1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/16979939.csml convertedTime:2009.07.01.10:57

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Innate immune recognition of, and regulation by, DNA.
Authors Ishii KJ, Akira S.
Affiliation Exploratory Research for Advanced Technology (ERATO), Japan Science andTechnology Agency (JST) and Department of Host Defense, Research Institute forMicrobial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871,Japan.
Abstract DNA in microbes or host cells is normally sequestered from the immune system,and therefore inert, but becomes an active immunostimulatory molecule duringinfection or tissue damage. Recent evidence suggests that Toll-like receptor(TLR)9, currently the only known immune sensor for DNA, recognizes more diverseelements in its ligand than initially thought, and must cooperate withadditional host factors to provoke an optimal innate immune response in thephysiological environment. Moreover, the innate immune system possesses aTLR9-independent, as-yet-undefined intracellular recognition machinery ofdouble-stranded DNA that induces type I interferons through distinct signalingpathways. TLR9-dependent and TLR9-independent immune recognition of DNA mightplay crucial roles in DNA-associated protective immunity and in pathologicalautoimmunity.
PMID 16979939
Model Abstract

Entity

G010227:IFNalpha G010228:IFN-beta G010240:MHC G010262:IL-6 G010329:TNF-alpha G010453:IFN-gamma G010657:IL-12 p40 G010691:CD40 G012390:IL15 G013255:TLR9 MO000000030:PI3K MO000000058:NF-kappaB MO000000077:MAPKs MO000000090:GM-CSFR MO000000099:GM-CSF MO000000105:TGFalpha MO000000210:IKK-alpha MO000000212:TRAF6 MO000000213:IRAK MO000000215:IkappaB MO000000265:chemokines MO000000276:AP-1 MO000000289:TNF-alpha MO000007384:IL-6 MO000007694:IRF-3 MO000007700:IRF-5 MO000007702:IRF-7 MO000016573:MyD88 MO000016574:TBK1 MO000016608:IKK-i MO000016658:IFN Type I MO000016660:IFNbeta MO000016665:IFNgamma MO000016922:CD40 MO000016932:CD40L MO000016963:TRAF3 MO000017063:IL-15 MO000017265:IL-12 MO000018212:FcgammaRIII MO000018215:FcgammaRIIA MO000019002:MHC MO000019331:TBK1 MO000019397:TLR2 MO000019398:TLR3 MO000021014:NO MO000022136:Ubc13 MO000022224:dsRNA MO000039077:IRAK-4 MO000042012:TLR9 MO000061307:Osteopontin MO000070306:CXCL16 MO000094908:MAVS MO000103999:Mda-5 e1: e10: e11: e12:CpG DNA e13:CpG DNA: TLR9 e14:hemozoin e15:hemozoin: TLR9 e16:Host DNA: Anti-DNA antibody e17:Host DNA: Anti-DNA antibody: FcgammaRIII e18:Host DNA: Anti-DNA antibody: FcgammaRIIA e19:Host DNA: Anti-DNA antibody: CXCL16 e2: e20:Mycobacterium tuberculosis/ Brucella abortus DNA e21:cytomegalovirus DNA e22:TLR2: TLR9 e23:Mycobacterium tuberculosis/ Brucella abortus DNA : TLR2: TLR9 e24:TLR3: TLR9 e25:cytomegalovirus DNA: TLR3: TLR9 e26:DNA (non IgG complex) e27:DNA (non IgG complex): e28:IKK-alpha:IKK-beta:IKK-gamma e29:IFNbeta: IFNbeta receptor e3: e30:IFNgamma: IFNgamma receptor e31:IFNbeta receptor e32:IFNgamma receptor e33:TGFalpha: TGFalpha receptor e34:TGFalpha receptor e35:GM-CSF: GM-CSFR e36:CpG DNA: TLR9: MyD88 e37:CpG DNA: TLR9: MyD88: IRAK-4: TRAF6: IRF-5 e38:TRAF6: TBK1: Ubc13 e39:CpG DNA: TLR9: MyD88: IRAK-4: IRF-5 e4: e40:IKK-alpha:IKK-beta:IKK-gamma {activated} e41:NF-kappaB {activated} e42:MAPKs {activated} e43:AP-1 {activated} e44:IkappaB {activated} e45:CpG DNA: TLR9: MyD88: IRAK-4: TRAF6: IRF-5: IRAK-1: IRF-7: TRAF3: IKKalpha: Osteopontin e46:IFNalpha e47:IRF-7 {p} (nuclear) e48:IRF-7 {p} e49:CpG DNA: TLR9: MyD88: IRAK-4: TRAF6: IRF-5: IRAK-1: TRAF3: IKKalpha: Osteopontin e5: e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6: e60: e61: e62: e64:RIG-I e65:dsRNA: RIG-I e66:B-DNA e67:dsRNA: Mda-5 e68:TBK1 {activated} e69:IKK-i {activated} e7: e70:Type I IFN e71:IRF-3 {activated} e72:chemokines e73:dsDNA e74:dsRNA: RIG-I: MAVS e75:dsRNA: Mda-5: MAVS e76:ELAM-1 e77:CD40L: CD40 e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p55 p56 p57 p58 p59 p6 p60 p61 p7 p8 p9
Model Detail
707.0, 939.0
34.0, 34.0

IFNalpha

--

G010227

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p42

p31

true true true true

csml-variable:Double

m93216

10

false

infinite

0

unit false false false
TRANSFACG010227

--

Go back
741.0, 1021.0
30.0, 30.0

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p41 p52 p53

p32

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
826.0, 998.0
28.0, 28.0

MHC

--

G010240

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p43

true true true true

csml-variable:Double

m93228

10

false

infinite

0

unit false false false
TRANSFACG010240

--

Go back
565.0, 1109.0
30.0, 30.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p46

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
508.0, 1116.0
32.0, 32.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p45

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
524.0, 980.0
32.0, 32.0

IFN-gamma

--

G010453

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p57

true true true true

csml-variable:Double

m93423

10

false

infinite

0

unit false false false
TRANSFACG010453

--

Go back
597.0, 913.0
30.0, 30.0

IL-12 p40

--

G010657

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p56

true true true true

csml-variable:Double

m93589

10

false

infinite

0

unit false false false
TRANSFACG010657

--

Go back
573.0, 1029.0
30.0, 30.0

CD40

--

G010691

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p59

p60

true true true true

csml-variable:Double

m93612

10

false

infinite

0

unit false false false
TRANSFACG010691

--

Go back
549.0, 933.0
30.0, 30.0

IL15

--

G012390

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p58

true true true true

csml-variable:Double

m95141

10

false

infinite

0

unit false false false
TRANSFACG012390

--

Go back
666.0, 1142.0
36.0, 36.0

TLR9

--

G013255

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p13 p14 p16 p17

--

true true true true

csml-variable:Double

m95738

10

false

infinite

0

unit false false false
TRANSFACG013255

--

Go back
385.0, 153.0
30.0, 30.0

PI3K

--

MO000000030

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m27

10

false

infinite

0

unit false false false
TRANSPATHMO000000030

--

Go back
1109.0, 589.0
38.0, 38.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m26

