1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18191460.csml convertedTime:2009.07.01.11:13

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title MyDths and un-TOLLed truths: sensor, instructive and effector immunity totuberculosis.
Authors Reiling N, Ehlers S, Holscher C.
Affiliation Microbial Interface Biology, Research Center Borstel, D-23845 Borstel, Germany.
Abstract Controversy exists concerning the role of Toll-like receptors and MyD88 inimmunity to tuberculosis (TB). This mini-review argues that (i) Toll-likereceptors are not essential for an effective immune response against TB, (ii)MyD88 is essential, but not because it transduces signals from TLRs, (iii)adaptive immunity to TB is largely TLR/MyD88-independent. Some of thediscrepancies may be resolved by cogent attribution of distinct immune functionsto the individual components of the TLR/MyD88 system. In mice, TLRs and MyD88are fully dispensable in sensing Mtb infection and instructing T cell-mediatedadaptive immunity, and while TLRs are also redundant during macrophage effectorimmunity, MyD88 is essential for efficient killing of mycobacteria. Thisdistinction should help to molecularly pinpoint the MyD88-dependent, yetTLR-independent critical mechanisms of macrophage activation involved inintracellular growth restriction of Mtb. Disrupted IL-1R and/or IFN-gammasignaling pathways likely play a much more prominent role in explaining theexquisite susceptibility of MyD88-deficient mice to TB than the function ofMyD88 as a TLR adaptor.
PMID 18191460
Model Abstract

Entity

G010262:IL-6 G010329:TNF-alpha G010453:IFN-gamma G010657:IL-12 p40 MO000000011:ERK MO000000022:p38 MO000000023:JNK MO000000058:NF-kappaB MO000000145:Jak1 MO000000146:Jak2 MO000000212:TRAF6 MO000000213:IRAK-1 MO000000214:IL-1 MO000000289:TNF-alpha MO000007330:proIL-18 MO000007384:IL-6 MO000013119:STAT1 MO000016573:MyD88 MO000016594:IL-1RAcP MO000016595:IL-1RI MO000016597:IL-1beta MO000016602:IL-18R MO000016625:IL-18 MO000016665:IFNgamma {extracellular} MO000016828:Caspase-1 MO000016835:IFNGR2: IFNGR1: IFNGR2 MO000016856:STAT1:STAT1 {p} MO000016913:MLK3 MO000017265:IL-12 MO000018229:proCaspase-1 MO000019394:TLR4 MO000019395:TLRs MO000019397:TLR2 MO000019449:proIL-1beta MO000019704:STAT1{p} MO000039077:IRAK-4 MO000042012:TLR9 e1: e10: e11:LAM e12:LAM: TLR2 e13:PIM2 e14:PIM6 e15:PIM2: TLR2 e16:PIM6: TLR2 e17:19 kDa mycobacterial lipoprotein e18:19 kDa mycobacterial lipoprotein: TLR2 e19:heat- sensitive cell-associated mycobacterial factors e2: e20:heat- sensitive cell-associated mycobacterial factors: TLR4 e21:Mtb CpG motifs e22:Mtb CpG motifs: TLR9 e23:TLR ligand e24:TLR ligand: TLR e25:TLR ligand: TLR: MyD88 e26:TLR ligand: TLR: MyD88: IRAK-4: IRAK-1 e27:TRAF6 {activated} e28:TLR4 ligand: TLR4 e29:TLR4 ligand e3: e30:TLR4 ligand: TLR4: MyD88 e31:TLR ligand: TLR: MyD88: IRAK-4 e32:TLR4 ligand: TLR4: MyD88: IRAK-4 e33:TLR4 ligand: TLR4: MyD88: IRAK-4: IRAK-1 e34:TLR4 ligand: TLR4: MyD88: IRAK-4: IRAK-1{p} e35:TLR ligand: TLR: MyD88: IRAK-4: IRAK-1{p} e36:NF-kappaB {activated} e37:JNK {activated} e38:p38 {activated} e39:ERK {activated} e4: e40:IL-1: IL-1R1 e41:IL-1: IL-1R1: IL-1RAcP e42:IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88 e43:IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88: IRAK-4 e44:IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88: IRAK-4: IRAK-1 e45:IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88: IRAK-4: IRAK-1{p} e46:MyD88s e47:IFNgamma: IFNGR2: IFNGR1: IFNGR2 e48:IFNgamma: IFNGR2: IFNGR1{p}: IFNGR2 e49:Jak1{pY} e5:GAF e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:Nos2 e60: e61: e62: e63:Jak2{pY} e64:STAT1:STAT1{p}: GAF e65:STAT1:STAT1{p}: GAF {nucleus} e66:IFNgamma activator sequence: STAT1:STAT1{p}: GAF {nucleus} e67:IFNgamma activator sequence e68:IFNgamma: IFNGR1: MyD88 e69:unknown domain e7: e70:IFNgamma: IFNGR1: MyD88: unknown domain e71:IFNgamma: IFNGR1: MyD88: unknown domain: MLK3 e72:il-18: IL-18R e73:AcPL e74:il-18: IL-18R: AcPL e75:IL-1: IL-1R1: IL-1R1: IL-1RAcP e76:il-18: IL-18R: AcPL: MyD88 e77:NALP3 inflammasome e78:PAMP e79:NALP e8: e80:PAMP: NALP e81:MDP: NALP3 inflammasome e82:MDP e83:inflammasome e84:Cytokines e85:cytokines e86:IFNgamma e87:IP-10 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 p54 p55 p56 p57 p58 p59 p6 p60 p61 p62 p63 p64 p65 p7 p8 p9
Model Detail
549.0, 965.0
30.0, 30.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p61

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
722.0, 1080.0
30.0, 30.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p64

p23

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
491.0, 995.0
34.0, 34.0

IFN-gamma

--

G010453

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p60

true true true true

csml-variable:Double

m93423

10

false

infinite

0

unit false false false
TRANSFACG010453

--

Go back
715.0, 1037.0
28.0, 28.0

IL-12 p40

--

G010657

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p24

true true true true

csml-variable:Double

m93589

10

false

infinite

0

unit false false false
TRANSFACG010657

--

Go back
883.0, 908.0
30.0, 30.0

ERK

--

MO000000011

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p22 p32

true true true true

csml-variable:Double

m5

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
788.0, 869.0
28.0, 28.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21 p31 p47 p63

true true true true

csml-variable:Double

m20

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
775.0, 777.0
33.0, 33.0

JNK

--

MO000000023

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p20 p30

true true true true

csml-variable:Double

m21

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
780.0, 673.0
36.0, 36.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19 p29

true true true true

csml-variable:Double

m6

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
205.0, 667.0
28.0, 28.0

Jak1

--

MO000000145

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p37

true true true true

csml-variable:Double

m129

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000145

--

Go back
203.0, 745.0
24.0, 24.0

Jak2

--

MO000000146

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m130

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000146

--

Go back
884.0, 765.0
28.0, 28.0

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10 p18

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
832.0, 497.0
28.0, 28.0

IRAK-1

--

MO000000213

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9 p15 p33

true true true true

csml-variable:Double

m184

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000213

--

Go back
313.0, 30.0
26.0, 26.0

IL-1

--

MO000000214

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m185

10

false

infinite

0

unit false false false
TRANSPATHMO000000214

--

Go back
1101.0, 1083.0
32.0, 32.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p23

