1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18406369.csml convertedTime:2009.07.01.11:18

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins.
Authors Dalpke A, Heeg K, Bartz H, Baetz A.
Affiliation Department of Hygiene and Medical Microbiology, Institute of Hygiene, Universityof Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.alexander.dalpke@med.uni-heidelberg.de
Abstract Innate immunity represents the first line of defense against invading pathogens.Toll-like receptors (TLRs) are important for activation of innate immunity.Moreover, cytokines mediate communication of cells and are necessary to mount anappropriately regulated immune response. However, activation of innate immunityhas to be tightly controlled to avoid overshooting immune reactions. Suppressorof cytokine signaling (SOCS) proteins have been identified as inducible feedbackinhibitors of cytokine receptors and have been shown to be of crucial importancefor the limitation of inflammatory responses. In this review, we describe therole of SOCS proteins in macrophages and dendritic cells (DCs). Based on our ownfindings, we show that SOCS proteins are directly induced by stimulation ofTLRs. However, SOCS proteins do not interfere with direct TLR signaling, butavoid overshooting activation by regulating paracrine IFN-beta signaling. Inaddition, SOCS proteins in macrophages and DCs regulate the sensitivity towardsIFN-gamma and GM-CSF, thereby modulating anti-microbial activity of macrophagesand differentiation of DCs. We discuss that SOCS induction can also be used bymicrobes to evade immune defense, and this is exemplified by the parasiteToxoplasma gondii which induces SOCS1 to inhibit IFN-gamma-mediated macrophageactivation. Taken together, the findings indicate that SOCS proteins play animportant role in the balanced activation of innate immunity during infectiousencounter.
PMID 18406369
Model Abstract

Entity

G010539:SOCS1 G011948:SOCS3 MO000000058:NF-kappaB MO000000077:MAPKs MO000000146:Jak2 MO000000289:TNF-alpha MO000007384:IL-6 MO000007694:IRF-3 MO000013119:STAT1 MO000016573:MyD88 MO000016656:STATs MO000016876:STAT5 MO000016882:LPS MO000016886:SHP-2 MO000017004:SOCS-1 MO000017116:CIS MO000017120:SOCS-2 MO000017121:SOCS-3 MO000018458:IL-6R MO000018946:elongin C MO000018947:elongin B MO000019394:TLR4 MO000019396:TLR1 MO000019397:TLR2 MO000019398:TLR3 MO000019422:TLR6 MO000022528:TIRAP MO000041125:TRIF MO000041132:TRAM MO000042012:TLR9 e1: e10: e11:cytokine:Receptor:JAKs e12:Jak2{active} e13:Receptor:JAKs e14:cytokine:Receptor:Jaks e15:cytokine:Receptor:Jaks{active} e16:cytokine:Receptor{pY}:Jaks{active} e17:STAT dimer e18:Cytokine:receptor{pY}:JAKs{active}:STATs e19:Cytokine:receptor{pY}:JAKs:STATs{p} e2: e20:STAT{p} dimer e21:DNA:STATdimer e22:DNA e23:mRNA e24:STAT5{active} e25:LPS:TLR4 e26:LPS:TLR4:TIRAP e27:LPS:TLR4:TIRAP:MyD88 e28:MAPKs{active} e29:NF-kappaB{active} e3: e30:proinflammatory cytokines e31:LPS:TLR4:TRAM e32:LPS:TLR4:TRAM:TRIF e33:IRF-3{active} e34:IFN-beta e35:CpGmotif e36:TLR9:CpGmotif e37:Bacteria e38:CIS e39:TNF-alpha receptor e4: e40:TNF-alpha:receptor e41:SOCS-1:JAK2:Receptor e42:Cytokine:receptor{pY}:JAKs{active}:SOCS-2 e43:SOCS-1:JAKs e44:Cytokine:receptor{pY}:JAKs {active}:SOCS-3 e45:SOCS-3:SHP-2 e46:Cytokine:receptor{pY}:JAKs {active}:SOCS-3:SHP-2 e47:TIRAP{ub} e48:dergradants e49:NF-kappaB{active} e5:Cytokine e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:Receptor e60: e61: e62: e63:SOCS-1 e64:NF-KappaB{active}:SOCS-1 e65:SOCS:Elongin B e66:JaKs e67:Cytokine:receptor{pY}:JAKs{active}:CIS e68:SOCS e69:SOCS:ElonginC e7: e70:IL-6:IL-6R e71:STAT1{pY} e72:LPS(2):TLR4(2) e73: e74: e75: e76:microbacterial stimuli e77:TLR3:microbacterial stimuli e78:TLR3:miccrobial stimuli:TRIF e79:microbial stimuli:TLR3(2) e8: e80:TLR2:TLR1 e81:TLR2:TLR6 e82:TLR2:TLR1:microbial stimuli e83:TLR2:TLR6:microbial stimuli e84:TLR2:TLR1:microbial stimuli:TIRAP e85:TLR2:TLR6:microbial stimuli:TIRAP e86:TLR2:TLR1:microbial stimuli:TIRAP:MyD88 e87:TLR2:TLR6:microbial stimuli:TIRAP:MyD88 e88:HPV-E7 e89:CpGmotif:TLR9(2) e9: e90:CpGmotif:TLR9(2):MyD88 e91:STAT{p} dimer

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p55 p56 p57 p58 p59 p6 p60 p61 p62 p63 p64 p65 p66 p67 p68 p69 p7 p70 p71 p72 p73 p74 p8 p9
Model Detail
487.0, 560.0
28.0, 28.0

SOCS1

--

G010539

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p26 p30 p39

true true true true

csml-variable:Double

m93501

10

false

infinite

0

unit false false false
TRANSFACG010539

--

Go back
548.0, 469.0
25.0, 25.0

SOCS3

--

G011948

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p32

p27 p28 p31 p40

true true true true

csml-variable:Double

m94757

10

false

infinite

0

unit false false false
TRANSFACG011948

--

Go back
949.0, 786.0
24.0, 24.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18 p66 p67 p73

true true true true

csml-variable:Double

m29

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
927.0, 596.0
20.0, 20.0

MAPKs

--

MO000000077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p17 p68 p69 p72

true true true true

csml-variable:Double

m69

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
590.0, 187.0
22.0, 22.0

Jak2

--

MO000000146

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35 p42

true true true true

csml-variable:Double

m130

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000146

--

Go back
284.0, 541.0
26.0, 26.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p29

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
205.0, 754.0
24.0, 24.0

IL-6

--

MO000007384

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p50

true true true true

csml-variable:Double

m871

10

false

infinite

0

unit false false false
InterProIPR003573
TRANSPATHMO000007384

--

Go back
1021.0, 910.0
24.0, 24.0

IRF-3

--

MO000007694

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p23 p56

true true true true

csml-variable:Double

m977

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
813.0, 502.0
24.0, 24.0

STAT1

--

MO000013119

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p52

true true true true

csml-variable:Double

m1357

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
979.0, 560.0
28.0, 28.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16 p64 p65 p71

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
907.0, 256.0
20.5, 20.5

STATs

--

MO000016656

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m1633

10

false

infinite

0

unit false false false
TRANSPATHMO000016656

--

Go back
717.0, 218.0
24.0, 24.0

STAT5

--

MO000016876

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13

true true true true

csml-variable:Double

m1798

10

false

infinite

0

unit false false false
TRANSPATHMO000016876

--

Go back
1239.0, 348.0
20.0, 20.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
371.0, 328.0
20.0, 20.0

