1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/17449723.csml convertedTime:2009.07.01.11:03

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling.
Authors Sheedy FJ, O'Neill LA.
Affiliation School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.sheedyf@tcd.ie
Abstract Signaling by two of the most important bacteria-sensing TLRs, TLR2 and TLR4,involves two adaptor proteins, MyD88 adaptor-like (Mal) and Toll/IL-1 receptor(TIR) domain-containing adaptor-inducing IFN-beta (Trif)-related adaptormolecule (TRAM). Recently, new insights into the functioning of these twoadapters have emerged. Mal is required by both TLRs to act as a bridge torecruit the adaptor MyD88, leading ultimately to NF-kappaB activation.Similarly, TRAM acts as a bridge to recruit TRIF to the TLR4 complex, leading toactivation of the transcription factor IFN regulatory factor 3. Consistent withMal and TRAM being key points of control, recent evidence suggests that they aresubject to regulation by phosphorylation. Further, a variant in Mal in humanshas been found to protect against multiple infectious diseases. Finally, anotherTIR domain-containing adaptor, sterile alpha and HEAT/armadillo motif protein(SARM), has been shown to act as an inhibitor of TRIF-dependent signaling. Theserecent discoveries add to the complexity of TLR signaling and highlight specificcontrol mechanisms for TLR2 and TLR4 signaling.
PMID 17449723
Model Abstract

Entity

G010329:TNF-alpha G010539:SOCS1 MO000000022:p38 MO000000023:JNK MO000000065:RIP1 MO000000077:MAPKs MO000000179:ARF6 MO000000212:TRAF6 MO000000213:IRAK-1 MO000000289:TNF-alpha MO000000331:PIP2 MO000001935:Btk MO000007685:IRF-1 MO000007700:IRF-5 MO000007702:IRF-7 MO000016573:MyD88 MO000016597:IL-1beta MO000016645:PKCepsilon MO000016828:Caspase-1 MO000016882:LPS MO000017004:SOCS-1 MO000017291:integrins MO000019331:TBK1 MO000019394:TLR4 : TLR4 MO000019395:TLRs MO000019397:TLR2 MO000019449:proIL-1beta MO000019479:protein remnants MO000022224:dsRNA MO000033294:p50:RelA-p65{p} MO000039077:IRAK-4 MO000041125:TRIF MO000041132:TRAM MO000041456:IRF-3{p} MO000068831:MAL e1: e10: e11:LPS: TLR4: TLR4 e12:p38 {activated} e13:LPS: TLR4: TLR4: MAL e14:MAPKs {activated} e15:TLR adaptor e16:TLR ligand: TLR: TLR adaptor e17:TLR ligand: TLR: TLR adaptor: IRAK-1 e18:TLR ligand: TLR: TLR adaptor: IRAK: TRAF6 e19:IRFs e2: e20:IRFs {activated} e21:p50:RelA-p65 e22:cytokines e23:MAL: PIP2 e24:LPS: TLR4: TLR4: MAL: MyD88 e25:LPS: TLR4: TLR4: MAL: MyD88: IRAK-1: IRAK-4 e26:MAL: TRAF6 e27:LPS: TLR4: TLR4: MAL: MyD88: IRAK-1: IRAK-4: TRAF6 e28:Btk {activated} e29:TLR2 ligand e3: e30:TLR2 ligand: TLR2 e31:LPS: TLR4: TLR4: MAL {p}: MyD88: IRAK-1: IRAK-4: TRAF6 e32:LPS: TLR4: TLR4: MAL {p}: MyD88: IRAK-1: IRAK-4: TRAF6: SOCS-1 e33:LPS: TLR4: MAL {p}{ub}: MyD88: IRAK-1: IRAK-4: TRAF6: SOCS-1 e34:E3 ligase e35:TLR2 ligand: TLR2: MAL e36:TLR2 ligand: TLR2: MAL: MyD88 e37:LPS: TLR4: TLR4: TRAM {myristoylated} e38:LPS: TLR4: TLR4: TRAM{myristpylated}: TRIF e39:IRF-1 [activated} e4: e40:IRF-3 e41:IRF-5 {activated} e42:IRF-7 {activated} e43:JNK {activated} e44:LPS: TLR4: TLR4: TRAM{myristpylated}: TRIF: TBK1 e45:TRAM {myristpylated} e46:LPS: TLR4: TLR4: TRAM{myristpylated}: TRIF: TRAF6: RIP1 e47:PKCepsilon {activated} e48:LPS: TLR4: TLR4: TRAM{myristpylated} {p}: TRIF: TBK1 e49:LPS: TLR4: TLR4: TRAM{myristpylated} {p}: TRIF: TRAF6: RIP1 e5:TLR ligand e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:TLR ligand: TLR e60: e61: e62: e63:diacyglycerol e64:ARF6 {activated} e65:PI-5K e66:PI-5K {activated} e67:CD11b e69:SopB e7: e70:Nalp1: Nalp3: Ipaf e71:PAMP e72:PAMP: Nalp1: Nalp3: Ipaf e73:Caspase-1 {activated} e74:Caspase-1 {activated}: MAL e75:SARM e76:TRIF: SARM e77:SARM e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 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 p55 p56 p57 p58 p59 p6 p60 p61 p62 p7 p8 p9
Model Detail
537.0, 1097.0
29.0, 29.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
718.0, 1046.0
28.0, 28.0

SOCS1

--

G010539

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p23

--

true true true true

csml-variable:Double

m93501

10

false

infinite

0

unit false false false
TRANSFACG010539

--

Go back
443.0, 219.0
25.0, 25.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m20

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
525.0, 285.0
30.0, 30.0

JNK

--

MO000000023

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m21

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
379.0, 771.0
25.0, 25.0

RIP1

--

MO000000065

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m48

10

false

infinite

0

unit false false false
InterProIPR000198
TRANSPATHMO000000065

--

Go back
528.0, 220.0
32.0, 32.0

MAPKs

--

MO000000077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p40

true true true true

csml-variable:Double

m69

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
1001.0, 1073.0
30.0, 30.0

ARF6

--

MO000000179

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m158

10

false

infinite

0

unit false false false
InterProIPR006688
TRANSPATHMO000000179

--

Go back
629.0, 453.0
30.0, 30.0

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
631.0, 419.0
25.5, 25.5

IRAK-1

--

MO000000213

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m184

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000213

--

Go back
598.0, 722.0
28.0, 28.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
1074.0, 254.0
28.0, 28.0

