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

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1-629-32, 3436, 39, 405718, 366210-1336, 417, 967, 6854, 556725445826, 65, 665951-5323, 25-286149, 507042, 4316-1836-3845-486920, 2242, 436519-2144629, 14, 1549, 63, 6418, 23, 2429-346029-32, 341651-53564435cytosolmitochondrial outer membranenucleoplasmprocaspase-8/10CBP/p300dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3dsRNA:RIG-I/MDA5:IPS-1:ATG5-ATG12TAX1BP1:TNFAIP3dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKiIRF7-P : IRF7-PdsRNA:RIG-I/MDA5IRF3-P dimer:CBP/p300dsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomainISG15:UBEIL/UbcH8:CEB1IRF3-P:IRF3-PRIG-I/MDA5E3 ubiquitin-protein ligase Itchy homologRIG-I E3 ubiquitin ligasesK-63 polyubiquitinated TRAF3IRF3-P:IRF7-PdsRNA bound to RIG-ICasp-8 linker regionDihydroxyacetone kinase (DAK)IRF3-P:IRF3-PViral dsRNA (-) StrandedRNF125VAF/pIRF7:CBP/p300 bound to type I IFN gene promoterdsRNA:MDA5RIG-IdsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANKp-IRF3 dimer:PIN1CYLDPhospho-NF-kappaB InhibitorRIP1dsRNA:RIG-1/MDA5:IPS-1:TRAF3AGER ligands:AGERphosphorylated IRF3/IRF7IRF3-P:IRF7-PdsRNA:RIG-I/MDA5:IPS-1:PCBP2NLRC5MDA5:DAKSIKE1p10 subunit of Caspase 8dsRNA:RIG-I/MDA5:IPS-1ATPIPS-1:ATG5-ATG12 conjugateATPdsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:MEKK1Casp-10 p23/p17Activated IKK ComplexE2 enzyme (UBE2K, UbcH5a-c)dsRNA:Ub-RIG-I:TRIM25CBP/p300:pIRF7:pIRF7ATPVAF (virus-activated factor)IKK complexubiquitinDeubiquitinase enzyme A (DUBA)p-IRF3:p-IRF3dsRNA:RIG-I/MDA5:NLRC5RNF125:E2 enzyme (UBE2K, UbcH5a-c):K48-polyubiquitinK48-polyubiquitin TRAF3dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7VAF/pIRF7:CBP/p300K63-ubiquitinNFkB ComplexATPADPdsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:procaspase-8/10 dimerdsRNA:RIG-I/MDA5:K48 Ub-IPS-1:PCBP2:AIP4dsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADDIkBs:NFkB ComplexdsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6IPS-1:NLRX1ADPADPNFkB ComplexIRF3/ IRF7K63-polyubiquitinPIN1NLRX1IRF7- P : IRF7-PPromotor region of interferon betaK48-polyubiquitindsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKi:IRF7p18 subunit of Caspase 8IKK complexADPdsRNA:RIG-I/MDA5:TRAF2/TRAF6:IPS-1:RIP-1/FADD:Casp-8/10 prodomain:IKK complexIFN alpha/beta (IFNA/B)TANKPromoter region of type-I IFN genesdsRNA:RIG-I/MDA5:IPS-1:RIP-1/FADD:Procasp-8/10IRF7dsRNA:RIG-I/MDA5:IPS-1:TRAF2/TRAF6:TANK:TBK1/IKKiFADDphospho IRF7IPS-1PCBP2Casp-10 p10TAX1BP1:TNFAIP3:TBK1/IKKiK-63-linked polyubiquitin RIG-ITRAF2 and TRAF6MEKK1ISG15:RIG-I conjugateK48-Ub RIG-I/MDA5IFNB1LGP2TBK1/IKKi:SIKE1IKK related kinases TBK1/IKK epsilonIRF3 bound to IFN-beta promoterATP778


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.