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
903.0, 519.0
33.0, 33.0

MAPKs

--

MO000000077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p24

true true true true

csml-variable:Double

m69

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
958.0, 1358.0
36.0, 36.0

GM-CSFR

--

MO000000090

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18

true true true true

csml-variable:Double

m81

10

false

infinite

0

unit false false false
TRANSPATHMO000000090

--

Go back
902.0, 1482.0
27.0, 27.0

GM-CSF

--

MO000000099

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18

true true true true

csml-variable:Double

m88

10

false

infinite

0

unit false false false
InterProIPR000773
TRANSPATHMO000000099

--

Go back
801.0, 1489.0
30.0, 30.0

TGFalpha

--

MO000000105

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15

true true true true

csml-variable:Double

m93

10

false

infinite

0

unit false false false
InterProIPR006209
TRANSPATHMO000000105

--

Go back
776.0, 556.0
32.0, 32.0

IKK-alpha

--

MO000000210

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m181

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000210

--

Go back
696.0, 212.0
32.0, 32.0

TRAF6

--

MO000000212

cso30:c:Protein

cso30:i:CC_CellComponent

--

p22

p20 p21

true true true true

csml-variable:Double

m183

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000000212

--

Go back
696.0, 444.0
32.0, 32.0

IRAK

--

MO000000213

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m184

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000213

--

Go back
1056.0, 420.0
32.0, 32.0

IkappaB

--

MO000000215

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p27

true true true true

csml-variable:Double

m186

10

false

infinite

0

unit false false false
TRANSPATHMO000000215

--

Go back
1021.0, 1065.0
30.5, 30.5

chemokines

--

MO000000265

cso30:c:Protein

cso30:i:CC_CellComponent

--

p44 p48

--

true true true true

csml-variable:Double

m211

10

false

infinite

0

unit false false false
TRANSPATHMO000000265

--

Go back
1024.0, 552.0
32.0, 32.0

AP-1

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p26

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
428.0, 1288.0
32.0, 32.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p45

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
485.0, 1301.0
30.0, 30.0

IL-6

--

MO000007384

cso30:c:Protein

cso30:i:CC_CellComponent

--

p46

--

true true true true

csml-variable:Double

m871

10

false

infinite

0

unit false false false
InterProIPR003573
TRANSPATHMO000007384

--

Go back
912.0, 736.0
32.0, 32.0

IRF-3

--

MO000007694

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p40 p50

true true true true

csml-variable:Double

m977

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
721.0, 173.0
30.0, 30.0

IRF-5

--

MO000007700

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p20

true true true true

csml-variable:Double

m979

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007700

--

Go back
750.0, 466.0
36.0, 36.0

IRF-7

--

MO000007702

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m980

10

false

infinite

0

unit false false false
TRANSPATHMO000007702

--

Go back
496.0, 160.0
32.0, 32.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
769.0, 273.0
38.0, 38.0

TBK1

--

MO000016574

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21

true true true true

csml-variable:Double

m1573

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016574

--

Go back
1043.0, 791.0
34.0, 34.0

IKK-i

--

MO000016608

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36 p39

true true true true

csml-variable:Double

m1599

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016608

--

Go back
1056.0, 896.0
32.0, 32.0

IFN Type I

--

MO000016658

cso30:c:Protein

cso30:i:CC_CellComponent

--

p37

--

true true true true

csml-variable:Double

m1634

10

false

infinite

0

unit false false false
TRANSPATHMO000016658

--

Go back
240.0, 1308.0
24.0, 24.0

IFNbeta

--

MO000016660

cso30:c:Protein

cso30:i:CC_CellComponent

--

p32

p11

true true true true

csml-variable:Double

m1636

10

false

infinite

0

unit false false false
InterProIPR000471
TRANSPATHMO000016660

--

Go back
561.0, 1489.0
30.0, 30.0

IFNgamma

--

MO000016665

cso30:c:Protein

cso30:i:CC_CellComponent

--

p57

p12

true true true true

csml-variable:Double

m1639

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
319.0, 1075.0
26.0, 26.0

CD40

--

MO000016922

cso30:c:Protein

cso30:i:CC_CellComponent

--

p60

p61

true true true true

csml-variable:Double

m1837

10

false

infinite

0

unit false false false
InterProIPR006209
TRANSPATHMO000016922

--

Go back
170.0, 1070.0
28.0, 28.0

CD40L

--

MO000016932

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p61

true true true true

csml-variable:Double

m1845

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000016932

--

Go back
709.0, 501.0
30.0, 30.0

TRAF3

--

MO000016963

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m1872

10

false

infinite

0

unit false false false
InterProIPR001841
TRANSPATHMO000016963

--

Go back
370.0, 1030.0
27.0, 27.0

IL-15

--

MO000017063

cso30:c:Protein

cso30:i:CC_CellComponent

--

p58

p59

true true true true

csml-variable:Double

m1956

10

false

infinite

0

unit false false false
InterProIPR003443
TRANSPATHMO000017063

--

Go back
542.0, 754.0
28.0, 28.0

IL-12

--

MO000017265

cso30:c:Protein

cso30:i:CC_CellComponent

--

p56

--

true true true true

csml-variable:Double

m2121

10

false

infinite

0

unit false false false
TRANSPATHMO000017265

--

Go back
301.0, 697.0
30.0, 30.0

FcgammaRIII

--

MO000018212

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m2893

10

false

infinite

0

unit false false false
TRANSPATHMO000018212

--

Go back
304.0, 788.0
32.0, 32.0

FcgammaRIIA

--

MO000018215

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4 p10

true true true true

csml-variable:Double

m2896

10

false

infinite

0

unit false false false
TRANSPATHMO000018215

--

Go back
1014.0, 990.0
35.0, 35.0

MHC

--

MO000019002

cso30:c:Protein

cso30:i:CC_CellComponent

--

p43

--

true true true true

csml-variable:Double

m3610

10

false

infinite

0

unit false false false
TRANSPATHMO000019002

--

Go back
1036.0, 688.0
32.0, 32.0

TBK1

--

MO000019331

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35 p38

true true true true

csml-variable:Double

m3902

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000019331

--

Go back
395.0, 402.0
25.5, 25.5

TLR2

--

MO000019397

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m3964

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019397

--

Go back
382.0, 546.0
28.0, 28.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
542.0, 1310.0
27.0, 27.0

NO

--

MO000021014

cso30:c:Protein

cso30:i:CC_CellComponent

--

p49

--

true true true true

csml-variable:Double

m218100

10

false

infinite

0

unit false false false
TRANSPATHMO000021014

--

Go back
752.0, 356.0
23.0, 23.0

Ubc13

--

MO000022136

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21

true true true true

csml-variable:Double

m6443

10

false

infinite

0

unit false false false
InterProIPR000608
TRANSPATHMO000022136

--

Go back
1264.0, 740.0
32.0, 32.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33 p34 p35 p36

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false

--

Go back
665.0, 149.0
30.0, 30.0

IRAK-4

--

MO000039077

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p20

true true true true

csml-variable:Double

m17258

10

false

infinite

0

unit false false false
TRANSPATHMO000039077

--

Go back
388.0, 315.0
24.0, 24.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p2 p8 p9

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
727.0, 567.0
33.5, 33.5

Osteopontin

--

MO000061307

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m36205

10

false

infinite

0

unit false false false
TRANSPATHMO000061307

--

Go back
297.0, 869.0
38.0, 38.0

CXCL16

--

MO000070306

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m45147

10

false

infinite

0

unit false false false
TRANSPATHMO000070306

--

Go back
967.0, 1247.0
34.0, 34.0

MAVS

--

MO000094908

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p47 p51

true true true true

csml-variable:Double

m68199

10

false

infinite

0

unit false false false
TRANSPATHMO000094908

--

Go back
1065.0, 1245.0
29.0, 29.0

Mda-5

--

MO000103999

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m76904

10

false

infinite

0

unit false false false
TRANSPATHMO000103999

--

Go back
293.28915864383663, 70.28509334298828
936.5843558089936, 1359.920484634658

--

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
313.86999464318205, 158.05023465865332
863.2608063779625, 1214.365218955205

--

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
400.0, 232.92486678171167
271.849999051827, 453.85126960347384