SHP-2

--

MO000016886

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m1807

10

false

infinite

0

unit false false false
InterProIPR000242
TRANSPATHMO000016886

--

Go back
647.0, 236.0
20.0, 20.0

SOCS-1

--

MO000017004

cso30:c:Protein

cso30:i:CC_CellComponent

--

p26 p30 p39

p35 p44 p52

true true true true

csml-variable:Double

m1906

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017004

--

Go back
798.0, 255.0
22.0, 22.0

CIS

--

MO000017116

cso30:c:Protein

cso30:i:CC_CellComponent

--

p41

p13 p34

true true true true

csml-variable:Double

m2003

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017116

--

Go back
730.0, 167.0
22.0, 22.0

SOCS-2

--

MO000017120

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33

true true true true

csml-variable:Double

m2004

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017120

--

Go back
530.0, 298.0
20.0, 20.0

SOCS-3

--

MO000017121

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27 p28 p31 p40

p36 p37

true true true true

csml-variable:Double

m2005

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017121

--

Go back
285.0, 770.0
24.0, 24.0

IL-6R

--

MO000018458

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p50

true true true true

csml-variable:Double

m3096

10

false

infinite

0

unit false false false
InterProIPR003961
TRANSPATHMO000018458

--

Go back
1010.0, 479.0
22.0, 22.0

elongin C

--

MO000018946

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p49

true true true true

csml-variable:Double

m3558

10

false

infinite

0

unit false false false
InterProIPR001232
TRANSPATHMO000018946

--

Go back
809.0, 442.0
24.0, 24.0

elongin B

--

MO000018947

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p47

true true true true

csml-variable:Double

m3559

10

false

infinite

0

unit false false false
InterProIPR000626
TRANSPATHMO000018947

--

Go back
1167.0, 376.0
20.0, 20.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
1165.0, 1218.0
24.0, 24.0

TLR1

--

MO000019396

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p58

true true true true

csml-variable:Double

m3963

10

false

infinite

0

unit false false false
InterProIPR003016
TRANSPATHMO000019396

--

Go back
1166.0, 1167.0
22.0, 22.0

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p58 p59

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
619.0, 1028.0
20.0, 20.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p54

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
1169.0, 1270.0
23.0, 23.0

TLR6

--

MO000019422

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p59

true true true true

csml-variable:Double

m3987

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019422

--

Go back
1073.0, 541.0
22.0, 22.0

TIRAP

--

MO000022528

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15 p44 p62 p63

true true true true

csml-variable:Double

m6810

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000022528

--

Go back
1054.0, 759.0
22.0, 22.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p22 p55

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
1030.0, 723.0
22.0, 22.0

TRAM

--

MO000041132

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21

true true true true

csml-variable:Double

m19005

10

false

infinite

0

unit false false false
TRANSPATHMO000041132

--

Go back
284.0, 381.0
26.0, 26.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
262.5041549343006, 73.44878678774495
953.6410969608465, 1438.7964522070372

--

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
290.69242050367075, 102.44012433299383
924.3702531122026, 1351.1421449887714

--

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
435.5, 87.0
27.16993943842908, 37.91154340245919

cytokine:Receptor:JAKs

--

e11

cso30:c:Complex

cso30:i:CC_Cytosol

--

p1

p4

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
386.0, 367.0
22.0, 22.0

Jak2{active}

--

e12

cso30:c:Protein

cso30:i:CC_CellComponent

--

p42

--

true true true true

csml-variable:Double

m12

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000146

--

Go back
307.0, 94.0
28.93922651933702, 32.1546961325967

Receptor:JAKs

--

e13

cso30:c:Complex

cso30:i:CC_Cytosol

--

p2

p1

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
590.5, 86.0
28.298403376766384, 39.48614424665077

cytokine:Receptor:Jaks

--

e14

cso30:c:Complex

cso30:i:CC_Cytosol

--

p4

p3

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
758.5, 78.0
28.298403376766384, 39.48614424665077

cytokine:Receptor:Jaks{active}

--

e15

cso30:c:Complex

cso30:i:CC_Cytosol

--

p3

p5

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
958.5, 82.0
28.298403376766384, 39.48614424665077

cytokine:Receptor{pY}:Jaks{active}

--

e16

cso30:c:Complex

cso30:i:CC_Cytosol

--

p5 p9

p7 p33 p34 p37 p38

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
999.5, 315.0
18.772037993667716, 22.986168971838033

STAT dimer

--

e17

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

p7

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
1167.0, 71.0
27.264705882352942, 45.44117647058824

Cytokine:receptor{pY}:JAKs{active}:STATs

--

e18

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

p8

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
1163.0, 307.0
27.264705882352942, 45.44117647058824

Cytokine:receptor{pY}:JAKs:STATs{p}

--

e19

cso30:c:Complex

cso30:i:CC_Cytosol

--

p8

p9

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
262.5041549343006, 73.44878678774495
953.6410969608465, 1438.7964522070372

--

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
631.5, 463.0
18.772037993667716, 22.986168971838033

STAT{p} dimer

--

e20

cso30:c:Complex

cso30:i:CC_Cytosol

--

p10

p11

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
528.0, 518.5
49.43173052198509, 14.00565698122911

DNA:STATdimer

--

e21

cso30:c:Complex

cso30:i:CC_Cytosol

--

p11

p12

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
708.0, 521.5
41.9315468293977, 9.085168479702839

DNA

--

e22

cso30:c:Dna

cso30:i:CC_Cytosol

--

--

p11

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
515.0, 607.0
34.51557093425605, 18.408304498269896

mRNA

--

e23

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p12 p51

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
849.0, 302.0
24.0, 24.0

STAT5{active}

--

e24

cso30:c:Protein

cso30:i:CC_CellComponent

--

p13

--

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
TRANSPATHMO000016876

--

Go back
1169.5, 413.0
22.05547029160272, 42.688007016005265

LPS:TLR4

--

e25

cso30:c:Complex

cso30:i:CC_Cytosol

--

p14

p53

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
1169.5, 602.0
22.97173793356579, 32.05358781427785

LPS:TLR4:TIRAP

--

e26

cso30:c:Complex

cso30:i:CC_Cytosol

--

p15

p16

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1169.0, 655.0
23.38235294117647, 38.970588235294116

LPS:TLR4:TIRAP:MyD88

--

e27

cso30:c:Complex

cso30:i:CC_Cytosol

--

p16

p17 p18

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
879.0, 660.0
20.0, 20.0

MAPKs{active}

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

p17 p68 p69 p72

p19 p32 p51

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
865.0, 722.0
24.0, 24.0

NF-kappaB{active}

--

e29

cso30:c:Protein

cso30:i:CC_CellComponent

--

p18 p66 p67 p73

p45

true true true true

csml-variable:Double

m30

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
281.5769768735175, 93.2669197382551
915.4954530824125, 1399.1601863060182

--

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
580.0, 625.0
34.51557093425605, 18.408304498269896

proinflammatory cytokines

--

e30

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p19 p20

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
1168.5, 780.0
25.54432005872637, 35.64323729124609

LPS:TLR4:TRAM

--

e31

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p21

p22

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
1166.0, 839.0
22.588235294117652, 37.647058823529406

LPS:TLR4:TRAM:TRIF

--

e32

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p22

p23

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
897.0, 842.0
24.0, 24.0

IRF-3{active}

--

e33

cso30:c:Protein

cso30:i:CC_CellComponent

--

p23 p56

p24

true true true true

csml-variable:Double

m34

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
551.0, 693.8685121107266
44.688581314878896, 23.833910034602077