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
795.0, 1168.0
30.0, 30.0

proIL-18

--

MO000007330

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p56

true true true true

csml-variable:Double

m841

10

false

infinite

0

unit false false false
InterProIPR008996
TRANSPATHMO000007330

--

Go back
525.0, 789.0
30.0, 30.0

IL-6

--

MO000007384

cso30:c:Protein

cso30:i:CC_CellComponent

--

p61

--

true true true true

csml-variable:Double

m871

10

false

infinite

0

unit false false false
InterProIPR003573
TRANSPATHMO000007384

--

Go back
339.0, 661.0
32.0, 32.0

STAT1

--

MO000013119

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p39

true true true true

csml-variable:Double

m1357

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
875.0, 364.0
30.0, 30.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8 p12 p27 p44 p52

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
403.0, 180.0
30.5, 30.5

IL-1RAcP

--

MO000016594

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p26

true true true true

csml-variable:Double

m1588

10

false

infinite

0

unit false false false
InterProIPR003599
TRANSPATHMO000016594

--

Go back
310.0, 151.0
32.0, 32.0

IL-1RI

--

MO000016595

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m1589

10

false

infinite

0

unit false false false
InterProIPR004076
TRANSPATHMO000016595

--

Go back
702.0, 1427.0
32.0, 32.0

IL-1beta

--

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

--

p55 p57

--

true true true true

csml-variable:Double

m1591

10

false

infinite

0

unit false false false
TRANSPATHMO000016597

--

Go back
249.0, 154.0
34.0, 34.0

IL-18R

--

MO000016602

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p48

true true true true

csml-variable:Double

m1596

10

false

infinite

0

unit false false false
InterProIPR003599
TRANSPATHMO000016602

--

Go back
200.0, 25.0
28.0, 28.0

IL-18

--

MO000016625

cso30:c:Protein

cso30:i:CC_CellComponent

--

p56

p48

true true true true

csml-variable:Double

m1611

10

false

infinite

0

unit false false false
InterProIPR008996
TRANSPATHMO000016625

--

Go back
57.0, 581.0
30.0, 30.0

IFNgamma {extracellular}

--

MO000016665

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m1639

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
819.0, 1296.0
29.0, 29.0

Caspase-1

--

MO000016828

cso30:c:Protein

cso30:i:CC_CellComponent

--

p51

p55 p56

true true true true

csml-variable:Double

m1765

10

false

infinite

0

unit false false false
TRANSPATHMO000016828

--

Go back
205.0, 521.0
30.0, 30.0

IFNGR2: IFNGR1: IFNGR2

--

MO000016835

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m1772

10

false

infinite

0

unit false false false
InterProIPR008355
TRANSPATHMO000016835

--

Go back
341.0, 751.0
36.0, 36.0

STAT1:STAT1 {p}

--

MO000016856

cso30:c:Protein

cso30:i:CC_CellComponent

--

p40

p41

true true true true

csml-variable:Double

m1788

10

false

infinite

0

unit false false false
TRANSPATHMO000016856

--

Go back
345.0, 362.0
26.0, 26.0

MLK3

--

MO000016913

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p46

true true true true

csml-variable:Double

m1828

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000016913

--

Go back
1105.0, 1035.0
32.0, 32.0

IL-12

--

MO000017265

cso30:c:Protein

cso30:i:CC_CellComponent

--

p24

p60

true true true true

csml-variable:Double

m2121

10

false

infinite

0

unit false false false
TRANSPATHMO000017265

--

Go back
815.0, 1152.0
29.0, 29.0

proCaspase-1

--

MO000018229

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m2906

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000018229

--

Go back
994.0, 151.0
24.0, 24.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5 p11

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
997.0, 446.0
30.0, 30.0

TLRs

--

MO000019395

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m3962

10

false

infinite

0

unit false false false
TRANSPATHMO000019395

--

Go back
204.0, 881.0
28.0, 28.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p2 p3 p4

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
795.0, 1128.0
30.0, 30.0

proIL-1beta

--

MO000019449

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p55 p57

true true true true

csml-variable:Double

m4012

10

false

infinite

0

unit false false false
InterProIPR003297
TRANSPATHMO000019449

--

Go back
343.0, 701.0
32.0, 32.0

STAT1{p}

--

MO000019704

cso30:c:Protein

cso30:i:CC_CellComponent

--

p39

p40

true true true true

csml-variable:Double

m4238

10

false

infinite

0

unit false false false
TRANSPATHMO000019704

--

Go back
857.0, 438.0
26.0, 26.0

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14 p13 p28

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
205.0, 1088.0
30.0, 30.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
183.75, 161.9969080091176
856.2594311764528, 1243.2886940682085

--

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
192.0, 181.0
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
67.0, 930.0
45.87047939444911, 25.993271656854496

LAM

--

e11

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
207.5, 925.0
28.848025329111817, 35.32411264789202

LAM: TLR2

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
71.0, 980.0
37.77123633305298, 21.403700588730025

PIM2

--

e13

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p2

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
64.0, 1031.0
43.523969722455845, 24.663582842724978

PIM6

--

e14

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p3

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
207.5, 973.0
29.868688551908022, 36.57390434927512

PIM2: TLR2

--

e15

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p2

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
207.5, 1025.0
29.99933344442593, 36.73387768705216

PIM6: TLR2

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p3

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
59.5, 830.25
45.0, 25.5

19 kDa mycobacterial lipoprotein

--

e17

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p4

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
206.625, 819.5
31.230253291118146, 38.24112647892018

19 kDa mycobacterial lipoprotein: TLR2

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

--

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
1114.5, 100.25
39.70142977291842, 22.497476871320433

heat- sensitive cell-associated mycobacterial factors

--

e19

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p5

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
183.75, 161.9969080091176
856.2594311764528, 1243.2886940682085

--

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
951.625, 161.5
29.278745209131806, 35.85152474587569

heat- sensitive cell-associated mycobacterial factors: TLR4

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
103.5, 1091.125
45.0, 15.75

Mtb CpG motifs

--

e21

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p6

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
208.625, 1138.5
27.678345275787372, 33.89185135810698

Mtb CpG motifs: TLR9

--

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p6

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1129.5, 448.375
37.478031634446396, 24.36072056239016

TLR ligand

--

e23

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p7

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
996.625, 487.5
31.1894267622063, 38.19113481086486

TLR ligand: TLR

--

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p7

p8 p23 p24

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
995.875, 536.5
32.25, 45.0

TLR ligand: TLR: MyD88

--

e25

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8

p14

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
993.875, 652.5
32.25, 45.0

TLR ligand: TLR: MyD88: IRAK-4: IRAK-1

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p9

p17

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
884.0, 809.0
28.0, 28.0

TRAF6 {activated}

--

e27

cso30:c:Protein

cso30:i:CC_CellComponent

--

p10 p18

p19 p20 p21 p22

true true true true

csml-variable:Double

m31

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
996.625, 196.5
29.8993084485919, 36.61139810031661

TLR4 ligand: TLR4

--

e28

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p11

p12

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
1136.5, 151.375
34.525483304042176, 22.441564147627414

TLR4 ligand

--

e29

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p11

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
200.87518862352903, 179.12209663264667
822.0090539293948, 1209.0383168211513

--

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
995.875, 239.5
28.36745274362268, 39.58249220040375