--

e11

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false true false

--

Go back
189.0, 273.5
54.03118040089087, 18.910913140311802

CpG DNA

--

e12

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
389.5, 265.0
29.4114314280953, 36.01399766705548

CpG DNA: TLR9

--

e13

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p1

p19

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
169.0, 363.0
45.214465937762824, 25.621530698065598

hemozoin

--

e14

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p2

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
387.625, 355.5
32.422387935344105, 39.70088318613564

hemozoin: TLR9

--

e15

cso30:c:Complex

cso30:i:CC_EndosomeMembrane

--

p2

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
137.5, 875.25
45.0, 25.5

Host DNA: Anti-DNA antibody

--

e16

cso30:c:Complex

cso30:i:CC_Extracellular

--

--

p3 p4 p5

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
313.625, 742.5
28.33973504415931, 34.70171638060324

Host DNA: Anti-DNA antibody: FcgammaRIII

--

e17

cso30:c:Complex

cso30:i:CC_Cytosol

--

p3

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
305.625, 826.5
28.37239626728879, 34.741709715047485

Host DNA: Anti-DNA antibody: FcgammaRIIA

--

e18

cso30:c:Complex

cso30:i:CC_Cytosol

--

p4

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
303.625, 915.5
33.3369021829695, 40.8206965505749

Host DNA: Anti-DNA antibody: CXCL16

--

e19

cso30:c:Complex

cso30:i:CC_Cytosol

--

p5

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
293.28915864383663, 70.28509334298828
936.5843558089936, 1359.920484634658

--

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
173.5, 444.125
45.0, 15.75

Mycobacterium tuberculosis/ Brucella abortus DNA

--

e20

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p6

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
181.5, 632.125
45.0, 15.75

cytomegalovirus DNA

--

e21

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p7

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
398.875, 434.5
25.408194164066792, 35.453294182418794

TLR2: TLR9

--

e22

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p8

p6

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
395.875, 477.5
32.25, 45.0

Mycobacterium tuberculosis/ Brucella abortus DNA : TLR2: TLR9

--

e23

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p6

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
391.875, 581.5
32.25, 45.0

TLR3: TLR9

--

e24

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p9

p7

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
467.875, 653.5
32.25, 45.0

cytomegalovirus DNA: TLR3: TLR9

--

e25

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p7

--

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
137.5, 924.125
45.0, 15.75

DNA (non IgG complex)

--

e26

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p10

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
304.625, 968.5
31.23025329111815, 38.24112647892018

DNA (non IgG complex):

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p10

p1

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
868.0, 356.0
40.0, 40.0

IKK-alpha:IKK-beta:IKK-gamma

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p23

true true true true

csml-variable:Double

m30

10

false

infinite

0

unit false false false
TRANSPATHMO000016661

--

Go back
616.875, 1351.5
29.606395668930077, 41.311249770600114

IFNbeta: IFNbeta receptor

--

e29

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p11

p13 p48 p49

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
312.0208457600164, 89.01678045916817
899.120981576634, 1322.457110402299

--

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
736.875, 1378.5
30.695402826206646, 42.830794641218574

IFNgamma: IFNgamma receptor

--

e30

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p12

p14

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
587.375, 1385.5
24.292179261862916, 37.37258347978911

IFNbeta receptor

--

e31

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p11

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
667.375, 1360.5
25.274604569420035, 38.88400702987697

IFNgamma receptor

--

e32

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p12

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
804.375, 1361.5
23.25, 45.0

TGFalpha: TGFalpha receptor

--

e33

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

p15

p16

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
845.375, 1369.5
29.25, 45.0

TGFalpha receptor

--

e34

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p15

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
899.625, 1351.5
32.830653224462594, 40.20079986668888

GM-CSF: GM-CSFR

--

e35

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p18

p17

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
431.875, 213.5
32.25, 45.0

CpG DNA: TLR9: MyD88

--

e36

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p19

p20

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
545.875, 230.5
36.314048449256745, 50.67076527803266

CpG DNA: TLR9: MyD88: IRAK-4: TRAF6: IRF-5

--

e37

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p20

p22 p28

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
639.875, 345.5
32.25, 45.0

TRAF6: TBK1: Ubc13

--

e38

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p21

p23 p24

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
607.875, 289.5
32.25, 45.0

CpG DNA: TLR9: MyD88: IRAK-4: IRF-5

--

e39

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p22

--

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
346.67446692494934, 121.79723291248271
829.8137392467687, 1256.8962054956687

--

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
876.0, 416.0
40.0, 40.0

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

--

e40

cso30:c:Protein

cso30:i:CC_CellComponent

--

p23

p27

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
TRANSPATHMO000016661

--

Go back
1061.0, 617.0
38.0, 38.0

NF-kappaB {activated}

--

e41

cso30:c:Protein

cso30:i:CC_CellComponent

--

p25

--

true true true true

csml-variable:Double

m43

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
959.0, 483.0
33.0, 33.0

MAPKs {activated}

--

e42

cso30:c:Protein

cso30:i:CC_CellComponent

--

p24

p26

true true true true

csml-variable:Double

m44

10

false

infinite

0

unit false false false
TRANSPATHMO000000077

--

Go back
964.0, 628.0
32.0, 32.0

AP-1 {activated}

--

e43

cso30:c:Protein

cso30:i:CC_CellComponent

--

p26

--

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
1060.0, 464.0
32.0, 32.0

IkappaB {activated}

--

e44

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27

p25

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
TRANSPATHMO000000215

--

Go back
615.875, 544.5
39.62052670214719, 55.28445586346119

CpG DNA: TLR9: MyD88: IRAK-4: TRAF6: IRF-5: IRAK-1: IRF-7: TRAF3: IKKalpha: Osteopontin

--

e45

cso30:c:Complex

cso30:i:CC_Cytosol

--

p28

p29 p31 p32 p56 p57

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
817.0, 713.0
30.0, 30.0

IFNalpha

--

e46

cso30:c:Protein

cso30:i:CC_CellComponent

--

p31

--

true true true true

csml-variable:Double

m48

10

false

infinite

0

unit false false false
Affymetrix101317_f_at
EnsemblENSMUSG00000070903
InterProIPR000471
MGDMGI:107668
ProteomeHumanPSD/Ifna1
RefSeqNM_010502
TRANSPATHMO000032829
UnigeneMm.57127
UniProtP01572

--

Go back
673.5, 887.125
45.64000000000001, 34.22999999999999

IRF-7 {p} (nuclear)

--

e47

cso30:c:Protein

cso30:i:CC_Cytosol

--

p30

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
673.5, 747.125
45.64000000000001, 34.22999999999999

IRF-7 {p}

--

e48

cso30:c:Protein

cso30:i:CC_Cytosol

--

p29

p30

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
563.875, 621.5
32.25, 45.0

CpG DNA: TLR9: MyD88: IRAK-4: TRAF6: IRF-5: IRAK-1: TRAF3: IKKalpha: Osteopontin

--

e49

cso30:c:Complex

cso30:i:CC_Cytosol

--

p29

p58

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
400.0, 232.92486678171167
271.849999051827, 453.85126960347384

--

e5

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false true false

--

Go back
452.807525296123, 859.0409652699409
458.229296892632, 415.5636267908974

--

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
502.2997026141354, 868.8892190903977
267.94040823889486, 402.76392576037694

--

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
458.7807191103659, 864.5875023831665
446.28290926414655, 404.4705525644462

--

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
459.6340325124006, 865.4408157852009
444.5762824600768, 402.76392576037694

--

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
452.807525296123, 859.0409652699409
458.229296892632, 415.5636267908974

