Entity
NF-kappaB{active}
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m48
10
infinite
0
TRANSPATH | MO000000058 |
--
IKK-alpha
--
MO000000210
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m181
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000000210 |
--
TRAF6
--
MO000000212
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m183
10
infinite
0
InterPro | IPR001841 |
TRANSPATH | MO000000212 |
--
MyD88
--
MO000016573
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1572
10
infinite
0
InterPro | IPR000157 |
TRANSPATH | MO000016573 |
--
PKCepsilon
--
MO000016645
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m1629
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000016645 |
--
IRAK-4
--
MO000039077
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m17258
10
infinite
0
TRANSPATH | MO000039077 |
--
IRF-3{p}
--
MO000041456
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m19324
10
infinite
0
TRANSPATH | MO000041456 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m1
0
infinite
0
--
--
e10
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytosol
--
--
--
csml-variable:Double
m10
0
infinite
0
--
IFN:IFNAR1:IFNAR2
--
e11
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m11
0
infinite
0
--
STAT1:STAT2:IRF9
--
e12
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m12
0
infinite
0
--
STAT1:STAT2:IRF9{active}
--
e13
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m13
0
infinite
0
--
STAT1:STAT2:IRF9{active}
--
e14
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m14
0
infinite
0
--
IFN inducible genes
--
e15
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m15
0
infinite
0
--
TLR4:MD2
--
e16
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m16
0
infinite
0
--
LPS:TLR4:MD2
--
e17
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m17
0
infinite
0
--
fusion protein
--
e18
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m18
0
infinite
0
--
fusion protein:TLR4:MD2
--
e19
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
envelope protein
--
e20
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m20
0
infinite
0
--
envelope protein:TLR4:MD2
--
e21
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m21
0
infinite
0
--
LPS:TLR4:MD2:TIRAP
--
e22
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m22
0
infinite
0
--
LPS:TLR4:MD2:TIRAP:MYD88
--
e23
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m23
0
infinite
0
--
LPS:TLR4:MD2:TIRAP:MYD88:IRAK4
--
e24
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m24
0
infinite
0
--
IRAK1
--
e25
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m25
0
infinite
0
--
LPS:TLR4:MD2:MyD88:IRAK4:IRAK1
--
e26
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m26
0
infinite
0
--
LPS:TLR4:MD2:MyD88:IRAK4:IRAK1:TRAF6
--
e27
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m27
0
infinite
0
--
LPS:TLR4:MD2:MyD88:IRAK1:IRAK4:TRAF6{ub}
--
e28
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m28
0
infinite
0
--
IRAK1:TRAF6{ub}
--
e29
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m29
0
infinite
0
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
TAK1:TAB1:TAB2
--
e30
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m30
0
infinite
0
--
IRAK1:TRAF6{ub}:TAK1:TAB1:TAB2
--
e31
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m31
0
infinite
0
--
IRAK1:TRAF6{ub}:TAK1{active}:TAB1:TAB2
--
e32
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m32
0
infinite
0
--
NF-kappaB:IkappaB-alpha
--
e34
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m34
0
infinite
0
--
NF-kappaB:IkappaB-alpha{p}
--
e35
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m35
0
infinite
0
--
NF-kappaB{active}:IkappaB-alpha{p}
--
e36
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m36
10
infinite
0
TRANSPATH | MO000000058 |
--
IkappaB-alpha{p}
--
e37
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m37
0
infinite
0
--
cytokines
--
e38
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m38
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
LPS:TLR4:MD2:TRAM
--
e41
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m41
0
infinite
0
--
LPS:TLR4:MD2:TRAM{p}:TRIF
--
e42
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m42
0
infinite
0
--
TLR3:CD14:c-Src:dsRNA
--
e43
cso30:c:Complex
cso30:i:CC_EndosomeLumen
--
csml-variable:Double
m43
0
infinite
0
--
LPS:TLR4:MD2:TRAM{p}
--
e44
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m44
0
infinite
0
--
LPS:TLR4:MD2:TRAM{p}:TRIF:RIP1
