1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/16982211.csml convertedTime:2009.07.01.10:58

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Ubiquitin: tool and target for intracellular NF-kappaB inhibitors.
Authors Wullaert A, Heyninck K, Janssens S, Beyaert R.
Affiliation Unit of Molecular Signal Transduction in Inflammation, Department for MolecularBiomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB)- Ghent University, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium.
Abstract The transcription factor nuclear factor-kappaB (NF-kappaB) has a pivotal role ininitiating inflammation and raising an effective immune response. BecauseNF-kappaB activation depends on ubiquitination, cells have developed ubiquitin(Ub)-mediated strategies for inhibiting NF-kappaB activation and preventingexcessive inflammation. Recent findings concerning tumor necrosis factor (TNF)receptor and toll-like receptor (TLR)-interleukin-1 (IL-1) receptor signallingpathways show that Ub can be a tool as well as a target for NF-kappaB inhibitoryproteins, either by labelling specific signalling proteins forproteasome-dependent degradation or by serving as a target for specificde-ubiquitinating enzymes that prevent the formation of pertinent signallingcomplexes. Interfering with ubiquitination therefore seems to be a versatilemeans for regulating NF-kappaB activity, indicating that studies of Ub-mediatedsignalling might hold the key for developing new therapeutic strategies forinflammatory disease.
PMID 16982211
Model Abstract

Entity

G010329:TNF-alpha G010334:SELE G010389:IL-1beta G010405:A20 G010431:ICAM-1 G010514:iNOS G010819:IkappaBalpha G013179:CYLD G029941:COX2 MO000000204:TNF MO000000205:TNFR MO000000207:TRADD MO000000208:RIP MO000000209:TRAF2 MO000000212:TRAF6 MO000000213:IRAK-1 MO000000214:IL-1 MO000000233:IkappaB-alpha MO000000238:Bcl-3 MO000000254:p50:RelA-p65:IkappaB-alpha{p} MO000000306:ICAM-1 MO000016573:MyD88 MO000016574:TAK1 MO000016591:A20 MO000016597:IL-1beta MO000016632:p50:RelA-p65 {activated} MO000016661:IKK-alpha:IKK-beta:(IKK-gamma)2 MO000016921:TNFR2 MO000017004:SOCS-1 MO000017121:SOCS-3 MO000017264:IL-8 MO000017266:COX-2 MO000018939:Cullin-2 MO000018946:elongin C MO000018947:elongin B MO000019394:TLR4 MO000019479:protein remnants MO000021201:iNOS MO000021586:Siah-2 MO000022125:TAB2 MO000038724:p50:RelA-p65:IkappaB-alpha MO000039077:IRAK-4 MO000039096:IL-1beta:IL-1RI:IL-1RAcP:MyD88 MO000041169:CYLD MO000041541:TAB3 MO000042012:TLR9 MO000042409:LPS MO000067812:SELE MO000068831:MAL MO000090775:USP31 MO000099670:E2 e1: e10: e100: e101: e102: e103: e104: e105: e106:TNF-alpha: TNFR2 e11:TNF-alpha: TNFR: TRADD e12:TNF-alpha: TNFR: TRADD: TRAF2: RIP e13:TNF-alpha: TNFR: TRADD: TRAF2 {ubK63}n: RIP e14:TRAF2 {ub}n: RIP {ubK63}n e15:TRAF2 {ubK63}n: RIP e16:TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2 e17:TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 : TAK1 e18:IL-1RI: IL-RAcP e19:TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2: TAK1 e2: e20:IL-1beta: IL-1RI: IL-RAcP e21:TLR4: MD-2: CD14 e22:LPS: TLR4: MD-2: CD14 e23:LPS: TLR4: MD-2: CD14: MyD88 e24:LPS: TLR4: MD-2: CD14: MAL e25:LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4 e26:LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4: TRAF6 e27:IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4 e28:IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4: TRAF6 e29:IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1{p}: IRAK-4: TRAF6 e3: e30:LPS: TLR4: MD-2: CD14: MyD88: IRAK-1{p}: IRAK-4: TRAF6 e31:IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-4 e32:LPS: TLR4: MD-2: CD14: MyD88: IRAK-4 e33:IRAK-1 {p}: TRAF6 {ubK63}n e34:IRAK-1 {p}: TRAF6 e35:TAK1: TAB2: TAB3 e36:IRAK-1 {p}: TRAF6 {ubK63}n: TAK1: TAb2: TAb3 e37:IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 e38:p50:RelA-p65:IkappaB-alpha{p} {ubK48} e39:p50:RelA-p65 {nucleus} e4: e40:NF-kappaB responsive genes: p50:RelA-p65 e41:NF-kappaB responsive genes e42:IkappaB-alpha (cytoplasmic) e43:p50:RelA-p65:IkappaB-alpha {nucleus} e44:IL-8 e45:Eotaxin e46:Eotaxin e47:TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 {ub}: TAK1 e48:OTUD7B e49:TRAF6: OTUD7B e5:TNF-alpha e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:TNF-alpha: TNFR e60: e61: e62: e63:Bcl-3 {ub} e64:Bcl-3 {ub}{nucleus} e65:TRAF2: USP31 e66:TLR4: TRIAD3A e67:TLR9: TRIAD3A e68:TRIAD3A e69:TLR9 {ub}n: TRIAD3A e7: e70:TLR4 {ub}n: TRIAD3A e71:ASB3 e72:Rbx2 e73:TNFR2 {ubK48}n e74:ASB3: elongin B: elongin C: cullin-2: Rbx2: E2 e75:TNF: TNFR2 e76:TNF: TNFR2: TRAF2 e77:BIRC2 e78:TNF-alpha: TNFR2: TRAF2 {ub}: BIRC2 e79:TNF: TNFR2: TRAF2: BIRC2 e8: e80: e81: e82: e83: e84: e85: e86:TNF-alpha: TNFR2: TRAF2: BIRC2 e87:e87 e88:RABGEF1 e89:Zfand6 e9: e90:OTUD7B e91:Zfand5 e92:LPS: TLR4: MD-2: CD14: MAL {ub} e93:LPS: TLR4: MD-2: CD14: MAL {p} e94:p50: RelA-p65 {ub}n e95:IRAK1: SOCS-1 e96:TRAF6: TAK1: SOCS-1 e97:IRAK-1 {p}: TRAF6 {ubK63}n: TAK1 {activated}: TAb2: TAb3 e98: e99:

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 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 p75 p76 p77 p78 p79 p8 p80 p81 p82 p83 p84 p85 p86 p87 p88 p89 p9 p90 p91 p92 p93 p94
Model Detail
540.0, 1007.0
28.0, 28.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p37

--

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
527.0, 1158.0
30.0, 30.0

SELE

--

G010334

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p45

p46

true true true true

csml-variable:Double

m93313

10

false

infinite

0

unit false false false
TRANSFACG010334

--

Go back
527.0, 1046.0
29.0, 29.0

IL-1beta

--

G010389

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p40

--

true true true true

csml-variable:Double

m93364

10

false

infinite

0

unit false false false
TRANSFACG010389

--

Go back
698.0, 1265.0
23.0, 23.0

A20

--

G010405

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p53 p54

p28

true true true true

csml-variable:Double

m93378

10

false

infinite

0

unit false false false
TRANSFACG010405

--

Go back
528.0, 1199.0
28.0, 28.0

ICAM-1

--

G010431

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p48

p47

true true true true

csml-variable:Double

m93403

10

false

infinite

0

unit false false false
TRANSFACG010431

--

Go back
540.0, 1243.0
28.0, 28.0

iNOS

--

G010514

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p49

p50

true true true true

csml-variable:Double

m93479

10

false

infinite

0

unit false false false
TRANSFACG010514

--

Go back
860.0, 1231.0
35.0, 35.0

IkappaBalpha

--

G010819

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p30

p33

true true true true

csml-variable:Double

m93713

10

false

infinite

0

unit false false false
TRANSFACG010819

--

Go back
784.0, 1235.0
28.0, 28.0

CYLD

--

G013179

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p62

--

true true true true

csml-variable:Double

m95668

10

false

infinite

0

unit false false false
TRANSFACG013179

--

Go back
589.0, 1280.0
26.0, 26.0

COX2

--

G029941

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p51

p52

true true true true

csml-variable:Double

m108639

10

false

infinite

0

unit false false false
TRANSFACG029941

--

Go back
177.0, 213.0
30.0, 30.0

TNF

--

MO000000204

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p75

true true true true

csml-variable:Double

m175

10

false

infinite

0

unit false false false
TRANSPATHMO000000204

--

Go back
306.0, 305.0
32.0, 32.0

TNFR

--

MO000000205

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m176

10

false

infinite

0

unit false false false
TRANSPATHMO000000205

--

Go back
379.0, 378.0
30.0, 30.0

TRADD

--

MO000000207

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m178

10

false

infinite

0

unit false false false
InterProIPR000488
TRANSPATHMO000000207

--

Go back
379.0, 486.0
29.0, 29.0

RIP

--

MO000000208

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m179

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000208

--

Go back
383.0, 450.0
30.0, 30.0

TRAF2

--

MO000000209

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p66 p77

true true true true

csml-variable:Double

m180

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000209

--

Go back
932.0, 395.0
28.0, 28.0

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16 p18 p59 p93

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
915.0, 358.0
28.0, 28.0

IRAK-1

--

MO000000213

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15 p17 p92

true true true true

csml-variable:Double

m184

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000213

--

Go back
744.0, 1467.0
28.0, 28.0

IL-1

--

MO000000214

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p53

true true true true

csml-variable:Double

m185

10

false

infinite

0

unit false false false
TRANSPATHMO000000214

--

Go back
802.0, 1113.0
32.0, 32.0

IkappaB-alpha

--

MO000000233

cso30:c:Protein

cso30:i:CC_CellComponent

--

p34

p32 p36

true true true true

csml-variable:Double

m199

10

false

infinite

0

unit false false false
InterProIPR002110
TRANSPATHMO000000233

--

Go back
919.0, 914.0
30.0, 30.0

Bcl-3

--

MO000000238

cso30:c:Protein

cso30:i:CC_CellComponent

--

p64

p63

true true true true

csml-variable:Double

m204

10

false

infinite

0

unit false false false
InterProIPR002110
TRANSPATHMO000000238

--

Go back
779.0, 690.0
38.0, 38.0

p50:RelA-p65:IkappaB-alpha{p}

--

MO000000254

cso30:c:Protein

cso30:i:CC_CellComponent

--

p26

p27

true true true true

csml-variable:Double

m208

10

false

infinite

0

unit false false false
TRANSPATHMO000000254

--

Go back
358.0, 1201.0
32.0, 32.0

ICAM-1

--

MO000000306

cso30:c:Protein

cso30:i:CC_CellComponent

--

p47

--

true true true true

csml-variable:Double

m242

10

false

infinite

0

unit false false false
InterProIPR003987
TRANSPATHMO000000306

--

Go back
826.0, 265.0
32.0, 32.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11 p13

