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

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7, 16, 22, 27, 40...14, 20, 32, 34, 75564229, 666, 31, 6948, 52, 734328, 50, 6141213, 38, 7211, 39, 57, 59, 6021, 65191, 671349, 73206, 3011, 39, 57, 59, 60181711, 39, 57-604, 6, 62422613, 15, 37, 44555633, 53, 6486, 446324, 5033, 53, 6429, 669, 12, 35, 712, 55, 755638, 454610, 32, 445, 25, 51, 54cytosolnucleoplasmmitochondrionMAVS K63polyUb-DDX58 FADD TAX1BP1 MAVS NFKB2(1-454) K48polyUb-TRAF3 TAX1BP1:TNFAIP3Promotor region ofinterferon betaIKBKE RNF135 NFKB1(1-433) IFIH1 TRAF3 RNF135 unknown ligaseTBK1 NFkB ComplexIKBKB RNF135 NFKBIA ATPp-T,4S-IRF3:p-T,4S-IRF3IRF3 IFIH1 ISG15:UBEIL/UbcH8:CEB1dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7ISG15 SIKE1p-4S,T404-IRF3 IRF3/ IRF7DHX36:CpG:MyD88TNFAIP3 p-4S,T404-IRF3 RNF135 NLRX1K63polyUb-DDX58 ITCHK63polyUbRNF125ATG5 IFIH1 K48polyUbFADDEP300 dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7IKBKG TRIM25 HERC5 ATP dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerRIPK1 CYLDTBK1 Viral dsRNA (-)StrandedATP TRAF6 RIG-I E3 ubiquitinligasesEP300 IKBKE K63polyUb-DDX58 IRF7TANK FADD Activated IKKComplexDHX36 VAF (virus-activatedfactor)dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10p-S477,S479-IRF7 TRAF2 and TRAF6NLRX1 CASP10(220-415)IFIH1 TBK1/IKKi:SIKE1K63polyUb-DDX58 RNF135 DHX9:CpG:MyD88RIPK1 p-5S,T404-IRF3 ATG5 RNF135 ATP CASP10(1-219) TRAF2 EP300 K63-UbITCH RNF135 IKBKE MAVS CASP8(385-479)RNF135 IFIH1 DHX58ATP CREBBP APP(672-711) FADD DHX9 MAVS K63polyUb-DDX58 PIN1 Peptide ATPdsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainp-S177,S181-IKBKB K63polyUb-TRAF3K63polyUb-DDX58 IPS-1:NLRX1IFIH1 RNF135 MAVS IFIH1 dsRNA:Ub-RIG-I:TRIM25RNF135 DAK MAVS ATP dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiK63polyUb-DDX58 K63polyUb-DDX58 TRIM25 IRF7 TRIM25 MAP3K1phosphorylatedIRF3/IRF7K63polyUb-DDX58 dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKAGER ligands:AGERTRAF6 CASP8(1-479) ATP TRAF6 MAVS TANK ATP TRIM25 CASP8(1-216) IRF3 bound toIFN-beta promoterIFIH1 VAF/pIRF7:CBP/p300bound to type I IFNgene promoterISG15:RIG-Iconjugatep-T,4S-IRF3:p-T,4S-IRF3NFKB2(1-454) RELA IRF2:promoters ofINF alpha, INF betaK63polyUb-DDX58 ADPSAA1(19-122) K48polyUb-MAVS IKKA:IKBKB:IKBKGNLRC5 TAX1BP1 MYD88 ATP dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1ATP CASP8(1-479) APP(672-713) TRAF6 CASP8(1-216) ADPTRIM25 MAVS OTUD5RNF135 ATPTRIM25 TRIM25 ATP TRAF6 NFKBIB dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6TNFAIP3 CASP8(217-374)K63polyUb-DDX58 DAKTRAF2 IFIH1 MAVS p-S477,S479-IRF7 IKBKE IFIH1 