1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18388328.csml convertedTime:2009.07.01.11:18

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Regulation of endogenous apolipoprotein E secretion by macrophages.
Authors Kockx M, Jessup W, Kritharides L.
Affiliation Macrophage Biology Group, Centre for Vascular Research, Room 405C Wallace WurthBuilding, University of New South Wales, High Street, Kensington, Sydney, NSW2050, Australia.
Abstract Apolipoprotein E has critical roles in the protection against atherosclerosisand is understood to follow the classical constitutive secretion pathway. Recentstudies have indicated that the secretion of apoE from macrophages is aregulated process of unexpected complexity. Cholesterol acceptors such asapolipoprotein A-I, high density lipoprotein, and phospholipid vesicles canstimulate apoE secretion. The ATP binding cassette transporter ABCA1 is involvedin basal apoE secretion and in lipidating apoE-containing particles secreted bymacrophages. However, the stimulation of apoE secretion by apoA-I isABCA1-independent, indicating the existence of both ABCA1-dependent and-independent pathways of apoE secretion. The release of apoE under basalconditions is also regulated, requiring intact protein kinase A activity,intracellular calcium, and an intact microtubular network. Mathematical modelingof apoE turnover indicates that whereas some pools of apoE are committed toeither secretion or degradation, other pools can be diverted from degradationtoward secretion. Targeted inhibition or stimulation of specific apoEtrafficking pathways will provide unique opportunities to regulate the biologyof this important molecule.
PMID 18388328
Model Abstract

Entity

G010197:apoE MO000000047:MEKK1 MO000000049:c-Jun {nuclear} MO000000058:NF-kappaB MO000000132:PLC MO000000276:AP-1 MO000000290:LDL MO000016808:TGFbeta MO000016882:LPS MO000017793:Lp {extracellular} MO000019288:IP3R:IP3 MO000019387:cytokines MO000019479:protein remnants MO000021830:small-molecule hormones MO000034006:oleic acid MO000047193:PPAR-gamma MO000056000:LXR:RXR ligand: LXR:RXR MO000056221:cholesterol MO000061802:LDL receptor MO000062475:APOA1 MO000065296:APOA2 MO000066885:LTF MO000069146:APOA4 MO000069735:HSPG2 MO000090073:ABCA1 MO000113441:ApoE3 {extracellular} e1: e10: e11:oxysterol e12:apo-E e13:apo-E: LXR:RXR e14:lipid e15:PPAR-gamma: apoE-apoC1 intergenic region e16:apoE-apoC1 intergenic region e17:c-Jun: AP-1 e18:Tpl-2 e19:Tpl-2 {activated} e2: e20:MEKK1 {activated} e21:NF-kappaB {activated} e22:c-Jun {activated} e23:c-Jun e24:NF-kappaB {nuclear} e25: e26: e27: e28: e29: e3: e30: e31: e32:Apo-E {ER} e33:Apo-E {golgi} e34: e35: e36: e37:Apo-E {glyT194}{recycling endosomes} e38: e39: e4: e40: e41:Apo-E {early endosome} e42: e43: e44: e45:Apo-E {lysosome} e46: e47: e48: e49:Apo-E {late endosome} e5:Apo-E: LDL receptor e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:Lp e60: e61: e62: e63:preapoE e64:Apo-E{cell surface} e65:Apo-E {glyT194} e66:Apo-E{cell surface}: HSPG2 e67:HDL e68:Apo-E{extracellular} e69:Apo-E{extracellular}: HDL e7: e70:brefeldin A e71:monensin e72:ALLN e73:chloroquine e74:H89 e75:heparinase e76:Apo-E e77:ApoE2 e78:ApoE3 e79:ApoE4 e8: e80:suramin e81:Ca e82:Ca {extracellular} e83:ApoE3 {exogenous} e84:Apo-E {exogenous} e85:synthetic alpha-hecal peptides 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 p6 p7 p8 p9
Model Detail
452.0, 1167.0
30.0, 30.0

apoE

--

G010197

cso30:c:mRNA

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m93187

10

false

infinite

0

unit false false false
TRANSFACG010197

--

Go back
938.0, 1464.0
32.0, 32.0

MEKK1

--

MO000000047

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m44

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000047

--

Go back
509.0, 1329.0
30.0, 30.0

c-Jun {nuclear}

--

MO000000049

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
InterProIPR002112
TRANSPATHMO000000049

--

Go back
760.0, 1344.0
32.0, 32.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16 p17 p21

true true true true

csml-variable:Double

m21

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
833.0, 645.0
30.0, 30.0

PLC

--

MO000000132

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m119

10

false

infinite

0

unit false false false
TRANSPATHMO000000132

--

Go back
540.0, 1292.0
28.0, 28.0

AP-1

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
1300.0, 628.0
32.5, 32.5

LDL

--

MO000000290

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p41

true true true true

csml-variable:Double

m290118

10

false

infinite

0

unit false false false
TRANSPATHMO000000290

--

Go back
257.0, 1293.0
30.0, 30.0

TGFbeta

--

MO000016808

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m1746

10

false

infinite

0

unit false false false
TRANSPATHMO000016808

--

Go back
794.0, 1606.0
28.0, 28.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p14