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
513.0, 780.0
34.0, 34.0

TAK1

--

MO000016574

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8 p93

true true true true

csml-variable:Double

m1573

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016574

--

Go back
524.0, 519.0
28.0, 28.0

A20

--

MO000016591

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p55 p56 p58

true true true true

csml-variable:Double

m1585

10

false

infinite

0

unit false false false
InterProIPR002653
TRANSPATHMO000016591

--

Go back
192.0, 71.0
28.0, 28.0

IL-1beta

--

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m1591

10

false

infinite

0

unit false false false
TRANSPATHMO000016597

--

Go back
706.0, 797.0
32.0, 32.0

p50:RelA-p65 {activated}

--

MO000016632

cso30:c:Protein

cso30:i:CC_CellComponent

--

p28

p29 p90

true true true true

csml-variable:Double

m1617

10

false

infinite

0

unit false false false
TRANSPATHMO000016632

--

Go back
513.0, 708.0
32.0, 32.0

IKK-alpha:IKK-beta:(IKK-gamma)2

--

MO000016661

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7 p25

true true true true

csml-variable:Double

m1637

10

false

infinite

0

unit false false false
TRANSPATHMO000016661

--

Go back
297.0, 272.0
26.0, 26.0

TNFR2

--

MO000016921

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p76 p74 p75

true true true true

csml-variable:Double

m1836

10

false

infinite

0

unit false false false
InterProIPR001368
TRANSPATHMO000016921

--

Go back
960.0, 659.0
28.0, 28.0

SOCS-1

--

MO000017004

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p87 p89 p90 p91 p92

true true true true

csml-variable:Double

m1906

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017004

--

Go back
803.0, 414.0
30.0, 30.0

SOCS-3

--

MO000017121

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p93

true true true true

csml-variable:Double

m2005

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017121

--

Go back
353.0, 1084.0
26.0, 26.0

IL-8

--

MO000017264

cso30:c:Protein

cso30:i:CC_CellComponent

--

p42

--

true true true true

csml-variable:Double

m2120

10

false

infinite

0

unit false false false
InterProIPR002473
TRANSPATHMO000017264

--

Go back
419.0, 1278.0
30.0, 30.0

COX-2

--

MO000017266

cso30:c:Protein

cso30:i:CC_CellComponent

--

p52

--

true true true true

csml-variable:Double

m2122

10

false

infinite

0

unit false false false
InterProIPR002016
TRANSPATHMO000017266

--

Go back
555.0, 382.0
30.0, 30.0

Cullin-2

--

MO000018939

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p73

true true true true

csml-variable:Double

m3551

10

false

infinite

0

unit false false false
TRANSPATHMO000018939

--

Go back
520.0, 339.0
28.5, 28.5

elongin C

--

MO000018946

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p73

true true true true

csml-variable:Double

m3558

10

false

infinite

0

unit false false false
InterProIPR001232
TRANSPATHMO000018946

--

Go back
520.0, 303.0
28.0, 28.0

elongin B

--

MO000018947

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p73

true true true true

csml-variable:Double

m3559

10

false

infinite

0

unit false false false
InterProIPR000626
TRANSPATHMO000018947

--

Go back
1134.0, 685.0
24.0, 24.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p67

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
921.0, 844.0
26.0, 26.0

protein remnants

--

MO000019479

cso30:c:Protein

cso30:i:CC_CellComponent

--

p28 p71 p72 p81 p82 p89 p91

--

true true true true

csml-variable:Double

m360980

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
375.0, 1246.0
30.0, 30.0

iNOS

--

MO000021201

cso30:c:Protein

cso30:i:CC_CellComponent

--

p50

--

true true true true

csml-variable:Double

m5576

10

false

infinite

0

unit false false false
TRANSPATHMO000021201

--

Go back
681.0, 352.0
26.0, 26.0

Siah-2

--

MO000021586

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p60 p78 p81

true true true true

csml-variable:Double

m5930

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000021586

--

Go back
522.0, 637.0
30.0, 30.0

TAB2

--

MO000022125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m6433

10

false

infinite

0

unit false false false
TRANSPATHMO000022125

--

Go back
808.0, 631.0
36.0, 36.0

p50:RelA-p65:IkappaB-alpha

--

MO000038724

cso30:c:Complex

cso30:i:CC_CellComponent

--

p35

p26

true true true true

csml-variable:Double

m16910

10

false

infinite

0

unit false false false
TRANSPATHMO000038724

--

Go back
928.0, 303.0
28.0, 28.0

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15 p17

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
788.0, 183.0
36.0, 36.0

IL-1beta:IL-1RI:IL-1RAcP:MyD88

--

MO000039096

cso30:c:Protein

cso30:i:CC_CellComponent

--

p11

p17

true true true true

csml-variable:Double

m17272

10

false

infinite

0

unit false false false
TRANSPATHMO000039096

--

Go back
517.0, 465.0
30.0, 30.0

CYLD

--

MO000041169

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p60 p61 p64 p65

true true true true

csml-variable:Double

m19042

10

false

infinite

0

unit false false false
TRANSPATHMO000041169

--

Go back
519.0, 670.0
28.5, 28.5

TAB3

--

MO000041541

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m19389

10

false

infinite

0

unit false false false
TRANSPATHMO000041541

--

Go back
1129.0, 804.0
26.0, 26.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p68

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
1235.0, 90.0
30.0, 30.0

LPS

--

MO000042409

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m157177

10

false

infinite

0

unit false false false
TRANSPATHMO000042409

--

Go back
357.0, 1156.0
33.0, 33.0

SELE

--

MO000067812

cso30:c:Protein

cso30:i:CC_CellComponent

--

p46

--

true true true true

csml-variable:Double

m42664

10

false

infinite

0

unit false false false
TRANSPATHMO000067812

--

Go back
1020.0, 247.0
28.0, 28.0

MAL

--

MO000068831

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m43675

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
517.0, 420.0
26.0, 26.0

USP31

--

MO000090775

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28 p66

true true true true

csml-variable:Double

m64276

10

false

infinite

0

unit false false false
TRANSPATHMO000090775

--

Go back
622.0, 385.0
24.0, 24.0

E2

--

MO000099670

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p73

true true true true

csml-variable:Double

m72721

10

false

infinite

0

unit false false false
TRANSPATHMO000099670

--

Go back
271.75, 145.9969080091176
902.3578822932036, 1310.2236450897306

--

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
285.0, 221.0
829.9775981223105, 1167.545103664102

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
7.075838238238688, 61.62947042877505
177.6316185176711, 261.266505569741

--

e100

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m100

0

false

infinite

0

unit false true false

--

Go back
3.375179519120536, 57.928811709656884
185.03293595590736, 268.6678230079772

--

e101

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m101

0

false

infinite

0

unit false true false

--

Go back
5.806242411641236, 59.0099522684926
181.45966340753205, 257.12365589849543

--

e102

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m102

0

false

infinite

0

unit false true false

--

Go back
5.157958973635715, 62.035274979185004
179.35357692609853, 252.3000512766251

--

e103

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m103

0

false

infinite

0

unit false true false

--

Go back
6.454525849646743, 63.54793633453119
174.07641733852614, 252.75895797553983

--

e104

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m104

0

false

infinite

0

unit false true false

--

Go back
8.183281684328122, 68.08592040056992
173.2816630064738, 249.44408757735476

--

e105

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m105

0

false

infinite

0

unit false true false

--

Go back
327.625, 148.5
25.269580069988336, 30.942342942842853

TNF-alpha: TNFR2

--

e106

cso30:c:Complex

cso30:i:CC_Extracellular

--

p74

--

true true true true

csml-variable:Double

m106

0

false

infinite

0

unit false false false

--

Go back
290.25, 408.0
29.028353826390166, 40.50467975775371

TNF-alpha: TNFR: TRADD

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2 p5

p3

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
294.25, 492.0
30.772343549275096, 42.938153789686176

TNF-alpha: TNFR: TRADD: TRAF2: RIP

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3 p60

p4

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
291.25, 543.0
36.66718663975041, 51.1635162415122

TNF-alpha: TNFR: TRADD: TRAF2 {ubK63}n: RIP

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

p5 p60

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
381.75, 661.0
30.28920179970005, 37.088818530244964