TLR4 ligand: TLR4: MyD88

--

e30

cso30:c:Complex

cso30:i:CC_Extracellular

--

p12

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
995.875, 594.5
32.25, 45.0

TLR ligand: TLR: MyD88: IRAK-4

--

e31

cso30:c:Complex

cso30:i:CC_Cytosol

--

p14

p9

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
997.875, 288.5
32.25, 45.0

TLR4 ligand: TLR4: MyD88: IRAK-4

--

e32

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p13

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
993.875, 340.5
32.25, 45.0

TLR4 ligand: TLR4: MyD88: IRAK-4: IRAK-1

--

e33

cso30:c:Complex

cso30:i:CC_Extracellular

--

p15

p16

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
993.875, 396.5
32.25, 45.0

TLR4 ligand: TLR4: MyD88: IRAK-4: IRAK-1{p}

--

e34

cso30:c:Complex

cso30:i:CC_Extracellular

--

p16

p10

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
993.875, 708.5
32.25, 45.0

TLR ligand: TLR: MyD88: IRAK-4: IRAK-1{p}

--

e35

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p17

p18

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
780.0, 725.0
36.0, 36.0

NF-kappaB {activated}

--

e36

cso30:c:Protein

cso30:i:CC_CellComponent

--

p19 p29

p62

true true true true

csml-variable:Double

m40

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
779.0, 821.0
33.0, 33.0

JNK {activated}

--

e37

cso30:c:Protein

cso30:i:CC_CellComponent

--

p20 p30

--

true true true true

csml-variable:Double

m41

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
816.0, 925.0
28.0, 28.0

p38 {activated}

--

e38

cso30:c:Protein

cso30:i:CC_CellComponent

--

p21 p31 p47 p63

p64 p65

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
885.0, 965.0
30.0, 30.0

ERK {activated}

--

e39

cso30:c:Protein

cso30:i:CC_CellComponent

--

p22 p32

--

true true true true

csml-variable:Double

m43

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
232.55678757705792, 209.09117672382234
758.6458560223374, 1149.1001566387988

--

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
360.625, 186.5
27.319071821363103, 33.45192467922013

IL-1: IL-1R1

--

e40

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p25

p26

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
445.875, 172.5
32.25, 45.0

IL-1: IL-1R1: IL-1RAcP

--

e41

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p26

p50

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
562.875, 152.5
37.47407781244265, 52.28941090108276

IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88

--

e42

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p27

p28

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
609.875, 143.5
39.360111947146265, 54.92108643787851

IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88: IRAK-4

--

e43

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p28

p33

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
665.875, 131.5
39.691548908056525, 55.38355661589282

IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88: IRAK-4: IRAK-1

--

e44

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p33

p34

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
729.875, 121.5
39.8967241695724, 55.66984767847312

IL-1: IL-1R1: IL-1RI: IL-1RAcP: MyD88: IRAK-4: IRAK-1{p}

--

e45

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p34

p29 p30 p31 p32

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
565.5, 498.125
33.480000000000004, 25.109999999999996

MyD88s

--

e46

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p8 p12 p27

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
207.5, 568.0
32.22846192301283, 39.46342276287286

IFNgamma: IFNGR2: IFNGR1: IFNGR2

--

e47

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p35

p36 p44 p63

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
209.625, 622.5
28.56019830028329, 34.97167138810198

IFNgamma: IFNGR2: IFNGR1{p}: IFNGR2

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p36

p37 p38

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
201.5, 703.125
35.88, 26.909999999999997

Jak1{pY}

--

e49

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p37

p39

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
276.0, 810.0
29.0, 29.0

GAF

--

e5

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p41

true true true true

csml-variable:Double

m11

10

false

infinite

0

unit false false false
TRANSFACT00300
TRANSPATHMO000024844

--

Go back
373.46395122712346, 909.0
401.1861197477627, 363.8317324341912

--

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
416.79504051086684, 917.6222831305478
234.58555232923192, 352.6254162401196

--

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
378.6935654510235, 913.8560703507643
390.7268912999628, 354.11959173266234

--

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
379.4406531972949, 914.6031580970357
389.23271580741977, 352.6254162401196

--

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
373.46395122712346, 909.0
401.1861197477627, 363.8317324341912

--

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
373.46395122712346, 909.0
401.1861197477627, 363.8317324341912

--

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
379.4406531972949, 914.6031580970357
389.23271580741977, 352.6254162401196

--

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
666.3223477655272, 1058.4175492542877
25.063904443070882, 22.68942928530631

--

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
600.5786260936409, 1163.0098337322895
70.97333589578669, 64.24954617934387

--

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
373.46395122712346, 909.0
401.1861197477627, 363.8317324341912

--

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
608.0, 1004.0
32.0, 32.0

Nos2

--

e6

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p62

--

true true true true

csml-variable:Double

m12

10

false

infinite

0

unit false false false
Affymetrix104420_at
EnsemblENSMUSG00000020826
MGDNos2
ProteomeHumanPSD/Nos2
RefSeqNM_010927
TRANSFACG001073
UnigeneMm.2893

--

Go back
468.02126233275, 1070.6838155274
12.70497493133005, 6.117210152121884

--

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
467.5970072573248, 1052.4408472841164
43.48614523108281, 78.27506141594908

--

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
485.8399755006087, 1103.3514563351405
6.788081206803163, 6.788081206803169

--

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
205.5, 783.125
35.88, 26.909999999999997

Jak2{pY}

--

e63

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p38

--

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
344.875, 868.5
28.935630390897412, 40.37529821985685

STAT1:STAT1{p}: GAF

--

e64

cso30:c:Complex

cso30:i:CC_Cytosol

--

p41

p42

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
424.875, 991.5
28.935630390897412, 40.37529821985685

STAT1:STAT1{p}: GAF {nucleus}

--

e65

cso30:c:Complex

cso30:i:CC_Cytosol

--

p42

p43

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
416.5, 1105.625
45.0, 12.75

IFNgamma activator sequence: STAT1:STAT1{p}: GAF {nucleus}

--

e66

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p43

--

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
476.5, 1063.125
45.0, 9.75

IFNgamma activator sequence

--

e67

cso30:c:Dna

cso30:i:CC_NuclearChromosome

--

--

p43

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
204.875, 464.5
32.25, 45.0

IFNgamma: IFNGR1: MyD88

--

e68

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p44

p45

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
337.5, 416.25
38.313708999158955, 21.711101766190076

unknown domain

--

e69

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p45

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
195.0, 167.0
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
209.875, 406.5
29.67741787483942, 41.41035052303175

IFNgamma: IFNGR1: MyD88: unknown domain

--

e70

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p45

p46

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
204.875, 352.5
32.25, 45.0

IFNgamma: IFNGR1: MyD88: unknown domain: MLK3

--

e71

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p46

p47

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
199.625, 153.5
29.27874520913181, 35.851524745875686

il-18: IL-18R

--

e72

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p48

p49 p58 p59 p60 p61

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
239.125, 197.5
19.38795532300262, 31.439927550815057

AcPL

--

e73

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p49

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
196.875, 204.5
25.81854468709855, 36.02587630757937

il-18: IL-18R: AcPL

--

e74

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p49

p52

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
501.875, 164.5
32.25, 45.0

IL-1: IL-1R1: IL-1R1: IL-1RAcP

--

e75

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p50

--

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
197.875, 248.5
32.25, 45.0

il-18: IL-18R: AcPL: MyD88

--

e76

cso30:c:Complex

cso30:i:CC_Cytosol

--

p52

--

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
925.875, 1204.5
32.25, 45.0

NALP3 inflammasome

--

e77

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p54

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
1107.5, 1151.375
36.56414762741652, 23.766695957820737

PAMP

--

e78

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p53

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false false false

--

Go back
930.125, 1116.5
23.349315757697724, 37.86375528275307

NALP

--

e79

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p53

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
198.0, 188.0
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
926.625, 1160.5
31.00979003499417, 37.97117147142143

