1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18086373.csml convertedTime:2009.07.01.11:12

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Role of Toll-like receptor responses for sepsis pathogenesis.
Authors Weighardt H, Holzmann B.
Affiliation Department of Surgery, Technische Universitat Munchen, Ismaninger Strasse 22,81675, Munich, Germany. Heike.Weighardt@uni-duesseldorf.de
Abstract Sepsis remains a serious clinical problem because of high patient morbidity andmortality. Despite significant advances in critical care, there is still noefficient causal therapy applicable to patients indicating the need to furtherelucidate the molecular pathways leading to the immunopathology of sepsis. Theimportance of Toll-like receptors (TLR) for the induction of immune responsesagainst sepsis was demonstrated in humans exhibiting polymorphisms in TLR genesand in animal models using genetically modified mouse strains. Because of theclinical heterogeneity in human sepsis and the complex pathomechanismsunderlying sepsis, several different animal models might be used to cover thediverse features of sepsis. TLR receptors induce signaling through the adapterproteins MyD88 and TRIF. TLR signaling is tightly controlled at different stepsof the signaling cascade by series of regulatory proteins. Using a model ofsevere polymicrobial septic peritonitis we could show that single TLRs aredispensable for the induction of innate immune responses under those conditions.However, genetic ablation of MyD88 or TRIF/type-I interferon signaling pathwaysprevented hyper-inflammation and attenuated the pathogenic consequences ofsepsis indicating that dampening common signaling pathways may create a moderatesignal strength which is associated with favorable immune responses. Therefore,broad knowledge about the regulation of TLR-induced signaling pathways mayfurther elucidate the immune mechanisms during sepsis and targeting of TLRadapter molecules may provide a new therapeutic strategy against severe sepsis.
PMID 18086373
Model Abstract

Entity

G010228:IFN-beta G010815:MCP1 MO000000058:NF-kappaB MO000000077:MAPKs MO000000212:TRAF6 MO000000213:IRAK1 MO000000276:AP-1 MO000007694:IRF-3 MO000007697:IRF-4 MO000007702:IRF-7 MO000016569:IRAK-M MO000016573:MyD88 MO000016591:A20 MO000016608:IKK-i MO000016653:RP105 MO000016658:IFN Type I MO000016660:IFNbeta MO000016882:LPS MO000017072:beta-arrestin MO000017146:SHIP2 MO000017280:MCP-1 MO000017765:Smad6 MO000019331:TBK1 MO000019394:TLR4 MO000019395:TLRs MO000019398:TLR3 MO000019399:TLR5 MO000019406:Tollip MO000019479:protein remnants MO000019907:CCR2 MO000022185:flagellin MO000039077:IRAK-4 MO000041125:TRIF MO000041132:TRAM MO000041420:Pellino MO000041456:IRF-3{p} MO000042007:TLR8 MO000042012:TLR9 MO000042126:TLR7 MO000044794:ST2L MO000061958:TRIAD3 MO000066718:SIGIRR MO000068831:MAL e1: e10: e11:TLR ligand: TLR: MAL e12:TLR ligand: TLR: MAL: MyD88 e13:TLR ligand: TLR: MyD88: MAL: IRAK-4 e14:IRAK1 {p} e15:IRAK1 {p}: TRAF6 e16:TAk1: TAB2 e17:TAk1: TAB2 (activated} e18:MAPKs {activated} e19:NF-kappaB {activated} e2: e20:AP-1 {activated} e21:TLR7 ligand: TLR7: MyD88 e22:TLR3 ligand e23:LPS: TLR4 e24:TLR3 ligand: TLR3 e25:LPS: TLR4: TRAM e26:LPS: TLR4: TRAM: TRIF e27:TLR3 ligand: TLR3: TRIF e28:IRF-3{p} e29: e3: e30: e31: e32:TLR7 ligand: TLR7 e33:TLR8 ligand: TLR8 e34:TLR9 ligand: TLR9 e35:TLR7 ligand e36:TLR8 ligand e37:TLR9 ligand e38:Type I IFN e39:TLR8 ligand: TLR8: MyD88 e4: e40:TLR9 ligand: TLR9: MyD88 e41:protein remnants e42:LPS: TLR4: MyD88 e43:LPS: TLR4: MyD88: MAL e44:MyD88s e45:TLR ligand: TLR: MyD88: MAL: IRAK-4: IRAK1 e46:MyD88: IRAK: TRAF6 e47:MyD88: IRAK: TRAF6: IRF-4 e48:TLR ligand: TLR: MyD88: MAL: IRAK-4: IRAK1{p} e49:Smad6: Pellino: IRAK1: TRAF6 e5:TLR ligand e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:TLR ligand: TLR e60: e61: e62: e63:IRAK 1{p}: TRAF6 {ub} e64:TRAF6: beta-arrestin e65:flagellin: TLR5 e66:MCP-5 e67:MCP5 e68:MCP-1: CCr2 e69:MCP-5: CCR2 e7: e70:IRF-7 {activated} e71:SARM e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p5 p6 p7 p8 p9
Model Detail
388.0, 1079.0
32.0, 32.0

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p18

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
556.0, 1036.0
30.0, 30.0

MCP1

--

G010815

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p41

--

true true true true

csml-variable:Double

m93710

10

false

infinite

0

unit false false false
TRANSFACG010815

--

Go back
559.0, 619.0
32.0, 32.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m19

