1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/16343886.csml convertedTime:2009.07.01.10:53

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title How Toll-like receptors signal: what we know and what we don't know.
Authors O'Neill LA.
Affiliation School of Biochemistry and Immunology, Trinity College Dublin, Ireland.laoneill@tcd.ie
Abstract Signal transduction pathways activated by Toll-like receptors (TLRs) havecontinued to be a major focus of research for investigators interested in theinitiation of innate immune responses and the induction of pro-inflammatorycytokines and type I interferons during infection. Biochemical details of themajor signalling pathways have now been obtained, and the specific signallingpathways activated by different TLRs are being elucidated. New insights into theactivation of IRF family members, notably IRF3, IRF5 and IRF7, have beenobtained, and interesting spatiotemporal aspects of signalling by MyD88 leadingto IRF7 activation revealed. Adapters in TLR signalling are targets forinhibition, both by endogenous regulators and by virally derived proteins.Selective targeting of pathways by anti-inflammatory glucocorticoids alsoindicates the potential for modulating TLR signalling therapeutically.
PMID 16343886
Model Abstract

Entity

G010228:IFN-beta G010262:IL-6 G010329:TNF-alpha G010657:IL-12 p40 MO000000022:p38 MO000000023:JNK MO000000058:NF-kappaB MO000000200:p50 MO000000212:TRAF6 MO000000214:IL-1 MO000000289:TNF-alpha MO000007700:IRF-5{active} MO000007702:IRF-7 MO000016573:MyD88 MO000016574:TAK1 MO000016595:IL-1RI MO000016808:TGFbeta MO000016882:LPS MO000018132:CD14 MO000019331:TBK1 MO000019394:TLR4 MO000019395:TLRs MO000019396:TLR1 MO000019397:TLR2 MO000019398:TLR3 MO000019399:TLR5 MO000019422:TLR6 MO000019479:protein remnants MO000022185:flagellin MO000022224:dsRNA MO000039077:IRAK-4 MO000041125:TRIF MO000041132:TRAM MO000042012:TLR9 MO000042130:TLR11 MO000044786:ST2 MO000068831:MAL e1: e10: e11:TLR2: TLR6 e12:TLR2: TLR1 e13:glycerophosphatidylinositol e14:TLR4: TLR4 e15:LPS: CD14 e16:LPS: CD14: TLR4: TLR4 e17:CD36 e18:lipopeptides: CD36 e19:glycerophosphatidylinositol: CD36 e2: e20:glycerophosphatidylinositol: CD36: TLR2: TLR1 e21:lipopeptides: CD36: TLR2: TLR6 e22:glycerophosphatidylinositol: CD36: TLR2: TLR6 e23:lipopeptides: CD36: TLR2: TLR1 e24:TLR ligand e25:TLR ligand: TLR e26:dsRNA: TLR3 e27:flagellin: TLR5 e28:flagellin: TLR11 e29:CpG DNA e3: e30:CpG DNA: TLR9 e31:TLR ligand: TLR: TLR e32:TLR ligand: TLR: TLR: MyD88 e33:TLR ligand: TLR: TLR: MyD88: IRAK-4: IRAK1 e34:TLR ligand: TLR: TLR: MyD88: IRAK-4: IRAK1{p} e35:TLR ligand: TLR: TLR: MyD88: IRAK-4 (activated): IRAK1 e36:TLR ligand: TLR: TLR: MyD88: IRAK-4 e37:IRAK1 {p} e38:IRAK1 {p}: TRAF6 e39:IRAK1 {p}: TRAF6 {activated} e4: e40:IRAK1 {p}: TRAF6 {ub} e41:IRAK1 {p}: TRAF6 {ub}: TAK1 e42:IRAK1 {p}: TRAF6 {ub}: TAK1 {ub} e43:IKK-alpha:IKK-beta:IKK-gamma e44:IKK-alpha:IKK-beta:IKK-gamma {activated} e45:p38 {activated} e46:JNK {activated} e47:NF-kappaB {activated} e48:LPS: CD14: TLR4: TLR4: MyD88: MAL e49:TLR ligand: TLR: TLR: MyD88: MyD88 e5:Irak1 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:lipopeptides e60: e61: e62: e63:LPS: CD14: TLR4: TLR4: TRIF: TRAM e64:dsRNA: TLR3: TRIF e65:LPS: CD14: TLR4: TLR4: TRIF: TRAM: TBK1 e66:dsRNA: TLR3: TRIF: TBK1 e67:RelA p65: IRF-3 {p} e68:IL-1AcP: MyD88 e69:IL-1AcP e7: e70:IL-1: IL-1RI e71:IL-1: IL-1RI: IL-AcP: MyD88 e72:CpG DNA: TLR9: MyD88 e73:IFN-alpha e74: e75: e76: e77:CpG DNA: TLR9: MyD88: IRF-7 e78:MyD88s e79:TLR ligand: TLR: TLR: MyD88s e8: e80:NS3/4A e81:MyD88 {ub} e82:TRIF {inactive} e83:IRF-7 {activated} e84:iRAK-4: iRAK1: IRF-7 e85:MyD88: TRAF6: IRF-5 e86:IRF-3: IRF-3 e87:IRF-3: IRF-3 {p} e88:RelA p65: IRF-3 e89:IkappaB-zeta e9: e90:IkappaB-zeta: p50 e91:IRF-5

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p55 p56 p57 p58 p59 p6 p60 p61 p62 p7 p8 p9
Model Detail
802.0, 1000.0
28.0, 28.0

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p40 p60

--

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
860.0, 1062.0
32.0, 32.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p57

--

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
754.0, 1036.0
28.0, 28.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p45

p44

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
716.0, 1183.0
28.0, 28.0

IL-12 p40

--

G010657

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p59

--

true true true true

csml-variable:Double

m93589

10

false

infinite

0

unit false false false
TRANSFACG010657

--

Go back
603.0, 597.0
25.0, 25.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p29

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
896.0, 611.0
28.0, 28.0

JNK

--

MO000000023

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p30

true true true true

csml-variable:Double

m48

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
728.0, 782.0
32.0, 32.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p31

true true true true

csml-variable:Double

m20

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
381.0, 1187.0
30.0, 30.0

p50

--

MO000000200

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p61

true true true true

csml-variable:Double

m172

10

false

infinite

0

unit false false false
TRANSPATHMO000000200

--

Go back
765.0, 355.0
30.0, 30.0

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p23 p56

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
183.0, 777.0
26.0, 26.0

IL-1

--

MO000000214

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m185

10

false

infinite

0

unit false false false
TRANSPATHMO000000214

--

Go back
1023.0, 1033.0
34.0, 34.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p44