PAMP: NALP

--

e80

cso30:c:Complex

cso30:i:CC_Cytosol

--

p53

--

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false false false

--

Go back
925.875, 1260.5
32.25, 45.0

MDP: NALP3 inflammasome

--

e81

cso30:c:Complex

cso30:i:CC_Cytosol

--

p54

p57

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false false false

--

Go back
1104.5, 1215.25
42.527333894028594, 24.098822539949538

MDP

--

e82

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p54

true true true true

csml-variable:Double

m86

0

false

infinite

0

unit false false false

--

Go back
878.875, 1293.5
26.22100385391815, 36.58744723802533

inflammasome

--

e83

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p51

true true true true

csml-variable:Double

m87

0

false

infinite

0

unit false false false

--

Go back
388.5, 804.125
31.400000000000006, 23.55

Cytokines

--

e84

cso30:c:Protein

cso30:i:CC_Cytosol

--

p59

--

true true true true

csml-variable:Double

m88

0

false

infinite

0

unit false false false

--

Go back
453.5, 960.0
37.88927335640139, 20.207612456747405

cytokines

--

e85

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p59

true true true true

csml-variable:Double

m89

0

false

infinite

0

unit false false false

--

Go back
465.0, 785.0
30.0, 30.0

IFNgamma

--

e86

cso30:c:Protein

cso30:i:CC_CellComponent

--

p60

--

true true true true

csml-variable:Double

m90

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
609.0, 1057.0
29.0, 29.0

IP-10

--

e87

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p65

--

true true true true

csml-variable:Double

m91

10

false

infinite

0

unit false false false
Affymetrix1418930_at
EnsemblENSMUSG00000034855
MGDCxcl10
ProteomeHumanPSD/Cxcl10
RefSeqNM_021274
TRANSFACG001062
UnigeneMm.263514

--

Go back
206.0, 209.0
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
138.0, 931.0
23.0, 23.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019397 e11

e12

true true true true

--

and

mass

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

m3964*m13*0.1

nodelay

--

true

0

false

PMID: 18191460, 12775723, 11404392, 10586073, 11222859 For example, the mycobacterial lipoglycans phosphoinositol-capped lipoarabinomannan (LAM), phosphatidyl myo-inositol mannosides (PIM)2 and PIM6 and the 19 kDa mycobacterial lipoprotein represent TLR2 agonists.

Go back
941.0, 766.0
25.0, 25.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000212 e34

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c47 : 1
stoichiometry:c29 : 1

m183*m38*0.1

nodelay

--

true

0

false

PMID: 18191460, 9734363 Studies by Medzhitov et al. then demonstrated that signaling by Toll-like receptor (TLR)4 also employs MyD88, and induces activation of the NF-kappaB pathway via the IRAK1 kinase and the Tumor-necrosis-factor receptor-associated factor (TRAF) 6 protein.

Go back
1069.0, 150.0
25.0, 25.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e29 MO000019394

e28

true true true true

--

and

mass

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

m33*m3961*0.1

nodelay

--

true

0

false

PMID: 18191460, 9734363 Studies by Medzhitov et al. then demonstrated that signaling by Toll-like receptor (TLR)4 also employs MyD88, and induces activation of the NF-kappaB pathway via the IRAK1 kinase and the Tumor-necrosis-factor receptor-associated factor (TRAF) 6 protein.

Go back
928.0, 245.0
27.0, 27.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016573 e28 e46

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c35 : 1
stoichiometry:c99 : 1
stoichiometry:c36 : 1

m1572*m32*0.1

nodelay

--

true

0

false

PMID: 18191460, 9734363 Studies by Medzhitov et al. then demonstrated that signaling by Toll-like receptor (TLR)4 also employs MyD88, and induces activation of the NF-kappaB pathway via the IRAK1 kinase and the Tumor-necrosis-factor receptor-associated factor (TRAF) 6 protein. PMID: 18191460, 9575168 A MyD88 splice variant termed MyD88short (MyD88s), which lacks the linker domain between the DD and the TIR domain does not bind IRAK4 and acts as a negative regulator of IL1R/MYD88 signals, thus leading to a controlled negative regulation of innate immune responses.

Go back
929.0, 298.0
25.0, 25.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000039077

e32

true true true true

--

and

mass

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

m17258*0.1

nodelay

--

true

0

false

PMID: 18191460, 12888566 It facilitates the association of IL-1R-associated kinase (IRAK) 4 with the receptor complex through a homophilic DD interaction.

Go back
936.0, 605.0
23.0, 23.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e25 MO000039077

e31

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c40 : 1
stoichiometry:c41 : 1

m29*m17258*0.1

nodelay

--

true

0

false

PMID: 18191460, 12888566 It facilitates the association of IL-1R-associated kinase (IRAK) 4 with the receptor complex through a homophilic DD interaction.

Go back
938.0, 347.0
23.0, 23.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213

e33

true true true true

--

and

mass

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

m184*0.1

nodelay

--

true

0

false

PMID: 18191460 In TLR signaling, MyD88 couples TLR and IRAK through interactions of TIR domain?TIR domain and death domain?death domain (DD?DD).

Go back
938.0, 407.0
23.0, 23.0

p16

p16

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e33

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c44 : 1

m37*0.1

nodelay

--

true

0

false

PMID: 18191460 The binding of MyD88 to IRAK4 is a mandatory step in the IRAK4-mediated phosphorylation of a crucial residue or residues in the kinase-activation loop of IRAK1, which induces the kinase activity of IRAK1.

Go back
938.0, 719.0
23.0, 23.0

p17

p17

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e26

e35

true true true true

--

and

mass

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

m30*0.1

nodelay

--

true

0

false

PMID: 18191460 The binding of MyD88 to IRAK4 is a mandatory step in the IRAK4-mediated phosphorylation of a crucial residue or residues in the kinase-activation loop of IRAK1, which induces the kinase activity of IRAK1.

Go back
941.0, 810.0
25.0, 25.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e35 MO000000212

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c49 : 1
stoichiometry:c50 : 1

m39*m183*0.1

nodelay

--

true

0

false

PMID: 18191460, 9734363 Studies by Medzhitov et al. then demonstrated that signaling by Toll-like receptor (TLR)4 also employs MyD88, and induces activation of the NF-kappaB pathway via the IRAK1 kinase and the Tumor-necrosis-factor receptor-associated factor (TRAF) 6 protein.

Go back
836.0, 728.0
27.0, 27.0

p19

p19

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000058 e27

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c59 : 1
stoichiometry:c52 : 1

m6*m31*0.1

nodelay

--

true

0

false

PMID: 18191460 MyD88 mediates a signaling cascade in TLR-triggered cells that leads to activation of NF-¦ÊB and the three MAPK pathways (extracellular signal-regulated kinase (Erk), Jun N-terminal kinase (Jnk) and p38). PMID: 18191460, 9734363 Studies by Medzhitov et al. then demonstrated that signaling by Toll-like receptor (TLR)4 also employs MyD88, and induces activation of the NF-kappaB pathway via the IRAK1 kinase and the Tumor-necrosis-factor receptor-associated factor (TRAF) 6 protein.

Go back
138.0, 979.0
24.0, 24.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e13 MO000019397

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c8 : 1
stoichiometry:c5 : 1

m15*m3964*0.1

nodelay

--

true

0

false

PMID: 18191460, 12775723, 11404392, 10586073, 11222859 For example, the mycobacterial lipoglycans phosphoinositol-capped lipoarabinomannan (LAM), phosphatidyl myo-inositol mannosides (PIM)2 and PIM6 and the 19 kDa mycobacterial lipoprotein represent TLR2 agonists.

Go back
840.0, 826.0
24.0, 24.0

p20

p20

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000023 e27

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c60 : 1
stoichiometry:c54 : 1

m21*m31*0.1

nodelay

--

true

0

false

PMID: 18191460 MyD88 mediates a signaling cascade in TLR-triggered cells that leads to activation of NF-¦ÊB and the three MAPK pathways (extracellular signal-regulated kinase (Erk), Jun N-terminal kinase (Jnk) and p38).