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
739.0, 711.0
32.0, 32.0

MAPKs

--

MO000000077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m69

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
801.0, 513.0
27.5, 27.5

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6 p35 p37

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
674.0, 310.0
27.0, 27.0

IRAK1

--

MO000000213

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p32 p35

true true true true

csml-variable:Double

m184

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000213

--

Go back
653.0, 781.0
28.0, 28.0

AP-1

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
448.0, 471.0
32.0, 32.0

IRF-3

--

MO000007694

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m977

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
849.0, 797.0
28.0, 28.0

IRF-4

--

MO000007697

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33

true true true true

csml-variable:Double

m978

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007697

--

Go back
282.0, 654.0
27.0, 27.0

IRF-7

--

MO000007702

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p43

true true true true

csml-variable:Double

m980

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
894.0, 446.0
26.0, 26.0

IRAK-M

--

MO000016569

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m1571

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016569

--

Go back
596.0, 316.0
30.0, 30.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2 p25 p26 p27 p30 p41 p42

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
813.0, 605.0
28.0, 28.0

A20

--

MO000016591

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m1585

10

false

infinite

0

unit false false false
InterProIPR002653
TRANSPATHMO000016591

--

Go back
300.0, 527.0
32.0, 32.0

IKK-i

--

MO000016608

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m1599

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016608

--

Go back
399.0, 203.0
23.0, 23.0

RP105

--

MO000016653

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m1632

10

false

infinite

0

unit false false false
InterProIPR000483
TRANSPATHMO000016653

--

Go back
500.0, 840.0
30.0, 30.0

IFN Type I

--

MO000016658

cso30:c:Protein

cso30:i:CC_CellComponent

--

p22 p23 p24

--

true true true true

csml-variable:Double

m1634

10

false

infinite

0

unit false false false
TRANSPATHMO000016658

--

Go back
256.0, 1159.0
32.0, 32.0

IFNbeta

--

MO000016660

cso30:c:Protein

cso30:i:CC_CellComponent

--

p18

--

true true true true

csml-variable:Double

m1636

10

false

infinite

0

unit false false false
InterProIPR000471
TRANSPATHMO000016660

--

Go back
299.0, 87.0
32.0, 32.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
898.0, 490.0
25.0, 25.0

beta-arrestin

--

MO000017072

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p37

true true true true

csml-variable:Double

m1964

10

false

infinite

0

unit false false false
TRANSPATHMO000017072

--

Go back
422.0, 394.0
34.0, 34.0

SHIP2

--

MO000017146

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m2023

10

false

infinite

0

unit false false false
InterProIPR000300
TRANSPATHMO000017146

--

Go back
1031.0, 1047.0
34.0, 34.0

MCP-1

--

MO000017280

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p39

true true true true

csml-variable:Double

m2133

10

false

infinite

0

unit false false false
InterProIPR008097
TRANSPATHMO000017280

--

Go back
606.0, 446.0
25.0, 25.0

Smad6

--

MO000017765

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m2522

10

false

infinite

0

unit false false false
TRANSPATHMO000017765

--

Go back
299.0, 482.0
34.0, 34.0

TBK1

--

MO000019331

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m3902

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000019331

--

Go back
163.0, 234.0
26.0, 26.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11 p28

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
615.0, 207.0
32.0, 32.0

TLRs

--

MO000019395

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m3962

10

false

infinite

0

unit false false false
TRANSPATHMO000019395

--

Go back
157.0, 301.0
27.0, 27.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
948.0, 892.0
30.0, 30.0

TLR5

--

MO000019399

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m3966

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019399

--

Go back
725.0, 349.0
28.0, 28.0

Tollip

--

MO000019406

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m3973

10

false

infinite

0

unit false false false
InterProIPR000008
TRANSPATHMO000019406

--

Go back
214.0, 674.0
27.5, 27.5

protein remnants

--

MO000019479

cso30:c:Protein

cso30:i:CC_CellComponent

--

p29

--

true true true true

csml-variable:Double

m360980

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
938.0, 1134.0
36.0, 36.0

CCR2

--

MO000019907

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p39 p40

true true true true

csml-variable:Double

m4436

10

false

infinite

0

unit false false false
InterProIPR000276
TRANSPATHMO000019907

--

Go back
1035.0, 887.0
32.0, 32.0

flagellin

--

MO000022185

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m6485

10

false

infinite

0

unit false false false
TRANSPATHMO000022185

--

Go back
778.0, 266.0
28.0, 28.0

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
304.0, 368.0
31.0, 31.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14 p15

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
290.0, 286.0
28.0, 28.0

TRAM

--

MO000041132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13

true true true true

csml-variable:Double

m19005

10

false

infinite

0

unit false false false
TRANSPATHMO000041132

--

Go back
580.0, 496.0
25.0, 25.0

Pellino

--

MO000041420

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m19288

10

false

infinite

0

unit false false false
TRANSPATHMO000041420

--

Go back
387.0, 567.0
32.0, 32.0

IRF-3{p}

--

MO000041456

cso30:c:Protein

cso30:i:CC_CellComponent

--

p16

p17

true true true true

csml-variable:Double

m19324

10

false

infinite

0

unit false false false
TRANSPATHMO000041456

--

Go back
234.0, 813.0
27.0, 27.0

TLR8

--

MO000042007

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p20

true true true true

csml-variable:Double

m19823

10

false

infinite

0

unit false false false
TRANSPATHMO000042007

--

Go back
231.0, 906.0
25.0, 25.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21 p29