IFN-beta

--

e34

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p24

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
175.0, 343.0
52.84232365145228, 14.091286307053942

CpGmotif

--

e35

cso30:c:Dna

cso30:i:CC_Cytosol

--

--

p25

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
289.5, 413.0
22.211795658846743, 42.99057224292918

TLR9:CpGmotif

--

e36

cso30:c:Complex

cso30:i:CC_Cytosol

--

p25

p26 p27 p70

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
204.5, 688.0
24.82048854383639, 36.32266616171179

Bacteria

--

e37

cso30:c:Cell

cso30:i:CC_Extracellular

--

--

p39 p40 p41

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
730.0, 576.0
37.681660899653984, 20.096885813148788

CIS

--

e38

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p41

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
284.5, 603.0
24.560632688927942, 37.78558875219684

TNF-alpha receptor

--

e39

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p29

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
316.8616974610689, 127.94865240164768
844.92601190731, 1329.7967209792318

--

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
289.5, 479.0
23.448805086603816, 45.38478403858803

TNF-alpha:receptor

--

e40

cso30:c:Complex

cso30:i:CC_Cytosol

--

p29

p31

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
288.5, 217.0
24.400073407964765, 34.04661405762526

SOCS-1:JAK2:Receptor

--

e41

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p48

p5

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
1163.0, 199.0
27.264705882352942, 45.44117647058824

Cytokine:receptor{pY}:JAKs{active}:SOCS-2

--

e42

cso30:c:Complex

cso30:i:CC_Cytosol

--

p33

p7

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
432.5, 259.0
24.471421429761705, 29.965005832361282

SOCS-1:JAKs

--

e43

cso30:c:Complex

cso30:i:CC_Cytosol

--

p35

p48

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
287.0, 323.0
27.264705882352942, 45.44117647058824

Cytokine:receptor{pY}:JAKs {active}:SOCS-3

--

e44

cso30:c:Complex

cso30:i:CC_Cytosol

--

p37

p5

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
611.5, 325.0
24.569405099150142, 30.084985835694052

SOCS-3:SHP-2

--

e45

cso30:c:Complex

cso30:i:CC_Cytosol

--

p36

p38

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
283.0, 263.0
27.264705882352942, 45.44117647058824

Cytokine:receptor{pY}:JAKs {active}:SOCS-3:SHP-2

--

e46

cso30:c:Complex

cso30:i:CC_Cytosol

--

p38

p5

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
990.0, 631.0
22.0, 22.0

TIRAP{ub}

--

e47

cso30:c:Protein

cso30:i:CC_CellComponent

--

p44

p43

true true true true

csml-variable:Double

m48

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000022528

--

Go back
898.0, 911.0
29.999999999999993, 29.0

dergradants

--

e48

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p43 p74

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
701.0, 738.0
24.0, 24.0

NF-kappaB{active}

--

e49

cso30:c:Protein

cso30:i:CC_CellComponent

--

p45

p20 p46

true true true true

csml-variable:Double

m63

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
414.0, 28.5
29.595782073813695, 19.237258347978912

Cytokine

--

e5

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
389.10594778014104, 426.2009673551984
432.2201039406579, 407.29344654007053

--

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
435.7889385223348, 435.8532299266613
252.7320533284294, 394.7484738540313

--

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
394.7401018352334, 431.63712218581514
420.95179583047315, 396.4211368788365

--

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
395.54498098596093, 432.4734536982177
419.34203752901794, 394.7484738540313

--

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
389.10594778014104, 426.2009673551984
432.2201039406579, 407.29344654007053

--

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
389.10594778014104, 426.2009673551984
432.2201039406579, 407.29344654007053

--

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
395.54498098596093, 432.4734536982177
419.34203752901794, 394.7484738540313

--

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
704.6185748653135, 593.4672698357198
27.002737259090377, 25.39980719057029

--

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
633.7892096012959, 710.5536815720857
76.46351931911074, 71.92451006662439

--

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
389.10594778014104, 426.2009673551984
432.2201039406579, 407.29344654007053

--

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
287.5, 162.0
26.182776801405975, 40.28119507908612

Receptor

--

e6

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p2 p48

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
490.9777943438229, 607.1988095041501
13.687775611069226, 6.8479447611631485

--

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
490.52072077180355, 586.7766177364985
46.85004113196753, 87.62545072399405

--

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
510.17488436862936, 643.7687808090144
7.313177152307124, 7.598955076335518

--

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
478.0, 739.0
22.0, 22.0

SOCS-1

--

e63

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p46

true true true true

csml-variable:Double

m64

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017004

--

Go back
517.5, 648.0
23.230294950841525, 28.44525912347942

NF-KappaB{active}:SOCS-1

--

e64

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p46

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
868.5, 334.0
22.952674554240957, 28.105315780703215

SOCS:Elongin B

--

e65

cso30:c:Complex

cso30:i:CC_Cytosol

--

p47

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
440.0, 180.5
26.24000000000001, 19.680000000000003

JaKs

--

e66

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p2

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
1163.0, 259.0
27.264705882352942, 45.44117647058824

Cytokine:receptor{pY}:JAKs{active}:CIS

--

e67

cso30:c:Complex

cso30:i:CC_Cytosol

--

p34

p7

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
712.5, 321.0
16.51559669953713, 26.782048701952107

SOCS

--

e68

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p47 p49 p74

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
917.5, 504.0
23.254790868188635, 28.475254124312613

SOCS:ElonginC

--

e69

cso30:c:Complex

cso30:i:CC_Cytosol

--

p49

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
275.0336079834416, 79.23861745289226
935.2248105026086, 1376.9739887097464

--

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
290.5, 858.0
20.288313966235474, 39.26770445077834

IL-6:IL-6R

--

e70

cso30:c:Complex

cso30:i:CC_Cytosol

--

p50

p51

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
861.0, 546.0
24.0, 24.0

STAT1{pY}

--

e71

cso30:c:Protein

cso30:i:CC_CellComponent

--

p52

--

true true true true

csml-variable:Double

m73

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
1174.5, 470.0
21.15829861872396, 40.951545713659286

LPS(2):TLR4(2)

--

e72

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p53

p15 p21 p28 p30 p42 p52

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
529.0, 988.0
183.9133369996015, 307.041757533233

--

e73

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false true false

--

Go back
529.0, 988.0
183.9133369996015, 307.041757533233

--

e74

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false true false

--

Go back
529.0, 988.0
183.9133369996015, 307.041757533233

--

e75

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false true false

--

Go back
1239.0, 917.5
27.1353251318102, 17.637961335676625

microbacterial stimuli

--

e76

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p54 p60 p61

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
603.5, 1083.0
19.79215084411313, 38.30738873054155

TLR3:microbacterial stimuli

--

e77

cso30:c:Complex

cso30:i:CC_Cytosol

--

p54

p57

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
580.5, 1196.0
25.315470728574052, 35.323912644521926

TLR3:miccrobial stimuli:TRIF

--

e78

cso30:c:Complex

cso30:i:CC_Cytosol

--

p55

p56

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
586.5, 1134.0
21.15829861872396, 40.951545713659286

microbial stimuli:TLR3(2)

--

e79

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p57

p55

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
278.37479546321254, 103.54087777304454
897.1723046392389, 1353.599727452128

--

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
1163.5, 1114.0
26.741376437260456, 32.7445425762373