Go back
859.0, 868.0
27.0, 27.0

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000022 e27

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c61 : 1
stoichiometry:c56 : 1

m20*m31*0.1

nodelay

--

true

0

false

PMID: 18191460 MyD88 mediates a signaling cascade in TLR-triggered cells that leads to activation of NF-¦ÊB and the three MAPK pathways (extracellular signal-regulated kinase (Erk), Jun N-terminal kinase (Jnk) and p38).

Go back
945.0, 910.0
25.0, 25.0

p22

p22

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000011 e27

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c62 : 1
stoichiometry:c58 : 1

m5*m31*0.1

nodelay

--

true

0

false

PMID: 18191460 MyD88 mediates a signaling cascade in TLR-triggered cells that leads to activation of NF-¦ÊB and the three MAPK pathways (extracellular signal-regulated kinase (Erk), Jun N-terminal kinase (Jnk) and p38).

Go back
823.0, 1085.0
27.0, 27.0

p23

p23

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010329 e24

MO000000289

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c68 : 1
stoichiometry:c63 : 1

m93309*m28*0.1

nodelay

--

true

0

false

PMID: 18191460 In vitro, the initial recognition of mycobacterial components by macrophages and dendritic cells leads to the release of IL-12 and TNF and involves a number of different pattern recognition receptors (PRR), among them TLRs.

Go back
824.0, 1038.0
25.0, 25.0

p24

p24

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010657 e24

MO000017265

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c67 : 1
stoichiometry:c65 : 1

m93589*m28*0.1

nodelay

--

true

0

false

PMID: 18191460 In vitro, the initial recognition of mycobacterial components by macrophages and dendritic cells leads to the release of IL-12 and TNF and involves a number of different pattern recognition receptors (PRR), among them TLRs.

Go back
313.0, 82.0
25.0, 25.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000000214 MO000016595

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c71 : 1

m185*m1589*0.1

nodelay

--

true

0

false

PMID: 18191460 IL-1 binding to IL-1R1 mediates recruitment of IL-1AcP. PMID: 18191460 IL-1RI and IL-18R directly bind theirs ligands, whereas IL-1RAcP and AcPL have accessory function. PMID: 18191460 Eventually, NALP3-mediated secretion of IL-1beta may induce IL-1R1/MyD88-dependent proinflammatory responses.

Go back
405.0, 66.0
25.0, 25.0

p26

p26

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e40 MO000016594

e41

true true true true

--

and

mass

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

m44*m1588*0.1

nodelay

--

true

0

false

PMID: 18191460 IL-1 binding to IL-1R1 mediates recruitment of IL-1AcP.

Go back
569.0, 234.0
25.0, 25.0

p27

p27

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016573 e46

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c98 : 1
stoichiometry:c77 : 1

m1572*0.1

nodelay

--

true

0

false

PMID: 18191460 This leads to coupling of IRAKs via MyD88 and induces a signaling cascade leading to activation of NF-kappaB and MAPKs pathways. PMID: 18191460, 9575168, 9374458, 9430229 MyD88 was first shown to act as an adaptor molecule that functions to recruit IRAK to the cytoplasmic TIR domain of the IL-1R complex following stimulation with IL-1. PMID: 18191460, 9575168 A MyD88 splice variant termed MyD88short (MyD88s), which lacks the linker domain between the DD and the TIR domain does not bind IRAK4 and acts as a negative regulator of IL1R/MYD88 signals, thus leading to a controlled negative regulation of innate immune responses.

Go back
618.0, 227.0
23.0, 23.0

p28

p28

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e42 MO000039077

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c89 : 1
stoichiometry:c79 : 1

m46*m17258*0.1

nodelay

--

true

0

false

PMID: 18191460 This leads to coupling of IRAKs via MyD88 and induces a signaling cascade leading to activation of NF-kappaB and MAPKs pathways.

Go back
733.0, 730.0
25.0, 25.0

p29

p29

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000058 e45

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c94 : 1
stoichiometry:c82 : 1

m6*m49*0.1

nodelay

--

true

0

false

PMID: 18191460 This leads to coupling of IRAKs via MyD88 and induces a signaling cascade leading to activation of NF-kappaB and MAPKs pathways. PMID: 18191460, 14989423 With respect to protective immune mechanisms possibly mediated by IL-1s, the most significant property is the induction of NF-kappaB followed by the initiation of an inflammatory response and expression of NOS2 in macrophages.

Go back
137.0, 1030.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e14 MO000019397

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c9 : 1
stoichiometry:c7 : 1

m16*m3964*0.1

nodelay

--

true

0

false

PMID: 18191460, 12775723, 11404392, 10586073, 11222859 For example, the mycobacterial lipoglycans phosphoinositol-capped lipoarabinomannan (LAM), phosphatidyl myo-inositol mannosides (PIM)2 and PIM6 and the 19 kDa mycobacterial lipoprotein represent TLR2 agonists.

Go back
711.0, 823.0
25.0, 25.0

p30

p30

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000023 e45

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c95 : 1
stoichiometry:c84 : 1

m21*m49*0.1

nodelay

--

true

0

false

PMID: 18191460 This leads to coupling of IRAKs via MyD88 and induces a signaling cascade leading to activation of NF-kappaB and MAPKs pathways.

Go back
720.0, 873.0
27.0, 27.0

p31

p31

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000022 e45

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c96 : 1
stoichiometry:c86 : 1

m20*m49*0.1

nodelay

--

true

0

false

PMID: 18191460 This leads to coupling of IRAKs via MyD88 and induces a signaling cascade leading to activation of NF-kappaB and MAPKs pathways.

Go back
944.0, 965.0
27.0, 27.0

p32

p32

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000011 e45

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c97 : 1
stoichiometry:c88 : 1

m5*m49*0.1

nodelay

--

true

0

false

PMID: 18191460 This leads to coupling of IRAKs via MyD88 and induces a signaling cascade leading to activation of NF-kappaB and MAPKs pathways.

Go back
672.0, 225.0
25.0, 25.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213 e43

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c90 : 1
stoichiometry:c91 : 1
stoichiometry:c92 : 1

m184*m47*0.1

nodelay

--

true

0

false

PMID: 18191460 The binding of MyD88 to IRAK4 is a mandatory step in the IRAK4-mediated phosphorylation of a crucial residue or residues in the kinase-activation loop of IRAK1, which induces the kinase activity of IRAK1.

Go back
736.0, 225.0
27.0, 27.0

p34

p34

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e44

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c93 : 1

m48*0.1

nodelay

--

true

0

false

PMID: 18191460 The binding of MyD88 to IRAK4 is a mandatory step in the IRAK4-mediated phosphorylation of a crucial residue or residues in the kinase-activation loop of IRAK1, which induces the kinase activity of IRAK1.

Go back
123.0, 575.0
26.0, 26.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016835 MO000016665

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c102 : 1
stoichiometry:c103 : 1

m1772*m1639*0.1

nodelay

--

true

0

false

PMID: 18191460 In classical IFN-gamma signaling, IFN-gammaRalpha as well as JAK1 and JAK2 are tyrosine phosphorylated. PMID: 18191460, 9143700 The IFN-gamma receptor (IFN-gammaR) contains two ligand-binding IFN-gammaRalpha chains associated with two signal-transducing IFN-gammaRbeta chains (Fig. 2). Both chains are required for IFN-gamma responses.

Go back
119.0, 627.0
25.0, 25.0

p36

p36

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

e47

e48

true true true true

--

and

mass

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

m64*0.1

nodelay

--

true

0

false

PMID: 18191460 In classical IFN-gamma signaling, IFN-gammaRalpha as well as JAK1 and JAK2 are tyrosine phosphorylated.