--
e45
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m46
0
infinite
0
--
LPS:TLR4:MD2:TRAM{p}:TRIF:TRAF6
--
e46
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m47
0
infinite
0
--
csml-variable:Double
m49
0
infinite
0
--
TBK1:IKK-i:NAP1:TRAF3
--
e48
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m63
0
infinite
0
--
e49
--
e49
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m64
0
infinite
0
--
IFNAR1:IFNAR2
--
e5
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m5
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
--
--
e56
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
--
--
--
csml-variable:Double
m56
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
--
IFN
--
e6
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m6
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
--
csml-variable:Double
m66
0
infinite
0
--
csml-variable:Double
m67
0
infinite
0
--
--
e66
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeMembrane
--
--
--
csml-variable:Double
m68
0
infinite
0
--
--
e67
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeLumen
--
--
--
csml-variable:Double
m69
0
infinite
0
--
--
e68
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Endosome
--
--
--
csml-variable:Double
m70
0
infinite
0
--
TLR3:CD14:c-Src
--
e69
cso30:c:Complex
cso30:i:CC_EndosomeLumen
--
csml-variable:Double
m71
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
TLR3:CD14:c-Src:dsRNA:TRIF
--
e70
cso30:c:Complex
cso30:i:CC_EndosomeLumen
--
csml-variable:Double
m72
0
infinite
0
--
TLR3:CD14:c-Src:dsRNA:TRIF:RIP1
--
e71
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m73
0
infinite
0
--
TBK1:IKK-i:NAP1:TRAF3:TLR3:CD14:c-Src:dsRNA:TRIF
--
e72
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m74
0
infinite
0
--
IFN-beta
--
e73
cso30:c:mRNA
cso30:i:CC_Cytosol
--
csml-variable:Double
m75
0
infinite
0
--
TLR3:CD14:c-Src:dsRNA:TRIF:TRAF1:TRAF6
--
e74
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m76
0
infinite
0
--
TLR3:CD14:c-Src:dsRNA:TRIF:RIP1:TRAF6
--
e75
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m78
0
infinite
0
--
CpG DNA:TLR9
--
e76
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m79
0
infinite
0
--
IFN-alpha
--
e77
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m80
0
infinite
0
--
IFN-alpha
--
e78
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m81
0
infinite
0
--
ssRNA
--
e79
cso30:c:Rna
cso30:i:CC_Cytosol
--
csml-variable:Double
m82
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
ssRNA:TLR7
--
e80
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m83
0
infinite
0
--
ssRNA:TLR8
--
e81
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m84
0
infinite
0
--
CpG DNA:TLR9:MYD88
--
e82
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m85
0
infinite
0
--
ssRNA:TLR7:MYD88
--
e83
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m86
0
infinite
0
--
csml-variable:Double
m87
0
infinite
0
--
CPG DNA:TLR9:MYD88:IRAK1:IRAK4:TRAF6:IRF7
--
e85
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m88
0
infinite
0
--
CPG DNA:TLR9:MYD88:IRAK1:IRAK4:TRAF6:IRF7{p}
--
e86
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m89
0
infinite
0
--
CPG DNA:TLR9:MYD88:IRAK1:IRAK4:TRAF6
--
e87
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m90
0
infinite
0
--
CpG DNA:TLR9:MYD88:IRF1
--
e88
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m91
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
IL-12 p35
--
e90
cso30:c:mRNA
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m93
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
m6*m5*0.1
nodelay
--
0
PMID: 17395581 Type I IFNs are the key cytokines that mediate antiviral responses. Secreted IFNs bind and activate the type I IFN receptor (a heterodimer of IFNAR1 and IFNAR2) in an autocrine and paracrine manner.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c25 : 1
stoichiometry:c26 : 1
m22*m1572*0.1
nodelay
--
0
PMID: 17395581 A TIR domain-containing adapter, MyD88, associates with the cytoplasmic TIR domain of TLRs and recruits IRAKs to the receptor upon ligand binding.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1
m17258*m23*0.1
nodelay
--
0
PMID: 17395581 The association of TLRs with MyD88, which is utilized by all TLRs except TLR3, recruits IL-1R-associated kinase (IRAK)-1 and IRAK-4 and tumor necrosis factor receptor-associated factor 6 (TRAF6).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c31 : 1
stoichiometry:c32 : 1