--

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
452.807525296123, 859.0409652699409
458.229296892632, 415.5636267908974

--

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
459.6340325124006, 865.4408157852009
444.5762824600768, 402.76392576037694

--

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
787.3063788937236, 1029.7036456768797
28.627648727113097, 25.91555568980768

--

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
712.2147995146706, 1149.1675219617377
81.06477319329612, 73.384952574984

--

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
452.807525296123, 859.0409652699409
458.229296892632, 415.5636267908974

--

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
400.0, 232.92486678171167
271.849999051827, 453.85126960347384

--

e6

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false true false

--

Go back
560.8095922949296, 1043.7140071852994
14.511448535363614, 6.986993739249157

--

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
560.3250139524948, 1022.8771384606027
49.66928009956674, 89.40470417922013

--

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
581.1618826771914, 1081.0265395527774
7.7532534789567515, 7.753253478956759

--

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
1061.5, 1151.0
21.9103690685413, 33.70826010544816

RIG-I

--

e64

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p33

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
1097.5, 1196.0
21.001973251479935, 40.64898048673536

dsRNA: RIG-I

--

e65

cso30:c:Complex

cso30:i:CC_Cytosol

--

p33

p47

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
1245.5, 696.125
45.0, 15.75

B-DNA

--

e66

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p38 p39

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
1093.5, 1286.0
29.91768038660223, 36.63389435094152

dsRNA: Mda-5

--

e67

cso30:c:Complex

cso30:i:CC_Cytosol

--

p34

p51

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
1040.0, 740.0
32.0, 32.0

TBK1 {activated}

--

e68

cso30:c:Protein

cso30:i:CC_CellComponent

--

p35 p38

p37 p40

true true true true

csml-variable:Double

m71

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000019331

--

Go back
1047.0, 843.0
34.0, 34.0

IKK-i {activated}

--

e69

cso30:c:Protein

cso30:i:CC_CellComponent

--

p36 p39

p37 p40

true true true true

csml-variable:Double

m72

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016608

--

Go back
304.990298642944, 75.48881599309746
873.3977768550728, 1237.5820897134618

--

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
805.5, 960.0
45.0, 24.0

Type I IFN

--

e70

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p37

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

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912.0, 784.0
32.0, 32.0

IRF-3 {activated}

--

e71

cso30:c:Protein

cso30:i:CC_CellComponent

--

p40 p50

p41 p42 p43 p44

true true true true

csml-variable:Double

m74

10

false

infinite

0

unit false false false
InterProIPR008984
TRANSPATHMO000007694

--

Go back
826.0, 1036.0
44.11764705882352, 23.529411764705884

chemokines

--

e72

cso30:c:mRNA

cso30:i:CC_Extracellular

--

--

p44 p48

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

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230.0, 1180.5
44.632516703786195, 15.621380846325165

dsDNA

--

e73

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p45 p46 p50

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
946.5, 1197.0
27.911726922371084, 38.94659570563407

dsRNA: RIG-I: MAVS

--

e74

cso30:c:Complex

cso30:i:CC_Cytosol

--

p47

p52 p55

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
946.5, 1285.0
26.956872820701044, 37.61424114516426

dsRNA: Mda-5: MAVS

--

e75

cso30:c:Complex

cso30:i:CC_Cytosol

--

p51

p53 p54

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
716.5, 1118.0
38.564013840830455, 20.567474048442907

ELAM-1

--

e76

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p54 p55

--

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
318.625, 1131.5
27.44971671388102, 33.611898016997166

CD40L: CD40

--

e77

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p61

p56

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
308.110602642706, 97.33094399143133
837.8608945444223, 1216.5740188785014

--

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
316.431413308738, 119.17307198976522
834.0355999653096, 1200.618955466776

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
290.0, 269.0
27.0, 27.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e12 MO000042012 MO000000030 e27

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c7 : 1
stoichiometry:c32 : 1
stoichiometry:c3 : 1

m12*m19828*m27*0.1

nodelay

--

true

0

false

PMID: 16979939 Currently, Toll-like receptor (TLR)9 is the only known receptor to detect immunostimulatory DNA such as CpG DNA. PMID: 16979939, 16467569, 12119352, 16670302 It is of note that a phosphoinositide 3-kinase (PI 3-kinase), possibly class III vacuolar protein sorting 34 (VPS34), which is required for endosome fusion and membrane trafficking [33], has been shown to play a crucial role in internalization of CpG ODNs as well as TLR9-mediated immune activation. PMID: 16979939, 12960360 By contrast, Fcgamma receptor IIa inhibits TLR9-mediated activation if DNA does not form a complex with IgG.

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217.0, 921.0
22.0, 22.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000018215 e26

e27

true true true true

--

and

mass

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

m2896*m28*0.1

nodelay

--

true

0

false

PMID: 16979939, 12960360 By contrast, Fcgamma receptor IIa inhibits TLR9-mediated activation if DNA does not form a complex with IgG.

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618.0, 1442.0
27.0, 27.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016660 e31

e29

true true true true

--

and

mass

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

m1636*m33*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha). PMID: 16979939, 16827891 Very recently, Shirota et al. showed that dsDNA-induced IFNbeta was necessary for the production of chemokines and nitric oxide by stimulated macrophages.

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666.0, 1454.0
27.0, 27.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e32 MO000016665

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c38 : 1
stoichiometry:c36 : 1

m34*m1639*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

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615.0, 1211.0
25.0, 25.0

p13

p13

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e29

G013255

true true true true

--

and

mass

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

m31*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

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650.0, 1218.0
27.0, 27.0

p14

p14

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e30

G013255

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c42 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

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803.0, 1439.0
25.0, 25.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000000105 e34

e33

true true true true

--

and

mass

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

m93*m36*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

Go back
686.0, 1218.0
27.0, 27.0

p16

p16

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e33

G013255

true true true true

--

and

mass

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

m35*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

Go back
718.0, 1202.0
27.0, 27.0

p17

p17

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e35

G013255

true true true true

--

and

mass

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

m37*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

Go back
902.0, 1434.0
27.0, 27.0

p18

p18

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000000099 MO000000090

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c52 : 1
stoichiometry:c50 : 1

m88*m81*0.1

nodelay

--

true

0

false

PMID: 16979939, 16791898, 16301648, 15661046 Moreover, growing recent evidence indicates that TLR9 expression and/or function can be upregulated in B cells [53] and other cell types, such as macrophages or cDCs stimulated with IFNbeta [52] or IFNgamma [54 and 55], monocytes infected with Yersinia pestis [56], granulocytes stimulated with granulocyte?macrophage colony-stimulating factor [57 and 58], and even epithelial cells cultured with transforming growth factor (TGFalpha).

Go back
436.0, 164.0
23.0, 23.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_EndosomeMembrane

--

e13 MO000016573

e36

true true true true

--

and

mass

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

m13*m1572*0.1

nodelay

--

true

0

false

PMID: 16979939, 16497588 Following TLR9 stimulation, MyD88 subsequently associates with IL-1R-associated kinase 4 (IRAK4), IFN regulatory factor (IRF5) and tumor necrosis factor receptor-associated factor 6 (TRAF6), culminating in the activation of nuclear factor (NF)-kappaB and/or the mitogen-activated protein (MAP) kinase pathway, resulting in the production of pro-inflammatory molecules including cytokines and chemokines.

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250.0, 362.0
27.0, 27.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

MO000042012 e14

e15

true true true true

--

and

mass

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

m19828*m14*0.1

nodelay

--

true

0

false

PMID: 16979939, 15630134 Moreover, a heme polymer, so-called hemozoin, generated as a heme metabolite during malarial infection of red blood cells, was found to be a unique non-DNA TLR9 ligand.