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
242.0, 725.0
28.0, 28.0

TLR7

--

MO000042126

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m19940

10

false

infinite

0

unit false false false
TRANSPATHMO000042126

--

Go back
497.0, 325.0
30.0, 30.0

ST2L

--

MO000044794

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p30 p31

true true true true

csml-variable:Double

m22464

10

false

infinite

0

unit false false false
TRANSPATHMO000044794

--

Go back
254.0, 398.0
34.0, 34.0

TRIAD3

--

MO000061958

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28 p29

true true true true

csml-variable:Double

m36851

10

false

infinite

0

unit false false false
TRANSPATHMO000061958

--

Go back
441.0, 193.0
27.0, 27.0

SIGIRR

--

MO000066718

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11 p21

true true true true

csml-variable:Double

m41575

10

false

infinite

0

unit false false false
TRANSPATHMO000066718

--

Go back
684.0, 264.0
30.0, 30.0

MAL

--

MO000068831

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p31

true true true true

csml-variable:Double

m43675

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
134.75, 188.9969080091176
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
143.0, 208.0
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
799.875, 193.5
32.25, 45.0

TLR ligand: TLR: MAL

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

p2

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
947.875, 189.5
32.25, 45.0

TLR ligand: TLR: MAL: MyD88

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p4

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
955.875, 248.5
32.25, 45.0

TLR ligand: TLR: MyD88: MAL: IRAK-4

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4 p34

p32

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
735.5, 435.125
30.760000000000005, 23.069999999999993

IRAK1 {p}

--

e14

cso30:c:Protein

cso30:i:CC_Cytosol

--

p34

p6

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
735.875, 472.5
27.712470178014314, 38.66856303908974

IRAK1 {p}: TRAF6

--

e15

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

p36

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
734.875, 604.5
32.25, 45.0

TAk1: TAB2

--

e16

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p7

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
734.875, 656.5
32.25, 45.0

TAk1: TAB2 (activated}

--

e17

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

p8 p9

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
743.0, 755.0
32.0, 32.0

MAPKs {activated}

--

e18

cso30:c:Protein

cso30:i:CC_CellComponent

--

p8

p10

true true true true

csml-variable:Double

m18

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
555.0, 663.0
32.0, 32.0

NF-kappaB {activated}

--

e19

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9

--

true true true true

csml-variable:Double

m20

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
134.75, 188.9969080091176
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
653.0, 817.0
28.0, 28.0

AP-1 {activated}

--

e20

cso30:c:Protein

cso30:i:CC_CellComponent

--

p10

--

true true true true

csml-variable:Double

m21

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
333.875, 760.5
27.578317122407782, 38.48137272894109

TLR7 ligand: TLR7: MyD88

--

e21

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p25

p24

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
92.5, 253.375
31.99472759226714, 20.796572934973643

TLR3 ligand

--

e22

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p12

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
212.625, 212.5
29.899308448591903, 36.61139810031663

LPS: TLR4

--

e23

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p11

p13 p30

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
164.625, 343.5
31.524204299283447, 38.60106648891851

TLR3 ligand: TLR3

--

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p12

p15

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
280.625, 191.5
31.1894267622063, 38.19113481086486

LPS: TLR4: TRAM

--

e25

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p13

p14

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
342.875, 180.5
32.25, 45.0

LPS: TLR4: TRAM: TRIF

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p14

p16 p43

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
150.875, 460.5
32.25, 45.0

TLR3 ligand: TLR3: TRIF

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p15

p16 p41 p42

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
388.0, 1011.0
32.0, 32.0

IRF-3{p}

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

p17

p18

true true true true

csml-variable:Double

m29

10

false

infinite

0

unit false false false
TRANSPATHMO000041456

--

Go back
231.06828741016065, 727.4446551495269
142.6660345514192, 238.17973564940328

--

e29

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false true false

--

Go back
151.87518862352903, 206.12209663264667
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
231.06828741016065, 727.4446551495269
142.6660345514192, 238.17973564940328

--

e30

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false true false

--

Go back
231.06828741016065, 727.4446551495269
142.6660345514192, 238.17973564940328

--

e31

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false true false

--

Go back
233.875, 759.5
27.578317122407782, 38.48137272894109

TLR7 ligand: TLR7

--

e32

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p19

p25

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
226.875, 856.5
26.489309965131216, 36.96182785832263

TLR8 ligand: TLR8

--

e33

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p20

p26

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
278.875, 937.5
25.684391631492016, 35.83868599743072

TLR9 ligand: TLR9

--

e34

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p21

p27

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
89.5, 767.375
35.298769771528995, 22.944200351493848

TLR7 ligand

--

e35

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p19

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
84.5, 814.375
36.10720562390157, 23.469683655536024

TLR8 ligand

--

e36

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p20

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
83.5, 908.375
32.803163444639715, 21.322056239015815

TLR9 ligand

--

e37

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p21

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
473.5, 964.0
45.0, 24.0

Type I IFN

--

e38

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p22 p23 p24

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
354.875, 832.5
24.59538447421545, 34.31914112681226

TLR8 ligand: TLR8: MyD88

--

e39

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p26

p23

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
183.55678757705792, 236.09117672382234
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
341.875, 891.5
27.238988805285373, 38.00789135621215

TLR9 ligand: TLR9: MyD88

--

e40

cso30:c:Complex

cso30:i:CC_Cytosol

--

p27

p22

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
313.0, 445.0
27.5, 27.5

protein remnants

--

e41

cso30:c:Protein

cso30:i:CC_CellComponent

--

p28

--

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
493.875, 180.5
26.489309965131216, 36.96182785832263

