1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18515054.csml convertedTime:2009.07.01.11:19

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Calcium signaling in lymphocytes.
Authors Oh-hora M, Rao A.
Affiliation Department of Pathology, Harvard Medical School, Immune Disease Institute,Boston, MA 02115, USA.
Abstract In cells of the immune system, calcium signals are essential for diversecellular functions including differentiation, effector function, and genetranscription. After the engagement of immunoreceptors such as T-cell and B-cellantigen receptors and the Fc receptors on mast cells and NK cells, theintracellular concentration of calcium ions is increased through the sequentialoperation of two interdependent processes: depletion of endoplasmic reticulumCa(2+) stores as a result of binding of inositol trisphosphate (IP(3)) to IP(3)receptors, followed by 'store-operated' Ca(2+) entry through plasma membraneCa(2+) channels. In lymphocytes, mast cells and other immune cell types,store-operated Ca(2+) entry through specialized Ca(2+) release-activated calcium(CRAC) channels constitutes the major pathway of intracellular Ca(2+) increase.A recent breakthrough in our understanding of CRAC channel function is theidentification of stromal interaction molecule (STIM) and ORAI, two essentialregulators of CRAC channel function. This review focuses on the signalingpathways upstream and downstream of Ca(2+) influx (the STIM/ORAI andcalcineurin/NFAT pathways, respectively).
PMID 18515054
Model Abstract

Entity

G011587:FOXP3 MO000000003:Ras family MO000000049:c-Jun MO000000058:NF-kappaB{active} MO000000104:PKC MO000000138:Lck MO000000276:AP-1 MO000000279:c-Fos MO000000331:PIP2 MO000000332:IP3 MO000016695:DAG MO000016711:calmodulin:(Ca)4 MO000016724:calcineurin MO000016774:IP3R MO000016894:MAPK{active} MO000016941:GSK3 MO000017189:CREB MO000017450:Smad3 MO000017617:PLCgamma1 MO000017690:BCR MO000017772:ZAP-70 MO000017777:TCR MO000019288:IP3R:IP3 MO000036737:Dyrk1 MO000038437:PLCgamma1{p} MO000042243:FOXP3 MO000062470:STIM1 MO000066199:STIM2 MO000069405:DYRK2 e1: e10: e11:Lck{active} e12:antigen Ig:MHC peptide:BCR e13:ZAP-70{active} e14: e15: e16: e17: e18: e19: e2: e20:ca2+ e21:ca2+ e22:CRAC channels e23:ca2+ e24:MAPK e25:PKC{active} e26:AP-1{active} e27:CREB{active} e28:NF-kappaB e29:NFAT{p} e3: e30:NFAT{active} e31:NFAT{active} e32:CAMK e33:CAMK{active} e34:MEF2 e35:MEF2{active} e36:DNA e37:NFAT:Fos:Jun e38:activation associated genes e39:Ras family{active} e4: e40:RasGEF e41:RasGAP1 e42:CAPRI e43:RasGRP1 e44:ca2+:RasGRP1 e45: e46: e47: e48: e49:RasGRP1 e5:antigen Ig:MHC peptide e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:TCR:antigen Ig:MHC peptide e60: e61: e62: e63:anti-CD3 e64:low affinity peptide e65:calmodulin:(ca)4:calcineurin e66:calmodulin:(ca)4:calcineurin{active} e67:NFAT{p} e68:CK1 e69:cyclosporin A e7: e70:notch ligand:notch e71:calcipressin e72:calcipressin e73:ca2+:STIM1 e74:ca2+:STIM2 e75:ORAI1 e76:STIM1:ORAI1 e77:target genes e78:NFAT:FOXP3 e79:FOXP3 e8: e80:Smad3:NFAT:FOXP3 e81:TGF-beta e82:SIS3 e83:Fc receptor e84:antigen Ig:MHC peptide:Fc receptor e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 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 p6 p8 p9
Model Detail
1068.0, 1572.0
32.0, 32.0

FOXP3

--

G011587

cso30:c:mRNA

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m94442

10

false

infinite

0

unit false false false
TRANSFACG011587

--

Go back
841.0, 321.0
30.0, 30.0

Ras family

--

MO000000003

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p27

true true true true

csml-variable:Double

m41

10

false

infinite

0

unit false false false
TRANSPATHMO000000003

--

Go back
921.0, 1137.0
22.0, 22.0

c-Jun

--

MO000000049

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
InterProIPR002112
TRANSPATHMO000000049