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
4.0, 352.0
32.0, 32.0

Lp {extracellular}

--

MO000017793

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m2549

10

false

infinite

0

unit false false false
TRANSPATHMO000017793

--

Go back
819.0, 287.0
34.0, 34.0

IP3R:IP3

--

MO000019288

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m3862

10

false

infinite

0

unit false false false
TRANSPATHMO000019288

--

Go back
258.0, 1210.0
28.0, 28.0

cytokines

--

MO000019387

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5 p40

true true true true

csml-variable:Double

m3957

10

false

infinite

0

unit false false false
TRANSPATHMO000019387

--

Go back
659.0, 863.0
28.0, 28.0

protein remnants

--

MO000019479

cso30:c:Protein

cso30:i:CC_CellComponent

--

p30

--

true true true true

csml-variable:Double

m360980

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
258.0, 1246.0
28.0, 28.0

small-molecule hormones

--

MO000021830

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m6165

10

false

infinite

0

unit false false false
EnsemblENSG00000035862
TRANSPATHMO000021830

--

Go back
919.0, 879.0
33.5, 33.5

oleic acid

--

MO000034006

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m349132

10

false

infinite

0

unit false false false
TRANSPATHMO000034006

--

Go back
416.0, 980.0
24.0, 24.0

PPAR-gamma

--

MO000047193

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m357146

10

false

infinite

0

unit false false false
TRANSFACT09963
TRANSPATHMO000047193

--

Go back
360.0, 1032.0
32.0, 32.0

LXR:RXR ligand: LXR:RXR

--

MO000056000

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8 p38

true true true true

csml-variable:Double

m31324

10

false

infinite

0

unit false false false
TRANSPATHMO000056000

--

Go back
265.0, 1125.0
30.0, 30.0

cholesterol

--

MO000056221

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p39

true true true true

csml-variable:Double

m360460

10

false

infinite

0

unit false false false
TRANSPATHMO000056221

--

Go back
144.0, 284.0
32.0, 32.0

LDL receptor

--

MO000061802

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m36695

10

false

infinite

0

unit false false false
TRANSPATHMO000061802

--

Go back
1309.0, 841.0
30.0, 30.0

APOA1

--

MO000062475

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p30 p31

true true true true

csml-variable:Double

m37363

10

false

infinite

0

unit false false false
TRANSPATHMO000062475

--

Go back
829.0, 601.0
30.0, 30.0

APOA2

--

MO000065296

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m40163

10

false

infinite

0

unit false false false
TRANSPATHMO000065296

--

Go back
821.0, 461.0
30.0, 30.0

LTF

--

MO000066885

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p46

true true true true

csml-variable:Double

m41742

10

false

infinite

0

unit false false false
TRANSPATHMO000066885

--

Go back
829.0, 561.0
30.0, 30.0

APOA4

--

MO000069146

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p43

true true true true

csml-variable:Double

m43990

10

false

infinite

0

unit false false false
TRANSPATHMO000069146

--

Go back
1067.0, 363.0
28.0, 28.0

HSPG2

--

MO000069735

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m44578

10

false

infinite

0

unit false false false
TRANSPATHMO000069735

--

Go back
612.0, 360.0
32.0, 32.0

ABCA1

--

MO000090073

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m63632

10

false

infinite

0

unit false false false
TRANSPATHMO000090073

--

Go back
434.0, 222.0
28.0, 28.0

ApoE3 {extracellular}

--

MO000113441

cso30:c:Protein

cso30:i:CC_CellComponent

--

p47 p48 p49

--

true true true true

csml-variable:Double

m355280

10

false

infinite

0

unit false false false
Affymetrix203381_s_at
EnsemblENSG00000130203
HGNCAPOE
OMIM104310
ProteomeHumanPSD/APOE
RefSeqNM_000041
TRANSPATHMO000113441
UnigeneHs.654439
UniProtP02649

--

Go back
67.1410783537019, 283.71144056356525
999.8925357855506, 1302.4252751757435

--

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
139.98525988802712, 434.4084784598021
860.6268872177197, 1086.0631520683394

--

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
253.5, 1173.125
36.52344536123969, 22.522791306097805

oxysterol

--

e11

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p4

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
473.5, 1043.125
45.0, 9.75

apo-E

--

e12

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p8

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
441.5, 1081.625
45.0, 12.75

apo-E: LXR:RXR

--

e13

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p8

p7

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
255.5, 1084.25
41.34146341463414, 23.426829268292682

lipid

--

e14

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p7

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
545.5, 1069.625
45.0, 12.75

PPAR-gamma: apoE-apoC1 intergenic region

--

e15

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
569.5, 1027.125
45.0, 9.75

apoE-apoC1 intergenic region

--

e16

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p9

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
524.625, 1237.5
29.8993084485919, 36.61139810031661

c-Jun: AP-1

--

e17

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
934.5, 1318.125
33.11833366874623, 20.422972429060174

Tpl-2

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p13

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
939.5, 1382.125
33.11833366874623, 20.422972429060174

Tpl-2 {activated}

--

e19

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
67.1410783537019, 283.71144056356525
999.8925357855506, 1302.4252751757435

--

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
938.0, 1424.0
32.0, 32.0

MEKK1 {activated}

--

e20

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m20

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000047

--

Go back
759.0, 1387.0
32.0, 32.0

NF-kappaB {activated}

--

e21

cso30:c:Protein

cso30:i:CC_CellComponent

--

p16 p17

--

true true true true

csml-variable:Double

m22

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
704.0, 1439.0
30.0, 30.0

c-Jun {activated}

--

e22

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m23

10

false

infinite

0

unit false false false
InterProIPR002112
TRANSPATHMO000000049

--

Go back
704.0, 1475.0
30.0, 30.0

c-Jun

--

e23

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p18 p19

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
InterProIPR002112
TRANSPATHMO000000049

