Entity
NF-kappaB
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m5
10
infinite
0
TRANSPATH | MO000000058 |
--
IKK-i
--
MO000016608
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1599
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000016608 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m1
0
infinite
0
--
PolyI:C:IFIH1
--
e10
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m11
0
infinite
0
--
DDX58:dsRNA:Efp
--
e11
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m12
0
infinite
0
--
DDX58 {ub}:dsRNA:Efp
--
e12
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m13
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS
--
e13
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m14
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3
--
e14
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m15
0
infinite
0
--
TANK:TRAF2:TBK1:IKK-i
--
e15
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m16
0
infinite
0
--
NAP1
--
e16
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m17
0
infinite
0
--
NAP1:IKK-i:TBK1
--
e17
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m18
0
infinite
0
--
TANK:TRAF2
--
e18
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m19
0
infinite
0
--
TANK{p}:TRAF2:TBK1:IKK-i
--
e19
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m20
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
TANK{p}:TBK1:IKK-i
--
e20
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m21
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6
--
e21
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m22
0
infinite
0
--
IKK:TANK{p}:TBK1:Ikk-i
--
e22
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m23
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3:IKK:TANK{p}:TBK1:IKK-i
--
e23
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m24
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3:IKK:TANK{p}:TBK1:IKK-i{active}
--
e24
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m25
0
infinite
0
--
IRF-3{p} dimer
--
e27
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m28
0
infinite
0
--
IRF-3{p} dimer
--
e28
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m29
0
infinite
0
--
IRF-3{p}dimer:CBP
--
e29
cso30:c:Complex
cso30:i:CC_NuclearLumen
--
csml-variable:Double
m30
0
infinite
0
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6:IKK:TANK{p}:TBK1:IKK-i
--
e30
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m31
0
infinite
0
--
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6:IKK{active}:TANK{p}:TBK1:IKK-i
--
e31
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m32
0
infinite
0
--
NF-KappaB:IkappaB-alpha
--
e32
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m33
0
infinite
0
--
IKappaB-alpha{p}
--
e33
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m34
0
infinite
0
--
proinflammatory genes
--
e34
cso30:c:mRNA
cso30:i:CC_NuclearLumen
--
--
csml-variable:Double
m35
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
DDX58:dsRNA
--
e5
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m6
0
infinite
0
--
--
e50
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelopeLumen
--
--
--
csml-variable:Double
m50
0
infinite
0
--
--
e51
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearPore
--
--
--
csml-variable:Double
m51
0
infinite
0
--
--
e52
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearInnerMembrane
--
--
--
csml-variable:Double
m52
0
infinite
0
--
--
e53
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearLumen
--
--
--
csml-variable:Double
m53
0
infinite
0
--
--
e54
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearOuterMembrane
--
--
--
csml-variable:Double
m54
0
infinite
0
--
--
e55
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleus
--
--
--
csml-variable:Double
m55
0
infinite
0
--
--
e57
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearBody
--
--
--
csml-variable:Double
m57
0
infinite
0
--
--
e58
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleolus
--
--
--
csml-variable:Double
m58
0
infinite
0
--
--
e59
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
--
--
--
csml-variable:Double
m59
0
infinite
0
--
PolyI:C
--
e6
cso30:c:mRNA
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m10
0
infinite
0
--
--
e60
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
--
--
--
csml-variable:Double
m60
0
infinite
0
--
--
e61
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearChromosome
--
--
--
csml-variable:Double
m61
0
infinite
0
--
--
e62
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
--
--
--
csml-variable:Double
m62
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
m119368*m41844*0.1
nodelay
--
0
PMID: 17706453 Furthermore, MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1
m16*0.1
nodelay
--
0
PMID: 17706543,10759890 Overexpression of IKKvar epsilon or TBK-1 induces phosphorylation of I-TRAF/TANK, which results in its dissociation from TRAF2 and subsequent activation of NF-¦ÊB transcription through the classical IKK pathway
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c36 : 1
stoichiometry:c37 : 1
m20*0.1
nodelay
--
0
PMID: 17706543,10759890 Overexpression of IKKvar epsilon or TBK-1 induces phosphorylation of I-TRAF/TANK, which results in its dissociation from TRAF2 and subsequent activation of NF-¦ÊB transcription through the classical IKK pathway
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c43 : 1
stoichiometry:c39 : 1
m14*m183*0.1
nodelay
--
0
PMID: 17706453 TRAF3 and/or TRAF6 are also recruited to MAVS through a direct interaction with a TRAF-interaction motif within MAVS.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c41 : 1
stoichiometry:c42 : 1
m207*m21*0.1
nodelay
--
0
PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKKvar epsilon PMID: 17706453,12133833,17468758 Physical association between TANK and NEMO suggest that the canonical IKK complex and the IKK-related kinases may exist as a physically associated signaling complex responsible for phosphorylation of additional transcription factors PMID: 17706453 NEMO acts downstream of MAVS and RIG-I, and physically interacts with the TANK adapter to mediate recruitment of TBK1 and IKKvar epsilon to the RIG-I?MAVS complex.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c45 : 1
stoichiometry:c46 : 1
m15*m23*0.1
nodelay
--
0
PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c48 : 1
m24*0.1
nodelay
--
0
PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon
p17
p17
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c50 : 1
stoichiometry:c51 : 1
m25*m977*0.1
nodelay
--
0
PMID: 17706453,15367631,14679297,16914100 Both TBK-1 and IKKvar epsilon directly phosphorylate IRF-3 and IRF-7 at key resides within their C-terminal signal-responsive domain in vitro and both kinases target identical serine residues PMID: 17706543 Activated TBK1 and IKKvar epsilon phosphorylate IRF3 and IRF7, which provoke IFN expression and development of an antiviral state.