--

Go back
589.0, 1033.0
29.0, 29.0

NF-kappaB{active}

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
953.0, 721.0
30.0, 30.0

PKC

--

MO000000104

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m92

10

false

infinite

0

unit false false false
TRANSPATHMO000000104

--

Go back
1298.0, 326.0
28.0, 28.0

Lck

--

MO000000138

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m123

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000000138

--

Go back
1245.0, 973.0
38.0, 38.0

AP-1

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
828.0, 1140.0
24.0, 24.0

c-Fos

--

MO000000279

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m221

10

false

infinite

0

unit false false false
InterProIPR002114
TRANSPATHMO000000279

--

Go back
1339.0, 855.0
34.0, 34.0

PIP2

--

MO000000331

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m290229

10

false

infinite

0

unit false false false
TRANSPATHMO000000331

--

Go back
1170.0, 874.0
28.0, 28.0

IP3

--

MO000000332

cso30:c:Protein

cso30:i:CC_CellComponent

--

p5

p6

true true true true

csml-variable:Double

m290230

10

false

infinite

0

unit false false false
TRANSPATHMO000000332

--

Go back
1205.0, 817.0
30.0, 30.0

DAG

--

MO000016695

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m290231

10

false

infinite

0

unit false false false
TRANSPATHMO000016695

--

Go back
768.0, 432.0
24.0, 24.0

calmodulin:(Ca)4

--

MO000016711

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p31

true true true true

csml-variable:Double

m1665

10

false

infinite

0

unit false false false
TRANSPATHMO000016711

--

Go back
504.0, 488.0
23.0, 23.0

calcineurin

--

MO000016724

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p31

true true true true

csml-variable:Double

m1676

10

false

infinite

0

unit false false false
TRANSPATHMO000016724

--

Go back
903.0, 967.0
26.0, 26.0

IP3R

--

MO000016774

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m1719

10

false

infinite

0

unit false false false
TRANSPATHMO000016774

--

Go back
859.0, 703.0
34.0, 34.0

MAPK{active}

--

MO000016894

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m1812

10

false

infinite

0

unit false false false
TRANSPATHMO000016894

--

Go back
608.0, 1356.0
24.0, 24.0

GSK3

--

MO000016941

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33

true true true true

csml-variable:Double

m1853

10

false

infinite

0

unit false false false
TRANSPATHMO000016941

--

Go back
1125.0, 925.0
30.0, 30.0

CREB

--

MO000017189

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p16 p21

true true true true

csml-variable:Double

m2057

10

false

infinite

0

unit false false false
InterProIPR003102
TRANSPATHMO000017189

--

Go back
983.0, 1451.0
26.0, 26.0

Smad3

--

MO000017450

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p48

true true true true

csml-variable:Double

m2276

10

false

infinite

0

unit false false false
TRANSPATHMO000017450

--

Go back
1174.0, 722.0
28.0, 28.0

PLCgamma1

--

MO000017617

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m2395

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000017617

--

Go back
1302.0, 166.0
36.0, 36.0

BCR

--

MO000017690

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m2450

10

false

infinite

0

unit false false false
TRANSPATHMO000017690

--

Go back
1259.0, 551.0
34.0, 34.0

ZAP-70

--

MO000017772

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m2529

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000017772

--

Go back
1436.0, 184.0
32.0, 32.0

TCR

--

MO000017777

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m2534

10

false

infinite

0

unit false false false
TRANSPATHMO000017777

--

Go back
894.0, 938.0
28.0, 28.0

IP3R:IP3

--

MO000019288

cso30:c:Protein

cso30:i:CC_CellComponent

--

p6

p8

true true true true

csml-variable:Double

m3862

10

false

infinite

0

unit false false false
TRANSPATHMO000019288

--

Go back
790.0, 1538.0
28.0, 28.0

Dyrk1

--

MO000036737

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m15070

10

false

infinite

0

unit false false false
TRANSPATHMO000036737

--

Go back
1289.0, 793.0
30.0, 30.0

PLCgamma1{p}

--

MO000038437

cso30:c:Protein

cso30:i:CC_CellComponent

--

p4

p5

true true true true

csml-variable:Double

m16647

10

false

infinite

0

unit false false false
TRANSPATHMO000038437

--

Go back
815.0, 1371.0
34.0, 34.0

FOXP3

--

MO000042243

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m20050

10

false

infinite

0

unit false false false
InterProIPR007087
TRANSPATHMO000042243

--

Go back
834.0, 990.0
28.0, 28.0

STIM1

--

MO000062470

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m37358

10

false

infinite

0

unit false false false
TRANSPATHMO000062470

--

Go back
948.0, 1004.0
24.0, 24.0

STIM2

--

MO000066199

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p41

true true true true

csml-variable:Double

m41059

10

false

infinite

0

unit false false false
TRANSPATHMO000066199

--

Go back
837.0, 1433.0
22.0, 22.0

DYRK2

--

MO000069405

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m44249

10

false

infinite

0

unit false false false
TRANSPATHMO000069405

--

Go back
336.4807458384688, 144.4872440371714
1161.870062973257, 1678.9399506749724

--

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
347.67528299686165, 170.14906375938446
1126.2078864017078, 1576.6556296289061

--

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
1314.0, 446.0
28.0, 28.0

Lck{active}

--

e11

cso30:c:Protein

cso30:i:CC_CellComponent

--

p2

p3

true true true true

csml-variable:Double

m11

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000000138

--

Go back
1228.5, 166.89103266827448
22.27296645472484, 43.108967331725495

antigen Ig:MHC peptide:BCR

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p51

--

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
1299.0, 635.0
34.0, 34.0

ZAP-70{active}

--

e13

cso30:c:Protein

cso30:i:CC_CellComponent

--

p3

p4

true true true true

csml-variable:Double

m13

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000017772

--

Go back
748.4396060896007, 953.6251598662343
247.61356423543677, 69.692559470239

--

e14

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_ExtrinsicToInternalSideOfMembrane_

--

--

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false true false

--

Go back
749.2595185539566, 954.4450723305903
245.97373930672535, 68.05273454152744

--

e15

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulumLumen

--

--

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false true false

--

Go back
744.75, 949.9355537766336
254.99277641463866, 77.07177164944082

--

e16

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_Membrane_

--

--

--

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false true false

--

Go back
744.75, 949.9355537766336
254.99277641463866, 77.07177164944082

--

e17

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_ExtrinsicToExternalSideOfMembrane_

--

--

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false true false

--

Go back
747.2097373930673, 952.3952911697008
250.07330162850423, 72.15229686330625

--

e18

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum

--

--

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false true false

--

Go back
744.75, 949.9355537766336
254.99277641463866, 77.07177164944082

--

e19

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_IntegralToMembrane_

--

--

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false true false

--

Go back
336.4807458384688, 144.4872440371714
1161.870062973257, 1678.9399506749724

--

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
783.5, 967.0206185567012
25.54639175257731, 25.97938144329896

ca2+

--

e20

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
640.5, 747.8689450642564
31.59553735348114, 32.13105493574353

ca2+

--

e21

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
358.5, 521.5644998993762
27.40189172871805, 44.43550010062387

