1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18706831.csml convertedTime:2009.07.01.11:21

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Signalling adaptors used by Toll-like receptors: an update.
Authors Kenny EF, O'Neill LA.
Affiliation School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.kennyef@tcd.ie
Abstract Research into the five Toll/IL1 receptor (TIR) adaptor proteins involved ininnate immunity continues to advance. Here we outline some of the more recentfindings. MyD88 has a key role in signalling by the IL1 receptor complex andTLRs. However, a MyD88-independent pathway of IL1beta signalling in neurons hasbeen described which involves the protein kinase Akt, and which has ananti-apoptotic effect. This pathway may also be important for the mechanismwhereby Alum exerts its adjuvant effect since this depends on IL1beta but isMyD88-independent. MyD88 is also involved in tumourigenesis in models ofhepatocarcinoma and familial associated polyposis (FAP); negative regulation ofTLR3 signalling and in PKCepsilon activation. The adaptor Mal is regulated byphosphorylation and caspase-1 cleavage. A variant form of Mal in humans termedS180L confers protection in multiple infectious diseases. TRAM is controlled bymyristoylation and phosphorylation and the localisation of TRAM with TLR4 toendosomes is required for activation of IRF3 and induction of IFNbeta. FinallySARM has been shown to regulate TRIF and also appears to be involved in neuronalinjury mediated by oxidative stress in mouse neurons. These advances confirm theimportance for the TIR domain-containing adapters in host defence andinflammation.
PMID 18706831
Model Abstract

Entity

G010228:IFN-beta G010262:IL-6 G010329:TNF-alpha G010453:IFN-gamma G010522:RANTES G011345:IL10 G011715:SRC G030718:COX MO000000022:p38 MO000000030:PI3K MO000000048:AKT MO000000058:NF-kappaB MO000000074:14-3-3 MO000000085:Src {activated} MO000000104:PKC MO000000193:RelA-p65 MO000000211:IKK-beta MO000000220:IkappaB-alpha{p} MO000000233:IkappaB-alpha MO000000276:AP-1 MO000000289:TNF-alpha MO000001935:Btk MO000004690:p38gamma MO000007384:IL-6 MO000007694:IRF-3 MO000007702:IRF-7 MO000013119:STAT1 MO000016573:MyD88 MO000016597:IL-1beta MO000016645:PKCepsilon MO000016660:IFNbeta MO000016665:IFNgamma MO000016828:Caspase-1 MO000016882:LPS MO000016961:p38delta MO000016963:TRAF3 MO000017247:IL-10 MO000019394:TLR4 MO000019397:TLR2 MO000019398:TLR3 MO000019704:STAT1{p} MO000022224:dsRNA MO000039096:IL-1beta:IL-1RI:IL-1RAcP:MyD88 MO000039108:IL-1beta:IL-1RII:IL-1RAcP MO000041125:TRIF MO000041132:TRAM MO000041437:dsRNA:TLR3:TRIF MO000041446:dsRNA:TLR3 MO000041456:IRF-3{p} MO000068831:MAL {activated} MO000094908:IPS1 MO000103999:MDA-5 e1: e10: e11:TLR2 ligand: TLR2: MAL {activated} e12:TLR2 ligand e13:TLR2 ligand: TLR2 e14:MAL e15:MAL {p} e16:LPS: TLR4: MAL {activated}: MyD88 e17:TLR2 ligand: TLR2: MAL {activated} : MyD88 e18:LPS: TLR4: TRAM {myristoylated} e19:LPS: TLR4: TRAM {myristoylated}: TRIF e2: e20:LPS: TLR4: MAL {activated}: MyD88: PKCepsilon e21:LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{p} e22:LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{p}: 14-3-3 e23:LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{pS346} e25:GSK e26:LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{pS346, p368} e27:LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{p350} e28:TRAM{p} e29:dynasore e3: e30:TRAM {myristoylated} e31:TRAM {myristoylated} e32: e33: e34: e35:LPS: TLR4: TRAM {myristoylated} e36:LPS: TLR4: TRAM {myristoylated}: TRIF: TRAF3 e37:NF-kappaB {activated} e38:SARM e39:TRIF: SARM e4: e40:JNK3 e41:SARM: JNK3 e42:IRF-7 {activated} e43:RIG 1 e44:dsRNA: RIG 1 e45:dsRNA: MDA-5 e46:dsRNA: RIG 1: IPS1 e47:dsRNA: MDA-5: IPS1 e48:AP-1 {activated} e49:IFN-alpha e5:LPS: TLR4 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:LPS: TLR4: MAL {activated} e60: e61: e62: e63:IL-1RII:IL-1RAcP e64:IL-1beta:IL-1RII{p}:IL-1RAcP e65:IL-1beta:IL-1RII{p}:IL-1RAcP: PI3K e66:AKT {activated} e67:diethylnitrosamine e68:Estrogen e69:YVAD-Cmk e7: e70:p38 {activated} e71:Pam3Cys e72:NLR e73:Nalp3 e74:Nalp3: NLR e75:lipid A e76:CCL3 e77:CCL3 e78:RelA: TNF-alpha e79:TNF-alpha e8: e80:Src e9:

Process

p1 p10 p11 p12 p13 p15 p16 p17 p18 p19 p2 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p55 p56 p57 p58 p59 p6 p60 p61 p62 p63 p64 p65 p66 p67 p68 p69 p7 p70 p71 p72 p73 p74 p75 p8 p9
Model Detail
583.0, 1063.0
33.0, 33.0

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
545.0, 1229.0
29.0, 29.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
360.0, 1156.0
32.0, 32.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p69

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
528.0, 960.0
32.0, 32.0

IFN-gamma

--

G010453

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p49 p50

true true true true

csml-variable:Double

m93423

10

false

infinite

0

unit false false false
TRANSFACG010453

--

Go back
640.0, 1068.0
32.0, 32.0

RANTES

--

G010522

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p27 p54

--

true true true true

csml-variable:Double

m93487

10

false

infinite

0

unit false false false
TRANSFACG010522

--

Go back
384.0, 1024.0
32.0, 32.0

IL10

--

G011345

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p71

true true true true

csml-variable:Double

m94230

10

false

infinite

0

unit false false false
TRANSFACG011345

--

Go back
419.0, 1203.0
34.0, 34.0

SRC

--

G011715

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p59

--

true true true true

csml-variable:Double

m94540

10

false

infinite

0

unit false false false
TRANSFACG011715

--

Go back
487.0, 1243.0
26.0, 26.0

COX

--

G030718

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p61

--

true true true true

csml-variable:Double

m109413

10

false

infinite

0

unit false false false
TRANSFACG030718

--

Go back
264.0, 280.0
23.0, 23.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p67

true true true true

csml-variable:Double

m74

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
280.0, 421.0
31.5, 31.5

PI3K

--

MO000000030

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p63

true true true true

csml-variable:Double

m27

10

false

infinite

0

unit false false false
TRANSPATHMO000000030

--

Go back
296.0, 476.0
24.0, 24.0

AKT

--

MO000000048

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p65

true true true true

csml-variable:Double

m70

10

false

infinite

0

unit false false false
TRANSPATHMO000000048

--

Go back
397.0, 497.0
30.0, 30.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m39

