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

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14, 16, 22, 40, 50...11, 53, 8121, 33, 702036, 63, 74, 822413, 66, 8144, 522741, 4755, 71693754718, 9, 173, 12, 24, 32, 763149, 58, 65, 68, 8634, 38, 4810, 23, 3012, 19, 758026, 57, 62, 648059, 81288, 4235, 49, 58, 65, 68...38, 436080548323, 7944, 5232, 46, 64571, 5, 51, 7749, 58, 65, 68, 8621, 33, 7064, 817819nucleoplasmcytosolmitochondrionRV RNA p-IRF3:p-IRF3Influenza A dsRNA intermediate form K48polyUb-RNF125 NFKB2(1-454) TRIM25 RNF135 p-T,4S-IRF3:p-T,4S-IRF3ATPRNF135 TRIM25 5'-ppp poly-U/UC RNA variants CHUK TAX1BP1 viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS5'-ppp poly-U/UC RNA variants Influenza A dsRNA intermediate form TRAF2 FADD ATP IFIH1 VAF/pIRF7:CBP/p300bound to type I IFNgene promoterCASP10(220-415)IRF7ATP Influenza A dsRNA intermediate form p-S19,S23-NFKBIB RNF135 Influenza A dsRNA intermediate form 5'-ppp poly-U/UC RNA variants p-4S,T404-IRF3 RV RNA MAVS DDX58ATP 5'-ppp poly-U/UC RNA variants RNF135 Influenza A dsRNA intermediate form TRIM25 IRF3 TRIM25 HMGB1 IFIH1 ATG12 dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12K63polyUb-TRAF3 NFKBIA 5'-ppp poly-U/UC RNA variants TRIM25 TRIM25 TRAF2 IFIH1 K63polyUb-DDX58 CREBBP TBK1 FADD p-S477,S479-IRF7K63polyUb-TRAF3 IFIH1 IRF3 TRAF6 ATP TRAF2 Influenza A dsRNA intermediate form K48polyUb-MAVS IFIH1 RNF135,TRIM25TAX1BP1 UBE2D2 K63polyUb-DDX58 CASP8(1-216) SIKE1 CASP8(1-479) p-S477,S479-IRF7 IFNA ATPK63polyUb-DDX58 K63polyUbMV dsRNA intermediate form TBK1 p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300:Promotor region of interferon betaPromotor region of interferon beta dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKTRAF2, TRAF6K63polyUb-DDX58 MAVS RNF125viraldsRNA:IFIH1,2xviraldsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATPK63polyUb-DDX58 IFIH1 RV RNA Influenza A dsRNA intermediate form TRIM25 5'-ppp poly-U/UC RNA variants RV RNA NECML ISG15:DDX58conjugatep-S477,S479-IRF7 Promotor region of interferon beta RV RNA MV dsRNA intermediate form ADPRV RNA NLRC5p-T,4S-IRF3:p-T,4S-IRF3ATP MV dsRNA intermediate form IKBKG:p-S176,S180-CHUK:p-S177,S181-IKBKBMV dsRNA intermediate form p-S477,S479-IRF7 IKBKE CHUK TRAF2 Influenza A dsRNA intermediate form K48polyUb-TRAF3CBP/p300:pIRF7:pIRF7K63polyUb-DDX58 p-S477,S479-IRF7 5'-ppp poly-U/UC RNA variants RV RNA HERC5 2xp-S477,S479-IRF7IRF3,IRF7TRAF6 viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADDEP300 Influenza A dsRNA intermediate form DHX9:CpG:MyD88CASP8(1-216) MAVS K48polyUbK63polyUb-DDX58 CASP10(1-521) p-S32,S36-NFKBIA RNF135 CHUK:IKBKB:IKBKGPeptide IRF3-P:IRF7-PUBE2D2 ATP TRIM25 TRIM25 dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1TRIM25 DHX36 RV RNA RV RNA K63polyUb-DDX58 MV dsRNA intermediate form UBA7 CASP8(385-479)RELA RNF135 RNF135 p-4S,T404-IRF3 CASP10(1-521) viral dsRNA:IFIH1Influenza A dsRNA intermediate form K63polyUb-DDX58 MAVS UBE2K NFKB2(1-454) MV dsRNA intermediate form DDX58 p-4S,T404-IRF3 RIPK1 MV dsRNA intermediate form RNF135 IFIH1 IKBKG CASP8(375-384)IRF7 NLRC5 MAVS NFKB2(1-454) IKBKE RV RNA K63polyUb-DDX58 TBK1 Influenza A dsRNA intermediate form TAX1BP1:TNFAIP3:TBK1/IKKiADPITCHMAVS UBC(533-608) RIPK1 PIN1 MYD88 DHX36:CpG:MyD88RV RNA K63polyUb-DDX58 RNF135 Influenza A dsRNA intermediate form RNF135 TBK1 TANK APP(672-713) Promotor region of interferon beta 5'-ppp poly-U/UC RNA variants TRIM25 IRF2:promoters ofINF alpha, INF betaCASP10(416-521)MV dsRNA intermediate form CHUK NKIRASS100B K63polyUb-DDX58 TRIM25 viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-216), CASP10(1-219)MV dsRNA intermediate form ATPVAF (virus-activatedfactor)TNFAIP3 dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainIFIH1 Influenza A dsRNA intermediate form IFIH1 TBK1 Influenza A dsRNA intermediate form K63polyUb-DDX58TANK RV RNA RPS27A(1-76) K63polyUb-DDX58 UBC(77-152) ISG15 UBC(457-532) K63polyUb-DDX58 Influenza A dsRNA intermediate form ATP CASP8(1-216) Unmethylated CpG DNA IFIH1 RV RNA E2 enzyme (UBE2K,UbcH5a-c)FADD dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiISGylated IRF3IFIH1 DDX58 MV dsRNA intermediate form K63polyUb-TRAF3 MV dsRNA intermediate form FADD IFIH1 ATP p-4S,T404-IRF3 MAVS TRIM25 AGER DDX58, IFIH1p-4S,T404-IRF3,p-S477,S479-IRF7p-S477,S479-IRF7 viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3MAVS p-S477,S479-IRF7 IKBKE IFIH1 RV RNA 5'-ppp poly-U/UC RNA variants NKIRAS2 RV RNA p-5S,T404-IRF3 TANK 5'-ppp poly-U/UC RNA variants RIPK1 MAVS MYD88 MAP3K1 IFIH1 dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7EP300 ATP ISG15 MAVS IKBKG IFIH1:DAKATP Influenza A dsRNA intermediate form TRIM25 EP300 p-S477,S479-IRF7 FADD Influenza A dsRNA intermediate form UBC(153-228) ISG15 ATG12 IFNB1 RNF135 CHUK:IKBKB:IKBKGIRF7 TRIM25 IKBKG K48polyUb-DDX58 UBC(1-76) NFKB1(1-433) MAP3K1MAVS MV dsRNA intermediate form TRAF2 RNF135 CREBBP RNF135 IFIH1 ligandMV dsRNA intermediate form viraldsRNA:IFIH1,2xviraldsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP:NLRC5IKBKB MV dsRNA intermediate form 5'-ppp poly-U/UC RNA variants p-4S,T404-IRF3 p-IRF3 dimer:PIN1RV RNA 5'-ppp poly-U/UC RNA variants TRIM25 PIN1PCBP2 2xviraldsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATPCASP10(1-521) K63polyUb-DDX58 Phospho-NF-kappaBInhibitorviraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:PCBP2:ITCHIFIH1 RV RNA p-S477,S479-IRF7 RV RNA K63polyUb-TRAF3K63polyUb5'-ppp poly-U/UC RNA variants ATP RNF135 MAVS MAVS RELA RV RNA UBB(1-76) IKBKE NFkB ComplexATP 5'-ppp poly-U/UC RNA variants viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:CASP8(1-479), CASP10(1-521)CREBBP K48polyUb-IFIH1 MV dsRNA intermediate form MAVS ATP UbATP TRIM25 RV RNA ATP RNF125:E2enzyme(UBE2K,UbcH5a-c):K48-polyubiquitinp-S177,S181-IKBKB MV dsRNA intermediate form MAVS:NLRX1RNF135 AGER ligands:AGEREP300 2x DDX58 ligand:2xDDX58:2xATPIRF1:Promotors ofIFN alpha, IFN betaPromotor region of interferon alpha RNF135 TBK1/IKKi:SIKE1ATPK63polyUb-DDX58 TRIM25 IRF2 ADPCREBBP viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:TRAF3N-epsilon-(1-(1-carboxy)ethyl)lysine Influenza A dsRNA intermediate form K48polyUbp-S176,S180-CHUK NLRX1 p-4S,T404-IRF3 UBE2D3 IFIH1 CASP10(1-219) DAK RELA IKBKB Influenza A dsRNA intermediate form MV dsRNA intermediate form UBE2L6 IRF1 PCBP2Influenza A dsRNA intermediate form IFIH1 MV dsRNA intermediate form UBE2L6 DDX58 RNF135 UBC(229-304) ATG5:ATG12:MAVSMAVS Influenza A dsRNA intermediate form CASP8(217-374)K63polyUb-DDX58 UBE2L6 CASP10(1-219) p-4S,T404-IRF3 TRIM25 TRIM25 IKBKE MAVS TBK1 ATP Influenza A dsRNA intermediate form SIKE1EP300 DAKATG5 TRIM25 TRIM25 TRIM25 CASP10(1-219) IFIH1 5'-ppp poly-U/UC RNA variants IRF7 Influenza A dsRNA intermediate form CREBBP dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomain:IKK complexATG5 p-2S-IRF7:p-2S-IRF7p-4S,T404-IRF3 UBE2L6 Promotor region of interferon alpha RNF135 K63polyUb-DDX58 TRAF3 Promotor region of interferon beta TAX1BP1:TNFAIP3UBE2D1 IKBKB UBA7 5'-ppp poly-U/UC RNA variants IFIH1 MV dsRNA intermediate form RNF135 TBK1 NFKB1(1-433):NFKB2(1-454):RELAInfluenza A dsRNA intermediate form RNF135 RIPK1 TRAF6 IFIH1 CREBBP UBC(609-684) DDX58 ligandInfluenza A dsRNA intermediate form RV RNA MV dsRNA intermediate form CREBBP, EP300IRF3-P:IRF7-PRNF135 IKK related kinasesTBK1/IKK epsilonITCH FADDp-4S,T404-IRF3 MAVS DHX58UBE2D3 5'-ppp poly-U/UC RNA variants CREBBP p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300VAF/pIRF7:CBP/p3005'-ppp poly-U/UC RNA variants RNF216viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-479), CASP10(1-521)RIPK1 K63polyUb-DDX58 K63polyUb-DDX58 UBC(381-456) NFKBIB p-S477,S479-IRF7 UBE2K Promotor region of interferon alpha HERC5 RIPK15'-ppp poly-U/UC RNA variants SAA1(19-122) ATP IKBKE viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilonMV dsRNA intermediate form viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon:IRF3,IRF7IFIH1 IKBKG TRAF6 K48polyUb-DDX58,K48polyUb-IFIH15'-ppp poly-U/UC RNA variants UBA52(1-76) K63polyUb-DDX58 ATP ATP Promoter region oftype-I IFN genesCASP8(1-479) 5'-ppp poly-U/UC RNA variants 5'-ppp poly-U/UC RNA variants TRAF6 S100A12 EP300 TRAF2 UBB(77-152) ATP MAVS DHX9 NFKB1(1-433) ADPATP TNFAIP3 CASP8(1-479) p-4S,T404-IRF3 APP(672-711) OTUD5IRF3 K63polyUb-DDX58 Promotor region of interferon alpha p-5S,T404-IRF3 IFIH1 IkBs:NFkBNLRX1MAVSH2ONFKB1(1-433) Promotor region ofinterferon betaCYLDPCBP2 MV dsRNA intermediate form 5'-ppp poly-U/UC RNA variants RIPK1 IFIH1 EP300 IKBKE dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6RV RNA RNF135 ATP Promotor region of interferon beta RV RNA viraldsRNA:IFIH1,viraldsRNA:K63polyUb-DDX58:MAVS:PCBP2unknown ligaseIFIH1 MAVS FADD UBB(153-228) ATPMAVS RV RNA CASP8(1-479),CASP10(1-521)5'-ppp poly-U/UC RNA variants TANKRNF135 IFN alpha/beta(IFNA/B)NKIRAS1 TRAF6 MV dsRNA intermediate form ATP ISG15:UBEIL/UbcH8:CEB1Unmethylated CpG DNA Influenza A dsRNA intermediate form UBE2D1 UBC(305-380) IFNB141, 5, 7946145614572, 735441, 5, 797971, 5, 793741, 5, 7944154441, 5, 79611, 5, 794461441, 5, 794415611, 5, 7941, 5, 791541, 5, 791, 5, 79611, 5, 79418, 28, 67441, 5, 791, 5, 7979479424791, 5, 794441, 5, 791, 5, 791, 5, 791, 5, 79418, 28, 671, 5, 791, 5, 796, 25, 29, 39, 56...18, 671, 5, 796141, 5, 79