CRAC channels

--

e22

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p9

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
156.5, 591.8689450642564
31.59553735348114, 32.13105493574353

ca2+

--

e23

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p9 p43

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
915.0, 559.0
34.0, 34.0

MAPK

--

e24

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
TRANSPATHMO000016894

--

Go back
1017.0, 845.0
30.0, 30.0

PKC{active}

--

e25

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m25

10

false

infinite

0

unit false false false
TRANSPATHMO000000104

--

Go back
1277.0, 1165.0
38.0, 38.0

AP-1{active}

--

e26

cso30:c:Protein

cso30:i:CC_CellComponent

--

p12

--

true true true true

csml-variable:Double

m26

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
1125.0, 1141.0
30.0, 30.0

CREB{active}

--

e27

cso30:c:Protein

cso30:i:CC_CellComponent

--

p13 p16 p21

--

true true true true

csml-variable:Double

m27

10

false

infinite

0

unit false false false
InterProIPR003102
TRANSPATHMO000017189

--

Go back
590.0, 810.0
27.0, 27.0

NF-kappaB

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14 p15 p24

true true true true

csml-variable:Double

m29

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
483.0, 770.0975609756098
34.8780487804878, 27.902439024390247

NFAT{p}

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
359.718147097934, 167.61313867456792
1115.3952604543272, 1632.6881614001813

--

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
664.0, 1288.32834424696
16.757717492984096, 38.67165575304022

NFAT{active}

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
438.0, 956.4602432179607
20.600561272217025, 47.53975678203929

NFAT{active}

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
583.0, 475.53999999999996
33.279999999999994, 24.959999999999997

CAMK

--

e32

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p20

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
525.0, 541.18
29.76, 22.32

CAMK{active}

--

e33

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
645.0, 948.3945461863553
37.468303481585835, 23.105453813644598

MEF2

--

e34

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p22 p23

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
660.0, 1064.4190984101429
39.05011068625478, 24.080901589857113

MEF2{active}

--

e35

cso30:c:Protein

cso30:i:CC_Cytosol

--

p22 p23

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
727.0, 1194.0035818519502
57.67577606792253, 12.49641814804988

DNA

--

e36

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p25

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
865.0, 1256.0736693237336
54.44587297505785, 15.426330676266394

NFAT:Fos:Jun

--

e37

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
1002.0, 1316.4429065743948
44.169550173010386, 23.557093425605537

activation associated genes

--

e38

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p26

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
901.0, 473.0
30.0, 30.0

Ras family{active}

--

e39

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27

--

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
TRANSPATHMO000000003

--

Go back
402.70733942794504, 208.0834542900111
1029.4168757943064, 1551.7475301692928

--

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
693.0, 339.57546790098615
38.796538538941434, 23.924532099013884

RasGEF

--

e40

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p27

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1059.5, 333.4429462668545
17.610183135439726, 28.5570537331455

RasGAP1

--

e41

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p27

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
1035.0, 434.9223573433115
18.666978484565014, 43.0776426566885

CAPRI

--

e42

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p27

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
549.0, 317.34000000000003
38.879999999999995, 29.16

RasGRP1

--

e43

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p28 p29 p30

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
512.0, 375.03314917127074
23.37016574585635, 25.966850828729278

ca2+:RasGRP1

--

e44

cso30:c:Complex

cso30:i:CC_Cytosol

--

p28

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
769.0, 789.3915075443983
205.1114968620644, 84.6084924556015

--

e45

cso30:c:EntityBiologicalCompartment

cso30:i:CC_GolgiMembrane

--

--

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false true false

--

Go back
769.0, 789.3915075443983
205.1114968620644, 84.6084924556015

--

e46

cso30:c:EntityBiologicalCompartment

cso30:i:CC_GolgiLumen

--

--

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false true false

--

Go back
811.7315618462634, 800.0743980059642
114.52058574798598, 12.819468553879014

--

e47

cso30:c:EntityBiologicalCompartment

cso30:i:CC_GolgiTransFace

--

--

--

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false true false

--

Go back
769.0, 789.3915075443983
205.1114968620644, 84.6084924556015

--

e48

cso30:c:EntityBiologicalCompartment

cso30:i:CC_GolgiApparatus

--

--

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false true false

--

Go back
821.0, 802.7
30.4, 22.799999999999997

RasGRP1

--

e49

cso30:c:Protein

cso30:i:CC_Cytosol

--

p29 p30

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
1681.5, 183.4542576237293
20.862356273954333, 25.545742376270617

antigen Ig:MHC peptide

--

e5

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p1 p51 p52

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
582.4213349243786, 1112.7298908531427
631.8469117983957, 570.2660640948673

--

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
650.6655078932928, 1126.2443675357351
369.4598329696394, 552.7014009297278

--

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
590.6577006275234, 1120.34124489137
615.374180392107, 555.0433560184132

--

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
591.8343242994016, 1121.5122224357124
613.0209330483508, 552.7014009297278

--

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
582.4213349243786, 1112.7298908531427
631.8469117983957, 570.2660640948673

--

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
582.4213349243786, 1112.7298908531427
631.8469117983957, 570.2660640948673

--

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
591.8343242994016, 1121.5122224357124
613.0209330483508, 552.7014009297278

--

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
1043.6578143004897, 1346.9253997216713
39.47432336373286, 35.563174900998526

--

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
940.1149311752407, 1510.8622559296437
111.77924882839412, 100.70406881346743

--

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
582.4213349243786, 1112.7298908531427
631.8469117983957, 570.2660640948673

--

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
1445.5, 263.90374917781185
21.233062924797192, 41.09625082218812