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
853.0, 477.0
30.0, 30.0

14-3-3

--

MO000000074

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15

true true true true

csml-variable:Double

m66

10

false

infinite

0

unit false false false
TRANSPATHMO000000074

--

Go back
300.0, 1296.0
24.0, 24.0

Src {activated}

--

MO000000085

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m77

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000000085

--

Go back
820.0, 400.0
31.5, 31.5

PKC

--

MO000000104

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18

true true true true

csml-variable:Double

m92

10

false

infinite

0

unit false false false
TRANSPATHMO000000104

--

Go back
443.0, 1175.0
26.0, 26.0

RelA-p65

--

MO000000193

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p74

true true true true

csml-variable:Double

m166

10

false

infinite

0

unit false false false
TRANSPATHMO000000193

--

Go back
494.0, 1338.0
28.0, 28.0

IKK-beta

--

MO000000211

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p66

true true true true

csml-variable:Double

m182

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000211

--

Go back
362.0, 714.0
28.0, 28.0

IkappaB-alpha{p}

--

MO000000220

cso30:c:Protein

cso30:i:CC_CellComponent

--

p73

--

true true true true

csml-variable:Double

m190

10

false

infinite

0

unit false false false
TRANSPATHMO000000220

--

Go back
361.0, 657.0
30.0, 30.0

IkappaB-alpha

--

MO000000233

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p73

true true true true

csml-variable:Double

m199

10

false

infinite

0

unit false false false
InterProIPR002110
TRANSPATHMO000000233

--

Go back
936.0, 950.0
28.0, 28.0

AP-1

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p45 p46

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
213.0, 1177.0
30.0, 30.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p69

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
391.0, 317.0
24.0, 24.0

Btk

--

MO000001935

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m367

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000001935

--

Go back
715.0, 355.0
26.0, 26.0

p38gamma

--

MO000004690

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m567

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000004690

--

Go back
669.0, 1329.0
30.0, 30.0

IL-6

--

MO000007384

cso30:c:Protein

cso30:i:CC_CellComponent

--

p66

--

true true true true

csml-variable:Double

m871

10

false

infinite

0

unit false false false
InterProIPR003573
TRANSPATHMO000007384

--

Go back
761.0, 833.0
30.0, 30.0

IRF-3

--

MO000007694

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p24 p25 p43 p44

true true true true

csml-variable:Double

m977

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
629.0, 605.0
29.0, 29.0

IRF-7

--

MO000007702

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m980

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
331.0, 851.0
30.0, 30.0

STAT1

--

MO000013119

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p75

true true true true

csml-variable:Double

m1357

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
604.0, 324.0
32.0, 32.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7 p8 p53

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
84.0, 200.0
32.0, 32.0

IL-1beta

--

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p52

true true true true

csml-variable:Double

m1591

10

false

infinite

0

unit false false false
TRANSPATHMO000016597

--

Go back
673.0, 317.0
29.0, 29.0

PKCepsilon

--

MO000016645

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13

true true true true

csml-variable:Double

m1629

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016645

--

Go back
255.0, 927.0
26.0, 26.0

IFNbeta

--

MO000016660

cso30:c:Protein

cso30:i:CC_CellComponent

--

p72

--

true true true true

csml-variable:Double

m1636

10

false

infinite

0

unit false false false
InterProIPR000471
TRANSPATHMO000016660

--

Go back
567.0, 835.0
26.0, 26.0

IFNgamma

--

MO000016665

cso30:c:Protein

cso30:i:CC_CellComponent

--

p49 p50

--

true true true true

csml-variable:Double

m1639

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
523.0, 325.0
30.0, 30.0

Caspase-1

--

MO000016828

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m1765

10

false

infinite

0

unit false false false
TRANSPATHMO000016828

--

Go back
391.0, 101.0
30.0, 30.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p6 p32

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
750.0, 394.0
28.0, 28.0

p38delta

--

MO000016961

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p17

true true true true

csml-variable:Double

m1870

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016961

--

Go back
912.0, 816.0
21.0, 21.0

TRAF3

--

MO000016963

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p29

true true true true

csml-variable:Double

m1872

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000016963

--

Go back
252.0, 968.0
32.0, 32.0

IL-10

--

MO000017247

cso30:c:Protein

cso30:i:CC_CellComponent

--

p71

--

true true true true

csml-variable:Double

m2103

10

false

infinite

0

unit false false false
InterProIPR000098
TRANSPATHMO000017247

--

Go back
446.0, 206.0
28.0, 28.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
151.0, 610.0
28.0, 28.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
1003.0, 499.0
25.0, 25.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
335.0, 903.0
30.0, 30.0

STAT1{p}

--

MO000019704

cso30:c:Protein

cso30:i:CC_CellComponent

--

p75

--

true true true true

csml-variable:Double

m4238

10

false

infinite

0

unit false false false
TRANSPATHMO000019704

--

Go back
1148.0, 492.0
32.0, 32.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9 p39 p40

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
150.0, 359.0
44.0, 44.0

IL-1beta:IL-1RI:IL-1RAcP:MyD88

--

MO000039096

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m17272

10

false

infinite

0

unit false false false
TRANSPATHMO000039096

--

Go back
151.0, 288.0
42.0, 42.0

IL-1beta:IL-1RII:IL-1RAcP

--

MO000039108

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m17284

10

false

infinite

0

unit false false false
TRANSPATHMO000039108

--

Go back
899.0, 551.0
26.0, 26.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
878.0, 394.0
28.0, 28.0

TRAM

--

MO000041132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21

true true true true

csml-variable:Double

m19005

10

false

infinite

0

unit false false false
TRANSPATHMO000041132

--

Go back
995.0, 587.0
34.0, 34.0

dsRNA:TLR3:TRIF

--

MO000041437

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19305

10

false

infinite

0

unit false false false
TRANSPATHMO000041437

--

Go back
1001.0, 533.0
29.0, 29.0

dsRNA:TLR3

--

MO000041446

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19314

10

false

infinite

0

unit false false false
TRANSPATHMO000041446

--

Go back
756.0, 916.0
32.0, 32.0

IRF-3{p}

--

MO000041456

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19324

10

false

infinite

0

unit false false false
TRANSPATHMO000041456

--

Go back
578.0, 260.0
32.0, 32.0

MAL {activated}

--

MO000068831

cso30:c:Protein

cso30:i:CC_CellComponent

--

p5

p2 p4

true true true true

csml-variable:Double

m43675

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
781.0, 1129.0
30.0, 30.0

IPS1

--

MO000094908

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p41 p42

true true true true

csml-variable:Double

m68199

10

false

infinite

0

unit false false false
TRANSPATHMO000094908

--

Go back
921.0, 1137.0
30.0, 30.0

MDA-5

--

MO000103999

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p40

true true true true

csml-variable:Double

m76904

10

false

infinite

0

unit false false false
TRANSPATHMO000103999

--

Go back
135.3756716836872, 178.8473758449243
913.4999911225358, 1317.3003880118586

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
141.85099591261692, 240.21493703658288
852.6459693133218, 1191.2027727461007

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
159.875, 705.5
26.22100385391815, 36.58744723802533

TLR2 ligand: TLR2: MAL {activated}

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

p8

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
73.5, 590.375
29.04217926186291, 18.877416520210893

TLR2 ligand

--

e12

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p3

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
155.625, 659.5
26.208590234960838, 32.09215130811531

TLR2 ligand: TLR2

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

p4

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
440.0, 262.0
28.0, 28.0

MAL

--

e14

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5 p6

true true true true

csml-variable:Double

m14

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
348.5, 312.125
31.239999999999995, 23.43