Go back
115.0, 669.0
23.0, 23.0

p37

p37

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

MO000000145 e48

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c110 : 1
stoichiometry:c107 : 1

m129*m65*0.1

nodelay

--

true

0

false

PMID: 18191460 In classical IFN-gamma signaling, IFN-gammaRalpha as well as JAK1 and JAK2 are tyrosine phosphorylated.

Go back
114.0, 744.0
25.0, 25.0

p38

p38

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

MO000000146 e48

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c111 : 1
stoichiometry:c109 : 1

m130*m65*0.1

nodelay

--

true

0

false

PMID: 18191460 In classical IFN-gamma signaling, IFN-gammaRalpha as well as JAK1 and JAK2 are tyrosine phosphorylated.

Go back
278.0, 704.0
25.0, 25.0

p39

p39

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000013119 e49

MO000019704

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c114 : 1
stoichiometry:c113 : 1

m1357*m66*0.1

nodelay

--

true

0

false

PMID: 18191460 JAK1 phosphorylates STAT1.

Go back
132.0, 825.0
27.0, 27.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 MO000019397

e18

true true true true

--

and

mass

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

m19*m3964*0.1

nodelay

--

true

0

false

PMID: 18191460, 12775723, 11404392, 10586073, 11222859 For example, the mycobacterial lipoglycans phosphoinositol-capped lipoarabinomannan (LAM), phosphatidyl myo-inositol mannosides (PIM)2 and PIM6 and the 19 kDa mycobacterial lipoprotein represent TLR2 agonists.

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278.0, 756.0
25.0, 25.0

p40

p40

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

MO000019704

MO000016856

true true true true

--

and

mass

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

m4238*0.1

nodelay

--

true

0

false

PMID: 18191460 After phosphorylation, two STAT1 molecules dimerize, bind to the IFN-gamma activator factor (GAF), and enter the nucleus to bind to the IFN-gamma activator sequence.

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346.0, 812.0
25.0, 25.0

p41

p41

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016856 e5

e64

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c118 : 1
stoichiometry:c119 : 1

m1788*m11*0.1

nodelay

--

true

0

false

PMID: 18191460 After phosphorylation, two STAT1 molecules dimerize, bind to the IFN-gamma activator factor (GAF), and enter the nucleus to bind to the IFN-gamma activator sequence.

Go back
347.0, 1000.0
23.0, 23.0

p42

p42

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e64

e65

true true true true

--

and

mass

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

m68*0.1

nodelay

--

true

0

false

PMID: 18191460 After phosphorylation, two STAT1 molecules dimerize, bind to the IFN-gamma activator factor (GAF), and enter the nucleus to bind to the IFN-gamma activator sequence.

Go back
427.0, 1056.0
23.0, 23.0

p43

p43

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

e65 e67

e66

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1
stoichiometry:c123 : 1
stoichiometry:c124 : 1

m69*m71*0.1

nodelay

--

true

0

false

PMID: 18191460 After phosphorylation, two STAT1 molecules dimerize, bind to the IFN-gamma activator factor (GAF), and enter the nucleus to bind to the IFN-gamma activator sequence.

Go back
273.0, 471.0
23.0, 23.0

p44

p44

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e47 MO000016573

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c125 : 1
stoichiometry:c126 : 1
stoichiometry:c127 : 1

m64*m1572*0.1

nodelay

--

true

0

false

PMID: 18191460 Importantly, MyD88 has been shown to interact with IFN-gammaRalpha thereby transducing IFN-gamma-mediated signals without affecting IFN-gamma-induced Jak-STAT signaling.

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280.0, 414.0
25.0, 25.0

p45

p45

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e68 e69

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c128 : 1
stoichiometry:c130 : 1
stoichiometry:c129 : 1

m72*m73*0.1

nodelay

--

true

0

false

PMID: 18191460 Because IFN-gammaRalpha lacks a TIR domain and MLK3 lacks a death domain, interactions of MyD88 with IFN-gammaRalpha and MLK3 must occur through yet undefined structures. PMID: 18191460 In MyD88-dependent IFN-gamma signaling, MyD88 bridges IFN-gammaRalpha and MLK3 through yet unknown domainst.

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280.0, 362.0
25.0, 25.0

p46

p46

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e70 MO000016913

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c131 : 1
stoichiometry:c132 : 1
stoichiometry:c133 : 1

m74*m1828*0.1

nodelay

--

true

0

false

PMID: 18191460 Because IFN-gammaRalpha lacks a TIR domain and MLK3 lacks a death domain, interactions of MyD88 with IFN-gammaRalpha and MLK3 must occur through yet undefined structures.

Go back
724.0, 925.0
27.0, 27.0

p47

p47

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000022 e71

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c136 : 1
stoichiometry:c135 : 1

m20*m75*0.1

nodelay

--

true

0

false

PMID: 18191460 Subsequently, MyD88 induces a mixed-lineage kinase 3 (MLK-3) ? p38 signaling cascade able control gene expression by ARE-mRNA stabilization. PMID: 18191460 After activation with IFN-gamma, MyD88 controls p38 activation, which in turn regulates the stability of AREs-containing transcripts encoding inflammatory mediators.

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200.0, 81.0
27.0, 27.0

p48

p48

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016602 MO000016625

e72

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c138 : 1
stoichiometry:c139 : 1

m1596*m1611*0.1

nodelay

--

true

0

false

PMID: 18191460, 10770283 The IL-1RI and IL-1R accessory protein (IL-1RAcP) mediate the pleiotropic effects of the proinflammatory cytokines IL-1alpha and IL-1beta, whereas IL-18R and AcPL function as receptor subunits for IL-18. PMID: 18191460 IL-1RI and IL-18R directly bind theirs ligands, whereas IL-1RAcP and AcPL have accessory function.

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112.0, 157.0
27.0, 27.0

p49

p49

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e73 e72

e74

true true true true

--

and

mass

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

m77*m76*0.1

nodelay

--

true

0

false

PMID: 18191460, 10770283 The IL-1RI and IL-1R accessory protein (IL-1RAcP) mediate the pleiotropic effects of the proinflammatory cytokines IL-1alpha and IL-1beta, whereas IL-18R and AcPL function as receptor subunits for IL-18.

Go back
953.0, 98.0
25.0, 25.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e19 MO000019394

e20

true true true true

--

and

mass

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

m23*m3961*0.1

nodelay

--

true

0

false

PMID: 18191460, 10586073 TLR4 can mediate cellular activation in response to not yet fully characterized heat- sensitive cell-associated mycobacterial factors.

Go back
501.0, 70.0
25.0, 25.0

p50

p50

cso30:i:ME_Dimerization

cso30:i:CC_Extracellular

--

e41

e75

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c143 : 1

m45*0.1

nodelay

--

true

0

false

PMID: 18191460 IL-1R1-like receptors dimerize and undergo a conformational change that is required for the recruitment of downstream signaling molecules.

Go back
821.0, 1214.0
26.0, 26.0

p51

p51

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000018229 e83

MO000016828

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c155 : 1
stoichiometry:c145 : 1

m2906*m87*0.1

nodelay

--

true

0

false

PMID: 18191460, 12563287 In these organelles, the IL-1beta and IL-18 precursors colocalize with procaspase-1 which is converted to active caspase-1 (IL-1beta converting enzyme, ICE) by a complex of proteins termed the ¡Èinflammasome¡É.

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315.0, 260.0
21.0, 21.0

p52

p52

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e74 MO000016573

e76

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c146 : 1
stoichiometry:c148 : 1
stoichiometry:c147 : 1

m78*m1572*0.1

nodelay

--

true

0

false

PMID: 18191460 As summarized above, MyD88 also serves a critical role in IL-1 and IL-18 receptor/IRAK signal-transducing function and the contribution of these signals in defective immune responses observed in MyD88¡Ý/¡Ý mice cannot be excluded.