MAVSNLRC5dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3SIKE1 TRIM25 dsRNA:RIG-I/MDA5:IPS-1IKKA ATP RNF135 K63polyUb-DDX58 K63polyUb-DDX58 FADD IKKA:IKBKB:IKBKGIKBKG ATP IFIH1 MAVS p-S477,S479-IRF7 p-4S,T404-IRF3 IKBKB K63polyUb-TRAF3 CASP10(416-521)MAVS TANK ADPIPS-1:ATG5-ATG12conjugateK63polyUb-DDX58 TBK1 EP300 IKKA IRF3-Pdimer:CBP/p300Phospho-NF-kappaBInhibitorTRIM25 TRIM25 CASP8(375-384)p-S477,S479-IRF7 IKBKE VAF/pIRF7:CBP/p300TRIM25 2xp-S477,S479-IRF7CREBBP dsRNA:RIG-I/MDA5:NLRC5MDA5:DAKISG15 dsRNA:RIG-I/MDA5:IPS-1:PCBP2IFIH1 RNF135 CREBBP NFKB1(1-433) K63polyUb-DDX58 TRIM25 N-epsilon-(1-(1-carboxy)ethyl)lysine RNF135 E2 enzyme (UBE2K,UbcH5a-c)FADD IFNB1DDX58IRF3 dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDATP IRF1:Promotors ofIFN alpha, IFN betap-4S,T404-IRF3 dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiK63polyUb-DDX58 IRF3-P:IRF7-PCASP10(1-219) dsRNA:MDA5TRIM25 UBA7 procaspase-8/10HERC5 NECML NFKB1(1-433) ATG12 IFIH1 TRIM25 MAVS p-S176,S180-IKKA PIN1IRF7 RELA PCBP2 NFkB ComplexATP ATPK63polyUb-DDX58 dsRNA:RIG-I/MDA5:K48Ub-IPS-1:PCBP2:AIP4p-IRF3 dimer:PIN1TRIM25 K63polyUb-TRAF3 p-5S,T404-IRF3 CASP10(1-521) MAVS RIPK1 K63polyUb-DDX58 CREBBP p-2S-IRF7:p-2S-IRF7IFIH1 K48polyUbK63polyUb-DDX58NFKB2(1-454) p-IRF3:p-IRF3TANKp-4S,T404-IRF3 p-S477,S479-IRF7 ATP TRAF2 MAVS PCBP2 K63polyUb-TRAF3 CBP/p300IkBs:NFkBp-4S,T404-IRF3 dsRNA bound to RIG-IATG12 RNF135 IKBKB TBK1 ATP IKBKE MAVS CREBBP dsRNA:RIG-I/MDA5UBE2L6 ATP K48polyUb RIG-I/MDA5HMGB1 IFIH1 ATP RNF135 IFIH1 TRIM25 p-S477,S479-IRF7 ATP IKBKG dsRNA:RIG-1/MDA5:IPS-1:TRAF3IKK related kinasesTBK1/IKK epsilonRNF125:E2enzyme(UBE2K,UbcH5a-c):K48-polyubiquitinTBK1 UBA7 DDX58/IFIH1p-S477,S479-IRF7 dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12PCBP2ATP DDX58 MAVS MAVS IKKA TRIM25 CASP10(1-521) RNF135 MYD88 K63polyUb-TRAF3 RNF135 ISGylated IRF3dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomain:IKK complexTBK1 TRIM25 S100B IFIH1 Promoter region oftype-I IFN genesRNF135 IKBKG IFN alpha/beta(IFNA/B)TAX1BP1:TNFAIP3:TBK1/IKKiMAVS RIPK1 K63polyUb-DDX58 ATPp-S477,S479-IRF7TRAF2 p-4S,T404-IRF3 UbS100A12 RELA RNF135 RIPK1 ADPATP K48polyUb-RNF125 MAVS DDX58 RIPK1IFIH1 ISG15 EP300 MAP3K1 TRIM25 UBE2L6 IFIH1 K63polyUb-DDX58 TRAF2 K63polyUb-DDX58 IFIH1 IRF3-P:IRF7-Pp-4S,T404-IRF3 K48polyUb-TRAF3TRIM25 IFIH1 AGER CBP/p300:pIRF7:pIRF724, 51, 5424, 51, 5424, 51, 5424, 51, 5424, 51, 5424, 51, 5424, 51, 54266824, 51, 5424, 51, 5424, 51, 5424, 51, 5424, 51, 54364224, 51, 54683624, 51, 542924, 51, 542668687424242424, 51, 546824, 51, 5423, 4724, 51, 5424, 51, 5424, 51, 5424, 51, 5424, 51, 5468


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. Source:Reactome.

