1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/15608698.csml convertedTime:2009.07.01.10:49

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title LPS, TLR4 and infectious disease diversity.
Authors Miller SI, Ernst RK, Bader MW.
Affiliation Department of Medicine, University of Washington Medical School, Seattle,Washington 98195, USA. millersi@u.washington.edu
Abstract Innate immune receptors recognize microorganism-specific motifs. One suchreceptor-ligand complex is formed between the mammalian Toll-like receptor 4(TLR4)-MD2-CD14 complex and bacterial lipopolysaccharide (LPS). Recent researchindicates that there is significant phylogenetic and individual diversity inTLR4-mediated responses. In addition, the diversity of LPS structures and thedifferential recognition of these structures by TLR4 have been associated withseveral bacterial diseases. This review will examine the hypothesis that thevariability of bacterial ligands such as LPS and their innate immune receptorsis an important factor in determining the outcome of infectious disease.
PMID 15608698
Model Abstract

Entity

G010262:IL-6 G010329:TNF-alpha MO000000058:NF-kappaB {activated} MO000000212:TRAF6 MO000000213:IRAK MO000016573:MyD88 MO000016882:LPS MO000018132:CD14 MO000019394:TLR4 MO000019397:TLR2 MO000019398:TLR3 MO000019399:TLR5 MO000019420:LBP MO000021928:LPS:LBP MO000021929:LPS:LBP:CD14 MO000022224:dsRNA MO000038321:LPS:LBP:CD14:TLR4:MD-2:MyD88 MO000039077:IRAK-4 MO000041446:dsRNA:TLR3 MO000042007:TLR8 MO000042012:TLR9 MO000042126:TLR7 e1: e10: e11:LPS:LBP:CD14:TLR4:MD-2 e12:lipopeptide e13:flagellin e14:flagellin: TLR5 e15:ssDNA e16:ssDNA:TLR9 e17:ssRNA: TLR7 e18:ssRNA e19:ssRNA: TLR9 e2: e20:LPS:LBP:CD14:TLR4:MD-2:MyD88: IRAK: IRAK-4 e21:LPS:LBP:CD14:TLR4:MD-2:MyD88: IRAK: IRAK-4: TRAF6 e22:IKK-alpha:IKK-beta:IKK-gamma e23:IKK-alpha:IKK-beta:IKK-gamma {p} e24:IkappB: NFkappaB e25:IkappB {p}: NFkappaB e26:IkappaB {degraded} e27:NF-kappaB {nucleus} e28:lipid IV A e29:lipid IV A: TLR4 e3: e4: e5:lipopeptide: TLR2 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:TLR4:MD-2 e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p19 p2 p20 p21 p3 p4 p5 p6 p7 p8 p9
Model Detail
724.0, 964.0
40.0, 40.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p20

--

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
706.0, 902.0
36.0, 36.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p21

--

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
745.0, 573.0
46.0, 46.0

NF-kappaB {activated}

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

p15

p16

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
711.0, 219.0
33.5, 33.5

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
567.0, 219.0
33.5, 33.5

IRAK

--

MO000000213

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m184

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000213

--

Go back
435.0, 215.0
42.0, 42.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
75.0, 89.0
30.0, 30.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
256.0, 102.0
35.0, 35.0

CD14

--

MO000018132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m2828

10

false

infinite

0

unit false false false
InterProIPR001611
TRANSPATHMO000018132

--

Go back
166.0, 166.0
35.5, 35.5

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
162.0, 302.0
35.0, 35.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
163.0, 935.0
34.5, 34.5

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
167.0, 423.0
34.0, 34.0

TLR5

--

MO000019399

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m3966

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019399

--

Go back
186.0, 32.0
32.0, 32.0

LBP

--

MO000019420

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m3985

10

false

infinite

0

unit false false false
InterProIPR001124
TRANSPATHMO000019420

--

Go back
188.0, 86.0
35.0, 35.0

LPS:LBP

--

MO000021928

cso30:c:Protein

cso30:i:CC_CellComponent

--

p1

p2

true true true true

csml-variable:Double

m6254

10

false

infinite

0

unit false false false
TRANSPATHMO000021928

--

Go back
315.0, 85.0
38.0, 38.0

LPS:LBP:CD14

--

MO000021929

cso30:c:Protein

cso30:i:CC_CellComponent

--

p2

p3

true true true true

csml-variable:Double

m6255

10

false

infinite

0

unit false false false
TRANSPATHMO000021929

--

Go back
96.0, 872.0
39.0, 39.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
614.0, 126.0
60.0, 60.0