p17
p18
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c53 : 1
stoichiometry:c54 : 1
m25*m980*0.1
nodelay
--
0
PMID: 17706453,15367631,14679297,16914100 Both TBK-1 and IKKvar epsilon directly phosphorylate IRF-3 and IRF-7 at key resides within their C-terminal signal-responsive domain in vitro and both kinases target identical serine residues PMID: 17706543 Activated TBK1 and IKKvar epsilon phosphorylate IRF3 and IRF7, which provoke IFN expression and development of an antiviral state.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c56 : 1
m26*0.1
nodelay
--
0
PMID: 17706453,10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1
m10*m76904*0.1
nodelay
--
0
PMID: 17706453 Furthermore, MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c58 : 1
m28*0.1
nodelay
--
0
PMID: 17706453,10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300
p21
p21
cso30:i:ME_Binding
cso30:i:CC_NuclearChromosome
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c60 : 1
stoichiometry:c61 : 1
m29*m72733*0.1
nodelay
--
0
PMID: 17706453,10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c63 : 1
m30*0.1
nodelay
--
0
PMID: 17706453,17395583 Inactive IRF-3 constitutively shuttles into and out of the nucleus, whereas phosphorylation-dependent association with CBP/p300 retains IRF-3 in the nucleus and induces transcription of IFN-¦Â and other genes
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c65 : 1
stoichiometry:c66 : 1
m22*m23*0.1
nodelay
--
0
PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c68 : 1
m31*0.1
nodelay
--
0
p25
p25
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c71 : 1
stoichiometry:c72 : 1
m33*m32*0.1
nodelay
--
0
PMID: 17706453,17047224 Inducible activation of canonical NF-¦ÊB signaling requires phosphorylation of the I¦ÊB inhibitor by the 700?900 kDa multi-protein canonical IKK complex composed of two catalytic kinase subunits, IKKgreek small letter alpha and IKK¦Â, and a non-enzymatic regulatory subunit NF-¦ÊB Essential Modulator (NEMO) or IKK¦Ã PMID: 17706543 MAVS-TRAF complexes also activate the canonical NEMO-IKKalpha-IKK¦Â complex which phosphorylates the inhibitory subunit I¦ÊBalpha, resulting in the release of NF-¦ÊB and activation of proinflammatory gene transcription.
p26
p26
cso30:i:ME_GeneExpression
cso30:i:CC_NuclearLumen
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c74 : 1
m5*0.1
nodelay
--
0
PMID: 17706543 MAVS-TRAF complexes also activate the canonical NEMO-IKKalpha-IKK¦Â complex which phosphorylates the inhibitory subunit I¦ÊBalpha, resulting in the release of NF-¦ÊB and activation of proinflammatory gene transcription.
p27
p27
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c76 : 1
stoichiometry:c77 : 1
m1599*m1357*0.1
nodelay
--
0
PMID: 17706453 The structural and functional consequences of this phosphorylation remain to be determined, although it is suggested that IKKvar epsilon-dependent phosphorylation of STAT1 appears to guide the transcriptional machinery to a subset of ISGs required for the direct antiviral response, whereas the IKK-independent genes may function in regulating the IFN signaling required for integration of innate and adaptive immune systems.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1
m6*m63891*0.1
nodelay
--
0
PMID:17706453 TRIM25 alpha contains a RING-finger domain, a B box/coiled-coil domain and a SPRY domain and induces robust ubiquitination of the CARD domains of RIG-I. PMID: 17706453 The carboxy-terminal SPRY domain of TRIM25 alpha interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signaling activity.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
m12*0.1
nodelay
--
0
PMID: 17706453 The carboxy-terminal SPRY domain of TRIM25 alpha interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signaling activity.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1
m68199*m13*0.1
nodelay
--
0
PMID: 17706453,16785313,16125763,16153868,16177806 The adaptor molecule providing a link between RIG-I sensing of incoming viral RNA and downstream activation events was independently elucidated as mitochondrial antiviral signaling adapter (MAVS), also known as (IPS-1/VISA/Cardif) PMID: 17706453,16177806 MAVS interacts with RIG-I and recruits IKKvar epsilon through its C-terminal region; knockdown by siRNA inhibited RIG-I-dependent antiviral responses
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1
m14*m1872*0.1
nodelay
--
0
PMID: 17706453 TRAF3 and/or TRAF6 are also recruited to MAVS through a direct interaction with a TRAF-interaction motif within MAVS.
p7
p7
cso30:i:ME_Binding
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c21 : 1
m181*m182*m1593*0.1
nodelay
--
0
PMID: 17706453,17047224 Inducible activation of canonical NF-¦ÊB signaling requires phosphorylation of the I¦ÊB inhibitor by the 700?900 kDa multi-protein canonical IKK complex composed of two catalytic kinase subunits, IKKgreek small letter alpha and IKK¦Â, and a non-enzymatic regulatory subunit NF-¦ÊB Essential Modulator (NEMO) or IKK¦Ã
p8
p8
cso30:i:ME_Binding
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c32 : 1
stoichiometry:c25 : 1
m1599*m3902*m19*0.1
nodelay
--
0
PMID: 17706453,10759890 Both TBK-1 and IKK epsilon interact with the TNF-receptor-associated factor (TRAF)-interacting protein/TRAF family member-associated NF-¦ÊB activator (I-TRAF/TANK) protein, a modulator of TNF alpha-induced NF-¦ÊB activation
p9
p9
cso30:i:ME_Binding
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1
m1599*m17*m3902*0.1
nodelay
--
0
PMID: 17706543,14560022 Associated Protein 1 (NAP1), a homologue of I-TRAF/TANK, has also been shown to directly interact with TBK-1 and IKK epsilon
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--