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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
2xp-S477,S479-IRF7ComplexR-HSA-450306 (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)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated IKK ComplexComplexR-HSA-177663 (Reactome)
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(217-374)ProteinQ14790 (Uniprot-TrEMBL)
CASP8(375-384)ProteinQ14790 (Uniprot-TrEMBL)
CASP8(385-479)ProteinQ14790 (Uniprot-TrEMBL)
CBP/p300:pIRF7:pIRF7ComplexR-HSA-933471 (Reactome)
CBP/p300R-HSA-1027362 (Reactome)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CYLDProteinQ9NQC7 (Uniprot-TrEMBL)
DAK ProteinQ3LXA3 (Uniprot-TrEMBL)
DAKProteinQ3LXA3 (Uniprot-TrEMBL)
DDX58 ProteinO95786 (Uniprot-TrEMBL)
DDX58/IFIH1R-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)R-HSA-936441 (Reactome)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
FADD ProteinQ13158 (Uniprot-TrEMBL)
FADDProteinQ13158 (Uniprot-TrEMBL)
HERC5 ProteinQ9UII4 (Uniprot-TrEMBL)
HMGB1 ProteinP09429 (Uniprot-TrEMBL)
IFIH1 ProteinQ9BYX4 (Uniprot-TrEMBL)
IFN alpha/beta (IFNA/B)R-HSA-909690 (Reactome)
IFNB1ProteinP01574 (Uniprot-TrEMBL)
IKBKB ProteinO14920 (Uniprot-TrEMBL)
IKBKE ProteinQ14164 (Uniprot-TrEMBL)
IKBKG ProteinQ9Y6K9 (Uniprot-TrEMBL)
IKK related kinases TBK1/IKK epsilonR-HSA-450329 (Reactome)
IKKA ProteinO15111 (Uniprot-TrEMBL)
IKKA:IKBKB:IKBKGComplexR-HSA-168113 (Reactome)
IPS-1:ATG5-ATG12 conjugateComplexR-HSA-936373 (Reactome)
IPS-1:NLRX1ComplexR-HSA-936561 (Reactome)
IRF1:Promotors of IFN alpha, IFN betaR-HSA-1008247 (Reactome)
IRF2:promoters of INF alpha, INF betaR-HSA-1018386 (Reactome)
IRF3 ProteinQ14653 (Uniprot-TrEMBL)
IRF3 bound to IFN-beta promoterComplexR-HSA-1027359 (Reactome)
IRF3-P dimer:CBP/p300ComplexR-HSA-1027364 (Reactome)
IRF3-P:IRF7-PComplexR-HSA-1027365 (Reactome)
IRF3-P:IRF7-PComplexR-HSA-1027367 (Reactome)
IRF3/ IRF7R-HSA-450317 (Reactome)
IRF7 ProteinQ92985 (Uniprot-TrEMBL)
IRF7ProteinQ92985 (Uniprot-TrEMBL)
ISG15 ProteinP05161 (Uniprot-TrEMBL)
ISG15:RIG-I 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)
K48polyUb RIG-I/MDA5R-HSA-983460 (Reactome)
K48polyUb-MAVS ProteinQ7Z434 (Uniprot-TrEMBL)
K48polyUb-RNF125 ProteinQ96EQ8 (Uniprot-TrEMBL)
K48polyUb-TRAF3 ProteinQ13114 (Uniprot-TrEMBL)
K48polyUb-TRAF3ComplexQ13114 (Uniprot-TrEMBL)
K48polyUbR-HSA-912740 (Reactome)
K63-UbR-HSA-450143 (Reactome)
K63polyUb-DDX58 ProteinO95786 (Uniprot-TrEMBL)
K63polyUb-DDX58ComplexO95786 (Uniprot-TrEMBL)
K63polyUb-TRAF3 ProteinQ13114 (Uniprot-TrEMBL)
K63polyUb-TRAF3ComplexQ13114 (Uniprot-TrEMBL)
K63polyUbR-HSA-450152 (Reactome)
MAP3K1 ProteinQ13233 (Uniprot-TrEMBL)
MAP3K1ProteinQ13233 (Uniprot-TrEMBL)