TCR:antigen Ig:MHC peptide

--

e6

cso30:c:Complex

cso30:i:CC_Cytosol

--

p1

p2

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
731.3440968773948, 1366.1514175896227
20.009663295141184, 9.588051414186891

--

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
730.6759175809851, 1337.5575793669325
68.48837788194552, 122.68751516480553

--

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
759.4076273265821, 1417.3543371977005
10.690868742547584, 10.639567710769036

--

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
271.0, 348.92307692307685
25.384615384615387, 38.07692307692307

anti-CD3

--

e63

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p29

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
264.5, 241.37472328436309
23.202253974642787, 37.62527671563695

low affinity peptide

--

e64

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p30

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
812.5, 569.8646892184637
22.977170471588064, 28.1353107815364

calmodulin:(ca)4:calcineurin

--

e65

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
414.5, 595.8553574404267
26.251458090318273, 32.1446425595734

calmodulin:(ca)4:calcineurin{active}

--

e66

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
682.0, 1433.3170731707316
35.85365853658536, 28.682926829268286

NFAT{p}

--

e67

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
702.5, 1523.6272891929964
19.963171664318775, 32.372710807003415

CK1

--

e68

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

--

p34

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
433.0, 1483.2497897392768
45.44154751892346, 25.750210260723296

cyclosporin A

--

e69

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p37 p49 p50

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
351.7460237817321, 151.24343112426607
1139.432552703244, 1606.798958350776

--

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
355.5, 1332.4314843236132
24.57706643279982, 47.56851567638676

notch ligand:notch

--

e70

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p38 p39

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
873.0, 1547.5570934256054
45.83044982698962, 24.442906574394463

calcipressin

--

e71

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
502.0, 1586.02
36.64, 27.48

calcipressin

--

e72

cso30:c:Protein

cso30:i:CC_Cytosol

--

p38

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
912.0, 999.2541436464089
23.17127071823204, 25.74585635359116

ca2+:STIM1

--

e73

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
838.5, 939.7853691051491
26.308615230794867, 32.214630894850856

ca2+:STIM2

--

e74

cso30:c:Complex

cso30:i:CC_Cytosol

--

p41

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
370.0, 1064.358278765201
20.211412535079514, 46.64172123479888

ORAI1

--

e75

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p43 p44 p47

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
371.0, 1177.0552486187844
26.95027624309392, 29.944751381215468

STIM1:ORAI1

--

e76

cso30:c:Complex

cso30:i:CC_Cytosol

--

p44 p47

--

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
1078.0, 1273.2733564013843
42.61245674740485, 22.726643598615915

target genes

--

e77

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p45

--

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
928.5, 1389.484752541243
23.287452091318116, 28.51524745875688

NFAT:FOXP3

--

e78

cso30:c:Complex

cso30:i:CC_Cytosol

--

p46

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
982.0, 1377.5
60.0, 13.0

FOXP3

--

e79

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p48

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false false false

--

Go back
355.8167645666023, 179.60188007694367
1093.0712250248714, 1579.5233969030605

--

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
1134.0, 1391.5
60.0, 17.0

Smad3:NFAT:FOXP3

--

e80

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
256.0, 1592.3669752465285
39.13463473535923, 24.133024753471524

TGF-beta

--

e81

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p48 p49 p50

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false false false

--

Go back
650.0, 1695.650126156434
44.73507148864592, 25.349873843566023

SIS3

--

e82

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p49 p50

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false false false

--

Go back
1114.5, 167.34797891036902
27.073813708260108, 41.65202108963093

Fc receptor

--

e83

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p52

true true true true

csml-variable:Double

m86

0

false

infinite

0

unit false false false

--

Go back
1028.5, 166.08857706643278
22.687568515676386, 43.911422933567195

antigen Ig:MHC peptide:Fc receptor

--

e84

cso30:c:Complex

cso30:i:CC_Cytosol

--

p52

--

true true true true

csml-variable:Double

m87

0

false

infinite

0

unit false false false

--

Go back
366.67207332625634, 207.96032902962108
1088.0807552954725, 1558.8083433454271

--

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
1546.0, 190.0
19.0, 19.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m2534*m5*0.1

nodelay

--

true

0

false

PMID: 18515054 CRAC channels open in response to a lengthy signaling cascade, initiated when immunoreceptors, such as T-cell and B-cell antigen receptors (TCR, BCR) as well as mast cell and NK cell Fc receptors, are bound by antigenic complexes (MHC?peptide and antigen?Ig).

Go back
867.0, 619.0
17.0, 17.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m24*m290231*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

Go back
979.0, 783.0
17.0, 17.0

p11

p11

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m92*m290231*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

Go back
1249.0, 1081.0
21.0, 21.0

p12

p12

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m219*m25*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

Go back
1128.0, 1060.0
23.0, 23.0

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c47 : 1
stoichiometry:c37 : 1

m2057*m1812*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

Go back
593.0, 929.0
21.0, 21.0

p14

p14

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m29*m25*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

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541.0, 917.0
21.0, 21.0

p15

p15

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m29*m1812*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

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1070.0, 1054.0
19.0, 19.0

p16

p16

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m2057*m25*0.1

nodelay

--

true

0

false

PMID: 18515054, 17098202, 16036612 DAG production activates the Ras-mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to the activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NF¦ÊB.

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504.0, 572.0
23.0, 23.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c51 : 1
stoichiometry:c97 : 1

m21*m68*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB). PMID: 18515054 An increase in [Ca2+]i results in binding of Ca2+-calmodulin to calcineurin and activation of its phosphatase activity.

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514.0, 1071.5
21.5, 21.5

p19

p19

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c98 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 18515054, 12975316 Dephosphorylation of cytoplasmic NFAT proteins by calcineurin unmasks the nuclear localization sequence and then NFAT proteins translocate into nucleus.