m24*m25*0.1
nodelay
--
0
PMID: 17395581 The association of TLRs with MyD88, which is utilized by all TLRs except TLR3, recruits IL-1R-associated kinase (IRAK)-1 and IRAK-4 and tumor necrosis factor receptor-associated factor 6 (TRAF6).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1
stoichiometry:c35 : 1
m26*m183*0.1
nodelay
--
0
PMID: 17395581 The association of TLRs with MyD88, which is utilized by all TLRs except TLR3, recruits IL-1R-associated kinase (IRAK)-1 and IRAK-4 and tumor necrosis factor receptor-associated factor 6 (TRAF6).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c37 : 1
m27*0.1
nodelay
--
0
PMID: 17395581 IRAKs then activate TRAF6, leading to the activation of TAK1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c40 : 1
m28*0.1
nodelay
--
0
PMID: 17395581 IRAK-1 and TRAF6 then dissociate from this receptor complex and associate with another complex composed of transforming growth factor-beta-activated kinase (TAK1) and TAK1-binding proteins 1 (Tab1) and 2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c43 : 1
m29*m30*0.1
nodelay
--
0
PMID: 17395581 IRAK-1 and TRAF6 then dissociate from this receptor complex and associate with another complex composed of transforming growth factor-beta-activated kinase (TAK1) and TAK1-binding proteins 1 (Tab1) and 2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c45 : 1
m31*0.1
nodelay
--
0
PMID: 17395581 This complex formation leads to the activation of TAK1.
p18
p18
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c47 : 1
m207*m32*0.1
nodelay
--
0
PMID: 17395581 TAK1 activates the IKK complex consisting of IKK{alpha}, IKKbeta, and NEMO/IKK{gamma}.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c51 : 1
stoichiometry:c50 : 1
m34*m33*0.1
nodelay
--
0
PMID: 17395581 The IKK complex phosphorylates I{kappa}B, resulting in nuclear translocation of NF-{kappa}B, which induces expression of inflammatory cytokines.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c8 : 1
stoichiometry:c5 : 1
m12*m11*0.1
nodelay
--
0
PMID: 17395581, 16497588 This binding leads to the activation of IFN-stimulated gene factor 3 (ISGF3; a heterotrimer of signal transducer and activator of transcription 1 (STAT1), STAT2, and IFN regulatory factor 9 (IRF9)), which translocates to the nucleus and induces the transcription of hundreds of effector molecules, called IFN-inducible genes.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c54 : 1
stoichiometry:c53 : 1
m36*0.1
nodelay
--
0
PMID: 17395581 The IKK complex phosphorylates I{kappa}B, resulting in nuclear translocation of NF-{kappa}B, which induces expression of inflammatory cytokines.
p21
p21
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c55 : 1
m48*0.1
nodelay
--
0
PMID: 17395581 The IKK complex phosphorylates I{kappa}B, resulting in nuclear translocation of NF-{kappa}B, which induces expression of inflammatory cytokines.
p22
p22
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c59 : 1
stoichiometry:c58 : 1
m219*m33*0.1
nodelay
--
0
PMID: 17395581 This complex formation leads to the activation of TAK1, which in turn activates the transcription factors nuclear factor-{kappa}B (NF-{kappa}B) and activator protein 1 (AP-1) through the canonical I{kappa}B kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
p23
p23
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c61 : 1
stoichiometry:c62 : 1
m32*m1812*0.1
nodelay
--
0
PMID: 17395581 This complex formation leads to the activation of TAK1, which in turn activates the transcription factors nuclear factor-{kappa}B (NF-{kappa}B) and activator protein 1 (AP-1) through the canonical I{kappa}B kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c64 : 1
stoichiometry:c65 : 1
m19005*m17*0.1
nodelay
--
0
PMID: 17395581 TLR4 also requires another adapter, TRAM, for IRF3 activation. PMID: 17395581 The N terminus of TRAM has a myristoylation site, mutation of which alters its normal membrane localization and abolishes TLR4 signaling, suggesting that TRAM acts as a bridging adapter between TLR4 and TRIF
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c70 : 1
stoichiometry:c68 : 1
m18998*m44*0.1
nodelay
--
0
PMID: 17395581 TLR4 also requires another adapter, TRAM, for IRF3 activation.A TIR domain-containing adapter, TRIF, is responsible for TLR3- and TLR4-mediated IRF3 activation
p26
p26
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c71 : 1
stoichiometry:c69 : 1
m41*m1629*0.1
nodelay
--
0
