1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/16027039.csml convertedTime:2009.07.01.10:52

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title TLR3 in antiviral immunity: key player or bystander?
Authors Schroder M, Bowie AG.
Affiliation Viral Immune Evasion Group, Department of Biochemistry, Trinity College Dublin,College Green, Dublin 2, Ireland.
Abstract Toll-like receptor 3 (TLR3), which recognizes double-stranded (ds)RNA, was thefirst identified antiviral TLR and, because dsRNA is a universal viral molecularpattern, TLR3 has been assumed to have a central role in the host response toviruses. However, this role has recently been questioned by in vivo studies andthe discovery of several other antiviral pattern-recognition receptors. In thisreview, the function of TLR3 in the context of these other receptors, namelyTLR7, 8 and 9 and the newly identified dsRNA-receptor retinoic-acid induciblegene-I (RIG-I) is discussed. Also, recent research concerning the expressionprofile of TLR3, its evasion by viruses and a potential role in crosspriming isaddressed, which reveals a clearer appreciation of the contribution of TLR3 toantiviral immunity.
PMID 16027039
Model Abstract

Entity

G010228:IFN-beta G010657:IL-12 p40 G012252:CXCL10 G016992:IFN-alpha1 MO000000030:PI3K MO000000058:NF-kappaB MO000000065:RIP1 MO000000077:MAPKs MO000000212:TRAF6 MO000007694:IRF-3 MO000007702:IRF-7 MO000008179:PKR MO000016608:IKK-i MO000016658:IFN Type I MO000016882:LPS MO000016899:FADD MO000016900:Caspase-8 MO000017271:CXCL10 MO000017793:Lp MO000019241:RIP3 MO000019331:TBK1 MO000019387:cytokines MO000019394:TLR4 MO000019397:TLR2 MO000019398:TLR3 MO000022224:dsRNA MO000022225:dsRNA:PKR MO000022570:eIF-2alpha MO000041125:TRIF MO000041132:TRAM MO000041437:dsRNA:TLR3:TRIF MO000041446:dsRNA:TLR3 MO000042012:TLR9 MO000042126:TLR7 MO000103999:MDA-5 e1: e10: e11: e12:Lp: TLR2 e13:LPS: TLR4 e14:polyI:C e15:polyI:C: TLR3 e16:RIG1 e17:dsRNA: RIG1 e18:dsRNA:TLR3{p} e19:dsRNA:TLR3{p}: PI3K e2: e20:Lp: TLR2:{p} e21:e21 e22:LPS: TLR4: TRAM e23:LPS: TLR4: TRAM: TRIF e24:LPS: TLR4: TRAM: TRIF: TBK1 e25:IRF-3{activated} e26:IFN Type I e27:dsRNA:TLR3:TRIF: TRAF6 e28:NF-kappaB{activated} e29:dsRNA:TLR3{p}: TRIF: RIP1 e3: e30:MAPKs {activated} e31:FADD {activated} e32:Caspase-8{activated} e33:cytokine e34:CCL5 e35:CCL5 e36:CpG DNA e37:CpG DNA: TLR9 e38:ssRNA e39:ssRNA: TLR7 e4: e40:dsRNA: MDA-5 e41:A46R e42:A46R: TRIF e43:A52R e44:NS3-4a e45:e45 e46:dsRNA:TLR3:TRIF:TBK1:IKK-i e47:IRF-3{activated} e48:IRF-7{activated} e49:eIF-2alpha{p} e5: e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6: e60: e61: e62: e63:dsRNA:TLR3{p}: TRIF: RIP1: FADD e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p6 p7 p8 p9
Model Detail
681.0, 1129.0
30.5, 30.5

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p51

--

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
688.0, 1172.0
32.0, 32.0

IL-12 p40

--

G010657

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p52

--

true true true true

csml-variable:Double

m93589

10

false

infinite

0

unit false false false
TRANSFACG010657

--

Go back
497.0, 1080.0
30.0, 30.0

CXCL10

--

G012252

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p31

true true true true

csml-variable:Double

m95041

10

false

infinite

0

unit false false false
TRANSFACG012252

--

Go back
613.0, 1164.0
30.0, 30.0

IFN-alpha1

--

G016992

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p47 p48

--

true true true true

csml-variable:Double

m98717

10

false

infinite

0

unit false false false
TRANSPATHG016992

--

Go back
333.0, 780.0
27.5, 27.5

PI3K

--

MO000000030

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7 p9

true true true true

csml-variable:Double

m27

10

false

infinite

0

unit false false false
TRANSPATHMO000000030

--

Go back
784.0, 813.0
32.0, 32.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m13

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
564.0, 720.0
23.0, 23.0

RIP1

--

MO000000065

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m15

10

false

infinite

0

unit false false false
InterProIPR000198
TRANSPATHMO000000065

--

Go back
860.0, 739.0
32.5, 32.5

MAPKs

--

MO000000077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21

true true true true

csml-variable:Double

m69

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
598.0, 634.0
28.0, 28.0

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p17

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
740.0, 541.0
35.5, 35.5

IRF-3

--

MO000007694

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15 p30 p36 p40

true true true true

csml-variable:Double

m977

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
844.0, 660.0
32.0, 32.0

IRF-7

--

MO000007702

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p44 p45

true true true true

csml-variable:Double

m980

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
681.0, 220.0
30.0, 30.0

PKR

--

MO000008179

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m1055

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000008179

--

Go back
719.0, 491.0
26.0, 26.0

IKK-i

--

MO000016608

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p40

true true true true

csml-variable:Double

m1599

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016608

--

Go back
923.0, 1027.0
26.0, 26.0

IFN Type I

--

MO000016658

cso30:c:Protein

cso30:i:CC_CellComponent

--

p26

--

true true true true

csml-variable:Double

m1634

10

false

infinite

0

unit false false false
TRANSPATHMO000016658

--

Go back
715.0, 57.0
32.0, 32.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
448.5, 841.0
30.5, 30.5