LPS:LBP:CD14:TLR4:MD-2:MyD88

--

MO000038321

cso30:c:Protein

cso30:i:CC_CellComponent

--

p10

p11

true true true true

csml-variable:Double

m16536

10

false

infinite

0

unit false false false
TRANSPATHMO000038321

--

Go back
628.0, 268.0
31.5, 31.5

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
161.0, 997.0
38.0, 38.0

dsRNA:TLR3

--

MO000041446

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9

--

true true true true

csml-variable:Double

m19314

10

false

infinite

0

unit false false false
TRANSPATHMO000041446

--

Go back
166.0, 790.0
36.5, 36.5

TLR8

--

MO000042007

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m19823

10

false

infinite

0

unit false false false
TRANSPATHMO000042007

--

Go back
166.0, 534.0
35.5, 35.5

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
161.0, 649.0
38.0, 38.0

TLR7

--

MO000042126

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m19940

10

false

infinite

0

unit false false false
TRANSPATHMO000042126

--

Go back
150.75, 132.9969080091176
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
159.0, 152.0
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
494.0, 138.0
60.0, 60.0

LPS:LBP:CD14:TLR4:MD-2

--

e11

cso30:c:Protein

cso30:i:CC_CellComponent

--

p3

p10

true true true true

csml-variable:Double

m11

10

false

infinite

0

unit false false false
TRANSPATHMO000022054

--

Go back
13.0, 365.5
38.879999999999995, 29.159999999999993

lipopeptide

--

e12

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p4

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
21.0, 477.5
38.879999999999995, 29.159999999999997

flagellin

--

e13

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p5

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
164.0, 469.0
40.574585635359114, 45.0828729281768

flagellin: TLR5

--

e14

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p5

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
18.0, 545.0
51.84647302904565, 13.825726141078837

ssDNA

--

e15

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p6

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
170.5, 581.0
27.921069940802454, 54.0407805305854

ssDNA:TLR9

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p6

--

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
164.5, 698.0
31.0, 60.0

ssRNA: TLR7

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p7

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
36.0, 750.5
47.79270633397313, 26.28598848368522

ssRNA

--

e18

cso30:c:Rna

cso30:i:CC_Extracellular

--

--

p7 p8

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
168.5, 846.0
31.0, 60.0

ssRNA: TLR9

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
150.75, 132.9969080091176
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
736.5, 114.0
47.13549660162246, 91.22999342249507

LPS:LBP:CD14:TLR4:MD-2:MyD88: IRAK: IRAK-4

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p11

p12

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
831.5, 101.0
48.36570927428196, 93.61105020828766

LPS:LBP:CD14:TLR4:MD-2:MyD88: IRAK: IRAK-4: TRAF6

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p12

p13

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
738.0, 314.0
52.0, 52.0

IKK-alpha:IKK-beta:IKK-gamma

--

e22

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13

true true true true

csml-variable:Double

m22

10

false

infinite

0

unit false false false
TRANSPATHMO000021655

--

Go back
826.0, 372.0
60.0, 48.0

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

--

e23

cso30:c:Protein

cso30:i:CC_Cytosol

--

p13

p14

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
753.5, 433.0
44.25595734044327, 54.19096817197135

IkappB: NFkappaB

--

e24

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p14

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
830.0, 511.0
51.951219512195124, 41.5609756097561

IkappB {p}: NFkappaB

--

e25

cso30:c:Protein

cso30:i:CC_Cytosol

--

p14

p15

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
835.0, 644.0
42.06203331418724, 40.65996553704768

IkappaB {degraded}

--

e26

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p15

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
670.0, 838.0
43.0, 43.0

NF-kappaB {nucleus}

--

e27

cso30:c:Protein

cso30:i:CC_CellComponent

--

p16

p20 p21

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
91.0, 180.0
42.79226240538267, 24.24894869638352

lipid IV A

--

e28

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p19

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
168.5, 226.0
31.0, 60.0

lipid IV A: TLR4

--

e29

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p19

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
167.87518862352903, 150.12209663264667
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
199.5567875770579, 180.09117672382234
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
167.5, 348.0
32.94387195790397, 63.76233282174961

lipopeptide: TLR2

--

e5

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
331.0, 769.0
465.6500709748862, 422.29345356567933

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
381.2936761946803, 779.0077409313898
272.27955732982184, 409.2864683429171

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
337.06992643728904, 774.6363602631969
453.51021810030846, 411.0207330392853

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
337.93705878547314, 775.503492611381
451.7759534039399, 409.2864683429171

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
331.0, 769.0
465.6500709748862, 422.29345356567933

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
331.0, 769.0
465.6500709748862, 422.29345356567933

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
337.93705878547314, 775.503492611381
451.7759534039399, 409.2864683429171

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
670.9158804881849, 942.4264696368291
29.091257918298922, 26.33524401024959

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
594.6082338479803, 1063.8249983826097
82.37757307749382, 74.57338194383664

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
331.0, 769.0
465.6500709748862, 422.29345356567933