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. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 168928
Reactome-version 
Reactome version: 63
Reactome Author 
Reactome Author: Garapati, Phani Vijay

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Bibliography

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  1. Lee FS, Peters RT, Dang LC, Maniatis T.; ''MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta.''; PubMed Europe PMC Scholia
  2. Bowie AG, Unterholzner L.; ''Viral evasion and subversion of pattern-recognition receptor signalling.''; PubMed Europe PMC Scholia
  3. Gao D, Yang YK, Wang RP, Zhou X, Diao FC, Li MD, Zhai ZH, Jiang ZF, Chen DY.; ''REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I.''; PubMed Europe PMC Scholia
  4. Broquet AH, Hirata Y, McAllister CS, Kagnoff MF.; ''RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium.''; PubMed Europe PMC Scholia
  5. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S.; ''Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5.''; PubMed Europe PMC Scholia
  6. Mori M, Yoneyama M, Ito T, Takahashi K, Inagaki F, Fujita T.; ''Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation.''; PubMed Europe PMC Scholia
  7. Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG, Accavitti-Loper MA, Madden VJ, Sun L, Ye Z, Lich JD, Heise MT, Chen Z, Ting JP.; ''NLRX1 is a regulator of mitochondrial antiviral immunity.''; PubMed Europe PMC Scholia
  8. Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M.; ''Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA.''; PubMed Europe PMC Scholia
  9. Maelfait J, Beyaert R.; ''Non-apoptotic functions of caspase-8.''; PubMed Europe PMC Scholia
  10. Li X, Massa PE, Hanidu A, Peet GW, Aro P, Savitt A, Mische S, Li J, Marcu KB.; ''IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program.''; PubMed Europe PMC Scholia
  11. Yoneyama M, Fujita T.; ''RIG-I family RNA helicases: cytoplasmic sensor for antiviral innate immunity.''; PubMed Europe PMC Scholia
  12. Rothwarf DM, Zandi E, Natoli G, Karin M.; ''IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex.''; PubMed Europe PMC Scholia
  13. Lin R, Mamane Y, Hiscott J.; ''Structural and functional analysis of interferon regulatory factor 3: localization of the transactivation and autoinhibitory domains.''; PubMed Europe PMC Scholia
  14. Huang J, Liu T, Xu LG, Chen D, Zhai Z, Shu HB.; ''SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways.''; PubMed Europe PMC Scholia
  15. Lamkanfi M, Declercq W, Vanden Berghe T, Vandenabeele P.; ''Caspases leave the beaten track: caspase-mediated activation of NF-kappaB.''; PubMed Europe PMC Scholia
  16. Pomerantz JL, Baltimore D.; ''NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.''; PubMed Europe PMC Scholia
  17. Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O'Rourke KM, Eby M, Pietras E, Cheng G, Bazan JF, Zhang Z, Arnott D, Dixit VM.; ''DUBA: a deubiquitinase that regulates type I interferon production.''; PubMed Europe PMC Scholia
  18. Tsuchida T, Kawai T, Akira S.; ''Inhibition of IRF3-dependent antiviral responses by cellular and viral proteins.''; PubMed Europe PMC Scholia
  19. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB.; ''VISA is an adapter protein required for virus-triggered IFN-beta signaling.''; PubMed Europe PMC Scholia
  20. Konno H, Yamamoto T, Yamazaki K, Gohda J, Akiyama T, Semba K, Goto H, Kato A, Yujiri T, Imai T, Kawaguchi Y, Su B, Takeuchi O, Akira S, Tsunetsugu-Yokota Y, Inoue J.; ''TRAF6 establishes innate immune responses by activating NF-kappaB and IRF7 upon sensing cytosolic viral RNA and DNA.''; PubMed Europe PMC Scholia
  21. Pothlichet J, Meunier I, Davis BK, Ting JP, Skamene E, von Messling V, Vidal SM.; ''Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells.''; PubMed Europe PMC Scholia
  22. Solis M, Goubau D, Romieu-Mourez R, Genin P, Civas A, Hiscott J.; ''Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages.''; PubMed Europe PMC Scholia
  23. Solt LA, Madge LA, May MJ.; ''NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation.''; PubMed Europe PMC Scholia
  24. Wang J, Chun HJ, Wong W, Spencer DM, Lenardo MJ.; ''Caspase-10 is an initiator caspase in death receptor signaling.''; PubMed Europe PMC Scholia
  25. Seth RB, Sun L, Ea CK, Chen ZJ.; ''Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3.''; PubMed Europe PMC Scholia
  26. Oshiumi H, Matsumoto M, Hatakeyama S, Seya T.; ''Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection.''; PubMed Europe PMC Scholia
  27. Taniguchi T, Ogasawara K, Takaoka A, Tanaka N.; ''IRF family of transcription factors as regulators of host defense.''; PubMed Europe PMC Scholia
  28. Takahasi K, Suzuki NN, Horiuchi M, Mori M, Suhara W, Okabe Y, Fukuhara Y, Terasawa H, Akira S, Fujita T, Inagaki F.; ''X-ray crystal structure of IRF-3 and its functional implications.''; PubMed Europe PMC Scholia
  29. Yoneyama M, Fujita T.; ''Function of RIG-I-like receptors in antiviral innate immunity.''; PubMed Europe PMC Scholia
  30. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM.; ''FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.''; PubMed Europe PMC Scholia
  31. Diao F, Li S, Tian Y, Zhang M, Xu LG, Zhang Y, Wang RP, Chen D, Zhai Z, Zhong B, Tien P, Shu HB.; ''Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.''; PubMed Europe PMC Scholia
  32. Panne D, McWhirter SM, Maniatis T, Harrison SC.; ''Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch.''; PubMed Europe PMC Scholia
  33. Bonizzi G, Karin M.; ''The two NF-kappaB activation pathways and their role in innate and adaptive immunity.''; PubMed Europe PMC Scholia
  34. Paz S, Sun Q, Nakhaei P, Romieu-Mourez R, Goubau D, Julkunen I, Lin R, Hiscott J.; ''Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway.''; PubMed Europe PMC Scholia
  35. Shikama Y, Yamada M, Miyashita T.; ''Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK and IKKalpha kinases.''; PubMed Europe PMC Scholia
  36. Qin BY, Liu C, Lam SS, Srinath H, Delston R, Correia JJ, Derynck R, Lin K.; ''Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation.''; PubMed Europe PMC Scholia
  37. Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K.; ''Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125.''; PubMed Europe PMC Scholia
  38. Parvatiyar K, Barber GN, Harhaj EW.; ''TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases.''; PubMed Europe PMC Scholia
  39. Kawagoe T, Takeuchi O, Takabatake Y, Kato H, Isaka Y, Tsujimura T, Akira S.; ''TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis.''; PubMed Europe PMC Scholia
  40. Guo B, Cheng G.; ''Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK.''; PubMed Europe PMC Scholia
  41. Jacobs MD, Harrison SC.; ''Structure of an IkappaBalpha/NF-kappaB complex.''; PubMed Europe PMC Scholia
  42. Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T.; ''Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo.''; PubMed Europe PMC Scholia
  43. Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, Xu M, Chen ZJ.; ''Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity.''; PubMed Europe PMC Scholia