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
990.0, 1177.0
32.0, 32.0

IRF-5{active}

--

MO000007700

cso30:c:Protein

cso30:i:CC_CellComponent

--

p62

p56

true true true true

csml-variable:Double

m979

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007700

--

Go back
488.0, 762.0
32.0, 32.0

IRF-7

--

MO000007702

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p48 p53 p54 p55

true true true true

csml-variable:Double

m980

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
617.0, 315.0
30.0, 30.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18 p32 p41 p46 p50 p56

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
711.0, 593.0
34.0, 34.0

TAK1

--

MO000016574

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p26

true true true true

csml-variable:Double

m1573

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016574

--

Go back
312.0, 774.0
32.0, 32.0

IL-1RI

--

MO000016595

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m1589

10

false

infinite

0

unit false false false
InterProIPR004076
TRANSPATHMO000016595

--

Go back
545.0, 351.0
30.0, 30.0

TGFbeta

--

MO000016808

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p50

true true true true

csml-variable:Double

m1746

10

false

infinite

0

unit false false false
TRANSPATHMO000016808

--

Go back
1254.0, 192.0
28.0, 28.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
1125.0, 155.0
29.5, 29.5

CD14

--

MO000018132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m2828

10

false

infinite

0

unit false false false
InterProIPR001611
TRANSPATHMO000018132

--

Go back
982.0, 608.0
28.0, 28.0

TBK1

--

MO000019331

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36 p37

true true true true

csml-variable:Double

m3902

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000019331

--

Go back
1108.0, 398.0
24.0, 24.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
461.0, 179.0
30.0, 30.0

TLRs

--

MO000019395

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m3962

10

false

infinite

0

unit false false false
TRANSPATHMO000019395

--

Go back
316.0, 430.0
24.0, 24.0

TLR1

--

MO000019396

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m3963

10

false

infinite

0

unit false false false
InterProIPR003016
TRANSPATHMO000019396

--

Go back
319.0, 393.0
26.0, 26.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p2

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
1107.0, 717.0
26.0, 26.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
1103.0, 1067.0
26.0, 26.0

TLR5

--

MO000019399

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m3966

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019399

--

Go back
295.0, 281.0
25.0, 25.0

TLR6

--

MO000019422

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m3987

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019422

--

Go back
464.0, 598.0
32.0, 32.0

protein remnants

--

MO000019479

cso30:c:Protein

cso30:i:CC_CellComponent

--

p51

--

true true true true

csml-variable:Double

m360980

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
1172.0, 1132.0
32.0, 32.0

flagellin

--

MO000022185

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8 p15

true true true true

csml-variable:Double

m6485

10

false

infinite

0

unit false false false
TRANSPATHMO000022185

--

Go back
1182.0, 652.0
28.0, 28.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
786.0, 280.0
28.0, 28.0

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19 p55

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
964.0, 446.0
24.0, 24.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34 p35 p52

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
963.0, 397.0
25.0, 25.0

TRAM

--

MO000041132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m19005

10

false

infinite

0

unit false false false
TRANSPATHMO000041132

--

Go back
380.0, 1006.0
24.0, 24.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
1103.0, 1159.0
26.0, 26.0

TLR11

--

MO000042130

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15

true true true true

csml-variable:Double

m19944

10

false

infinite

0

unit false false false
TRANSPATHMO000042130

--

Go back
889.0, 231.0
30.0, 30.0

ST2

--

MO000044786

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18 p32

true true true true

csml-variable:Double

m22456

10

false

infinite

0

unit false false false
TRANSPATHMO000044786

--

Go back
1051.0, 234.0
30.5, 30.5

MAL

--

MO000068831

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p32

true true true true

csml-variable:Double

m43675

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
296.75, 140.9969080091176
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
305.0, 160.0
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
319.75, 247.0
24.5, 30.0

TLR2: TLR6

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p11 p13

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
319.75, 471.0
24.5, 30.0

TLR2: TLR1

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p12 p14

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
180.0, 414.5
40.218671152228765, 22.790580319596298

glycerophosphatidylinositol

--

e13

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p9

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
1106.0, 348.5
36.47999999999999, 27.359999999999992

TLR4: TLR4

--

e14

cso30:c:Complex

cso30:i:CC_Cytosol

--

p5

p7

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
1104.625, 187.5
29.989126812197973, 36.72137977003833

LPS: CD14

--

e15

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

p7

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
1101.625, 231.5
36.75, 45.0

LPS: CD14: TLR4: TLR4

--

e16

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

p32 p34

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
292.0, 334.0
32.0, 32.0

CD36

--

e17

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9 p10

true true true true

csml-variable:Double

m17

10

false

infinite

0

unit false false false
Affymetrix109884_f_at
EnsemblENSMUSG00000002944
InterProIPR005429
MGDMGI:107899
ProteomeHumanPSD/Cd36
RefSeqNM_007643
TRANSPATHMO000031132
UnigeneMm.18628
UniProtQ08857

--

Go back
315.875, 175.5
32.25, 45.0

lipopeptides: CD36

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p10

p13 p14

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
311.875, 515.5
32.25, 45.0

glycerophosphatidylinositol: CD36

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p9

p11 p12

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
296.75, 140.9969080091176
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
311.875, 571.5
32.25, 45.0

glycerophosphatidylinositol: CD36: TLR2: TLR1

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p12

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
355.875, 143.5
32.25, 45.0

lipopeptides: CD36: TLR2: TLR6

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p13

--

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
403.875, 127.5
32.25, 45.0

glycerophosphatidylinositol: CD36: TLR2: TLR6

--

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p11

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
311.875, 643.5
32.25, 45.0

lipopeptides: CD36: TLR2: TLR1

--

e23

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p14

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
384.5, 59.375
31.924428822495592, 20.750878734622145

TLR ligand

--

e24

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p3

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
516.625, 167.5
29.989126812197966, 36.72137977003833

TLR ligand: TLR

--

e25

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

p17 p62

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1103.875, 647.5
32.25, 45.0

dsRNA: TLR3

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

p35

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
1100.875, 1103.5
29.74054872453661, 41.498440080748765

flagellin: TLR5

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
1102.875, 1197.5
25.81854468709855, 36.02587630757938

flagellin: TLR11

--

e28

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p15

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
221.5, 934.125
45.0, 15.75

CpG DNA

--

e29

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p16

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
313.875188623529, 158.12209663264667
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
374.625, 925.5
27.270079986668886, 33.39193467755375