TLR2:TLR1

--

e80

cso30:c:Complex

cso30:i:CC_Cytosol

--

p58

p60

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false false false

--

Go back
1167.5, 1062.0
26.741376437260456, 32.7445425762373

TLR2:TLR6

--

e81

cso30:c:Complex

cso30:i:CC_Cytosol

--

p59

p61

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
1170.5, 1009.0
21.34860776145582, 41.319885989914496

TLR2:TLR1:microbial stimuli

--

e82

cso30:c:Complex

cso30:i:CC_Cytosol

--

p60

p63

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false false false

--

Go back
1170.5, 953.0
21.34860776145582, 41.319885989914496

TLR2:TLR6:microbial stimuli

--

e83

cso30:c:Complex

cso30:i:CC_Cytosol

--

p61

p62

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false false false

--

Go back
1165.0, 1326.0
24.17647058823529, 40.294117647058826

TLR2:TLR1:microbial stimuli:TIRAP

--

e84

cso30:c:Complex

cso30:i:CC_Cytosol

--

p62

p64

true true true true

csml-variable:Double

m86

0

false

infinite

0

unit false false false

--

Go back
1161.0, 1402.0
24.17647058823529, 40.294117647058826

TLR2:TLR6:microbial stimuli:TIRAP

--

e85

cso30:c:Complex

cso30:i:CC_Cytosol

--

p63

p65

true true true true

csml-variable:Double

m87

0

false

infinite

0

unit false false false

--

Go back
1057.0, 1446.0
24.17647058823529, 40.294117647058826

TLR2:TLR1:microbial stimuli:TIRAP:MyD88

--

e86

cso30:c:Complex

cso30:i:CC_Cytosol

--

p64

p67 p69

true true true true

csml-variable:Double

m88

0

false

infinite

0

unit false false false

--

Go back
765.0, 1450.0
24.17647058823529, 40.294117647058826

TLR2:TLR6:microbial stimuli:TIRAP:MyD88

--

e87

cso30:c:Complex

cso30:i:CC_Cytosol

--

p65

p66 p68

true true true true

csml-variable:Double

m89

0

false

infinite

0

unit false false false

--

Go back
617.0, 925.0
15.10383536014967, 34.85500467726846

HPV-E7

--

e88

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p74

true true true true

csml-variable:Double

m90

0

false

infinite

0

unit false false false

--

Go back
290.5, 950.0
21.15829861872396, 40.951545713659286

CpGmotif:TLR9(2)

--

e89

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p70

p71

true true true true

csml-variable:Double

m91

0

false

infinite

0

unit false false false

--

Go back
287.2846287426015, 127.84313809319681
893.0762209386947, 1335.8476062079949

--

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
290.0, 1032.0
21.17647058823529, 35.294117647058826

CpGmotif:TLR9(2):MyD88

--

e90

cso30:c:Complex

cso30:i:CC_Cytosol

--

p71

p72 p73

true true true true

csml-variable:Double

m92

0

false

infinite

0

unit false false false

--

Go back
1050.5, 353.0
18.772037993667716, 22.986168971838033

STAT{p} dimer

--

e91

cso30:c:Complex

cso30:i:CC_Cytosol

--

p9

p10

true true true true

csml-variable:Double

m93

0

false

infinite

0

unit false false false

--

Go back
346.0, 27.0
21.0, 21.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e5 e13

e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m5*m13*0.1

nodelay

--

true

0

false

PMID: 18406369 Hematopoietic cytokines act on membrane-bound receptors that lack kinase activity themselves.

Go back
713.0, 422.0
23.0, 23.0

p10

p10

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e91

e20

true true true true

--

and

mass

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

m93*0.1

nodelay

--

true

0

false

PMID: 18406369 STAT dimers dissociate from the receptor and translocate to the nucleus where they act as transcription factors by binding to specific DNA sequences.

Go back
631.0, 516.0
19.0, 19.0

p11

p11

cso30:i:ME_DNABinding

cso30:i:CC_Cytosol

--

e20 e22

e21

true true true true

--

and

mass

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

m20*m22*0.1

nodelay

--

true

0

false

PMID: 18406369 STAT dimers dissociate from the receptor and translocate to the nucleus where they act as transcription factors by binding to specific DNA sequences.

Go back
586.0, 571.0
21.0, 21.0

p12

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e21

e23

true true true true

--

and

mass

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

m21*0.1

nodelay

--

true

0

false

PMID: 18406369 STAT dimers dissociate from the receptor and translocate to the nucleus where they act as transcription factors by binding to specific DNA sequences.

Go back
769.0, 301.0
21.0, 21.0

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016876 MO000017116

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c32 : 1
stoichiometry:c31 : 1

m1798*0.1

nodelay

--

true

0

false

PMID: 18406369 CIS also plays a role in limiting GM-CSF, IL-2, prolactin and growth hormone signaling by inhibition of STAT5 activation.

Go back
1242.0, 407.0
21.0, 21.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016882 MO000019394

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1
stoichiometry:c35 : 1

m155666*m3961*0.1

nodelay

--

true

0

false

PMID: 18406369,9826711 Similar results were obtained for LPS-mediated activation of TLR4

Go back
1103.0, 496.0
19.0, 19.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000022528 e72

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c119 : 1
stoichiometry:c38 : 1

m6810*m74*0.1

nodelay

--

true

0

false

PMID: 18406369 In the case of TLR2 and 4 this association is facilitated by TIR domain-containing adaptor/MyD88-adaptor-like protein (TIRAP/Mal).

Go back
1026.0, 599.0
21.0, 21.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e26 MO000016573

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c40 : 1
stoichiometry:c41 : 1

m26*m1572*0.1

nodelay

--

true

0

false

PMID: 18406369 With the exception of TLR3 all TLRs use myeloid differentiation factor 88 (MyD88) as a central adaptor.

Go back
946.0, 659.0
21.0, 21.0

p17

p17

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000077 e27

e28

true true true true

--

and

mass

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

m69*m27*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
943.0, 728.0
19.0, 19.0

p17

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e27 MO000000058

e29

true true true true

--

and

mass

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

m27*m29*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
663.0, 644.0
19.0, 19.0

p19

p19

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e28

e30

true true true true

--

and

mass

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

m28*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
382.0, 171.0
21.0, 21.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e6 e66

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c3 : 1
stoichiometry:c2 : 1

m6*m67*0.1

nodelay

--

true

0

false

PMID: 18406369 However, the receptor chains are tightly associated with janus kinases (JAKs)

Go back
627.0, 688.0
20.0, 20.0

p19

p20

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e49

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c129 : 1
stoichiometry:c51 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
1091.0, 724.0
19.0, 19.0

p21

p21

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000041132 e72

e31

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c150 : 1
stoichiometry:c54 : 1

m19005*m74*0.1

nodelay

--

true

0

false

PMID: 18406369 TLR3 and TLR4 further bind to TIR domain-containing protein inducing IFN-¦Â (TRIF) and the latter TLR therefore uses TRIF-related adaptor molecule in addition.

Go back
1099.0, 788.0
20.0, 20.0

p21

p22

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000041125 e31

e32

true true true true

--

and

mass

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

m18998*m32*0.1

nodelay

--

true

0

false

PMID: 18406369 TLR3 and TLR4 further bind to TIR domain-containing protein inducing IFN-¦Â (TRIF) and the latter TLR therefore uses TRIF-related adaptor molecule in addition.

Go back
1022.0, 843.0
21.0, 21.0

p23

p23

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e32 MO000007694

e33

true true true true

--

and

mass

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

m33*m977*0.1

nodelay

--

true

0

false

PMID: 18406369 TRIF in contrast mainly activates IRF3, thereby inducing IFN-¦Â, which in turn can signal in an autocrine or paracrine manner.