  44. Yoneyama M, Fujita T.; ''Structural mechanism of RNA recognition by the RIG-I-like receptors.''; PubMed Europe PMC Scholia
  45. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S.; ''IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction.''; PubMed Europe PMC Scholia
  46. Kell A, Stoddard M, Li H, Marcotrigiano J, Shaw GM, Gale M.; ''Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length.''; PubMed Europe PMC Scholia
  47. Nyman TA, Tölö H, Parkkinen J, Kalkkinen N.; ''Identification of nine interferon-alpha subtypes produced by Sendai virus-induced human peripheral blood leucocytes.''; PubMed Europe PMC Scholia
  48. Kim MJ, Hwang SY, Imaizumi T, Yoo JY.; ''Negative feedback regulation of RIG-I-mediated antiviral signaling by interferon-induced ISG15 conjugation.''; PubMed Europe PMC Scholia
  49. Saha SK, Pietras EM, He JQ, Kang JR, Liu SY, Oganesyan G, Shahangian A, Zarnegar B, Shiba TL, Wang Y, Cheng G.; ''Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif.''; PubMed Europe PMC Scholia
  50. Chen ZJ.; ''Ubiquitin signalling in the NF-kappaB pathway.''; PubMed Europe PMC Scholia
  51. Nakhaei P, Mesplede T, Solis M, Sun Q, Zhao T, Yang L, Chuang TH, Ware CF, Lin R, Hiscott J.; ''The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation.''; PubMed Europe PMC Scholia
  52. Son KN, Liang Z, Lipton HL.; ''Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses.''; PubMed Europe PMC Scholia
  53. Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF.; ''NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways.''; PubMed Europe PMC Scholia
  54. Chen W, Royer WE.; ''Structural insights into interferon regulatory factor activation.''; PubMed Europe PMC Scholia
  55. Li X, Lu C, Stewart M, Xu H, Strong RK, Igumenova T, Li P.; ''Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5.''; PubMed Europe PMC Scholia
  56. Potter JA, Randall RE, Taylor GL.; ''Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain.''; PubMed Europe PMC Scholia
  57. Krappmann D, Hatada EN, Tegethoff S, Li J, Klippel A, Giese K, Baeuerle PA, Scheidereit C.; ''The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not IKAP as a regular component.''; PubMed Europe PMC Scholia
  58. Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu KP, Yamaoka S.; ''Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1.''; PubMed Europe PMC Scholia
  59. Gil J, Alcamí J, Esteban M.; ''Activation of NF-kappa B by the dsRNA-dependent protein kinase, PKR involves the I kappa B kinase complex.''; PubMed Europe PMC Scholia
  60. Takahashi K, Kawai T, Kumar H, Sato S, Yonehara S, Akira S.; ''Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA.''; PubMed Europe PMC Scholia
  61. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, García-Sastre A, Katze MG, Gale M.; ''Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity.''; PubMed Europe PMC Scholia
  62. You F, Sun H, Zhou X, Sun W, Liang S, Zhai Z, Jiang Z.; ''PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4.''; PubMed Europe PMC Scholia
  63. Yang H, Lin CH, Ma G, Baffi MO, Wathelet MG.; ''Interferon regulatory factor-7 synergizes with other transcription factors through multiple interactions with p300/CBP coactivators.''; PubMed Europe PMC Scholia
  64. Sato M, Tanaka N, Hata N, Oda E, Taniguchi T.; ''Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-beta gene.''; PubMed Europe PMC Scholia
  65. Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T.; ''IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.''; PubMed Europe PMC Scholia
  66. Kawai T, Akira S.; ''Antiviral signaling through pattern recognition receptors.''; PubMed Europe PMC Scholia
  67. Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L.; ''Activation of the NF-kappaB pathway by caspase 8 and its homologs.''; PubMed Europe PMC Scholia
  68. Mattei F, Schiavoni G, Tough DF.; ''Regulation of immune cell homeostasis by type I interferons.''; PubMed Europe PMC Scholia
  69. Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T.; ''Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300.''; PubMed Europe PMC Scholia
  70. Yazdi S, Naumann M, Stein M.; ''Double phosphorylation-induced structural changes in the signal-receiving domain of IκBα in complex with NF-κB.''; PubMed Europe PMC Scholia
  71. Schnell G, Loo YM, Marcotrigiano J, Gale M.; ''Uridine composition of the poly-U/UC tract of HCV RNA defines non-self recognition by RIG-I.''; PubMed Europe PMC Scholia
  72. Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U.; ''Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.''; PubMed Europe PMC Scholia
  73. Goutagny N, Severa M, Fitzgerald KA.; ''Pin-ning down immune responses to RNA viruses.''; PubMed Europe PMC Scholia
  74. Friedman CS, O'Donnell MA, Legarda-Addison D, Ng A, Cárdenas WB, Yount JS, Moran TM, Basler CF, Komuro A, Horvath CM, Xavier R, Ting AT.; ''The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response.''; PubMed Europe PMC Scholia
  75. Marié I, Durbin JE, Levy DE.; ''Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7.''; PubMed Europe PMC Scholia
  76. Berghäll H, Sirén J, Sarkar D, Julkunen I, Fisher PB, Vainionpää R, Matikainen S.; ''The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines.''; PubMed Europe PMC Scholia
  77. Lee MK, Kim HE, Park EB, Lee J, Kim KH, Lim K, Yum S, Lee YH, Kang SJ, Lee JH, Choi BS.; ''Structural features of influenza A virus panhandle RNA enabling the activation of RIG-I independently of 5'-triphosphate.''; PubMed Europe PMC Scholia
  78. Häcker H, Karin M.; ''Regulation and function of IKK and IKK-related kinases.''; PubMed Europe PMC Scholia
  79. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T.; ''The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.''; PubMed Europe PMC Scholia
  80. Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S.; ''Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6.''; PubMed Europe PMC Scholia
  81. Thomas LR, Stillman DJ, Thorburn A.; ''Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen.''; PubMed Europe PMC Scholia
  82. Marié I, Smith E, Prakash A, Levy DE.; ''Phosphorylation-induced dimerization of interferon regulatory factor 7 unmasks DNA binding and a bipartite transactivation domain.''; PubMed Europe PMC Scholia
  83. Zhang M, Wu X, Lee AJ, Jin W, Chang M, Wright A, Imaizumi T, Sun SC.; ''Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD.''; PubMed Europe PMC Scholia
  84. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU.; ''TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity.''; PubMed Europe PMC Scholia
  85. Lee FS, Hagler J, Chen ZJ, Maniatis T.; ''Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway.''; PubMed Europe PMC Scholia
  86. Oganesyan G, Saha SK, Guo B, He JQ, Shahangian A, Zarnegar B, Perry A, Cheng G.; ''Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response.''; PubMed Europe PMC Scholia
  87. Honda K, Yanai H, Takaoka A, Taniguchi T.; ''Regulation of the type I IFN induction: a current view.''; PubMed Europe PMC Scholia

