RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways (Homo sapiens)

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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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CompareRevisionActionTimeUserComment
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

View all 101...

Name Type Database reference
dsRNA:RIG-I/MDA5:

IPS-1:ATG5-ATG12

ComplexREACT_26782 (Reactome)
Viral dsRNA (-)

Stranded

UnknownREACT_6589 (Reactome)
VAF (virus-activated

factor)

ComplexREACT_25426 (Reactome)
RIG-I ProteinO95786 (UniProt)
NLRC5 ProteinQ86WI3 (UniProt)
dsRNA bound to

RIG-I

ComplexREACT_25966 (Reactome)
K48-Ub RIG-I/MDA5 ComplexREACT_25791 (Reactome)
LGP2 ProteinQ96C10 (UniProt)
K48-polyubiquitin

TRAF3

ComplexREACT_26176 (Reactome)
K63-polyubiquitin UnknownREACT_21645 (Reactome)
IRF3-P:IRF3-P ComplexREACT_7444 (Reactome)
RIG-I E3 ubiquitin

ligases

ProteinREACT_25644 (Reactome)
IkBs:NFkB Complex ComplexREACT_7272 (Reactome)
dsRNA:Ub-RIG-I:

TRIM25

ComplexREACT_26009 (Reactome)
p-IRF3:p-IRF3 ComplexREACT_26064 (Reactome)
MDA5:DAK ComplexREACT_25465 (Reactome)
dsRNA:RIG-

1/MDA5:IPS-1: TRAF3

ComplexREACT_25597 (Reactome)
dsRNA:MDA5 ComplexREACT_26245 (Reactome)
ISG15:RIG-I

conjugate

ComplexREACT_26209 (Reactome)
Dihydroxyacetone

kinase (DAK)

ProteinQ3LXA3 (UniProt)
E3 ubiquitin-protein

ligase Itchy homolog

ProteinQ96J02 (UniProt)
dsRNA:RIG-I/MDA5 ComplexREACT_25628 (Reactome)
CBP/p300 ProteinREACT_25880 (Reactome)
IPS-1 ProteinQ7Z434 (UniProt)
IFN alpha/beta

(IFNA/B)

ProteinREACT_26595 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1

ComplexREACT_26220 (Reactome)
NFkB Complex ComplexREACT_7108 (Reactome)
K-63

polyubiquitinated TRAF3

ComplexREACT_26596 (Reactome)
E2 enzyme (UBE2K,

UbcH5a-c)

ProteinREACT_26340 (Reactome)
dsRNA:RIG-

1/MDA5:IPS-1:Ub- TRAF3

ComplexREACT_26564 (Reactome)
p-IRF3 dimer:PIN1 ComplexREACT_26699 (Reactome)
TBK1/IKKi:SIKE1 ComplexREACT_25799 (Reactome)
ubiquitin ProteinREACT_3316 (Reactome)
dsRNA:RIG-

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

ComplexREACT_26022 (Reactome)
Deubiquitinase

enzyme A (DUBA)

ProteinQ96G74 (UniProt)
SIKE1 ProteinQ9BRV8 (UniProt)
IPS-1:NLRX1 ComplexREACT_26115 (Reactome)
IRF3/ IRF7 ProteinREACT_21735 (Reactome)
IKK related kinases

TBK1/IKK epsilon

ProteinREACT_21591 (Reactome)
dsRNA:RIG-

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

ComplexREACT_25519 (Reactome)
PCBP2 ProteinQ15366 (UniProt)
phosphorylated

IRF3/IRF7

ProteinREACT_21760 (Reactome)
NFkB Complex ComplexREACT_7143 (Reactome)
FADD ProteinQ13158 (UniProt)
Promotor region of

interferon beta

UnknownREACT_25836 (Reactome)
RIP1 ProteinQ13546 (UniProt)
IRF3-P:IRF3-P ComplexREACT_7146 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:RIP-1/FADD