MAL {p}

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

p6

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
623.875, 181.5
32.25, 45.0

LPS: TLR4: MAL {activated}: MyD88

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
156.875, 747.5
32.25, 45.0

TLR2 ligand: TLR2: MAL {activated} : MyD88

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
995.875, 437.5
32.25, 45.0

LPS: TLR4: TRAM {myristoylated}

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
912.875, 723.5
27.649339328317122, 38.58047348137273

LPS: TLR4: TRAM {myristoylated}: TRIF

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
135.3756716836872, 178.8473758449243
913.4999911225358, 1317.3003880118586

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
668.875, 173.5
37.647687649109926, 52.53165718480456

LPS: TLR4: MAL {activated}: MyD88: PKCepsilon

--

e20

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
995.875, 225.5
32.25, 45.0

LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{p}

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p15

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
994.875, 279.5
34.751559919251235, 48.49054872453661

LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{p}: 14-3-3

--

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
784.5, 149.0
38.25729491649844, 53.38227197650945

LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{pS346}

--

e23

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
785.5, 445.125
36.30609780639968, 22.38876031394647

GSK

--

e25

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p19

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
906.5, 135.0
35.140209212699574, 49.032850064231965

LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{pS346, p368}

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
733.5, 162.0
37.03413470361534, 51.67553679574234

LPS: TLR4: MAL {activated}: MyD88: PKCepsilon{p350}

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
930.5, 323.125
34.76, 26.069999999999993

TRAM{p}

--

e28

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
913.5, 859.125
28.783457436103845, 17.749798752264038

dynasore

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p24

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
153.64567150613783, 196.99200928861384
876.9599914776344, 1281.01112112448

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
929.5, 358.125
36.199999999999996, 27.15

TRAM {myristoylated}

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
993.5, 402.125
36.199999999999996, 27.15

TRAM {myristoylated}

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
830.4699524017219, 632.0
104.13976068116722, 173.86044791686388

--

e32

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false true false

--

Go back
830.4699524017219, 632.0
104.13976068116722, 173.86044791686388

--

e33

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false true false

--

Go back
830.4699524017219, 632.0
104.13976068116722, 173.86044791686388

--

e34

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false true false

--

Go back
915.875, 679.5
22.551523215268855, 31.46724169572398

LPS: TLR4: TRAM {myristoylated}

--

e35

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
885.5, 760.0
27.82492200403744, 38.82547256377317

LPS: TLR4: TRAM {myristoylated}: TRIF: TRAF3

--

e36

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
397.0, 581.0
30.0, 30.0

NF-kappaB {activated}

--

e37

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m40

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
503.0, 846.5
25.28, 18.959999999999997

SARM

--

e38

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
779.625, 708.5
24.608190301616396, 30.13247792034661

TRIF: SARM

--

e39

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
187.44517117767177, 228.74511781507033
809.3609921345667, 1217.5049040715658

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
215.5, 758.125
33.11833366874623, 20.422972429060174

JNK3

--

e40

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p33

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
152.625, 848.5
24.510206632227963, 30.012497917013828

SARM: JNK3

--

e41

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
629.0, 641.0
29.0, 29.0

IRF-7 {activated}

--

e42

cso30:c:Protein

cso30:i:CC_CellComponent

--

p36

--

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
926.5, 1065.125
34.9054135640974, 21.5250050311934

RIG 1

--

e43

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p39

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
926.625, 1095.5
26.16776370604899, 32.042159640059985

dsRNA: RIG 1

--

e44

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
874.625, 1167.5
27.31907182136311, 33.45192467922013

dsRNA: MDA-5

--

e45

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
787.875, 1005.5
32.25, 45.0

dsRNA: RIG 1: IPS1

--

e46

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
831.875, 1033.5
32.25, 45.0

dsRNA: MDA-5: IPS1

--

e47

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
936.0, 990.0
28.0, 28.0

AP-1 {activated}

--

e48

cso30:c:Protein

cso30:i:CC_CellComponent

--

p45 p46

--

true true true true

csml-variable:Double

m64

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
557.0, 1169.0
30.0, 30.0

IFN-alpha

--

e49

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p55 p57

--

true true true true

csml-variable:Double

m65

10

false

infinite

0

unit false false false
EnsemblENSG00000147877
HGNCIFNA7
OMIM147567
ProteomeHumanPSD/IFNA7
RefSeqNM_021057
TRANSFACG000306
UnigeneHs.282274

--

Go back
499.5, 203.0
33.83702716213965, 41.43309448425262

LPS: TLR4

--

e5

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
307.5334716992939, 930.8469964873099
435.83356992887695, 392.5409868972331

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
354.6067436841632, 940.1496472119404
254.84495522843096, 380.4504020852034

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
313.21472866298507, 936.0862499058558
424.4710560014949, 382.0624800601404

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
314.02633680065514, 936.8922888933245
422.8478397261544, 380.4504020852034

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
307.5334716992939, 930.8469964873099
435.83356992887695, 392.5409868972331

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
307.5334716992939, 930.8469964873099
435.83356992887695, 392.5409868972331

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
314.02633680065514, 936.8922888933245
422.8478397261544, 380.4504020852034

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
625.6838616659974, 1092.05479398104
27.228486759830734, 24.47980802609104

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
554.2623455510231, 1204.9002522266514
77.10277307866538, 69.31935292230399

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
307.5334716992939, 930.8469964873099
435.83356992887695, 392.5409868972331

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
549.5, 191.0
29.46632409616444, 41.11580106441549

LPS: TLR4: MAL {activated}

--

e6

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p7

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
410.2569918648254, 1105.2889674715639
13.802208769485587, 6.599907309091105

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
409.79609704573426, 1085.6064820812912
47.24171895683867, 84.45159429081916

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
429.61457426665226, 1140.5343482867027
7.37431710545774, 7.323715494054774

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
154.5, 249.0
26.735914846760874, 37.3059276931547

IL-1RII:IL-1RAcP

--

e63

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p52

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
155.875, 414.5
32.25, 45.0

IL-1beta:IL-1RII{p}:IL-1RAcP

--

e64

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
151.875, 474.5
32.25, 45.0

IL-1beta:IL-1RII{p}:IL-1RAcP: PI3K

--

e65

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
296.0, 508.0
28.0, 28.0

AKT {activated}

--

e66

cso30:c:Protein

cso30:i:CC_CellComponent

--

p65

--

true true true true

csml-variable:Double

m71

10

false

infinite

0

unit false false false
TRANSPATHMO000000048

--

Go back
591.5, 1520.25
40.13036164844407, 22.74053826745164

diethylnitrosamine

--

e67

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p66

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
667.5, 1524.25
41.54331370899916, 23.541211101766187

Estrogen

--

e68

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p66

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
310.5, 114.25
35.05887300252312, 19.866694701429772

YVAD-Cmk

--

e69

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p5 p30 p67

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
146.93293199586407, 183.95184421461695
862.6582934620591, 1213.9768117172741

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
264.0, 312.0
23.0, 23.0

p38 {activated}

--

e70

cso30:c:Protein

cso30:i:CC_CellComponent

--

p67

--

true true true true

csml-variable:Double

m76

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
253.5, 139.25
39.70142977291842, 22.497476871320433

Pam3Cys

--

e71

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p67

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
151.375, 180.5
25.960017574692444, 39.93848857644991

NLR

--

e72

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p68

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
101.5, 102.125
35.19521030388408, 21.703713020728518

Nalp3

--

e73

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p68

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
232.375, 177.5
23.25, 45.0

Nalp3: NLR

--

e74

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
66.5, 1138.25
35.28595458368376, 19.995374264087467

lipid A

--

e75

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false false false

--

Go back
359.5, 1119.0
33.68512110726644, 17.965397923875432

CCL3

--

e76

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p70

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
262.5, 1057.125
34.5190179110485, 21.286727711813242