CpG DNA: TLR9

--

e30

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p16

p46

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
574.625, 157.5
27.63751874687552, 33.841859690051656

TLR ligand: TLR: TLR

--

e31

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p17

p18 p49

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
632.875, 144.5
31.224123692420626, 43.56854468709855

TLR ligand: TLR: TLR: MyD88

--

e32

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p18

p33

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
903.875, 147.5
32.25, 45.0

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

--

e33

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p19

p21

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
1031.875, 127.5
32.25, 45.0

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

--

e34

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p20

p22

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
975.875, 135.5
32.25, 45.0

TLR ligand: TLR: TLR: MyD88: IRAK-4 (activated): IRAK1

--

e35

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p21

p20

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
1087.875, 115.5
32.25, 45.0

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

--

e36

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p22

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
908.5, 346.125
31.560000000000002, 23.66999999999999

IRAK1 {p}

--

e37

cso30:c:Protein

cso30:i:CC_Cytosol

--

p22

p23

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
769.625, 400.5
29.27874520913181, 35.851524745875686

IRAK1 {p}: TRAF6

--

e38

cso30:c:Complex

cso30:i:CC_Cytosol

--

p23

p24

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
771.875, 463.5
32.25, 45.0

IRAK1 {p}: TRAF6 {activated}

--

e39

cso30:c:Complex

cso30:i:CC_Cytosol

--

p24

p25

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
345.5567875770579, 188.09117672382234
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
775.875, 527.5
32.25, 45.0

IRAK1 {p}: TRAF6 {ub}

--

e40

cso30:c:Complex

cso30:i:CC_Cytosol

--

p25

p26

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
843.875, 587.5
32.25, 45.0

IRAK1 {p}: TRAF6 {ub}: TAK1

--

e41

cso30:c:Complex

cso30:i:CC_Cytosol

--

p26

p27

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
779.875, 647.5
32.25, 45.0

IRAK1 {p}: TRAF6 {ub}: TAK1 {ub}

--

e42

cso30:c:Complex

cso30:i:CC_Cytosol

--

p27

p28 p29 p30

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
692.0, 714.0
32.0, 32.0

IKK-alpha:IKK-beta:IKK-gamma

--

e43

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m44

10

false

infinite

0

unit false false false
TRANSPATHMO000016661

--

Go back
840.0, 714.0
32.0, 32.0

IKK-alpha:IKK-beta:IKK-gamma {activated}

--

e44

cso30:c:Protein

cso30:i:CC_CellComponent

--

p28

p31

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
TRANSPATHMO000016661

--

Go back
603.0, 657.0
25.0, 25.0

p38 {activated}

--

e45

cso30:c:Protein

cso30:i:CC_CellComponent

--

p29

--

true true true true

csml-variable:Double

m47

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
892.0, 667.0
28.0, 28.0

JNK {activated}

--

e46

cso30:c:Protein

cso30:i:CC_CellComponent

--

p30

--

true true true true

csml-variable:Double

m49

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
752.0, 834.0
32.0, 32.0

NF-kappaB {activated}

--

e47

cso30:c:Protein

cso30:i:CC_CellComponent

--

p31

p45

true true true true

csml-variable:Double

m63

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
1110.875, 295.5
26.284134703615344, 36.67553679574234

LPS: CD14: TLR4: TLR4: MyD88: MAL

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p32

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
791.875, 155.5
32.25, 45.0

TLR ligand: TLR: TLR: MyD88: MyD88

--

e49

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p33

p19

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
792.0, 211.0
27.0, 27.0

Irak1

--

e5

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19 p55

true true true true

csml-variable:Double

m5

10

false

infinite

0

unit false false false
Affymetrix1100_at
EnsemblENSG00000184216
HGNCIRAK1
InterProIPR000719
OMIM300283
ProteomeHumanPSD/IRAK1
RefSeqNM_001025242
TRANSPATHMO000080465
UnigeneHs.522819
UniProtP51617

--

Go back
497.0, 887.0
437.93653931780335, 397.16032522862275

--

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
544.3004083434498, 896.412122327623
256.0746244800565, 384.9274610018685

--

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
502.7086699724854, 892.3009078315935
426.51919937283304, 386.55850956543554

--

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
503.52419425426893, 893.1164321133771
424.8881508092656, 384.9274610018685

--

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
497.0, 887.0
437.93653931780335, 397.16032522862275

--

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
497.0, 887.0
437.93653931780335, 397.16032522862275

--

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
503.52419425426893, 893.1164321133771
424.8881508092656, 384.9274610018685

--

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
816.6855184591786, 1050.1048563567238
27.359868732476983, 24.767881168347607

--

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
744.9193816622202, 1164.2782558064305
77.47480676944379, 70.13508823339131

--

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
497.0, 887.0
437.93653931780335, 397.16032522862275

--

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
204.0, 61.5
39.05096660808435, 25.38312829525483

lipopeptides

--

e6

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p10

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
600.2191782179073, 1063.494766768816
13.868806720043954, 6.677573605947093

--

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
599.7560595047361, 1043.5806621024549
47.4696681000465, 85.44540258008368

--

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
619.6701641710974, 1099.1549076829979
7.409899410738959, 7.40989941073896

--

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
1106.875, 438.5
27.238988805285373, 38.00789135621215

LPS: CD14: TLR4: TLR4: TRIF: TRAM

--

e63

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p34

p36

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
1103.875, 563.5
32.25, 45.0

dsRNA: TLR3: TRIF

--

e64

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p35

p37

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
1107.875, 495.5
32.25, 45.0

LPS: CD14: TLR4: TLR4: TRIF: TRAM: TBK1

--

e65

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p36

p39 p53

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
1103.875, 799.5
32.25, 45.0

dsRNA: TLR3: TRIF: TBK1

--

e66

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p37

p38 p54

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
980.5, 955.125
39.72, 29.79

RelA p65: IRF-3 {p}

--

e67

cso30:c:Complex

cso30:i:CC_Cytosol

--

p39

p40 p44

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
433.625, 488.5
28.870479920013324, 35.351608065322445

