Entity
NF-kappaB
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m41
10
infinite
0
TRANSPATH | MO000000058 |
--
MAPKs{active}
--
MO000000077
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m69
10
infinite
0
TRANSPATH | MO000000077 |
--
TRAF6
--
MO000000212
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m183
10
infinite
0
InterPro | IPR001841 |
TRANSPATH | MO000000212 |
--
TNF-alpha
--
MO000000289
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m230
10
infinite
0
InterPro | IPR003636 |
TRANSPATH | MO000000289 |
--
MyD88
--
MO000016573
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1572
10
infinite
0
InterPro | IPR000157 |
TRANSPATH | MO000016573 |
--
Tollip
--
MO000019406
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3973
10
infinite
0
InterPro | IPR000008 |
TRANSPATH | MO000019406 |
--
IRAK-4
--
MO000039077
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m17258
10
infinite
0
TRANSPATH | MO000039077 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m1
0
infinite
0
--
TLR9:Ligand
--
e10
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m10
0
infinite
0
--
IL-33R
--
e11
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m11
0
infinite
0
--
IRAK1
--
e12
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m12
0
infinite
0
--
IFN-alpha
--
e13
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m13
0
infinite
0
--
IFN_alpha
--
e14
cso30:c:mRNA
cso30:i:CC_Cytosol
--
csml-variable:Double
m14
0
infinite
0
--
Activating Ligand
--
e15
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m15
0
infinite
0
--
TLR7:Ligand
--
e16
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m16
0
infinite
0
--
IL-12
--
e17
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m17
0
infinite
0
--
IRAK1:Tollip
--
e18
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m18
0
infinite
0
--
TLR
--
e19
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
TLR:Ligand
--
e20
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m20
0
infinite
0
--
IL-1:IL-1R:MyD88
--
e21
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m21
0
infinite
0
--
TLR:Ligand:MyD88
--
e22
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m22
0
infinite
0
--
IL-1:IL-1R:MyD88:IRAK1:Tollip
--
e23
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m23
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1:Tollip
--
e24
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m24
0
infinite
0
--
IL-1:IL-1R:MyD88:IRAK1:Tollip:IRAK-4
--
e25
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m25
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1:Tollip:IRAK-4
--
e26
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m26
0
infinite
0
--
IL-1:IL-1R:MyD88:IRAK1:Tollip:IRAK-4:TRAF6
--
e27
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m27
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1:Tollip:IRAK-4:TRAF6
--
e28
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m28
0
infinite
0
--
IL-1:IL-1R:MyD88:IRAK1{p}:Tollip:IRAK-4:TRAF6
--
e29
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m29
0
infinite
0
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1{p}:Tollip:IRAK-4:TRAF6
--
e30
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m30
0
infinite
0
--
IL-1:IL-1R:MyD88:IRAK1{p}{p}:Tollip:IRAK-4:TRAF6
--
e31
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m31
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1{p}{p}:Tollip:IRAK-4:TRAF6
--
e32
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m32
0
infinite
0
--
IRAK1{p}:TRAF6
--
e33
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m33
0
infinite
0
--
IL-1:IL-1R:MyD88::Tollip:IRAK-4
--
e34
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m34
0
infinite
0
--
TLR:Ligand:MyD88:IRAK4:Tollip
--
e35
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m35
0
infinite
0
--
IRAK1:TRAF6:IRAK-4:Pellino1
--
e36
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m36
0
infinite
0
--
IRAK1:TRAF6:IRAK-4:Pellino1:TAK1
--
e37
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m37
0
infinite
0
--
Uev1A
--
e38
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m38
0
infinite
0
--
IRAK1:TRAF6:Pellino1:IRAK-4:TAK1:TAB1:TAB2
--
e39
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m39
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
NF-kappaB{active}
--
e41
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m42
10
infinite
0
TRANSPATH | MO000000058 |
--
Proinflammatory cytokines
--
e42
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m43
0
infinite
0
--
IRAK1{sumo}
--
e43
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m44
0
infinite
0
--
IRAK1
--
e44
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m45
0
infinite
0
--
IL10gene
--
e46
cso30:c:Dna