CCL3

--

e77

cso30:c:Protein

cso30:i:CC_Cytosol

--

p70

--

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false false false

--

Go back
509.5, 1125.625
45.0, 12.75

RelA: TNF-alpha

--

e78

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p74

--

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false false false

--

Go back
513.5, 1099.125
45.0, 9.75

TNF-alpha

--

e79

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p74

true true true true

csml-variable:Double

m86

0

false

infinite

0

unit false false false

--

Go back
150.0148680791112, 205.3773618662801
827.558380156286, 1193.3694426671448

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
304.0, 1260.0
24.0, 24.0

Src

--

e80

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p60

true true true true

csml-variable:Double

m21

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000000085

--

Go back
158.23336430110368, 226.80287951794327
823.7801222066387, 1177.7187014578903

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
502.0, 104.0
23.0, 23.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m155666*m3961*0.1

nodelay

--

true

0

false

PMID: 18706831, 16166516 TLR4 signalling therefore involves all four adaptor proteins with MyD88/Mal believed to be involved in the early LPS responses and TRIF/TRAM pathway initiated at a later stage.

Go back
914.0, 634.0
25.0, 25.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1
stoichiometry:c90 : 1
stoichiometry:c31 : 1

m19314*m18998*0.1

nodelay

--

true

0

false

PMID: 18706831 TLR3 uses the adaptor TRIF to signal in response to double-stranded RNA. PMID: 18706831 As it contains a TIR domain it binds directly to the TIR domain of TRIF thus blocking the interaction of TRIF with TLR3 or TRAM in the case of TLR4 signalling.

Go back
1131.0, 95.0
25.0, 25.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c68 : 1
stoichiometry:c34 : 1

m5*m33*0.1

nodelay

--

true

0

false

PMID: 18706831, 12855817 In TLR4 signalling TRIF is coupled to TLR4 through the bridging adaptor TRAM. PMID: 18706831, 16603631 It is regulated by myristoylation [34], which is required to localise it to the plasma membrane, and as stated in Section 2.2 it is also regulated by PKCepsilon.

Go back
874.0, 682.0
25.0, 25.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c73 : 1
stoichiometry:c91 : 1
stoichiometry:c37 : 1

m18998*m37*0.1

nodelay

--

true

0

false

PMID: 18706831, 12855817 In TLR4 signalling TRIF is coupled to TLR4 through the bridging adaptor TRAM. PMID: 18706831, 18222170 One study published stated that stimulation with LPS led to TLR4 and TRAM co-localisation at the plasma membrane and also recruited TRIF. PMID: 18706831 This LPS stimulation then caused co-translocation of TRAM and TLR4 to endosomes where TRAF3 was recruited to TRIF allowing the activation of IFNbeta. PMID: 18706831 As it contains a TIR domain it binds directly to the TIR domain of TRIF thus blocking the interaction of TRIF with TLR3 or TRAM in the case of TLR4 signalling.

Go back
675.0, 263.0
25.0, 25.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c33 : 1
stoichiometry:c39 : 1

m1629*m16*0.1

nodelay

--

true

0

false

PMID: 18706831 The interaction between MyD88 and PKCepsilon leads its phosphorylation allowing it to interact with TLR4 and 14-3-3.

Go back
855.0, 291.0
25.0, 25.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c43 : 1
stoichiometry:c40 : 1
stoichiometry:c44 : 1

m22*m66*m28*0.1

nodelay

--

true

0

false

PMID: 18706831 The interaction between MyD88 and PKCepsilon leads its phosphorylation allowing it to interact with TLR4 and 14-3-3. PMID: 18706831, 18237277 These sites must be phosphorylated to allow the kinase to interact with 14-3-3 and induce downstream signals.

Go back
715.0, 291.0
25.0, 25.0

p16

p16

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c45 : 1
stoichiometry:c59 : 1

m567*m20*0.1

nodelay

--

true

0

false

PMID: 18706831 This is initiated however by the phosphorylation of S350 by the gamma/delta isoforms of p-38.

Go back
750.0, 290.0
27.0, 27.0

p17

p17

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c46 : 1
stoichiometry:c225 : 1

m1870*m20*0.1

nodelay

--

true

0

false

PMID: 18706831 This is initiated however by the phosphorylation of S350 by the gamma/delta isoforms of p-38.

Go back
823.0, 323.0
25.0, 25.0

p18

p18

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c52 : 1
stoichiometry:c54 : 1

m92*m24*0.1

nodelay

--

true

0

false

PMID: 18706831 PKCepsilon is phosphorylated on S346 by glycogen synthase kinase (GSK) and S368 by PKC.

Go back
790.0, 294.0
27.0, 27.0

p19

p19

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c47 : 1
stoichiometry:c48 : 1

m26*m29*0.1

nodelay

--

true

0

false

PMID: 18706831 PKCepsilon is phosphorylated on S346 by glycogen synthase kinase (GSK) and S368 by PKC.

Go back
549.0, 103.0
25.0, 25.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c6 : 1
stoichiometry:c5 : 1

m5*m43675*0.1

nodelay

--

true

0

false

PMID: 18706831, 12447441 Mal acts a bridging adaptor for MyD88, but only in the context of TLR2 and TLR4 stimulation.

Go back
879.0, 323.0
25.0, 25.0

p21

p21

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c62 : 1
stoichiometry:c61 : 1

m19005*m23*0.1

nodelay

--

true

0

false

PMID: 18706831 A key target for PKC¦Å is TRAM, which is required for TLR4 to signal IRF3 activation via TRIF. PMID: 18706831, 16757566 TRAM undergoes phosphorylation by PKCepsilon on serine 16 and this is required for TLR4 to signal.

Go back
1086.0, 322.0
27.0, 27.0

p22

p22

cso30:i:ME_Myristoylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c65 : 1
stoichiometry:c64 : 1

m30*m23*0.1

nodelay

--

true

0

false

PMID: 18706831, 16603631 It is regulated by myristoylation [34], which is required to localise it to the plasma membrane, and as stated in Section 2.2 it is also regulated by PKCepsilon.

Go back
936.0, 404.0
23.0, 23.0

p23

p23

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c67 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 18706831, 16603631 It is regulated by myristoylation [34], which is required to localise it to the plasma membrane, and as stated in Section 2.2 it is also regulated by PKCepsilon.

Go back
855.0, 835.0
25.0, 25.0

p24

p24

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c83 : 1
stoichiometry:c74 : 1
stoichiometry:c108 : 1
stoichiometry:c70 : 1

m977*m38*0.1

nodelay

--

true

0

false

PMID: 18706831 The ability of TRIF/TRAM to lead to the phosphorylation of IRF3 with subsequent induction of IFNbeta and RANTES was blocked in the presence of dynasore indicating TLR4 must be endocytosed to activate the TRIF-dependent pathway. PMID: 18706831 This interaction prevents the activation of IRF3, IRF7, NFkappaB and apoptosis by TRIF.

Go back
845.0, 879.0
25.0, 25.0

p25

p25

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c98 : 1
stoichiometry:c107 : 1
stoichiometry:c72 : 1

m977*m19305*0.1

nodelay

--

true

0

false

PMID: 18706831 This interaction prevents the activation of IRF3, IRF7, NFkappaB and apoptosis by TRIF.