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552.0, 176.0
23.0, 23.0

p20

p20

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e36 MO000039077 MO000007700 MO000000212

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c57 : 1
stoichiometry:c59 : 1
stoichiometry:c60 : 1
stoichiometry:c58 : 1

m38*m17258*m979*m183*0.1

nodelay

--

true

0

false

PMID: 16979939, 16497588 Following TLR9 stimulation, MyD88 subsequently associates with IL-1R-associated kinase 4 (IRAK4), IFN regulatory factor (IRF5) and tumor necrosis factor receptor-associated factor 6 (TRAF6), culminating in the activation of nuclear factor (NF)-kappaB and/or the mitogen-activated protein (MAP) kinase pathway, resulting in the production of pro-inflammatory molecules including cytokines and chemokines.

Go back
695.0, 355.0
25.0, 25.0

p21

p21

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016574 MO000022136 MO000000212

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c63 : 1
stoichiometry:c65 : 1
stoichiometry:c64 : 1

m1573*m6443*m183*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

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643.0, 243.0
25.0, 25.0

p22

p22

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e37

e39 MO000000212

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c66 : 1
stoichiometry:c149 : 1

m39*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

Go back
786.0, 422.0
27.0, 27.0

p23

p23

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e28 e38

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c71 : 1
stoichiometry:c68 : 1

m30*m40*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

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846.0, 486.0
27.0, 27.0

p24

p24

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000077 e38

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c72 : 1
stoichiometry:c70 : 1

m69*m40*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

Go back
1066.0, 522.0
27.0, 27.0

p25

p25

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000058 e44

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c81 : 1
stoichiometry:c74 : 1

m26*m46*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

Go back
966.0, 558.0
27.0, 27.0

p26

p26

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000276 e42

e43

true true true true

--

and

mass

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

m219*m44*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

Go back
957.0, 421.0
30.0, 30.0

p27

p27

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000215 e40

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c80 : 1
stoichiometry:c79 : 1

m186*m42*0.1

nodelay

--

true

0

false

PMID: 16979939, 16186825, 16862162 TRAF6 forms a complex with ubiquitin-conjugating (Ubc) enzymes such as Ubc13, and activates TGFbeta-activated kinase 1 (TAK1), and both Ubc13 and TAK1 are necessary for TLR9-mediated activation of NF-kappaB and activator protein-1 (AP-1) through the canonical IkappaB kinase (IKK) complex and MAP kinase.

Go back
581.0, 469.0
30.0, 30.0

p28

p28

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

e37 MO000000213 MO000007702 MO000016963 MO000000210 MO000061307

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c83 : 1
stoichiometry:c84 : 1
stoichiometry:c85 : 1
stoichiometry:c86 : 1
stoichiometry:c87 : 1
stoichiometry:c88 : 1

m39*m184*m980*m1872*m181*m36205*0.1

nodelay

--

true

0

false

PMID: 16979939 In pDCs, additional molecules such as IRF7, IRAK1, TRAF3, IKK alpha and osteopontin (Opn-i) are recruited to the MyD88-containing complex, leading to robust production of type I IFNs. PMID: 16979939, 16424890 In addition to the NF-kappaB-dependent signaling pathways controlled by these IKK complexes, TLR9 stimulation of pDCs by D/A-type CpG DNA activates another signaling pathway, resulting in type I IFN (IFNalpha and IFNbeta) production.

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654.0, 678.0
27.0, 27.0

p29

p29

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e45

e49 e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c90 : 1
stoichiometry:c91 : 1

m47*0.1

nodelay

--

true

0

false

PMID: 16979939 IRF7 is phosphorylated by IRAK1 and translocates to the nucleus.

Go back
216.0, 700.0
24.0, 24.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

e16 MO000018212

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m16*m2893*0.1

nodelay

--

true

0

false

PMID: 16979939, 15197227, 15668740, 16849465 Supporting this notion, these processes can be further enhanced either by coupling microbial or host DNA with anti-DNA antibody [through Fcgamma receptor IIa (human) and III (mouse)] [42 and 43], or by encapsulation with cationic liposomes [44], or by a certain scavenger receptor (such as CXCL16 [45]).

Go back
681.0, 817.0
30.0, 30.0

p30

p30

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e48

e47

true true true true

--

and

mass

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

m63*0.1

nodelay

--

true

0

false

PMID: 16979939 IRF7 is phosphorylated by IRAK1 and translocates to the nucleus.

Go back
742.0, 714.0
28.0, 28.0

p31

p31

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e45 G010227

e46

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c96 : 1
stoichiometry:c98 : 1

m47*m93216*0.1

nodelay

--

true

0

false

PMID: 16979939 In pDCs, additional molecules such as IRF7, IRAK1, TRAF3, IKK alpha and osteopontin (Opn-i) are recruited to the MyD88-containing complex, leading to robust production of type I IFNs. PMID: 16979939, 16424890 In addition to the NF-kappaB-dependent signaling pathways controlled by these IKK complexes, TLR9 stimulation of pDCs by D/A-type CpG DNA activates another signaling pathway, resulting in type I IFN (IFNalpha and IFNbeta) production. PMID: 16979939, 16306936, 16306937, 16612387 Furthermore, TRAF3, IKKalpha and osteopontin, all of which are able to associate with MyD88, have recently been reported to be non-redundant for TLR9-mediated pDC production of IFNalpha [79, 80 and 81], suggesting that a large and unique signaling complex in pDCs plays an important role in robust TLR9-mediated IFNalpha production.

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606.0, 810.0
27.0, 27.0

p32

p32

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e45 G010228

MO000016660

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c97 : 1
stoichiometry:c99 : 1

m47*m93217*0.1

nodelay

--

true

0

false

PMID: 16979939 In pDCs, additional molecules such as IRF7, IRAK1, TRAF3, IKK alpha and osteopontin (Opn-i) are recruited to the MyD88-containing complex, leading to robust production of type I IFNs. PMID: 16979939, 16424890 In addition to the NF-kappaB-dependent signaling pathways controlled by these IKK complexes, TLR9 stimulation of pDCs by D/A-type CpG DNA activates another signaling pathway, resulting in type I IFN (IFNalpha and IFNbeta) production. PMID: 16979939, 16413926 As expected, IRF3 was a necessary transcription factor for dsDNA-induced IFNbeta. PMID: 16979939, 16715101 CpG ODNs activate cDCs to secrete IL-15 to upregulate CD40 expression, whereas CpG-activated pDCs further enhance cDC production of IL-12 through CD40 interaction with its ligand CD40L.

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1239.0, 1155.0
25.0, 25.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e64 MO000022224

e65

true true true true

--

and

mass

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

m66*m119368*0.1

nodelay

--

true

0

false

PMID: 16979939, 16286919, 16625202 Moreover, RIG-I and Mda-5, recently described intracellular receptors for RNA virus and/or dsRNA [82], were not required for B-DNA recognition.

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1266.0, 1246.0
27.0, 27.0

p34

p34

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000103999 MO000022224

e67

true true true true

--

and

mass

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

m76904*m119368*0.1

nodelay

--

true

0

false

PMID: 16979939, 16286919, 16625202 Moreover, RIG-I and Mda-5, recently described intracellular receptors for RNA virus and/or dsRNA [82], were not required for B-DNA recognition.

Go back
1095.0, 743.0
25.0, 25.0

p35

p35

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000022224 MO000019331

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c108 : 1
stoichiometry:c109 : 1

m119368*m3902*0.1

nodelay

--

true

0

false

PMID: 16979939 By contrast, dsRNA-induced type I IFN production is mediated by TBK1 and partially by IKKi, a second non-canonical IKK family member.