--

Go back
692.0, 1260.0
32.0, 32.0

NF-kappaB {nuclear}

--

e24

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m25

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
850.3245687164281, 1073.9693719980673
115.38896520363622, 32.47702663016251

--

e25

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_ExtrinsicToInternalSideOfMembrane_

--

--

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false true false

--

Go back
850.7066513826653, 1074.3514546643046
114.62479987116178, 31.712861297688114

--

e26

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulumLumen

--

--

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false true false

--

Go back
848.6051967183606, 1072.25
118.82770919977101, 35.915770626297416

--

e27

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_IntegralToMembrane_

--

--

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false true false

--

Go back
848.6051967183606, 1072.25
118.82770919977101, 35.915770626297416

--

e28

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_Membrane_

--

--

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false true false

--

Go back
849.7514447170722, 1073.3962479987117
116.53521320234788, 33.623274628874135

--

e29

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum

--

--

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false true false

--

Go back
87.13892906941292, 301.65118264587585
959.8968343541283, 1266.545791011124

--

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
848.6051967183606, 1072.25
118.82770919977101, 35.915770626297416

--

e30

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndoplasmicReticulum_ExtrinsicToExternalSideOfMembrane_

--

--

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false true false

--

Go back
807.0, 936.0
130.93491124260356, 54.556213017751475

--

e31

cso30:c:EntityBiologicalCompartment

cso30:i:CC_GolgiApparatus

--

--

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false true false

--

Go back
925.0, 1077.0
30.0, 30.0

Apo-E {ER}

--

e32

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m33

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
825.0, 956.0
30.0, 30.0

Apo-E {golgi}

--

e33

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m34

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
725.0, 618.0
45.315419187225935, 75.65370830409756

--

e34

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false true false

--

Go back
725.0, 618.0
45.315419187225935, 75.65370830409756

--

e35

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false true false

--

Go back
725.0, 618.0
45.315419187225935, 75.65370830409756

--

e36

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false true false

--

Go back
837.5, 741.125
39.72, 29.789999999999996

Apo-E {glyT194}{recycling endosomes}

--

e37

cso30:c:Protein

cso30:i:CC_GolgiApparatus

--

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
838.0, 710.0
45.315419187225935, 75.65370830409756

--

e38

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false true false

--

Go back
838.0, 710.0
45.315419187225935, 75.65370830409756

--

e39

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false true false

--

Go back
124.13495289347838, 333.0457312899192
885.9047867059975, 1203.7566937230354

--

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
838.0, 710.0
45.315419187225935, 75.65370830409756

--

e40

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false true false

--

Go back
729.0, 413.0
30.0, 30.0

Apo-E {early endosome}

--

e41

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
747.0, 776.5
58.33272167368041, 54.61865325250979

--

e42

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Lysosome

--

--

--

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false true false

--

Go back
747.0, 776.5
58.33272167368041, 54.61865325250979

--

e43

cso30:c:EntityBiologicalCompartment

cso30:i:CC_LysosomalLumen

--

--

--

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false true false

--

Go back
747.0, 776.5
58.33272167368041, 54.61865325250979

--

e44

cso30:c:EntityBiologicalCompartment

cso30:i:CC_LysosomalMembrane

--

--

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false true false

--

Go back
761.0, 789.0
30.0, 30.0

Apo-E {lysosome}

--

e45

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m48

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
725.0, 394.0
45.315419187225935, 75.65370830409756

--

e46

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false true false

--

Go back
725.0, 394.0
45.315419187225935, 75.65370830409756

--

e47

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false true false

--

Go back
725.0, 394.0
45.315419187225935, 75.65370830409756

--

e48

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false true false

--

Go back
729.0, 641.0
30.0, 30.0

Apo-E {late endosome}

--

e49

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m65

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
88.5, 294.0
30.195300783202793, 36.97383769371771

Apo-E: LDL receptor

--

e5

cso30:c:Complex

cso30:i:CC_Cytosol

--

p1

p2

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
311.42594666782935, 984.2626351674814
515.1488829284992, 419.10255730226925

--

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
367.06586325973433, 994.1947564962621
301.2229967216924, 406.1938543052795

--

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
318.1411090151282, 989.8564064661768
501.7185582339019, 407.9150147048781

--

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
319.1004179218853, 990.7169866659762
499.79994042038766, 406.1938543052795

--

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
311.42594666782935, 984.2626351674814
515.1488829284992, 419.10255730226925

--

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
311.42594666782935, 984.2626351674814
515.1488829284992, 419.10255730226925

--

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
319.1004179218853, 990.7169866659762
499.79994042038766, 406.1938543052795

--

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
687.4750381165661, 1156.3786751273456
32.18367171773675, 26.136251979947556

--

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
603.0558543219522, 1276.8599030992505
91.13434614191327, 74.00989718274165

--

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
311.42594666782935, 984.2626351674814
515.1488829284992, 419.10255730226925

--

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
184.0, 352.0
32.0, 32.0

Lp

--

e6

cso30:c:Protein

cso30:i:CC_CellComponent

--

p2

--

true true true true

csml-variable:Double

m6

10

false

infinite

0

unit false false false
TRANSPATHMO000017793

--

Go back
432.8436398308235, 1170.50834855967
16.314008190573162, 7.046494820990933

--

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
432.29886891920916, 1149.4940335289511
55.83901844047714, 90.16607263180428

--

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
455.7240181186294, 1208.138633614678
8.716334585830575, 7.819280011430179

--

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
865.5, 1085.125
36.24572348561079, 22.351529482793318

preapoE

--

e63

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
1065.5, 410.125
45.0, 33.75