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Bibliography

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History

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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
ADP Metabolite16761 (ChEBI)
AGER ligands:AGER ComplexREACT_24620 (Reactome)
ATP Metabolite15422 (ChEBI)
Activated IKK

Complex

ComplexREACT_7826 (Reactome)
CBP/p300 ProteinREACT_25880 (Reactome)
CBP/p300:pIRF7:

pIRF7

ComplexREACT_25574 (Reactome)
CYLD ProteinQ9NQC7 (UniProt)
Casp-10 p10 ProteinQ92851 (UniProt)
Casp-10 p23/p17 ProteinQ92851 (UniProt)
Casp-8 linker region ProteinQ14790 (UniProt)
Deubiquitinase

enzyme A (DUBA)

ProteinQ96G74 (UniProt)
Dihydroxyacetone

kinase (DAK)

ProteinQ3LXA3 (UniProt)
E2 enzyme (UBE2K,

UbcH5a-c)

ProteinREACT_26340 (Reactome)
E3 ubiquitin-protein

ligase Itchy homolog

ProteinQ96J02 (UniProt)
FADD ProteinQ13158 (UniProt)
IFN alpha/beta

(IFNA/B)

ProteinREACT_26595 (Reactome)
IFNB1 ProteinP01574 (UniProt)
IKK complex ComplexREACT_7693 (Reactome)
IKK related kinases

TBK1/IKK epsilon

ProteinREACT_21591 (Reactome)
IPS-1 ProteinQ7Z434 (UniProt)
IPS-1:ATG5-ATG12

conjugate

ComplexREACT_25931 (Reactome)
IPS-1:NLRX1 ComplexREACT_26115 (Reactome)
IRF3 bound to IFN-

beta promoter

ComplexREACT_25617 (Reactome)
IRF3-P dimer:

CBP/p300

ComplexREACT_26303 (Reactome)
IRF3-P:IRF3-P ComplexREACT_7146 (Reactome)
IRF3-P:IRF3-P ComplexREACT_7444 (Reactome)
IRF3-P:IRF7-P ComplexREACT_26495 (Reactome)
IRF3-P:IRF7-P ComplexREACT_26957 (Reactome)
IRF3/ IRF7 ProteinREACT_21735 (Reactome)
IRF7 ProteinQ92985 (UniProt)
IRF7- P : IRF7-P ComplexREACT_21965 (Reactome)
IRF7-P : IRF7-P ComplexREACT_21640 (Reactome)
ISG15:RIG-I

conjugate

ComplexREACT_26209 (Reactome)
ISG15:UBEIL/UbcH8:

CEB1

ComplexREACT_26934 (Reactome)
IkBs:NFkB Complex ComplexREACT_7272 (Reactome)
K-63

polyubiquitinated TRAF3

ComplexREACT_26596 (Reactome)
K-63-linked

polyubiquitin RIG-I

ComplexREACT_26331 (Reactome)
K48-Ub RIG-I/MDA5 ComplexREACT_25791 (Reactome)
K48-polyubiquitin UnknownREACT_24769 (Reactome)
K48-polyubiquitin

TRAF3

ComplexREACT_26176 (Reactome)
K63-polyubiquitin UnknownREACT_21645 (Reactome)
K63-ubiquitin ProteinREACT_21627 (Reactome)
LGP2 ProteinQ96C10 (UniProt)
MDA5:DAK ComplexREACT_25465 (Reactome)
MEKK1 ProteinQ13233 (UniProt)
NFkB Complex ComplexREACT_7108 (Reactome)
NFkB Complex ComplexREACT_7143 (Reactome)
NLRC5 ProteinQ86WI3 (UniProt)
NLRX1 ProteinQ86UT6 (UniProt)
PCBP2 ProteinQ15366 (UniProt)
PIN1 ProteinQ13526 (UniProt)
Phospho-NF-kappaB

Inhibitor

ProteinREACT_7645 (Reactome)
Promoter region of

type-I IFN genes

UnknownREACT_25653 (Reactome)
Promotor region of

interferon beta

UnknownREACT_25836 (Reactome)
RIG-I ProteinO95786 (UniProt)
RIG-I E3 ubiquitin

ligases

ProteinREACT_25644 (Reactome)
RIG-I/MDA5 ProteinREACT_25428 (Reactome)
RIP1 ProteinQ13546 (UniProt)
RNF125 ProteinQ96EQ8 (UniProt)
RNF125:E2 enzyme