FADD

--

MO000016899

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25 p54

true true true true

csml-variable:Double

m1814

10

false

infinite

0

unit false false false
InterProIPR001875
TRANSPATHMO000016899

--

Go back
360.0, 891.0
28.0, 28.0

Caspase-8

--

MO000016900

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p23

true true true true

csml-variable:Double

m1815

10

false

infinite

0

unit false false false
TRANSPATHMO000016900

--

Go back
348.0, 1052.0
31.0, 31.0

CXCL10

--

MO000017271

cso30:c:Protein

cso30:i:CC_CellComponent

--

p31

--

true true true true

csml-variable:Double

m2127

10

false

infinite

0

unit false false false
InterProIPR002473
TRANSPATHMO000017271

--

Go back
118.0, 671.0
27.0, 27.0

Lp

--

MO000017793

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m2549

10

false

infinite

0

unit false false false
TRANSPATHMO000017793

--

Go back
622.0, 890.0
28.0, 28.0

RIP3

--

MO000019241

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18 p20 p25

true true true true

csml-variable:Double

m3825

10

false

infinite

0

unit false false false
TRANSPATHMO000019241

--

Go back
689.0, 452.0
30.0, 30.0

TBK1

--

MO000019331

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p14 p40

true true true true

csml-variable:Double

m3902

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000019331

--

Go back
915.0, 1091.0
34.0, 34.0

cytokines

--

MO000019387

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27

--

true true true true

csml-variable:Double

m3957

10

false

infinite

0

unit false false false
TRANSPATHMO000019387

--

Go back
721.0, 143.0
26.0, 26.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
197.0, 674.0
30.0, 30.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
511.0, 286.0
26.5, 26.5

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p4

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
629.0, 276.0
30.0, 30.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p5 p35 p38

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
716.0, 267.0
32.0, 32.0

dsRNA:PKR

--

MO000022225

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m6524

10

false

infinite

0

unit false false false
TRANSPATHMO000022225

--

Go back
470.0, 182.0
28.0, 28.0

eIF-2alpha

--

MO000022570

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p53

true true true true

csml-variable:Double

m6843

10

false

infinite

0

unit false false false
InterProIPR003029
TRANSPATHMO000022570

--

Go back
694.0, 384.0
30.0, 30.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10 p12 p39

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
717.0, 198.0
29.0, 29.0

TRAM

--

MO000041132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m19005

10

false

infinite

0

unit false false false
TRANSPATHMO000041132

--

Go back
580.0, 450.0
34.0, 34.0

dsRNA:TLR3:TRIF

--

MO000041437

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19305

10

false

infinite

0

unit false false false
TRANSPATHMO000041437

--

Go back
569.0, 331.0
32.0, 32.0

dsRNA:TLR3

--

MO000041446

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19314

10

false

infinite

0

unit false false false
TRANSPATHMO000041446

--

Go back
314.0, 265.0
28.5, 28.5

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
307.0, 350.0
26.0, 26.0

TLR7

--

MO000042126

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m19940

10

false

infinite

0

unit false false false
TRANSPATHMO000042126

--

Go back
586.0, 194.0
27.0, 27.0

MDA-5

--

MO000103999

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m76904

10

false

infinite

0

unit false false false
TRANSPATHMO000103999

--

Go back
178.75, 114.99690800911759
879.7667843825748, 1277.4213709234966

--

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
187.0, 134.0
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
309.23067149602707, 257.1308668196387
294.22464111656814, 491.2055449149486

--

e11

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false true false

--

Go back
196.5, 722.0
30.677053824362613, 37.56373937677054

Lp: TLR2

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p8

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
790.5, 129.0
31.82836193967672, 38.973504415930684

LPS: TLR4

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
387.0, 68.0
42.716568544995795, 24.206055508830946

polyI:C

--

e14

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p4

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
392.625, 236.5
31.099608398600232, 38.08115314114314

polyI:C: TLR3

--

e15

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
791.375, 260.5
24.26933216168717, 37.33743409490334

RIG1

--

e16

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
792.375, 304.5
23.25, 45.0

dsRNA: RIG1

--

e17

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
578.625, 380.5
29.139935010831522, 35.68155307448759

dsRNA:TLR3{p}

--

e18

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
362.875, 723.5
32.25, 45.0

dsRNA:TLR3{p}: PI3K

--

e19

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
178.75, 114.99690800911759
879.7667843825748, 1277.4213709234966

--

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
191.625, 772.5
33.45938176970505, 40.970671554740875

Lp: TLR2:{p}

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8

p9

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
191.875, 826.5
32.25, 45.0

e21

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p9

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
851.875, 118.5
32.25, 45.0

LPS: TLR4: TRAM

--

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
947.875, 106.5
32.25, 45.0

LPS: TLR4: TRAM: TRIF

--

e23

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
1007.875, 192.5
32.25, 45.0

LPS: TLR4: TRAM: TRIF: TBK1

--

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
743.0, 597.0
35.5, 35.5

IRF-3{activated}

--

e25

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
683.5, 1029.0
41.00346020761246, 21.86851211072664

IFN Type I

--

e26

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
539.875, 645.5
32.25, 45.0

dsRNA:TLR3:TRIF: TRAF6

--

e27

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
784.0, 869.0
32.0, 32.0

NF-kappaB{activated}

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m31

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
503.875, 697.5
32.25, 45.0

dsRNA:TLR3{p}: TRIF: RIP1

--

e29

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
196.34533568765144, 132.5922436967691
844.5761130072718, 1242.2306995481947