Apo-E{cell surface}

--

e64

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
892.5, 948.125
39.72, 29.789999999999996

Apo-E {glyT194}

--

e65

cso30:c:Protein

cso30:i:CC_GolgiApparatus

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
1066.625, 298.5
36.75, 45.0

Apo-E{cell surface}: HSPG2

--

e66

cso30:c:Complex

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
1145.5, 215.25
45.0, 25.5

HDL

--

e67

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p30 p35 p37

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
1144.5, 286.125
45.0, 33.75

Apo-E{extracellular}

--

e68

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
989.625, 205.5
36.75, 45.0

Apo-E{extracellular}: HDL

--

e69

cso30:c:Complex

cso30:i:CC_Extracellular

--

p35

--

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
65.32645461441265, 286.5049493910472
870.7329285010466, 1106.8270766630915

--

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
1149.5, 891.25
45.0, 25.5

brefeldin A

--

e70

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
1149.5, 563.25
45.0, 25.5

monensin

--

e71

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
571.5, 813.25
39.70142977291842, 22.497476871320437

ALLN

--

e72

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p30

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
572.5, 775.25
41.54331370899916, 23.541211101766187

chloroquine

--

e73

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p30

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
1169.0, 681.0
37.94785534062237, 21.503784693019345

H89

--

e74

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
1151.0, 495.5
32.64, 24.479999999999997

heparinase

--

e75

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p45

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
825.0, 525.0
30.0, 30.0

Apo-E

--

e76

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p44

true true true true

csml-variable:Double

m79

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
509.5, 227.125
29.00080499094385, 17.883829744415372

ApoE2

--

e77

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p48

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
434.0, 378.0
28.0, 28.0

ApoE3

--

e78

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p47 p48 p49

true true true true

csml-variable:Double

m81

10

false

infinite

0

unit false false false
Affymetrix203381_s_at
EnsemblENSG00000130203
HGNCAPOE
OMIM104310
ProteomeHumanPSD/APOE
RefSeqNM_000041
TRANSPATHMO000113441
UnigeneHs.654439
UniProtP02649

--

Go back
365.0, 233.0
30.0, 30.0

ApoE4

--

e79

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p49

true true true true

csml-variable:Double

m82

10

false

infinite

0

unit false false false
Affymetrix203381_s_at
EnsemblENSG00000130203
HGNCAPOE
OMIM104310
ProteomeHumanPSD/APOE
RefSeqNM_000041
TRANSPATHMO000114092
UnigeneHs.654439
UniProtP02649

--

Go back
68.43723816747993, 306.0393777586186
835.3044737646837, 1088.0385843102542

--

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
209.5, 207.25
45.0, 25.5

suramin

--

e80

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1 p25

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
720.875, 360.5
29.902026549922326, 30.408840559243053

Ca

--

e81

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p50 p51

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false false false

--

Go back
725.875, 214.5
29.902026549922326, 30.408840559243053

Ca {extracellular}

--

e82

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p50 p51

--

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false false false

--

Go back
466.0, 170.0
28.0, 28.0

ApoE3 {exogenous}

--

e83

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p47

true true true true

csml-variable:Double

m86

10

false

infinite

0

unit false false false
Affymetrix203381_s_at
EnsemblENSG00000130203
HGNCAPOE
OMIM104310
ProteomeHumanPSD/APOE
RefSeqNM_000041
TRANSPATHMO000113441
UnigeneHs.654439
UniProtP02649

--

Go back
630.0, 219.0
30.0, 30.0

Apo-E {exogenous}

--

e84

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m87

10

false

infinite

0

unit false false false
TRANSPATHMO000067564

--

Go back
1148.5, 957.25
38.212783851976454, 21.65391084945332

synthetic alpha-hecal peptides

--

e85

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p52

true true true true

csml-variable:Double

m88

0

false

infinite

0

unit false false false

--

Go back
162.79767261052044, 325.57380612619
831.4908506487152, 1073.7692309148258

--

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
148.0, 208.0
23.0, 23.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c172 : 1
stoichiometry:c1 : 1
stoichiometry:c3 : 1

m36695*m67*0.1

nodelay

--

true

0

false

PMID: 18388328 As a constituent of plasma lipopoproteins, apoE directs movement of lipids from the periphery to the liver, where high affinity binding of apoE to the LDL receptor and other members of the LDL-receptor family facilitates uptake of the lipoprotein particles. PMID: 18388328, 10357834, 9541497 Cell surface apoE can also be bound to lipoprotein receptors, such that antiserum to the LDL receptor (LDLr) and suramin (which blocks ligand binding to the LDL-receptor related protein LRP) can reduce sequestration on the macrophage surface and increase apoE secretion.

Go back
504.0, 1096.0
23.0, 23.0

p10

p10

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m15*0.1

nodelay

--

true

0

false

PMID: 18388328, 11439103 Regulation of apoE transcription by PPARgamma is mediated via a PPRE element present in the intergenic region between the apoE and apoC1 genes, which is also well outside the proximal promoter. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.

Go back
432.0, 1292.0
27.0, 27.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1

m1746*m219*m46*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

Go back
455.0, 1243.0
25.0, 25.0

p12

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m17*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.

Go back
866.0, 1314.0
27.0, 27.0

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c36 : 1
stoichiometry:c37 : 1

m155666*m18*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

Go back
869.0, 1467.0
25.0, 25.0

p14

p14

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m155666*m44*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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527.0, 1191.0
25.0, 25.0

p15

p15

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c40 : 1

m25*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.