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
2x DDX58 ligand:2x DDX58:2xATPComplexR-HSA-168906 (Reactome)
2xp-S477,S479-IRF7ComplexR-HSA-450306 (Reactome)
2xviral dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATPComplexR-HSA-918190 (Reactome)
5'-ppp poly-U/UC RNA variants R-HCV-9013887 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
AGER ProteinQ15109 (Uniprot-TrEMBL)
AGER ligands:AGERComplexR-HSA-879365 (Reactome)
APP(672-711) ProteinP05067 (Uniprot-TrEMBL)
APP(672-713) ProteinP05067 (Uniprot-TrEMBL)
ATG12 ProteinO94817 (Uniprot-TrEMBL)
ATG5 ProteinQ9H1Y0 (Uniprot-TrEMBL)
ATG5:ATG12:MAVSComplexR-HSA-936373 (Reactome)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
CASP10(1-219) ProteinQ92851 (Uniprot-TrEMBL)
CASP10(1-521) ProteinQ92851 (Uniprot-TrEMBL)
CASP10(220-415)ProteinQ92851 (Uniprot-TrEMBL)
CASP10(416-521)ProteinQ92851 (Uniprot-TrEMBL)
CASP8(1-216) ProteinQ14790 (Uniprot-TrEMBL)
CASP8(1-479) ProteinQ14790 (Uniprot-TrEMBL)
CASP8(1-479), CASP10(1-521)ComplexR-HSA-933463 (Reactome)
CASP8(217-374)ProteinQ14790 (Uniprot-TrEMBL)
CASP8(375-384)ProteinQ14790 (Uniprot-TrEMBL)
CASP8(385-479)ProteinQ14790 (Uniprot-TrEMBL)
CBP/p300:pIRF7:pIRF7ComplexR-HSA-933471 (Reactome)
CHUK ProteinO15111 (Uniprot-TrEMBL)
CHUK:IKBKB:IKBKGComplexR-HSA-168113 (Reactome) Co-immunoprecipitation studies and size exclusion chromatography analysis indicate that the high molecular weight (around 700 to 900 kDa) IKK complex is composed of two kinase subunits (IKK1/CHUK/IKBKA and/or IKK2/IKBKB/IKKB) bound to a regulatory gamma subunit (IKBKG/NEMO) (Rothwarf DMet al. 1998; Krappmann D et al. 2000; Miller BS & Zandi E 2001). Variants of the IKK complex containing IKBKA or IKBKB homodimers associated with NEMO may also exist. Crystallographic and quantitative analyses of the binding interactions between N-terminal NEMO and C-terminal IKBKB fragments showed that IKBKB dimers would interact with NEMO dimers resulting in 2:2 stoichiometry (Rushe M et al. 2008). Chemical cross-linking and equilibrium sedimentation analyses of IKBKG (NEMO) suggest a tetrameric oligomerization (dimers of dimers) (Tegethoff S et al. 2003). The tetrameric NEMO could sequester four kinase molecules, yielding an 2xIKBKA:2xIKBKB:4xNEMO stoichiometry (Tegethoff S et al. 2003). The above data suggest that the core IKK complex consists of an IKBKA:IKBKB heterodimer associated with an IKBKG dimer or higher oligomeric assemblies. However, the exact stoichiometry of the IKK complex remains unclear.
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CREBBP, EP300ComplexR-HSA-1027362 (Reactome)
CYLDProteinQ9NQC7 (Uniprot-TrEMBL)
DAK ProteinQ3LXA3 (Uniprot-TrEMBL)
DAKProteinQ3LXA3 (Uniprot-TrEMBL)
DDX58 ProteinO95786 (Uniprot-TrEMBL)
DDX58 ligandComplexR-NUL-9013905 (Reactome)
DDX58, IFIH1ComplexR-HSA-936436 (Reactome)
DDX58ProteinO95786 (Uniprot-TrEMBL)
DHX36 ProteinQ9H2U1 (Uniprot-TrEMBL)
DHX36:CpG:MyD88ComplexR-HSA-3134859 (Reactome)
DHX58ProteinQ96C10 (Uniprot-TrEMBL)
DHX9 ProteinQ08211 (Uniprot-TrEMBL)
DHX9:CpG:MyD88ComplexR-HSA-3134868 (Reactome)
E2 enzyme (UBE2K, UbcH5a-c)ComplexR-HSA-936441 (Reactome)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
FADD ProteinQ13158 (Uniprot-TrEMBL)
FADDProteinQ13158 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HERC5 ProteinQ9UII4 (Uniprot-TrEMBL)
HMGB1 ProteinP09429 (Uniprot-TrEMBL)
IFIH1 ProteinQ9BYX4 (Uniprot-TrEMBL)
IFIH1 ligandComplexR-NUL-9013950 (Reactome)
IFIH1:DAKComplexR-HSA-918203 (Reactome)
IFN alpha/beta (IFNA/B)ComplexR-HSA-909690 (Reactome)
IFNA R-HSA-909688 (Reactome)
IFNB1 ProteinP01574 (Uniprot-TrEMBL)
IFNB1ProteinP01574 (Uniprot-TrEMBL)
IKBKB ProteinO14920 (Uniprot-TrEMBL)
IKBKE ProteinQ14164 (Uniprot-TrEMBL)
IKBKG ProteinQ9Y6K9 (Uniprot-TrEMBL)
IKBKG:p-S176,S180-CHUK:p-S177,S181-IKBKBComplexR-HSA-177663 (Reactome) Co-immunoprecipitation studies and size exclusion chromatography analysis indicate that the high molecular weight (around 700 to 900 kDa) IKK complex is composed of two kinase subunits (IKK1/CHUK/IKBKA and/or IKK2/IKBKB/IKKB) bound to a regulatory gamma subunit (IKBKG/NEMO) (Rothwarf DMet al. 1998; Krappmann D et al. 2000; Miller BS & Zandi E 2001). Variants of the IKK complex containing IKBKA or IKBKB homodimers associated with NEMO may also exist. Crystallographic and quantitative analyses of the binding interactions between N-terminal NEMO and C-terminal IKBKB fragments showed that IKBKB dimers would interact with NEMO dimers resulting in 2:2 stoichiometry (Rushe M et al. 2008). Chemical cross-linking and equilibrium sedimentation analyses of IKBKG (NEMO) suggest a tetrameric oligomerization (dimers of dimers) (Tegethoff S et al. 2003). The tetrameric NEMO could sequester four kinase molecules, yielding an 2xIKBKA:2xIKBKB:4xNEMO stoichiometry (Tegethoff S et al. 2003). The above data suggest that the core IKK complex consists of an IKBKA:IKBKB heterodimer associated with an IKBKG dimer or higher oligomeric assemblies. However, the exact stoichiometry of the IKK complex remains unclear.
IKK related kinases TBK1/IKK epsilonComplexR-HSA-450329 (Reactome)
IRF1 ProteinP10914 (Uniprot-TrEMBL)
IRF1:Promotors of IFN alpha, IFN betaComplexR-HSA-1008247 (Reactome)
IRF2 ProteinP14316 (Uniprot-TrEMBL)
IRF2:promoters of INF alpha, INF betaComplexR-HSA-1018386 (Reactome)
IRF3 ProteinQ14653 (Uniprot-TrEMBL)
IRF3,IRF7ComplexR-HSA-450317 (Reactome)
IRF3-P:IRF7-PComplexR-HSA-1027365 (Reactome)
IRF3-P:IRF7-PComplexR-HSA-1027367 (Reactome)
IRF7 ProteinQ92985 (Uniprot-TrEMBL)
IRF7ProteinQ92985 (Uniprot-TrEMBL)
ISG15 ProteinP05161 (Uniprot-TrEMBL)
ISG15:DDX58 conjugateComplexR-HSA-936557 (Reactome)
ISG15:UBEIL/UbcH8:CEB1ComplexR-HSA-936560 (Reactome)
ISGylated IRF3ComplexR-HSA-1169389 (Reactome)
ITCH ProteinQ96J02 (Uniprot-TrEMBL)
ITCHProteinQ96J02 (Uniprot-TrEMBL)
IkBs:NFkBComplexR-HSA-168130 (Reactome)
Influenza A dsRNA intermediate form R-FLU-6790580 (Reactome)
K48polyUb-DDX58 ProteinO95786 (Uniprot-TrEMBL)
K48polyUb-DDX58,K48polyUb-IFIH1ComplexR-HSA-983460 (Reactome)
K48polyUb-IFIH1 ProteinQ9BYX4 (Uniprot-TrEMBL)
K48polyUb-MAVS ProteinQ7Z434 (Uniprot-TrEMBL)
K48polyUb-RNF125 ProteinQ96EQ8 (Uniprot-TrEMBL)
K48polyUb-TRAF3ProteinQ13114 (Uniprot-TrEMBL)
K48polyUbR-HSA-912740 (Reactome)
K63polyUb-DDX58 ProteinO95786 (Uniprot-TrEMBL)
K63polyUb-DDX58ProteinO95786 (Uniprot-TrEMBL)
K63polyUb-TRAF3 ProteinQ13114 (Uniprot-TrEMBL)
K63polyUb-TRAF3ProteinQ13114 (Uniprot-TrEMBL)
K63polyUbR-HSA-450152 (Reactome)
MAP3K1 ProteinQ13233 (Uniprot-TrEMBL)
MAP3K1ProteinQ13233 (Uniprot-TrEMBL)
MAVS ProteinQ7Z434 (Uniprot-TrEMBL)
MAVS:NLRX1ComplexR-HSA-936561 (Reactome)
MAVSProteinQ7Z434 (Uniprot-TrEMBL)
MV dsRNA intermediate form R-MVI-9013943 (Reactome)
MYD88 ProteinQ99836 (Uniprot-TrEMBL)
N-epsilon-(1-(1-carboxy)ethyl)lysine MetaboliteCHEBI:60125 (ChEBI)
NECML MetaboliteCHEBI:53014 (ChEBI)
NFKB1(1-433) ProteinP19838 (Uniprot-TrEMBL)
NFKB1(1-433):NFKB2(1-454):RELAComplexR-HSA-168155 (Reactome)
NFKB2(1-454) ProteinQ00653 (Uniprot-TrEMBL)
NFKBIA ProteinP25963 (Uniprot-TrEMBL)
NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
NFkB ComplexComplexR-HSA-177673 (Reactome)
NKIRAS1 ProteinQ9NYS0 (Uniprot-TrEMBL)
NKIRAS2 ProteinQ9NYR9 (Uniprot-TrEMBL)
NKIRASComplexR-HSA-8952687 (Reactome)
NLRC5 ProteinQ86WI3 (Uniprot-TrEMBL)
NLRC5ProteinQ86WI3 (Uniprot-TrEMBL)
NLRX1 ProteinQ86UT6 (Uniprot-TrEMBL)
NLRX1ProteinQ86UT6 (Uniprot-TrEMBL)
OTUD5ProteinQ96G74 (Uniprot-TrEMBL)
PCBP2 ProteinQ15366 (Uniprot-TrEMBL)
PCBP2ProteinQ15366 (Uniprot-TrEMBL)
PIN1 ProteinQ13526 (Uniprot-TrEMBL)
PIN1ProteinQ13526 (Uniprot-TrEMBL)
Peptide MetaboliteCHEBI:16670 (ChEBI)
Phospho-NF-kappaB InhibitorComplexR-HSA-177678 (Reactome)
Promoter region of type-I IFN genesComplexR-HSA-1027363 (Reactome)
Promotor region of interferon betaR-ALL-1008217 (Reactome)
Promotor region of interferon alpha R-ALL-994028 (Reactome)
Promotor region of interferon beta R-ALL-1008217 (Reactome)
RELA ProteinQ04206 (Uniprot-TrEMBL)
RIPK1 ProteinQ13546 (Uniprot-TrEMBL)
RIPK1ProteinQ13546 (Uniprot-TrEMBL)
RNF125:E2