IL-1AcP: MyD88

--

e68

cso30:c:Complex

cso30:i:CC_Cytosol

--

p41

p43

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
430.5, 320.125
26.92, 20.189999999999998

IL-1AcP

--

e69

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p41

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
308.0, 146.0
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
315.875, 715.5
32.25, 45.0

IL-1: IL-1RI

--

e70

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p42

p43

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
311.875, 815.5
32.25, 45.0

IL-1: IL-1RI: IL-AcP: MyD88

--

e71

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p43

--

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
411.875, 915.5
32.25, 45.0

CpG DNA: TLR9: MyD88

--

e72

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p46

p48

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
612.0, 951.0
28.0, 28.0

IFN-alpha

--

e73

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p47 p58

--

true true true true

csml-variable:Double

m76

10

false

infinite

0

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

--

Go back
379.0, 916.3051789202209
98.46498397587827, 164.38645629871195

--

e74

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false true false

--

Go back
379.0, 916.3051789202209
98.46498397587827, 164.38645629871195

--

e75

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false true false

--

Go back
379.0, 916.3051789202209
98.46498397587827, 164.38645629871195

--

e76

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false true false

--

Go back
455.5, 984.0
25.220774454028266, 35.191778307946414

CpG DNA: TLR9: MyD88: IRF-7

--

e77

cso30:c:Complex

cso30:i:CC_EndosomeMembrane

--

p48

p47

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
658.0, 292.5
36.16, 27.120000000000005

MyD88s

--

e78

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p49

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
720.875, 165.5
29.606395668930077, 41.311249770600114

TLR ligand: TLR: TLR: MyD88s

--

e79

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p49

p19

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false false false

--

Go back
311.0, 167.0
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
1199.5, 458.125
32.06782048701952, 19.77515596699537

NS3/4A

--

e80

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p52 p60

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
515.5, 474.125
32.68000000000001, 24.509999999999994

MyD88 {ub}

--

e81

cso30:c:Protein

cso30:i:CC_Cytosol

--

p50

p51

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false false false

--

Go back
964.0, 566.0
24.0, 24.0

TRIF {inactive}

--

e82

cso30:c:Protein

cso30:i:CC_CellComponent

--

p52

--

true true true true

csml-variable:Double

m85

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
510.0, 805.0
32.0, 32.0

IRF-7 {activated}

--

e83

cso30:c:Protein

cso30:i:CC_CellComponent

--

p53 p54

--

true true true true

csml-variable:Double

m86

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
691.5, 425.0
28.858689667828965, 40.26793907138925

iRAK-4: iRAK1: IRF-7

--

e84

cso30:c:Complex

cso30:i:CC_Cytosol

--

p55

--

true true true true

csml-variable:Double

m87

0

false

infinite

0

unit false false false

--

Go back
917.875, 1222.5
32.25, 45.0

MyD88: TRAF6: IRF-5

--

e85

cso30:c:Complex

cso30:i:CC_Cytosol

--

p56

p57 p58 p59

true true true true

csml-variable:Double

m88

0

false

infinite

0

unit false false false

--

Go back
984.5, 698.125
31.400000000000006, 23.549999999999997

IRF-3: IRF-3

--

e86

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p38

true true true true

csml-variable:Double

m89

0

false

infinite

0

unit false false false

--

Go back
985.5, 736.125
36.52, 27.389999999999997

IRF-3: IRF-3 {p}

--

e87

cso30:c:Protein

cso30:i:CC_Cytosol

--

p38

p60

true true true true

csml-variable:Double

m90

0

false

infinite

0

unit false false false

--

Go back
957.875, 877.5
29.140805652413288, 40.66158928243715

RelA p65: IRF-3

--

e88

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p39

true true true true

csml-variable:Double

m91

0

false

infinite

0

unit false false false

--

Go back
416.0, 1150.0
32.0, 32.0

IkappaB-zeta

--

e89

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p61

true true true true

csml-variable:Double

m92

10

false

infinite

0

unit false false false
Affymetrix1417483_at
EnsemblENSMUSG00000035356
MGDNfkbiz
ProteomeHumanPSD/Nfkbiz
RefSeqNM_030612
TRANSPATHMO000063280
UnigeneMm.247272
UniProtQ5NT97

--

Go back
319.0, 188.0
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
481.625, 1251.5
36.75, 45.0

IkappaB-zeta: p50

--

e90

cso30:c:Complex

cso30:i:CC_Cytosol

--

p61

--

true true true true

csml-variable:Double

m93

0

false

infinite

0

unit false false false

--

Go back
960.0, 1108.0
32.0, 32.0

IRF-5

--

e91

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p62

true true true true

csml-variable:Double

m94

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007700

--

Go back
223.0, 281.0
25.0, 25.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019397 MO000019422

e11

true true true true

--

and

mass

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

m3964*m3987*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

Go back
212.0, 142.0
23.0, 23.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 e17

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c15 : 1
stoichiometry:c19 : 1

m6*m17*0.1

nodelay

--

true

0

false

PMID: 16343886, 15690042 A role for other co-receptors is also emerging, with CD36 shown to be an essential co-receptor for TLR2.

Go back
387.0, 389.0
25.0, 25.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e19 e11

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c30 : 1

m19*m11*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

Go back
232.0, 582.0
23.0, 23.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e12 e19

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c25 : 1
stoichiometry:c26 : 1

m12*m19*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

Go back
251.0, 81.0
25.0, 25.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e18 e11

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1

m18*m11*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

Go back
377.0, 655.0
21.0, 21.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e18 e12

e23

true true true true

--

and

mass

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

m18*m12*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

Go back
1175.0, 1203.0
25.0, 25.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000022185 MO000042130

e28

true true true true

--

and

mass

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

m6485*m19944*0.1

nodelay

--

true

0

false

PMID: 16343886, 15860593 Finally, TLR5 and TLR11 recognize proteins from pathogens (flagellin in the case of TLR5 and profilin in the case of TLR11 [only in the mouse]).

Go back
319.0, 929.0
25.0, 25.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e29 MO000042012

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c46 : 1
stoichiometry:c47 : 1

m30*m19828*0.1

nodelay

--

true

0

false

PMID: 16343886 he most characterised are the recognition of double stranded RNA (dsRNA) by TLR3 and recognition of CpG motifs in DNA by TLR9.

Go back
518.0, 84.0
27.0, 27.0

p17

p17

cso30:i:ME_Dimerization

cso30:i:CC_Extracellular

--

e25

e31

true true true true

--

and

mass

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

m26*0.1

nodelay

--

true

0

false

PMID: 16343886, 15795223 The hypothesised model here involves the assembly of a TIR?TIR platform by the dimerization of two TLRs.