--

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
856.0, 773.0
32.5, 32.5

MAPKs {activated}

--

e30

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m33

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
484.5, 889.0
30.5, 30.5

FADD {activated}

--

e31

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m34

10

false

infinite

0

unit false false false
InterProIPR001875
TRANSPATHMO000016899

--

Go back
360.0, 935.0
28.0, 28.0

Caspase-8{activated}

--

e32

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m35

10

false

infinite

0

unit false false false
TRANSPATHMO000016900

--

Go back
680.5, 1065.0
39.965397923875436, 21.314878892733564

cytokine

--

e33

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
348.5, 1160.125
39.204065204266456, 24.175840209297647

CCL5

--

e34

cso30:c:Protein

cso30:i:CC_Cytosol

--

p32

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
509.5, 1131.0
45.0, 24.0

CCL5

--

e35

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p32

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
117.5, 271.125
45.0, 15.75

CpG DNA

--

e36

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p33

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
300.625, 304.5
30.07894517580403, 36.83136143976004

CpG DNA: TLR9

--

e37

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
113.5, 350.625
45.0, 24.75

ssRNA

--

e38

cso30:c:Rna

cso30:i:CC_Extracellular

--

--

p34

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
309.625, 393.5
28.739835027495417, 35.191634727545406

ssRNA: TLR7

--

e39

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
228.89670670980684, 163.384081150159
779.4733709629614, 1180.6470246414135

--

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
535.625, 231.5
33.059281786368935, 40.4807532077987

dsRNA: MDA-5

--

e40

cso30:c:Complex

cso30:i:CC_Cytosol

--

p38

--

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1093.125, 400.5
22.627037633326626, 36.69249345944858

A46R

--

e41

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p39

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
841.625, 464.5
29.409390101649727, 36.011498083652725

A46R: TRIF

--

e42

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
639.5, 820.125
33.160000000000004, 24.869999999999997

A52R

--

e43

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p18 p20

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
1088.125, 316.5
23.31208492654458, 37.80338096196418

NS3-4a

--

e44

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p10 p41

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
937.5, 332.5
28.0, 28.0

e45

--

e45

cso30:c:ObjectUnknown

cso30:i:CC_Cytosol

--

p41

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
576.0, 559.0
32.0, 32.0

dsRNA:TLR3:TRIF:TBK1:IKK-i

--

e46

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m49

10

false

infinite

0

unit false false false
TRANSPATHMO000041441

--

Go back
746.0, 645.0
35.5, 35.5

IRF-3{activated}

--

e47

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m63

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
844.0, 700.0
32.0, 32.0

IRF-7{activated}

--

e48

cso30:c:Protein

cso30:i:CC_CellComponent

--

p44 p45

--

true true true true

csml-variable:Double

m64

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
468.5, 240.125
31.560000000000002, 23.67

eIF-2alpha{p}

--

e49

cso30:c:Protein

cso30:i:CC_Cytosol

--

p53

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
309.23067149602707, 257.1308668196387
294.22464111656814, 491.2055449149486

--

e5

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false true false

--

Go back
471.41612214530625, 933.042181535874
354.2339488295799, 321.25127202980514

--

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
509.6760272330448, 940.6553696570904
207.13121030258495, 311.3564689898727

--

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
476.03369689727475, 937.3299295198449
344.9987993256432, 312.6757760618636

--

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
476.69335043327015, 937.9895830558402
343.6794922536521, 311.3564689898727

--

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
471.41612214530625, 933.042181535874
354.2339488295799, 321.25127202980514

--

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
471.41612214530625, 933.042181535874
354.2339488295799, 321.25127202980514

--

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
476.69335043327015, 937.9895830558402
343.6794922536521, 311.3564689898727

--

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
730.0003082555397, 1064.9728887349731
22.130590782997203, 20.034008498292206

--

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
671.9507970879363, 1157.3243837743412
62.667085919571846, 56.730204095612436

--

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
471.41612214530625, 933.042181535874
354.2339488295799, 321.25127202980514

--

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
309.23067149602707, 257.1308668196387
294.22464111656814, 491.2055449149486

--

e6

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false true false

--

Go back
554.9070707471988, 1075.8035923048049
11.218068667319496, 5.40129232130198

--

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
554.5324676807384, 1059.6956604470083
38.39681431219049, 69.11426576194283

--

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
570.6403995385357, 1104.6480284222562
5.993649063366314, 5.9936490633663135

--

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
447.875, 713.5
32.25, 45.0

dsRNA:TLR3{p}: TRIF: RIP1: FADD

--

e63

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
190.0, 120.0
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
193.0, 141.0
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
203.0, 178.0
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
119.0, 728.0
25.0, 25.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m2549*m3964*0.1

nodelay

--

true

0

false

PMID: 16027039, 11607032 The first described ligands for TLRs were of bacterial origin, such as lipopolysaccharide (for TLR4) or peptidoglycan (for TLR2), but since the discovery of double-stranded (ds)RNA as the ligand for TLR3 it has been recognized that TLRs also have a role in the host defense against viruses.

Go back
637.0, 387.0
23.0, 23.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c123 : 1
stoichiometry:c28 : 1

m20*m18998*0.1

nodelay

--

true

0

false

PMID: 16027039 On dsRNA binding, TLR3 recruits the TIR adaptor molecule TRIF, which induces signaling pathways leading to the activation of IRF3 and NF-kappaB, and the initiation of an apoptotic cascade. PMID: 16027039, 15767257, 15710891 Also, NS3?4a, a protease from HCV, besides targeting some as yet unknown component of the RIG-I pathway, has been described recently to cleave TRIF specifically, thereby abrogating TLR3 signaling.