TRAF2 {ub}n: RIP {ubK63}n

--

e14

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

p7 p56

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
381.75, 610.0
31.742626228961836, 38.868521913014504

TRAF2 {ubK63}n: RIP

--

e15

cso30:c:Complex

cso30:i:CC_Cytosol

--

p5 p56

p6 p82

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
376.25, 716.0
35.23885116535144, 49.17048999816479

TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2

--

e16

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

p8

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
384.25, 835.0
42.514681592952854, 59.322811525050454

TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 : TAK1

--

e17

cso30:c:Complex

cso30:i:CC_Cytosol

--

p9 p58

p57

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
567.0, 151.75
46.96000000000001, 35.21999999999999

IL-1RI: IL-RAcP

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p10

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
377.25, 769.0
40.71545237658286, 56.81225913011561

TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2: TAK1

--

e19

cso30:c:Complex

cso30:i:CC_Cytosol

--

p8

p9

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
271.75, 145.9969080091176
902.3578822932036, 1310.2236450897306

--

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
618.25, 127.0
31.301064415489083, 43.67590383556615

IL-1beta: IL-1RI: IL-RAcP

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

p10

p11

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
1121.25, 122.0
33.45540466140576, 46.6819599926592

TLR4: MD-2: CD14

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p12

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
1152.25, 176.0
35.791246100201874, 49.941273628188654

LPS: TLR4: MD-2: CD14

--

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p12

p14

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
1129.25, 389.0
33.99201688383192, 47.43072123325381

LPS: TLR4: MD-2: CD14: MyD88

--

e23

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p13

p15

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
1150.25, 238.0
32.29537529821985, 45.0633143696091

LPS: TLR4: MD-2: CD14: MAL

--

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p14

p13 p88

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
1127.25, 443.0
37.740411084602684, 52.661038722701406

LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4

--

e25

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p15

p16

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1124.25, 503.0
42.60937786749863, 59.45494586162598

LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4: TRAF6

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p16

p20

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
881.25, 173.0
33.89732060928611, 47.29858689667828

IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p17

p18

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
942.25, 161.0
40.05257845476234, 55.88731877408699

IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4: TRAF6

--

e28

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

p18

p19

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
1007.25, 145.0
45.29243897962928, 63.19875206459899

IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1{p}: IRAK-4: TRAF6

--

e29

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

p19

p22

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
289.79715764586405, 164.0440656549817
866.2635670014756, 1274.1293297980035

--

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
1127.25, 567.0
37.795650578087724, 52.7381170857038

LPS: TLR4: MD-2: CD14: MyD88: IRAK-1{p}: IRAK-4: TRAF6

--

e30

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p20

p21

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
1077.25, 133.0
34.02358230868049, 47.47476601211231

IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-4

--

e31

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p22

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
1126.25, 631.0
31.861350706551658, 44.457698660304644

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

--

e32

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p21

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
727.75, 494.0
37.22971171471421, 45.587402099650056

IRAK-1 {p}: TRAF6 {ubK63}n

--

e33

cso30:c:Complex

cso30:i:CC_Cytosol

--

p23

p24 p55 p61

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
730.25, 420.0
30.701321343365752, 42.83905303725453

IRAK-1 {p}: TRAF6

--

e34

cso30:c:Complex

cso30:i:CC_Cytosol

--

p21 p22 p55 p61

p23

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
783.25, 560.0
29.486052486694806, 41.14332905120205

TAK1: TAB2: TAB3

--

e35

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p24

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
657.25, 557.0
34.10249587080199, 47.584877959258584

IRAK-1 {p}: TRAF6 {ubK63}n: TAK1: TAb2: TAb3

--

e36

cso30:c:Complex

cso30:i:CC_Cytosol

--

p24

p25 p94

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
661.25, 626.0
30.91438796109378, 43.13635529454945

IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2

--

e37

cso30:c:Complex

cso30:i:CC_Cytosol

--

p25

p26

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
781.25, 737.0
33.9604514589833, 47.38667645439531

p50:RelA-p65:IkappaB-alpha{p} {ubK48}

--

e38

cso30:c:Complex

cso30:i:CC_Cytosol

--

p27

p28

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
742.0, 1033.0
32.0, 32.0

p50:RelA-p65 {nucleus}

--

e39

cso30:c:Protein

cso30:i:CC_CellComponent

--

p29 p36

p31 p32

true true true true

csml-variable:Double

m5

10

false

infinite

0

unit false false false
TRANSPATHMO000016632

--

Go back
323.18439929071263, 195.62659153524362
799.4890837117784, 1210.9642780374784

--

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
645.0, 1120.75
57.894060169709434, 16.403317048084336

NF-kappaB responsive genes: p50:RelA-p65

--

e40

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p31

p30 p36 p37 p40 p41 p44 p45 p48 p49 p51 p62

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
636.0, 984.75
44.87750556792873, 15.707126948775056

NF-kappaB responsive genes

--

e41

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

p36

p31

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
978.0, 1177.0
32.0, 32.0

IkappaB-alpha (cytoplasmic)

--

e42

cso30:c:Protein

cso30:i:CC_CellComponent

--

p33

p34

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
InterProIPR002110
TRANSPATHMO000000233

--

Go back
769.75, 962.0
24.5, 30.0

p50:RelA-p65:IkappaB-alpha {nucleus}

--

e43

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p32

p35

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
505.0, 1086.0
42.04152249134948, 22.422145328719726

IL-8

--

e44

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p41

p42

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
524.0, 1128.0
35.346020761245676, 18.85121107266436

Eotaxin

--

e45

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p44

p43

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
349.0, 1126.75
33.45341114912457, 20.62960354196015

Eotaxin

--

e46

cso30:c:Protein

cso30:i:CC_Cytosol

--

p43

--

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
375.5, 903.0
36.97100385391815, 51.58744723802533

TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 {ub}: TAK1

--

e47

cso30:c:Complex

cso30:i:CC_Cytosol

--

p57

p58

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
990.0, 512.5
32.32000000000001, 24.240000000000002

OTUD7B

--

e48

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p59

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
933.625, 573.5
32.52037160473254, 39.82086318946842

TRAF6: OTUD7B

--

e49

cso30:c:Complex

cso30:i:CC_Cytosol

--

p59

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
156.0, 355.0
28.0, 28.0

TNF-alpha

--

e5

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p54 p74

true true true true

csml-variable:Double

m6

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
479.0, 934.0
485.7879030631462, 440.5562547332447

--

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
531.4687120626861, 944.4405427691244
284.0547515117839, 426.9867602342741

--

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
485.33243076618623, 939.880114282887
473.123041530774, 428.7960261674701

--

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
486.23706373278435, 940.7847472494852
471.31377559757766, 426.9867602342741

--

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
479.0, 934.0
485.7879030631462, 440.5562547332447

--

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
479.0, 934.0
485.7879030631462, 440.5562547332447

--

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
486.23706373278435, 940.7847472494852
471.31377559757766, 426.9867602342741

--

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
833.6161229064305, 1114.9265933196075
30.349359019772955, 27.474156586320824

--

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
754.0084218458035, 1241.5752086433326
85.94013182681354, 77.79843512743135

--

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
479.0, 934.0
485.7879030631462, 440.5562547332447

--

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
288.5, 351.0
33.59206798866857, 41.133144475920695

TNF-alpha: TNFR

--

e6

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p2

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
593.4974754115927, 1129.7795592571524
15.384189099665587, 7.407202159098256

--

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
592.9837537913526, 1107.6895295868233
52.656466074621605, 94.7816389343189

--

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
615.0737834616821, 1169.3361240156491
8.219545923843366, 8.219545923843372

--

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
996.5, 972.125
34.120000000000005, 25.589999999999996

Bcl-3 {ub}

--

e63

cso30:c:Protein

cso30:i:CC_Cytosol

--

p63

p64 p65

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
824.5, 1276.125
34.120000000000005, 25.589999999999996

Bcl-3 {ub}{nucleus}

--

e64

cso30:c:Protein

cso30:i:CC_Cytosol

--

p65

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
456.625, 424.5
26.812822862856198, 32.83202799533411

TRAF2: USP31

--

e65

cso30:c:Complex

cso30:i:CC_Cytosol

--

p66

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
1132.625, 721.5
25.90647392101316, 31.722212964505914

TLR4: TRIAD3A

--

e66

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p67

p70

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
1129.625, 766.5
23.80799033494418, 29.15264122646225

TLR9: TRIAD3A

--

e67

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p68

p69

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
1003.0, 726.0
30.0, 30.0

TRIAD3A

--

e68

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p67 p68

true true true true

csml-variable:Double

m68

10

false

infinite

0

unit false false false
TRANSPATHMO000061958

--

Go back
1133.625, 842.5
24.069280119980007, 29.47258790201633

TLR9 {ub}n: TRIAD3A

--

e69

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p69

p72

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
283.0, 151.0
839.7237354966342, 1189.8668429177399

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
1129.3550449925012, 877.7204632561239
25.04095150808198, 30.662389601733047

TLR4 {ub}n: TRIAD3A

--

e70

cso30:c:Complex

cso30:i:CC_Extracellular

--

p70

p71

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
637.0, 354.5
34.292614208090164, 21.147112094988927

ASB3

--

e71

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p73

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
576.0, 446.5
27.84, 20.88

Rbx2

--

e72

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p73

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
448.5, 136.125
34.599999999999994, 25.950000000000003

TNFR2 {ubK48}n

--

e73

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p76

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
577.875, 270.5
32.25, 45.0

ASB3: elongin B: elongin C: cullin-2: Rbx2: E2

--

e74

cso30:c:Complex

cso30:i:CC_Cytosol

--

p73

p76

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
297.625, 233.5
25.269580069988336, 30.942342942842853