PMID: 17395581, 16757566 It has also been reported that phosphorylation of TRAM by PKC{epsilon} is crucial for the activation of IRF3 and the induction of IFN-inducible genes.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c73 : 1
stoichiometry:c74 : 1
m42*m45*0.1
nodelay
--
0
PMID: 17395581, 15064760 Receptor-interacting protein-1 (RIP1) binds the C terminus of TRIF via a Rip homotypic interaction motif and mediates the TLR3-mediated NF-{kappa}B but not IRF3 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c75 : 1
stoichiometry:c77 : 1
m183*m46*0.1
nodelay
--
0
PMID: 17395581 TRAF6 binds the N terminus of TRIF and cooperatively activates NF-kappaB.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
stoichiometry:c80 : 1
m63*m42*0.1
nodelay
--
0
PMID: 17395581 TRIF interacts with TBK1, IKK{iota}, RIP1, and TRAF6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c7 : 1
m13*0.1
nodelay
--
0
PMID: 17395581, 16497588 This binding leads to the activation of IFN-stimulated gene factor 3 (ISGF3; a heterotrimer of signal transducer and activator of transcription 1 (STAT1), STAT2, and IFN regulatory factor 9 (IRF9)), which translocates to the nucleus and induces the transcription of hundreds of effector molecules, called IFN-inducible genes.
p30
p30
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c83 : 1
stoichiometry:c82 : 1
m977*m64*0.1
nodelay
--
0
PMID: 17395581 IRF3 is activated by TBK1 and IKK{iota}, which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c85 : 1
m19324*0.1
nodelay
--
0
PMID: 17395581 IRF3 is activated by TBK1 and IKK{iota}, which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c87 : 1
stoichiometry:c88 : 1
m65*m66*0.1
nodelay
--
0
PMID: 17395581 IRF3 is activated by TBK1 and IKK{iota}, which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
p33
p33
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c90 : 1
stoichiometry:c91 : 1
stoichiometry:c92 : 1
m3965*m77*m2828*0.1
nodelay
--
0
PMID: 17395581, 16473828, 16858407 TLR3 interacts with CD14 and c-Src for ligand uptake and signal transduction.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c95 : 1
m119368*m71*0.1
nodelay
--
0
PMID: 17395581, 16497588 TLR3 recognizes a synthetic analog of viral dsRNA, polyinosinic acid-cytidylic acid (poly(I?C)), and viral dsRNAs derived from dsRNA viruses such as reovirus or ssRNA viruses such as West Nile virus, respiratory syncytial virus, and encephalomyocarditis virus.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c97 : 1
stoichiometry:c98 : 1
m43*m18998*0.1
nodelay
--
0
PMID: 17395581, 12872135, 12855817 TLR3 signaling activates the transcription factors interferon regulatory factor 3 (IRF3) and NF-{kappa}B via the adapter molecule TRIF.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c100 : 1
stoichiometry:c101 : 1
m72*m45*0.1
nodelay
--
0
PMID: 17395581, 15064760 Receptor-interacting protein-1 (RIP1) binds the C terminus of TRIF via a Rip homotypic interaction motif and mediates the TLR3-mediated NF-{kappa}B but not IRF3 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c104 : 1
m63*m72*0.1
nodelay
--
0
PMID: 17395581, 16306936, 16306937, 15611223, 12702806 TRIF interacts with noncanonical IKKs TBK1 (also called NAK or T2K) and IKK{iota} (also called IKK{epsilon}) through TRAF3 and NAK-associated protein 1 (NAP1), which mediate phosphorylation of IRF3.
p38
p38
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c107 : 1
stoichiometry:c114 : 1
stoichiometry:c106 : 1
m977*m74*0.1
nodelay
--
0
PMID: 17395581, 16306936, 16306937, 15611223, 12702806 TRIF interacts with noncanonical IKKs TBK1 (also called NAK or T2K) and IKK{iota} (also called IKK{epsilon}) through TRAF3 and NAK-associated protein 1 (NAP1), which mediate phosphorylation of IRF3. PMID: 17395581, 16699525 IRF3 activation is negatively regulated by the peptidyl-prolyl isomerase Pin1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c109 : 1
m67*0.1
nodelay
--
0
PMID: 17395581 Activated IRF3 translocates into the nucleus and induces expression of IFN-beta.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c10 : 1
m14*0.1
nodelay
--
0
PMID: 17395581, 16497588 This binding leads to the activation of IFN-stimulated gene factor 3 (ISGF3; a heterotrimer of signal transducer and activator of transcription 1 (STAT1), STAT2, and IFN regulatory factor 9 (IRF9)), which translocates to the nucleus and induces the transcription of hundreds of effector molecules, called IFN-inducible genes.