enzyme (UBE2K,

UbcH5a-c):K48-polyubiquitin		ComplexR-HSA-936388 (Reactome)
RNF125ProteinQ96EQ8 (Uniprot-TrEMBL)
RNF135 ProteinQ8IUD6 (Uniprot-TrEMBL)
RNF135,TRIM25ComplexR-HSA-936435 (Reactome)
RNF216ProteinQ9NWF9 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
RV RNA R-ROT-9013911 (Reactome)
S100A12 ProteinP80511 (Uniprot-TrEMBL)
S100B ProteinP04271 (Uniprot-TrEMBL)
SAA1(19-122) ProteinP0DJI8 (Uniprot-TrEMBL)
SIKE1 ProteinQ9BRV8 (Uniprot-TrEMBL)
SIKE1ProteinQ9BRV8 (Uniprot-TrEMBL)
TANK ProteinQ92844 (Uniprot-TrEMBL)
TANKProteinQ92844 (Uniprot-TrEMBL)
TAX1BP1 ProteinQ86VP1 (Uniprot-TrEMBL)
TAX1BP1:TNFAIP3:TBK1/IKKiComplexR-HSA-937333 (Reactome)
TAX1BP1:TNFAIP3ComplexR-HSA-937339 (Reactome)
TBK1 ProteinQ9UHD2 (Uniprot-TrEMBL)
TBK1/IKKi:SIKE1ComplexR-HSA-918197 (Reactome)
TNFAIP3 ProteinP21580 (Uniprot-TrEMBL)
TRAF2 ProteinQ12933 (Uniprot-TrEMBL)
TRAF2, TRAF6ComplexR-HSA-918188 (Reactome)
TRAF3 ProteinQ13114 (Uniprot-TrEMBL)
TRAF6 ProteinQ9Y4K3 (Uniprot-TrEMBL)
TRIM25 ProteinQ14258 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBA7 ProteinP41226 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UBE2D1 ProteinP51668 (Uniprot-TrEMBL)
UBE2D2 ProteinP62837 (Uniprot-TrEMBL)
UBE2D3 ProteinP61077 (Uniprot-TrEMBL)
UBE2K ProteinP61086 (Uniprot-TrEMBL)
UBE2L6 ProteinO14933 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
Unmethylated CpG DNA R-ALL-3134861 (Reactome)
VAF (virus-activated factor)ComplexR-HSA-1027360 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN

gene promoter		ComplexR-HSA-1027368 (Reactome)
VAF/pIRF7:CBP/p300ComplexR-HSA-1027361 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12ComplexR-HSA-936400 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1ComplexR-HSA-933482 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7ComplexR-HSA-933470 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiComplexR-HSA-933479 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKComplexR-HSA-933472 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6ComplexR-HSA-933467 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomain:IKK complexComplexR-HSA-933478 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainComplexR-HSA-933473 (Reactome)
p-2S-IRF7:p-2S-IRF7ComplexR-HSA-450344 (Reactome)
p-4S,T404-IRF3 ProteinQ14653 (Uniprot-TrEMBL)
p-4S,T404-IRF3,p-S477,S479-IRF7ComplexR-HSA-450240 (Reactome)
p-5S,T404-IRF3 ProteinQ14653 (Uniprot-TrEMBL)
p-IRF3 dimer:PIN1ComplexR-HSA-936444 (Reactome)
p-IRF3:p-IRF3ComplexR-HSA-936446 (Reactome)
p-S176,S180-CHUK ProteinO15111 (Uniprot-TrEMBL)
p-S177,S181-IKBKB ProteinO14920 (Uniprot-TrEMBL)
p-S19,S23-NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
p-S32,S36-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
p-S477,S479-IRF7 ProteinQ92985 (Uniprot-TrEMBL)
p-S477,S479-IRF7ProteinQ92985 (Uniprot-TrEMBL)
p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300:Promotor region of interferon betaComplexR-HSA-1027359 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300ComplexR-HSA-1027364 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ComplexR-HSA-166272 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ComplexR-HSA-177675 (Reactome)
unknown ligaseR-HSA-5244779 (Reactome)
viral

dsRNA:IFIH1, 2xviral

dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP:NLRC5		ComplexR-HSA-937325 (Reactome)
viral