Go back
795.0, 200.0
25.0, 25.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m14*m19005*0.1

nodelay

--

true

0

false

PMID: 16027039, 14519765 However, its recruitment to TLR4 is mediated by an additional adaptor molecule, TRIF-related adaptor molecule (TRAM).

Go back
855.0, 204.0
25.0, 25.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m24*m18998*0.1

nodelay

--

true

0

false

PMID: 16027039 TRIF is not a TLR3-specific adaptor molecule but is also involved in IRF3 activation by TLR4.

Go back
635.0, 454.0
25.0, 25.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c36 : 1
stoichiometry:c37 : 1
stoichiometry:c125 : 1

m3902*m19305*m1599*0.1

nodelay

--

true

0

false

PMID: 16027039, 14679297, 12524442 However, TBK1 mediates both TLR4- and TLR3-induced IRF3 activation [30], so the observed differences between TLR3- and TLR4-induced IRF3 activation might be quantitative rather than qualitative. PMID: 16027039, 15210742, 15210743 RIG-I and TLR3 even seem to depend on the same kinases, IKK-i and TBK1, to phosphorylate IRF3.

Go back
915.0, 202.0
25.0, 25.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m3902*m25*0.1

nodelay

--

true

0

false

PMID: 16027039, 14679297, 12524442 However, TBK1 mediates both TLR4- and TLR3-induced IRF3 activation [30], so the observed differences between TLR3- and TLR4-induced IRF3 activation might be quantitative rather than qualitative.

Go back
683.0, 601.0
27.0, 27.0

p15

p15

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c46 : 1
stoichiometry:c128 : 1
stoichiometry:c42 : 1

m977*m49*0.1

nodelay

--

true

0

false

PMID: 16027039 TBK1 recruitment to the amino-terminal region of TRIF mediates IRF3 activation, which is important for the induction of type I interferons. PMID: 16027039, 12566418, 15767367 Whereas A46R, a TIR domain-containing protein, binds to TRIF directly and inhibits poly(I:C)-induced IRF3 activation, A52R potently blocks TLR3 signaling, leading to NF-kappaB activation. PMID: 16027039, 15210742, 15210743 RIG-I and TLR3 even seem to depend on the same kinases, IKK-i and TBK1, to phosphorylate IRF3.

Go back
753.0, 1012.0
22.0, 22.0

p16

p16

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m63*0.1

nodelay

--

true

0

false

PMID: 16027039 TBK1 recruitment to the amino-terminal region of TRIF mediates IRF3 activation, which is important for the induction of type I interferons. PMID: 16027039, 12646618 In addition, TLR3 engagement leads to a much stronger induction of type I IFNs than does TLR4 signaling

Go back
543.0, 583.0
25.0, 25.0

p17

p17

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c43 : 1
stoichiometry:c48 : 1

m183*m19305*0.1

nodelay

--

true

0

false

PMID: 16027039, 14530355, 16006187, 11101877 NF-kappaB activation was originally thought to be mediated by TRAF6 11 and 13 but it is now clear that it is at least partially mediated by RIP1, which interacts at the carboxy-terminal of TRIF.

Go back
708.0, 818.0
25.0, 25.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c51 : 1
stoichiometry:c71 : 1
stoichiometry:c116 : 1
stoichiometry:c50 : 1

m13*m30*0.1

nodelay

--

true

0

false

PMID: 16027039, 14530355, 16006187, 11101877 NF-kappaB activation was originally thought to be mediated by TRAF6 11 and 13 but it is now clear that it is at least partially mediated by RIP1, which interacts at the carboxy-terminal of TRIF. PMID: 16027039 RIP3 blocks TRIF-induced NF-kappaB activation, and can also by itself induce apoptosis, similarly to RIP1. PMID: 16027039, 12566418, 15767367 Whereas A46R, a TIR domain-containing protein, binds to TRIF directly and inhibits poly(I:C)-induced IRF3 activation, A52R potently blocks TLR3 signaling, leading to NF-kappaB activation.

Go back
509.0, 645.0
21.0, 21.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c52 : 1
stoichiometry:c53 : 1

m15*m19305*0.1

nodelay

--

true

0

false

PMID: 16027039, 14530355, 16006187, 11101877 NF-kappaB activation was originally thought to be mediated by TRAF6 11 and 13 but it is now clear that it is at least partially mediated by RIP1, which interacts at the carboxy-terminal of TRIF.

Go back
793.0, 59.0
27.0, 27.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m155666*m3961*0.1

nodelay

--

true

0

false

PMID: 16027039, 11607032 The first described ligands for TLRs were of bacterial origin, such as lipopolysaccharide (for TLR4) or peptidoglycan (for TLR2), but since the discovery of double-stranded (ds)RNA as the ligand for TLR3 it has been recognized that TLRs also have a role in the host defense against viruses.

Go back
706.0, 871.0
27.0, 27.0

p20

p20

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c57 : 1
stoichiometry:c72 : 1
stoichiometry:c117 : 1
stoichiometry:c56 : 1

m13*m32*0.1

nodelay

--

true

0

false

PMID: 16027039, 14530355, 16006187, 11101877 NF-kappaB activation was originally thought to be mediated by TRAF6 11 and 13 but it is now clear that it is at least partially mediated by RIP1, which interacts at the carboxy-terminal of TRIF. PMID: 16027039 RIP3 blocks TRIF-induced NF-kappaB activation, and can also by itself induce apoptosis, similarly to RIP1. PMID: 16027039, 12566418, 15767367 Whereas A46R, a TIR domain-containing protein, binds to TRIF directly and inhibits poly(I:C)-induced IRF3 activation, A52R potently blocks TLR3 signaling, leading to NF-kappaB activation.