LPS: TLR4: MyD88

--

e42

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p30

p31

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
550.875, 168.5
32.25, 45.0

LPS: TLR4: MyD88: MAL

--

e43

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p31

--

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
775.5, 335.125
31.400000000000002, 23.549999999999997

MyD88s

--

e44

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5 p32

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
953.875, 324.5
26.284134703615344, 36.67553679574234

TLR ligand: TLR: MyD88: MAL: IRAK-4: IRAK1

--

e45

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p32

p5

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
893.875, 660.5
26.481418608919068, 36.950816663607995

MyD88: IRAK: TRAF6

--

e46

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p33

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
891.875, 774.5
29.472242613323544, 41.12405946045146

MyD88: IRAK: TRAF6: IRF-4

--

e47

cso30:c:Complex

cso30:i:CC_Cytosol

--

p33

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
948.5, 387.0
29.237474766012113, 40.79647641769132

TLR ligand: TLR: MyD88: MAL: IRAK-4: IRAK1{p}

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

p34

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
636.5, 367.0
28.503578638282253, 39.77243530923104

Smad6: Pellino: IRAK1: TRAF6

--

e49

cso30:c:Complex

cso30:i:CC_Cytosol

--

p35

p6 p32

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
668.0, 86.5
37.60984182776802, 24.44639718804921

TLR ligand

--

e5

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
316.0, 906.0
465.6500709748862, 422.29345356567933

--

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
366.29367619468036, 916.0077409313898
272.27955732982184, 409.2864683429171

--

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
322.06992643728904, 911.6363602631969
453.51021810030846, 411.0207330392853

--

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
322.93705878547314, 912.503492611381
451.7759534039399, 409.2864683429171

--

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
316.0, 906.0
465.6500709748862, 422.29345356567933

--

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
316.0, 906.0
465.6500709748862, 422.29345356567933

--

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
322.93705878547314, 912.503492611381
451.7759534039399, 409.2864683429171

--

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
655.9158804881849, 1079.426469636829
29.091257918298922, 26.33524401024959

--

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
579.6082338479803, 1200.8249983826097
82.37757307749382, 74.57338194383664

--

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
316.0, 906.0
465.6500709748862, 422.29345356567933

--

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
672.625, 195.5
31.10777370438261, 38.09115147475419

TLR ligand: TLR

--

e6

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p3

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
425.7511016961721, 1093.6637213250547
14.746453546866459, 7.100144300343119

--

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
425.25867587120234, 1072.489410851356
50.4736470593979, 90.85256470691624

--

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
446.43298634490145, 1131.5805098477247
7.878813199515761, 7.8788131995157675

--

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
673.875, 543.5
27.238988805285373, 38.00789135621215

IRAK 1{p}: TRAF6 {ub}

--

e63

cso30:c:Complex

cso30:i:CC_Cytosol

--

p36

p7

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
891.625, 551.5
31.09960839860024, 38.08115314114314

TRAF6: beta-arrestin

--

e64

cso30:c:Complex

cso30:i:CC_Cytosol

--

p37

p36

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
948.625, 936.5
36.75, 45.0

flagellin: TLR5

--

e65

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p38

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
1036.125, 1212.5
24.34710203260213, 39.48178707989535

MCP-5

--

e66

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p40

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
497.5, 1100.0
42.6643598615917, 22.75432525951557

MCP5

--

e67

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p42

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
943.875, 1065.5
32.25, 45.0

MCP-1: CCr2

--

e68

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p39

--

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
943.875, 1209.5
32.25, 45.0

MCP-5: CCR2

--

e69

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p40

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
146.0, 194.0
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
338.0, 638.0
27.0, 27.0

IRF-7 {activated}

--

e70

cso30:c:Protein

cso30:i:CC_CellComponent

--

p43

--

true true true true

csml-variable:Double

m72

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
415.0, 315.5
41.5375327027571, 25.614811833366876

SARM

--

e71

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p14 p15

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
149.0, 215.0
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
157.0, 236.0
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
674.0, 133.0
27.0, 27.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

e5 MO000019395

e6

true true true true

--

and

mass

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

m5*m3962*0.1

nodelay

--

true

0

false

PMID: 18086373, 9697844, 10435584 MyD88 is the central adapter protein for signal transduction of all TLRs, except TLR3, and the interleukin (IL)-1 receptor family.

Go back
744.0, 816.0
30.0, 30.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000276 e18

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c30 : 1
stoichiometry:c29 : 1

m219*m18*0.1

nodelay

--

true

0

false

PMID: 18086373 Finally, nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors are activated resulting in the transcription of inflammatory genes.

Go back
215.0, 127.0
23.0, 23.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019394 MO000016882 MO000016653 MO000066718

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c31 : 1
stoichiometry:c75 : 1
stoichiometry:c85 : 1
stoichiometry:c33 : 1

m3961*m155666*0.1

nodelay

--

true

0

false

PMID: 18086373, 12872135, 12471095, 14625548 Engagement of TLR4 and TLR3 induces the TRIF-dependent signaling pathway, which is essential for the production of interferon (IFN)-betaand contributes to the expression of cytokines and costimulatory molecules through both IFN-beta-dependent and -independent mechanisms. PMID: 18086373, 15852007 Radioprotective 105 (RP105) is a member of the TLR family and interferes with TLR4 signaling by inhibition of ligand binding. PMID: 18086373, 15866876 SIGIRR is not able to induce NF-¦ÊB signaling by itself, but inhibits LPS-induced signaling probably by interference with the TIR domain of TLR4 and TLR9.