(UBE2K, UbcH5a-c): K48-polyubiquitin

ComplexREACT_25756 (Reactome)
SIKE1 ProteinQ9BRV8 (UniProt)
TANK ProteinQ92844 (UniProt)
TAX1BP1:TNFAIP3 ComplexREACT_26309 (Reactome)
TAX1BP1:TNFAIP3:

TBK1/IKKi

ComplexREACT_25569 (Reactome)
TBK1/IKKi:SIKE1 ComplexREACT_25799 (Reactome)
TRAF2 and TRAF6 ProteinREACT_26063 (Reactome)
VAF (virus-activated

factor)

ComplexREACT_25426 (Reactome)
VAF/pIRF7:

CBP/p300

ComplexREACT_25775 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN gene promoter

ComplexREACT_26244 (Reactome)
Viral dsRNA (-)

Stranded

UnknownREACT_6589 (Reactome)
dsRNA bound to

RIG-I

ComplexREACT_25966 (Reactome)
dsRNA:MDA5 ComplexREACT_26245 (Reactome)
dsRNA:RIG-

1/MDA5:IPS-1: TRAF3

ComplexREACT_25597 (Reactome)
dsRNA:RIG-

1/MDA5:IPS-1:Ub- TRAF3

ComplexREACT_26564 (Reactome)
dsRNA:RIG-

1/MDA5:IPS-1:Ub- TRAF3:TBK1/IKKi

ComplexREACT_26022 (Reactome)
dsRNA:RIG-

1/MDA5:IPS-1:Ub- TRAF3:TBK1/IKKi: IRF3/IRF7

ComplexREACT_25519 (Reactome)
dsRNA:RIG-I/MDA5 ComplexREACT_25628 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1

ComplexREACT_26220 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:ATG5-ATG12

ComplexREACT_26782 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:PCBP2

ComplexREACT_25961 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:RIP-1/FADD

ComplexREACT_26077 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:RIP-1/FADD: Procasp-8/10

ComplexREACT_26650 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:RIP-1/FADD: procaspase-8/10 dimer

ComplexREACT_26858 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6

ComplexREACT_26067 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6: MEKK1

ComplexREACT_26122 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6: TANK

ComplexREACT_27050 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6: TANK:TBK1/IKKi

ComplexREACT_25493 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6: TANK:TBK1/IKKi:IRF7

ComplexREACT_26674 (Reactome)
dsRNA:RIG-I/MDA5:

K48 Ub-IPS-1: PCBP2:AIP4

ComplexREACT_26024 (Reactome)
dsRNA:RIG-I/MDA5:

NLRC5

ComplexREACT_26732 (Reactome)
dsRNA:RIG-I/MDA5:

TRAF2/TRAF6:IPS-1: RIP-1/FADD:Casp- 8/10 prodomain

ComplexREACT_26324 (Reactome)
dsRNA:RIG-I/MDA5:

TRAF2/TRAF6:IPS-1: RIP-1/FADD:Casp- 8/10 prodomain:IKK complex

ComplexREACT_27017 (Reactome)
dsRNA:Ub-RIG-I:

TRIM25

ComplexREACT_26009 (Reactome)
p-IRF3 dimer:PIN1 ComplexREACT_26699 (Reactome)
p-IRF3:p-IRF3 ComplexREACT_26064 (Reactome)
p10 subunit of

Caspase 8

ProteinQ14790 (UniProt)
p18 subunit of

Caspase 8

ProteinQ14790 (UniProt)
phospho IRF7 ProteinQ92985 (UniProt)
phosphorylated

IRF3/IRF7

ProteinREACT_21760 (Reactome)
procaspase-8/10 ProteinREACT_26572 (Reactome)
ubiquitin ProteinREACT_3316 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1904"