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1334.0, 390.0
19.0, 19.0

p2

p2

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m123*m6*0.1

nodelay

--

true

0

false

PMID: 18515054 The binding of antigen/MHC complexes to T-cell receptor (TCR) triggers the activation of protein tyrosine kinases, such as LCK and ZAP70, which eventually results in tyrosine phosphorylation and activation of PLC-¦Ã1.

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590.0, 542.0
19.0, 19.0

p20

p20

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m33*m21*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB).

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1179.0, 1081.5
18.5, 18.5

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c62 : 1
stoichiometry:c61 : 1

m2057*m34*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB).

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722.0, 974.0
19.0, 19.0

p22

p22

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m35*m34*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB).

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646.0, 1014.0
19.0, 19.0

p23

p23

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c68 : 1
stoichiometry:c67 : 1

m35*m69*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB).

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631.0, 899.0
17.0, 17.0

p24

p24

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m29*m21*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB).

Go back
829.0, 1189.0
21.0, 21.0

p25

p25

cso30:i:ME_DNABinding

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c74 : 1
stoichiometry:c76 : 1
stoichiometry:c75 : 1
stoichiometry:c73 : 1

m37*m46*m221*m31*0.1

nodelay

--

true

0

false

PMID: 18515054, 12975316, 15928679 A notable example of such integration involves the formation of a cooperative NFAT:Fos:Jun complex on DNA, which drives the transcription of a large number of activation-associated genes.

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891.0, 1319.0
17.0, 17.0

p26

p26

cso30:i:ME_Transcription

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m38*0.1

nodelay

--

true

0

false

PMID: 18515054, 12975316, 15928679 A notable example of such integration involves the formation of a cooperative NFAT:Fos:Jun complex on DNA, which drives the transcription of a large number of activation-associated genes.

Go back
844.0, 416.0
23.0, 23.0

p27

p27

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c81 : 1
stoichiometry:c82 : 1
stoichiometry:c83 : 1
stoichiometry:c80 : 1

m41*m43*0.1

nodelay

--

true

0

false

PMID: 18515054, 11988768 Ras is activated by Ras guanine nucleotide exchange factor (RasGEF) and inactivated by RasGAPs, including GAP1 and Ca2+-activated CAPRI.

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603.0, 407.0
17.0, 17.0

p28

p28

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c85 : 1
stoichiometry:c86 : 1

m45*m21*0.1

nodelay

--

true

0

false

PMID: 18515054, 9582122 RasGRP1 has a DAG-binding C1 domain and a pair of EF-hand motifs that bind to Ca2+ directly.

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721.0, 492.0
19.0, 19.0

p29

p29

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m45*m66*0.1

nodelay

--

true

0

false

PMID: 18515054, 12845332, 17086201 RasGRP1 localizes in the cytoplasm of resting T cells and translocates to the Golgi apparatus in response to weak stimulation, such as with soluble anti-CD3 antibodies or with low-affinity peptides that induce positive selection of thymocytes.

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1307.0, 579.0
17.0, 17.0

p3

p3

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m2529*m11*0.1

nodelay

--

true

0

false

PMID: 18515054 The binding of antigen/MHC complexes to T-cell receptor (TCR) triggers the activation of protein tyrosine kinases, such as LCK and ZAP70, which eventually results in tyrosine phosphorylation and activation of PLC-¦Ã1.

Go back
691.0, 531.0
17.0, 17.0

p30

p30

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m45*m67*0.1

nodelay

--

true

0

false

PMID: 18515054, 12845332, 17086201 RasGRP1 localizes in the cytoplasm of resting T cells and translocates to the Golgi apparatus in response to weak stimulation, such as with soluble anti-CD3 antibodies or with low-affinity peptides that induce positive selection of thymocytes.

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774.0, 518.0
19.0, 19.0

p31

p31

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c96 : 1
stoichiometry:c95 : 1

m1665*m1676*m21*0.1

nodelay

--

true

0

false

PMID: 18515054 An increase in [Ca2+]i results in binding of Ca2+-calmodulin to calcineurin and activation of its phosphatase activity.

Go back
438.0, 834.0
19.0, 19.0

p32

p32

cso30:i:ME_Dephosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c55 : 1
stoichiometry:c54 : 1

m30*m69*0.1

nodelay

--

true

0

false

PMID: 18515054 As a result, several Ca2+-dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target nuclear factor of activated T cells (NFATs), Ca2+-calmodulin-dependent kinase (CaMK) and its target cyclic-AMP-responsive-element-binding protein (CREB), myocyte enhancer factor 2 (MEF2) which is acted upon by both the calcineurin and CaMK pathways, and nuclear factor kappa B (NF¦ÊB). PMID: 18515054, 12975316 Dephosphorylation of cytoplasmic NFAT proteins by calcineurin unmasks the nuclear localization sequence and then NFAT proteins translocate into nucleus.

Go back
673.0, 1361.0
21.0, 21.0

p33

p33

cso30:i:ME_Phosphorylation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c101 : 1
stoichiometry:c116 : 1
stoichiometry:c100 : 1

m31*m1853*m21*0.1

nodelay

--

true

0

false

PMID: 18515054, 11030334, 15121840, 16511445 NFAT-driven gene expression is highly dependent on sustained Ca2+ influx and calcineurin activity, because a decrease in intracellular Ca2+ levels or treatment with the calcineurin inhibitor cyclosporin A results in the immediate export of NFAT from nucleus by NFAT kinases, which include glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and dual-specificity tyrosine-phosphorylation regulated kinases (DYRK1 and DYRK2).