Go back
97.0, 301.0
27.0, 27.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

MO000019398 e22

e24

true true true true

--

and

mass

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

m3965*m23*0.1

nodelay

--

true

0

false

PMID: 18086373, 12872135, 12471095, 14625548 Engagement of TLR4 and TLR3 induces the TRIF-dependent signaling pathway, which is essential for the production of interferon (IFN)-betaand contributes to the expression of cytokines and costimulatory molecules through both IFN-beta-dependent and -independent mechanisms.

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235.0, 290.0
25.0, 25.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e23 MO000041132

e25

true true true true

--

and

mass

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

m24*m19005*0.1

nodelay

--

true

0

false

PMID: 18086373, 14517278, 12539043, 12539043 TLR4-induced TRIF signaling involves the adapter Toll-receptor-associated molecule (TRAM), whereas the interaction of TLR3 with TRIF is TRAM-independent.

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332.0, 292.0
23.0, 23.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000041125 e25 e71

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c43 : 1
stoichiometry:c146 : 1
stoichiometry:c44 : 1

m18998*m26*0.1

nodelay

--

true

0

false

PMID: 18086373, 12872135, 12471095, 14625548 Engagement of TLR4 and TLR3 induces the TRIF-dependent signaling pathway, which is essential for the production of interferon (IFN)-betaand contributes to the expression of cytokines and costimulatory molecules through both IFN-beta-dependent and -independent mechanisms. PMID: 18086373, 16964262 TRIF-induced signaling, however, is negatively regulated by the TIR adapter sterile a HEAT-Armadillo motif protein (SARM) in humans.

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231.0, 350.0
25.0, 25.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000041125 e24 e71

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c147 : 1
stoichiometry:c45 : 1

m18998*m25*0.1

nodelay

--

true

0

false

PMID: 18086373, 12872135, 12471095, 14625548 Engagement of TLR4 and TLR3 induces the TRIF-dependent signaling pathway, which is essential for the production of interferon (IFN)-betaand contributes to the expression of cytokines and costimulatory molecules through both IFN-beta-dependent and -independent mechanisms. PMID: 18086373, 16964262 TRIF-induced signaling, however, is negatively regulated by the TIR adapter sterile a HEAT-Armadillo motif protein (SARM) in humans.

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391.0, 471.0
25.0, 25.0

p16

p16

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000007694 MO000019331 MO000016608 e26 e27 MO000017146

MO000041456

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c49 : 1
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c109 : 1
stoichiometry:c47 : 1

m977*m3902*m1599*m27*m28*0.1

nodelay

--

true

0

false

PMID: 18086373, 14530355, 14739303 TRIF-induced production of IFN-beta is critically regulated by the noncanonical inhibitory factor kappaB (IkappaB) kinases TRAF family member associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1) and IkappaB kinase (IKK)epsilon followed by phosphorylation and nuclear translocation of interferon regulatory factor (IRF)3. PMID: 18086373, 17157040 Furthermore, the TRIF pathway is negatively regulated by Src homology 2(SH2)-domain-containing inositol-5-phosphatase (SHIP)-2 through interference with TANK-binding kinase 1 (TBK)1-induced signaling.

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389.0, 928.0
30.0, 30.0

p17

p17

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

MO000041456

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c53 : 1

m19324*0.1

nodelay

--

true

0

false

PMID: 18086373, 14530355, 14739303 TRIF-induced production of IFN-beta is critically regulated by the noncanonical inhibitory factor kappaB (IkappaB) kinases TRAF family member associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1) and IkappaB kinase (IKK)epsilon followed by phosphorylation and nuclear translocation of interferon regulatory factor (IRF)3.

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257.0, 1080.0
30.0, 30.0

p18

p18

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

G010228 e28

MO000016660

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c56 : 1
stoichiometry:c55 : 1

m93217*m29*0.1

nodelay

--

true

0

false

PMID: 18086373, 14530355, 14739303 TRIF-induced production of IFN-beta is critically regulated by the noncanonical inhibitory factor kappaB (IkappaB) kinases TRAF family member associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1) and IkappaB kinase (IKK)epsilon followed by phosphorylation and nuclear translocation of interferon regulatory factor (IRF)3.

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171.0, 767.0
23.0, 23.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e35 MO000042126

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c58 : 1
stoichiometry:c59 : 1

m36*m19940*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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868.0, 204.0
23.0, 23.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

MO000016573 e11

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c7 : 1
stoichiometry:c9 : 1

m1572*m11*0.1

nodelay

--

true

0

false

PMID: 18086373, 9697844, 10435584 MyD88 is the central adapter protein for signal transduction of all TLRs, except TLR3, and the interleukin (IL)-1 receptor family.

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160.0, 815.0
23.0, 23.0

p20

p20

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e36 MO000042007

e33

true true true true

--

and

mass

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

m37*m19823*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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160.0, 907.0
23.0, 23.0

p21

p21

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e37 MO000042012 MO000066718

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c64 : 1
stoichiometry:c86 : 1
stoichiometry:c65 : 1

m38*m19828*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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418.0, 881.0
27.0, 27.0

p22

p22

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e38 e40

MO000016658

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c81 : 1
stoichiometry:c74 : 1

m39*m41*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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424.0, 842.0
25.0, 25.0

p23

p23

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e38 e39

MO000016658

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c80 : 1
stoichiometry:c73 : 1

m39*m40*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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428.0, 788.0
29.0, 29.0

p24

p24

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e38 e21

MO000016658

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c79 : 1
stoichiometry:c72 : 1

m39*m22*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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291.0, 767.0
23.0, 23.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

e32 MO000016573

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c76 : 1
stoichiometry:c82 : 1

m33*m1572*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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287.0, 851.0
23.0, 23.0

p26

p26

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

e33 MO000016573

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c77 : 1
stoichiometry:c83 : 1

m34*m1572*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

Go back
298.0, 894.0
25.0, 25.0

p27

p27

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

e34 MO000016573

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c78 : 1
stoichiometry:c84 : 1

m35*m1572*0.1

nodelay

--

true

0

false

PMID: 18086373, 12356687, 15361868 Type-I interferon production can also be triggered by TLR7, TLR8 and TLR9 in an MyD88-dependent fashion.