PIP2

--

MO000000331

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m290229

10

false

infinite

0

unit false false false
TRANSPATHMO000000331

--

Go back
867.0, 215.0
26.0, 26.0

Btk

--

MO000001935

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18 p20

true true true true

csml-variable:Double

m367

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000001935

--

Go back
641.0, 497.0
29.0, 29.0

IRF-1

--

MO000007685

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p32 p35

true true true true

csml-variable:Double

m970

10

false

infinite

0

unit false false false
InterProIPR001346
TRANSPATHMO000007685

--

Go back
677.0, 561.0
30.0, 30.0

IRF-5

--

MO000007700

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33 p36

true true true true

csml-variable:Double

m979

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007700

--

Go back
720.0, 636.0
32.0, 32.0

IRF-7

--

MO000007702

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34 p37

true true true true

csml-variable:Double

m980

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
906.0, 398.0
28.0, 28.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
806.0, 770.0
28.0, 28.0

IL-1beta

--

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

--

p59

--

true true true true

csml-variable:Double

m1591

10

false

infinite

0

unit false false false
TRANSPATHMO000016597

--

Go back
504.0, 830.0
30.0, 30.0

PKCepsilon

--

MO000016645

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p46

true true true true

csml-variable:Double

m1629

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016645

--

Go back
637.0, 273.0
29.0, 29.0

Caspase-1

--

MO000016828

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p57

true true true true

csml-variable:Double

m1765

10

false

infinite

0

unit false false false
TRANSPATHMO000016828

--

Go back
1105.0, 61.0
29.0, 29.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
1016.0, 616.0
23.0, 23.0

SOCS-1

--

MO000017004

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m1906

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017004

--

Go back
1157.0, 1029.0
30.0, 30.0

integrins

--

MO000017291

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m2142

10

false

infinite

0

unit false false false
TRANSPATHMO000017291

--

Go back
346.0, 644.0
26.0, 26.0

TBK1

--

MO000019331

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m3902

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000019331

--

Go back
1077.0, 129.0
30.0, 30.0

TLR4 : TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
414.0, 168.0
26.0, 26.0

TLRs

--

MO000019395

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m3962

10

false

infinite

0

unit false false false
TRANSPATHMO000019395

--

Go back
946.0, 154.0
28.0, 28.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
800.0, 728.0
32.0, 32.0

proIL-1beta

--

MO000019449

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p59

true true true true

csml-variable:Double

m4012

10

false

infinite

0

unit false false false
InterProIPR003297
TRANSPATHMO000019449

--

Go back
946.0, 802.0
28.0, 28.0

protein remnants

--

MO000019479

cso30:c:Protein

cso30:i:CC_CellComponent

--

p25 p49 p50

--

true true true true

csml-variable:Double

m360980

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
118.0, 398.0
30.0, 30.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p61

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
394.0, 410.0
36.0, 36.0

p50:RelA-p65{p}

--

MO000033294

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m11984

10

false

infinite

0

unit false false false
TRANSPATHMO000033294

--

Go back
850.0, 458.0
28.0, 28.0

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
342.0, 582.0
28.0, 28.0

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
514.0, 562.0
28.0, 28.0

TRAM

--

MO000041132

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19005

10

false

infinite

0

unit false false false
TRANSPATHMO000041132

--

Go back
357.0, 719.0
28.0, 28.0

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
922.0, 310.0
28.0, 28.0

MAL

--

MO000068831

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p15 p26 p58

true true true true

csml-variable:Double

m43675

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
188.75, 126.99690800911759
933.9056330923531, 1356.0309792500955

--

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
243.0, 255.0
829.9775981223105, 1167.545103664102

--

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
1072.625, 196.5
31.279245125812363, 38.301116480586565

LPS: TLR4: TLR4

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
444.0, 268.0
23.0, 23.0

p38 {activated}

--

e12

cso30:c:Protein

cso30:i:CC_CellComponent

--

p38

--

true true true true

csml-variable:Double

m12

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
1076.875, 343.5
30.01674619196183, 41.88383189576069

LPS: TLR4: TLR4: MAL

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
552.0, 264.0
32.0, 32.0

MAPKs {activated}

--

e14

cso30:c:Protein

cso30:i:CC_CellComponent

--

p40

--

true true true true

csml-variable:Double

m14

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
334.25, 217.5
16.520579981290926, 38.1244153414406

TLR adaptor

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
303.875, 156.5
29.606395668930077, 41.311249770600114

TLR ligand: TLR: TLR adaptor

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

p6

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
223.875, 172.5
29.606395668930077, 41.311249770600114

TLR ligand: TLR: TLR adaptor: IRAK-1

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p6

p7

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
228.875, 269.5
28.114929344833914, 39.23013396953569

TLR ligand: TLR: TLR adaptor: IRAK: TRAF6

--

e18

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
297.125, 440.5
20.422972429060174, 33.118333668746224

IRFs

--

e19

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p9

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
188.75, 126.99690800911759
933.9056330923531, 1356.0309792500955

--

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
353.125, 428.5
20.422972429060174, 33.118333668746224

IRFs {activated}

--

e20

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
397.0, 357.0
30.0, 30.0

p50:RelA-p65

--

e21

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m17

10

false

infinite

0

unit false false false
TRANSPATHMO000016632

--

Go back
480.5, 1053.0
45.0, 24.0

cytokines

--

e22

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p10 p11

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
1076.625, 293.5
29.8993084485919, 36.61139810031661

MAL: PIP2

--

e23

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
1077.875, 391.5
28.785694622866583, 40.166085520278955

LPS: TLR4: TLR4: MAL: MyD88

--

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1075.875, 441.5
32.25, 45.0

LPS: TLR4: TLR4: MAL: MyD88: IRAK-1: IRAK-4

--

e25

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
854.625, 395.5
27.27007998666889, 33.39193467755374

MAL: TRAF6

--

e26

cso30:c:Complex

cso30:i:CC_Cytosol

--

p15

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
1075.875, 513.5
32.25, 45.0