Go back
576.0, 234.0
23.0, 23.0

p18

p18

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e31 MO000016573 MO000044786

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c92 : 1
stoichiometry:c141 : 1
stoichiometry:c52 : 1

m32*m1572*0.1

nodelay

--

true

0

false

PMID: 16343886 This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain). PMID: 16343886, 15004556 An early demonstration of this was the observation that ST2, which is another member of the IL-1R subgroup of TIR proteins, inhibits TLR signalling in macrophages by sequestering MyD88 and Mal from signalling pathways.

Go back
851.0, 214.0
21.0, 21.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000039077 e5 e49 e79

e33

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c54 : 1
stoichiometry:c91 : 1
stoichiometry:c140 : 1
stoichiometry:c56 : 1

m17258*m5*m65*0.1

nodelay

--

true

0

false

PMID: 16343886 This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain). PMID: 16343886 MyD88s lacks a region important for IRAK-4 recruitment and so IRAK-4 is not engaged, hence limiting NF-kappaB activation.

Go back
232.0, 422.0
23.0, 23.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019396 MO000019397

e12

true true true true

--

and

mass

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

m3963*m3964*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

Go back
1037.0, 47.0
21.0, 21.0

p20

p20

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e35

e34

true true true true

--

and

mass

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

m36*0.1

nodelay

--

true

0

false

PMID: 16343886 This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain).

Go back
908.0, 50.0
24.0, 24.0

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e33

e35

true true true true

--

and

mass

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

m34*0.1

nodelay

--

true

0

false

PMID: 16343886 This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain).

Go back
988.0, 346.0
23.0, 23.0

p22

p22

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e34

e36 e37

true true true true

--

and

mass

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

m35*0.1

nodelay

--

true

0

false

PMID: 16343886 Phosphorylated IRAK-1 is active, and then somehow activates Traf-6.

Go back
855.0, 345.0
25.0, 25.0

p23

p23

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e37 MO000000212

e38

true true true true

--

and

mass

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

m38*m183*0.1

nodelay

--

true

0

false

PMID: 16343886 Phosphorylated IRAK-1 is active, and then somehow activates Traf-6.

Go back
856.0, 406.0
23.0, 23.0

p24

p24

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e38

e39

true true true true

--

and

mass

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

m39*0.1

nodelay

--

true

0

false

PMID: 16343886 Phosphorylated IRAK-1 is active, and then somehow activates Traf-6.

Go back
854.0, 472.0
27.0, 27.0

p25

p25

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e39

e40

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
847.0, 537.0
25.0, 25.0

p26

p26

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e40 MO000016574

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c72 : 1
stoichiometry:c73 : 1

m41*m1573*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
784.0, 598.0
23.0, 23.0

p27

p27

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e41

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c75 : 1

m42*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
783.0, 717.0
25.0, 25.0

p28

p28

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e42 e43

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c77 : 1
stoichiometry:c78 : 1

m43*m44*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
692.0, 658.0
23.0, 23.0

p29

p29

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e42 MO000000022

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c81 : 1
stoichiometry:c82 : 1

m43*m46*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
463.0, 93.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019395 e24

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c34 : 1
stoichiometry:c35 : 1

m3962*m25*0.1

nodelay

--

true

0

false

PMID: 16343886, 15795223 The hypothesised model here involves the assembly of a TIR?TIR platform by the dimerization of two TLRs.

Go back
843.0, 669.0
25.0, 25.0

p30

p30

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e42 MO000000023

e46

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c83 : 1
stoichiometry:c84 : 1

m43*m48*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
783.0, 785.0
25.0, 25.0

p31

p31

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000058 e44

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c87 : 1
stoichiometry:c86 : 1

m20*m45*0.1

nodelay

--

true

0

false

PMID: 16343886 A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.

Go back
1040.0, 318.0
23.0, 23.0

p32

p32

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000068831 e16 MO000016573 MO000044786

e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c89 : 1
stoichiometry:c136 : 1
stoichiometry:c142 : 1
stoichiometry:c90 : 1

m43675*m16*m1572*0.1

nodelay

--

true

0

false

PMID: 16343886, 11544529, 11526399 The discovery of the second TIR domain-containing adaptor, MyD88 adaptor-like (Mal), also known as TIRAP, indicated that there might be specificity in the signalling pathways, particularly when Mal was shown to have a role in TLR4, but not IL-1, signalling to NF-kappaB. PMID: 16343886, 15004556 An early demonstration of this was the observation that ST2, which is another member of the IL-1R subgroup of TIR proteins, inhibits TLR signalling in macrophages by sequestering MyD88 and Mal from signalling pathways.

Go back
711.0, 49.0
25.0, 25.0

p33

p33

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e32

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c55 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 16343886, 15849357 MyD88 homodimerization has been shown to involve another region of the TIR domain called Box 3.

Go back
1044.0, 446.0
23.0, 23.0

p34

p34

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000041125 MO000041132 e16

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c97 : 1
stoichiometry:c99 : 1

m18998*m19005*m16*0.1

nodelay

--

true

0

false

PMID: 16343886, 12471095, 12692549 A third adaptor was then described, termed TIR-related adaptor protein inducing interferon (Trif), which is recruited by both TLR4 and TLR3, and is responsible for activation of IRF3 [10, 11 and 12], acting via an IKK-like kinase termed TBK-1. PMID: 16343886, 14517278, 14519765, 14556004 The fourth adaptor to be described was named Trif-related adaptor molecule (Tram), and interestingly acts only in TLR4 signalling, where it interacts with Trif.

Go back
1039.0, 573.0
25.0, 25.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000041125 e26

e64

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c98 : 1
stoichiometry:c100 : 1

m18998*m27*0.1

nodelay

--

true

0

false

PMID: 16343886, 12471095, 12692549 A third adaptor was then described, termed TIR-related adaptor protein inducing interferon (Trif), which is recruited by both TLR4 and TLR3, and is responsible for activation of IRF3 [10, 11 and 12], acting via an IKK-like kinase termed TBK-1.

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1048.0, 506.0
24.0, 24.0

p36

p36

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019331 e63

e65

true true true true

--

and

mass

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

m3902*m66*0.1

nodelay

--

true

0

false

PMID: 16343886 The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta ¡½ both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.