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215.0, 447.0
23.0, 23.0

p28

p28

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

MO000061958 MO000019394

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c91 : 1
stoichiometry:c89 : 1

m36851*m3961*0.1

nodelay

--

true

0

false

PMID: 18086373, 15107846 The E3-ubiqiutin ligase TLR-ubiquitinating enzyme 3A (Triad3A), however, inhibits TLR signaling by the promotion of proteolytic degradation of TLR4 and TLR9.

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215.0, 623.0
25.0, 25.0

p29

p29

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

MO000061958 MO000042012

MO000019479

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c92 : 1
stoichiometry:c90 : 1

m36851*m19828*0.1

nodelay

--

true

0

false

PMID: 18086373, 15107846 The E3-ubiqiutin ligase TLR-ubiquitinating enzyme 3A (Triad3A), however, inhibits TLR signaling by the promotion of proteolytic degradation of TLR4 and TLR9.

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739.0, 203.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000068831 e6

e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c4 : 1
stoichiometry:c6 : 1

m43675*m6*0.1

nodelay

--

true

0

false

PMID: 18086373 MyD88 needs the bridging adapter MyD88-adapter-like /TIR-associated protein (Mal/TIRAP) for signaling induced by TLR2 and TLR4.

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434.0, 262.0
25.0, 25.0

p30

p30

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e23 MO000016573 MO000044794

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c99 : 1
stoichiometry:c95 : 1

m24*m1572*0.1

nodelay

--

true

0

false

PMID: 18086373, 15004556 ST2L inhibits signaling induced by TLR4 and IL1-R but not by TLR3, probably by sequestering MyD88 and Mal.

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554.0, 266.0
25.0, 25.0

p31

p31

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e42 MO000068831 MO000044794

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c97 : 1
stoichiometry:c100 : 1
stoichiometry:c98 : 1

m43*m43675*0.1

nodelay

--

true

0

false

PMID: 18086373, 15004556 ST2L inhibits signaling induced by TLR4 and IL1-R but not by TLR3, probably by sequestering MyD88 and Mal.

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867.0, 283.0
23.0, 23.0

p32

p32

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e13 MO000000213 e44 e49

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c15 : 1
stoichiometry:c104 : 1
stoichiometry:c118 : 1
stoichiometry:c101 : 1

m13*m184*0.1

nodelay

--

true

0

false

PMID: 18086373, 12538665 MyD88-signaling is inhibited by a splice variant of MyD88, MyD88s, which lacks the intermediate domain of MyD88 and acts as dominant negative inhibitor of the MyD88/IRAK complex by preventing the phosphorylation of IRAK-1. PMID: 18086373, 16951688 Recently, Smad6 was identified to abrogate TLR signaling by complex formation with Pelle-interacting protein (Pellino), IRAK-1 and TRAF6.

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893.0, 717.0
27.0, 27.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e46 MO000007697

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c107 : 1
stoichiometry:c108 : 1

m47*m978*0.1

nodelay

--

true

0

false

PMID: 18086373, 16243976, 16236719 In addition, IRF-4 interacts with the IRAK-1/MyD88/TRAF-6 complex and selectively inhibits IRF-5-dependent TLR signaling.

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871.0, 395.0
23.0, 23.0

p34

p34

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e48 MO000016569

e14 e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c103 : 1
stoichiometry:c112 : 1
stoichiometry:c110 : 1
stoichiometry:c111 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18086373 IRAK-M inhibits the dissociation of IRAK-1 and IRAK-4 from the TLR/MyD88/IRAK signaling complex.

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647.0, 515.0
23.0, 23.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213 MO000017765 MO000000212 MO000041420

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c115 : 1
stoichiometry:c116 : 1
stoichiometry:c117 : 1
stoichiometry:c120 : 1

m184*m2522*m183*m19288*0.1

nodelay

--

true

0

false

PMID: 18086373, 16951688 Recently, Smad6 was identified to abrogate TLR signaling by complex formation with Pelle-interacting protein (Pellino), IRAK-1 and TRAF6.

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738.0, 558.0
27.0, 27.0

p36

p36

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e15 MO000016591 e64

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c123 : 1
stoichiometry:c127 : 1
stoichiometry:c121 : 1

m15*0.1

nodelay

--

true

0

false

PMID: 18086373 Moreover, A20 removes K63-linked ubiquitin residues from TRAF6 and therefore inhibits TRAF6 dependent NF-kappaB activation, while beta-arrestin complexes with TRAF6 and averts autoubiqitination and NF-kappaB activation by TRAF6.

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851.0, 491.0
23.0, 23.0

p37

p37

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017072 MO000000212

e64

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c125 : 1
stoichiometry:c126 : 1

m1964*m183*0.1

nodelay

--

true

0

false

PMID: 18086373 Moreover, A20 removes K63-linked ubiquitin residues from TRAF6 and therefore inhibits TRAF6 dependent NF-kappaB activation, while beta-arrestin complexes with TRAF6 and averts autoubiqitination and NF-kappaB activation by TRAF6.