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m47
0
infinite
0
--
IRAK1:IL-10promoter
--
e47
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m48
0
infinite
0
--
IRF7
--
e48
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m49
0
infinite
0
--
TLR9:Ligand:MyD88:IRAK1:TRAF6:IRF7{p}
--
e49
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m63
0
infinite
0
--
IL-1R
--
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
--
IL-1:IL-1R
--
e6
cso30:c:Complex
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
--
TLR7:Ligand:MyD88
--
e63
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m64
0
infinite
0
--
IRF7
--
e64
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m65
0
infinite
0
--
degradants
--
e66
cso30:c:EntityBiological
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m67
0
infinite
0
--
LPS:TLR4
--
e67
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m68
0
infinite
0
--
PKC specific inhibitors
--
e68
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m70
0
infinite
0
--
IRAK1c
--
e69
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m71
0
infinite
0
--
IL-33
--
e7
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m7
0
infinite
0
--
IRAK1:IRAK1c
--
e70
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m72
0
infinite
0
--
IRAK1:IRAK1c:Tollip
--
e71
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m73
0
infinite
0
--
csml-variable:Double
m74
0
infinite
0
--
IRAK2:IRAK1c
--
e73
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m75
0
infinite
0
--
IRAK1c:IRAK2:Tollip
--
e74
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m76
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1c:IRAK2:Tollip
--
e75
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m77
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1c:IRAK2:Tollip:TRAF6
--
e76
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m78
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1c:IRAK1:Tollip
--
e77
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m79
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1c:IRAK1:Tollip:TRAF6
--
e78
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m80
0
infinite
0
--
GMCSF
--
e79
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m81
0
infinite
0
--
IL-33:IL-33R
--
e8
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m8
0
infinite
0
--
GMCSF-R
--
e80
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m82
0
infinite
0
--
GMCSF:GMCSF-R
--
e81
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m83
0
infinite
0
--
IFN-gammaR
--
e82
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m84
0
infinite
0
--
GMCSF:GMCSF-R
--
e83
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m85
0
infinite
0
--
TLR:Ligand:MyD88:IRAK1:Tollip:IRAK-4:TRAF6:BCL-10
--
e84
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m86
0
infinite
0
--
TLR9:Ligand:MyD88
--
e85
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m87
0
infinite
0
--
TLR9:Ligand:MyD88:IRAK1
--
e86
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m88
0
infinite
0
--
TLR9:Ligand:MyD88:IRAK1:TRAF6
--
e87
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m89
0
infinite
0
--
TLR9:Ligand:MyD88:IRAK1:TRAF6:IRF7
--
e88
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m90
0
infinite
0
--
TLR7:Ligand:MyD88:IRAK1
--
e89
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m91
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
TLR7:Ligand:MyD88:IRAK1:TRAF6
--
e90
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m92
0
infinite
0
--
TLR7:Ligand:MyD88:IRAK1:TRAF6:IRF7
--
e91
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m93
0
infinite
0
--
TLR7:Ligand:MyD88:IRAK1:TRAF6:IRF7{P}
--
e92
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m94
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
m185*m5*0.1
nodelay
--
0
PMID: 17890055 IL-1 induces a wide variety of inflammatory mediators including IL-6 and tumor necrosis factor (TNF) alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1
stoichiometry:c31 : 1
m15*m19828*0.1
nodelay
--
0
PMID: 17890055,15767370 IFN-alpha production induced by intravenous injection of TLR7 agonists is completely blocked in IRAK1-deficient mice but IL-12 production remains normal PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
p11
p11
cso30:i:ME_Translation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c34 : 1
stoichiometry:c36 : 1
stoichiometry:c35 : 1
m12*m17*m10*0.1
nodelay
--
0
PMID: 17890055,12626533 However, another study using splenocytes from IRAK1-deficient animals reported a significant reduction in TNF-alpha and IL-12 upon TLR9 activation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c40 : 1
m14*m12*m10*0.1
nodelay
--
0