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1044.0, 642.0
24.0, 24.0

p37

p37

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019331 e64

e66

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c105 : 1
stoichiometry:c106 : 1

m3902*m67*0.1

nodelay

--

true

0

false

PMID: 16343886 The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta ¡½ both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.

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1044.0, 698.0
23.0, 23.0

p38

p38

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e66 e86

e87

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c107 : 1
stoichiometry:c109 : 1
stoichiometry:c110 : 1

m69*m89*0.1

nodelay

--

true

0

false

PMID: 16343886 The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta ¡½ both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3. PMID: 16343886 TLR3 activates IRF3 homodimers which then bind the interferon sensitive response element (ISRE) on target genes, such as IFN-beta.

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1032.0, 886.0
23.0, 23.0

p39

p39

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e65 e88

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c111 : 1
stoichiometry:c112 : 1

m68*m91*0.1

nodelay

--

true

0

false

PMID: 16343886 The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta ¡½ both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3. PMID: 16343886, 1455726 For TLR4, a complex of p65 and IRF3 is activated.

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1184.0, 718.0
23.0, 23.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000022224 MO000019398

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c37 : 1
stoichiometry:c40 : 1

m119368*m3965*0.1

nodelay

--

true

0

false

PMID: 16343886 he most characterised are the recognition of double stranded RNA (dsRNA) by TLR3 and recognition of CpG motifs in DNA by TLR9.

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860.0, 1002.0
23.0, 23.0

p40

p40

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e67

G010228

true true true true

--

and

mass

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

m70*0.1

nodelay

--

true

0

false

PMID: 16343886 The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta ¡½ both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3. PMID: 16343886 This limits the induction of IFN-beta by TLR3 during infection and might contribute to the persistence of the virus.

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491.0, 317.0
25.0, 25.0

p41

p41

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016573 e69

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c116 : 1
stoichiometry:c115 : 1

m1572*m72*0.1

nodelay

--

true

0

false

PMID: 16343886, 15849357 A recent study has, however, identified three other amino acids in the BB loop of MyD88 (Asp195, Arg196 and Asp197) as important for interaction with the IL-1 receptor accessory protein (IL-1AcP, which also has a TIR domain and is required for IL-1 signalling in complex with IL-1RI.

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244.0, 778.0
23.0, 23.0

p42

p42

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016595 MO000000214

e70

true true true true

--

and

mass

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

m1589*m185*0.1

nodelay

--

true

0

false

PMID: 16343886, 15849357 A recent study has, however, identified three other amino acids in the BB loop of MyD88 (Asp195, Arg196 and Asp197) as important for interaction with the IL-1 receptor accessory protein (IL-1AcP, which also has a TIR domain and is required for IL-1 signalling in complex with IL-1RI.

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385.0, 727.0
22.0, 22.0

p43

p43

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e70 e68

e71

true true true true

--

and

mass

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

m73*m71*0.1

nodelay

--

true

0

false

PMID: 16343886, 15849357 A recent study has, however, identified three other amino acids in the BB loop of MyD88 (Asp195, Arg196 and Asp197) as important for interaction with the IL-1 receptor accessory protein (IL-1AcP, which also has a TIR domain and is required for IL-1 signalling in complex with IL-1RI.

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919.0, 1035.0
25.0, 25.0

p44

p44

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e67 G010329

MO000000289

true true true true

--

and

mass

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

m70*m93309*0.1

nodelay

--

true

0

false

PMID: 16343886 It appears that activation of Trif by LPS leads to the rapid production of TNF, which is dependent on IRF3.

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756.0, 970.0
24.0, 24.0

p45

p45

cso30:i:ME_GeneExpression

cso30:i:CC_NuclearBody

--

e47

G010329

true true true true

--

and

mass

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

m63*0.1

nodelay

--

true

0

false

PMID: 16343886 Perhaps TNF induction requires an interplay between NF-kappaB, activated by MyD88, and IRF3, activated by Trif, whereas IFN-beta only requires IRF3.

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415.0, 845.0
25.0, 25.0

p46

p46

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e30 MO000016573

e72

true true true true

--

and

mass

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

m31*m1572*0.1

nodelay

--

true

0

false

PMID: 16343886 TLR9, similar to IL-1, apparently only requires MyD88 for signalling, and yet, unlike IL-1, is a strong inducer of IFN-alpha, but only in plasmacytoid dendritic cells.

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558.0, 953.0
23.0, 23.0

p47

p47

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e77

e73

true true true true

--

and

mass

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

m80*0.1

nodelay

--

true

0

false

PMID: 16343886 TLR9, similar to IL-1, apparently only requires MyD88 for signalling, and yet, unlike IL-1, is a strong inducer of IFN-alpha, but only in plasmacytoid dendritic cells.

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468.0, 910.0
23.0, 23.0

p48

p48

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000007702 e72

e77

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c131 : 1
stoichiometry:c133 : 1
stoichiometry:c134 : 1

m980*m75*0.1

nodelay

--

true

0

false

PMID: 16343886, 15815647, 15800576, 15767370 Honda and colleagues now provide an explanation for this: IFN-alpha production requires the transcription factor IRF7, and this protein has been shown to associate with MyD88.In plasmacytoid dendritic cells, the IFN-alpha-inducing TLR9 ligand CpG-A is retained for long periods in endosomal vesicles together with the MyD88?IRF7 complex.

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699.0, 253.0
25.0, 25.0

p49

p49

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e78 e31

e79

true true true true

--

and

mass

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

m81*m32*0.1

nodelay

--

true

0

false

PMID: 16343886 MyD88s lacks a region important for IRAK-4 recruitment and so IRAK-4 is not engaged, hence limiting NF-kappaB activation.

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1197.0, 399.0
21.0, 21.0

p5

p5

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

MO000019394

e14

true true true true

--

and

mass

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

m3961*0.1

nodelay

--

true

0

false

PMID: 16343886 Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.

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547.0, 409.0
25.0, 25.0

p50

p50

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000016573 MO000016808

e81

true true true true

--

and

mass

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

m1572*m1746*0.1

nodelay

--

true

0

false

PMID: 16343886, 15623538 TGF-beta blocks TLR signalling by causing the ubiquitinylation and proteasomal degradation of MyD88 [36]. This may be a key aspect of the anti-inflammatory effects of TGF-beta.