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1039.0, 947.0
23.0, 23.0

p38

p38

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019399 MO000022185

e65

true true true true

--

and

mass

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

m3966*m6485*0.1

nodelay

--

true

0

false

PMID: 18086373 Bacterial flagellin is recognized by TLR5.

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1037.0, 1105.0
27.0, 27.0

p39

p39

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019907 MO000017280

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c138 : 1
stoichiometry:c141 : 1

m4436*m2133*0.1

nodelay

--

true

0

false

PMID: 18086373, 15517610 Antibody blockade of CCR2, which functions as a receptor for MCP-1 and MCP-5, demonstrated that this pathway is essential for neutrophil recruitment, bacterial clearance and prevention of kidney injury in septic peritonitis.

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865.0, 249.0
27.0, 27.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

MO000039077 e12

e13

true true true true

--

and

mass

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

m17258*m12*0.1

nodelay

--

true

0

false

PMID: 18086373, 12885415 MyD88 recruits IL-1 receptor-associated kinase (IRAK)-4 which phosphorylates IRAK-1.

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1034.0, 1158.0
27.0, 27.0

p40

p40

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019907 e66

e69

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c140 : 1
stoichiometry:c142 : 1

m4436*m67*0.1

nodelay

--

true

0

false

PMID: 18086373, 15517610 Antibody blockade of CCR2, which functions as a receptor for MCP-1 and MCP-5, demonstrated that this pathway is essential for neutrophil recruitment, bacterial clearance and prevention of kidney injury in septic peritonitis.

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557.0, 985.0
27.0, 27.0

p41

p41

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000016573 e27

G010815

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c133 : 1
stoichiometry:c135 : 1
stoichiometry:c132 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 18086373, 15517610, 16714594 In the absence of MyD88, TRIF-regulated inflammatory genes including Monocyte chemoattractant protein-1 (MCP-1) and Monocyte chemoattractant protein-5 (MCP-5) were found to be induced during sepsis.

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505.0, 1041.0
27.0, 27.0

p42

p42

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

MO000016573 e27

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c136 : 1
stoichiometry:c131 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 18086373, 15517610, 16714594 In the absence of MyD88, TRIF-regulated inflammatory genes including Monocyte chemoattractant protein-1 (MCP-1) and Monocyte chemoattractant protein-5 (MCP-5) were found to be induced during sepsis.

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339.0, 587.0
25.0, 25.0

p43

p43

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000007702 e26

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c143 : 1
stoichiometry:c145 : 1
stoichiometry:c144 : 1

m980*m27*0.1

nodelay

--

true

0

false

PMID: 18086373 TLR signaling procedes via the adapters TIRAP/MyD88 or TRAM/TRIF to activate NF-kappaB or IRF3 and IRF7 transcription factors.

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871.0, 351.0
24.0, 24.0

p5

p5

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e44 e45 MO000019406

e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c14 : 1
stoichiometry:c113 : 1
stoichiometry:c102 : 1

m46*0.1

nodelay

--

true

0

false

PMID: 18086373, 12885415 MyD88 recruits IL-1 receptor-associated kinase (IRAK)-4 which phosphorylates IRAK-1. PMID: 18086373, 12538665 MyD88-signaling is inhibited by a splice variant of MyD88, MyD88s, which lacks the intermediate domain of MyD88 and acts as dominant negative inhibitor of the MyD88/IRAK complex by preventing the phosphorylation of IRAK-1. PMID: 18086373, 11751856 Toll-interacting protein (Tollip) was shown to inhibit phosphorylation and kinase activity of IRAK-1.

Go back
802.0, 438.0
26.0, 26.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e14 MO000000212 e49

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c119 : 1
stoichiometry:c18 : 1

m14*m183*0.1

nodelay

--

true

0

false

PMID: 18086373, 11960013, 9734363,10882101 Activated IRAK-1 further recruits TNF-receptor-associated factor (TRAF)-6, which activates the transforming growth factor -¦Â-activated kinase (TAK)-1/TAK1-binding protein (TAB)-2 complex as well as MAP-kinases. PMID: 18086373, 16951688 Recently, Smad6 was identified to abrogate TLR signaling by complex formation with Pelle-interacting protein (Pellino), IRAK-1 and TRAF6.

Go back
673.0, 613.0
27.0, 27.0

p7

p7

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e16 e63

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c122 : 1
stoichiometry:c21 : 1

m16*m64*0.1

nodelay

--

true

0

false

PMID: 18086373, 11960013, 9734363,10882101 Activated IRAK-1 further recruits TNF-receptor-associated factor (TRAF)-6, which activates the transforming growth factor -¦Â-activated kinase (TAK)-1/TAK1-binding protein (TAB)-2 complex as well as MAP-kinases.

Go back
648.0, 740.0
29.0, 29.0

p8

p8

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000077 e17

e18

true true true true

--

and

mass

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

m69*m17*0.1

nodelay

--

true

0

false

PMID: 18086373, 11960013, 9734363,10882101 Activated IRAK-1 further recruits TNF-receptor-associated factor (TRAF)-6, which activates the transforming growth factor -¦Â-activated kinase (TAK)-1/TAK1-binding protein (TAB)-2 complex as well as MAP-kinases.

Go back
633.0, 665.0
27.0, 27.0

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e17 MO000000058

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1
stoichiometry:c27 : 1

m17*m19*0.1

nodelay

--

true

0

false

PMID: 18086373 Finally, nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors are activated resulting in the transcription of inflammatory genes.