Go back
587.0, 967.0
25.0, 25.0

p26

p26

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c77 : 1

m19324*0.1

nodelay

--

true

0

false

PMID: 18706831 The ability of TRIF/TRAM to lead to the phosphorylation of IRF3 with subsequent induction of IFNbeta and RANTES was blocked in the presence of dynasore indicating TLR4 must be endocytosed to activate the TRIF-dependent pathway.

Go back
644.0, 1016.0
23.0, 23.0

p27

p27

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c78 : 1

m19324*0.1

nodelay

--

true

0

false

PMID: 18706831 The ability of TRIF/TRAM to lead to the phosphorylation of IRF3 with subsequent induction of IFNbeta and RANTES was blocked in the presence of dynasore indicating TLR4 must be endocytosed to activate the TRIF-dependent pathway.

Go back
1000.0, 684.0
23.0, 23.0

p28

p28

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c79 : 1

m18*0.1

nodelay

--

true

0

false

PMID: 18706831 This LPS stimulation then caused co-translocation of TRAM and TLR4 to endosomes where TRAF3 was recruited to TRIF allowing the activation of IFNbeta.

Go back
967.0, 767.0
23.0, 23.0

p29

p29

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c81 : 1
stoichiometry:c82 : 1

m19*m1872*0.1

nodelay

--

true

0

false

PMID: 18706831 This LPS stimulation then caused co-translocation of TRAM and TLR4 to endosomes where TRAF3 was recruited to TRIF allowing the activation of IFNbeta.

Go back
76.0, 663.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m3964*m12*0.1

nodelay

--

true

0

false

PMID: 18706831, 12447441 Mal acts a bridging adaptor for MyD88, but only in the context of TLR2 and TLR4 stimulation.

Go back
466.0, 466.0
27.0, 27.0

p30

p30

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c86 : 1
stoichiometry:c189 : 1
stoichiometry:c85 : 1

m39*m16*0.1

nodelay

--

true

0

false

PMID: 18706831 Mal is recruited to TLR4 to initiate the MyD88-dependent pathway at the plasma membrane leading to NFkappaB activation. PMID: 18706831 The caspase-1 inhibitor YVAD-Cmk prevented NFkappaB activation in response to LPS and phosphorylation of p-38 in response to Pam3Cys linking caspase-1 activity to both these TLRs.

Go back
752.0, 628.0
23.0, 23.0

p31

p31

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c88 : 1
stoichiometry:c89 : 1

m18998*m41*0.1

nodelay

--

true

0

false

PMID: 18706831 As it contains a TIR domain it binds directly to the TIR domain of TRIF thus blocking the interaction of TRIF with TLR3 or TRAM in the case of TLR4 signalling.

Go back
465.0, 881.0
23.0, 23.0

p32

p32

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c92 : 1

m155666*0.1

nodelay

--

true

0

false

PMID: 18706831 It found that SARM protein levels but not mRNA levels were greatly upregulated after LPS stimulation.

Go back
219.0, 803.0
25.0, 25.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c94 : 1
stoichiometry:c96 : 1

m43*m41*0.1

nodelay

--

true

0

false

PMID: 18706831 SARM was then shown to interact with JNK3, which is involved in neuronal cell death during stress, and this interaction became more pronounced after induction of stress through UV light. PMID: 18706831 It binds the membrane via its ARM domain and recruits JNK3 to mitochondria when the cell is stressed. This leads to the activation of cell death.

Go back
71.0, 850.0
27.0, 27.0

p34

p34

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

e41

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1

m44*0.1

nodelay

--

true

0

false

PMID: 18706831 SARM was then shown to interact with JNK3, which is involved in neuronal cell death during stress, and this interaction became more pronounced after induction of stress through UV light.

Go back
494.0, 498.0
27.0, 27.0

p35

p35

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c105 : 1
stoichiometry:c101 : 1
stoichiometry:c100 : 1

m39*m19305*0.1

nodelay

--

true

0

false

PMID: 18706831 This interaction prevents the activation of IRF3, IRF7, NFkappaB and apoptosis by TRIF.

Go back
690.0, 610.0
27.0, 27.0

p36

p36

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c104 : 1
stoichiometry:c106 : 1
stoichiometry:c103 : 1

m980*m19305*0.1

nodelay

--

true

0

false

PMID: 18706831 This interaction prevents the activation of IRF3, IRF7, NFkappaB and apoptosis by TRIF.

Go back
1118.0, 542.0
27.0, 27.0

p37

p37

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c110 : 1

m19305*0.1

nodelay

--

true

0

false

PMID: 18706831 This interaction prevents the activation of IRF3, IRF7, NFkappaB and apoptosis by TRIF.

Go back
490.0, 538.0
27.0, 27.0

p38

p38

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c111 : 1
stoichiometry:c113 : 1
stoichiometry:c112 : 1

m39*m19*0.1

nodelay

--

true

0

false

PMID: 18706831 The downstream effect of TRAM is the activation of IRF3 and late activation of NFkappaB. PMID: 18706831 This interaction prevents the activation of IRF3, IRF7, NFkappaB and apoptosis by TRIF.

Go back
1071.0, 1063.0
25.0, 25.0

p39

p39

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c116 : 1
stoichiometry:c118 : 1

m46*m119368*0.1

nodelay

--

true

0

false

PMID: 18706831 These receptors are found in the cytoplasm and are crucial for binding dsRNA.

Go back
85.0, 712.0
24.0, 24.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m43675*m13*0.1

nodelay

--

true

0

false

PMID: 18706831, 12447441 Mal acts a bridging adaptor for MyD88, but only in the context of TLR2 and TLR4 stimulation.

Go back
1067.0, 1139.0
25.0, 25.0

p40

p40

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c115 : 1
stoichiometry:c117 : 1
stoichiometry:c119 : 1

m76904*m119368*0.1

nodelay

--

true

0

false

PMID: 18706831 These receptors are found in the cytoplasm and are crucial for binding dsRNA.

Go back
792.0, 1080.0
23.0, 23.0

p41

p41

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c120 : 1
stoichiometry:c121 : 1
stoichiometry:c122 : 1

m68199*m47*0.1

nodelay

--

true

0

false

PMID: 18706831 IPS1 is the downstream adaptor used by the receptors Retinoic acid-inducible gene I (RIG I) and Melanoma differentiation-associated gene 5 (Mda5).

Go back
835.0, 1107.0
25.0, 25.0

p42

p42

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c123 : 1
stoichiometry:c124 : 1
stoichiometry:c125 : 1

m68199*m48*0.1

nodelay

--

true

0

false

PMID: 18706831 IPS1 is the downstream adaptor used by the receptors Retinoic acid-inducible gene I (RIG I) and Melanoma differentiation-associated gene 5 (Mda5).

Go back
838.0, 918.0
27.0, 27.0

p43

p43

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c130 : 1
stoichiometry:c127 : 1

m977*m63*0.1

nodelay

--

true

0

false

PMID: 18706831, 16410796 IPS1 is then recruited to activate the transcription factors IRF3, NFkappaB and AP1.

Go back
819.0, 951.0
25.0, 25.0

p44

p44

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c128 : 1
stoichiometry:c131 : 1
stoichiometry:c129 : 1

m977*m49*0.1

nodelay

--

true

0

false

PMID: 18706831, 16410796 IPS1 is then recruited to activate the transcription factors IRF3, NFkappaB and AP1.

Go back
892.0, 950.0
27.0, 27.0

p45

p45

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c136 : 1
stoichiometry:c133 : 1

m219*m49*0.1

nodelay

--

true

0

false

PMID: 18706831, 16410796 IPS1 is then recruited to activate the transcription factors IRF3, NFkappaB and AP1.