TNF: TNFR2

--

e75

cso30:c:Complex

cso30:i:CC_Extracellular

--

p75

p77

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
296.875, 186.5
26.55244081482841, 37.04991741603964

TNF: TNFR2: TRAF2

--

e76

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p77

p79

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
375.0, 310.0
30.0, 30.0

BIRC2

--

e77

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p60 p79

true true true true

csml-variable:Double

m77

10

false

infinite

0

unit false false false
TRANSPATHMO000068463

--

Go back
675.875, 203.5
36.10887318774087, 50.38447421545238

TNF-alpha: TNFR2: TRAF2 {ub}: BIRC2

--

e78

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p78

p81

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
374.875, 160.5
29.74054872453661, 41.498440080748765

TNF: TNFR2: TRAF2: BIRC2

--

e79

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p79

p78 p80

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
286.0, 172.0
805.5569854171277, 1169.6687428256696

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
589.0342161107274, 212.09505054141403
138.32321399812625, 41.8083026232279

--

e80

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_IntegralToMembrane_

--

--

--

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false true false

--

Go back
589.0342161107274, 212.09505054141403
138.32321399812625, 41.8083026232279

--

e81

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_Membrane_

--

--

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false true false

--

Go back
591.4804465833633, 214.5412810140497
133.4307530528549, 36.915841677956514

--

e82

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulumLumen

--

--

--

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false true false

--

Go back
590.3685236412562, 213.42935807194257
135.65459893706932, 39.13968756217078

--

e83

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum

--

--

--

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false true false

--

Go back
591.0356774065199, 214.09651183720686
134.32029140654075, 37.805380031642194

--

e84

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_ExtrinsicToInternalSideOfMembrane_

--

--

--

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false true false

--

Go back
589.0342161107274, 212.09505054141403
138.32321399812625, 41.8083026232279

--

e85

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_ExtrinsicToExternalSideOfMembrane_

--

--

--

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false true false

--

Go back
618.875, 220.5
29.74054872453661, 41.498440080748765

TNF-alpha: TNFR2: TRAF2: BIRC2

--

e86

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p80

p78

true true true true

csml-variable:Double

m86

0

false

infinite

0

unit false false false

--

Go back
777.5, 288.5
24.0, 24.0

e87

--

e87

cso30:c:ObjectUnknown

cso30:i:CC_Cytosol

--

p81 p89

--

true true true true

csml-variable:Double

m87

0

false

infinite

0

unit false false false

--

Go back
865.0, 1096.0
26.0, 26.0

RABGEF1

--

e88

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p86

p28

true true true true

csml-variable:Double

m88

10

false

infinite

0

unit false false false
Affymetrix1553717_at
EnsemblENSG00000154710
HGNCKCTD7
OMIM609700
ProteomeHumanPSD/RABGEF1
RefSeqNM_014504
TRANSFACG007098
UnigeneHs.103838

--

Go back
849.0, 1024.0
26.0, 26.0

Zfand6

--

e89

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p85

p28

true true true true

csml-variable:Double

m89

10

false

infinite

0

unit false false false
Affymetrix1422031_a_at
EnsemblENSMUSG00000030629
MGD3110005P07Rik
ProteomeHumanPSD/Zfand6
RefSeqNM_022985
TRANSFACG045281
UnigeneMm.1608

--

Go back
294.0, 193.0
801.8791759029863, 1154.3288303559784

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
879.5, 1071.0
37.214532871972324, 19.847750865051903

OTUD7B

--

e90

cso30:c:mRNA

cso30:i:CC_Cytosol

--

p84

p28

true true true true

csml-variable:Double

m90

0

false

infinite

0

unit false false false

--

Go back
931.5, 1123.0
37.110726643598625, 19.792387543252595

Zfand5

--

e91

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p83

p28

true true true true

csml-variable:Double

m91

0

false

infinite

0

unit false false false

--

Go back
1135.5, 332.0
29.79776105707469, 41.57827124242981

LPS: TLR4: MD-2: CD14: MAL {ub}

--

e92

cso30:c:Complex

cso30:i:CC_Cytosol

--

p87

p89

true true true true

csml-variable:Double

m92

0

false

infinite

0

unit false false false

--

Go back
1150.5, 297.0
26.467608735547806, 36.931547072857406

LPS: TLR4: MD-2: CD14: MAL {p}

--

e93

cso30:c:Complex

cso30:i:CC_Extracellular

--

p88

p87

true true true true

csml-variable:Double

m93

0

false

infinite

0

unit false false false

--

Go back
868.5, 749.0
26.25962339610065, 32.15464089318447

p50: RelA-p65 {ub}n

--

e94

cso30:c:Complex

cso30:i:CC_Cytosol

--

p90

p91

true true true true

csml-variable:Double

m94

0

false

infinite

0

unit false false false

--

Go back
763.5, 352.0
28.2601233127812, 34.60423262789535

IRAK1: SOCS-1

--

e95

cso30:c:Complex

cso30:i:CC_Cytosol

--

p92

--

true true true true

csml-variable:Double

m95

0

false

infinite

0

unit false false false

--

Go back
855.5, 520.0
29.995044962378415, 41.85355111029546

TRAF6: TAK1: SOCS-1

--

e96

cso30:c:Complex

cso30:i:CC_Cytosol

--

p93

p23 p28 p94

true true true true

csml-variable:Double

m96

0

false

infinite

0

unit false false false

--

Go back
557.25, 569.0
34.10249587080199, 47.584877959258584

IRAK-1 {p}: TRAF6 {ubK63}n: TAK1 {activated}: TAb2: TAb3

--

e97

cso30:c:Complex

cso30:i:CC_Cytosol

--

p94

p25

true true true true

csml-variable:Double

m97

0

false

infinite

0

unit false false false

--

Go back
13.922056868607257, 68.10562318723177
163.93918125693398, 248.31420005282737

--

e98

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m98

0

false

infinite

0

unit false true false

--

Go back
3.375179519120536, 57.928811709656884
185.03293595590736, 268.6678230079772

--

e99

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m99

0

false

infinite

0

unit false true false

--

Go back
217.0, 360.0
23.0, 23.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e5 MO000000205

e6

true true true true

--

and

mass

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

m6*m176*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of TNF to TNF receptor-1 (TNF-R1; the main receptor for soluble TNF on most cell types) (A) leads to the recruitment of TNF receptor-1 associated death domain protein (TRADD; red), which in turn recruits TNF receptor-associated factor 2 (TRAF2; orange) and receptor-interacting protein (RIP; dark grey).

Go back
578.0, 73.0
23.0, 23.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016597 e18

e20

true true true true

--

and

mass

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

m1591*m19*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
830.0, 77.0
23.0, 23.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e20 MO000016573

MO000039096

true true true true

--

and

mass

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

m21*m1572*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
1237.0, 172.0
25.0, 25.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000042409 e21

e22

true true true true

--

and

mass

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

m157177*m22*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
1237.0, 268.0
26.0, 26.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e24 MO000016573

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c37 : 1
stoichiometry:c39 : 1

m25*m1572*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
1238.0, 213.0
23.0, 23.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000068831 e22

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c60 : 1
stoichiometry:c41 : 1

m43675*m23*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

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982.0, 361.0
23.0, 23.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213 MO000039077 e23

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c43 : 1
stoichiometry:c44 : 1
stoichiometry:c45 : 1

m184*m17258*m24*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
992.0, 395.0
27.0, 27.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000212 e25

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c47 : 1

m183*m26*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
767.0, 238.0
22.5, 22.5

p17

p17

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000039077 MO000000213 MO000039096

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c50 : 1
stoichiometry:c258 : 1
stoichiometry:c52 : 1

m17258*m184*m17272*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
886.0, 245.0
24.0, 24.0

p18

p18

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e27 MO000000212

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c54 : 1
stoichiometry:c55 : 1

m28*m183*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of IL-1beta to the IL-1 receptor (IL-1R)?IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4?MD2?CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.

Go back
950.0, 77.0
23.0, 23.0

p19

p19

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e28

e29

true true true true

--

and

mass

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

m29*0.1

nodelay

--

true

0

false

PMID: 16982211 The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1?TRAF6 complex from the receptor.

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217.0, 416.0
23.0, 23.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e6 MO000000207

e11

true true true true

--

and

mass

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

m11*m178*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of TNF to TNF receptor-1 (TNF-R1; the main receptor for soluble TNF on most cell types) (A) leads to the recruitment of TNF receptor-1 associated death domain protein (TRADD; red), which in turn recruits TNF receptor-associated factor 2 (TRAF2; orange) and receptor-interacting protein (RIP; dark grey).

Go back
1221.0, 520.0
25.0, 25.0

p20

p20

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

e26

e30

true true true true

--

and

mass

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

m27*0.1

nodelay

--

true

0

false

PMID: 16982211 The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1?TRAF6 complex from the receptor.

Go back
997.0, 468.0
25.0, 25.0

p21

p21

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e30

e32 e34

true true true true

--

and

mass

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

m31*0.1

nodelay

--

true

0

false

PMID: 16982211 The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1?TRAF6 complex from the receptor.

Go back
939.0, 242.0
30.0, 30.0

p22

p22

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e29

e31 e34

true true true true

--

and

mass

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

m30*0.1

nodelay

--

true

0

false

PMID: 16982211 The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1?TRAF6 complex from the receptor.

Go back
672.0, 427.0
28.0, 28.0

p23

p23

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e34 e96

e33

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c252 : 1
stoichiometry:c68 : 1

m35*0.1

nodelay

--

true

0

false

PMID: 16982211 Once released from the receptor, the Ub-ligase activity of TRAF6 mediates its K63 auto-polyubiquitination (BC3). PMID: 16982211, 16543409 This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6?TAK1 complex.