Go back
687.0, 111.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
806.0, 267.46625942893377

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
525.0, 293.9558233756533

c100

c100

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
890.0, 301.0

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
895.0, 370.0

c102

c102

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
902.0, 407.0

c103

c103

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
807.0, 304.05798302171013

c104

c104

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
807.0, 350.0

c105

c105

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
907.0, 697.0

c106

c106

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
871.0, 751.0180979353481

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
907.0, 744.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
411.75534119402, 428.0

c109

c109

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
892.0, 264.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
773.6725927903685, 411.0

c110

c110

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
891.0, 300.6969247617094

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
889.6844452258185, 421.6280358709937

c112

c112

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
753.0, 363.0

c113

c113

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
662.1126747623384, 337.0

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
626.0, 471.0

c115

c115

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
678.0, 527.0

c116

c116

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
605.0, 512.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
665.0, 301.4887310259279

c118

c118

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
665.0, 392.0

c119

c119

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
898.8923076923077, 222.0

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
652.4437601569801, 414.9876828256433

c120

c120

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
708.9279394432826, 566.0713431680111

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
687.0, 582.0

c122

c122

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
768.3919932160203, 582.1199957600127

c123

c123

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
882.0, 503.0

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
829.0, 512.5777087639997

c125

c125

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
870.0, 514.0

c126

c126

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
768.9998760055178, 571.0

c127

c127

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
978.0, 916.0

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1051.0, 919.0

c129

c129

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
897.7471339191503, 275.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
993.0, 959.0

c130

c130

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
519.0, 1068.0

c131

c131

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
571.0, 1012.0

c132

c132

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
572.2374521781439, 346.0

c133

c133

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
521.5024630177766, 346.0

c134

c134

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
19.6364792886759, 468.35177633939475

c135

c135

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
48.404676416390885, 483.0

c136

c136

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
974.0, 1126.6374626626937

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1049.0, 1081.0

c138

c138

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
974.0, 1156.0

c139

c139

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
902.7838630032043, 346.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1048.0, 1193.0

c140

c140

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
983.5643006869286, 1095.604103515172

c141

c141

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
982.6387405546145, 1182.0

c142

c142

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
307.0, 618.145770236779

c143

c143

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
352.0, 612.0

c144

c144

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
352.1550954989402, 226.0

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
358.864939758405, 308.03065060224134

c146

c146

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
259.93508305456845, 332.0

c147

c147

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
701.0, 298.19138408877325

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
766.0, 448.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
815.0, 472.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
770.7639112242477, 459.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
751.0, 511.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
643.0, 166.41634488272317

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
708.0, 627.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
700.0, 638.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
684.6488945988958, 732.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
677.0, 757.0

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
683.0592796928046, 693.0

c24

c24

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
668.0, 679.0

c25

c25

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
591.0, 645.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
595.0, 679.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
681.0, 800.0

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
689.0, 831.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
688.0, 160.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
759.0, 787.0

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
245.40244110928538, 110.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
182.0, 157.22288415059145

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
227.0, 150.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
132.0, 315.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
109.0, 274.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
124.0, 324.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
233.0, 249.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
267.99555925583326, 301.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
255.0, 237.10740725485942

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
704.0, 215.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
325.0, 322.6586216862937

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
263.7218109753596, 368.09132380582656

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
196.0, 363.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
306.0, 230.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
346.0, 233.90972403379814

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
185.31020551776967, 375.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
423.99609660869663, 485.24987801902176

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
403.1126648820378, 496.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
333.0, 487.3592553320612

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
332.0, 497.4114641099937

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
626.0, 224.15868398546525

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
363.0, 226.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
183.0, 483.0

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
403.0, 599.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
404.0, 958.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
295.0, 1095.0

c54

c54

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
272.0, 1110.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
294.1126650331973, 1035.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
125.0, 779.0

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
201.03433573229418, 747.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
194.0, 779.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
764.0, 216.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
121.0, 826.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
191.0, 827.0

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
183.0, 835.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
116.0, 919.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
191.0, 919.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
183.0, 922.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
446.94257241545523, 914.2905467105794

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
261.0, 779.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
253.0, 866.6132233653639

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
300.0, 926.5067449345369

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
832.0, 216.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
446.48836691527464, 874.1993955485456

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
449.3417141767529, 824.6495996440594

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
457.0, 813.0

c72

c72

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
449.0, 855.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
445.0, 865.5253855251153

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
241.98505981902218, 140.34539577127524

c75

c75

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
315.53820605174326, 346.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
310.04540524877643, 346.0

c77

c77

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
321.6912296856306, 346.0

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
361.0, 783.0

c79

c79

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
712.0, 234.14577023677901

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
379.0, 851.0

c80

c80

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
369.0, 899.599680095968

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
314.0, 779.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
310.0, 853.5689290811055

c83

c83

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
323.0, 908.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
241.99999151536161, 139.00823875203034

c85

c85

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
66.90376426057219, 82.71584469249103

c86

c86

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
243.65685424949237, 432.0

c87

c87

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
232.52145379964855, 432.0

c88

c88

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
238.0, 459.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
891.0, 213.4204706649821

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
228.0, 648.0

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
179.0, 260.0

c91

c91

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
78.51867452992303, 635.4709351281349

c92

c92

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
243.0, 234.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
466.5670832793401, 281.59600667247435

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
457.0, 222.23370760249932

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
520.0, 217.0

c96

c96

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
587.0, 279.0

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
567.0, 222.0

c98

c98

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
461.8284271247462, 289.8284271247462

c99

c99

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back