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
354.0, 150.0
44.0, 44.0

TLR4:MD-2

--

e6

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m6

10

false

infinite

0

unit false false false
TRANSPATHMO000022039

--

Go back
440.7511016961721, 956.6637213250547
14.746453546866459, 7.100144300343119

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
440.2586758712023, 935.4894108513561
50.4736470593979, 90.85256470691624

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
461.43298634490134, 994.5805098477247
7.878813199515761, 7.8788131995157675

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
162.0, 138.0
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
165.0, 159.0
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
173.0, 180.0
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
131.0, 89.0
30.0, 30.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016882 MO000019420

MO000021928

true true true true

--

and

mass

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

m155666*m3985*0.1

nodelay

--

true

0

false

PMID: 15608698 Recognition of lipid A also requires an accessory protein ¡½ LPS-binding protein (LBP) ¡½ which converts oligomeric micelles of LPS to a monomer for delivery to CD14.

Go back
509.0, 225.0
30.0, 30.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e11 MO000016573

MO000038321

true true true true

--

and

mass

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

m11*m1572*0.1

nodelay

--

true

0

false

PMID: 15608698 Upon ligand binding, this domain associates with the myeloid differentiation factor 88 (MyD88) adaptor protein.

Go back
629.0, 221.0
30.0, 30.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213 MO000039077 MO000038321

e20

true true true true

--

and

mass

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

m184*m17258*m16536*0.1

nodelay

--

true

0

false

PMID: 15608698, 11905821 Upon ligand binding, this domain associates with the myeloid differentiation factor 88 (MyD88) adaptor protein, which is necessary for the recruitment of the protein kinases interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4, and TNF-receptor-associated factor 6 (TRAF6) to the complex.

Go back
773.0, 221.0
30.0, 30.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e20 MO000000212

e21

true true true true

--

and

mass

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

m20*m183*0.1

nodelay

--

true

0

false

PMID: 15608698, 11905821 Upon ligand binding, this domain associates with the myeloid differentiation factor 88 (MyD88) adaptor protein, which is necessary for the recruitment of the protein kinases interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4, and TNF-receptor-associated factor 6 (TRAF6) to the complex.

Go back
841.0, 285.0
30.0, 30.0

p13

p13

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e21 e22

e23

true true true true

--

and

mass

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

m21*m22*0.1

nodelay

--

true

0

false

PMID: 15608698 Through a series of other intermediate compounds, the I¦ÊB kinase (IKK) complex is phosphorylated, and in turn phosphorylates I¦ÊB, which allows nuclear factor (NF)-¦ÊB to translocate to the nucleus.

Go back
841.0, 445.0
30.0, 30.0

p14

p14

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e23 e24

e25

true true true true

--

and

mass

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

m23*m25*0.1

nodelay

--

true

0

false

PMID: 15608698 Through a series of other intermediate compounds, the I¦ÊB kinase (IKK) complex is phosphorylated, and in turn phosphorylates I¦ÊB, which allows nuclear factor (NF)-¦ÊB to translocate to the nucleus.

Go back
841.0, 581.0
30.0, 30.0

p15

p15

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

e25

e26 MO000000058

true true true true

--

and

mass

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

m26*0.1

nodelay

--

true

0

false

PMID: 15608698 Through a series of other intermediate compounds, the I¦ÊB kinase (IKK) complex is phosphorylated, and in turn phosphorylates I¦ÊB, which allows nuclear factor (NF)-¦ÊB to translocate to the nucleus.

Go back
677.0, 757.0
30.0, 30.0

p16

p16

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

MO000000058

e27

true true true true

--

and

mass

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

m24*0.1

nodelay

--

true

0

false

PMID: 15608698 Through a series of other intermediate compounds, the I¦ÊB kinase (IKK) complex is phosphorylated, and in turn phosphorylates I¦ÊB, which allows nuclear factor (NF)-¦ÊB to translocate to the nucleus.

Go back
97.0, 241.0
30.0, 30.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e28 MO000019394

e29

true true true true

--

and

mass

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

m29*m3961*0.1

nodelay

--

true

0

false

PMID: 15608698, 6361124, 1918061 lipidIVA, which is an intermediate in the biosynthetic pathway of lipid A and is the major component of Yersinia pestis lipid A, stimulates mouse TLR4 but is not recognized by human TLR4, even at very high concentrations.

Go back
259.0, 33.0
30.0, 30.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000021928 MO000018132

MO000021929

true true true true

--

and

mass

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

m6254*m2828*0.1

nodelay

--

true

0

false

PMID: 15608698 Recognition of lipid A also requires an accessory protein ¡½ LPS-binding protein (LBP) ¡½ which converts oligomeric micelles of LPS to a monomer for delivery to CD14.