LPS: TLR4: TLR4: MAL: MyD88: IRAK-1: IRAK-4: TRAF6

--

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
868.0, 264.0
24.0, 24.0

Btk {activated}

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m30

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000001935

--

Go back
866.5, 26.375
32.170474516695954, 20.910808435852374

TLR2 ligand

--

e29

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p19

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
207.42811266184708, 145.67502067096473
896.5494077686591, 1318.6747539264024

--

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
869.625, 144.5
27.670179970004998, 33.88185302449591

TLR2 ligand: TLR2

--

e30

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
1067.875, 568.5
39.360111947146265, 54.92108643787851

LPS: TLR4: TLR4: MAL {p}: MyD88: IRAK-1: IRAK-4: TRAF6

--

e31

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
1072.875, 645.5
37.797623417140755, 52.740869884382455

LPS: TLR4: TLR4: MAL {p}: MyD88: IRAK-1: IRAK-4: TRAF6: SOCS-1

--

e32

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
1068.875, 715.5
46.39920168838319, 64.74307212332538

LPS: TLR4: MAL {p}{ub}: MyD88: IRAK-1: IRAK-4: TRAF6: SOCS-1

--

e33

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
1013.5, 677.125
28.359999999999996, 21.269999999999996

E3 ligase

--

e34

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p24

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
803.875, 137.5
32.25, 45.0

TLR2 ligand: TLR2: MAL

--

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
721.875, 126.5
36.57446320425766, 51.03413470361534

TLR2 ligand: TLR2: MAL: MyD88

--

e36

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
210.875, 542.5
32.25, 45.0

LPS: TLR4: TLR4: TRAM {myristoylated}

--

e37

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
210.875, 590.5
32.25, 45.0

LPS: TLR4: TLR4: TRAM{myristpylated}: TRIF

--

e38

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
645.0, 525.0
29.0, 29.0

IRF-1 [activated}

--

e39

cso30:c:Protein

cso30:i:CC_CellComponent

--

p32 p35

--

true true true true

csml-variable:Double

m41

10

false

infinite

0

unit false false false
InterProIPR001346
TRANSPATHMO000007685

--

Go back
241.9826210862642, 178.36171782919683
827.4403909198251, 1253.3013596099365

--

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
358.0, 684.0
26.0, 26.0

IRF-3

--

e40

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
669.0, 593.0
30.0, 30.0

IRF-5 {activated}

--

e41

cso30:c:Protein

cso30:i:CC_CellComponent

--

p33 p36

--

true true true true

csml-variable:Double

m43

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007700

--

Go back
716.0, 668.0
32.0, 32.0

IRF-7 {activated}

--

e42

cso30:c:Protein

cso30:i:CC_CellComponent

--

p34 p37

--

true true true true

csml-variable:Double

m44

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
549.0, 333.0
30.0, 30.0

JNK {activated}

--

e43

cso30:c:Protein

cso30:i:CC_CellComponent

--

p4

--

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
202.5, 669.0
40.35639566893008, 56.311249770600114

LPS: TLR4: TLR4: TRAM{myristpylated}: TRIF: TBK1

--

e44

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
339.5, 537.125
31.240000000000002, 23.429999999999996

TRAM {myristpylated}

--

e45

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
204.5, 759.0
36.76582859240227, 51.30115617544504

LPS: TLR4: TLR4: TRAM{myristpylated}: TRIF: TRAF6: RIP1

--

e46

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
329.0, 829.0
30.0, 30.0

PKCepsilon {activated}

--

e47

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m63

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016645

--

Go back
205.5, 833.0
34.87190310148651, 48.65846944393466

LPS: TLR4: TLR4: TRAM{myristpylated} {p}: TRIF: TBK1

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
208.5, 893.0
38.39144797210497, 53.5694622866581

LPS: TLR4: TLR4: TRAM{myristpylated} {p}: TRIF: TRAF6: RIP1

--

e49

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
410.0, 54.5
33.49736379613357, 21.77328646748682

TLR ligand

--

e5

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
410.0, 925.0
424.12779856071256, 384.6373145234026

--

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
455.80896148327986, 934.1153451795033
248.00023975430878, 372.7901693122095

--

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
415.5286677652234, 930.1337629248503
413.0704630302659, 374.3697886737018

--

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
416.3184774459696, 930.9235726055964
411.4908436687733, 372.7901693122095

--

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
410.0, 925.0
424.12779856071256, 384.6373145234026

--

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
410.0, 925.0
424.12779856071256, 384.6373145234026

--

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
416.3184774459696, 930.9235726055964
411.4908436687733, 372.7901693122095

--

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
719.6053948525126, 1082.9619361492414
26.497174482156286, 23.986915847004674

--

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
650.1021429468466, 1193.5352914537102
75.03191967088955, 67.92363254417378

--

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
410.0, 925.0
424.12779856071256, 384.6373145234026

--

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
356.625, 158.5
29.499208465255794, 36.12147975337444

TLR ligand: TLR

--

e6

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p5

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
509.9645357178972, 1095.9296442899054
13.431504190080103, 6.467020535964499

--

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
509.51601977402197, 1076.6434587032716
45.972884247208384, 82.7511916449751

--

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
528.8022053606561, 1130.4653719682963
7.1762551020032515, 7.176255102003254

--

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
378.0, 888.0
43.62489486963835, 24.72077375946173

diacyglycerol

--

e63

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p46

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
945.0, 1029.0
30.0, 30.0

ARF6 {activated}

--

e64

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m67

10

false

infinite

0

unit false false false
InterProIPR006688
TRANSPATHMO000000179

--

Go back
1002.0, 921.5
27.839999999999996, 20.880000000000003

PI-5K

--

e65

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p52

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
938.0, 965.5
27.839999999999996, 20.880000000000003

PI-5K {activated}

--

e66

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
949.5, 353.125
28.52, 21.39

CD11b

--

e67

cso30:c:Protein

cso30:i:CC_Cytoplasm

--

--

p3

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
1192.5, 344.125
31.720000000000002, 23.789999999999996

SopB

--

e69

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p12

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
200.0, 132.0
839.7237354966342, 1189.8668429177399

--

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
602.875, 208.5
27.238988805285373, 38.00789135621215

Nalp1: Nalp3: Ipaf

--

e70

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p56

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
593.5, 59.25
38.313708999158955, 21.711101766190076

PAMP

--

e71

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p56

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
692.875, 259.5
29.535373463020736, 41.212149018168475