MAVS ProteinQ7Z434 (Uniprot-TrEMBL)
MAVSProteinQ7Z434 (Uniprot-TrEMBL)
MDA5:DAKComplexR-HSA-918203 (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)
NFKB2(1-454) ProteinQ00653 (Uniprot-TrEMBL)
NFKBIA ProteinP25963 (Uniprot-TrEMBL)
NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
NFkB ComplexComplexR-HSA-168155 (Reactome)
NFkB ComplexComplexR-HSA-177673 (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 InhibitorR-HSA-177678 (Reactome)
Promoter region of type-I IFN genesR-HSA-1027363 (Reactome)
Promotor region of interferon betaR-NUL-1008217 (Reactome)
RELA ProteinQ04206 (Uniprot-TrEMBL)
RIG-I E3 ubiquitin ligasesR-HSA-936435 (Reactome)
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)
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 and TRAF6R-HSA-918188 (Reactome)
TRAF3 ProteinQ13114 (Uniprot-TrEMBL)
TRAF6 ProteinQ9Y4K3 (Uniprot-TrEMBL)
TRIM25 ProteinQ14258 (Uniprot-TrEMBL)
UBA7 ProteinP41226 (Uniprot-TrEMBL)
UBE2L6 ProteinO14933 (Uniprot-TrEMBL)
UbR-HSA-113595 (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/p300R-HSA-1027361 (Reactome)
Viral dsRNA (-) StrandedR-NUL-167931 (Reactome)
dsRNA bound to RIG-IComplexR-HSA-168906 (Reactome)
dsRNA:MDA5ComplexR-HSA-913727 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:TRAF3ComplexR-HSA-936558 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7ComplexR-HSA-918199 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiComplexR-HSA-918196 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3ComplexR-HSA-918200 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12ComplexR-HSA-936400 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:PCBP2ComplexR-HSA-983462 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10ComplexR-HSA-933468 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerComplexR-HSA-933483 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDComplexR-HSA-918291 (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:IPS-1ComplexR-HSA-918201 (Reactome)
dsRNA:RIG-I/MDA5:K48 Ub-IPS-1:PCBP2:AIP4ComplexR-HSA-983459 (Reactome)
dsRNA:RIG-I/MDA5:NLRC5ComplexR-HSA-937325 (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)
dsRNA:RIG-I/MDA5R-HSA-918192 (Reactome)
dsRNA:Ub-RIG-I:TRIM25ComplexR-HSA-918190 (Reactome)
p-2S-IRF7:p-2S-IRF7ComplexR-HSA-450344 (Reactome)
p-4S,T404-IRF3 ProteinQ14653 (Uniprot-TrEMBL)
p-5S,T404-IRF3 ProteinQ14653 (Uniprot-TrEMBL)
p-IRF3 dimer:PIN1ComplexR-HSA-936444 (Reactome)
p-IRF3:p-IRF3ComplexR-HSA-936446 (Reactome)
p-S176,S180-IKKA ProteinO15111 (Uniprot-TrEMBL)
p-S177,S181-IKBKB ProteinO14920 (Uniprot-TrEMBL)
p-S477,S479-IRF7 ProteinQ92985 (Uniprot-TrEMBL)
p-S477,S479-IRF7ProteinQ92985 (Uniprot-TrEMBL)
p-T,4S-IRF3:p-T,4S-IRF3ComplexR-HSA-166272 (Reactome)