Go back
1098.0, 846.0
27.0, 27.0

p36

p36

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000022224 MO000016608

e69

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c107 : 1
stoichiometry:c110 : 1
stoichiometry:c111 : 1

m119368*m1599*0.1

nodelay

--

true

0

false

PMID: 16979939 By contrast, dsRNA-induced type I IFN production is mediated by TBK1 and partially by IKKi, a second non-canonical IKK family member.

Go back
982.0, 898.0
27.0, 27.0

p37

p37

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

e70 e69 e68

MO000016658

true true true true

--

and

mass

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

m73*m72*m71*0.1

nodelay

--

true

0

false

PMID: 16979939 By contrast, dsRNA-induced type I IFN production is mediated by TBK1 and partially by IKKi, a second non-canonical IKK family member. PMID: 16979939 Further studies are required to identify adaptor molecules and receptor molecules that mediate B-DNA-induced type I IFN production.

Go back
1095.0, 691.0
25.0, 25.0

p38

p38

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000019331 e66

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c120 : 1
stoichiometry:c116 : 1

m3902*m68*0.1

nodelay

--

true

0

false

PMID: 16979939, 16286919 Nevertheless, B-DNA activates IRF3 and the IFNbeta promoter through a TBK1/IKKi-dependent pathway, whereas substantial NF-kappaB activation was observed independently of TBK1/IKKi.

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1095.0, 795.0
25.0, 25.0

p39

p39

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016608 e66

e69

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c118 : 1
stoichiometry:c121 : 1
stoichiometry:c119 : 1

m1599*m68*0.1

nodelay

--

true

0

false

PMID: 16979939, 16286919 Nevertheless, B-DNA activates IRF3 and the IFNbeta promoter through a TBK1/IKKi-dependent pathway, whereas substantial NF-kappaB activation was observed independently of TBK1/IKKi.

Go back
224.0, 792.0
23.0, 23.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e16 MO000018215

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1

m16*m2896*0.1

nodelay

--

true

0

false

PMID: 16979939, 15197227, 15668740, 16849465 Supporting this notion, these processes can be further enhanced either by coupling microbial or host DNA with anti-DNA antibody [through Fcgamma receptor IIa (human) and III (mouse)] [42 and 43], or by encapsulation with cationic liposomes [44], or by a certain scavenger receptor (such as CXCL16 [45]).

Go back
984.0, 788.0
23.0, 23.0

p40

p40

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000007694 e68 e69

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1
stoichiometry:c125 : 1
stoichiometry:c126 : 1
stoichiometry:c123 : 1

m977*m71*m72*0.1

nodelay

--

true

0

false

PMID: 16979939, 16286919 Nevertheless, B-DNA activates IRF3 and the IFNbeta promoter through a TBK1/IKKi-dependent pathway, whereas substantial NF-kappaB activation was observed independently of TBK1/IKKi.

Go back
775.0, 923.0
25.0, 25.0

p41

p41

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e71

G010228

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c127 : 1
stoichiometry:c124 : 1

m74*0.1

nodelay

--

true

0

false

PMID: 16979939, 16286919 Nevertheless, B-DNA activates IRF3 and the IFNbeta promoter through a TBK1/IKKi-dependent pathway, whereas substantial NF-kappaB activation was observed independently of TBK1/IKKi. PMID: 16979939, 16413926 As expected, IRF3 was a necessary transcription factor for dsDNA-induced IFNbeta.

Go back
744.0, 892.0
23.0, 23.0

p42

p42

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e71

G010227

true true true true

--

and

mass

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

m74*0.1

nodelay

--

true

0

false

PMID: 16979939 This results in the robust production of type I IFNs and chemokines, and the upregulation of MHC and co-stimulatory molecules.

Go back
959.0, 995.0
26.0, 26.0

p43

p43

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010240 e71

MO000019002

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c134 : 1
stoichiometry:c130 : 1

m93228*m74*0.1

nodelay

--

true

0

false

PMID: 16979939 This results in the robust production of type I IFNs and chemokines, and the upregulation of MHC and co-stimulatory molecules.

Go back
935.0, 1035.0
25.0, 25.0

p44

p44

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e72 e71

MO000000265

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c133 : 1
stoichiometry:c135 : 1
stoichiometry:c131 : 1

m75*m74*0.1

nodelay

--

true

0

false

PMID: 16979939 This results in the robust production of type I IFNs and chemokines, and the upregulation of MHC and co-stimulatory molecules.

Go back
478.0, 1214.0
27.0, 27.0

p45

p45

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e73 G010329

MO000000289

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c136 : 1
stoichiometry:c138 : 1
stoichiometry:c140 : 1

m76*m93309*0.1

nodelay

--

true

0

false

PMID: 16979939, 15879108, Yasuda et al. demonstrated that transfection with mammalian or bacterial dsDNA, but not ssODNs, using the transfection reagent DOTAP (which is known to retain DNA in the endosomes), activates macrophages and DCs to upregulate co-stimulatory markers and produce substantial amounts of TNFalpha or IL-6 in a TLR9-independent manner.

Go back
515.0, 1251.0
25.0, 25.0

p46

p46

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e73 G010262

MO000007384

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c139 : 1
stoichiometry:c141 : 1

m76*m93248*0.1

nodelay

--

true

0

false

PMID: 16979939, 15879108, Yasuda et al. demonstrated that transfection with mammalian or bacterial dsDNA, but not ssODNs, using the transfection reagent DOTAP (which is known to retain DNA in the endosomes), activates macrophages and DCs to upregulate co-stimulatory markers and produce substantial amounts of TNFalpha or IL-6 in a TLR9-independent manner.

Go back
1016.0, 1204.0
23.0, 23.0

p47

p47

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e65 MO000094908

e74

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c143 : 1
stoichiometry:c144 : 1
stoichiometry:c153 : 1

m67*m68199*0.1

nodelay

--

true

0

false

PMID: 16979939, 16424890, 16286919 IPS-1 (also known as MAVS, Cardif or VISA), an essential adaptor molecule for RIG-I- and Mda-5-mediated RNA recognition [78], was shown to be involved in B-DNA-transfected 293 cell activation of IFNbeta and the ELAM-1 (NF-kappaB) promoter.

Go back
938.0, 1066.0
27.0, 27.0

p48

p48

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e29 e72

MO000000265

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c146 : 1
stoichiometry:c147 : 1

m31*m75*0.1

nodelay

--

true

0

false

PMID: 16979939, 16827891 Very recently, Shirota et al. showed that dsDNA-induced IFNbeta was necessary for the production of chemokines and nitric oxide by stimulated macrophages.

Go back
579.0, 1279.0
26.0, 26.0

p49

p49

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e29

MO000021014

true true true true

--

and

mass

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

m31*0.1

nodelay

--

true

0

false

PMID: 16979939, 16827891 Very recently, Shirota et al. showed that dsDNA-induced IFNbeta was necessary for the production of chemokines and nitric oxide by stimulated macrophages.

Go back
216.0, 876.0
23.0, 23.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e16 MO000070306

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c15 : 1
stoichiometry:c16 : 1

m16*m45147*0.1

nodelay

--

true

0

false

PMID: 16979939, 15197227, 15668740, 16849465 Supporting this notion, these processes can be further enhanced either by coupling microbial or host DNA with anti-DNA antibody [through Fcgamma receptor IIa (human) and III (mouse)] [42 and 43], or by encapsulation with cationic liposomes [44], or by a certain scavenger receptor (such as CXCL16 [45]).

Go back
842.0, 786.0
27.0, 27.0

p50

p50

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000007694 e73

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c152 : 1
stoichiometry:c151 : 1

m977*m76*0.1

nodelay

--

true

0

false

PMID: 16979939, 16413926 As expected, IRF3 was a necessary transcription factor for dsDNA-induced IFNbeta.