Go back
619.0, 764.0
19.0, 19.0

p24

p24

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e33

e34

true true true true

--

and

mass

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

m34*0.1

nodelay

--

true

0

false

PMID: 18406369 TRIF in contrast mainly activates IRF3, thereby inducing IFN-¦Â, which in turn can signal in an autocrine or paracrine manner.

Go back
189.0, 422.0
23.0, 23.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e35 MO000042012

e36

true true true true

--

and

mass

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

m36*m19828*0.1

nodelay

--

true

0

false

PMID: 18406369,11390452 Using murine macrophages and DCs, we were the first to show that triggering of TLR9 by CpG-DNA resulted in induction of SOCS1 and SOCS3

Go back
426.0, 379.0
22.0, 22.0

p26

p26

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010539 e36

MO000017004

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c68 : 1
stoichiometry:c110 : 1

m93501*m37*0.1

nodelay

--

true

0

false

PMID: 18406369,11390452 Using murine macrophages and DCs, we were the first to show that triggering of TLR9 by CpG-DNA resulted in induction of SOCS1 and SOCS3

Go back
530.0, 387.0
22.0, 22.0

p26

p27

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G011948 e36

MO000017121

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c80 : 1

m94757*m37*0.1

nodelay

--

true

0

false

PMID: 18406369,11390452 Using murine macrophages and DCs, we were the first to show that triggering of TLR9 by CpG-DNA resulted in induction of SOCS1 and SOCS3

Go back
610.0, 371.0
21.0, 21.0

p28

p28

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G011948 e72

MO000017121

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c152 : 1
stoichiometry:c112 : 1

m94757*m74*0.1

nodelay

--

true

0

false

PMID: 18406369,9826711 Similar results were obtained for LPS-mediated activation of TLR4

Go back
182.0, 543.0
21.0, 21.0

p29

p29

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e39 MO000000289

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c76 : 1
stoichiometry:c77 : 1

m40*m230*0.1

nodelay

--

true

0

false

Go back
626.0, 19.0
22.0, 22.0

p3

p3

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e14

e15

true true true true

--

and

mass

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

m14*0.1

nodelay

--

true

0

false

PMID: 18406369,10071751 Upon binding of cytokines, these receptors aggregate and perform conformational changes that lead to autoactivation of the JAKs

Go back
682.0, 347.0
21.0, 21.0

p28

p30

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010539 e72

MO000017004

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c153 : 1
stoichiometry:c111 : 1

m93501*m74*0.1

nodelay

--

true

0

false

PMID: 18406369,9826711 Similar results were obtained for LPS-mediated activation of TLR4

Go back
394.0, 451.0
21.0, 21.0

p31

p31

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

e40 G011948

MO000017121

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c81 : 1
stoichiometry:c82 : 1
stoichiometry:c67 : 1

m41*m94757*0.1

nodelay

--

true

0

false

PMID: 18406369,11727828,10606755 Moreover, it turned out that also MAP-kinase activation itself The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription, or stimulation with TNF was able to induce SOCS3

Go back
734.0, 623.0
21.0, 21.0

p32

p32

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e28

G011948

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c86 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 18406369,11727828,10606755 Moreover, it turned out that also MAP-kinase activation itself The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription, or stimulation with TNF was able to induce SOCS3

Go back
802.0, 167.0
21.0, 21.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017120 e16

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c88 : 1
stoichiometry:c89 : 1

m2004*m16*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, SOCS2 and CIS interfere with STAT recruitment PMID: 18406369 SOCS2 and CIS are assumed to mainly act by competition with STAT factors for recruitment to the activated receptor complex.

Go back
846.0, 215.0
21.0, 21.0

p33

p34

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017116 e16

e67

true true true true

--

and

mass

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

m2003*m16*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, SOCS2 and CIS interfere with STAT recruitment PMID: 18406369 SOCS2 and CIS are assumed to mainly act by competition with STAT factors for recruitment to the activated receptor complex.

Go back
646.0, 187.0
21.0, 21.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017004 MO000000146

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c98 : 1
stoichiometry:c97 : 1

m1906*m130*0.1

nodelay

--

true

0

false

PMID: 18406369 In contrast, SOCS1 and SOCS3 are reported to inhibit JAK activity by use of their KIR domain PMID: 18406369 However, although it has been suggested that SOCS1 directly binds to JAK2 and acts as a pseudosubstrate, it was shown that SOCS3 binds to cytokine receptor chains with special affinity for gp130.

Go back
450.0, 327.0
21.0, 21.0

p35

p36

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016886 MO000017121

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c114 : 1
stoichiometry:c104 : 1

m1807*m2005*0.1

nodelay

--

true

0

false

PMID: 18406369 In contrast, SOCS1 and SOCS3 are reported to inhibit JAK activity by use of their KIR domain PMID: 18406369 However, although it has been suggested that SOCS1 directly binds to JAK2 and acts as a pseudosubstrate, it was shown that SOCS3 binds to cytokine receptor chains with special affinity for gp130.

Go back
529.0, 169.0
21.0, 21.0

p35

p37

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017121 e16

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c100 : 1
stoichiometry:c96 : 1

m2005*m16*0.1

nodelay

--

true

0

false

PMID: 18406369 In contrast, SOCS1 and SOCS3 are reported to inhibit JAK activity by use of their KIR domain PMID: 18406369 However, although it has been suggested that SOCS1 directly binds to JAK2 and acts as a pseudosubstrate, it was shown that SOCS3 binds to cytokine receptor chains with special affinity for gp130.

Go back
709.0, 265.0
21.0, 21.0

p35

p38

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e45 e16

e46

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c107 : 1
stoichiometry:c108 : 1

m46*m16*0.1

nodelay

--

true

0

false

PMID: 18406369 In contrast, SOCS1 and SOCS3 are reported to inhibit JAK activity by use of their KIR domain PMID: 18406369 However, although it has been suggested that SOCS1 directly binds to JAK2 and acts as a pseudosubstrate, it was shown that SOCS3 binds to cytokine receptor chains with special affinity for gp130.

Go back
347.0, 680.0
19.0, 19.0

p39

p39

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010539 e37

MO000017004

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c74 : 1
stoichiometry:c83 : 1

m93501*m38*0.1

nodelay

--

true

0

false

PMID: 18406369,12811837 In a further study, we showed that not only various TLR ligands but also whole bacteria were able to stimulate rapid production of SOCS1, -3 and CIS

Go back
494.0, 27.0
21.0, 21.0

p4

p4

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e11

e14

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 18406369,10071751 Upon binding of cytokines, these receptors aggregate and perform conformational changes that lead to autoactivation of the JAKs

Go back
351.0, 600.0
19.0, 19.0

p39

p40

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e37 G011948

MO000017121

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c103 : 1
stoichiometry:c115 : 1

m38*m94757*0.1

nodelay

--

true

0

false

PMID: 18406369,12811837 In a further study, we showed that not only various TLR ligands but also whole bacteria were able to stimulate rapid production of SOCS1, -3 and CIS

Go back
355.0, 524.0
19.0, 19.0

p39

p41

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e37 e38

MO000017116

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c117 : 1
stoichiometry:c118 : 1

m38*m39*0.1

nodelay

--

true

0

false

PMID: 18406369,12811837 In a further study, we showed that not only various TLR ligands but also whole bacteria were able to stimulate rapid production of SOCS1, -3 and CIS