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821.0, 1387.0
27.0, 27.0

p16

p16

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c44 : 1
stoichiometry:c42 : 1

m21*m20*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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822.0, 1348.0
25.0, 25.0

p17

p17

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c43 : 1
stoichiometry:c39 : 1

m21*m19*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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775.0, 1442.0
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:c47 : 1
stoichiometry:c49 : 1
stoichiometry:c48 : 1

m24*m19*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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774.0, 1477.0
25.0, 25.0

p19

p19

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c50 : 1
stoichiometry:c46 : 1

m24*m20*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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89.0, 353.0
29.0, 29.0

p2

p2

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

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

m2549*m5*0.1

nodelay

--

true

0

false

PMID: 18388328 As a constituent of plasma lipopoproteins, apoE directs movement of lipids from the periphery to the liver, where high affinity binding of apoE to the LDL receptor and other members of the LDL-receptor family facilitates uptake of the lipoprotein particles.

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587.0, 1371.0
25.0, 25.0

p20

p20

cso30:i:ME_Translocation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m23*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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696.0, 1340.0
24.0, 24.0

p21

p21

cso30:i:ME_Translocation

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m21*0.1

nodelay

--

true

0

false

PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.

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869.0, 1169.0
29.0, 29.0

p22

p22

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m93187*0.1

nodelay

--

true

0

false

PMID: 18388328 Secretion via tubular and vesicular transport from the Golgi (G), after transport to the Golgi from the endoplasmic reticulum (ER). PMID: 18388328, 6325438 ApoE is synthesized as a 38 500 Mr protein designated preapoE, containing a NH2-terminal 18-AA extension23 which mediates entry into the ER.

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826.0, 1017.0
27.0, 27.0

p23

p23

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c87 : 1
stoichiometry:c59 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 18388328 Secretion via tubular and vesicular transport from the Golgi (G), after transport to the Golgi from the endoplasmic reticulum (ER). PMID: 18388328, 6286633, 2498325 After cleavage of the signal peptide in the ER, the protein is trafficked to the Golgi, where apoE is O-glycosylated on threonine 194 and extensively sialylated. PMID: 18388328, 8576639 Brefeldin A, which perturbs ER to Golgi transport, inhibits apoE degradation and causes intracellular accumulation of unglycosylated apoE with lower molecular weight.

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842.0, 886.0
27.0, 27.0

p24

p24

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m68*0.1

nodelay

--

true

0

false

PMID: 18388328 Secretion via recycling endosomes (RE). PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE.

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1151.0, 352.0
27.0, 27.0

p25

p25

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c171 : 1
stoichiometry:c173 : 1
stoichiometry:c74 : 1

m67*m83*0.1

nodelay

--

true

0

false

PMID: 18388328 Secretion via recycling endosomes (RE). PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328 Secretion of apoE (or displacement of cell surface apoE), releases apoE into extracellular medium. PMID: 18388328, 10671508 Cell surface pools may be reinternalized and subsequently degraded (Figure 1, pathways 3 and 4), or transported to the Golgi network for further modification22 (Figure 1, pathways 3 and 5), or released into the extracellular medium (Figure 1, pathway 3, 2, and 6). PMID: 18388328, 8662812 Increased secretion when proteoglycan synthesis is inhibited suggests that cell surface binding can sequester apoE and inhibit its secretion. PMID: 18388328, 10357834, 9541497 Cell surface apoE can also be bound to lipoprotein receptors, such that antiserum to the LDL receptor (LDLr) and suramin (which blocks ligand binding to the LDL-receptor related protein LRP) can reduce sequestration on the macrophage surface and increase apoE secretion.

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819.0, 415.0
25.0, 25.0

p26

p26

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c65 : 1

m67*0.1

nodelay

--

true

0

false

PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 10671508 Cell surface pools may be reinternalized and subsequently degraded (Figure 1, pathways 3 and 4), or transported to the Golgi network for further modification22 (Figure 1, pathways 3 and 5), or released into the extracellular medium (Figure 1, pathway 3, 2, and 6).

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730.0, 546.0
27.0, 27.0

p27

p27

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m42*0.1

nodelay

--

true

0

false

PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE.

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762.0, 730.0
27.0, 27.0

p28

p28

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1

m65*0.1

nodelay

--

true

0

false

PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE.

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762.0, 886.0
27.0, 27.0

p29

p29

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m48*0.1

nodelay

--

true

0

false

PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328, 10671508 Cell surface pools may be reinternalized and subsequently degraded (Figure 1, pathways 3 and 4), or transported to the Golgi network for further modification22 (Figure 1, pathways 3 and 5), or released into the extracellular medium (Figure 1, pathway 3, 2, and 6).

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399.0, 1126.0
23.0, 23.0

p3

p3

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m360460*0.1

nodelay

--

true

0

false

PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.

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660.0, 792.0
24.0, 24.0

p30

p30

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c91 : 1
stoichiometry:c92 : 1
stoichiometry:c88 : 1
stoichiometry:c94 : 1
stoichiometry:c96 : 1
stoichiometry:c73 : 1

m48*0.1

nodelay

--

true

0

false

PMID: 18388328 Degradation of apoE in lysosomes or proteasomes (Lys/P), probably via late endosomes (LE). PMID: 18388328, 8576639 Brefeldin A, which perturbs ER to Golgi transport, inhibits apoE degradation and causes intracellular accumulation of unglycosylated apoE with lower molecular weight. PMID: 18388328, 8473293, 9388269 Degradation of apoE is inhibited by ALLN, an inhibitor of Ca2+ dependent proteases, in HepG2 cells, macrophages, and CHO cells expressing apoE. PMID: 18388328, 8576639 Concentrations of the lysosomal inhibitor chloroquine, which effectively inhibited apoE degradation (25 to 100 ?mol/L), did not stimulate apoE secretion. PMID: 18388328, 15066991, 2072040, 1730636 However, as a number of studies have shown that stimulation of apoE secretion by HDL and apoA-I decreases net degradation of apoE, it is likely that there are other "uncommitted" pools of apoE otherwise destined for degradation which can be redirected to secretion. PMID: 18388328, 15066991 ApoA-I stimulates secretion and decreases degradation of Em without affecting Es.