PAMP: Nalp1: Nalp3: Ipaf

--

e72

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
693.0, 353.0
29.0, 29.0

Caspase-1 {activated}

--

e73

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m77

10

false

infinite

0

unit false false false
TRANSPATHMO000016828

--

Go back
801.625, 326.5
28.25808198633561, 34.60173304449258

Caspase-1 {activated}: MAL

--

e74

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
436.5, 499.125
30.111692493459444, 18.568877037633328

SARM

--

e75

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p60 p61

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
413.625, 622.5
29.180761539743376, 35.73154474254291

TRIF: SARM

--

e76

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
713.5, 1138.0
37.110726643598625, 19.792387543252595

SARM

--

e77

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p62

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
203.0, 153.0
805.5569854171277, 1169.6687428256696

--

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
251.0, 174.0
801.8791759029863, 1154.3288303559784

--

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
414.0, 104.0
25.0, 25.0

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

m5*m3962*0.1

nodelay

--

true

0

false

PMID: 17449723 Upon activation, TLRs interact intracellularly with these adaptor proteins via TIR domains, and the adaptor proteins then recruit and activate downstream molecules such as IL-1R-associated kinases (IRAKs) and TNF-receptor-associated factor-6 (TRAF6), which then amplify the signal.

Go back
503.0, 997.0
23.0, 23.0

p10

p10

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c30 : 1

m11984*0.1

nodelay

--

true

0

false

PMID: 17449723, 16698941 TLR signaling ultimately results in the activation of transcription factors such as NF-{kappa}B and IFN regulatory factors (IRFs), which promote the transcription of proinflammatory cytokines and other proteins that promote host defense.

Go back
475.0, 1001.0
23.0, 23.0

p11

p11

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c29 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 17449723, 16698941 TLR signaling ultimately results in the activation of transcription factors such as NF-{kappa}B and IFN regulatory factors (IRFs), which promote the transcription of proinflammatory cytokines and other proteins that promote host defense.

Go back
970.0, 298.0
27.0, 27.0

p12

p12

cso30:i:ME_Colocalization

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c33 : 1
stoichiometry:c167 : 1
stoichiometry:c32 : 1
stoichiometry:c34 : 1

m11*m25*0.1

nodelay

--

true

0

false

PMID: 17449723 It colocalizes with TLR4. PMID: 17449723, 10589680 It was also shown that the localization of Mal to the plasma membrane by PIP2 binding is dependent on the ¦Â2-integrin CD11b in macrophages and also on the GTPase ADP ribosylation factor 6 (ARF6), which regulates production of PIP2 via activation of the enzyme PI-5K. PMID: 17449723, 16751103 his protein has been shown to interrupt Mal localization and therefore, disrupt TLR4 signaling.

Go back
1002.0, 398.0
27.0, 27.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c165 : 1
stoichiometry:c36 : 1

m1572*m13*0.1

nodelay

--

true

0

false

PMID: 17449723 This leads to MyD88 recruitment to the Mal/TLR4 complex. MyD88 can then interact with downstream signaling molecules such as IRAK-4 and IRAK-1.

Go back
1194.0, 494.0
27.0, 27.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c40 : 1

m184*m17258*m26*0.1

nodelay

--

true

0

false

PMID: 17449723 This leads to MyD88 recruitment to the Mal/TLR4 complex. MyD88 can then interact with downstream signaling molecules such as IRAK-4 and IRAK-1.

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880.0, 336.0
23.0, 23.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c43 : 1

m183*m43675*0.1

nodelay

--

true

0

false

PMID: 17449723 It was shown that Mal can bind TRAF6 directly and that mutating this TRAF6-binding site creates a dominant-negative mutant of NF-{kappa}B activation and activation of MAPKs by TLR2 and TLR4.

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922.0, 516.0
25.0, 25.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c46 : 1
stoichiometry:c45 : 1

m183*m27*0.1

nodelay

--

true

0

false

PMID: 17449723 MyD88 does, however, bind IRAK-1, which contains a TRAF6-binding site, leading to NF-{kappa}B activation.

Go back
489.0, 417.0
21.0, 21.0

p17

p17

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c49 : 1
stoichiometry:c48 : 1

m17*m29*0.1

nodelay

--

true

0

false

PMID: 17449723 MyD88 does, however, bind IRAK-1, which contains a TRAF6-binding site, leading to NF-{kappa}B activation. PMID: 17449723 This phosphorylation is required for the activation of a pathway culminating in transactivation by the NF-{kappa}B subunit p65 via phosphorylation on serine 536.

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988.0, 216.0
23.0, 23.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c52 : 1

m155666*m367*0.1

nodelay

--

true

0

false

PMID: 17449723 By an as-yet-unknown mechanism, Btk is activated following LPS stimulation of the cell.

Go back
869.0, 83.0
27.0, 27.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c57 : 1
stoichiometry:c58 : 1

m31*m3964*0.1

nodelay

--

true

0

false

PMID: 17449723 Mal recruits MyD88 to TLR2 and TLR4, and TRAM recruits TRIF to TLR4.

Go back
1188.0, 168.0
23.0, 23.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m155666*m3961*0.1

nodelay

--

true

0

false

PMID: 17449723 In cases of infection, LPS, derived from gram-negative bacteria, binds TLR4 dimers.

Go back
923.0, 263.0
25.0, 25.0

p20

p20

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c55 : 1
stoichiometry:c54 : 1

m367*m32*0.1

nodelay

--

true

0

false

PMID: 17449723, 16439361 Gray et al. [27 ] demonstrated that Mal can be tyrosine-phosphorylated at residues 86 and 187 by Bruton¡Çs tyrosine kinase (Btk) following activation of TLR2 and TLR4.

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975.0, 439.0
25.0, 25.0

p21

p21

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c166 : 1
stoichiometry:c60 : 1

m30*m29*0.1

nodelay

--

true

0

false

PMID: 17449723, 16439361 Gray et al. [27 ] demonstrated that Mal can be tyrosine-phosphorylated at residues 86 and 187 by Bruton¡Çs tyrosine kinase (Btk) following activation of TLR2 and TLR4.