Go back
702.0, 1346.0
19.0, 19.0

p34

p34

cso30:i:ME_Phosphorylation

cso30:i:CC_NuclearChromosome

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c104 : 1
stoichiometry:c115 : 1
stoichiometry:c103 : 1

m31*m71*m21*0.1

nodelay

--

true

0

false

PMID: 18515054, 11030334, 15121840, 16511445 NFAT-driven gene expression is highly dependent on sustained Ca2+ influx and calcineurin activity, because a decrease in intracellular Ca2+ levels or treatment with the calcineurin inhibitor cyclosporin A results in the immediate export of NFAT from nucleus by NFAT kinases, which include glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and dual-specificity tyrosine-phosphorylation regulated kinases (DYRK1 and DYRK2).

Go back
740.0, 1316.0
15.0, 15.0

p35

p35

cso30:i:ME_Phosphorylation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c109 : 1
stoichiometry:c113 : 1
stoichiometry:c106 : 1

m31*m15070*m21*0.1

nodelay

--

true

0

false

PMID: 18515054, 11030334, 15121840, 16511445 NFAT-driven gene expression is highly dependent on sustained Ca2+ influx and calcineurin activity, because a decrease in intracellular Ca2+ levels or treatment with the calcineurin inhibitor cyclosporin A results in the immediate export of NFAT from nucleus by NFAT kinases, which include glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and dual-specificity tyrosine-phosphorylation regulated kinases (DYRK1 and DYRK2).

Go back
778.0, 1358.0
19.0, 19.0

p36

p36

cso30:i:ME_Phosphorylation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c107 : 1
stoichiometry:c110 : 1
stoichiometry:c114 : 1
stoichiometry:c108 : 1

m31*m44249*m21*0.1

nodelay

--

true

0

false

PMID: 18515054, 11030334, 15121840, 16511445 NFAT-driven gene expression is highly dependent on sustained Ca2+ influx and calcineurin activity, because a decrease in intracellular Ca2+ levels or treatment with the calcineurin inhibitor cyclosporin A results in the immediate export of NFAT from nucleus by NFAT kinases, which include glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and dual-specificity tyrosine-phosphorylation regulated kinases (DYRK1 and DYRK2).

Go back
490.0, 1402.0
19.0, 19.0

p37

p37

cso30:i:ME_NuclearExport

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c111 : 1
stoichiometry:c117 : 1
stoichiometry:c112 : 1

m70*m72*0.1

nodelay

--

true

0

false

PMID: 18515054, 11030334, 15121840, 16511445 NFAT-driven gene expression is highly dependent on sustained Ca2+ influx and calcineurin activity, because a decrease in intracellular Ca2+ levels or treatment with the calcineurin inhibitor cyclosporin A results in the immediate export of NFAT from nucleus by NFAT kinases, which include glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and dual-specificity tyrosine-phosphorylation regulated kinases (DYRK1 and DYRK2).

Go back
609.0, 1614.0
25.0, 25.0

p38

p38

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c119 : 1
stoichiometry:c122 : 1
stoichiometry:c118 : 1

m74*0.1

nodelay

--

true

0

false

Go back
884.0, 1420.0
23.0, 23.0

p39

p39

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

1.0*0.1

nodelay

--

true

0

false

PMID: 18515054, 15866158 Notch signaling increases calcineurin/NFAT activity by downregulating calcipressin, an endogenous calcineurin inhibitor.

Go back
1253.0, 733.0
21.0, 21.0

p4

p4

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c16 : 1
stoichiometry:c11 : 1

m2395*m13*0.1

nodelay

--

true

0

false

PMID: 18515054 The binding of antigen/MHC complexes to T-cell receptor (TCR) triggers the activation of protein tyrosine kinases, such as LCK and ZAP70, which eventually results in tyrosine phosphorylation and activation of PLC-¦Ã1.

Go back
787.0, 1027.0
17.0, 17.0

p40

p40

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m20*m37358*0.1

nodelay

--

true

0

false

PMID: 18515054, 17434311, 15866891, 16005298 The first EF hand of each pair binds Ca2+ with low affinity matched to the high concentration of Ca2+ in the ER.

Go back
918.0, 1050.0
19.0, 19.0

p41

p41

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c127 : 1
stoichiometry:c128 : 1

m20*m41059*0.1

nodelay

--

true

0

false

PMID: 18515054, 17434311, 15866891, 16005298 The first EF hand of each pair binds Ca2+ with low affinity matched to the high concentration of Ca2+ in the ER.

Go back
834.0, 1054.0
19.0, 19.0

p42

p42

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c129 : 1
stoichiometry:c130 : 1
stoichiometry:c131 : 1

m76*0.1

nodelay

--

true

0

false

PMID: 18515054 After Ca2+ dissociates from the EF hands, STIM proteins aggregate into small clusters (¡Æpuncta¡Ç) in the ER membrane and trigger store-operated Ca2+ entry via the CRAC channel, ORAI1.

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256.0, 992.0
15.0, 15.0

p43

p43

cso30:i:ME_IonTransportThroughIonChannel

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c133 : 1

m23*m78*m37358*0.1

nodelay

--

true

0

false

PMID: 18515054 After Ca2+ dissociates from the EF hands, STIM proteins aggregate into small clusters (¡Æpuncta¡Ç) in the ER membrane and trigger store-operated Ca2+ entry via the CRAC channel, ORAI1.

Go back
454.0, 1118.0
19.0, 19.0

p44

p44

cso30:i:ME_Colocalization

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c136 : 1
stoichiometry:c137 : 1
stoichiometry:c138 : 1

m37358*m78*0.1

nodelay

--

true

0

false

PMID: 18515054, 17517596, 17045966, 16966422 The STIM1 clusters preferentially localize to sites of ER?plasma membrane apposition and colocalize partially with clusters of ORAI1.