dsRNA:IFIH1, 2xviral

dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP		ComplexR-HSA-918192 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon:IRF3,IRF7		ComplexR-HSA-918199 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon		ComplexR-HSA-918196 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3		ComplexR-HSA-918200 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:PCBP2:ITCH		ComplexR-HSA-983459 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:PCBP2		ComplexR-HSA-983462 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-216), CASP10(1-219)		ComplexR-HSA-8983916 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-479), CASP10(1-521)		ComplexR-HSA-933483 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:CASP8(1-479), CASP10(1-521)		ComplexR-HSA-933468 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD		ComplexR-HSA-918291 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:TRAF3		ComplexR-HSA-936558 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		ComplexR-HSA-918201 (Reactome)
viral dsRNA:IFIH1ComplexR-HSA-913727 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2x DDX58 ligand:2x DDX58:2xATPArrowR-HSA-168935 (Reactome)
2x DDX58 ligand:2x DDX58:2xATPR-HSA-918224 (Reactome)
2xp-S477,S479-IRF7ArrowR-HSA-1028816 (Reactome)
2xp-S477,S479-IRF7ArrowR-HSA-933531 (Reactome)
2xp-S477,S479-IRF7R-HSA-933536 (Reactome)
2xviral dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATPArrowR-HSA-918224 (Reactome)
ADPArrowR-HSA-168140 (Reactome)
ADPArrowR-HSA-918229 (Reactome)
ADPArrowR-HSA-933525 (Reactome)
ADPArrowR-HSA-933530 (Reactome)
AGER ligands:AGERArrowR-HSA-168166 (Reactome)
ATG5:ATG12:MAVSR-HSA-936378 (Reactome)
ATPR-HSA-168140 (Reactome)
ATPR-HSA-168935 (Reactome)
ATPR-HSA-918229 (Reactome)
ATPR-HSA-933525 (Reactome)
ATPR-HSA-933530 (Reactome)
CASP10(220-415)ArrowR-HSA-933532 (Reactome)
CASP10(416-521)ArrowR-HSA-933532 (Reactome)
CASP8(1-479), CASP10(1-521)R-HSA-933523 (Reactome)
CASP8(1-479), CASP10(1-521)R-HSA-933526 (Reactome)
CASP8(217-374)ArrowR-HSA-933532 (Reactome)
CASP8(375-384)ArrowR-HSA-933532 (Reactome)
CASP8(385-479)ArrowR-HSA-933532 (Reactome)
CBP/p300:pIRF7:pIRF7ArrowR-HSA-933536 (Reactome)
CHUK:IKBKB:IKBKGR-HSA-933530 (Reactome)
CHUK:IKBKB:IKBKGR-HSA-933539 (Reactome)
CREBBP, EP300R-HSA-1028817 (Reactome)
CREBBP, EP300R-HSA-1028820 (Reactome)
CREBBP, EP300R-HSA-933536 (Reactome)
CYLDmim-catalysisR-HSA-936390 (Reactome)
DAKArrowR-HSA-913725 (Reactome)
DDX58 ligandR-HSA-168935 (Reactome)
DDX58, IFIH1R-HSA-936412 (Reactome)
DDX58ArrowR-HSA-936390 (Reactome)
DDX58R-HSA-168935 (Reactome)
DDX58R-HSA-936563 (Reactome)
DHX36:CpG:MyD88ArrowR-HSA-933531 (Reactome)
DHX58TBarR-HSA-168935 (Reactome)
DHX9:CpG:MyD88ArrowR-HSA-168166 (Reactome)
E2 enzyme (UBE2K, UbcH5a-c)ArrowR-HSA-936412 (Reactome)
FADDR-HSA-168934 (Reactome)
H2OR-HSA-936381 (Reactome)
IFIH1 ligandR-HSA-913725 (Reactome)
IFIH1:DAKR-HSA-913725 (Reactome)
IFN alpha/beta (IFNA/B)ArrowR-HSA-994034 (Reactome)
IFNB1ArrowR-HSA-1028812 (Reactome)
IKBKG:p-S176,S180-CHUK:p-S177,S181-IKBKBArrowR-HSA-933530 (Reactome)
IKBKG:p-S176,S180-CHUK:p-S177,S181-IKBKBmim-catalysisR-HSA-168140 (Reactome)
IKK related kinases TBK1/IKK epsilonR-HSA-937337 (Reactome)
IRF1:Promotors of IFN alpha, IFN betaArrowR-HSA-994034 (Reactome)
IRF2:promoters of INF alpha, INF betaTBarR-HSA-994034 (Reactome)
IRF3,IRF7R-HSA-918232 (Reactome)
IRF3-P:IRF7-PArrowR-HSA-1028816 (Reactome)
IRF3-P:IRF7-PArrowR-HSA-1028821 (Reactome)
IRF3-P:IRF7-PR-HSA-1028816 (Reactome)
IRF3-P:IRF7-PR-HSA-1028820 (Reactome)
IRF7R-HSA-933538 (Reactome)
ISG15:DDX58 conjugateArrowR-HSA-936563 (Reactome)
ISG15:DDX58 conjugateTBarR-HSA-168935 (Reactome)
ISG15:UBEIL/UbcH8:CEB1R-HSA-936563 (Reactome)
ISGylated IRF3TBarR-HSA-936462 (Reactome)
ITCHR-HSA-990526 (Reactome)
ITCHmim-catalysisR-HSA-990526 (Reactome)
IkBs:NFkBR-HSA-168140 (Reactome)
K48polyUb-DDX58,K48polyUb-IFIH1ArrowR-HSA-936412 (Reactome)
K48polyUb-TRAF3ArrowR-HSA-936475 (Reactome)
K48polyUbR-HSA-936475 (Reactome)
K48polyUbR-HSA-990526 (Reactome)
K63polyUb-DDX58R-HSA-936390 (Reactome)
K63polyUb-TRAF3R-HSA-918227 (Reactome)
K63polyUbArrowR-HSA-936381 (Reactome)
K63polyUbR-HSA-918224 (Reactome)
MAP3K1R-HSA-933528 (Reactome)
MAVS:NLRX1ArrowR-HSA-936564 (Reactome)
MAVS:NLRX1TBarR-HSA-168909 (Reactome)
MAVSR-HSA-168909 (Reactome)
MAVSR-HSA-936564 (Reactome)
NFKB1(1-433):NFKB2(1-454):RELAArrowR-HSA-168140 (Reactome)
NFKB1(1-433):NFKB2(1-454):RELAR-HSA-168166 (Reactome)
NFkB ComplexArrowR-HSA-168166 (Reactome)
NKIRASTBarR-HSA-168140 (Reactome)
NLRC5R-HSA-937343 (Reactome)
NLRX1R-HSA-936564 (Reactome)
OTUD5mim-catalysisR-HSA-936381 (Reactome)
PCBP2R-HSA-990528 (Reactome)
PIN1ArrowR-HSA-936462 (Reactome)
PIN1R-HSA-936380 (Reactome)
Phospho-NF-kappaB InhibitorArrowR-HSA-168140 (Reactome)
Promoter region of type-I IFN genesR-HSA-1028819 (Reactome)
Promotor region of interferon betaR-HSA-1028815 (Reactome)
R-HSA-1028812 (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.
R-HSA-1028815 (Reactome) IRF3:CBP/p300 complex binds specifically to IFN-beta promoter region and induces IFN-beta mRNA expression.
R-HSA-1028816 (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.
R-HSA-1028817 (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.
R-HSA-1028819 (Reactome) IRF7 and VAF transcription factors binds to IFN-alpha and IFN-beta promoter regions and induce the IFN-alpha and beta mRNA.
R-HSA-1028820 (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).
R-HSA-1028821 (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.
R-HSA-168140 (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.

R-HSA-168166 (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.
R-HSA-168909 (Reactome) Upon binding viral dsRNA, Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I, RIG-1) and Interferon-induced helicase C domain-containing protein 1 (IFIH1, MDA5) recruit the downstream signal transducer Mitochondrial antiviral-signaling protein (MAVS, IPS-1). This mitochondria-bound adaptor has an N-terminal CARD-like domain (CLD) which associates with the CARD regions of DDX58 and IFIH1 to mediate induction of interferons.
R-HSA-168934 (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.