Go back
1200.0, 584.0
23.0, 23.0

p22

p22

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c63 : 1
stoichiometry:c62 : 1

m33*m1906*0.1

nodelay

--

true

0

false

PMID: 17449723 SOCS-1 recognizes a proline, glutamic acid, serine, and threonine-rich area domain (PEST) in Mal, N-terminal to its TIR domain and subsequently, targets Mal for degradation by the addition of ubiquitin to lysine side-chains at amino acid positions 15 and 16. PMID: 17449723 Phospho-Mal is recognized by the ubiquitin ligase SOCS-1 (whose expression also increases in response to LPS).

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721.0, 993.0
21.0, 21.0

p23

p23

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m155666*0.1

nodelay

--

true

0

false

PMID: 17449723 Phospho-Mal is recognized by the ubiquitin ligase SOCS-1 (whose expression also increases in response to LPS).

Go back
1011.0, 719.0
25.0, 25.0

p24

p24

cso30:i:ME_Ubiquitination

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c67 : 1
stoichiometry:c68 : 1

m36*m34*0.1

nodelay

--

true

0

false

PMID: 17449723 SOCS-1 uses its E3 ligase activity to attach ubiquitin residues to Mal.

Go back
972.0, 736.0
23.0, 23.0

p25

p25

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c71 : 1
stoichiometry:c141 : 1
stoichiometry:c142 : 1
stoichiometry:c143 : 1
stoichiometry:c144 : 1
stoichiometry:c145 : 1
stoichiometry:c146 : 1

m35*0.1

nodelay

--

true

0

false

PMID: 17449723 This ubiquitination step targets Mal for degradation by the 26S proteasome.Mal is removed from the membrane. MyD88 can no longer interact directly with TLR4 and also leaves the membrane.

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804.0, 228.0
23.0, 23.0

p26

p26

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c73 : 1
stoichiometry:c74 : 1

m43675*m32*0.1

nodelay

--

true

0

false

PMID: 17449723 Mal recruits MyD88 to TLR2 and TLR4, and TRAM recruits TRIF to TLR4.

Go back
755.0, 227.0
26.0, 26.0

p27

p27

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c76 : 1
stoichiometry:c77 : 1

m1572*m37*0.1

nodelay

--

true

0

false

PMID: 17449723 Mal recruits MyD88 to TLR2 and TLR4, and TRAM recruits TRIF to TLR4.

Go back
291.0, 553.0
23.0, 23.0

p28

p28

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c119 : 1
stoichiometry:c79 : 1

m11*m47*0.1

nodelay

--

true

0

false

PMID: 17449723 Mal recruits MyD88 to TLR2 and TLR4, and TRAM recruits TRIF to TLR4. PMID: 17449723 TRAM is myristoylated in its N-terminus and becomes attached to the membrane in association with TLR4.

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600.0, 800.0
23.0, 23.0

p29

p29

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c118 : 1
stoichiometry:c112 : 1

m93309*m19324*0.1

nodelay

--

true

0

false

PMID: 17449723, 16166516 The effect of TRIF here is to induce TNF-{alpha} production via activation of IRF3, with TNF-{alpha} acting in an autocrine manner to induce the late activation of NF-{kappa}B.

Go back
963.0, 255.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c161 : 1
stoichiometry:c6 : 1

m290229*m43675*m71*0.1

nodelay

--

true

0

false

PMID: 17449723 i) Mal is synthesized and produced and ii) binds PIP2 in the plasma membrane via its PIP2-binding domain. PMID: 17449723, 10589680 It was also shown that the localization of Mal to the plasma membrane by PIP2 binding is dependent on the ¦Â2-integrin CD11b in macrophages and also on the GTPase ADP ribosylation factor 6 (ARF6), which regulates production of PIP2 via activation of the enzyme PI-5K.

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291.0, 601.0
24.0, 24.0

p30

p30

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c193 : 1
stoichiometry:c164 : 1
stoichiometry:c82 : 1

m18998*m39*0.1

nodelay

--

true

0

false

PMID: 17449723 Mal recruits MyD88 to TLR2 and TLR4, and TRAM recruits TRIF to TLR4. PMID: 17449723 This leads to the recruitment of TRIF to the TRAM/TLR4 complex. PMID: 17449723 It was also shown that treatment of cells with LPS enhances SARM expression, and it has been speculated that following TLR4 activation, SARM levels increase in cells and eventually bind TRIF to limit the LPS-driven response.

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465.0, 377.0
25.0, 25.0

p31

p31

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c12 : 1
stoichiometry:c83 : 1

m38*m17*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
701.0, 537.0
21.0, 21.0

p32

p32

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c98 : 1
stoichiometry:c85 : 1

m970*m29*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
756.0, 596.0
23.0, 23.0

p33

p33

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c97 : 1
stoichiometry:c87 : 1

m979*m29*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
804.0, 672.0
23.0, 23.0

p34

p34

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c96 : 1
stoichiometry:c89 : 1

m980*m29*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
700.0, 500.0
23.0, 23.0

p35

p35

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c90 : 1
stoichiometry:c99 : 1
stoichiometry:c91 : 1

m970*m38*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
756.0, 564.0
23.0, 23.0

p36

p36

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c101 : 1
stoichiometry:c93 : 1

m979*m38*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
804.0, 640.0
23.0, 23.0

p37

p37

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c102 : 1
stoichiometry:c95 : 1

m980*m38*0.1

nodelay

--

true

0

false

PMID: 17449723 The MyD88 pathway leads to activation of the transcription factors NF-{kappa}B, IRF1, IRF5, and IRF7.

Go back
396.0, 220.0
23.0, 23.0

p38

p38

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c108 : 1
stoichiometry:c105 : 1

m20*m19*0.1

nodelay

--

true

0

false

PMID: 17449723, 12609980 Following the discovery that activation of NF-{kappa}B, p38 MAPK, and JNK was impaired in MyD88-deficient cells in response to all TLRs, except in the case of TLR3.

Go back
443.0, 1099.0
25.0, 25.0

p39

p39

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c111 : 1

m19324*0.1

nodelay

--

true

0

false

PMID: 17449723, 16166516 The effect of TRIF here is to induce TNF-{alpha} production via activation of IRF3, with TNF-{alpha} acting in an autocrine manner to induce the late activation of NF-{kappa}B.

Go back
485.0, 289.0
21.0, 21.0

p4

p4

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c110 : 1
stoichiometry:c103 : 1

m21*m19*0.1

nodelay

--

true

0

false

PMID: 17449723, 12609980 Following the discovery that activation of NF-{kappa}B, p38 MAPK, and JNK was impaired in MyD88-deficient cells in response to all TLRs, except in the case of TLR3.