p-T,4S-IRF3:p-T,4S-IRF3ComplexR-HSA-177675 (Reactome)
phosphorylated IRF3/IRF7R-HSA-450240 (Reactome)
procaspase-8/10R-HSA-933463 (Reactome)
unknown ligaseR-HSA-5244779 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
2xp-S477,S479-IRF7ArrowR-HSA-1028816 (Reactome)
2xp-S477,S479-IRF7ArrowR-HSA-933531 (Reactome)
2xp-S477,S479-IRF7R-HSA-933536 (Reactome)
ADPArrowR-HSA-168140 (Reactome)
ADPArrowR-HSA-918229 (Reactome)
ADPArrowR-HSA-933525 (Reactome)
ADPArrowR-HSA-933530 (Reactome)
AGER ligands:AGERArrowR-HSA-168166 (Reactome)
ATPR-HSA-168140 (Reactome)
ATPR-HSA-168935 (Reactome)
ATPR-HSA-918229 (Reactome)
ATPR-HSA-933525 (Reactome)
ATPR-HSA-933530 (Reactome)
Activated IKK ComplexArrowR-HSA-933530 (Reactome)
Activated IKK Complexmim-catalysisR-HSA-168140 (Reactome)
CASP10(220-415)ArrowR-HSA-933532 (Reactome)
CASP10(416-521)ArrowR-HSA-933532 (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)
CBP/p300R-HSA-1028817 (Reactome)
CBP/p300R-HSA-1028820 (Reactome)
CBP/p300R-HSA-933536 (Reactome)
CYLDmim-catalysisR-HSA-936390 (Reactome)
DAKArrowR-HSA-913725 (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)
IFN alpha/beta (IFNA/B)ArrowR-HSA-994034 (Reactome)
IFNB1ArrowR-HSA-1028812 (Reactome)
IKK related kinases TBK1/IKK epsilonR-HSA-937337 (Reactome)
IKKA:IKBKB:IKBKGR-HSA-933530 (Reactome)
IKKA:IKBKB:IKBKGR-HSA-933539 (Reactome)
IPS-1:ATG5-ATG12 conjugateR-HSA-936378 (Reactome)
IPS-1:NLRX1ArrowR-HSA-936564 (Reactome)
IPS-1:NLRX1TBarR-HSA-168909 (Reactome)
IRF1:Promotors of IFN alpha, IFN betaArrowR-HSA-994034 (Reactome)
IRF2:promoters of INF alpha, INF betaTBarR-HSA-994034 (Reactome)
IRF3 bound to IFN-beta promoterArrowR-HSA-1028812 (Reactome)
IRF3 bound to IFN-beta promoterArrowR-HSA-1028815 (Reactome)
IRF3-P dimer:CBP/p300ArrowR-HSA-1028817 (Reactome)
IRF3-P dimer:CBP/p300R-HSA-1028815 (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)
IRF3/ IRF7R-HSA-918232 (Reactome)
IRF7R-HSA-933538 (Reactome)
ISG15:RIG-I conjugateArrowR-HSA-936563 (Reactome)
ISG15:RIG-I 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 RIG-I/MDA5ArrowR-HSA-936412 (Reactome)
K48polyUb-TRAF3ArrowR-HSA-936475 (Reactome)
K48polyUbR-HSA-936475 (Reactome)
K48polyUbR-HSA-990526 (Reactome)
K63-UbArrowR-HSA-936381 (Reactome)
K63polyUb-DDX58R-HSA-936390 (Reactome)
K63polyUb-TRAF3R-HSA-918227 (Reactome)
K63polyUbR-HSA-918224 (Reactome)
MAP3K1R-HSA-933528 (Reactome)
MAVSR-HSA-168909 (Reactome)
MAVSR-HSA-936564 (Reactome)
MDA5:DAKR-HSA-913725 (Reactome)
NFkB ComplexArrowR-HSA-168140 (Reactome)
NFkB ComplexArrowR-HSA-168166 (Reactome)
NFkB ComplexR-HSA-168166 (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 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.