R-HSA-168935 (Reactome) Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I, RIG-1) has two caspase recruitment domains (CARD) in its N-terminus, a 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, DDX58 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 viral RNAs activates DDX58 by binding to its RNA helicase domain. This provokes a change in DDX58 conformation exposing the CARD leading to DDX58 dimerization, allowing it to interact with Mitochondrial antiviral-signaling protein (MAVS, IPS-1).
R-HSA-913725 (Reactome) Interferon-induced helicase C domain-containing protein 1 (IFIH1, MDA5) is the closest relative of Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I). It contains two Caspase activation and recruitment domain (CARD)-like regions, a DExD/H helicase domain, and a C-terminal region similar to the RD of DDX58. IFIH1, via its C-terminal domain (CTD), preferentially binds dsRNA with blunt ends. It does not associate with dsRNA having 5' or 3' overhangs. Upon binding dsRNA, IFIH1 is presumed to undergo a structural alteration that unmasks the CARDs enabling them to recruit downstream signal transducer proteins. Dihydroxyacetone kinase (DAK) binds to the CARD domains of IFIH1, acting as a negative regulator. It is released upon the conformational change induced by viral RNA binding, allowing the CARD domains to bind to the CARD of Mitochondrial antiviral-signaling protein (MAVS, IPS-1).
R-HSA-918224 (Reactome) On viral infection Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I, RIG-1) undergoes robust ubiquitination at its N-terminal Caspase activation and recruitment domain (CARD) region. E3 ubiquitin/ISG15 ligase TRIM25 (TRIM25), a member of the tripartite motif (TRIM) protein family and E3 ubiquitin-protein ligase RNF135 (RNF135, REUL) are the E3 ligases involved in K63-linked polyubiquitination (K63polyUb) of DDX58. 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 DDX58. The polyubiquitin chains added by TRIM25 are unanchored. The lysine-172 (K172) residue of DDX58 is critical for efficient TRIM25-mediated ubiquitination and for binding of Mitochondrial antiviral-signaling protein (MAVS, IPS-1), as well as the ability of DDX58 to induce antiviral signal transduction. RNF135 associates with DDX58 through its PRY and SPRY domains. The K154, K164, and K172 residues of the DDX58 CARD domain were determined to be critical for efficient RNF135-mediated ubiquitination and for the ability of DDX58 to induce antiviral signal transduction. (Michaela et al. Goa et al. 2009).
R-HSA-918225 (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.
R-HSA-918227 (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.
R-HSA-918229 (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]
R-HSA-918230 (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.
R-HSA-918232 (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.
R-HSA-933523 (Reactome) Procaspase-8/10 undergo dimerization and the subsequent conformational changes at the receptor complex results in the formation of catalytic active caspase dimers.
R-HSA-933525 (Reactome) IRF7 is activated through phosphorylation of residues Ser477 and Ser479 by TBK1/IKKi kinase complex.
R-HSA-933526 (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.
R-HSA-933527 (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.
R-HSA-933528 (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)
R-HSA-933530 (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.
R-HSA-933531 (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.
R-HSA-933532 (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.
R-HSA-933533 (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.
R-HSA-933536 (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.
R-HSA-933537 (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).
R-HSA-933538 (Reactome) TRAF6 associates with and activates IRF7 but not IRF3.
R-HSA-933539 (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.
R-HSA-936378 (Reactome) Autophagy protein 5 (ATG5) and autophagy-related protein 12 (ATG12) conjugate negatively regulates the type I IFN production pathway by directly associating with DDX58/IFIH1 and MAVS through the caspase recruitment domains (CARDs). The ATG5-ATG12 conjugate intercalates between the CARDs of DDX58/IFIH1 and MAVS and inhibits signal transmission, resulting in suppression of type I IFN production and innate antiviral immune responses.
R-HSA-936380 (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.
R-HSA-936381 (Reactome) OTUD5 (Deubiquitinating enzyme A (DUBA)) is a negative regulator of type I interferon (IFN-) production. TRAF3, an E3 ubiquitin ligase that preferentially assembles lysine-63-linked polyubiquitin chains, is one of the targets of OTUD5. Expression of DUBA increases the cleavage of K63-linked ubiquitin chains from TRAF3, resulting in its dissociation from the downstream signaling complex that contains TANK-binding kinase 1 (TBK1) (Kayagaki et al. 2007), which leads to blockade of IRF3 and IRF7 phosphorylation.
R-HSA-936390 (Reactome) CYLD is an ovarian tumor (OTU) domain-containing deubiquitinating enzyme (DUB) and has been identified as a negative regulator of DDX58 (RIG-I) mediated antiviral signaling. CYLD associates with the CARD domain of DDX58 and removes K63-linked ubiquitin from the DDX58 CARDs that are conjugated by the E3 ubiquitin ligase, TRIM25 and RNF135.
R-HSA-936412 (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.
R-HSA-936462 (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.
R-HSA-936475 (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.
R-HSA-936563 (Reactome) ISG15 is an 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 DDX58 negatively regulating DDX58-mediated antiviral signaling. ISGylated DDX58 becomes subject to an irreversible biochemical process, such as proteolysis or proteasomeal degradation.
R-HSA-936564 (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.
R-HSA-937337 (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.
R-HSA-937343 (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.
R-HSA-990526 (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.
R-HSA-990528 (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.
R-HSA-994034 (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).
RIPK1R-HSA-168934 (Reactome)
RNF125:E2