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992.0, 1149.0
27.0, 27.0

p53

p53

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e78 e79

e80

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c149 : 1
stoichiometry:c150 : 1
stoichiometry:c151 : 1

m82*m83*0.1

nodelay

--

true

0

false

PMID: 18191460, 15967716 In fact, similar to TLRs, activation of the inflammasome that is involved in processing IL-1beta is thought to occur through the recognition of PAMPs by the LRRs of the NACHT-, LLR-, and pyrin-domain (NALP) containing proteins.

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993.0, 1214.0
25.0, 25.0

p54

p54

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e82 e77

e81

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c152 : 1
stoichiometry:c153 : 1
stoichiometry:c154 : 1

m86*m81*0.1

nodelay

--

true

0

false

PMID: 18191460 However, little is known about the natural stimuli that lead to the assembly and activation of the inflammasome. For example, the only bacterial component that is currently known to activate the NALP3 inflammasome is muramyl dipeptide (MDP), a degradation product of peptidoglycan from bacterial cell walls.

Go back
707.0, 1259.0
25.0, 25.0

p55

p55

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

MO000016828 MO000019449

MO000016597

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c157 : 1
stoichiometry:c159 : 1
stoichiometry:c160 : 1

m1765*m4012*0.1

nodelay

--

true

0

false

PMID: 18191460 During initiation of IL-1beta and IL-18 synthesis, caspase-1 is activated and processes the IL-1beta and IL-18 precursors into a mature form ready for secretion.

Go back
742.0, 1298.0
27.0, 27.0

p56

p56

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

MO000016828 MO000007330

MO000016625

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c158 : 1
stoichiometry:c161 : 1

m1765*m841*0.1

nodelay

--

true

0

false

PMID: 18191460 During initiation of IL-1beta and IL-18 synthesis, caspase-1 is activated and processes the IL-1beta and IL-18 precursors into a mature form ready for secretion.

Go back
663.0, 1283.0
25.0, 25.0

p57

p57

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

MO000019449 e81

MO000016597

true true true true

--

and

mass

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

m4012*m85*0.1

nodelay

--

true

0

false

PMID: 18191460 Hence, the possibility remains that Mtb activates the inflammasome to process IL-1beta by triggering NALP3.

Go back
138.0, 82.0
27.0, 27.0

p58

p58

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e72

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c165 : 1

m76*0.1

nodelay

--

true

0

false

PMID: 18191460, 11544324, 8766574, 9759857, 7477296 During inflammatory immune responses, IL-18 enhances T and NK cell maturation, cytokine production, and cytotoxicity. PMID: 18191460, 10940889, 10227975 IL-18 can promote both TH1 and TH2 cell development dependent on underlying genetic influences and the cytokine milieu.

Go back
437.0, 853.0
30.0, 30.0

p59

p59

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e85 e72

e84

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c167 : 1
stoichiometry:c168 : 1
stoichiometry:c166 : 1

m89*m76*0.1

nodelay

--

true

0

false

PMID: 18191460, 11544324, 8766574, 9759857, 7477296 During inflammatory immune responses, IL-18 enhances T and NK cell maturation, cytokine production, and cytotoxicity.

Go back
112.0, 1141.0
27.0, 27.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000042012 e21

e22

true true true true

--

and

mass

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

m19828*m25*0.1

nodelay

--

true

0

false

PMID: 18191460, 11861616, 16365150 The genome of Mtb as well as other mycobacteria contain highly immunostimulatory CpG motifs [20], and the cognate receptor, TLR9, has also been shown to be a relevant PRR for Mtb.

Go back
494.0, 854.0
27.0, 27.0

p60

p60

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010453 e72 MO000017265

e86

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c170 : 1
stoichiometry:c171 : 1
stoichiometry:c172 : 1
stoichiometry:c169 : 1

m93423*m76*m2121*0.1

nodelay

--

true

0

false

PMID: 18191460, 10604994, 11069090 Direct effects of IL-18 on myeloid cells have also been observed and together with IL-12 costimulation of macrophages or dendritic cells can induce IFN-gamma production.

Go back
555.0, 851.0
25.0, 25.0

p61

p61

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e72 G010262

MO000007384

true true true true

--

and

mass

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

m76*m93248*0.1

nodelay

--

true

0

false

PMID: 18191460, 11069090 Additionally, IL-18 is able to directly induce IL-6 production in macrophages.

Go back
612.0, 952.0
23.0, 23.0

p62

p62

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e36

e6

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 18191460, 14989423 With respect to protective immune mechanisms possibly mediated by IL-1s, the most significant property is the induction of NF-kappaB followed by the initiation of an inflammatory response and expression of NOS2 in macrophages.

Go back
699.0, 903.0
25.0, 25.0

p63

p63

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000022 e47

e38

true true true true

--

and

mass

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

m20*m64*0.1

nodelay

--

true

0

false

PMID: 18191460, 16491077 In this context, MyD88-dependent signaling in IFN-gamma-treated macrophages influences activation of the p38 pathway and subsequent stabilization of adenine and uracil-rich elements (AREs) that are found in the 3¡ì-untranslated region of many short-lived mRNAs, including those encoding TNF and IP-10.

Go back
665.0, 1085.0
21.0, 21.0

p64

p64

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e38

G010329

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c184 : 1
stoichiometry:c181 : 1

m42*0.1

nodelay

--

true

0

false

PMID: 18191460, 16491077 In this context, MyD88-dependent signaling in IFN-gamma-treated macrophages influences activation of the p38 pathway and subsequent stabilization of adenine and uracil-rich elements (AREs) that are found in the 3¡ì-untranslated region of many short-lived mRNAs, including those encoding TNF and IP-10. PMID: 18191460 Sun and Ding have found that in the absence of MyD88, IFN-gamma-induced mRNA stabilization but not IFN-gamma-induced transcription of TNF and IFN-gamma-inducible protein 10 (IP-10) was diminished.

Go back
663.0, 1043.0
25.0, 25.0

p65

p65

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e38

e87

true true true true

--

and

mass

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

m42*0.1

nodelay

--

true

0

false

PMID: 18191460, 16491077 In this context, MyD88-dependent signaling in IFN-gamma-treated macrophages influences activation of the p38 pathway and subsequent stabilization of adenine and uracil-rich elements (AREs) that are found in the 3¡ì-untranslated region of many short-lived mRNAs, including those encoding TNF and IP-10. PMID: 18191460 Sun and Ding have found that in the absence of MyD88, IFN-gamma-induced mRNA stabilization but not IFN-gamma-induced transcription of TNF and IFN-gamma-inducible protein 10 (IP-10) was diminished.

Go back
1062.0, 447.0
27.0, 27.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019395 e23

e24

true true true true

--

and

mass

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

m3962*m27*0.1

nodelay

--

true

0

false

PMID: 18191460 In TLR signaling, MyD88 couples TLR and IRAK through interactions of TIR domain?TIR domain and death domain?death domain (DD?DD).

Go back
936.0, 545.0
23.0, 23.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016573 e24 e46

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c100 : 1
stoichiometry:c24 : 1

m1572*m28*0.1

nodelay

--

true

0

false

PMID: 18191460 In TLR signaling, MyD88 couples TLR and IRAK through interactions of TIR domain?TIR domain and death domain?death domain (DD?DD). PMID: 18191460, 9575168 A MyD88 splice variant termed MyD88short (MyD88s), which lacks the linker domain between the DD and the TIR domain does not bind IRAK4 and acts as a negative regulator of IL1R/MYD88 signals, thus leading to a controlled negative regulation of innate immune responses.