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994.0, 758.0
27.0, 27.0

p31

p31

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c89 : 1
stoichiometry:c90 : 1
stoichiometry:c95 : 1
stoichiometry:c97 : 1
stoichiometry:c196 : 1
stoichiometry:c209 : 1
stoichiometry:c64 : 1

m38*m37363*0.1

nodelay

--

true

0

false

PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 15066991 ApoA-I stimulates secretion and decreases degradation of Em without affecting Es. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328 As H89 is less effective at inhibiting apoA-I?induced apoE secretion than it is at inhibiting constitutive apoE secretion, a second, PKA-independent route of secretion of Em2 is also proposed. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

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897.0, 1016.0
30.0, 30.0

p32

p32

cso30:i:ME_O-Glycosylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m34*0.1

nodelay

--

true

0

false

PMID: 18388328, 6286633, 2498325 After cleavage of the signal peptide in the ER, the protein is trafficked to the Golgi, where apoE is O-glycosylated on threonine 194 and extensively sialylated.

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900.0, 1132.0
31.0, 31.0

p33

p33

cso30:i:ME_ProteinCleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m66*0.1

nodelay

--

true

0

false

PMID: 18388328, 6286633, 2498325 After cleavage of the signal peptide in the ER, the protein is trafficked to the Golgi, where apoE is O-glycosylated on threonine 194 and extensively sialylated.

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1158.0, 414.0
27.0, 27.0

p34

p34

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m67*m44578*0.1

nodelay

--

true

0

false

PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans.

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1070.0, 214.0
28.0, 28.0

p35

p35

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m71*m70*0.1

nodelay

--

true

0

false

PMID: 18388328, 15131109 These posttranslational modifications of apoE do not appear to affect receptor binding or lipoprotein clearance but may determine the preferential association with high density lipoprotein (HDL) particles.

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1003.0, 843.0
25.0, 25.0

p36

p36

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c83 : 1
stoichiometry:c103 : 1
stoichiometry:c105 : 1
stoichiometry:c107 : 1
stoichiometry:c198 : 1
stoichiometry:c211 : 1
stoichiometry:c101 : 1

m38*m349132*0.1

nodelay

--

true

0

false

PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans. PMID: 18388328, 15131109 This is supported by other studies showing that oleic acid stimulates secretion of macrophage apoE while apparently reducing its sialylation. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328 As H89 is less effective at inhibiting apoA-I?induced apoE secretion than it is at inhibiting constitutive apoE secretion, a second, PKA-independent route of secretion of Em2 is also proposed. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

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995.0, 795.0
25.0, 25.0

p37

p37

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c93 : 1
stoichiometry:c102 : 1
stoichiometry:c104 : 1
stoichiometry:c106 : 1
stoichiometry:c197 : 1
stoichiometry:c210 : 1
stoichiometry:c99 : 1

m38*m70*0.1

nodelay

--

true

0

false

PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 15066991, 2072040, 1730636 However, as a number of studies have shown that stimulation of apoE secretion by HDL and apoA-I decreases net degradation of apoE, it is likely that there are other "uncommitted" pools of apoE otherwise destined for degradation which can be redirected to secretion. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328 As H89 is less effective at inhibiting apoA-I?induced apoE secretion than it is at inhibiting constitutive apoE secretion, a second, PKA-independent route of secretion of Em2 is also proposed. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

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997.0, 729.0
21.0, 21.0

p38

p38

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c119 : 1
stoichiometry:c128 : 1
stoichiometry:c129 : 1
stoichiometry:c130 : 1
stoichiometry:c195 : 1
stoichiometry:c208 : 1
stoichiometry:c109 : 1

m38*m31324*0.1

nodelay

--

true

0

false

PMID: 18388328, 11149950, 3624230, 1466652 As distinct from factors that increase apoE secretion by stimulating its synthesis (eg, LXR/RXR ligands, cholesterol enrichment, cytokines, a number of agents have been shown to directly increase apoE secretion (independent of transcription). PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

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995.0, 695.0
26.0, 26.0

p39

p39

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c120 : 1
stoichiometry:c131 : 1
stoichiometry:c132 : 1
stoichiometry:c133 : 1
stoichiometry:c194 : 1
stoichiometry:c207 : 1
stoichiometry:c111 : 1

m38*m360460*0.1

nodelay

--

true

0

false

PMID: 18388328, 11149950, 3624230, 1466652 As distinct from factors that increase apoE secretion by stimulating its synthesis (eg, LXR/RXR ligands, cholesterol enrichment, cytokines, a number of agents have been shown to directly increase apoE secretion (independent of transcription). PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

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391.0, 1170.0
23.0, 23.0

p4

p4

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.