Go back
894.0, 992.0
23.0, 23.0

p46

p46

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c137 : 1
stoichiometry:c135 : 1

m219*m63*0.1

nodelay

--

true

0

false

PMID: 18706831, 16410796 IPS1 is then recruited to activate the transcription factors IRF3, NFkappaB and AP1.

Go back
489.0, 581.0
27.0, 27.0

p47

p47

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c138 : 1
stoichiometry:c143 : 1
stoichiometry:c139 : 1

m39*m63*0.1

nodelay

--

true

0

false

PMID: 18706831, 16410796 IPS1 is then recruited to activate the transcription factors IRF3, NFkappaB and AP1.

Go back
481.0, 625.0
27.0, 27.0

p48

p48

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c140 : 1
stoichiometry:c142 : 1
stoichiometry:c141 : 1

m39*m49*0.1

nodelay

--

true

0

false

PMID: 18706831, 16410796 IPS1 is then recruited to activate the transcription factors IRF3, NFkappaB and AP1.

Go back
567.0, 891.0
25.0, 25.0

p49

p49

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c149 : 1
stoichiometry:c146 : 1

m93423*m18998*0.1

nodelay

--

true

0

false

PMID: 18706831 Both were also required for the increase in Ag-specific CD8+ T cell activation and hence IFNgamma production.

Go back
524.0, 262.0
27.0, 27.0

p5

p5

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c15 : 1
stoichiometry:c188 : 1
stoichiometry:c197 : 1
stoichiometry:c14 : 1

m14*m1765*m81*0.1

nodelay

--

true

0

false

PMID: 18706831 Caspase-1 cleaves Mal on aspartic acid 198 releasing a 4 kDa fragment of Mal from the C-terminus. This cleavage of Mal is required for activation of the TLR2 or TLR4 MyD88-dependent pathway. PMID: 18706831 Treatment of Mal with caspase-1 led to the cleavage of Mal at this position and this cleavage could be blocked with the caspase-1 inhibitor. PMID: 18706831 This finding therefore points to an important synergy between TLRs and NLRs that activate caspase-1. Activation of NLRs such as Nalp3 will therefore potentiate signalling by TLR2 and TLR4 via cleavage of Mal.

Go back
612.0, 896.0
23.0, 23.0

p50

p50

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c41 : 1
stoichiometry:c147 : 1

m93423*m49*0.1

nodelay

--

true

0

false

PMID: 18706831 Both were also required for the increase in Ag-specific CD8+ T cell activation and hence IFNgamma production.

Go back
588.0, 1120.0
23.0, 23.0

p51

p51

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c150 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18706831 At the mRNA level the IPS1-deficient mice showed a marked reduction in the expression of many cytokines including IFNalpha and beta, RANTES and IL6.

Go back
86.0, 254.0
27.0, 27.0

p52

p52

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c162 : 1
stoichiometry:c164 : 1

m1591*m67*0.1

nodelay

--

true

0

false

PMID: 18706831 Stimulation of the IL1RI/IL1RAcP complex by IL1beta leads to the activation of two signalling pathways in neurons.

Go back
223.0, 327.0
25.0, 25.0

p53

p53

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c165 : 1
stoichiometry:c166 : 1
stoichiometry:c167 : 1

m17284*m1572*0.1

nodelay

--

true

0

false

PMID: 18706831 The first involves MyD88-dependent induction of Src resulting in an inflammatory response.

Go back
644.0, 1128.0
23.0, 23.0

p54

p54

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c152 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18706831 At the mRNA level the IPS1-deficient mice showed a marked reduction in the expression of many cytokines including IFNalpha and beta, RANTES and IL6.

Go back
624.0, 1172.0
23.0, 23.0

p55

p55

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c154 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18706831 At the mRNA level the IPS1-deficient mice showed a marked reduction in the expression of many cytokines including IFNalpha and beta, RANTES and IL6.

Go back
615.0, 1215.0
25.0, 25.0

p56

p56

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c156 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18706831 At the mRNA level the IPS1-deficient mice showed a marked reduction in the expression of many cytokines including IFNalpha and beta, RANTES and IL6.

Go back
664.0, 1200.0
23.0, 23.0

p57

p57

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c155 : 1

m18998*0.1

nodelay

--

true

0

false

PMID: 18706831 mRNA from the TRIF-deficient mice also showed a decrease in expression of these cytokines but not to the same extent as IPS1.

Go back
644.0, 1232.0
23.0, 23.0

p58

p58

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c159 : 1
stoichiometry:c157 : 1

m18998*0.1

nodelay

--

true

0

false

PMID: 18706831 mRNA from the TRIF-deficient mice also showed a decrease in expression of these cytokines but not to the same extent as IPS1.

Go back
359.0, 1207.0
25.0, 25.0

p59

p59

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c169 : 1
stoichiometry:c168 : 1

m17272*0.1

nodelay

--

true

0

false

PMID: 18706831 The first involves MyD88-dependent induction of Src resulting in an inflammatory response.

Go back
393.0, 263.0
25.0, 25.0

p6

p6

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c25 : 1
stoichiometry:c18 : 1

m367*m14*m155666*0.1

nodelay

--

true

0

false

PMID: 18706831 Mal becomes phosphorylated on tyrosine 86 and 106 by Brutons tyrosine kinase (Btk). The phosphorylation of Mal on tyrosine 86, 106 and 159 has been shown to be central to activation of Mal signalling. PMID: 18706831, 16439361, 18070880 Two separate studies have reported that LPS induces phosphorylation of Mal on tyrosine 86, 106 and 159.

Go back
244.0, 1296.0
23.0, 23.0

p60

p60

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c170 : 1
stoichiometry:c171 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 18706831, 16771830 Src activation leads to induction of cyclooxygenase (COX) and interleukin 6 (IL6) among other molecules.

Go back
424.0, 1252.0
23.0, 23.0

p61

p61

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c172 : 1

m77*0.1

nodelay

--

true

0

false

PMID: 18706831, 16771830 Src activation leads to induction of cyclooxygenase (COX) and interleukin 6 (IL6) among other molecules.

Go back
481.0, 1281.0
21.0, 21.0

p62

p62

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c175 : 1
stoichiometry:c173 : 1

m77*0.1

nodelay

--

true

0

false

PMID: 18706831, 16771830 Src activation leads to induction of cyclooxygenase (COX) and interleukin 6 (IL6) among other molecules.

Go back
224.0, 425.0
23.0, 23.0

p63

p63

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c178 : 1
stoichiometry:c179 : 1
stoichiometry:c180 : 1

m68*m27*0.1

nodelay

--

true

0

false

PMID: 18706831 The second involves MyD88-independent activation of Akt by PI3-kinase which binds directly to the IL1RI when the receptor is phosphorylated. PMID: 18706831 It was revealed that the p85 subunit of PI3-kinase binds directly to IL1RI when the receptor is phosphorylated leading to the activation of Akt in the absence of MyD88.

Go back
86.0, 423.0
27.0, 27.0

p64

p64

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c176 : 1
stoichiometry:c177 : 1

m17284*0.1

nodelay

--

true

0

false

PMID: 18706831 The second involves MyD88-independent activation of Akt by PI3-kinase which binds directly to the IL1RI when the receptor is phosphorylated. PMID: 18706831 It was revealed that the p85 subunit of PI3-kinase binds directly to IL1RI when the receptor is phosphorylated leading to the activation of Akt in the absence of MyD88.