Go back
487.0, 223.0
25.0, 25.0

p40

p40

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c109 : 1
stoichiometry:c107 : 1

m69*m19*0.1

nodelay

--

true

0

false

PMID: 17449723, 12609980 Following the discovery that activation of NF-{kappa}B, p38 MAPK, and JNK was impaired in MyD88-deficient cells in response to all TLRs, except in the case of TLR3.

Go back
340.0, 486.0
30.0, 30.0

p41

p41

cso30:i:ME_Myristoylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c78 : 1

m19005*0.1

nodelay

--

true

0

false

PMID: 17449723 TRAM is myristoylated in its N-terminus and becomes attached to the membrane in association with TLR4.

Go back
298.0, 684.0
25.0, 25.0

p42

p42

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c116 : 1
stoichiometry:c115 : 1

m42*m46*0.1

nodelay

--

true

0

false

PMID: 17449723 TRIF then interacts with downstream signaling molecules such as Tank-binding kinase-1, which phosphorylates and activates the transcription factor IRF3.

Go back
290.0, 644.0
25.0, 25.0

p43

p43

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

m3902*m40*0.1

nodelay

--

true

0

false

PMID: 17449723 TRIF then interacts with downstream signaling molecules such as Tank-binding kinase-1, which phosphorylates and activates the transcription factor IRF3.

Go back
335.0, 773.0
23.0, 23.0

p44

p44

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:c127 : 1
stoichiometry:c128 : 1

m40*m183*m48*0.1

nodelay

--

true

0

false

PMID: 17449723 TRIF also interacts with TRAF6 and receptor-interacting protein-1, which brings about the activation of NF-{kappa}B.

Go back
468.0, 456.0
23.0, 23.0

p45

p45

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c125 : 1
stoichiometry:c129 : 1
stoichiometry:c126 : 1

m17*m49*0.1

nodelay

--

true

0

false

PMID: 17449723 TRIF also interacts with TRAF6 and receptor-interacting protein-1, which brings about the activation of NF-{kappa}B.

Go back
387.0, 815.0
25.0, 25.0

p46

p46

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c130 : 1
stoichiometry:c138 : 1
stoichiometry:c156 : 1
stoichiometry:c131 : 1

m1629*m155666*m66*0.1

nodelay

--

true

0

false

PMID: 17449723 By an as-yet-unknown mechanism, PKC{epsilon} is activated in response to LPS. PMID: 17449723, 11696589, 9601053 The kinase responsible for phosphorylation of TRAM was found to be protein kinase C {epsilon} (PKC{epsilon}), which was known to have a role in LPS signaling [36 ], and its activation by other signaling molecules such as diacyglycerol [37 ] may again provide another level of control in the LPS response.

Go back
275.0, 833.0
23.0, 23.0

p47

p47

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c132 : 1
stoichiometry:c133 : 1

m63*m46*0.1

nodelay

--

true

0

false

PMID: 17449723 PKC{epsilon} phosphorylates TRAM at serine 16.

Go back
279.0, 881.0
23.0, 23.0

p48

p48

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c135 : 1
stoichiometry:c137 : 1
stoichiometry:c136 : 1

m49*m63*0.1

nodelay

--

true

0

false

PMID: 17449723 PKC{epsilon} phosphorylates TRAM at serine 16.

Go back
560.0, 848.0
23.0, 23.0

p49

p49

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c147 : 1
stoichiometry:c149 : 1
stoichiometry:c151 : 1
stoichiometry:c171 : 1

m64*0.1

nodelay

--

true

0

false

PMID: 17449723 This phosphorylation event may also cause TRAM to leave the membrane. viii) With TRAM depleted from the membrane, TRIF no longer interacts with TLR4 and also leaves the membrane. This disrupts the signaling pathway and limits the response to LPS. PMID: 17449723 TLR4 is also degraded at this point.

Go back
330.0, 88.0
25.0, 25.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m6*m15*0.1

nodelay

--

true

0

false

PMID: 17449723 Upon activation, TLRs interact intracellularly with these adaptor proteins via TIR domains, and the adaptor proteins then recruit and activate downstream molecules such as IL-1R-associated kinases (IRAKs) and TNF-receptor-associated factor-6 (TRAF6), which then amplify the signal.

Go back
516.0, 908.0
23.0, 23.0

p50

p50

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c140 : 1
stoichiometry:c148 : 1
stoichiometry:c150 : 1
stoichiometry:c152 : 1
stoichiometry:c153 : 1
stoichiometry:c172 : 1

m65*0.1

nodelay

--

true

0

false

PMID: 17449723 This phosphorylation event may also cause TRAM to leave the membrane. viii) With TRAM depleted from the membrane, TRIF no longer interacts with TLR4 and also leaves the membrane. This disrupts the signaling pathway and limits the response to LPS. PMID: 17449723 TLR4 is also degraded at this point.

Go back
1003.0, 1031.0
25.0, 25.0

p51

p51

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c155 : 1
stoichiometry:c157 : 1

m2142*m158*0.1

nodelay

--

true

0

false

PMID: 17449723 ARF6 is activated by integrins.

Go back
1003.0, 963.0
25.0, 25.0

p52

p52

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c160 : 1
stoichiometry:c159 : 1

m68*m67*0.1

nodelay

--

true

0

false

PMID: 17449723, 10589680 It was also shown that the localization of Mal to the plasma membrane by PIP2 binding is dependent on the ¦Â2-integrin CD11b in macrophages and also on the GTPase ADP ribosylation factor 6 (ARF6), which regulates production of PIP2 via activation of the enzyme PI-5K.

Go back
938.0, 886.0
27.0, 27.0

p53

p53

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m70*0.1

nodelay

--

true

0

false

PMID: 17449723, 10589680 It was also shown that the localization of Mal to the plasma membrane by PIP2 binding is dependent on the ¦Â2-integrin CD11b in macrophages and also on the GTPase ADP ribosylation factor 6 (ARF6), which regulates production of PIP2 via activation of the enzyme PI-5K.

Go back
509.0, 461.0
21.0, 21.0

p55

p55

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c168 : 1
stoichiometry:c170 : 1
stoichiometry:c169 : 1

m17*m230*0.1

nodelay

--

true

0

false

PMID: 17449723, 16166516 The effect of TRIF here is to induce TNF-{alpha} production via activation of IRF3, with TNF-{alpha} acting in an autocrine manner to induce the late activation of NF-{kappa}B.

