinated and then degraded through the proteasome-mediated pathway. The degradation of IkBs releases NF-kappa-B and and it can be transported into nucleus where it induces the expression of target genes.
RIG-I E3 ubiquitin ligasesREACT_25220 (Reactome)
RIG-I E3 ubiquitin ligasesmim-catalysisREACT_25220 (Reactome)
RIPK1REACT_25147 (Reactome)
RNF125:E2 enzyme

(UBE2K,

UbcH5a-c):K48-polyubiquitin
mim-catalysisREACT_25252 (Reactome)
RNF125ArrowREACT_25252 (Reactome)
SIKE1ArrowREACT_25051 (Reactome)
SIKE1ArrowREACT_25079 (Reactome)
TANKREACT_24986 (Reactome)
TAX1BP1:TNFAIP3:TBK1/IKKiArrowREACT_25179 (Reactome)
TAX1BP1:TNFAIP3REACT_25179 (Reactome)
TBK1/IKKi:SIKE1REACT_25051 (Reactome)
TBK1/IKKi:SIKE1REACT_25079 (Reactome)
TRAF2 and TRAF6REACT_25262 (Reactome)
UbArrowREACT_25235 (Reactome)
VAF (virus-activated factor)ArrowREACT_25196 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN

gene promoter
ArrowREACT_24975 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN

gene promoter
ArrowREACT_25209 (Reactome)
VAF/pIRF7:CBP/p300REACT_24975 (Reactome)
Viral dsRNA (-) StrandedREACT_25160 (Reactome)
Viral dsRNA (-) StrandedREACT_25357 (Reactome)
dsRNA bound to RIG-IArrowREACT_25357 (Reactome)
dsRNA bound to RIG-IREACT_25220 (Reactome)
dsRNA:MDA5ArrowREACT_25160 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:TRAF3ArrowREACT_25055 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:TRAF3REACT_24974 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7ArrowREACT_25170 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7REACT_25368 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7mim-catalysisREACT_25368 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiArrowREACT_25051 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiArrowREACT_25368 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiREACT_25170 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3ArrowREACT_25364 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3REACT_25051 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3REACT_25055 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12ArrowREACT_24982 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:PCBP2ArrowREACT_24967 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:PCBP2REACT_25398 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10ArrowREACT_25167 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10REACT_24946 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerArrowREACT_24946 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerREACT_24999 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimermim-catalysisREACT_24999 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDArrowREACT_25147 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDREACT_25167 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1ArrowREACT_25003 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1mim-catalysisREACT_24935 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7ArrowREACT_25308 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7REACT_25327 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7mim-catalysisREACT_25327 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiArrowREACT_25079 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiArrowREACT_25327 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiREACT_25308 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKArrowREACT_24986 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKREACT_25079 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6ArrowREACT_25262 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6REACT_24986 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6REACT_25003 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1ArrowREACT_24957 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1ArrowREACT_24974 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1REACT_24967 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1REACT_25147 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1REACT_25262 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1REACT_25364 (Reactome)
dsRNA:RIG-I/MDA5:K48 Ub-IPS-1:PCBP2:AIP4ArrowREACT_25398 (Reactome)
dsRNA:RIG-I/MDA5:NLRC5ArrowREACT_25113 (Reactome)
dsRNA:RIG-I/MDA5:NLRC5TBarREACT_24957 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10

prodomain:IKK

complex
ArrowREACT_25134 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainArrowREACT_24999 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainREACT_25134 (Reactome)
dsRNA:RIG-I/MDA5REACT_24957 (Reactome)
dsRNA:RIG-I/MDA5REACT_24982 (Reactome)
dsRNA:RIG-I/MDA5REACT_25113 (Reactome)
dsRNA:Ub-RIG-I:TRIM25ArrowREACT_25220 (Reactome)
p-2S-IRF7:p-2S-IRF7ArrowREACT_24920 (Reactome)
p-2S-IRF7:p-2S-IRF7ArrowREACT_24983 (Reactome)
p-2S-IRF7:p-2S-IRF7ArrowREACT_25292 (Reactome)
p-2S-IRF7:p-2S-IRF7ArrowREACT_25352 (Reactome)
p-2S-IRF7:p-2S-IRF7REACT_24920 (Reactome)
p-2S-IRF7:p-2S-IRF7REACT_25099 (Reactome)
p-2S-IRF7:p-2S-IRF7REACT_25352 (Reactome)
p-IRF3 dimer:PIN1ArrowREACT_25077 (Reactome)
p-IRF3 dimer:PIN1REACT_24932 (Reactome)
p-IRF3:p-IRF3REACT_25077 (Reactome)
p-S477,S479-IRF7ArrowREACT_25327 (Reactome)
p-S477,S479-IRF7REACT_25292 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ArrowREACT_24983 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ArrowREACT_25352 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3REACT_25275 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3REACT_25352 (Reactome)
phosphorylated IRF3/IRF7ArrowREACT_25368 (Reactome)
phosphorylated IRF3/IRF7REACT_24983 (Reactome)
procaspase-8/10REACT_24946 (Reactome)
procaspase-8/10REACT_25167 (Reactome)
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