Go back
239.0, 484.0
25.0, 25.0

p65

p65

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c181 : 1
stoichiometry:c182 : 1
stoichiometry:c183 : 1

m69*m70*0.1

nodelay

--

true

0

false

PMID: 18706831 The second involves MyD88-independent activation of Akt by PI3-kinase which binds directly to the IL1RI when the receptor is phosphorylated. PMID: 18706831 It was revealed that the p85 subunit of PI3-kinase binds directly to IL1RI when the receptor is phosphorylated leading to the activation of Akt in the absence of MyD88.

Go back
597.0, 1329.0
29.0, 29.0

p66

p66

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c184 : 1
stoichiometry:c185 : 1
stoichiometry:c187 : 1
stoichiometry:c219 : 1
stoichiometry:c186 : 1

m72*m93248*m182*0.1

nodelay

--

true

0

false

PMID: 18706831 Male mice treated with the carcinogen diethylnitrosamine had higher IL6 production than female mice. This IL6 production in males is dependent on IKKbeta and is produced mainly by Kupffer cells in the liver. PMID: 18706831 Estrogens act as inhibitors of IL6 production in female Kupffer cells hence less female mice developed the cancer.

Go back
316.0, 280.0
23.0, 23.0

p67

p67

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c190 : 1
stoichiometry:c191 : 1
stoichiometry:c193 : 1
stoichiometry:c192 : 1

m74*m78*0.1

nodelay

--

true

0

false

PMID: 18706831 The caspase-1 inhibitor YVAD-Cmk prevented NFkappaB activation in response to LPS and phosphorylation of p-38 in response to Pam3Cys linking caspase-1 activity to both these TLRs.

Go back
152.0, 128.0
23.0, 23.0

p68

p68

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c194 : 1
stoichiometry:c195 : 1
stoichiometry:c196 : 1

m80*m79*0.1

nodelay

--

true

0

false

PMID: 18706831 This finding therefore points to an important synergy between TLRs and NLRs that activate caspase-1. Activation of NLRs such as Nalp3 will therefore potentiate signalling by TLR2 and TLR4 via cleavage of Mal.

Go back
277.0, 1161.0
25.0, 25.0

p69

p69

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c199 : 1
stoichiometry:c200 : 1
stoichiometry:c209 : 1
stoichiometry:c211 : 1
stoichiometry:c198 : 1

m93309*0.1

nodelay

--

true

0

false

PMID: 18706831, 17785847 In a recent study cells tolerised with lipid A for 24 h then restimulated with lipid A over several time points showed, as expected, a marked time-dependent decrease in TNFalpha and CCL3 production in comparison to non-tolerised cells. PMID: 18706831 The tolerance-induced downregulation of TNFalpha and CCL3 was significantly reduced in the absence of both TRIF and IRF3.

Go back
626.0, 260.0
23.0, 23.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c21 : 1

m6*m1572*0.1

nodelay

--

true

0

false

PMID: 18706831, 12447441 Mal acts a bridging adaptor for MyD88, but only in the context of TLR2 and TLR4 stimulation.

Go back
267.0, 1115.0
25.0, 25.0

p70

p70

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c203 : 1
stoichiometry:c202 : 1
stoichiometry:c208 : 1
stoichiometry:c210 : 1
stoichiometry:c201 : 1

m83*0.1

nodelay

--

true

0

false

PMID: 18706831, 17785847 In a recent study cells tolerised with lipid A for 24 h then restimulated with lipid A over several time points showed, as expected, a marked time-dependent decrease in TNFalpha and CCL3 production in comparison to non-tolerised cells. PMID: 18706831 The tolerance-induced downregulation of TNFalpha and CCL3 was significantly reduced in the absence of both TRIF and IRF3.

Go back
304.0, 988.0
23.0, 23.0

p71

p71

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c206 : 1
stoichiometry:c223 : 1
stoichiometry:c205 : 1

m82*m94230*0.1

nodelay

--

true

0

false

PMID: 18706831 Conversely IFNbeta and the anti-inflammatory cytokine IL10 were upregulated upon restimulation.

Go back
304.0, 940.0
23.0, 23.0

p72

p72

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c207 : 1
stoichiometry:c224 : 1
stoichiometry:c204 : 1

m82*m93217*0.1

nodelay

--

true

0

false

PMID: 18706831 Conversely IFNbeta and the anti-inflammatory cytokine IL10 were upregulated upon restimulation.

Go back
299.0, 715.0
25.0, 25.0

p73

p73

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c212 : 1
stoichiometry:c214 : 1
stoichiometry:c213 : 1

m199*0.1

nodelay

--

true

0

false

PMID: 18706831 The tolerised cells displayed inhibition of I§ÜB¦Á phosphorylation and decreased binding of RelA to the TNFalpha gene promoter demonstrating defective NFkappaB activity.

Go back
445.0, 1117.0
25.0, 25.0

p74

p74

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c215 : 1
stoichiometry:c217 : 1
stoichiometry:c218 : 1
stoichiometry:c216 : 1

m166*m86*0.1

nodelay

--

true

0

false

PMID: 18706831 The tolerised cells displayed inhibition of I§ÜB¦Á phosphorylation and decreased binding of RelA to the TNFalpha gene promoter demonstrating defective NFkappaB activity.

Go back
266.0, 854.0
23.0, 23.0

p75

p75

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c220 : 1
stoichiometry:c222 : 1
stoichiometry:c221 : 1

m1357*m82*0.1

nodelay

--

true

0

false

PMID: 18706831 However, an upregulation of STAT1 phosphorylation was observed demonstrating intact STAT1 activity.

Go back
85.0, 758.0
23.0, 23.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1

m1572*m11*0.1

nodelay

--

true

0

false

PMID: 18706831, 12447441 Mal acts a bridging adaptor for MyD88, but only in the context of TLR2 and TLR4 stimulation.

Go back
1067.0, 519.0
25.0, 25.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c28 : 1

m3965*m119368*0.1

nodelay

--

true

0

false

PMID: 18706831 TLR3 uses the adaptor TRIF to signal in response to double-stranded RNA.

Go back
421.0, 116.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
67.86537160314299, 75.82486488693087

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
433.003930122297, 524.0

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
528.3860222152281, 520.0735445069428

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
658.0, 621.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
665.0649257556593, 632.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
724.98328322499, 605.0

c104

c104

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
524.2074149689574, 524.3900814247444

c105

c105

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
717.6599944439228, 639.9873783754824

c106

c106

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
798.0, 739.0

c107

c107

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
801.0, 739.0

c108

c108

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1029.0, 564.9278069192927

c109

c109

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
115.67818143325864, 685.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
804.0, 564.7705543502079

c110

c110

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
427.0, 519.0

c111

c111

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
434.2228841505914, 559.0

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
522.8205444025001, 569.4882841452065

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
961.0, 1076.0

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
951.0, 1152.0

c115

c115

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1103.9996735419309, 524.0

c116

c116

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1099.9998445726303, 524.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
960.753348248749, 1079.0

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
909.887241331094, 1154.0

c119

c119

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
109.0, 724.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
798.0, 1110.906973581205

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
822.9195959492894, 1095.1313708498985

c121

c121

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
804.0, 1059.0

c122

c122

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
811.0, 1129.3332376839458

c123

c123

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
860.1716000756318, 1138.8262546692156

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
848.0, 1087.0

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
790.0, 863.0

c126

c126

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
796.0, 932.0

c127

c127

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
783.0, 863.0

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.1089652564389, 944.669143358162