Go back
1028.0, 1292.0
23.0, 23.0

p51

p51

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000094908 e67

e75

true true true true

--

and

mass

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

m68199*m70*0.1

nodelay

--

true

0

false

PMID: 16979939, 16424890, 16286919 IPS-1 (also known as MAVS, Cardif or VISA), an essential adaptor molecule for RIG-I- and Mda-5-mediated RNA recognition [78], was shown to be involved in B-DNA-transfected 293 cell activation of IFNbeta and the ELAM-1 (NF-kappaB) promoter.

Go back
823.0, 1079.0
25.0, 25.0

p52

p52

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e74

G010228

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c159 : 1
stoichiometry:c157 : 1

m77*0.1

nodelay

--

true

0

false

PMID: 16979939, 16424890, 16286919 IPS-1 (also known as MAVS, Cardif or VISA), an essential adaptor molecule for RIG-I- and Mda-5-mediated RNA recognition [78], was shown to be involved in B-DNA-transfected 293 cell activation of IFNbeta and the ELAM-1 (NF-kappaB) promoter.

Go back
807.0, 1115.0
25.0, 25.0

p53

p53

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e75

G010228

true true true true

--

and

mass

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

m78*0.1

nodelay

--

true

0

false

PMID: 16979939, 16424890, 16286919 IPS-1 (also known as MAVS, Cardif or VISA), an essential adaptor molecule for RIG-I- and Mda-5-mediated RNA recognition [78], was shown to be involved in B-DNA-transfected 293 cell activation of IFNbeta and the ELAM-1 (NF-kappaB) promoter.

Go back
759.0, 1179.0
25.0, 25.0

p54

p54

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e75

e76

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c164 : 1
stoichiometry:c161 : 1

m78*0.1

nodelay

--

true

0

false

PMID: 16979939, 16424890, 16286919 IPS-1 (also known as MAVS, Cardif or VISA), an essential adaptor molecule for RIG-I- and Mda-5-mediated RNA recognition [78], was shown to be involved in B-DNA-transfected 293 cell activation of IFNbeta and the ELAM-1 (NF-kappaB) promoter.

Go back
771.0, 1143.0
25.0, 25.0

p55

p55

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e74

e76

true true true true

--

and

mass

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

m77*0.1

nodelay

--

true

0

false

PMID: 16979939, 16424890, 16286919 IPS-1 (also known as MAVS, Cardif or VISA), an essential adaptor molecule for RIG-I- and Mda-5-mediated RNA recognition [78], was shown to be involved in B-DNA-transfected 293 cell activation of IFNbeta and the ELAM-1 (NF-kappaB) promoter.

Go back
555.0, 819.0
25.0, 25.0

p56

p56

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e45 G010657 e77

MO000017265

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c167 : 1
stoichiometry:c169 : 1
stoichiometry:c181 : 1
stoichiometry:c166 : 1

m47*m93589*m80*0.1

nodelay

--

true

0

false

PMID: 16979939, 15057783, 16763660 In the best-characterized animal model, in which CpG ODNs trigger a TLR9-mediated protective innate immune response to various infectious agents such as Listeria monocytogenes 3 and 5, for example, the protection requires DC production of IL-12, IFNgamma and IL-15, but not IL-18 or type I IFNs.

Go back
379.0, 991.0
25.0, 25.0

p57

p57

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e45 G010453

MO000016665

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c168 : 1
stoichiometry:c170 : 1
stoichiometry:c165 : 1

m47*m93423*0.1

nodelay

--

true

0

false

PMID: 16979939, 15057783, 16763660 In the best-characterized animal model, in which CpG ODNs trigger a TLR9-mediated protective innate immune response to various infectious agents such as Listeria monocytogenes 3 and 5, for example, the protection requires DC production of IL-12, IFNgamma and IL-15, but not IL-18 or type I IFNs.

Go back
431.0, 947.0
25.0, 25.0

p58

p58

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G012390 e49

MO000017063

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c172 : 1
stoichiometry:c176 : 1
stoichiometry:c171 : 1

m95141*m64*0.1

nodelay

--

true

0

false

PMID: 16979939, 15057783, 16763660 In the best-characterized animal model, in which CpG ODNs trigger a TLR9-mediated protective innate immune response to various infectious agents such as Listeria monocytogenes 3 and 5, for example, the protection requires DC production of IL-12, IFNgamma and IL-15, but not IL-18 or type I IFNs. PMID: 16979939, 16715101 CpG ODNs activate cDCs to secrete IL-15 to upregulate CD40 expression, whereas CpG-activated pDCs further enhance cDC production of IL-12 through CD40 interaction with its ligand CD40L.

Go back
504.0, 1032.0
23.0, 23.0

p59

p59

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000017063

G010691

true true true true

--

and

mass

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

m1956*0.1

nodelay

--

true

0

false

PMID: 16979939, 16715101 CpG ODNs activate cDCs to secrete IL-15 to upregulate CD40 expression, whereas CpG-activated pDCs further enhance cDC production of IL-12 through CD40 interaction with its ligand CD40L.

Go back
251.0, 439.0
26.0, 26.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e20 e22

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c21 : 1
stoichiometry:c22 : 1

m20*m22*0.1

nodelay

--

true

0

false

PMID: 16979939, 16365150, 16148144, 14993594 urthermore, TLR9 was found to cooperate with TLR2 to combat intracellular bacteria such as Mycobacterium tuberculosis [46] and Brucella abortus [47], and with TLR3 against mouse cytomegaloviru.

Go back
384.0, 1076.0
23.0, 23.0

p60

p60

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010691

MO000016922

true true true true

--

and

mass

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

m93612*0.1

nodelay

--

true

0

false

PMID: 16979939, 16715101 CpG ODNs activate cDCs to secrete IL-15 to upregulate CD40 expression, whereas CpG-activated pDCs further enhance cDC production of IL-12 through CD40 interaction with its ligand CD40L.

Go back
172.0, 1136.0
23.0, 23.0

p61

p61

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016922 MO000016932

e77

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c178 : 1
stoichiometry:c179 : 1
stoichiometry:c180 : 1

m1837*m1845*0.1

nodelay

--

true

0

false

PMID: 16979939, 16715101 CpG ODNs activate cDCs to secrete IL-15 to upregulate CD40 expression, whereas CpG-activated pDCs further enhance cDC production of IL-12 through CD40 interaction with its ligand CD40L.

Go back
287.0, 619.0
25.0, 25.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

e24 e21

e25

true true true true

--

and

mass

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

m24*m21*0.1

nodelay

--

true

0

false

PMID: 16979939, 16365150, 16148144, 14993594 urthermore, TLR9 was found to cooperate with TLR2 to combat intracellular bacteria such as Mycobacterium tuberculosis [46] and Brucella abortus [47], and with TLR3 against mouse cytomegaloviru.

Go back
447.0, 446.0
25.0, 25.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

MO000042012 MO000019397

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c18 : 1
stoichiometry:c20 : 1

m19828*m3964*0.1

nodelay

--

true

0

false

PMID: 16979939, 16365150, 16148144, 14993594 urthermore, TLR9 was found to cooperate with TLR2 to combat intracellular bacteria such as Mycobacterium tuberculosis [46] and Brucella abortus [47], and with TLR3 against mouse cytomegaloviru.

Go back
489.0, 480.0
23.0, 23.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_EndosomeLumen

--

MO000042012 MO000019398

e24

true true true true

--

and

mass

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

m19828*m3965*0.1

nodelay

--

true

0

false

PMID: 16979939, 16365150, 16148144, 14993594 urthermore, TLR9 was found to cooperate with TLR2 to combat intracellular bacteria such as Mycobacterium tuberculosis [46] and Brucella abortus [47], and with TLR3 against mouse cytomegaloviru.