Go back
613.0, 969.0
30.0, 30.0

p20

p20

cso30:i:ME_Transcription

cso30:i:CC_Nucleoplasm

--

e27

G010262

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c54 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 15608698 Ligand binding to the extracellular domain of TLRs initiates a complex signal-transduction cascade,which ultimately leads to activation of the transcription factor nuclear factor-¦ÊB (NF-¦ÊB) and increased transcription of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour-necrosis factor (TNF).

Go back
609.0, 905.0
30.0, 30.0

p21

p21

cso30:i:ME_Transcription

cso30:i:CC_Nucleoplasm

--

e27

G010329

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c53 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 15608698 Ligand binding to the extracellular domain of TLRs initiates a complex signal-transduction cascade,which ultimately leads to activation of the transcription factor nuclear factor-¦ÊB (NF-¦ÊB) and increased transcription of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour-necrosis factor (TNF).

Go back
445.0, 41.0
30.0, 30.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000021929 e6

e11

true true true true

--

and

mass

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

m6255*m6*0.1

nodelay

--

true

0

false

PMID: 15608698 CD14 concentrates LPS for binding to the TLR4?MD2 complex.

Go back
85.0, 365.0
30.0, 30.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e12 MO000019397

e5

true true true true

--

and

mass

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

m12*m3964*0.1

nodelay

--

true

0

false

PMID: 15608698, 9851930, 11323673, 10426996 The ligands that are recognized by TLRs include lipopeptides (TLR2),lipopolysaccharide (TLR4), flagellin (TLR5)and CpG DNA (TLR9).

Go back
97.0, 477.0
30.0, 30.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e13 MO000019399

e14

true true true true

--

and

mass

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

m13*m3966*0.1

nodelay

--

true

0

false

PMID: 15608698, 9851930, 11323673, 10426996 The ligands that are recognized by TLRs include lipopeptides (TLR2),lipopolysaccharide (TLR4), flagellin (TLR5)and CpG DNA (TLR9).

Go back
97.0, 537.0
30.0, 30.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e15 MO000042012

e16

true true true true

--

and

mass

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

m15*m19828*0.1

nodelay

--

true

0

false

PMID: 15608698, 9851930, 11323673, 10426996 The ligands that are recognized by TLRs include lipopeptides (TLR2),lipopolysaccharide (TLR4), flagellin (TLR5)and CpG DNA (TLR9).

Go back
97.0, 713.0
30.0, 30.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000042126 e18

e17

true true true true

--

and

mass

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

m19940*m18*0.1

nodelay

--

true

0

false

PMID: 15608698, 14976262, 14976261, 15034168 viral products such as single-stranded and double-stranded RNA are recognized by TLR7 (human TLR8) and TLR3, respectively.

Go back
97.0, 793.0
30.0, 30.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000042007 e18

e19

true true true true

--

and

mass

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

m19823*m18*0.1

nodelay

--

true

0

false

PMID: 15608698, 14976262, 14976261, 15034168 viral products such as single-stranded and double-stranded RNA are recognized by TLR7 (human TLR8) and TLR3, respectively.

Go back
101.0, 937.0
30.0, 30.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000022224 MO000019398

MO000041446

true true true true

--

and

mass

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

m119368*m3965*0.1

nodelay

--

true

0

false

PMID: 15608698, 14976262, 14976261, 15034168 viral products such as single-stranded and double-stranded RNA are recognized by TLR7 (human TLR8) and TLR3, respectively.

Go back
105.0, 104.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
52.0, 380.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
121.41634488272317, 334.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
115.0, 380.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
60.0, 492.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
133.4768835471551, 452.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
127.0, 492.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
70.0, 552.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
135.0, 552.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
127.0, 564.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
79.0, 742.6839244307548

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
166.65685424949237, 64.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
132.99870284292075, 685.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
127.0, 728.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
135.0, 808.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
75.0, 777.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
127.0, 822.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
116.0, 911.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
139.0, 952.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
131.0, 967.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
524.0, 198.0

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
477.0, 237.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
161.0, 104.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
539.0, 181.55823697416474

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
601.0, 236.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
644.0, 259.0

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
644.0, 186.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
659.0, 179.37799490386163

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
776.0, 205.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
745.0, 236.0

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
800.0, 186.30652626788057

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.0, 195.0

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
790.0, 309.1687288914772

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
223.0, 65.12147519731585

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
856.0, 315.0

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.0, 420.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
798.0, 460.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
856.0, 475.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.0, 553.0

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
856.0, 611.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
799.0, 596.0

c46

c46

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
701.1898088913156, 619.0

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
692.0, 787.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
644.9368211420091, 879.0

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
274.0, 71.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
639.6423145269338, 881.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
639.0, 920.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
643.0, 984.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
112.0, 204.0

c55

c55

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
132.72800111696031, 202.0

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
127.0, 256.0

c57

c57

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
289.0, 62.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
353.0, 64.84458262757666

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
392.0, 77.48759860979487

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
469.0, 71.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back