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490.0, 532.0
27.0, 27.0

p51

p51

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e81

MO000019479

true true true true

--

and

mass

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

m84*0.1

nodelay

--

true

0

false

PMID: 16343886, 15623538 TGF-beta blocks TLR signalling by causing the ubiquitinylation and proteasomal degradation of MyD88 [36]. This may be a key aspect of the anti-inflammatory effects of TGF-beta.

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963.0, 501.0
25.0, 25.0

p52

p52

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

MO000041125 e80

e82

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c150 : 1
stoichiometry:c149 : 1

m18998*m83*0.1

nodelay

--

true

0

false

PMID: 16343886, 15710891 Also of interest is the observation that the hepatitis C virus protein NS3/4A can cleave and inactivate Trif.

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611.0, 765.0
25.0, 25.0

p53

p53

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000007702 e65

e83

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c152 : 1
stoichiometry:c156 : 1
stoichiometry:c153 : 1

m980*m68*0.1

nodelay

--

true

0

false

PMID: 16343886, 15800576, 15767370, 15361868 IRF7 is a key transcription factor for induction of type I interferons, and its activation occurs by both MyD88-dependent pathways (activated by TLR9) and Trif pathways (activated via TBK-1).

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610.0, 809.0
23.0, 23.0

p54

p54

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000007702 e66

e83

true true true true

--

and

mass

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

m980*m69*0.1

nodelay

--

true

0

false

PMID: 16343886, 15800576, 15767370, 15361868 IRF7 is a key transcription factor for induction of type I interferons, and its activation occurs by both MyD88-dependent pathways (activated by TLR9) and Trif pathways (activated via TBK-1).

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642.0, 353.0
23.0, 23.0

p55

p55

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e5 MO000039077 MO000007702

e84

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c159 : 1
stoichiometry:c161 : 1
stoichiometry:c160 : 1

m5*m17258*m980*0.1

nodelay

--

true

0

false

PMID: 16343886 IRF7 associates directly with both IRAK-4 and IRAK-1.

Go back
993.0, 1232.0
25.0, 25.0

p56

p56

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016573 MO000000212 MO000007700

e85

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c162 : 1
stoichiometry:c163 : 1
stoichiometry:c164 : 1
stoichiometry:c165 : 1

m1572*m183*m979*0.1

nodelay

--

true

0

false

PMID: 16343886 IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.

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862.0, 1113.0
23.0, 23.0

p57

p57

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e85

G010262

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c169 : 1
stoichiometry:c166 : 1

m88*0.1

nodelay

--

true

0

false

PMID: 16343886 IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.

Go back
653.0, 1000.0
25.0, 25.0

p58

p58

cso30:i:ME_GeneExpression

cso30:i:CC_NuclearChromosome

--

e85

e73

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c171 : 1
stoichiometry:c167 : 1

m88*0.1

nodelay

--

true

0

false

PMID: 16343886 IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.

Go back
773.0, 1180.0
25.0, 25.0

p59

p59

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e85

G010657

true true true true

--

and

mass

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

m88*0.1

nodelay

--

true

0

false

PMID: 16343886 IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.

Go back
1185.0, 195.0
21.0, 21.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

MO000016882 MO000018132

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c9 : 1
stoichiometry:c11 : 1

m155666*m2828*0.1

nodelay

--

true

0

false

PMID: 16343886 It now appears, however, that CD14 can influence signalling by TLR4, and is required for activation of the Trif?Tram pathway by TLR4 because when CD14 is absent LPS can only engage with the MyD88 pathway. PMID: 16343886 This is also the case with TLR4, but only when so-called ¡Æsmooth¡Ç LPS, which has longer O-polysaccharide chains compared to ¡Ærough¡Ç LPS, is used as a ligand.

Go back
803.0, 941.0
25.0, 25.0

p60

p60

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e87 e80

G010228

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c172 : 1
stoichiometry:c151 : 1
stoichiometry:c173 : 1

m90*0.1

nodelay

--

true

0

false

PMID: 16343886 The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta ¡½ both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3. PMID: 16343886 This limits the induction of IFN-b by TLR3 during infection and might contribute to the persistence of the virus.

Go back
487.0, 1189.0
25.0, 25.0

p61

p61

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e89 MO000000200

e90

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c175 : 1
stoichiometry:c176 : 1

m92*m172*0.1

nodelay

--

true

0

false

PMID: 16343886 A notable example of a gene activated by this pathway is IL-6, which is regulated by IkappaB-zeta in a complex with p50.

Go back
1005.0, 1129.0
30.0, 30.0

p62

p62

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e91 e25

MO000007700

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c177 : 1
stoichiometry:c179 : 1
stoichiometry:c178 : 1

m94*m26*0.1

nodelay

--

true

0

false

PMID: 16343886, 15665823 Another IRF, IRF5, is found downstream of MyD88, and so is activated by multiple TLRs

Go back
1196.0, 350.0
24.0, 24.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e15 e14

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1

m15*m14*0.1

nodelay

--

true

0

false

PMID: 16343886 It now appears, however, that CD14 can influence signalling by TLR4, and is required for activation of the Trif?Tram pathway by TLR4 because when CD14 is absent LPS can only engage with the MyD88 pathway. PMID: 16343886 This is also the case with TLR4, but only when so-called ¡Æsmooth¡Ç LPS, which has longer O-polysaccharide chains compared to ¡Ærough¡Ç LPS, is used as a ligand.

Go back
1175.0, 1067.0
25.0, 25.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019399 MO000022185

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c41 : 1

m3966*m6485*0.1

nodelay

--

true

0

false

PMID: 16343886, 15860593 Finally, TLR5 and TLR11 recognize proteins from pathogens (flagellin in the case of TLR5 and profilin in the case of TLR11 [only in the mouse]).

Go back
227.0, 525.0
25.0, 25.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e13 e17

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c20 : 1

m13*m17*0.1

nodelay

--

true

0

false

PMID: 16343886, 15690042 A role for other co-receptors is also emerging, with CD36 shown to be an essential co-receptor for TLR2.