Go back
995.0, 1215.0
25.0, 25.0

p45

p45

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m28*0.1

nodelay

--

true

0

false

PMID: 18515054, 12975316, 11244045 In contrast to NFAT, NF¦ÊB is selectively activated by a large transient increase of Ca2+ concentration and activates target gene expression.

Go back
824.0, 1280.0
15.0, 15.0

p46

p46

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c141 : 1
stoichiometry:c143 : 1

m20050*m31*0.1

nodelay

--

true

0

false

PMID: 18515054, 16873067 Foxp3 can also physically interact with NFAT, and this complex regulates the suppressive function of Foxp3-expressing T cells in a mouse model of autoimmune diabetes.

Go back
442.0, 1062.0
19.0, 19.0

p47

p47

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m78*m37358*0.1

nodelay

--

true

0

false

PMID: 18515054, 18187424 A coiled-coil domain in the cytoplasmic region of STIM1 is crucial for puncta formation and SOCE, and this region has been suggested to interact directly with a coiled-coil domain at the C-terminus of ORAI1, both in cell-free systems and by FRET after store depletion in cells.

Go back
1076.0, 1404.0
15.0, 15.0

p48

p48

cso30:i:ME_DNABinding

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c147 : 1
stoichiometry:c148 : 1
stoichiometry:c149 : 1
stoichiometry:c151 : 1
stoichiometry:c150 : 1

m82*m2276*m31*m84*0.1

nodelay

--

true

0

false

PMID: 18515054 Smad3 binds to a Foxp3 distal enhancer early during TGF¦Â treatment, whereas NFAT binding to the 5¡ì-enhancer occurs at later times, which suggests that NFAT is responsible for maintaining Foxp3 expression.

Go back
1102.0, 1326.0
19.0, 19.0

p49

p49

cso30:i:ME_Transcription

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c153 : 1
stoichiometry:c156 : 1
stoichiometry:c158 : 1
stoichiometry:c160 : 1
stoichiometry:c152 : 1

m83*m84*0.1

nodelay

--

true

0

false

PMID: 18515054, 16517728, 18157133 Foxp3 expression in activated, TGF¦Â-treated T cells is blocked by the treatment with either cyclosporin A or the Smad3 inhibitor SIS3.

Go back
1298.0, 906.0
19.0, 19.0

p5

p5

cso30:i:ME_Hydrolysis

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c15 : 1
stoichiometry:c12 : 1
stoichiometry:c13 : 1

m290229*m16647*0.1

nodelay

--

true

0

false

PMID: 18515054 PLC-¦Ã1 hydrolyzes the membrane phospholipid PIP2 to IP3 and DAG.

Go back
1248.0, 1472.0
15.0, 15.0

p50

p50

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c157 : 1
stoichiometry:c159 : 1
stoichiometry:c161 : 1
stoichiometry:c155 : 1

m94442*m84*0.1

nodelay

--

true

0

false

PMID: 18515054, 16517728, 18157133 Foxp3 expression in activated, TGF¦Â-treated T cells is blocked by the treatment with either cyclosporin A or the Smad3 inhibitor SIS3.

Go back
1355.0, 67.0
17.0, 17.0

p51

p51

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m2450*m5*0.1

nodelay

--

true

0

false

PMID: 18515054 CRAC channels open in response to a lengthy signaling cascade, initiated when immunoreceptors, such as T-cell and B-cell antigen receptors (TCR, BCR) as well as mast cell and NK cell Fc receptors, are bound by antigenic complexes (MHC?peptide and antigen?Ig).

Go back
1114.0, 78.0
19.0, 19.0

p52

p52

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c165 : 1
stoichiometry:c167 : 1
stoichiometry:c166 : 1

m86*m5*0.1

nodelay

--

true

0

false

PMID: 18515054 CRAC channels open in response to a lengthy signaling cascade, initiated when immunoreceptors, such as T-cell and B-cell antigen receptors (TCR, BCR) as well as mast cell and NK cell Fc receptors, are bound by antigenic complexes (MHC?peptide and antigen?Ig).

Go back
1106.0, 878.0
19.0, 19.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c18 : 1
stoichiometry:c19 : 1

m290230*m1719*0.1

nodelay

--

true

0

false

PMID: 18515054 IP3 opens IP3 receptors (IP3R), which permits Ca2+ efflux from ER Ca2+ stores. PMID: 18515054 IP3 binds to IP3 receptors in the ER membrane and causes the release of ER Ca2+ stores

Go back
728.0, 856.0
23.0, 23.0

p8

p8

cso30:i:ME_IonTransportThroughIonChannel

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m20*m3862*0.1

nodelay

--

true

0

false

PMID: 18515054 IP3 opens IP3 receptors (IP3R), which permits Ca2+ efflux from ER Ca2+ stores.

Go back
281.0, 597.0
21.0, 21.0

p9

p9

cso30:i:ME_IonTransportThroughIonChannel

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m23*m22*0.1

nodelay

--

true

0

false

PMID: 18515054 In turn, ER store depletion opens store-operated CRAC channels, which permit sustained Ca2+ influx into the cell

Go back
1468.0, 200.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1202.0, 737.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
686.0, 1382.0

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
632.0, 1369.0

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
681.0, 1318.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
703.0496697522246, 1365.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
712.0, 1373.0

c104

c104

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
681.0, 1310.0

c105

c105

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
708.8570997301327, 1331.0

c106

c106

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
681.0, 1313.0

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
721.9368211420091, 1377.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
751.9137853216664, 1338.7677168938224

c109

c109

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1270.0, 754.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
799.9425724154552, 1383.2905467105793

c110

c110

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
516.8745752222198, 1415.4110510513804

c111

c111

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
500.0, 806.0

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
659.0, 780.0

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
660.0, 780.0

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
658.0, 780.0

c115

c115

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
657.0, 780.0

c116

c116

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
463.0, 1428.108965256439

c117

c117

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
546.7206501967243, 1607.0956050533966