Go back
798.0, 741.0
27.0, 27.0

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c60 : 1
stoichiometry:c59 : 1

m69*m30*0.1

nodelay

--

true

0

false

PMID: 16027039 Ultimately, TLR3 activation leads to the production of proinflammatory cytokines, type I IFNs and the initiation of apoptosis.

Go back
553.0, 844.0
25.0, 25.0

p22

p22

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m66*0.1

nodelay

--

true

0

false

PMID: 16027039, 15814722 RIP1 also links TRIF to the apoptotic cascade [26], which is further mediated by FADD and caspase-8.

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427.0, 894.0
25.0, 25.0

p23

p23

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c66 : 1
stoichiometry:c65 : 1

m1815*m34*0.1

nodelay

--

true

0

false

PMID: 16027039, 15814722 RIP1 also links TRIF to the apoptotic cascade [26], which is further mediated by FADD and caspase-8. PMID: 16027039 RIP3 blocks TRIF-induced NF-kappaB activation, and can also by itself induce apoptosis, similarly to RIP1.

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115.0, 934.0
30.0, 30.0

p24

p24

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

e32

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1

m35*0.1

nodelay

--

true

0

false

PMID: 16027039, 15814722 RIP1 also links TRIF to the apoptotic cascade [26], which is further mediated by FADD and caspase-8. PMID: 16027039 RIP3 blocks TRIF-induced NF-kappaB activation, and can also by itself induce apoptosis, similarly to RIP1.

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553.0, 892.0
25.0, 25.0

p25

p25

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c70 : 1
stoichiometry:c69 : 1

m1814*m3825*0.1

nodelay

--

true

0

false

PMID: 16027039 RIP3 blocks TRIF-induced NF-kappaB activation, and can also by itself induce apoptosis, similarly to RIP1.

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843.0, 1027.0
25.0, 25.0

p26

p26

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m29*0.1

nodelay

--

true

0

false

PMID: 16027039 Ultimately, TLR3 activation leads to the production of proinflammatory cytokines, type I IFNs and the initiation of apoptosis.

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841.0, 1093.0
29.0, 29.0

p27

p27

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m36*0.1

nodelay

--

true

0

false

PMID: 16027039 Ultimately, TLR3 activation leads to the production of proinflammatory cytokines, type I IFNs and the initiation of apoptosis.

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862.0, 847.0
25.0, 25.0

p28

p28

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c80 : 1
stoichiometry:c79 : 1

m13*m25*0.1

nodelay

--

true

0

false

PMID: 16027039, 14557267 Consistent with this, IFN-stimulated response element induction by TLR4, but not by TLR3, requires the NF-kappaB subunit p65.

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775.0, 1063.0
25.0, 25.0

p29

p29

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c77 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 16027039, 15731229, 15579900 Apart from this somewhat specific case, it was demonstrated that cytokines are induced in a TLR3-dependent manner in bronchial epithelial cell lines, on infection with the ssRNA viruses respiratory syncytial virus or influenza, although no animal models were used to verify a role for TLR3 in vivo.

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632.0, 334.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m3965*m119368*0.1

nodelay

--

true

0

false

PMID: 16027039, 11607032 The first described ligands for TLRs were of bacterial origin, such as lipopolysaccharide (for TLR4) or peptidoglycan (for TLR2), but since the discovery of double-stranded (ds)RNA as the ligand for TLR3 it has been recognized that TLRs also have a role in the host defense against viruses.

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843.0, 602.0
25.0, 25.0

p30

p30

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c85 : 1
stoichiometry:c124 : 1
stoichiometry:c84 : 1

m977*m26*0.1

nodelay

--

true

0

false

PMID: 16027039 TRIF is not a TLR3-specific adaptor molecule but is also involved in IRF3 activation by TLR4. PMID: 16027039, 12566418, 15767367 Whereas A46R, a TIR domain-containing protein, binds to TRIF directly and inhibits poly(I:C)-induced IRF3 activation, A52R potently blocks TLR3 signaling, leading to NF-kappaB activation.

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403.0, 1082.0
25.0, 25.0

p31

p31

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c89 : 1
stoichiometry:c86 : 1

m95041*m19314*0.1

nodelay

--

true

0

false

PMID: 16027039, 15731229 Interestingly, however, Rudd et al. found that respiratory syncytial virus-induced CXCL10 and CCL5 production, but not CXCL8 production or viral replication, were impaired in the absence of TLR3.

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405.0, 1128.0
27.0, 27.0

p32

p32

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c90 : 1
stoichiometry:c88 : 1

m38*m19314*0.1

nodelay

--

true

0

false

PMID: 16027039, 15731229 Interestingly, however, Rudd et al. found that respiratory syncytial virus-induced CXCL10 and CCL5 production, but not CXCL8 production or viral replication, were impaired in the absence of TLR3.

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199.0, 266.0
25.0, 25.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c92 : 1
stoichiometry:c93 : 1

m19828*m39*0.1

nodelay

--

true

0

false

PMID: 16027039, 12900525, 14976261, 14976262 With the discovery that unmethylated viral CpG-DNA (from herpes simplex virus-2) can stimulate TLR9 [4] and the identification of ssRNA (from influenza virus and HIV-1) as the ligand for TLR7. PMID: 16027039, 15034168, 14993594, 12900525 TLR7 is involved in the response to the ssRNA viruses VSV and influenza [5], whereas TLR9 has a role in responding to the dsDNA viruses MCMV [6], herpes simplex virus-1 (HSV-1) and HSV-2.