PMID: 17890055 Together, these results suggest that IRAK1 plays a specific and essential role in IFN-alpha induction downstream of TLR7 and TLR9
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c43 : 1
m12*m3973*0.1
nodelay
--
0
PMID: 17890055,10854325,16428431 Prior to receptor activation, IRAK1 is associated with Tollip in the cytosol
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c45 : 1
stoichiometry:c46 : 1
m19*m15*0.1
nodelay
--
0
PMID: 17890055 Upon ligand binding to TLR/IL-1R, myeloid differentiation factor 88 (MyD88) is rapidly recruited to the receptor via interaction of Toll/IL-1R (TIR) domains which are present in both MyD88 and TLR/IL-1R.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c48 : 1
stoichiometry:c49 : 1
m6*m1572*0.1
nodelay
--
0
PMID: 17890055 Upon ligand binding to TLR/IL-1R, myeloid differentiation factor 88 (MyD88) is rapidly recruited to the receptor via interaction of Toll/IL-1R (TIR) domains which are present in both MyD88 and TLR/IL-1R.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c52 : 1
m1572*m20*0.1
nodelay
--
0
PMID: 17890055 Upon ligand binding to TLR/IL-1R, myeloid differentiation factor 88 (MyD88) is rapidly recruited to the receptor via interaction of Toll/IL-1R (TIR) domains which are present in both MyD88 and TLR/IL-1R.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c54 : 1
stoichiometry:c55 : 1
m18*m21*0.1
nodelay
--
0
PMID: 17890055,9430229,17276401 IRAK1 is also recruited to the receptor complex through a death domain interaction with MyD88
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c57 : 1
stoichiometry:c58 : 1
m18*m22*0.1
nodelay
--
0
PMID: 17890055,9430229,17276401 IRAK1 is also recruited to the receptor complex through a death domain interaction with MyD88
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c60 : 1
stoichiometry:c61 : 1
m23*m17258*0.1
nodelay
--
0
PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c9 : 1
stoichiometry:c8 : 1
m93309*m6*0.1
nodelay
--
0
PMID: 17890055 IL-1 induces a wide variety of inflammatory mediators including IL-6 and tumor necrosis factor (TNF) alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c63 : 1
stoichiometry:c64 : 1
m17258*m24*0.1
nodelay
--
0
PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c65 : 1
stoichiometry:c67 : 1
m183*m25*0.1
nodelay
--
0
PMID: 17890055,11287640 IRAK1 also binds tumor necrosis factor receptor-associated factor 6 (TRAF6) through multiple regions including the death domain, the undefined domain and the C-terminal C1 domain PMID: 17890055 IRAK1 also interacts with TRAF6
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
stoichiometry:c70 : 1
m183*m26*0.1
nodelay
--
0
PMID: 17890055,11287640 IRAK1 also binds tumor necrosis factor receptor-associated factor 6 (TRAF6) through multiple regions including the death domain, the undefined domain and the C-terminal C1 domain PMID: 17890055 IRAK1 also interacts with TRAF6
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c72 : 1
m27*0.1
nodelay
--
0
PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c74 : 1
m28*0.1
nodelay
--
0
PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c76 : 1
m29*0.1
nodelay
--
0
PMID: 17890055,8599092,17141195 This results in the activation of IRAK1 kinase activity and thus the formation of hyper-phosphorylated IRAK1 via auto-phosphorylation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c77 : 1
stoichiometry:c78 : 1
m30*0.1
nodelay
--
0
PMID: 17890055,8599092,17141195 This results in the activation of IRAK1 kinase activity and thus the formation of hyper-phosphorylated IRAK1 via auto-phosphorylation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c80 : 1
stoichiometry:c81 : 1
m31*0.1
nodelay
--
0
PMID: 17890055,9430229 Since MyD88 and Tollip only bind to non-phosphorylated IRAK1, hyper-phosphorylated IRAK1 is then released from MyD88 and the receptor complex, a key step in this signaling cascade PMID: 17890055 Hyper-phosphorylated IRAK1 then disengages from MyD88 and Tollip, and forms a cytosolic IRAK1-TRAF6 complex
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c83 : 1
stoichiometry:c84 : 1
m32*0.1
nodelay
--
0
PMID: 17890055,9430229 Since MyD88 and Tollip only bind to non-phosphorylated IRAK1, hyper-phosphorylated IRAK1 is then released from MyD88 and the receptor complex, a key step in this signaling cascade PMID: 17890055 Hyper-phosphorylated IRAK1 then disengages from MyD88 and Tollip, and forms a cytosolic IRAK1-TRAF6 complex
p29
p29
cso30:i:ME_Binding
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c86 : 1
stoichiometry:c87 : 1
stoichiometry:c88 : 1
m33*m19287*m17258*0.1
nodelay
--
0
PMID: 17890055,12496252 An intermediate cytosolic signaling complex composed of Pellino1, IRAK1, IRAK4 and TRAF6 may be formed prior to the interaction of TRAF6 with the downstream signaling molecule TGF-beta activated kinase-1 (TAK1)