p40
p40
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c111 : 1
stoichiometry:c112 : 1
stoichiometry:c110 : 1
stoichiometry:c113 : 1
m1871*m1873*m72*0.1
nodelay
--
0
PMID: 17395581, 16323247, 16052631 TRAF1 and TRAF4 interact with TRIF and negatively regulate TRIF-mediated signaling pathways.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c115 : 1
stoichiometry:c116 : 1
stoichiometry:c117 : 1
m73*m183*0.1
nodelay
--
0
PMID: 17395581, 14530355 TRAF6 binds the N terminus of TRIF and cooperatively activates NF-{kappa}B.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c118 : 1
stoichiometry:c120 : 1
stoichiometry:c119 : 1
m35*m78*0.1
nodelay
--
0
PMID: 17395581, 14530355 TRAF6 binds the N terminus of TRIF and cooperatively activates NF-{kappa}B.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c121 : 1
stoichiometry:c122 : 1
stoichiometry:c123 : 1
m19828*m49*0.1
nodelay
--
0
PMID: 17395581, 11130078 TLR9 mediates the recognition of CpG DNA.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c125 : 1
stoichiometry:c124 : 1
m79*0.1
nodelay
--
0
PMID: 17395581, 12900525 Mouse pDCs produce IFN-{alpha} by recognizing the CpG-containing DNA of herpes simplex virus type 2 (HSV-2) via TLR9.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c127 : 1
stoichiometry:c128 : 1
stoichiometry:c126 : 1
m80*m79*0.1
nodelay
--
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c129 : 1
stoichiometry:c130 : 1
stoichiometry:c131 : 1
m19940*m82*0.1
nodelay
--
0
PMID: 17395581, 14976261, 14976262 TLR7 and human TLR8 have been shown to recognize guanosine- or uridine-rich ssRNA from viruses such as human immunodeficiency virus, vesicular stomatitis virus, and influenza virus
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c133 : 1
stoichiometry:c134 : 1
m19823*m82*0.1
nodelay
--
0
PMID: 17395581, 14976261, 14976262 TLR7 and human TLR8 have been shown to recognize guanosine- or uridine-rich ssRNA from viruses such as human immunodeficiency virus, vesicular stomatitis virus, and influenza virus.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c135 : 1
stoichiometry:c136 : 1
stoichiometry:c137 : 1
m1572*m79*0.1
nodelay
--
0
PMID: 17395581, 12626561 The induction of type I IFNs by TLR7 and TLR9 depends entirely on MyD88 in pDCs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c138 : 1
stoichiometry:c139 : 1
stoichiometry:c140 : 1
m83*m1572*0.1
nodelay
--
0
PMID: 17395581, 12626561 The induction of type I IFNs by TLR7 and TLR9 depends entirely on MyD88 in pDCs.
PMID: 17395581 These effector molecules directly influence protein synthesis, cell growth, and survival, in the process of establishing an antiviral state.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c141 : 1
m86*0.1
nodelay
--
0
PMID: 17395581, 12626561 The induction of type I IFNs by TLR7 and TLR9 depends entirely on MyD88 in pDCs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c143 : 1
m85*0.1
nodelay
--
0
PMID: 17395581, 12626561 The induction of type I IFNs by TLR7 and TLR9 depends entirely on MyD88 in pDCs.