Go back
660.0, 60.0
23.0, 23.0

p56

p56

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c173 : 1
stoichiometry:c174 : 1
stoichiometry:c175 : 1

m75*m74*0.1

nodelay

--

true

0

false

PMID: 17449723, 16807108 These proteins, similar to TLRs, respond to PAMPs, usually in the cytoplasmic environment.

Go back
624.0, 320.0
23.0, 23.0

p57

p57

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c176 : 1
stoichiometry:c178 : 1
stoichiometry:c177 : 1

m1765*m76*0.1

nodelay

--

true

0

false

PMID: 17449723 Caspase-1 must be activated in inflammasomes, which consist of another group of an innate pathogen sensor, nucleotide oligomerization domain-like receptors (NLRs), including the proteins Nalp1, Nalp3, and Ipaf.

Go back
825.0, 277.0
23.0, 23.0

p58

p58

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c179 : 1
stoichiometry:c180 : 1
stoichiometry:c181 : 1

m43675*m77*0.1

nodelay

--

true

0

false

PMID: 17449723, 17360653 Another interesting feature of Mal is its recently discovered ability to interact with caspase-1 [32 ], which is an important inflammatory caspase, responsible for cleavage of pro-IL-1beta into a catalytically active form secreted by cells.

Go back
868.0, 732.0
28.0, 28.0

p59

p59

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c182 : 1
stoichiometry:c184 : 1
stoichiometry:c183 : 1

m4012*m78*0.1

nodelay

--

true

0

false

PMID: 17449723, 17360653 Another interesting feature of Mal is its recently discovered ability to interact with caspase-1 [32 ], which is an important inflammatory caspase, responsible for cleavage of pro-IL-1beta into a catalytically active form secreted by cells.

Go back
284.0, 232.0
23.0, 23.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m16*m184*0.1

nodelay

--

true

0

false

PMID: 17449723 Upon activation, TLRs interact intracellularly with these adaptor proteins via TIR domains, and the adaptor proteins then recruit and activate downstream molecules such as IL-1R-associated kinases (IRAKs) and TNF-receptor-associated factor-6 (TRAF6), which then amplify the signal.

Go back
452.0, 564.0
23.0, 23.0

p60

p60

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c185 : 1
stoichiometry:c186 : 1
stoichiometry:c188 : 1
stoichiometry:c187 : 1

m18998*m79*m155666*0.1

nodelay

--

true

0

false

PMID: 17449723 The SARM protein interacts with TRIF, and this interaction requires its TIR domain. PMID: 17449723 This interaction is weak in untreated cells but is enhanced by LPS or dsRNA treatment.

Go back
397.0, 541.0
23.0, 23.0

p61

p61

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c189 : 1
stoichiometry:c190 : 1
stoichiometry:c191 : 1
stoichiometry:c192 : 1

m119368*m79*m18998*0.1

nodelay

--

true

0

false

PMID: 17449723 The SARM protein interacts with TRIF, and this interaction requires its TIR domain. PMID: 17449723 This interaction is weak in untreated cells but is enhanced by LPS or dsRNA treatment.

Go back
780.0, 1136.0
23.0, 23.0

p62

p62

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m155666*0.1

nodelay

--

true

0

false

PMID: 17449723 It was also shown that treatment of cells with LPS enhances SARM expression, and it has been speculated that following TLR4 activation, SARM levels increase in cells and eventually bind TRIF to limit the LPS-driven response.

Go back
295.0, 301.0
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:c196 : 1
stoichiometry:c20 : 1

m183*m18*0.1

nodelay

--

true

0

false

PMID: 17449723 Upon activation, TLRs interact intracellularly with these adaptor proteins via TIR domains, and the adaptor proteins then recruit and activate downstream molecules such as IL-1R-associated kinases (IRAKs) and TNF-receptor-associated factor-6 (TRAF6), which then amplify the signal.

Go back
341.0, 361.0
23.0, 23.0

p8

p8

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c26 : 1
stoichiometry:c25 : 1

m17*m19*0.1

nodelay

--

true

0

false

PMID: 17449723, 16698941 TLR signaling ultimately results in the activation of transcription factors such as NF-{kappa}B and IFN regulatory factors (IRFs), which promote the transcription of proinflammatory cytokines and other proteins that promote host defense.

Go back
294.0, 370.0
27.0, 27.0

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m19*m22*0.1

nodelay

--

true

0

false

PMID: 17449723, 16698941 TLR signaling ultimately results in the activation of transcription factors such as NF-{kappa}B and IFN regulatory factors (IRFs), which promote the transcription of proinflammatory cytokines and other proteins that promote host defense.

Go back
427.0, 76.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
377.3478712813834, 511.1636668017067

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
514.0, 300.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
742.0, 178.0

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
744.0, 178.0

c102

c102

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
506.0, 307.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
427.0, 232.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
419.0, 243.0

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
520.0, 236.0

c106

c106

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
512.0, 244.0

c107

c107

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
257.0, 238.61127833952528

c108

c108

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
257.0, 240.60168305026764

c109

c109

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
495.91836614334574, 168.0

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
257.0, 290.0

c110

c110

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
468.0, 1112.0

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
612.0, 758.0

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
555.0, 830.8435424713513

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
331.0, 697.0

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
323.0, 704.0

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
243.0, 697.0

c116

c116

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
124.14222912360003, 734.0

c117

c117

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
385.0, 738.0

c118

c118

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
321.6462320697756, 553.0

c119

c119

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
427.0, 376.0

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
323.0, 657.0

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
243.0, 622.0

c121

c121

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
250.18573377638222, 664.0

c122

c122

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
243.0, 636.0

c123

c123

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
363.4728674874751, 483.0

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
423.0, 387.0

c125

c125

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
436.923410283849, 443.00829016433363

c126

c126

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
365.9909451017955, 784.0

c127

c127

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
249.0, 785.0

c128

c128

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
241.0, 486.9999991442437

c129

c129

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
349.77320112697305, 120.5039559906329