Go back
994.0, 662.0
26.0, 26.0

p40

p40

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c121 : 1
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c136 : 1
stoichiometry:c193 : 1
stoichiometry:c206 : 1
stoichiometry:c113 : 1

m38*m3957*0.1

nodelay

--

true

0

false

PMID: 18388328, 11149950, 3624230, 1466652 As distinct from factors that increase apoE secretion by stimulating its synthesis (eg, LXR/RXR ligands, cholesterol enrichment, cytokines, a number of agents have been shown to directly increase apoE secretion (independent of transcription). PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
997.0, 633.0
21.0, 21.0

p41

p41

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c118 : 1
stoichiometry:c144 : 1
stoichiometry:c150 : 1
stoichiometry:c156 : 1
stoichiometry:c192 : 1
stoichiometry:c205 : 1
stoichiometry:c115 : 1

m38*m290118*0.1

nodelay

--

true

0

false

PMID: 18388328, 9388269, 1400506 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
996.0, 604.0
23.0, 23.0

p42

p42

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c127 : 1
stoichiometry:c145 : 1
stoichiometry:c151 : 1
stoichiometry:c157 : 1
stoichiometry:c191 : 1
stoichiometry:c204 : 1
stoichiometry:c117 : 1

m38*m40163*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 17303773, 9869653 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 15066991 Stimulation of apoE secretion is a general property of {alpha}-helix containing molecules including apoA-II, A-IV, and apoE. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
996.0, 564.0
23.0, 23.0

p43

p43

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1
stoichiometry:c126 : 1
stoichiometry:c146 : 1
stoichiometry:c152 : 1
stoichiometry:c158 : 1
stoichiometry:c190 : 1
stoichiometry:c203 : 1
stoichiometry:c123 : 1

m38*m43990*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 17303773, 9869653 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 15066991 Stimulation of apoE secretion is a general property of {alpha}-helix containing molecules including apoA-II, A-IV, and apoE. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
996.0, 528.0
23.0, 23.0

p44

p44

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c142 : 1
stoichiometry:c147 : 1
stoichiometry:c153 : 1
stoichiometry:c159 : 1
stoichiometry:c189 : 1
stoichiometry:c202 : 1
stoichiometry:c125 : 1

m38*m79*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 17303773, 9869653 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 15066991 Stimulation of apoE secretion is a general property of {alpha}-helix containing molecules including apoA-II, A-IV, and apoE. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
996.0, 496.0
23.0, 23.0

p45

p45

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c141 : 1
stoichiometry:c148 : 1
stoichiometry:c154 : 1
stoichiometry:c160 : 1
stoichiometry:c188 : 1
stoichiometry:c201 : 1
stoichiometry:c138 : 1

m38*m78*0.1

nodelay

--

true

0

false

PMID: 18388328, 9488694, 8662812, 10671508 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
996.0, 464.0
23.0, 23.0

p46

p46

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c143 : 1
stoichiometry:c149 : 1
stoichiometry:c155 : 1
stoichiometry:c161 : 1
stoichiometry:c187 : 1
stoichiometry:c200 : 1
stoichiometry:c140 : 1

m38*m41742*0.1

nodelay

--

true

0

false

PMID: 18388328, 9488694, 8662812, 10671508 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
434.0, 302.0
27.0, 27.0

p47

p47

cso30:i:ME_Translocation

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c162 : 1
stoichiometry:c165 : 1
stoichiometry:c163 : 1

m81*m86*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 10441097 Exogenous apoE4 is less effective at stimulating apoE3 secretion from macrophages than are apoE3 and apoE2, which may be relevant for the increased atherosclerotic risk associated with the apoE4 phenotype.

Go back
512.0, 304.0
23.0, 23.0

p48

p48

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c164 : 1
stoichiometry:c167 : 1
stoichiometry:c166 : 1

m81*m80*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 10441097 Exogenous apoE4 is less effective at stimulating apoE3 secretion from macrophages than are apoE3 and apoE2, which may be relevant for the increased atherosclerotic risk associated with the apoE4 phenotype.

Go back
367.0, 303.0
25.0, 25.0

p49

p49

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

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

m81*m82*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 10441097 Exogenous apoE4 is less effective at stimulating apoE3 secretion from macrophages than are apoE3 and apoE2, which may be relevant for the increased atherosclerotic risk associated with the apoE4 phenotype.

Go back
395.0, 1206.0
24.0, 24.0

p5

p5

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c12 : 1

m3957*0.1

nodelay

--

true

0

false

PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.

Go back
726.0, 283.0
25.0, 25.0

p50

p50

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c176 : 1
stoichiometry:c175 : 1

m84*m67*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991, 6823554 Although the pathways stimulating apoE secretion and cholesterol efflux are distinct, apoE, whether added to cells or during its secretion from cells, can itself mediate cholesterol efflux.

Go back
684.0, 285.0
25.0, 25.0

p51

p51

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c177 : 1
stoichiometry:c179 : 1
stoichiometry:c180 : 1
stoichiometry:c178 : 1

m84*m87*m63632*0.1

nodelay

--

true

0

false

PMID: 18388328, 16254198 There is evidence to suggest that exogenous apoE removes cholesterol via an ABCA1-mediated pathway, whereas secreted apoE may also remove cholesterol in an ABCA1-independent manner.

Go back
1008.0, 888.0
23.0, 23.0

p52

p52

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c181 : 1
stoichiometry:c183 : 1
stoichiometry:c184 : 1
stoichiometry:c185 : 1
stoichiometry:c186 : 1
stoichiometry:c199 : 1
stoichiometry:c212 : 1
stoichiometry:c182 : 1

m38*m88*0.1

nodelay

--

true

0

false

PMID: 18388328, 15066991 Additionally, a range of synthetic alpha-helical peptides which stimulated apoE secretion to an extent similar to intact apoA-I were incapable of stimulating cholesterol efflux. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.