Go back
497.0, 225.0
21.0, 21.0

p42

p42

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000146 e72

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c120 : 1
stoichiometry:c154 : 1
stoichiometry:c121 : 1

m130*m74*0.1

nodelay

--

true

0

false

PMID: 18406369,16287972 Recent data furthermore suggest that TLR4 stimulation might activate JAK2, thereby becoming sensitive to SOCS1

Go back
1005.0, 778.0
23.0, 23.0

p43

p43

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

e47

e48

true true true true

--

and

mass

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

m48*0.1

nodelay

--

true

0

false

PMID: 18406369,16415872 Meanwhile, another group suggested that TIRAP/Mal becomes poly-ubiquitinated and degraded by SOCS1, resulting in prolonged NF¦ÊB signaling

Go back
1022.0, 535.0
21.0, 21.0

p44

p44

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000017004 MO000022528

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c122 : 1
stoichiometry:c37 : 1

m1906*m6810*0.1

nodelay

--

true

0

false

PMID: 18406369,16415872 Meanwhile, another group suggested that TIRAP/Mal becomes poly-ubiquitinated and degraded by SOCS1, resulting in prolonged NF¦ÊB signaling

Go back
794.0, 734.0
19.0, 19.0

p45

p45

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e29

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c128 : 1

m30*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
541.0, 750.0
23.0, 23.0

p46

p46

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e63 e49

e64

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c130 : 1
stoichiometry:c131 : 1
stoichiometry:c132 : 1

m64*m63*0.1

nodelay

--

true

0

false

PMID: 18406369 Interestingly, recent results suggested that SOCS1 might be found within the nucleus where it could interact with NF¦ÊB

Go back
755.0, 384.0
20.0, 20.0

p47

p47

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000018947 e68

e65

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c133 : 1
stoichiometry:c135 : 1

m3559*m70*0.1

nodelay

--

true

0

false

PMID: 18406360,12076535 It was shown that the SOCS-box associates with Elongin B and C and together with cullin-2 and Rbx1 builds up an ECS-type E3 ubiquitin ligase

Go back
402.0, 207.0
21.0, 21.0

p35

p48

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e43 e6

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c109 : 1
stoichiometry:c136 : 1

m44*m6*0.1

nodelay

--

true

0

false

PMID: 18406369 In contrast, SOCS1 and SOCS3 are reported to inhibit JAK activity by use of their KIR domain PMID: 18406369 However, although it has been suggested that SOCS1 directly binds to JAK2 and acts as a pseudosubstrate, it was shown that SOCS3 binds to cytokine receptor chains with special affinity for gp130.

Go back
998.0, 394.0
20.0, 20.0

p47

p49

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e68 MO000018946

e69

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c140 : 1
stoichiometry:c141 : 1

m70*m3558*0.1

nodelay

--

true

0

false

PMID: 18406360,12076535 It was shown that the SOCS-box associates with Elongin B and C and together with cullin-2 and Rbx1 builds up an ECS-type E3 ubiquitin ligase

Go back
831.0, 20.0
19.0, 19.0

p5

p5

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e15 e41 e46 e44

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c106 : 1
stoichiometry:c137 : 1
stoichiometry:c138 : 1
stoichiometry:c12 : 1

m15*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, JAKs induce tyrosine phosphorylation within the receptor chains and this generates docking sites for signal transducer and activator of transcription factors (STATs)

Go back
206.0, 819.0
21.0, 21.0

p50

p50

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000007384 MO000018458

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c142 : 1
stoichiometry:c143 : 1

m871*m3096*0.1

nodelay

--

true

0

false

PMISD: 18406369 Moreover, it turned out that also MAP-kinase activation itself The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription, or stimulation with TNF was able to induce SOCS3

Go back
442.0, 687.0
21.0, 21.0

p51

p51

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e70 e28

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c146 : 1
stoichiometry:c145 : 1

m72*0.1

nodelay

--

true

0

false

PMISD: 18406369 Moreover, it turned out that also MAP-kinase activation itself The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription, or stimulation with TNF was able to induce SOCS3

Go back
850.0, 451.0
21.0, 21.0

p52

p52

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000017004 MO000013119 e72

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c147 : 1
stoichiometry:c148 : 1
stoichiometry:c151 : 1
stoichiometry:c149 : 1

m1357*m74*0.1

nodelay

--

true

0

false

PMID: 18406369 Moreover, MAP-kinase and NF¦ÊB activation were not affected, yet STAT1 tyrosine phosphorylation upon TLR triggering was inhibited.

Go back
1247.0, 464.0
19.0, 19.0

p53

p53

cso30:i:ME_Dimerization

cso30:i:CC_Extracellular

--

e25

e72

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c78 : 1

m25*0.1

nodelay

--

true

0

false

PMID: 18406369 n turn, homo- (TLR3, 4, 9) or heterodimers (TLR1, 2, 6) are activated and associate with intracellular adaptor molecules.

Go back
734.0, 1023.0
21.0, 21.0

p54

p54

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019398 e76

e77

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c125 : 1
stoichiometry:c155 : 1

m3965*m78*0.1

nodelay

--

true

0

false

PMID: 18406369 microbial stimuli directly bind to TLRs, which results in conformational changes.

Go back
730.0, 1147.0
21.0, 21.0

p54

p55

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e79 MO000041125

e78

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c162 : 1
stoichiometry:c163 : 1

m81*m18998*0.1

nodelay

--

true

0

false

PMID: 18406369 TLR3 and TLR4 further bind to TIR domain-containing protein inducing IFN-¦Â (TRIF) and the latter TLR therefore uses TRIF-related adaptor molecule in addition.

Go back
722.0, 959.0
21.0, 21.0

p23

p56

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e78 MO000007694

e33

true true true true

--

and

mass

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

m80*m977*0.1

nodelay

--

true

0

false

PMID: 18406369 TRIF in contrast mainly activates IRF3, thereby inducing IFN-¦Â, which in turn can signal in an autocrine or paracrine manner.

Go back
723.0, 1092.0
19.0, 19.0

p53

p57

cso30:i:ME_Dimerization

cso30:i:CC_Extracellular

--

e77

e79

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c157 : 1

m79*0.1

nodelay

--

true

0

false

PMID: 18406369 n turn, homo- (TLR3, 4, 9) or heterodimers (TLR1, 2, 6) are activated and associate with intracellular adaptor molecules.

Go back
1245.0, 1170.0
23.0, 23.0

p58

p58

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019397 MO000019396

e80

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c164 : 1
stoichiometry:c165 : 1
stoichiometry:c166 : 1

m3964*m3963*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, homo- (TLR3, 4, 9) or heterodimers (TLR1, 2, 6) are activated and associate with intracellular adaptor molecules.

Go back
1237.0, 1270.0
23.0, 23.0

p58

p59

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019397 MO000019422

e81

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c167 : 1
stoichiometry:c168 : 1
stoichiometry:c169 : 1

m3964*m3987*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, homo- (TLR3, 4, 9) or heterodimers (TLR1, 2, 6) are activated and associate with intracellular adaptor molecules.

Go back
907.0, 316.0
20.0, 20.0

p6

p6

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

MO000016656

e17

true true true true

--

and

mass

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

m1633*0.1

nodelay

--

true

0

false

PMID: 18406369 According to recent research data , Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation?inactivation cycle, , STATs are found as pre-associated homo- or heterodimers in an anti-parallel conformation.

Go back
1241.0, 1118.0
23.0, 23.0

p60

p60

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e76 e80

e82

true true true true

--

and

mass

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

m78*m82*0.1

nodelay

--

true

0

false

PMID: 18406369 microbial stimuli directly bind to TLRs, which results in conformational changes.