Go back
734.0, 569.0
23.0, 23.0

p24

p24

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e35 e33

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c71 : 1

m36*m34*0.1

nodelay

--

true

0

false

PMID: 16982211 K63-polyubiquitinated TRAF6 then recruits the TAK1?TAB2?TAB3 complex, which subsequently phosphorylates and activates IKKalpha and IKKbeta (BC4).

Go back
575.0, 634.0
27.0, 27.0

p25

p25

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000016661 e36 e97

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c74 : 1
stoichiometry:c255 : 1
stoichiometry:c73 : 1

m1637*m37*m97*0.1

nodelay

--

true

0

false

PMID: 16982211 K63-polyubiquitinated TRAF6 then recruits the TAK1?TAB2?TAB3 complex, which subsequently phosphorylates and activates IKKalpha and IKKbeta (BC4).

Go back
722.0, 637.0
23.0, 23.0

p26

p26

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000038724 e37

MO000000254

true true true true

--

and

mass

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

m16910*m38*0.1

nodelay

--

true

0

false

PMID: 16982211 The IKKbeta catalytic subunit then phosphorylates the inhibitor of kappaB (IkappaB)¦Á protein (D1), which keeps NF-kappaB (shown here as a p65?p50 dimer) in the cytoplasm of resting cells.

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712.0, 695.0
27.0, 27.0

p27

p27

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000000254

e38

true true true true

--

and

mass

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

m208*0.1

nodelay

--

true

0

false

PMID: 16982211 IkappaBalpha phosphorylation leads to its K48 polyubiquitination (D2) and subsequent proteasomal degradation (D3).

Go back
709.0, 748.0
25.0, 25.0

p28

p28

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e38 MO000090775 G010405 e89 e90 e88 e91 e96

MO000019479 MO000016632

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c171 : 1
stoichiometry:c221 : 1
stoichiometry:c222 : 1
stoichiometry:c223 : 1
stoichiometry:c224 : 1
stoichiometry:c225 : 1
stoichiometry:c257 : 1
stoichiometry:c82 : 1
stoichiometry:c81 : 1

m39*0.1

nodelay

--

true

0

false

PMID: 16982211 IkappaBalpha phosphorylation leads to its K48 polyubiquitination (D2) and subsequent proteasomal degradation (D3). PMID: 16982211, 16214042 Recently, ubiquitin specific peptidase 31 (USP31) was identified as another TRAF2 binding DUB that inhibits TNF-induced NF-kappaB activation upon overexpression. PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation. PMID: 16982211, 16543409 This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6?TAK1 complex.

Go back
709.0, 936.0
25.0, 25.0

p29

p29

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

MO000016632

e39

true true true true

--

and

mass

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

m1617*0.1

nodelay

--

true

0

false

PMID: 16982211 This allows NF-kappaB to translocate to the nucleus (D4), where it induces the transcription of genes with an NF-kappaB consensus site in their promoter region, including IkappaBalpha.

Go back
199.0, 495.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e11 MO000000209 MO000000208

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1
stoichiometry:c10 : 1

m12*m180*m179*0.1

nodelay

--

true

0

false

PMID: 16982211 The binding of TNF to TNF receptor-1 (TNF-R1; the main receptor for soluble TNF on most cell types) (A) leads to the recruitment of TNF receptor-1 associated death domain protein (TRADD; red), which in turn recruits TNF receptor-associated factor 2 (TRAF2; orange) and receptor-interacting protein (RIP; dark grey).

Go back
818.0, 1185.0
23.0, 23.0

p30

p30

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G010819

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211 This allows NF-kappaB to translocate to the nucleus (D4), where it induces the transcription of genes with an NF-kappaB consensus site in their promoter region, including IkappaBalpha.

Go back
699.0, 978.0
30.0, 30.0

p31

p31

cso30:i:ME_DNABinding

cso30:i:CC_Nucleoplasm

--

e39 e41

e40

true true true true

--

and

mass

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

m5*m41*0.1

nodelay

--

true

0

false

PMID: 16982211 This allows NF-kappaB to translocate to the nucleus (D4), where it induces the transcription of genes with an NF-kappaB consensus site in their promoter region, including IkappaBalpha.

Go back
793.0, 1036.0
25.0, 25.0

p32

p32

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

MO000000233 e39

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c102 : 1
stoichiometry:c96 : 1

m199*m5*0.1

nodelay

--

true

0

false

PMID: 16982211 This newly synthesized I¦ÊB¦Á can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).

Go back
953.0, 1237.0
30.0, 30.0

p33

p33

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010819

e42

true true true true

--

and

mass

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

m93713*0.1

nodelay

--

true

0

false

PMID: 16982211 This newly synthesized I¦ÊB¦Á can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).

Go back
866.0, 1181.0
23.0, 23.0

p34

p34

cso30:i:ME_Translocation

cso30:i:CC_NuclearOuterMembrane

--

e42

MO000000233

true true true true

--

and

mass

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

m42*0.1

nodelay

--

true

0

false

PMID: 16982211 This newly synthesized I¦ÊB¦Á can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).

Go back
813.0, 876.0
25.0, 25.0

p35

p35

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e43

MO000038724

true true true true

--

and

mass

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

m43*0.1

nodelay

--

true

0

false

PMID: 16982211 This newly synthesized I¦ÊB¦Á can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).

Go back
734.0, 1117.0
23.0, 23.0

p36

p36

cso30:i:ME_Dissociation

cso30:i:CC_Nucleoplasm

--

e40 MO000000233

e39 e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c101 : 1
stoichiometry:c99 : 1
stoichiometry:c100 : 1

m40*m199*0.1

nodelay

--

true

0

false

PMID: 16982211 This newly synthesized I¦ÊB¦Á can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).

Go back
594.0, 1009.0
24.0, 24.0

p37

p37

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G010329

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211 TLR-induced activation of NF-kappaB leads to the expression of several NF-kappaB-dependent genes, including cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, both of which also directly activate the NF-kappaB pathway and thus establish a positive autoregulatory loop.

Go back
210.0, 557.0
23.0, 23.0

p4

p4

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e12

e13

true true true true

--

and

mass

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

m13*0.1

nodelay

--

true

0

false

PMID: 16982211 After its Ub ligase activity is turned on, TRAF2 catalyses K63 polyubiquitination of itself (A1).

Go back
581.0, 1048.0
25.0, 25.0

p40

p40

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G010389

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211 TLR-induced activation of NF-kappaB leads to the expression of several NF-kappaB-dependent genes, including cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, both of which also directly activate the NF-kappaB pathway and thus establish a positive autoregulatory loop.

Go back
573.0, 1084.0
25.0, 25.0

p41

p41

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c113 : 1

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
403.0, 1082.0
27.0, 27.0

p42

p42

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e44

MO000017264

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c111 : 1
stoichiometry:c114 : 1

m44*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
410.0, 1125.0
23.0, 23.0

p43

p43

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e45

e46

true true true true

--

and

mass

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

m45*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
578.0, 1125.0
23.0, 23.0

p44

p44

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

e45

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
578.0, 1161.0
23.0, 23.0

p45

p45

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G010334

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c119 : 1
stoichiometry:c120 : 1

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
425.0, 1160.0
25.0, 25.0

p46

p46

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010334

MO000067812

true true true true

--

and

mass

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

m93313*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
433.0, 1204.0
25.0, 25.0

p47

p47

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010431

MO000000306

true true true true

--

and

mass

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

m93403*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
577.0, 1200.0
25.0, 25.0

p48

p48

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G010431

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
598.0, 1245.0
23.0, 23.0

p49

p49

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G010514

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c127 : 1
stoichiometry:c128 : 1

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
385.0, 556.0
25.0, 25.0

p5

p5

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e13

e11 e15

true true true true

--

and

mass

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

m14*0.1

nodelay

--

true

0

false

PMID: 16982211 This causes the release of TRAF2 into the cytosol and TRAF2-mediated K63 polyubiqutination of RIP (A2).

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449.0, 1248.0
25.0, 25.0

p50

p50

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010514

MO000021201

true true true true

--

and

mass

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

m93479*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
637.0, 1280.0
25.0, 25.0

p51

p51

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G029941

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
493.0, 1280.0
25.0, 25.0

p52

p52

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G029941

MO000017266

true true true true

--

and

mass

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

m108639*0.1

nodelay

--

true

0

false

PMID: 16982211, 12360211 This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.

Go back
742.0, 1305.0
23.0, 23.0

p53

p53

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000000214

G010405

true true true true

--

and

mass

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

m185*0.1

nodelay

--

true

0

false

PMID: 16982211, 8557994, 8692885 Because overexpression of A20 was shown to inhibit NF-kappaB activation in response to many stimuli including TNF and IL-1 19 and 20, it was originally suggested that A20 is a feedback inhibitor of NF-kappaB signalling. PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.

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698.0, 1305.0
23.0, 23.0

p54

p54

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

G010405

true true true true

--

and

mass

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

m6*0.1

nodelay

--

true

0

false

PMID: 16982211, 8557994, 8692885 Because overexpression of A20 was shown to inhibit NF-kappaB activation in response to many stimuli including TNF and IL-1 19 and 20, it was originally suggested that A20 is a feedback inhibitor of NF-kappaB signalling. PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.