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
419.9213087993047, 831.1193153738147

c130

c130

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
366.69219158112656, 832.0

c131

c131

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
235.0, 725.0

c132

c132

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
247.84464540552736, 847.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
305.9958409147176, 844.0

c134

c134

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
239.0, 810.0

c135

c135

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
254.3292586792175, 898.0

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
307.87008539214537, 858.0

c137

c137

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
68.0924551694668, 4.133748673193111

c138

c138

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
240.0, 857.0

c139

c139

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
327.42562925821557, 113.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
247.0, 920.0

c140

c140

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
989.0, 82.55687957433355

c141

c141

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
992.0, 131.82177677024515

c142

c142

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
662.8577095679057, 449.4485996933218

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
665.1731640207805, 485.0884227391737

c144

c144

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
873.1973153928917, 493.3332921855315

c145

c145

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
988.0, 646.5001229944764

c146

c146

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
531.2256668621961, 597.9055512611654

c147

c147

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
528.0, 598.0

c148

c148

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
372.07014877936115, 616.1881815871177

c149

c149

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
343.0, 121.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
366.7659351571005, 617.0581677787167

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
377.77846408158626, 674.5325719930081

c151

c151

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
409.65685424949237, 801.6568542494924

c152

c152

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
531.0, 490.7491984334676

c153

c153

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1036.0, 1044.0

c154

c154

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1016.0, 1064.0

c155

c155

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
400.0, 848.0

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
983.0, 1044.0

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1016.0, 942.0

c158

c158

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
974.0, 976.0

c159

c159

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
302.6625609418811, 198.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
972.0, 994.1580636831471

c160

c160

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
965.0, 287.9398850427246

c161

c161

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
952.0, 921.0

c162

c162

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
965.0, 267.91045009529785

c163

c163

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
243.0, 575.0

c164

c164

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1035.7839864320406, 374.0

c165

c165

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1006.2389335532322, 467.0075650887785

c166

c166

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1000.9268780601832, 315.7613335014641

c167

c167

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
427.0, 386.0

c168

c168

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
437.4147970583408, 438.0034620995811

c169

c169

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
314.03887983332885, 253.80186410750787

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
525.6428033978249, 489.5508668509281

c170

c170

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
583.0, 818.8978722610858

c171

c171

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
539.0, 820.8727652066574

c172

c172

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
632.0, 71.0

c173

c173

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
623.0, 90.5339352927587

c174

c174

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
674.0, 83.0

c175

c175

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
642.8995700892395, 302.0

c176

c176

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
647.0, 338.0

c177

c177

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
653.5003060050375, 291.0

c178

c178

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
855.5476811172091, 295.65188796010045

c179

c179

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
259.03265276709044, 211.25424595843361

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
722.0, 300.1742798695929

c180

c180

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
825.7785148465888, 300.0

c181

c181

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
832.0, 744.0

c182

c182

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
840.8063839788744, 754.0

c183

c183

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
819.0, 361.0

c184

c184

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
370.0, 579.4395279122544

c185

c185

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
454.0, 518.0

c186

c186

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
441.88514344942905, 587.0

c187

c187

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
481.35858506765794, 87.0

c188

c188

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
148.0, 421.0

c189

c189

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
325.2684559213601, 321.3420874493714

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
425.5352429058849, 518.0

c190

c190

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
370.0, 568.0533836092978

c191

c191

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
411.0, 564.0

c192

c192

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
318.9129365004098, 616.8300168334202

c193

c193

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
759.0, 1148.0

c194

c194

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
810.999999355528, 56.09336608460217

c195

c195

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
251.0, 214.0

c196

c196

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
427.0, 137.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
264.50674493453687, 296.7656428706189

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
371.99632943316306, 372.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
256.0, 309.0

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
307.0, 404.99793468435956

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
320.0, 397.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
364.0, 383.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
257.0, 300.0

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
415.0, 446.0

c27

c27

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
367.0, 462.0

c28

c28

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
490.0, 1024.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
391.47152903105064, 129.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
507.6600336668405, 1020.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1002.8843608412727, 230.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
997.0, 318.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1005.0, 312.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
997.0, 277.15135438863337

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
934.0, 412.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1029.0, 412.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
657.0, 434.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
878.0, 473.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1107.0, 424.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
996.0, 268.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1115.4690009539725, 472.8660119939662

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
659.0, 357.48619056147976

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
910.0793457790559, 332.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
876.8311367793272, 359.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
659.0, 471.0

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
947.0, 530.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
954.399798510423, 471.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
427.0, 382.0

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
438.0, 428.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
517.8707366913484, 431.43230720708283

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
946.0, 286.5538553641523

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1013.9732628765121, 90.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
893.0, 228.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
899.4384529045702, 233.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
893.0, 239.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
900.0, 276.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
891.0, 178.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
883.0, 47.0

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
901.8874480940947, 114.41645224656706

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
883.0, 110.0

c58

c58

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
887.0, 288.0

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
988.0, 273.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
996.0, 464.0

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1107.0, 596.0

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1117.7711329135784, 604.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1039.0, 599.37072939801

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
749.9999997301861, 76.0

c64

c64

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.0, 1014.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1025.758472741024, 698.0

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1042.0509053796172, 689.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1036.0, 735.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1003.0, 748.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1131.0, 90.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
924.4957319032338, 433.85893033902505

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
967.6349772505464, 759.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
833.570059564753, 252.56446243446004

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
831.225866052374, 177.0

c73

c73

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
817.0, 190.99211045172967

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
785.294340964233, 258.9974956235452

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
780.4025068970706, 183.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
750.4832142536907, 185.60484365192784

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
355.0, 516.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
251.0, 565.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1107.0, 149.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
94.50823951542436, 11.561152718483811

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
322.6703849016671, 601.0

c81

c81

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
251.0, 613.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
436.94594513699565, 398.0

c83

c83

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
670.0, 521.0

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.913627698831, 543.1723892887157

c85

c85

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
707.0, 582.0

c86

c86

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
707.0, 608.0

c87

c87

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
752.0, 658.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
756.0, 684.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1111.616228490282, 184.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
670.0, 512.0

c90

c90

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0437687993774, 518.0

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
707.0, 576.0

c92

c92

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
706.5067449345369, 581.0

c93

c93

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
752.0, 652.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
755.4906334205524, 657.0

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
834.0564687191462, 545.0

c96

c96

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
786.8094964814716, 540.0

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
729.9961405583977, 537.0

c98

c98

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
713.6192544052071, 178.0

c99

c99

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back