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198.0, 349.0
27.0, 27.0

p34

p34

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

true true true true

--

and

mass

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

m19940*m41*0.1

nodelay

--

true

0

false

PMID: 16027039, 12900525, 14976261, 14976262 With the discovery that unmethylated viral CpG-DNA (from herpes simplex virus-2) can stimulate TLR9 [4] and the identification of ssRNA (from influenza virus and HIV-1) as the ligand for TLR7. PMID: 16027039, 15034168, 14993594, 12900525 TLR7 is involved in the response to the ssRNA viruses VSV and influenza [5], whereas TLR9 has a role in responding to the dsDNA viruses MCMV [6], herpes simplex virus-1 (HSV-1) and HSV-2.

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631.0, 222.0
25.0, 25.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c98 : 1
stoichiometry:c99 : 1

m119368*m1055*0.1

nodelay

--

true

0

false

PMID: 16027039, 12773480 Before the discovery of TLR3, it was well known that cells detected viral dsRNA through dsRNA-dependent protein kinase (PKR), which, in response, inhibits host translation by phosphorylating the initiation factor, the alpha subunit of eukaryotic protein synthesis initiation factor 2, and, similar to TLR3, activates NF-kappaB.

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817.0, 548.0
22.0, 22.0

p36

p36

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c102 : 1
stoichiometry:c101 : 1

m977*m19*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624 Apart from its helicase domain, RIG-I also contains a tandem caspase recruitment domain (CARD), which transmits signals leading to NF-kappaB and IRF3 activation.

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859.0, 816.0
26.0, 26.0

p37

p37

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c103 : 1
stoichiometry:c105 : 1
stoichiometry:c104 : 1

m13*m19*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624 Apart from its helicase domain, RIG-I also contains a tandem caspase recruitment domain (CARD), which transmits signals leading to NF-kappaB and IRF3 activation.

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587.0, 237.0
25.0, 25.0

p38

p38

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m76904*m119368*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624 Along with RIG-I, a homologous CARD domain-containing helicase, melanoma differentiation-associated gene-5 (mda-5), was identified and shown to have similar effects in dsRNA signaling.

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842.0, 405.0
27.0, 27.0

p39

p39

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c110 : 1
stoichiometry:c111 : 1

m44*m18998*0.1

nodelay

--

true

0

false

PMID: 16027039, 12566418, 15767367 Whereas A46R, a TIR domain-containing protein, binds to TRIF directly and inhibits poly(I:C)-induced IRF3 activation, A52R potently blocks TLR3 signaling, leading to NF-kappaB activation.

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396.0, 180.0
23.0, 23.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m16*m3965*0.1

nodelay

--

true

0

false

PMID: 16027039 It is now clear that TLR3 can mediate responses to the synthetic analog of viral dsRNA, polyriboinosinic:polyribocytidylic acid [poly(I:C)], which has been used extensively in experimental studies to mimic viral infection.

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680.0, 545.0
27.0, 27.0

p40

p40

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c114 : 1
stoichiometry:c115 : 1
stoichiometry:c126 : 1
stoichiometry:c127 : 1
stoichiometry:c113 : 1

m977*m17*m3902*m1599*0.1

nodelay

--

true

0

false

PMID: 16027039, 12566418, 15767367 Whereas A46R, a TIR domain-containing protein, binds to TRIF directly and inhibits poly(I:C)-induced IRF3 activation, A52R potently blocks TLR3 signaling, leading to NF-kappaB activation. PMID: 16027039, 15210742, 15210743 RIG-I and TLR3 even seem to depend on the same kinases, IKK-i and TBK1, to phosphorylate IRF3.

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938.0, 381.0
27.0, 27.0

p41

p41

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m47*0.1

nodelay

--

true

0

false

PMID: 16027039, 15767257, 15710891 Also, NS3?4a, a protease from HCV, besides targeting some as yet unknown component of the RIG-I pathway, has been described recently to cleave TRIF specifically, thereby abrogating TLR3 signaling.

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863.0, 888.0
25.0, 25.0

p42

p42

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c129 : 1
stoichiometry:c131 : 1
stoichiometry:c130 : 1

m13*m6524*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624, 14982987, 12773480 This is particularly perplexing because the signaling pathways elicited by TLR3, PKR and RIG-I overlap significantly, in that all three activate NF-kappaB, whereas RIG-I and TLR3 (and possibly also PKR) activate IRF3 and IRF7.

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686.0, 649.0
26.0, 26.0

p43

p43

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c118 : 1
stoichiometry:c132 : 1
stoichiometry:c119 : 1

m28*m21*0.1

nodelay

--

true

0

false

PMID: 16027039,12509442, 15733829, 15502848 Recently, it has been demonstrated that TLR3 is phosphorylated at two tyrosine residues on activation, and that phosphatidylinositol 3-kinase (PI3K; PtdIns 3-kinase) is recruited subsequently to these residues [18], a process that seems to be required for full activation of IRF3.

Go back
779.0, 703.0
25.0, 25.0

p44

p44

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c120 : 1
stoichiometry:c136 : 1
stoichiometry:c133 : 1

m980*m49*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624, 14982987, 12773480 This is particularly perplexing because the signaling pathways elicited by TLR3, PKR and RIG-I overlap significantly, in that all three activate NF-kappaB, whereas RIG-I and TLR3 (and possibly also PKR) activate IRF3 and IRF7.

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914.0, 702.0
27.0, 27.0

p45

p45

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m980*m19*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624, 14982987, 12773480 This is particularly perplexing because the signaling pathways elicited by TLR3, PKR and RIG-I overlap significantly, in that all three activate NF-kappaB, whereas RIG-I and TLR3 (and possibly also PKR) activate IRF3 and IRF7.