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650.0, 505.0
23.0, 23.0

p55

p55

cso30:i:ME_Deubiquitination

cso30:i:CC_Cytosol

--

e33 MO000016591

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c138 : 1
stoichiometry:c144 : 1
stoichiometry:c145 : 1

m34*m1585*0.1

nodelay

--

true

0

false

PMID: 16982211, 15334086, 15258597, 15653317 It was subsequently demonstrated that A20 can disassemble K63 polyubiquitin chains from RIP and TRAF6 in the TNF-receptor-induced and TLR4 [lipopolysaccharide (LPS)]-induced NF-kappaB signalling pathway, respectively.

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461.0, 564.0
25.0, 25.0

p56

p56

cso30:i:ME_Deubiquitination

cso30:i:CC_Cytosol

--

e14 MO000016591

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c143 : 1
stoichiometry:c146 : 1

m15*m1585*0.1

nodelay

--

true

0

false

PMID: 16982211, 15334086, 15258597, 15653317 It was subsequently demonstrated that A20 can disassemble K63 polyubiquitin chains from RIP and TRAF6 in the TNF-receptor-induced and TLR4 [lipopolysaccharide (LPS)]-induced NF-kappaB signalling pathway, respectively. PMID: 16982211, 15258597, 15653317 The de-ubiquitinating and Ub-conjugating activities of A20 are ordered in two steps: the N-terminal OTU domain of A20 first removes the K63-linked polyubiquitin chains from RIP and inactivates it, and the C-terminal zinc finger domain of A20 catalyses K48 polyubiquitination of RIP, thereby targeting it for proteasomal degradation.

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457.0, 916.0
25.0, 25.0

p57

p57

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e17

e47

true true true true

--

and

mass

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

m18*0.1

nodelay

--

true

0

false

PMID: 16982211, 16684768 Recently, TNF-induced IKKgamma ubiquitination was also reported to be sensitive to A20-mediated de-ubiquitination, indicating that A20 might act at different levels of the NF-kappaB signalling pathway.

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229.0, 852.0
25.0, 25.0

p58

p58

cso30:i:ME_Deubiquitination

cso30:i:CC_Cytosol

--

e47 MO000016591

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c149 : 1
stoichiometry:c151 : 1
stoichiometry:c150 : 1

m47*m1585*0.1

nodelay

--

true

0

false

PMID: 16982211, 16684768 Recently, TNF-induced IKKgamma ubiquitination was also reported to be sensitive to A20-mediated de-ubiquitination, indicating that A20 might act at different levels of the NF-kappaB signalling pathway.

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933.0, 512.0
25.0, 25.0

p59

p59

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000212 e48

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c152 : 1
stoichiometry:c153 : 1
stoichiometry:c154 : 1

m183*m48*0.1

nodelay

--

true

0

false

PMID: 16982211, 11463333, 12682062 One of them is OTUD7B (also known as Cezanne), which interacts with TRAF6 and inhibits NF-kappaB activation upon overexpression.

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452.0, 663.0
27.0, 27.0

p6

p6

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e15

e14

true true true true

--

and

mass

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

m16*0.1

nodelay

--

true

0

false

PMID: 16982211 This causes the release of TRAF2 into the cytosol and TRAF2-mediated K63 polyubiqutination of RIP (A2).

Go back
437.0, 504.0
25.0, 25.0

p60

p60

cso30:i:ME_Deubiquitination

cso30:i:CC_Cytosol

--

e13 MO000041169 e77 MO000021586

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c155 : 1
stoichiometry:c157 : 1
stoichiometry:c216 : 1
stoichiometry:c217 : 1
stoichiometry:c156 : 1

m14*m19042*m77*m5930*0.1

nodelay

--

true

0

false

PMID: 16982211, 12917690, 12917691, 12917689 Overexpression of CYLD interferes with IKK activation by catalysing the selective cleavage of K63 polyubiquitin chains from TRAF2 and TRAF6, consistent with its inhibitory effect on both TNF-receptor- and TLR?IL-1-receptor-initiated NF-kappaB activation. PMID: 16982211, 11907583, 12411493 For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).

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634.0, 453.0
23.0, 23.0

p61

p61

cso30:i:ME_Deubiquitination

cso30:i:CC_Cytosol

--

e33 MO000041169

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c135 : 1
stoichiometry:c158 : 1
stoichiometry:c136 : 1

m34*m19042*0.1

nodelay

--

true

0

false

PMID: 16982211, 12917690, 12917691, 12917689 Overexpression of CYLD interferes with IKK activation by catalysing the selective cleavage of K63 polyubiquitin chains from TRAF2 and TRAF6, consistent with its inhibitory effect on both TNF-receptor- and TLR?IL-1-receptor-initiated NF-kappaB activation. PMID: 16982211, 16543409 Instead, SOCS3 decreased TRAF6 polyubiquitination, thus preventing the association and activation of TAK1.

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754.0, 1189.0
23.0, 23.0

p62

p62

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40

G013179

true true true true

--

and

mass

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

m40*0.1

nodelay

--

true

0

false

PMID: 16982211, 16230348, 15226292 Moreover, endogenous expression of CYLD is upregulated by TNF, IL-1 and TLR2 ligands in an NF-kappaB-dependent way, supporting a negative-feedback role for CYLD in the NF-kappaB pathway.

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920.0, 971.0
27.0, 27.0

p63

p63

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000000238

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c161 : 1
stoichiometry:c162 : 1

m204*0.1

nodelay

--

true

0

false

PMID: 16982211, 16713561 For example, CYLD was recently shown to de-ubiquitinate B-cell CLL/lymphoma 3 (BCL3), preventing its nuclear translocation.

Go back
999.0, 914.0
30.0, 30.0

p64

p64

cso30:i:ME_Deubiquitination

cso30:i:CC_Cytosol

--

e63 MO000041169

MO000000238

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c167 : 1
stoichiometry:c164 : 1

m63*m19042*0.1

nodelay

--

true

0

false

PMID: 16982211, 16713561 For example, CYLD was recently shown to de-ubiquitinate B-cell CLL/lymphoma 3 (BCL3), preventing its nuclear translocation.

Go back
1000.0, 1275.0
27.0, 27.0

p65

p65

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e63 MO000041169

e64

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c165 : 1
stoichiometry:c199 : 1
stoichiometry:c166 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 16982211, 16713561 For example, CYLD was recently shown to de-ubiquitinate B-cell CLL/lymphoma 3 (BCL3), preventing its nuclear translocation.

Go back
458.0, 365.0
23.0, 23.0

p66

p66

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000090775 MO000000209

e65

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c168 : 1
stoichiometry:c169 : 1
stoichiometry:c170 : 1

m64276*m180*0.1

nodelay

--

true

0

false

PMID: 16982211, 16214042 Recently, ubiquitin specific peptidase 31 (USP31) was identified as another TRAF2 binding DUB that inhibits TNF-induced NF-kappaB activation upon overexpression.

Go back
1053.0, 684.0
25.0, 25.0

p67

p67

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000019394 e68

e66

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c172 : 1
stoichiometry:c173 : 1
stoichiometry:c174 : 1

m3961*m68*0.1

nodelay

--

true

0

false

PMID: 16982211, 15107846 In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.

Go back
1050.0, 769.0
23.0, 23.0

p68

p68

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e68 MO000042012

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c175 : 1
stoichiometry:c176 : 1
stoichiometry:c177 : 1

m68*m19828*0.1

nodelay

--

true

0

false

PMID: 16982211, 15107846 In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.

Go back
1187.0, 802.0
30.0, 30.0

p69

p69

cso30:i:ME_Ubiquitination

cso30:i:CC_Extracellular

--

e67

e69

true true true true

--

and

mass

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

m67*0.1

nodelay

--

true

0

false

PMID: 16982211, 15107846 In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.

Go back
434.0, 713.0
23.0, 23.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000022125 MO000041541 MO000016661 e14

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c27 : 1
stoichiometry:c21 : 1

m6433*m19389*m1637*m15*0.1

nodelay

--

true

0

false

PMID: 16982211 K63 polyubiquitinated RIP is recognized by the TAK1-binding proteins TAB2 and TAB3 (blue), as well as by IkappaB kinase gamma (IKKgamma; light green).

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1235.0, 802.0
30.0, 30.0

p70

p70

cso30:i:ME_Ubiquitination

cso30:i:CC_Extracellular

--

e66

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c180 : 1
stoichiometry:c181 : 1

m66*0.1

nodelay

--

true

0

false

PMID: 16982211, 15107846 In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.

Go back
1049.0, 880.0
25.0, 25.0

p71

p71

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Extracellular

--

e70

MO000019479

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c182 : 1
stoichiometry:c185 : 1

m70*0.1

nodelay

--

true

0

false

PMID: 16982211, 15107846 In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.

Go back
1049.0, 844.0
25.0, 25.0

p72

p72

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Extracellular

--

e69

MO000019479

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c183 : 1
stoichiometry:c184 : 1

m69*0.1

nodelay

--

true

0

false

PMID: 16982211, 15107846 In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.

Go back
578.0, 341.0
23.0, 23.0

p73

p73

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e71 e72 MO000018947 MO000018946 MO000018939 MO000099670

e74

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c186 : 1
stoichiometry:c188 : 1
stoichiometry:c189 : 1
stoichiometry:c190 : 1
stoichiometry:c191 : 1
stoichiometry:c195 : 1
stoichiometry:c187 : 1

m71*m72*m3559*m3558*m3551*m72721*0.1

nodelay

--

true

0

false

PMID: 16982211, 15899873 In addition, TNF-receptor-2 plasma-membrane levels are regulated by TNF-induced K48 polyubiquitination mediated by Ankyrin repeat and SOCS box-containing 3 (ASB3), which confers its Ub-ligase activity via an interaction with elongin B?elongin C and the recruitment of the Ub-transferase system composed of cullin-2, Rbx2 and E2. PMID: 16982211 SOCS proteins are characterized by a C-terminal SOCS-box domain that allows the binding of the elongin-B?elongin-C complex to form a functional E3 Ub ligase.