Go back
937.0, 662.0
26.0, 26.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213 e31

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1
stoichiometry:c30 : 1

m184*m35*0.1

nodelay

--

true

0

false

PMID: 18191460 In TLR signaling, MyD88 couples TLR and IRAK through interactions of TIR domain?TIR domain and death domain?death domain (DD?DD).

Go back
167.56101563440947, 905.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
105.0, 840.5909734841225

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
583.0, 523.0

c100

c100

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
155.7839864320407, 545.0

c101

c101

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
87.0, 590.8834522085988

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
149.0, 588.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
150.9726042969964, 597.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
144.0, 640.0

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
146.0, 681.0

c106

c106

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
138.0, 685.0

c107

c107

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
147.0, 757.0

c108

c108

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
139.0, 762.0

c109

c109

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
159.0, 839.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
145.3846153846154, 646.0

c110

c110

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
143.1005417122738, 657.0

c111

c111

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
309.74157007849715, 687.0

c112

c112

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
303.0, 717.0

c113

c113

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
237.0, 717.0

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
309.32332041740193, 729.0

c115

c115

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
303.0, 769.0

c116

c116

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
359.0, 787.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
305.0, 825.0

c118

c118

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
359.0, 837.0

c119

c119

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
165.3148177390106, 853.9115249081194

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
359.0, 909.0

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
370.0, 1012.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
439.0, 1032.0

c122

c122

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
458.0, 1068.0

c123

c123

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
439.0, 1079.0

c124

c124

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
236.0, 500.9170018559899

c125

c125

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
303.9999986445131, 394.0

c126

c126

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
244.9876828256433, 484.0

c127

c127

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
237.0, 443.13549325167475

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
248.0, 427.0

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
986.0, 111.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
313.0, 427.0

c130

c130

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
240.0, 389.9005733234865

c131

c131

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
313.0, 375.0

c132

c132

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
245.0, 375.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
756.9703634757481, 895.0

c134

c134

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
751.0, 939.0

c135

c135

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
237.0, 354.7273193203715

c136

c136

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
227.47082769657843, 114.63413142072926

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
214.0, 53.0

c138

c138

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
214.0, 108.0

c139

c139

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
966.0, 123.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
146.55086685092814, 177.64280339782485

c140

c140

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
147.0, 171.0

c141

c141

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
139.0, 179.0

c142

c142

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
514.0, 95.0

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
831.0, 1181.0

c144

c144

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
834.0, 1240.0

c145

c145

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
223.0, 228.0

c146

c146

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
238.0, 271.0

c147

c147

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
343.99999897083984, 271.00405790107186

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1027.0, 1163.0

c149

c149

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
979.9425724154552, 129.29054671057938

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
953.0, 1140.0

c150

c150

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
965.7336418228921, 1166.0

c151

c151

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1026.0, 1227.0

c152

c152

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
958.0, 1227.0

c153

c153

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
963.9887054413853, 1238.0

c154

c154

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
847.4376015698018, 1246.6564023547028

c155

c155

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
776.99840047984, 1311.0

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
739.5629838530102, 1278.6079254665553

c157

c157

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
765.0978598748408, 1198.0

c158

c158

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
733.6007364642682, 1158.0

c159

c159

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
145.97824442080574, 1111.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
718.1118771703556, 1284.0

c160

c160

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
39.792182222869315, 38.67284485148491

c161

c161

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
692.2850231591362, 1158.0

c162

c162

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
679.0, 1308.0

c163

c163

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
695.9914690707606, 1284.0

c164

c164

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
168.08084319674052, 115.17940388792766

c165

c165

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
420.4164522465671, 833.8874480940947

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
456.5296867331132, 890.8523918966476

c167

c167

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
229.0, 177.0

c168

c168

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
489.03645085005047, 822.4013489469979

c169

c169

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
126.0, 1107.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
508.0, 889.0

c170

c170

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
229.0, 176.0

c171

c171

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
528.4771787862662, 875.8446084788966

c172

c172

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
550.3954710098458, 826.2436714876709

c173

c173

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
229.0, 175.0

c174

c174

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
565.0, 883.9954589886285

c175

c175

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
624.0, 975.0

c176

c176

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
623.9807072454519, 752.0

c177

c177

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
731.4906334205524, 888.0

c178

c178

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
724.0, 918.0

c179

c179

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
139.0, 1155.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
240.0, 587.7711896429153

c180

c180

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
686.0, 1095.2221365379228

c181

c181

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
645.6193931775946, 1060.0

c182

c182

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
694.376010558525, 950.0

c183

c183

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
691.5919636045421, 953.0

c184

c184

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1027.0, 461.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
113.0, 943.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1097.0, 461.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1034.4452081011955, 471.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
889.8394662168449, 394.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
965.3596099683606, 519.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
959.0, 557.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
845.9384929162684, 525.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
968.8307845767519, 632.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
964.9703634757481, 574.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
912.0, 779.0

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
918.2679814327163, 789.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
161.0, 943.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
963.0, 675.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1102.0, 163.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1018.0, 163.0

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1033.436592636686, 173.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
889.6133994365134, 258.75197799531645

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
961.8021211735029, 225.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
955.0, 259.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
966.8307845767519, 378.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
869.7287240946107, 311.0573534425622

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
954.0, 311.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
109.0, 991.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
870.0, 464.0

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
959.0, 617.0

c41

c41

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
846.0, 359.0203082044266

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
961.0, 360.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
961.0, 419.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
966.8307845767519, 690.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
961.0, 731.0

c46

c46

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
973.9999996226984, 418.52212729426344

c47

c47

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
966.1518250739341, 754.0

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
912.0, 790.0

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
162.0, 991.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
920.0, 823.0

c50

c50

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
816.0, 708.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
823.9900187110228, 742.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
808.0, 806.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
820.0, 838.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
816.0, 882.1859962219901

c55

c55

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
845.7309093090201, 895.0

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
913.0, 923.0

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
920.7488171341328, 935.0

c58

c58

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
862.0784191224138, 761.8823322690733

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
108.0, 1043.0

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
871.5508668509282, 827.0

c60

c60

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
882.0938134100054, 837.0

c61

c61

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
906.0, 837.0

c62

c62

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
850.0, 1099.0

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
752.0, 1096.0

c64

c64

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
849.0, 1051.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
743.0, 1051.0

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
856.9683596535044, 510.0

c67

c67

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
857.9708225530395, 507.0

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
326.0, 56.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
162.0, 1043.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
326.0, 115.0

c70

c70

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
331.0, 107.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
380.0, 98.54101780128966

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
418.0, 99.0

c73

c73

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
422.0, 91.0

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
585.4619109616174, 266.8652918789008

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
472.0, 102.26367507600361

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
582.0, 213.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
706.0, 183.0

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
630.0, 206.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
162.64990554975276, 909.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
600.0, 202.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
763.6568542494924, 709.0

c81

c81

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
758.0, 743.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
742.8132665336364, 805.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
736.0, 836.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
754.9904988089992, 884.0

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
747.0, 894.0

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
913.0, 937.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
922.9952479948287, 979.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
630.0133358700433, 257.9999888846529

c89

c89

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
159.3600735024118, 909.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
685.0343538464612, 257.99992623798704

c90

c90

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
649.0, 195.0

c91

c91

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
685.0, 194.9972313548228

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
750.0, 185.0

c93

c93

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
746.0578646707215, 177.0

c94

c94

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
724.309365946458, 177.0

c95

c95

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
694.0354235676139, 177.0

c96

c96

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
750.0, 66.59021305777458

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
582.0, 263.0

c98

c98

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
584.0, 261.436510427984

c99

c99

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back