Go back
251.22351697655571, 312.05927969280464

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1214.0, 206.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1064.0, 586.0

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1005.0, 536.8132665336364

c101

c101

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1077.6568542494924, 471.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1072.0, 518.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1010.0, 629.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1072.506083455352, 603.0

c105

c105

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1061.0, 666.0

c106

c106

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1065.9596317713672, 727.9513535541778

c107

c107

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1062.9999766120557, 523.0

c108

c108

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1016.0, 710.0

c109

c109

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1143.0, 206.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1028.3302800111373, 719.0

c110

c110

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
987.0, 898.0

c111

c111

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1013.159575575166, 909.0

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
890.5816944733765, 977.0

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
838.0, 1014.0

c114

c114

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
456.3891571012332, 342.0

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
457.0, 330.0

c116

c116

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
275.0, 790.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
267.0, 753.4688030358325

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
209.0, 790.0

c119

c119

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1130.0, 224.0

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
348.0, 738.0

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
399.7679848247228, 524.0

c121

c121

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
347.5280520215392, 749.0

c122

c122

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
948.2850231591362, 985.0

c123

c123

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
944.0, 1048.0

c124

c124

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
782.0, 1048.1167758783465

c125

c125

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
768.0, 994.0

c126

c126

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
768.0, 866.0

c127

c127

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
396.0, 877.2560717419874

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
435.88083266852567, 345.0

c129

c129

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1142.0, 362.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
428.0, 870.0

c130

c130

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
483.29311368882685, 794.0

c131

c131

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
581.0, 965.0

c132

c132

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
444.0, 928.24

c133

c133

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
472.08784016584013, 933.0

c134

c134

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
481.0, 971.7339445046937

c135

c135

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
647.0, 330.0

c136

c136

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
689.0, 284.0455126623185

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
602.0, 185.0

c138

c138

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
716.0, 214.65339104343087

c139

c139

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1143.0797206054124, 283.1803267365851

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
750.0, 191.0

c140

c140

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
603.0, 246.0

c141

c141

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
919.0, 254.0

c142

c142

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
574.9251523357785, 345.0

c143

c143

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
540.2829174186304, 434.0

c144

c144

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
560.0, 381.0

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
514.3104235544095, 499.0

c146

c146

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
488.7029180288541, 559.0

c147

c147

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
976.0, 470.0

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
976.0, 526.0

c149

c149

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
232.13557914448734, 172.3599010474772

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
995.8544616852214, 471.0

c150

c150

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
831.9999460744459, 478.0

c151

c151

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
520.0, 778.0

c152

c152

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
549.3365604500259, 784.0

c153

c153

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
520.0, 784.0

c154

c154

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
550.0, 821.0

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
643.9997771249538, 517.7068099861854

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
640.9999962437057, 820.7855365387279

c157

c157

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
670.8837532708425, 238.0

c158

c158

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
672.1907186127962, 301.0

c159

c159

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
204.0, 437.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
661.0, 376.0

c160

c160

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
510.0, 383.5206202258813

c161

c161

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
639.0, 96.63067374005402

c162

c162

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.0, 371.0

c163

c163

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1006.0, 1209.0

c164

c164

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
958.0, 1245.0

c165

c165

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
874.0, 1101.9889426346601

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
643.0335858293437, 985.2179589656599

c167

c167

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
751.9810426273839, 1194.0

c168

c168

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
883.5446968516084, 1143.1718285137192

c169

c169

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
247.69969036663647, 366.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
805.5508668509282, 1199.6428033978248

c170

c170

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
684.0455126623185, 1028.2394443073426

c171

c171

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
833.4372473019363, 764.0

c172

c172

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
816.0, 966.0

c173

c173

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
448.0, 1174.0

c174

c174

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
411.0, 1202.0

c175

c175

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
500.0, 1214.0

c176

c176

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
992.0, 1131.0

c177

c177

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1012.1411509102887, 1159.0

c178

c178

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
541.0, 204.0

c179

c179

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
476.0, 126.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
235.0, 158.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
256.0, 294.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
252.0, 538.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
224.0, 87.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
340.0, 421.0703033307765

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
339.0, 277.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
259.0533836092979, 501.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
261.6564023547028, 549.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
255.0, 594.0

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
276.326060730508, 112.72942780301243

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
271.9983134039794, 113.41688052563323

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
276.0, 102.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
248.0, 268.5298221281347

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
401.0, 180.97533742417852

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
335.0, 221.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
337.0, 501.0

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
352.0, 666.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
416.0, 78.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
484.0, 118.0

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1196.0, 680.0

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1133.0, 730.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1129.0, 1080.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1188.0, 1100.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
262.9615792869974, 435.7831061593768

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1142.2723665956942, 687.9656235549245

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1137.8185818291893, 1088.0

c41

c41

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1188.0, 1164.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1129.0, 1180.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1137.0, 1216.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
267.0, 942.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
345.9532362754983, 960.2821533250223

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
344.0, 942.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
532.0, 119.0

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
542.0, 111.0

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
262.63583982428025, 410.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
588.0, 191.0

c50

c50

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
664.0, 80.49747802019165

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
597.0, 192.4

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
813.0, 240.97927454946927

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
819.0, 225.0

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
733.0, 74.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
872.0, 190.5663617266161

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
920.0, 82.0

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1048.0, 68.0

c58

c58

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
929.0, 74.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
255.0, 441.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1004.0, 74.98354785709812

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1004.802166365621, 173.0

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1006.0, 168.2394362184674

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
948.0, 358.0

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
888.0, 358.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.0, 361.0573097607281

c65

c65

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
805.5098677696539, 367.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
799.0, 418.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
810.1070902829529, 428.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
804.0, 486.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1132.0, 410.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
814.1676940130167, 498.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
808.0, 550.0

c71

c71

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
745.0, 559.2888620248546

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
860.0, 562.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
815.0, 610.0

c74

c74

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
796.0, 621.0

c75

c75

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
796.0, 693.0

c76

c76

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
724.0, 730.0

c77

c77

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
808.0, 730.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
723.0, 670.0

c79

c79

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1148.96921767363, 376.92810450695515

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
812.0, 673.0

c80

c80

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
628.0, 618.0

c81

c81

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
636.0, 670.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
873.5601767747798, 639.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
868.0, 681.3330443576974

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
760.0, 798.0

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
779.8102651883261, 810.0

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
813.2570816034594, 746.0

c87

c87

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1055.3393175972478, 265.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1068.3745195078866, 275.0

c89

c89

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1155.0, 179.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1063.0, 318.78700925063515

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
824.0, 192.0

c91

c91

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
597.6753833509902, 264.1057411452476

c92

c92

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
988.0, 458.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
988.0, 417.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
983.0, 470.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
524.0, 330.0

c96

c96

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1062.3939142903585, 277.0

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1067.026696856701, 604.2235294416298

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1067.0, 458.0

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back