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) 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).
R-HSA-913725 (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.
R-HSA-918224 (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)
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 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.
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) 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.
R-HSA-936390 (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.
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 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.
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).
RIG-I E3 ubiquitin ligasesR-HSA-918224 (Reactome)
RIG-I E3 ubiquitin ligasesmim-catalysisR-HSA-918224 (Reactome)
RIPK1R-HSA-168934 (Reactome)
RNF125:E2

enzyme (UBE2K,

UbcH5a-c):K48-polyubiquitin		mim-catalysisR-HSA-936412 (Reactome)
RNF125ArrowR-HSA-936412 (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)
TRAF2 and 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)
Viral dsRNA (-) StrandedR-HSA-168935 (Reactome)
Viral dsRNA (-) StrandedR-HSA-913725 (Reactome)
dsRNA bound to RIG-IArrowR-HSA-168935 (Reactome)
dsRNA bound to RIG-IR-HSA-918224 (Reactome)
dsRNA:MDA5ArrowR-HSA-913725 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:TRAF3ArrowR-HSA-936381 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:TRAF3R-HSA-936475 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7ArrowR-HSA-918232 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7R-HSA-918229 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7mim-catalysisR-HSA-918229 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiArrowR-HSA-918225 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiArrowR-HSA-918229 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiR-HSA-918232 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3ArrowR-HSA-918227 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3R-HSA-918225 (Reactome)
dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3R-HSA-936381 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12ArrowR-HSA-936378 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:PCBP2ArrowR-HSA-990528 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:PCBP2R-HSA-990526 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10ArrowR-HSA-933526 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10R-HSA-933523 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerArrowR-HSA-933523 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerR-HSA-933532 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimermim-catalysisR-HSA-933532 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDArrowR-HSA-168934 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDR-HSA-933526 (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:IPS-1ArrowR-HSA-168909 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1ArrowR-HSA-936475 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1R-HSA-168934 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1R-HSA-918227 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1R-HSA-918230 (Reactome)
dsRNA:RIG-I/MDA5:IPS-1R-HSA-990528 (Reactome)
dsRNA:RIG-I/MDA5:K48 Ub-IPS-1:PCBP2:AIP4ArrowR-HSA-990526 (Reactome)
dsRNA:RIG-I/MDA5:NLRC5ArrowR-HSA-937343 (Reactome)
dsRNA:RIG-I/MDA5:NLRC5TBarR-HSA-168909 (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 prodomainArrowR-HSA-933532 (Reactome)
dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainR-HSA-933539 (Reactome)
dsRNA:RIG-I/MDA5R-HSA-168909 (Reactome)
dsRNA:RIG-I/MDA5R-HSA-936378 (Reactome)
dsRNA:RIG-I/MDA5R-HSA-937343 (Reactome)
dsRNA:Ub-RIG-I:TRIM25ArrowR-HSA-918224 (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-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-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)
phosphorylated IRF3/IRF7ArrowR-HSA-918229 (Reactome)
phosphorylated IRF3/IRF7R-HSA-1028821 (Reactome)
procaspase-8/10R-HSA-933523 (Reactome)
procaspase-8/10R-HSA-933526 (Reactome)
unknown ligasemim-catalysisR-HSA-936462 (Reactome)
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