Go back
1265.0, 1042.0
23.0, 23.0

p60

p61

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e81 e76

e83

true true true true

--

and

mass

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

m83*m78*0.1

nodelay

--

true

0

false

PMID: 18406369 microbial stimuli directly bind to TLRs, which results in conformational changes.

Go back
1059.0, 1044.0
19.0, 19.0

p15

p62

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e83 MO000022528

e84

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c177 : 1
stoichiometry:c178 : 1
stoichiometry:c124 : 1

m85*m6810*0.1

nodelay

--

true

0

false

PMID: 18406369 In the case of TLR2 and 4 this association is facilitated by TIR domain-containing adaptor/MyD88-adaptor-like protein (TIRAP/Mal).

Go back
1011.0, 1156.0
19.0, 19.0

p15

p63

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e82 MO000022528

e85

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c176 : 1
stoichiometry:c179 : 1
stoichiometry:c180 : 1

m84*m6810*0.1

nodelay

--

true

0

false

PMID: 18406369 In the case of TLR2 and 4 this association is facilitated by TIR domain-containing adaptor/MyD88-adaptor-like protein (TIRAP/Mal).

Go back
954.0, 1215.0
21.0, 21.0

p16

p64

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e84 MO000016573

e86

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c181 : 1
stoichiometry:c183 : 1
stoichiometry:c185 : 1

m86*m1572*0.1

nodelay

--

true

0

false

PMID: 18406369 With the exception of TLR3 all TLRs use myeloid differentiation factor 88 (MyD88) as a central adaptor.

Go back
894.0, 1279.0
21.0, 21.0

p16

p65

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e85 MO000016573

e87

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c182 : 1
stoichiometry:c184 : 1
stoichiometry:c186 : 1

m87*m1572*0.1

nodelay

--

true

0

false

PMID: 18406369 With the exception of TLR3 all TLRs use myeloid differentiation factor 88 (MyD88) as a central adaptor.

Go back
730.0, 1215.0
21.0, 21.0

p17

p66

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e87 MO000000058

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c187 : 1
stoichiometry:c193 : 1
stoichiometry:c194 : 1

m89*m29*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
843.0, 1196.0
19.0, 19.0

p17

p67

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e86 MO000000058

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c189 : 1
stoichiometry:c197 : 1
stoichiometry:c198 : 1

m88*m29*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
798.0, 1183.0
21.0, 21.0

p17

p68

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e87 MO000000077

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c188 : 1
stoichiometry:c191 : 1
stoichiometry:c192 : 1

m89*m69*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
886.0, 1151.0
21.0, 21.0

p17

p69

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e86 MO000000077

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c190 : 1
stoichiometry:c195 : 1
stoichiometry:c196 : 1

m88*m69*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
1087.0, 152.0
20.0, 20.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e16 e17 e42 e67

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c17 : 1

m16*m17*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, JAKs induce tyrosine phosphorylation within the receptor chains and this generates docking sites for signal transducer and activator of transcription factors (STATs) PMID: 18406369 Upon cytokine receptor stimulation, STAT dimers change their conformation towards a parallel one and bind to tyrosine-phosphorylated cytokine receptor chains by use of their Src homology 2 (SH2) domain. PMID: 18406369 In turn, SOCS2 and CIS interfere with STAT recruitment PMID: 18406369 SOCS2 and CIS are assumed to mainly act by competition with STAT factors for recruitment to the activated receptor complex.

Go back
227.0, 916.0
19.0, 19.0

p53

p70

cso30:i:ME_Dimerization

cso30:i:CC_Extracellular

--

e36

e89

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c199 : 1
stoichiometry:c200 : 1

m37*0.1

nodelay

--

true

0

false

PMID: 18406369 n turn, homo- (TLR3, 4, 9) or heterodimers (TLR1, 2, 6) are activated and associate with intracellular adaptor molecules.

Go back
386.0, 859.0
21.0, 21.0

p16

p71

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e89 MO000016573

e90

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c201 : 1
stoichiometry:c202 : 1
stoichiometry:c203 : 1

m91*m1572*0.1

nodelay

--

true

0

false

PMID: 18406369 With the exception of TLR3 all TLRs use myeloid differentiation factor 88 (MyD88) as a central adaptor.

Go back
414.0, 903.0
21.0, 21.0

p17

p72

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e90 MO000000077

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c204 : 1
stoichiometry:c205 : 1
stoichiometry:c206 : 1

m92*m69*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
462.0, 939.0
21.0, 21.0

p17

p73

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e90 MO000000058

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c207 : 1
stoichiometry:c208 : 1
stoichiometry:c209 : 1

m92*m29*0.1

nodelay

--

true

0

false

PMID: 18406369 The net result is that the MyD88-dependent pathway activates MAP kinases and the NF¦ÊB signaling module

Go back
670.0, 859.0
21.0, 21.0

p74

p74

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e88 e68

e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c210 : 1
stoichiometry:c212 : 1
stoichiometry:c211 : 1

m90*m70*0.1

nodelay

--

true

0

false

PMID: 18406369,15021916 It was reported that human papilloma virus (HPV) E7 protein could be degraded by SOCS expression, resulting in a loss of proliferation of HPV-transformed HeLa cells

Go back
1086.0, 227.0
21.0, 21.0

p8

p8

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e18

e19

true true true true

--

and

mass

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

m18*0.1

nodelay

--

true

0

false

PMID: 18406369 In turn, STATs are tyrosine phosphorylated by JAKs, which uncovers a nuclear localization signal.

Go back
1083.0, 320.0
19.0, 19.0

p9

p9

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e19

e16 e91

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c22 : 1
stoichiometry:c21 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 18406369 STAT dimers dissociate from the receptor and translocate to the nucleus where they act as transcription factors by binding to specific DNA sequences.

Go back
375.0, 38.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
648.0, 35.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
557.8755395845095, 105.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
422.8466608896548, 235.01449926937056

c101

c101

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
391.0, 338.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
376.7367961643818, 490.0

c103

c103

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
471.0, 338.0

c104

c104

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
636.0, 287.4585775001349

c105

c105

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
313.0, 35.41556838966356

c106

c106

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
736.5982147532262, 112.0

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
317.9974886360164, 276.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
314.0, 186.0

c109

c109

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
787.0, 44.65685424949238

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
448.0, 257.3752741648123

c110

c110

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
662.4290863355067, 263.6223053976244

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
555.897233121606, 322.40579702813875

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
217.0, 778.0

c113

c113

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
478.4958416382905, 312.0

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
367.0, 324.88352148216984

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
229.0, 549.0682994431223

c116

c116

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
381.9282586084793, 536.0689786887838

c117

c117

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
374.0, 277.13495279227135

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1129.8025063917887, 492.0

c119

c119

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
850.0, 35.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
525.3846153846154, 202.0