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218.0, 313.0
23.0, 23.0

p74

p74

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e5 MO000016921

e106

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c196 : 1
stoichiometry:c197 : 1
stoichiometry:c105 : 1

m6*m1836*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 12411493 For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).

Go back
218.0, 273.0
23.0, 23.0

p75

p75

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016921 MO000000204

e75

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c198 : 1
stoichiometry:c51 : 1
stoichiometry:c200 : 1

m1836*m175*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 12411493 For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).

Go back
453.0, 272.0
25.0, 25.0

p76

p76

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000016921 e74

e73

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c192 : 1
stoichiometry:c194 : 1
stoichiometry:c193 : 1

m1836*m74*0.1

nodelay

--

true

0

false

PMID: 16982211, 15899873 In addition, TNF-receptor-2 plasma-membrane levels are regulated by TNF-induced K48 polyubiquitination mediated by Ankyrin repeat and SOCS box-containing 3 (ASB3), which confers its Ub-ligase activity via an interaction with elongin B?elongin C and the recruitment of the Ub-transferase system composed of cullin-2, Rbx2 and E2.

Go back
218.0, 193.0
23.0, 23.0

p77

p77

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e75 MO000000209

e76

true true true true

--

and

mass

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

m75*m180*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 12411493 For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).

Go back
654.0, 285.0
23.0, 23.0

p78

p78

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e79 MO000021586 e86

e78

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c208 : 1
stoichiometry:c209 : 1
stoichiometry:c212 : 1
stoichiometry:c205 : 1

m79*m5930*m86*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 15861135 Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2?BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling. PMID: 16982211, 11907583, 12411493 For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).

Go back
378.0, 221.0
23.0, 23.0

p79

p79

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e76 e77

e79

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c204 : 1
stoichiometry:c206 : 1
stoichiometry:c207 : 1

m76*m77*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 15861135 Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2?BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling.

Go back
466.0, 785.0
23.0, 23.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016574 e16

e19

true true true true

--

and

mass

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

m1573*m17*0.1

nodelay

--

true

0

false

PMID: 16982211 This brings the kinase TAK1 (light grey) in close proximity to the IKK complex, allowing it to phosphorylate the catalytic IKKalpha and IKKbeta subunits (pink; A3).

Go back
554.0, 225.0
23.0, 23.0

p80

p80

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e79

e86

true true true true

--

and

mass

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

m79*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 15861135 Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2?BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling.

Go back
710.0, 289.0
23.0, 23.0

p81

p81

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e78 MO000021586

MO000019479 e87

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c213 : 1
stoichiometry:c218 : 1
stoichiometry:c214 : 1
stoichiometry:c215 : 1

m78*m5930*0.1

nodelay

--

true

0

false

PMID: 16982211, 11907583, 15861135 Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2?BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling. PMID: 16982211, 12411493 Similarly, the triggering of TNF receptor-1 induces proteasomal degradation of TRAF2 upon overexpression of the E3 Ub ligase SIAH2.

Go back
618.0, 845.0
23.0, 23.0

p82

p82

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e15

MO000019479

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c219 : 1
stoichiometry:c220 : 1

m16*0.1

nodelay

--

true

0

false

PMID: 16982211, 15258597, 15653317 The de-ubiquitinating and Ub-conjugating activities of A20 are ordered in two steps: the N-terminal OTU domain of A20 first removes the K63-linked polyubiquitin chains from RIP and inactivates it, and the C-terminal zinc finger domain of A20 catalyses K48 polyubiquitination of RIP, thereby targeting it for proteasomal degradation.

Go back
902.0, 1161.0
23.0, 23.0

p83

p83

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

--

e91

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c226 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.

Go back
938.0, 1077.0
23.0, 23.0

p84

p84

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

--

e90

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c228 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.

Go back
910.0, 1033.0
23.0, 23.0

p85

p85

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

--

e89

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c229 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.

Go back
871.0, 1138.0
21.0, 21.0

p86

p86

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

--

e88

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c227 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 16982211, 8557994, 11463333, 16204640 Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.

Go back
1069.0, 340.0
25.0, 25.0

p87

p87

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000017004 e93

e92

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c230 : 1
stoichiometry:c231 : 1
stoichiometry:c232 : 1

m1906*m93*0.1

nodelay

--

true

0

false

PMID: 16982211, 16415872 Recently, it was observed that the TLR2 and TLR4 adaptor protein MyD88 adaptor-like (MAL, also known as TIRAP) is phosphorylated and ubiquitinated in a SOCS1-dependent manner upon TLR stimulation, thereby targeting MAL for proteasomal degradation.

Go back
1070.0, 301.0
23.0, 23.0

p88

p88

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e24

e93

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c233 : 1
stoichiometry:c234 : 1

m25*0.1

nodelay

--

true

0

false

PMID: 16982211, 16415872 Recently, it was observed that the TLR2 and TLR4 adaptor protein MyD88 adaptor-like (MAL, also known as TIRAP) is phosphorylated and ubiquitinated in a SOCS1-dependent manner upon TLR stimulation, thereby targeting MAL for proteasomal degradation.

Go back
1019.0, 658.0
22.0, 22.0

p89

p89

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e92 MO000017004

MO000019479 e87

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c235 : 1
stoichiometry:c238 : 1
stoichiometry:c236 : 1
stoichiometry:c237 : 1

m92*m1906*0.1

nodelay

--

true

0

false

PMID: 16982211, 16415872 Recently, it was observed that the TLR2 and TLR4 adaptor protein MyD88 adaptor-like (MAL, also known as TIRAP) is phosphorylated and ubiquitinated in a SOCS1-dependent manner upon TLR stimulation, thereby targeting MAL for proteasomal degradation.

Go back
457.0, 848.0
25.0, 25.0

p9

p9

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e19

e17

true true true true

--

and

mass

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

m20*0.1

nodelay

--

true

0

false

PMID: 16982211 This brings the kinase TAK1 (light grey) in close proximity to the IKK complex, allowing it to phosphorylate the catalytic IKKalpha and IKKbeta subunits (pink; A3).

Go back
780.0, 803.0
24.0, 24.0

p90

p90

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

MO000016632 MO000017004

e94

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c239 : 1
stoichiometry:c243 : 1
stoichiometry:c240 : 1

m1617*m1906*0.1

nodelay

--

true

0

false

PMID: 16982211, 12433373, 14690596 Indeed, an interaction of SOCS1 with IRAK1 as well as SOCS1-mediated ubiquitination and subsequent degradation of the p65 NF-¦ÊB subunit suggest a more downstream inhibitory effect of SOCS1 in TLR signalling pathways.

Go back
879.0, 802.0
21.0, 21.0

p91

p91

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

e94 MO000017004

MO000019479

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c241 : 1
stoichiometry:c244 : 1
stoichiometry:c242 : 1

m94*m1906*0.1

nodelay

--

true

0

false

PMID: 16982211, 12433373, 14690596 Indeed, an interaction of SOCS1 with IRAK1 as well as SOCS1-mediated ubiquitination and subsequent degradation of the p65 NF-¦ÊB subunit suggest a more downstream inhibitory effect of SOCS1 in TLR signalling pathways.

Go back
815.0, 386.0
21.0, 21.0

p92

p92

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000213 MO000017004

e95

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c245 : 1
stoichiometry:c246 : 1
stoichiometry:c247 : 1

m184*m1906*0.1

nodelay

--

true

0

false

PMID: 16982211, 12433373, 14690596 Indeed, an interaction of SOCS1 with IRAK1 as well as SOCS1-mediated ubiquitination and subsequent degradation of the p65 NF-¦ÊB subunit suggest a more downstream inhibitory effect of SOCS1 in TLR signalling pathways.

Go back
806.0, 465.0
23.0, 23.0

p93

p93

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017121 MO000000212 MO000016574

e96

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c248 : 1
stoichiometry:c249 : 1
stoichiometry:c250 : 1
stoichiometry:c251 : 1

m2005*m183*m1573*0.1

nodelay

--

true

0

false

PMID: 16982211, 16543409 This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6?TAK1 complex.

Go back
609.0, 544.0
25.0, 25.0

p94

p94

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e36 e96

e97

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c253 : 1
stoichiometry:c256 : 1
stoichiometry:c254 : 1

m37*0.1

nodelay

--

true

0

false

PMID: 16982211, 16543409 This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6?TAK1 complex. PMID: 16982211, 16543409 Instead, SOCS3 decreased TRAF6 polyubiquitination, thus preventing the association and activation of TAK1.