Go back
1085.0, 232.0
30.0, 30.0

p46

p46

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c138 : 1

m6524*0.1

nodelay

--

true

0

false

PMID: 16027039, 11232238, 15029200, 15711932 Furthermore, apoptosis, is induced not only by TLR3 but also by PKR and probably by RIG-I.

Go back
552.0, 1179.0
23.0, 23.0

p47

p47

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m42*0.1

nodelay

--

true

0

false

PMID: 16027039, 15688039, 14751761, 12480255 Importantly, this differential expression profile is reflected in distinct gene induction patterns: pDCs produce high amounts of type I IFNs (predominantly IFN-¦Á) in response to TLR7 or TLR9 engagement, whereas myeloid DCs mainly produce IL-12 and IFN-beta on TLR3 stimulation.

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593.0, 1212.0
23.0, 23.0

p48

p48

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16027039, 15688039, 14751761, 12480255 Importantly, this differential expression profile is reflected in distinct gene induction patterns: pDCs produce high amounts of type I IFNs (predominantly IFN-¦Á) in response to TLR7 or TLR9 engagement, whereas myeloid DCs mainly produce IL-12 and IFN-beta on TLR3 stimulation.

Go back
628.0, 992.0
23.0, 23.0

p49

p49

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m42*0.1

nodelay

--

true

0

false

PMID: 16027039, 15688039, 14751761, 12480255 Importantly, this differential expression profile is reflected in distinct gene induction patterns: pDCs produce high amounts of type I IFNs (predominantly IFN-¦Á) in response to TLR7 or TLR9 engagement, whereas myeloid DCs mainly produce IL-12 and IFN-beta on TLR3 stimulation.

Go back
707.0, 314.0
25.0, 25.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m18*m119368*0.1

nodelay

--

true

0

false

PMID: 16027039, 15208624 Furthermore, an additional pattern-recognition receptor (PRR) for dsRNA, retinoic-acid inducible gene-I (RIG-I), has recently been identified [9] and seems to be emerging as a key player in the induction of an interferon response by viruses.

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599.0, 1027.0
25.0, 25.0

p50

p50

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16027039, 15688039, 14751761, 12480255 Importantly, this differential expression profile is reflected in distinct gene induction patterns: pDCs produce high amounts of type I IFNs (predominantly IFN-¦Á) in response to TLR7 or TLR9 engagement, whereas myeloid DCs mainly produce IL-12 and IFN-beta on TLR3 stimulation.

Go back
745.0, 1129.0
25.0, 25.0

p51

p51

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c150 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 16027039, 15688039, 14751761, 12480255 Importantly, this differential expression profile is reflected in distinct gene induction patterns: pDCs produce high amounts of type I IFNs (predominantly IFN-¦Á) in response to TLR7 or TLR9 engagement, whereas myeloid DCs mainly produce IL-12 and IFN-beta on TLR3 stimulation.

Go back
747.0, 1175.0
25.0, 25.0

p52

p52

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c149 : 1
stoichiometry:c147 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 16027039, 15688039, 14751761, 12480255 Importantly, this differential expression profile is reflected in distinct gene induction patterns: pDCs produce high amounts of type I IFNs (predominantly IFN-¦Á) in response to TLR7 or TLR9 engagement, whereas myeloid DCs mainly produce IL-12 and IFN-beta on TLR3 stimulation.

Go back
522.0, 182.0
27.0, 27.0

p53

p53

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c151 : 1
stoichiometry:c153 : 1
stoichiometry:c152 : 1

m6843*m6524*0.1

nodelay

--

true

0

false

PMID: 16027039, 12773480 Before the discovery of TLR3, it was well known that cells detected viral dsRNA through dsRNA-dependent protein kinase (PKR), which, in response, inhibits host translation by phosphorylating the initiation factor, the alpha subunit of eukaryotic protein synthesis initiation factor 2, and, similar to TLR3, activates NF-kappaB.

Go back
452.0, 784.0
23.0, 23.0

p54

p54

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c156 : 1
stoichiometry:c155 : 1

m32*m1814*0.1

nodelay

--

true

0

false

PMID: 16027039, 14739303, 15814722 The pro-apoptotic effect is further mediated by Fas-associated death domain (FADD) and caspase-8 and it is conceivable that RIP1 engages FADD through its death domain.

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507.0, 333.0
27.0, 27.0

p6

p6

cso30:i:ME_Phosphorylation

cso30:i:CC_EndosomeLumen

--

true true true true

--

and

mass

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

m19314*0.1

nodelay

--

true

0

false

PMID: 16027039,12509442, 15733829, 15502848 Recently, it has been demonstrated that TLR3 is phosphorylated at two tyrosine residues on activation, and that phosphatidylinositol 3-kinase (PI3K; PtdIns 3-kinase) is recruited subsequently to these residues [18], a process that seems to be required for full activation of IRF3.

Go back
334.0, 641.0
25.0, 25.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1

m20*m27*0.1

nodelay

--

true

0

false

PMID: 16027039,12509442, 15733829, 15502848 Recently, it has been demonstrated that TLR3 is phosphorylated at two tyrosine residues on activation, and that phosphatidylinositol 3-kinase (PI3K; PtdIns 3-kinase) is recruited subsequently to these residues [18], a process that seems to be required for full activation of IRF3.

Go back
118.0, 779.0
27.0, 27.0

p8

p8

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 16027039, 11101877 The only other TLR that has been shown to be phosphorylated and to recruit PI3K is TLR2.

Go back
251.0, 782.0
25.0, 25.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c25 : 1
stoichiometry:c24 : 1

m22*m27*0.1

nodelay

--

true

0

false

PMID: 16027039, 11101877 The only other TLR that has been shown to be phosphorylated and to recruit PI3K is TLR2.