Go back
243.0, 283.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
183.0, 888.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1083.0, 1168.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1126.5894663844042, 1172.0

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1253.5418338843217, 772.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1094.0, 1260.0

c103

c103

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1280.0, 772.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1130.7579382497163, 1264.0

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1128.0, 756.0

c106

c106

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1131.803164025699, 766.0

c107

c107

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1068.0, 719.0

c108

c108

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1080.0, 756.0

c109

c109

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
248.0, 712.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1077.0, 825.0

c110

c110

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1089.0, 860.0

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1009.0, 912.0

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
851.0, 919.7016123601188

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1015.3596099683606, 873.0

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1003.8995700892395, 772.0

c115

c115

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1077.6568542494924, 716.0

c116

c116

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1068.0, 704.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1077.0, 808.0

c118

c118

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1083.2494297193982, 820.0

c119

c119

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
240.0, 718.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1128.0, 704.0

c120

c120

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1126.716561257217, 712.0

c121

c121

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
944.0, 763.0

c122

c122

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
952.0, 800.0

c123

c123

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
763.40404802577, 948.0

c124

c124

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1013.4698886744255, 768.0

c125

c125

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1013.020613557655, 815.2680368629482

c126

c126

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
805.7331159258329, 815.0

c127

c127

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
773.8599434057004, 810.0

c128

c128

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
738.2399915200255, 915.0

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
255.0, 804.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
985.0, 1008.0

c130

c130

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
960.0, 1052.0

c131

c131

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
854.0, 1008.3045410027452

c132

c132

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
870.0, 1048.0

c133

c133

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
931.0, 816.0

c134

c134

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
929.0, 816.0

c135

c135

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
275.0, 1192.0

c136

c136

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
275.0, 1194.0

c137

c137

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
499.5298221281347, 1148.0

c138

c138

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
535.7500950614661, 1139.0

c139

c139

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
247.0, 809.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
458.30428362337494, 1241.0

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
511.9088269514547, 1276.0

c141

c141

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
875.7039846776598, 763.0

c142

c142

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1047.0, 1216.0

c143

c143

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1000.0, 1232.9463531699773

c144

c144

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
646.0, 1098.3874280959983

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
870.0, 1055.0

c146

c146

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
965.0, 1080.0

c147

c147

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
574.9463531699773, 1303.0

c148

c148

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
668.0, 239.57770876399965

c149

c149

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
247.0, 888.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
602.5164229118466, 1312.1857337763822

c150

c150

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
869.0, 800.0

c151

c151

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
256.0, 799.5041450821668

c152

c152

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
982.0, 1216.0

c153

c153

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1001.0, 1276.0

c154

c154

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1059.0, 1304.0

c155

c155

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
981.0, 1304.0

c156

c156

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
777.5775375331502, 1051.5536798306425

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
770.601414015922, 1057.544233267089

c158

c158

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
853.6568542494924, 1109.6568542494924

c159

c159

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
239.0, 894.0

c16

c16

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
834.981966459253, 1146.2593937564973

c160

c160

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
745.9877689940647, 1145.9352504244603

c161

c161

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
760.8954737212622, 1143.0561610125071

c162

c162

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
803.5793677316384, 1162.5599189027387

c163

c163

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
790.8747843976927, 1203.091129365498

c164

c164

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
215.58140473080033, 1007.0

c165

c165

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
559.4871333448388, 789.8605619655765

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
573.0481110539788, 600.0

c167

c167

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
402.9364580533432, 600.0

c168

c168

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
576.3657998262198, 851.2575058752865

c169

c169

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
405.0, 339.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
411.99001871102274, 997.0

c170

c170

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
398.61788654201956, 972.0

c171

c171

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
463.9628001084424, 950.0

c172

c172

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
397.0, 1044.0

c173

c173

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
527.0, 1044.0

c174

c174

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
353.0, 1088.0

c175

c175

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
453.15135438863337, 667.0

c176

c176

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
414.7982845151553, 1047.0

c177

c177

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
202.39865987814244, 1093.0

c178

c178

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
184.0, 1098.0

c179

c179

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
421.0, 426.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
195.0, 1148.0

c180

c180

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
344.0, 850.410668592437

c181

c181

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
219.0, 452.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
324.25467728968613, 292.3718922614034

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
431.93280328948975, 455.03471347254214

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
285.0, 452.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
277.0, 456.0

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
407.0, 339.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
410.0, 504.33895262009196

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
429.1066869567562, 503.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
319.7378477230355, 608.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
227.0, 633.6643638388299

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
312.0, 635.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
240.68626797503146, 820.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
317.0, 283.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
183.0, 932.0

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
239.0, 939.0

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
100.0224347446719, 286.95108653077887

c32

c32

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
264.0, 1324.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
611.0, 1423.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
632.0, 1401.0

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
693.0, 1419.52380597346

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
680.0, 1399.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
591.0, 1475.6203457238362

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
628.2068273953847, 1243.9973259548751

c39

c39

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
284.5262345561611, 331.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
674.704144440259, 1252.0907907856388

c40

c40

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
639.0, 1184.009319187599

c41

c41

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
668.0, 1185.7136431424303

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
816.0, 1472.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
829.7618204050059, 1412.0

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
816.0, 1415.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
714.8328410093897, 1251.375237076216

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
689.7560975609756, 1185.8048780487804

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
704.2680368629482, 1184.020613557655

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
751.1100797331665, 1232.1640028712568

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
214.0, 376.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
916.0, 1400.0

c50

c50

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
916.0, 1469.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
933.0910636383645, 1394.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
411.0, 194.40134894699796

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
467.0, 176.0

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
448.0, 187.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
464.0, 196.02906276576402

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
582.8274742736284, 167.0

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
564.0, 199.0

c58

c58

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
583.0, 188.0

c59

c59

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
277.0, 375.07206914748457

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.7181105699019, 193.10493924633687

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
582.0, 256.0

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
725.7734525962109, 310.0

c62

c62

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
728.0, 368.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
680.0, 368.0

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
708.2161372907833, 244.0

c65

c65

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
640.8308170454446, 268.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
819.6377768816001, 390.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
813.0, 436.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
879.8599434057004, 512.1159660434203

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
321.13549325167475, 183.0

c7

c7

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
873.0, 500.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
672.0, 376.0

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
672.0, 378.0

c72

c72

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1093.3599068047633, 555.7075489304051

c73

c73

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1080.0, 549.0

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
995.0, 436.0

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1000.9834024717477, 569.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
980.0, 585.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
977.0, 516.0

c78

c78

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
987.0, 442.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
165.0, 731.4680387845025

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
916.0, 436.0

c80

c80

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1077.0, 496.0

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
568.0, 281.0

c82

c82

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
618.8264389163953, 463.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
619.0, 484.0

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
618.7703784930558, 489.90294983503406

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
618.2995050672691, 494.2737174241086

c86

c86

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
617.6122297273157, 498.5031564522236

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
603.0, 499.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
643.0, 600.0

c89

c89

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
172.0, 820.9463531699773

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
603.0554533493829, 656.7710181694978

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
673.0, 705.0

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
696.0, 781.0

c92

c92

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
696.0, 847.0

c93

c93

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
655.0, 597.0

c94

c94

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
621.4942918883096, 600.0

c95

c95

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
726.0, 749.9203980503625

c96

c96

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
632.3186590790551, 843.7341802588655

c97

c97

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
770.0, 728.0

c98

c98

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
265.76279945179095, 837.0

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back