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
410.9079094402277, 246.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1050.9298232054612, 548.0573097607281

c122

c122

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1002.0, 653.0

c123

c123

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1072.0, 1063.0

c124

c124

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
762.824777408088, 929.0

c125

c125

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
667.0, 254.0

c126

c126

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
929.8553088268978, 801.0

c127

c127

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
732.98659123298, 745.0

c128

c128

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
654.3002827331912, 705.2719828874046

c129

c129

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
917.0, 277.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
500.0, 752.0

c130

c130

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
571.9787730468599, 751.0

c131

c131

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
533.89081263318, 683.7733408252956

c132

c132

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
729.0, 345.0

c133

c133

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
779.5019571832863, 409.8076214712466

c134

c134

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
775.0, 355.9301186488645

c135

c135

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
320.9282586084793, 220.0

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
310.0, 36.70218430575631

c137

c137

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
314.0, 38.01756062843664

c138

c138

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
729.0, 336.0

c139

c139

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
927.0, 326.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1010.2164574740316, 421.90697358120497

c140

c140

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
943.538441890012, 414.0

c141

c141

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
233.84950128852486, 789.0

c142

c142

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
227.0, 836.0

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
311.0, 714.1012274749298

c144

c144

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
463.0, 630.7931034482758

c145

c145

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
466.99221031393154, 671.0

c146

c146

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
666.0, 256.0

c147

c147

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
833.0, 478.5538553641523

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
862.0, 472.0

c149

c149

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
987.0, 109.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1106.6254126948484, 511.0

c150

c150

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
878.9709005417346, 463.6817217568589

c151

c151

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
638.8576953209139, 385.50220645841

c152

c152

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
710.7293356559535, 363.06333960307234

c153

c153

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
525.4920383818378, 242.80523811557399

c154

c154

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
630.1165361451483, 1040.0

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
623.0, 1102.0

c156

c156

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
615.4717770319409, 1106.0

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
608.0, 1154.0

c158

c158

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
603.0, 986.9380247746784

c159

c159

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1015.0, 179.0437687993774

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
750.9016422671206, 924.0

c160

c160

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
743.0, 866.3873536724267

c161

c161

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
755.1313651147161, 781.0

c162

c162

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
613.4806698104644, 1162.0

c163

c163

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1188.0, 1178.0

c164

c164

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1189.0, 1193.151825073934

c165

c165

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1196.7492919018569, 1143.2950039375453

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1185.0, 1189.0

c167

c167

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1192.0, 1282.0

c168

c168

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1189.5168004731197, 1102.5937945309645

c169

c169

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1105.0, 123.99982060377062

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1253.0, 935.0

c170

c170

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1190.0, 1130.0

c171

c171

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1196.64145823744, 1051.5158932948675

c172

c172

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1194.0, 1058.965973361507

c173

c173

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1255.0, 935.0

c174

c174

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1198.1388717087389, 988.1297421127817

c175

c175

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1036.113663989329, 1039.0

c176

c176

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1084.5240571578818, 982.0

c177

c177

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1069.249359027349, 563.0

c178

c178

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1022.8186145148662, 563.0

c179

c179

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1107.0425633433638, 116.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1026.0, 1175.0

c180

c180

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
981.9706438516944, 1235.9255731164806

c181

c181

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
922.1786102703982, 1298.530942450074

c182

c182

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
965.3441786410823, 588.0

c183

c183

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
906.9767191771311, 588.0

c184

c184

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
969.0, 1236.0

c185

c185

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
793.6418452277261, 1300.0

c186

c186

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
743.1831076448378, 1243.9120323748532

c187

c187

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
779.0, 1211.9449841584299

c188

c188

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
865.1138113538517, 1221.1521486845832

c189

c189

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1106.0, 248.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
906.9389699418738, 1178.9630823488608

c190

c190

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
812.7091639613772, 616.0

c191

c191

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
811.0, 687.9102174484356

c192

c192

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
750.6548132754549, 810.0

c193

c193

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
744.0, 753.7093196029865

c194

c194

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
898.5667963590413, 616.0

c195

c195

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
889.1358615077703, 687.9988462699758

c196

c196

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
858.0438357915414, 810.0

c197

c197

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
854.0, 753.9904566101794

c198

c198

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
239.03471347254214, 456.0

c199

c199

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
341.65685424949237, 130.65685424949237

c2

c2

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1110.0, 330.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
246.0, 932.0

c200

c200

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
312.0, 885.8018287567196

c201

c201

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
414.16541101033556, 581.0

c202

c202

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
314.76229486254493, 880.0

c203

c203

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
311.0, 929.907883951425

c204

c204

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
441.8550209910808, 612.0

c205

c205

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
435.0, 678.729912613766

c206

c206

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
311.0, 960.028121803566

c207

c207

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
490.6387508759297, 802.0

c208

c208

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
483.0, 743.7828910926303

c209

c209

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1074.6568542494924, 339.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
632.0, 886.3276534527629

c210

c210

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
691.0, 872.0

c211

c211

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
682.5932737959531, 348.0

c212

c212

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
986.7332964614516, 128.07548567456064

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
743.8299770843672, 366.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
657.2228841505914, 440.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
641.0, 486.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
658.0, 526.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
585.0, 526.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
558.0, 533.0

c28

c28

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
556.1165361451483, 588.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
410.9279394432826, 184.07134316801117

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
736.0, 242.0

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
790.0, 312.0

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
789.1199957600127, 277.0

c32

c32

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1250.0, 368.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1187.0, 390.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1199.8131557336408, 421.0

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1091.0, 521.8132665336364

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1007.5298221281347, 556.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1118.0, 515.0

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1054.990498808999, 611.3897804297072

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
314.0, 182.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1007.0, 585.0

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1047.0, 614.0

c41

c41

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
974.9984319874409, 670.1583847918305

c42

c42

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
940.0, 616.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
907.0, 670.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
969.7033255371181, 677.0

c45

c45

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
955.017314527883, 754.9350533174868

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
896.9876828256433, 735.4437601569801

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
689.979874698584, 655.5670976943156

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
622.7611400011626, 640.9402850002907

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
329.0, 55.155417527999326

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
820.9284852929829, 736.0

c50

c50

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
607.2264150943396, 649.7924528301887

c51

c51

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
639.0, 1034.3365439158895

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1052.0, 734.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1110.0, 741.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1076.0, 777.0

c55

c55

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1127.0, 798.0

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1119.0, 807.0

c57

c57

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1050.9957730662131, 854.2600251403646

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1033.0, 872.0

c59

c59

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
367.0, 45.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
929.0, 854.0

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
645.6921915811266, 779.197769023179

c61

c61

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
588.0950515759703, 724.1676940130167

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
201.0, 357.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
219.3846153846154, 399.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
212.0, 434.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
443.6152512919958, 408.56045373504224

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
415.0, 324.02903021471184

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
312.0, 396.4696698274739

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
545.8178369248513, 416.79072967793434

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
463.0, 54.21795896565988

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
312.0, 401.16186132001656

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
372.21676231134836, 585.0

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1192.0, 440.0

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
569.0, 398.8678007676015

c73

c73

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
229.0, 691.9425419190263

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
209.71875868311227, 565.3426123195726

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
211.0, 554.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
203.0, 511.41038160660986

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1203.7873373466687, 476.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
513.0, 373.97412163750346

c79

c79

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
515.0, 45.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
540.1159298546768, 325.9991599726968

c80

c80

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
313.0, 468.85946652196094

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
422.93543867762463, 464.0143041918768

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
364.0, 262.63223974768493

c83

c83

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
762.7611400011626, 637.9402850002907

c84

c84

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
229.0, 621.4249868109393

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
579.1676940130167, 497.09505157597033

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
752.0, 178.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
830.238549617608, 109.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
823.0, 179.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
613.0, 48.36999649129108

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
820.0, 240.16753793172938

c90

c90

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
872.4754872673307, 117.0

c91

c91

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
867.0, 228.0

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1110.2, 172.4

c93

c93

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1106.2101486511465, 175.3339530500346

c94

c94

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
657.0, 216.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
320.5753347915585, 188.0

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
464.5276068929483, 202.0

c97

c97

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
612.0, 198.0

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
540.0, 198.0

c99

c99

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back