ComplexREACT_26077 (Reactome)
Promoter region of

type-I IFN genes

UnknownREACT_25653 (Reactome)
procaspase-8/10 ProteinREACT_26572 (Reactome)
ATP Metabolite15422 (ChEBI)
dsRNA:RIG-I/MDA5:

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

ComplexREACT_26650 (Reactome)
Phospho-NF-kappaB

Inhibitor

ProteinREACT_7645 (Reactome)
dsRNA:RIG-I/MDA5:

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

ComplexREACT_26858 (Reactome)
RIG-I/MDA5 ProteinREACT_25428 (Reactome)
Casp-10 p23/p17 ProteinQ92851 (UniProt)
RNF125 ProteinQ96EQ8 (UniProt)
p10 subunit of

Caspase 8

ProteinQ14790 (UniProt)
RNF125:E2 enzyme

(UBE2K, UbcH5a-c): K48-polyubiquitin

ComplexREACT_25756 (Reactome)
dsRNA:RIG-I/MDA5:

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

ComplexREACT_26324 (Reactome)
PIN1 ProteinQ13526 (UniProt)
p18 subunit of

Caspase 8

ProteinQ14790 (UniProt)
IPS-1:ATG5-ATG12

conjugate

ComplexREACT_25931 (Reactome)
Casp-8 linker region ProteinQ14790 (UniProt)
K-63-linked

polyubiquitin RIG-I

ComplexREACT_26331 (Reactome)
Casp-10 p10 ProteinQ92851 (UniProt)
CYLD ProteinQ9NQC7 (UniProt)
IKK complex ComplexREACT_7693 (Reactome)
K63-ubiquitin ProteinREACT_21627 (Reactome)
dsRNA:RIG-I/MDA5:

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

ComplexREACT_27017 (Reactome)
K48-polyubiquitin UnknownREACT_24769 (Reactome)
TRAF2 and TRAF6 ProteinREACT_26063 (Reactome)
NLRX1 ProteinQ86UT6 (UniProt)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6

ComplexREACT_26067 (Reactome)
ISG15:UBEIL/UbcH8:

CEB1

ComplexREACT_26934 (Reactome)
TANK ProteinQ92844 (UniProt)
TAX1BP1:TNFAIP3 ComplexREACT_26309 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6: TANK

ComplexREACT_27050 (Reactome)
TAX1BP1:TNFAIP3:

TBK1/IKKi

ComplexREACT_25569 (Reactome)
dsRNA:RIG-I/MDA5:

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

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

NLRC5

ComplexREACT_26732 (Reactome)
IRF7 ProteinQ92985 (UniProt)
dsRNA:RIG-I/MDA5:

IPS-1:PCBP2

ComplexREACT_25961 (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)
phospho IRF7 ProteinQ92985 (UniProt)
AGER ligands:AGER ComplexREACT_24620 (Reactome)
ADP Metabolite16761 (ChEBI)
IRF3-P dimer:

CBP/p300

ComplexREACT_26303 (Reactome)
IRF7- P : IRF7-P ComplexREACT_21965 (Reactome)
IRF3 bound to IFN-

beta promoter

ComplexREACT_25617 (Reactome)
IRF7-P : IRF7-P ComplexREACT_21640 (Reactome)
IRF3-P:IRF7-P ComplexREACT_26957 (Reactome)
CBP/p300:pIRF7:

pIRF7

ComplexREACT_25574 (Reactome)
IRF3-P:IRF7-P ComplexREACT_26495 (Reactome)
MEKK1 ProteinQ13233 (UniProt)
VAF/pIRF7:

CBP/p300

ComplexREACT_25775 (Reactome)
dsRNA:RIG-I/MDA5:

IPS-1:TRAF2/TRAF6: MEKK1

ComplexREACT_26122 (Reactome)
VAF/pIRF7:CBP/p300

bound to type I IFN gene promoter

ComplexREACT_26244 (Reactome)
Activated IKK

Complex

ComplexREACT_7826 (Reactome)
IFNB1 ProteinP01574 (UniProt)
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