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c6 : 1
stoichiometry:c5 : 1
m93248*m6*0.1
nodelay
--
0
PMID: 17890055 IL-1 induces a wide variety of inflammatory mediators including IL-6 and tumor necrosis factor (TNF) alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c90 : 1
stoichiometry:c91 : 1
m36*m1573*0.1
nodelay
--
0
PMID: 17890055,12496252 An intermediate cytosolic signaling complex composed of Pellino1, IRAK1, IRAK4 and TRAF6 may be formed prior to the interaction of TRAF6 with the downstream signaling molecule TGF-beta activated kinase-1 (TAK1)
p31
p31
cso30:i:ME_Binding
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c95 : 1
stoichiometry:c96 : 1
stoichiometry:c97 : 1
m37*m6433*m1583*m6443*m38*0.1
nodelay
--
0
PMID: 17890055,10882101,12242293,11057907 Cytosolic TRAF6 interacting with TAK1 eventually forms a macromolecular complex with ubiquitin conjugating enzymes Ubc13 and Uev1A, and TAK1 binding proteins TAB1 and TAB2
p32
p32
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c99 : 1
stoichiometry:c100 : 1
m39*m40*0.1
nodelay
--
0
PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-¦ÊB and MAPK pathways
p32
p33
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c103 : 1
stoichiometry:c102 : 1
m41*m39*0.1
nodelay
--
0
PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-¦ÊB and MAPK pathways
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c105 : 1
m69*0.1
nodelay
--
0
PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-¦ÊB and MAPK pathways
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c107 : 1
m42*0.1
nodelay
--
0
PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-¦ÊB and MAPK pathways
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c111 : 1
stoichiometry:c112 : 1
m44*0.1
nodelay
--
0
PMID: 17890055,10899313,15896328 IRAK1 has been reported to translocate to the nucleus upon IL-1 stimulation PMID: 17890055,16690127 A recent study also indicated that IRAK1 undergoes sumoylation followed by nuclear translocation in monocytes stimulated with TLR ligands
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c109 : 1
stoichiometry:c110 : 1
m33*0.1
nodelay
--
0
PMID: 17890055,16690127 A recent study also indicated that IRAK1 undergoes sumoylation followed by nuclear translocation in monocytes stimulated with TLR ligands
p38
p38
cso30:i:ME_Phosphorylation
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c114 : 1
stoichiometry:c115 : 1
m45*m1360*0.1
nodelay
--
0
PMID: 17890055,15465816 Within the nucleus, IRAK1 has been reported to phosphorylate transcription factor Stat3 and bind directly to the IL-10 gene promoter for IL-10 expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c119 : 1
stoichiometry:c120 : 1
m48*0.1
nodelay
--
0
PMID: 17890055,15465816 Within the nucleus, IRAK1 has been reported to phosphorylate transcription factor Stat3 and bind directly to the IL-10 gene promoter for IL-10 expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1
m7*m11*0.1
nodelay
--
0
PMID: 17890055,16286016 IL-33-treatment of Th2 T cells induces IL-5 and IL-13 production
p40
p40
cso30:i:ME_DNABinding
cso30:i:CC_NuclearEnvelopeLumen
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c117 : 1
stoichiometry:c118 : 1
m45*m47*0.1
nodelay
--
0
PMID: 17890055,15465816 Within the nucleus, IRAK1 has been reported to phosphorylate transcription factor Stat3 and bind directly to the IL-10 gene promoter for IL-10 expression
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c125 : 1
stoichiometry:c126 : 1
m65*0.1
nodelay
--
0
PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c121 : 1
stoichiometry:c122 : 1
m90*0.1
nodelay
--
0
PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c123 : 1
stoichiometry:c127 : 1
stoichiometry:c124 : 1
m63*0.1
nodelay
--
0
PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c128 : 1
stoichiometry:c129 : 1
stoichiometry:c130 : 1
m1572*m16*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7)
p45
p45
cso30:i:ME_ProteasomeDegradation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c131 : 1
stoichiometry:c137 : 1
stoichiometry:c138 : 1
stoichiometry:c166 : 1
stoichiometry:c170 : 1
stoichiometry:c132 : 1
stoichiometry:c133 : 1
m33*m68*0.1
nodelay
--
0
PMID: 17890055,9261174 The loss of IRAK1 protein is due to proteasome-mediated degradation as demonstrated by studies using proteasome inhibitors PMID: 17890055,11937546 TLR4 activation can also trigger rapid IRAK1 degradation that can be blocked by protein kinase C (PKC) specific inhibitors PMID: 17890055,12032143 Interestingly, degradation of IRAK1 in LPS-tolerant THP-1 cells can be prevented by pretreatment with GM-CSF and IFN-¦Ã