p52
p52
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c146 : 1
stoichiometry:c147 : 1
stoichiometry:c148 : 1
stoichiometry:c149 : 1
stoichiometry:c150 : 1
m85*m183*m25*m17258*m980*0.1
nodelay
--
0
PMID: 17395581 IRF7 is activated through forming a signaling complex with MyD88, IRAKs, and TRAF6 in the cytoplasm. PMID: 17395581, 15361868, 15492225 IRF7 forms a signaling complex with MyD88 and TRAF6 in the cytoplasm.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c151 : 1
stoichiometry:c152 : 1
m88*0.1
nodelay
--
0
PMID: 17395581, 15361868, 15492225, 17056502 After ligand stimulation, IRF7 is activated by its phosphorylation in TBK1/IKK{iota}-independent manner and translocates into the nucleus to induce the expression of type I IFNs. PMID: 17395581, 15767370 IRAK-1, but not IRAK-4, can directly bind and phosphorylate IRF7; thus, IRAK-1 specifically mediates IFN-{alpha} induction downstream of MyD88 and IRAK-4
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c153 : 1
stoichiometry:c154 : 1
stoichiometry:c155 : 1
m89*0.1
nodelay
--
0
PMID: 17395581, 15361868, 15492225, 17056502 After ligand stimulation, IRF7 is activated by its phosphorylation in TBK1/IKK{iota}-independent manner and translocates into the nucleus to induce the expression of type I IFNs.
p55
p55
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c158 : 1
stoichiometry:c157 : 1
m88*m181*0.1
nodelay
--
0
PMID: 17395581, 16612387 In addition to IRAKs, IKK{alpha} has been shown to be essential for the phosphorylation of IRF7, suggesting that the IRAK-4/IRAK-1/IKK{alpha} kinase cascade might lead to the full activation of IRF7.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c159 : 1
stoichiometry:c160 : 1
stoichiometry:c161 : 1
m85*m970*0.1
nodelay
--
0
PMID: 17395581, 17018642 After ligand stimulation, IRF1 interacts with MyD88, is activated by an unknown mechanism, and translocates into the nucleus to induce the expression of IFN-beta, inducible nitric-oxide synthase, and IL-12 p35.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c162 : 1
stoichiometry:c163 : 1
stoichiometry:c164 : 1
m91*0.1
nodelay
--
0
PMID: 17395581, 17018642 After ligand stimulation, IRF1 interacts with MyD88, is activated by an unknown mechanism, and translocates into the nucleus to induce the expression of IFN-beta, inducible nitric-oxide synthase, and IL-12 p35.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c166 : 1
stoichiometry:c165 : 1
m92*0.1
nodelay
--
0
MID: 17395581, 17018642 After ligand stimulation, IRF1 interacts with MyD88, is activated by an unknown mechanism, and translocates into the nucleus to induce the expression of IFN-beta, inducible nitric-oxide synthase, and IL-12 p35.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c168 : 1
stoichiometry:c167 : 1
m92*0.1
nodelay
--
0
MID: 17395581, 17018642 After ligand stimulation, IRF1 interacts with MyD88, is activated by an unknown mechanism, and translocates into the nucleus to induce the expression of IFN-beta, inducible nitric-oxide synthase, and IL-12 p35.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1
m16*m155666*0.1
nodelay
--
0
PMID: 17395581, 9851930, 10201887 TLR4, the first mammalian homologue of the Drosophila Toll protein recognizes lipopolysaccharide (LPS), which is a cell wall component of Gram-negative bacteria
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c170 : 1
stoichiometry:c169 : 1
m92*0.1
nodelay
--
0
MID: 17395581, 17018642 After ligand stimulation, IRF1 interacts with MyD88, is activated by an unknown mechanism, and translocates into the nucleus to induce the expression of IFN-beta, inducible nitric-oxide synthase, and IL-12 p35.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c15 : 1
m18*m16*0.1
nodelay
--
0
PMID: 17395581, 11062499, 11854525 TLR4 recognizes not only bacterial components but also viral proteins, such as the fusion (F) protein from respiratory syncytial virus and the envelope protein of mouse mammary tumor virus.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1
m16*m20*0.1
nodelay
--
0
PMID: 17395581, 11062499, 11854525 TLR4 recognizes not only bacterial components but also viral proteins, such as the fusion (F) protein from respiratory syncytial virus and the envelope protein of mouse mammary tumor virus.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1
m17*m6810*0.1
nodelay
--
0
PMID: 17395581, 16497588 Each TLR mediates distinctive responses in association with a different combination of four TIR domain-containing adapters (MyD88, TIRAP/MAL, TRIF, and TRAM) through the homophilic interaction of TIR domains.
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:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
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:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
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:InputAssociation
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
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: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: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:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
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:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
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:InputAssociation
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:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
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:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--