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
641.7743492274631, 1566.0

c119

c119

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1205.7964414929193, 892.7931815433714

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
896.0, 1443.0

c120

c120

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
380.0, 1358.0

c121

c121

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
380.0, 1369.0

c122

c122

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
796.0, 993.0

c123

c123

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
810.8599434057004, 1013.0

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
804.0, 1015.4567140814585

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
809.0, 988.0

c126

c126

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
939.7053735814004, 1028.0

c127

c127

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
868.7201327147385, 978.4591289780632

c128

c128

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
859.7257215188587, 1020.0

c129

c129

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1240.7931034482758, 851.5172413793103

c13

c13

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
845.0, 1025.9876828256433

c130

c130

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
806.9813556589606, 999.9389341484742

c131

c131

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
176.0, 624.0

c132

c132

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
271.0, 777.1295743105569

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
277.37673718523206, 1009.8308615039637

c134

c134

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
278.99979809515395, 1000.0568369314043

c135

c135

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
480.61644797844207, 1009.0

c136

c136

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
390.0, 1093.0

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
404.23607147834645, 1136.0

c138

c138

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
618.0, 1054.0

c139

c139

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1322.9195205871677, 888.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1020.0, 1235.0

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
681.0, 1289.9991090239637

c141

c141

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
832.0, 1303.0

c142

c142

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
839.0, 1295.0

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
390.0, 1075.79887605359

c144

c144

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
468.88477678882543, 1006.0

c145

c145

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
395.9768959417604, 1081.0

c146

c146

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1029.0, 1391.0

c147

c147

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1009.0, 1421.024550284402

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0, 1310.0

c149

c149

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1305.0, 823.0

c15

c15

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1091.0, 1406.1055682552917

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
295.0, 1415.8439794395015

c151

c151

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1086.8757621763357, 1345.0

c152

c152

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1124.0297771955363, 1351.2210402155317

c153

c153

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1100.0, 1489.2564349984868

c154

c154

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
856.8204058946332, 1393.6856012705225

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
295.0, 1341.4447122507459

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
295.0, 1482.0076502083593

c157

c157

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
478.0, 1338.9525537004668

c158

c158

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
478.0, 1480.0830989449873

c159

c159

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1273.9220899170605, 669.0

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
687.0, 1346.5873917245424

c160

c160

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
695.0, 1484.4553107708673

c161

c161

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1327.0, 91.38993690857306

c162

c162

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1379.5162213932392, 81.73978392721297

c163

c163

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1256.9349894126537, 84.0

c164

c164

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1124.3425427071375, 104.99266316654136

c165

c165

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1056.121475197316, 97.0

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1140.8602083542319, 91.48900121828801

c167

c167

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1133.0, 888.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
929.0, 896.3289916300824

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
929.6417282939941, 891.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1572.995328807718, 196.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
758.1654110103356, 877.5576516205163

c20

c20

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
749.5777087639997, 886.1554175279994

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
674.0075650887785, 786.2389335532322

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
188.0, 608.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
302.0, 612.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
308.2790621242674, 555.0

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
889.8421713081511, 592.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
876.0, 636.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
890.8844216113174, 637.0748912964184

c29

c29

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1473.1012274749298, 208.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
973.0, 751.0

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
993.0, 800.0

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1003.8838986192268, 794.3579921066611

c32

c32

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1260.3425427071375, 1011.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1264.0, 1102.0

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1047.0, 875.0

c35

c35

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1140.0, 955.0

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1140.0, 1083.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
604.0, 837.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
604.0, 950.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1320.0, 354.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
621.8649587693047, 863.0

c40

c40

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
560.5777087639997, 837.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
556.0, 938.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
568.7286916054303, 731.0

c43

c43

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1088.490188052155, 955.0

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1086.0, 1073.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1036.0, 875.0

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
889.0, 737.0

c47

c47

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1334.0872722011422, 409.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
535.0, 584.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
462.220185082879, 798.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
529.8856859712906, 601.3348301153176

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
448.0, 853.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
429.0, 628.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
459.0, 994.0

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
600.0, 500.0

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
563.0, 552.0

c58

c58

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
604.0664454253465, 568.7285058907958

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1358.5663617266162, 295.0

c6

c6

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1145.0, 955.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1155.7240799550736, 1100.0

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
554.0, 564.0

c62

c62

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
682.0, 966.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
690.9267498715262, 993.0

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
545.0, 564.0

c65

c65

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
658.1055682552917, 971.0

c66

c66

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
660.0, 1033.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
437.0, 628.0

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
610.0, 837.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1293.0, 576.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
609.9870028021417, 916.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
641.8687808592721, 780.0

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
785.0, 1200.0

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
848.0, 1210.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.969981021959, 1154.0

c74

c74

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0, 1211.3214615475792

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
840.0, 1164.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
893.0, 1272.0

c77

c77

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
908.0, 1328.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.0, 351.0

c79

c79

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1316.0, 596.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
867.0, 439.0

c80

c80

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
732.0, 363.0

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
870.7413184145154, 351.0

c82

c82

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
870.9564336888672, 430.5887550132243

c83

c83

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
576.0, 347.0

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
614.004336304561, 431.9367064067748

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
542.6437975294531, 394.36058453115464

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.0, 347.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
734.0, 511.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
296.0, 372.0

c89

c89

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1317.758472741024, 474.0

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
577.0, 347.0

c90

c90

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
704.0, 548.0

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
288.0, 268.0

c92

c92

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
780.0, 456.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
527.0, 501.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
790.0, 537.0

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
665.0, 544.0384062354069

c96

c96

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
448.62499413715636, 588.0

c97

c97

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
532.0, 1093.0

c98

c98

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
676.0, 1327.0

c99

c99

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back