Go back
184.0, 370.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
224.0, 509.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
667.3173289177635, 1006.735033111711

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
765.0, 1129.0

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
774.0, 1049.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
618.2399915200255, 1039.7839864320406

c103

c103

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
576.0, 1021.0

c104

c104

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
238.0, 185.6181666334406

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
612.0592796928046, 1076.2235169765556

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
564.0, 1061.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
239.74017719010317, 523.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
437.99928898368967, 1096.1066571864492

c111

c111

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
605.5019900857897, 1103.7785148465887

c112

c112

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
555.0, 1097.0

c113

c113

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
386.9930645847388, 1096.0

c114

c114

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
441.0, 1137.0

c115

c115

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
390.0, 1137.0

c116

c116

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
608.9671456517416, 1132.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
567.0, 1137.0

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
608.0793457790559, 1137.0

c119

c119

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
233.0, 569.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
565.0, 1173.0

c120

c120

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
398.0, 1173.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
458.0, 1173.0

c122

c122

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
607.6568542494924, 1137.0

c123

c123

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
564.0, 1213.0

c124

c124

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
398.0, 1217.0

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
465.9926631665414, 1213.0

c126

c126

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
619.5777087639997, 1137.0

c127

c127

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
576.0, 1257.0

c128

c128

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
413.0, 1261.0

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
328.0, 569.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
481.9917483216824, 1258.0

c130

c130

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
653.16235840874, 1137.0

c131

c131

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
623.0, 1293.0

c132

c132

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
457.0, 1293.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
526.0, 1293.0

c134

c134

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
664.0944596167918, 474.69711275804644

c135

c135

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
657.0, 446.81446268379943

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
411.0, 595.4

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0, 517.0

c138

c138

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
726.9322862329901, 1292.367306591753

c139

c139

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
398.0, 581.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
710.0, 1296.0

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
754.2301205639699, 1335.9966895979549

c141

c141

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
126.16374091462396, 368.820702170716

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
492.60245808999866, 543.0

c143

c143

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
552.0, 519.97232952362

c144

c144

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
673.0, 460.39169590017775

c145

c145

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
419.6564023547028, 586.0

c146

c146

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
427.0, 886.0

c147

c147

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
420.0, 929.0

c148

c148

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
261.38103049006196, 873.0855127458456

c149

c149

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
322.42321457403784, 455.66597125946544

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
254.0, 865.0

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
242.00602048629634, 534.0

c151

c151

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
946.0, 423.0

c152

c152

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
966.0, 525.0

c153

c153

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
947.0, 537.0

c154

c154

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
328.0, 524.756061624289

c155

c155

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
332.9949028347804, 513.2855322440993

c156

c156

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
469.2829318197008, 487.0

c157

c157

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
547.0, 468.00350491111504

c158

c158

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
774.0, 1212.0

c159

c159

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
413.0, 640.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
684.0, 1137.0

c160

c160

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
934.0, 944.0

c161

c161

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
947.0, 985.0

c162

c162

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1014.0, 952.0

c163

c163

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
957.0, 929.0

c164

c164

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1014.0, 998.0

c165

c165

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
867.0, 1289.0

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
547.0, 489.0

c167

c167

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
486.8161052203985, 392.4929882637097

c168

c168

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
410.0, 394.1783174000729

c169

c169

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
419.99750117126496, 678.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
470.0, 388.0

c170

c170

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
538.0, 446.0

c171

c171

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1086.0, 697.0

c172

c172

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1033.0, 714.3517178529796

c173

c173

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1078.0, 703.0

c174

c174

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1033.0, 754.0

c175

c175

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1080.3051030595002, 789.2612067229911

c176

c176

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1073.0, 781.0

c177

c177

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1153.0, 788.0

c178

c178

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1164.4795369723442, 828.0

c179

c179

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
463.2469504755442, 664.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1159.0, 747.0

c180

c180

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1160.5424513544062, 827.0

c181

c181

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1082.0, 893.0

c182

c182

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1082.0, 857.0

c183

c183

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
955.0, 857.0

c184

c184

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
954.714609183337, 863.1177358542493

c185

c185

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
608.8529231173486, 356.5269572728178

c186

c186

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
591.0, 323.974522228289

c187

c187

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
590.0, 372.0

c188

c188

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
548.0, 326.0

c189

c189

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
464.2464763453483, 691.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
549.0, 353.0

c190

c190

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
577.0, 371.3104923889621

c191

c191

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
323.0, 285.0

c192

c192

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
466.0, 170.0

c193

c193

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
485.98563876372623, 286.47913832582356

c194

c194

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
606.6568542494924, 369.65685424949237

c195

c195

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
184.0, 338.73912360382013

c196

c196

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
248.15541752799933, 291.0

c197

c197

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
249.0, 285.0

c198

c198

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
541.0, 495.0

c199

c199

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
247.02316458331507, 330.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
464.9987247947636, 724.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
241.0, 258.2132919606805

c200

c200

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
248.027871219063, 214.82217557527989

c201

c201

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
241.33766924727504, 222.72195101895605

c202

c202

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
241.0, 205.0

c203

c203

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
323.0, 210.0

c204

c204

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
671.0, 261.37755505462826

c205

c205

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
390.0, 252.0

c206

c206

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
390.0, 210.0

c207

c207

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
405.0, 187.0

c208

c208

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
674.029062765764, 315.40437564964543

c209

c209

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
418.6533910434309, 729.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
405.0, 186.0

c210

c210

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
577.0, 238.0

c211

c211

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
646.0, 262.0

c212

c212

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
704.0, 254.0

c213

c213

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
726.0, 312.0

c214

c214

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
733.0, 301.0

c215

c215

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
395.0, 340.0

c216

c216

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
468.7822460204546, 373.0

c217

c217

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
700.0, 319.3626473476678

c218

c218

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
413.0, 644.0

c219

c219

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
497.0, 797.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
641.0, 857.0

c220

c220

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
721.0, 776.7278882047459

c221

c221

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
729.8058976357186, 776.5691362721682

c222

c222

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
730.9285777850841, 776.5043669509456

c223

c223

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
728.6381697240132, 776.6491642817673

c224

c224

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
731.0936724234992, 776.4083039452313

c225

c225

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
925.0, 1148.9792745494692

c226

c226

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
879.9922778767136, 1129.9382230137094

c227

c227

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
924.9195959492894, 1085.1313708498985

c228

c228

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
882.9482613812512, 1039.908372729286

c229

c229

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
411.0, 753.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
979.0, 372.5816944733765

c230

c230

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1101.2785523863447, 321.0

c231

c231

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1094.0, 353.0

c232

c232

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1099.8173698057533, 271.0

c233

c233

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1093.0, 313.0

c234

c234

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1036.8435825769177, 374.0

c235

c235

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
944.6124855429656, 680.0

c236

c236

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
802.3701422443754, 319.7008847747089

c237

c237

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
988.0, 670.5150582239837

c238

c238

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
738.0, 814.0

c239

c239

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
426.0, 797.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
804.0, 775.8759986238862

c240

c240

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
884.0, 781.0

c241

c241

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
900.0, 823.0

c242

c242

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
810.3017444951216, 684.0

c243

c243

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
901.1159660434203, 687.0

c244

c244

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
843.7553309962642, 375.0

c245

c245

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
834.7777713001234, 414.0518397602303

c246

c246

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
798.9645027097611, 380.93645805334324

c247

c247

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
818.0, 444.0

c248

c248

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
836.0569260566433, 416.0

c249

c249

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
418.0, 815.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
545.0, 493.94432826277773

c250

c250

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
827.0, 488.0

c251

c251

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
703.5218843996887, 450.8963992921401

c252

c252

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
641.2170737730852, 565.451643978432

c253

c253

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
597.485433827199, 567.0

c254

c254

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
579.0, 617.0

c255

c255

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
637.9920697459979, 542.0

c256

c256

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
733.2311425889319, 562.0

c257

c257

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
789.0082901643336, 219.0

c258

c258

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
434.9822812628529, 862.0

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
412.0, 694.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
220.0, 85.0

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
590.0, 104.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
240.0, 372.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
598.0, 96.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
650.0, 95.2203172225662

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
814.3914365841244, 100.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
842.0, 108.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1250.0, 120.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1155.0, 151.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1195.8683773298562, 188.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
858.0, 281.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
943.0, 372.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1167.9738919359997, 294.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
246.44705450312753, 384.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1048.0, 228.3286560925143

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1190.332315026957, 230.0

c41

c41

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1183.0, 265.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
955.0, 331.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1012.7309133324296, 378.05742048363044

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1005.0, 380.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
960.0, 409.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1019.0, 421.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1026.3601918319166, 418.1348965210015

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
794.4993660488931, 266.8100751337898

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
240.0, 428.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
789.3665653791112, 267.7032161527097

c50

c50

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
202.0, 243.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
790.0, 207.21921163489571

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
898.0, 220.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
897.6824398144555, 276.9999794377718

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
909.0, 215.82071524948245

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
962.0, 108.0

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
971.0, 100.0

c57

c57

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1167.0, 533.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1171.619806195134, 542.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
247.81994093252123, 396.0

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1188.0, 207.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
973.5137101279801, 201.0

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
969.0, 173.64419836052127

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
766.9829820324691, 270.0

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1028.1601724872446, 496.1041429180026

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1019.0, 493.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
768.9085167916562, 444.2063839173713

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
708.0, 441.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
697.0, 455.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
765.0, 581.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
230.05458406215328, 441.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
746.0, 540.0

c70

c70

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
699.0, 581.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
542.0, 667.2859030265015

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
602.0, 648.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
608.2469504755443, 594.0

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
753.0, 649.0

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
745.0, 659.0

c76

c76

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
692.0, 648.0

c77

c77

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
747.0, 709.0

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
739.0, 718.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
231.79181270409907, 468.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
742.0, 761.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
722.0, 773.0

c81

c81

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
734.0, 766.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
722.0, 829.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
726.0, 961.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
730.8406661402685, 1014.3692975529848

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0, 993.0

c86

c86

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
678.3050019764223, 1008.0

c87

c87

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
703.0, 1129.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
809.2164574740316, 1068.906973581205

c89

c89

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
231.99401297105564, 502.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
693.0, 1137.0

c90

c90

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
840.0, 1208.0

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
975.0, 1216.3531602401445

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
895.0, 1249.0

c93

c93

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
897.0, 1193.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
838.4929882637098, 1150.8161052203986

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
789.5813914223052, 999.5720815054283

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
789.0, 908.1318814801737

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
826.0, 675.0

c98

c98

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
748.0, 1072.906973581205

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back