Go back
132.0, 698.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
408.0, 92.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
776.0, 559.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
785.1192895849364, 568.0

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
806.0, 350.0

c102

c102

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
816.0, 829.0

c103

c103

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
822.2753247325671, 839.0

c104

c104

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
816.0, 327.0

c105

c105

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
600.0, 221.0

c106

c106

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
617.8255999415425, 267.48291759203994

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
576.9876828256433, 250.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.0, 419.0

c109

c109

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
412.9878410806249, 210.749095936829

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
724.0, 406.0

c110

c110

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
856.0, 432.0

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
715.0, 559.0

c112

c112

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
707.0, 570.0

c113

c113

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
407.7712405640564, 275.0

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
710.6247325599811, 490.0

c115

c115

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
673.0, 831.1142390955955

c116

c116

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
671.0, 845.0

c117

c117

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
718.4247842258704, 629.0

c118

c118

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
712.0, 662.0

c119

c119

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
408.0, 203.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
810.8599434057004, 685.0

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
952.0, 369.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
972.4110758737629, 340.0

c122

c122

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
663.9612652535234, 337.0

c123

c123

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
856.0, 501.0

c124

c124

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
603.7186711919194, 479.0

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
695.8834522085988, 482.0

c126

c126

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
708.4920113466981, 517.0

c127

c127

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
608.0, 581.0

c128

c128

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
816.0, 844.0

c129

c129

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
738.9314397197344, 286.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
823.8248474318787, 889.6648611557189

c130

c130

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
748.0, 282.62520640148284

c131

c131

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
395.0, 682.9936557835333

c132

c132

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
804.0, 716.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
876.0, 685.0

c134

c134

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
884.0, 716.0

c135

c135

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
605.0, 591.0

c136

c136

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
816.0, 328.0

c137

c137

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
734.0, 247.01079267861846

c138

c138

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
575.0, 1183.4492994358154

c139

c139

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
659.0, 298.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
611.0, 1201.1554175279994

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
44.02394693185886, 323.0

c141

c141

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
104.1612910692482, 411.0

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
651.0, 1010.0

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
624.0, 1040.0

c144

c144

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
87.69343254071765, 399.91561654657346

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
63.511387379298185, 324.0

c146

c146

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
728.0, 1188.0

c147

c147

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
777.9998565211961, 663.0

c148

c148

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
779.9999997139449, 644.0001311217466

c149

c149

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.0, 327.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
719.996329433163, 1142.0

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
498.0, 196.0

c151

c151

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
500.4652570302059, 209.0

c152

c152

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
556.9999783581305, 195.6204892205602

c153

c153

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
477.7508183746969, 742.0

c154

c154

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
464.0, 767.0

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
464.0, 815.0

c156

c156

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
542.0, 347.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
534.0, 356.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
347.0249611950098, 396.40956015652137

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
347.0, 674.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
150.7335526581254, 699.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
351.0, 666.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
151.69575691178835, 751.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
145.0, 793.0

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
225.0, 793.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
229.75875436336548, 807.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
283.9987691360801, 794.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
608.0, 398.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
668.0, 399.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
614.9005733234865, 410.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
806.0, 168.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
144.0, 741.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
746.0, 213.0

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
819.0, 166.17098622832063

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
868.0, 164.0

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
880.0, 149.39003086148546

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
724.0, 236.9999986899282

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
668.0, 467.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
614.0, 467.0

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
667.3206894885279, 475.22606655426654

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
719.0, 234.9688349035924

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
937.0978598748408, 152.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
747.0, 73.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
940.0, 215.0

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
715.9463531699773, 576.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
710.0, 615.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
562.4605149764209, 484.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
764.0, 681.0

c44

c44

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.6921915811266, 1026.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
713.0843457775708, 495.0

c46

c46

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
573.848442145943, 612.4585460028801

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
556.0, 608.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
740.9938556058523, 829.0

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
746.0, 92.0140729029702

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
733.0, 839.0

c50

c50

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
572.0, 684.0

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
519.9457396929276, 467.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
520.0, 666.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
531.7618204050059, 672.428457546758

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
739.5357429061181, 840.0

c55

c55

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
733.0, 885.0

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
536.0, 733.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
833.0, 755.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
825.0, 762.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
806.1859962219901, 86.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
572.0, 673.0

c60

c60

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
530.5523315630031, 750.5819261136269

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
521.5214432661302, 866.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
480.0, 755.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
388.0, 905.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
394.735033111711, 915.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
459.99632943316306, 905.0

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
153.0, 949.0

c67

c67

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
479.0, 863.0

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
522.9972313548228, 904.2104534567059

c69

c69

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
538.0, 304.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
585.9979346843595, 904.0

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
650.0, 844.6117584882778

c71

c71

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
650.0, 888.9045188287974

c72

c72

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
868.0, 1040.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
725.0, 1040.0

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
720.0, 1080.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
870.0, 1108.0

c76

c76

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
728.0, 1076.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
816.0, 835.0

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
823.5559743736493, 864.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
644.0, 306.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
894.9996824734978, 129.0

c80

c80

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
807.9999953645336, 789.0

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
436.0, 1095.0

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
776.0, 569.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
787.0, 615.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
875.9999707971166, 238.0

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
386.1554175279993, 1079.5777087639997

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
439.99934261884107, 1142.1025556746006

c87

c87

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
394.89547372126214, 1151.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
299.58768977952303, 354.0

c89

c89

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
609.0, 347.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
283.81888246618854, 353.0

c90

c90

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
232.0, 279.0

c91

c91

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
163.0, 279.0

c92

c92

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
224.0, 284.0

c93

c93

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
233.0, 363.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
159.0, 363.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
225.0, 369.0

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
644.0, 255.0

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
664.0, 235.0

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
656.0, 242.0

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back