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
468.0, 276.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
849.0, 952.9954589886285

c130

c130

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
814.0, 983.3404450024794

c131

c131

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
927.0, 964.0

c132

c132

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
919.0, 976.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
922.9619305082008, 977.0

c134

c134

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
917.0, 1004.0

c135

c135

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
820.0, 977.2399915200255

c136

c136

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
864.0, 1020.3517178529796

c137

c137

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
427.0, 526.0

c138

c138

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
434.998959620257, 595.0

c139

c139

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
551.0, 276.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
422.0, 527.0

c140

c140

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
434.1020362515914, 607.68253731564

c141

c141

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
509.97822940819464, 658.2623663226759

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
517.7951884238822, 614.4036058575982

c143

c143

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
552.0, 923.1554175279994

c144

c144

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
560.0, 923.1675379317294

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
580.0, 869.0

c146

c146

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
593.7705920107007, 867.4219507836357

c147

c147

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
597.5836354663645, 577.0

c149

c149

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
538.0, 297.0

c15

c15

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
600.0, 1104.0

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
656.0, 1108.0

c152

c152

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
595.0, 1184.0

c154

c154

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
594.7181105699019, 1190.104939246337

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
581.7721627102651, 1231.0

c156

c156

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.0, 1244.0

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
694.9999994214583, 566.0

c158

c158

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
674.9999992396248, 565.0

c159

c159

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
404.0, 295.9952479948287

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
121.0, 268.0

c162

c162

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
100.0, 232.0

c163

c163

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
113.0, 275.0

c164

c164

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
193.0, 319.0

c165

c165

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
256.0, 340.0

c166

c166

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
200.69168903663802, 348.0

c167

c167

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
384.0, 1220.0

c168

c168

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
27.575965950852094, 379.79546805470886

c169

c169

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
426.0, 276.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
273.87628710416527, 1279.0

c170

c170

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
267.0, 1308.0

c171

c171

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
447.0, 1257.9922778767136

c172

c172

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
502.0, 1259.5774527681926

c173

c173

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
324.0, 1270.7097557461818

c174

c174

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
324.0, 1293.710556345397

c175

c175

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
111.90425353058824, 330.0

c176

c176

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
113.0, 437.0

c177

c177

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
188.0, 437.0

c178

c178

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
255.0, 437.0

c179

c179

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
380.2680368629481, 288.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
190.02061355765503, 448.0

c180

c180

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
184.0, 497.0

c181

c181

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
271.90409627000884, 490.0

c182

c182

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
264.0, 502.0

c183

c183

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
612.0, 1366.0

c184

c184

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
567.0, 1258.0

c185

c185

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
626.0, 1344.0

c186

c186

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
619.4584433642289, 1361.7246399763383

c187

c187

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
342.0, 134.0

c188

c188

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
332.0, 134.0

c189

c189

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
579.0, 224.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
328.0, 134.0

c190

c190

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
287.0, 292.0

c191

c191

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
293.79712132958497, 299.0

c192

c192

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
278.0, 162.0

c193

c193

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
137.0, 123.0

c194

c194

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
164.0, 159.0

c195

c195

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
175.0, 148.0

c196

c196

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
256.0, 203.0

c197

c197

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
250.67492401257016, 1178.0

c198

c198

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
309.9952479948287, 1172.0

c199

c199

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
467.0, 134.1006753912829

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
624.0, 290.72674269787734

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
102.0, 1150.0

c200

c200

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
280.0, 1086.0

c201

c201

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
300.0, 1128.0

c202

c202

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
102.0, 1129.4099510907167

c203

c203

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
288.74093817917475, 945.019375177176

c204

c204

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
291.5508668509281, 991.6428033978249

c205

c205

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
99.0, 1012.2843362028667

c206

c206

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
96.0, 967.1675379317294

c207

c207

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
295.7155612142828, 938.0

c208

c208

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
305.57455383267245, 940.0

c209

c209

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
638.0, 234.99632943316306

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
294.98610620632246, 576.0

c210

c210

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
304.85699489110436, 577.0

c211

c211

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
330.0509053796172, 685.0

c212

c212

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
324.0, 728.0

c213

c213

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
89.0, 743.5156253461047

c214

c214

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
456.0, 1149.996329433163

c215

c215

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
470.0, 1130.0

c216

c216

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
477.5894663844041, 1109.0

c217

c217

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
102.0, 1131.1863862465857

c218

c218

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
522.0, 1345.6379617782632

c219

c219

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
52.15612605530123, 63.6887136344441

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
297.0, 866.0

c220

c220

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
289.0, 874.0

c221

c221

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
91.0, 883.5974939468912

c222

c222

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
334.2299027111483, 1008.4246907579123

c223

c223

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
334.2975039966728, 960.2781756235054

c224

c224

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
755.8374782761443, 221.95604362337124

c225

c225

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
114.87157579366851, 732.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
108.0, 770.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
406.0, 131.0

c25

c25

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1028.0, 516.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1099.6921915811265, 512.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1037.7733408252955, 535.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
944.3149107106393, 562.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
514.0, 127.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
914.0, 577.0

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
939.0, 616.5777087639997

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
533.0, 107.80645664500668

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
655.0, 227.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1035.9059162095775, 120.0

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1028.0, 460.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
890.49689686312, 577.0

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
898.0, 707.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
688.0, 296.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
688.0, 234.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
525.0, 135.35822534464594

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
875.9230655859195, 184.0

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
641.6564023547028, 919.4376015698018

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
887.4584480808471, 254.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
868.0, 324.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
880.0, 304.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
698.0, 226.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
707.0, 225.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
763.0, 214.0

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
804.0, 210.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
728.0, 324.0

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
562.0, 128.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
764.0, 325.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
836.0, 356.0

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
809.0, 202.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
673.3682832363589, 1040.0

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
843.0, 191.16569817229885

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
618.1310810416544, 1036.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
804.0, 329.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
652.8608672678599, 1043.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
644.2906239429769, 1046.0

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
731.0, 221.83268858753473

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
565.6031698891896, 135.83771945826052

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
892.0, 356.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
904.0, 336.0

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
911.7354940600271, 309.0

c62

c62

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
965.0, 336.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
973.7761477093286, 339.0

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1030.0, 310.0

c65

c65

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
948.0, 385.0

c66

c66

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
959.0, 416.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1018.0, 127.3518111056537

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
791.0, 848.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
107.61541201655622, 634.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
794.003930122297, 859.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
791.0, 856.0

c71

c71

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.2299027111483, 898.0

c72

c72

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
907.0, 695.0

c73

c73

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
883.8057780742176, 853.2312811416587

c74

c74

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
619.7081432770395, 937.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
673.1514318217986, 945.0

c76

c76

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
600.0, 992.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
656.0, 1039.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
945.998959620257, 695.1290154777461

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
88.0, 609.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
941.0, 752.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
933.0, 794.191572848662

c81

c81

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
921.0, 779.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.2491077284276, 799.0

c83

c83

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
427.0, 490.352465419694

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
425.01139025930786, 493.0

c85

c85

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
498.3384768826856, 227.0

c86

c86

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
782.1322622749697, 571.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
527.0, 655.2699304724769

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
768.0, 651.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
101.0, 676.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
804.0, 655.9879530136906

c90

c90

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
804.0, 700.1493915422653

c91

c91

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
488.0, 870.4929882637098

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
407.0, 131.0

c93

c93

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
251.92382234326735, 819.1013807118055

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
232.0, 779.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
183.50986776965388, 825.0

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
106.0, 864.0

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
877.9999998088044, 606.0

c98

c98

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
427.0, 512.0

c99

c99

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back