p46
p46
cso30:i:ME_Binding
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c136 : 1
m3961*m155666*0.1
nodelay
--
0
PMID: 17890055,11937546 TLR4 activation can also trigger rapid IRAK1 degradation that can be blocked by protein kinase C (PKC) specific inhibitors
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c140 : 1
stoichiometry:c141 : 1
m12*m71*0.1
nodelay
--
0
PMID: 17890055 In resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c143 : 1
stoichiometry:c144 : 1
m72*m3973*0.1
nodelay
--
0
PMID: 17890055 n resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c146 : 1
stoichiometry:c147 : 1
m71*m74*0.1
nodelay
--
0
PMID: 17890055 In resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
stoichiometry:c15 : 1
m93275*m8*0.1
nodelay
--
0
PMID: 17890055,16286016 IL-33-treatment of Th2 T cells induces IL-5 and IL-13 production
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c149 : 1
stoichiometry:c150 : 1
m75*m3973*0.1
nodelay
--
0
PMID: 17890055 In resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c151 : 1
stoichiometry:c152 : 1
stoichiometry:c153 : 1
m76*m22*0.1
nodelay
--
0
PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c155 : 1
stoichiometry:c156 : 1
m183*m77*0.1
nodelay
--
0
PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c157 : 1
stoichiometry:c158 : 1
stoichiometry:c159 : 1
m22*m73*0.1
nodelay
--
0
PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c160 : 1
stoichiometry:c161 : 1
stoichiometry:c162 : 1
m79*m183*0.1
nodelay
--
0
PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c164 : 1
stoichiometry:c165 : 1
m81*m82*m83*0.1
nodelay
--
0
PMID: 17890055,12032143 Interestingly, degradation of IRAK1 in LPS-tolerant THP-1 cells can be prevented by pretreatment with GM-CSF and IFN-¦Ã
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c167 : 1
stoichiometry:c168 : 1
stoichiometry:c169 : 1
m1639*m84*0.1
nodelay
--
0
PMID: 17890055,12032143 Interestingly, degradation of IRAK1 in LPS-tolerant THP-1 cells can be prevented by pretreatment with GM-CSF and IFN-¦Ã
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c171 : 1
stoichiometry:c172 : 1
stoichiometry:c173 : 1
m28*m21910*0.1
nodelay
--
0
PMID: 17890055,16831874 IRAK1 also acts as an upstream adaptor by recruiting B-cell CLL/lymphoma 10 (BCL10) to the TLR signaling complex
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c175 : 1
stoichiometry:c199 : 1
m1572*m10*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c176 : 1
stoichiometry:c177 : 1
stoichiometry:c178 : 1
m12*m87*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c18 : 1
m93493*m8*0.1
nodelay
--
0
PMID: 17890055,16286016 IL-33-treatment of Th2 T cells induces IL-5 and IL-13 production
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c179 : 1
stoichiometry:c180 : 1
stoichiometry:c181 : 1
m88*m183*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c182 : 1
stoichiometry:c183 : 1
stoichiometry:c184 : 1
m89*m49*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c185 : 1
stoichiometry:c186 : 1
stoichiometry:c187 : 1
m64*m12*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c188 : 1
stoichiometry:c189 : 1
stoichiometry:c190 : 1
m91*m183*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c194 : 1
stoichiometry:c195 : 1
m93*0.1
nodelay
--
0
PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c191 : 1
stoichiometry:c192 : 1
stoichiometry:c193 : 1
m92*m49*0.1
nodelay
--
0
PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c196 : 1
stoichiometry:c197 : 1
stoichiometry:c198 : 1
m94*0.1
nodelay
--
0
PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c25 : 1
stoichiometry:c21 : 1
m14*m12*m16*0.1
nodelay
--
0
PMID: 17890055,15767370 IFN-alpha production induced by intravenous injection of TLR7 agonists is completely blocked in IRAK1-deficient mice but IL-12 production remains normal PMID: 17890055,15767370 IRAK1 deficiency in plasmacytoid dendritic cells abrogates IFN-alpha production without affecting the production of other inflammatory cytokines such as IL-6 and TNF-alpha
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1
m15*m19940*0.1
nodelay
--
0
PMID: 17890055,15767370 IFN-alpha production induced by intravenous injection of TLR7 agonists is completely blocked in IRAK1-deficient mice but IL-12 production remains normal PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.
p9
p9
cso30:i:ME_Translation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c33 : 1
stoichiometry:c28 : 1
m12*m93309*m10*0.1
nodelay
--
0
PMID: 17890055,12626533 However, another study using splenocytes from IRAK1-deficient animals reported a significant reduction in TNF-alpha and IL-12 upon TLR9 activation
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