enzyme (UBE2K,

UbcH5a-c):K48-polyubiquitin		mim-catalysisR-HSA-936412 (Reactome)
RNF125ArrowR-HSA-936412 (Reactome)
RNF135,TRIM25R-HSA-918224 (Reactome)
RNF135,TRIM25mim-catalysisR-HSA-918224 (Reactome)
RNF216mim-catalysisR-HSA-936475 (Reactome)
SIKE1ArrowR-HSA-918225 (Reactome)
SIKE1ArrowR-HSA-933527 (Reactome)
TANKR-HSA-933537 (Reactome)
TAX1BP1:TNFAIP3:TBK1/IKKiArrowR-HSA-937337 (Reactome)
TAX1BP1:TNFAIP3R-HSA-937337 (Reactome)
TBK1/IKKi:SIKE1R-HSA-918225 (Reactome)
TBK1/IKKi:SIKE1R-HSA-933527 (Reactome)
TBarR-HSA-168909 (Reactome)
TRAF2, TRAF6R-HSA-918230 (Reactome)
UbArrowR-HSA-936390 (Reactome)
VAF (virus-activated factor)ArrowR-HSA-1028820 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN

gene promoter		ArrowR-HSA-1028819 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN

gene promoter		ArrowR-HSA-994034 (Reactome)
VAF/pIRF7:CBP/p300R-HSA-1028819 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12ArrowR-HSA-936378 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1ArrowR-HSA-933528 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1mim-catalysisR-HSA-933530 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7ArrowR-HSA-933538 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7R-HSA-933525 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7mim-catalysisR-HSA-933525 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiArrowR-HSA-933525 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiArrowR-HSA-933527 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiR-HSA-933538 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKArrowR-HSA-933537 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKR-HSA-933527 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6ArrowR-HSA-918230 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6R-HSA-933528 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6R-HSA-933537 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomain:IKK complexArrowR-HSA-933539 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainR-HSA-933539 (Reactome)
p-2S-IRF7:p-2S-IRF7ArrowR-HSA-1028821 (Reactome)
p-2S-IRF7:p-2S-IRF7ArrowR-HSA-933533 (Reactome)
p-2S-IRF7:p-2S-IRF7R-HSA-1028816 (Reactome)
p-2S-IRF7:p-2S-IRF7R-HSA-933531 (Reactome)
p-4S,T404-IRF3,p-S477,S479-IRF7ArrowR-HSA-918229 (Reactome)
p-4S,T404-IRF3,p-S477,S479-IRF7R-HSA-1028821 (Reactome)
p-IRF3 dimer:PIN1ArrowR-HSA-936380 (Reactome)
p-IRF3 dimer:PIN1R-HSA-936462 (Reactome)
p-IRF3:p-IRF3R-HSA-936380 (Reactome)
p-S477,S479-IRF7ArrowR-HSA-933525 (Reactome)
p-S477,S479-IRF7R-HSA-933533 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300:Promotor region of interferon betaArrowR-HSA-1028812 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300:Promotor region of interferon betaArrowR-HSA-1028815 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300ArrowR-HSA-1028817 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300R-HSA-1028815 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ArrowR-HSA-1028816 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ArrowR-HSA-1028821 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3R-HSA-1028816 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3R-HSA-1028817 (Reactome)
unknown ligasemim-catalysisR-HSA-936462 (Reactome)
viral

dsRNA:IFIH1, 2xviral

dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP:NLRC5		ArrowR-HSA-937343 (Reactome)
viral

dsRNA:IFIH1, 2xviral

dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP		R-HSA-168909 (Reactome)
viral

dsRNA:IFIH1, 2xviral

dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP		R-HSA-936378 (Reactome)
viral

dsRNA:IFIH1, 2xviral

dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP		R-HSA-937343 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon:IRF3,IRF7		ArrowR-HSA-918232 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon:IRF3,IRF7		R-HSA-918229 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon:IRF3,IRF7		mim-catalysisR-HSA-918229 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon		ArrowR-HSA-918225 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon		ArrowR-HSA-918229 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:IKK related kinases TBK1/IKK epsilon		R-HSA-918232 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3		ArrowR-HSA-918227 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3		R-HSA-918225 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3		R-HSA-936381 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:PCBP2:ITCH		ArrowR-HSA-990526 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:PCBP2		ArrowR-HSA-990528 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:PCBP2		R-HSA-990526 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-216), CASP10(1-219)		ArrowR-HSA-933532 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-479), CASP10(1-521)		ArrowR-HSA-933523 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-479), CASP10(1-521)		R-HSA-933532 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:2xCASP8(1-479), CASP10(1-521)		mim-catalysisR-HSA-933532 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:CASP8(1-479), CASP10(1-521)		ArrowR-HSA-933526 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD:CASP8(1-479), CASP10(1-521)		R-HSA-933523 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD		ArrowR-HSA-168934 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:RIPK1:FADD		R-HSA-933526 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:TRAF3		ArrowR-HSA-936381 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS:TRAF3		R-HSA-936475 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		ArrowR-HSA-168909 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		ArrowR-HSA-936475 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		R-HSA-168934 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		R-HSA-918227 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		R-HSA-918230 (Reactome)
viral

dsRNA:IFIH1, viral

dsRNA:K63polyUb-DDX58:MAVS		R-HSA-990528 (Reactome)
viral dsRNA:IFIH1ArrowR-HSA-913725 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1904"
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