Go back
403.0, 1242.0
23.0, 23.0

p6

p6

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m6165*0.1

nodelay

--

true

0

false

PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.

Go back
455.0, 1118.0
23.0, 23.0

p7

p7

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m13*m14*0.1

nodelay

--

true

0

false

PMID: 18388328 The LXR/RXR heterodimer regulates apoE transcription in response to lipids through interaction with conserved LXR response elements in the multienhancer regions. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.

Go back
412.0, 1035.0
25.0, 25.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m31324*m12*0.1

nodelay

--

true

0

false

PMID: 18388328 The LXR/RXR heterodimer regulates apoE transcription in response to lipids through interaction with conserved LXR response elements in the multienhancer regions.

Go back
512.0, 980.0
23.0, 23.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c24 : 1
stoichiometry:c22 : 1

m357146*m16*0.1

nodelay

--

true

0

false

PMID: 18388328, 11439103 Regulation of apoE transcription by PPARgamma is mediated via a PPRE element present in the intergenic region between the apoE and apoC1 genes, which is also well outside the proximal promoter.

Go back
160.04241162526887, 127.64148313501323

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
422.0, 1147.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.0, 769.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1018.0, 451.8895422878879

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1019.3129483791348, 589.0

c102

c102

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1024.9519015594249, 589.0

c103

c103

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1023.371902879898, 703.0

c104

c104

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1030.8956272457326, 703.0

c105

c105

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1023.4531871764764, 817.0187863493246

c106

c106

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1031.8278336357143, 861.1609003649297

c107

c107

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
877.0, 741.8616253494672

c108

c108

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1011.0, 451.74981393081725

c109

c109

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
414.0, 1182.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.0, 714.4522509287157

c110

c110

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1012.0, 451.6979515464329

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.0, 685.7927985842801

c112

c112

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1011.0, 451.60673253838905

c113

c113

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.0, 656.7656612617058

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1012.0, 451.50199008578966

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
873.0, 632.4381173212795

c116

c116

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1013.0, 451.3626473476678

c117

c117

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1026.0, 644.0

c118

c118

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
23.62926490700727, 740.0002840621694

c119

c119

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
419.0, 1195.1464137287467

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
59.63853800935567, 707.5312882165762

c120

c120

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
92.47445754707144, 671.8942029107254

c121

c121

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
869.0, 593.1131089024344

c122

c122

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1014.0, 451.0343357322942

c123

c123

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
867.0, 557.5538553641524

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1017.0, 450.5465242812604

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
859.0, 576.0

c126

c126

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
859.0, 616.0

c127

c127

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1020.8284271247462, 589.0

c128

c128

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1021.866634540471, 697.0

c129

c129

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
286.0, 1254.3415685835566

c13

c13

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1020.8284271247462, 752.8284271247462

c130

c130

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1024.1121980852033, 589.0

c131

c131

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1024.9846577513015, 694.0

c132

c132

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1021.5642883534224, 724.0699226766325

c133

c133

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1023.4368969581915, 589.0

c134

c134

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1023.9824591959602, 676.3741907969359

c135

c135

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1018.3460392486073, 691.2397684861721

c136

c136

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
866.0, 525.8353715109598

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1019.0, 449.71047007950585

c138

c138

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
865.0, 494.0410966961658

c139

c139

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
424.0, 1203.51964259655

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1019.0, 445.09444140075664

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1027.0, 508.0

c141

c141

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
855.0, 540.0

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
851.0, 476.0

c143

c143

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1016.1391903733912, 657.3799207899581

c144

c144

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1015.9859719718607, 630.4721629176903

c145

c145

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1015.7888543819998, 590.5777087639997

c146

c146

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1014.6414587093152, 554.6476860207005

c147

c147

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1014.5299921576491, 522.6958252119834

c148

c148

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1013.4328186096214, 490.73457237604555

c149

c149

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
392.0, 1048.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1021.866634540471, 648.0242740504559

c150

c150

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1022.6879284224294, 622.5489299374203

c151

c151

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1022.3618364740742, 585.1674998319688

c152

c152

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1022.0535451414764, 551.5837689658647

c153

c153

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1021.7928536025216, 521.8635587570159

c154

c154

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1019.5638496415246, 490.07028907688743

c155

c155

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1021.6923076923077, 585.0

c156

c156

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1022.8857480191602, 581.0

c157

c157

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1023.0, 576.0

c158

c158

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1022.9054484373686, 542.8645649212496

c159

c159

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
445.0, 1048.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1022.6981274768032, 514.5244189599036

c160

c160

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1022.4207913262161, 485.0732068643734

c161

c161

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
448.0, 337.0

c162

c162

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
448.0, 258.0

c163

c163

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
462.0, 332.65685424949237

c164

c164

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
452.94028500029066, 198.0

c165

c165

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
466.54913349652696, 255.76256170793184

c166

c166

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
524.0, 245.0

c167

c167

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
396.3517178529796, 333.94635316997733

c168

c168

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
391.0, 256.098352633352

c169

c169

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
437.0, 1060.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
380.0, 263.0

c170

c170

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1103.0, 331.0

c171

c171

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
175.0, 220.0

c172

c172

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
231.52397593249782, 148.19124623945277

c173

c173

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
737.0, 315.9943100988534

c174

c174

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
740.0, 252.9972313548228

c175

c175

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
758.491610346158, 303.8063810185608

c176

c176

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
706.5212577361842, 317.18336578181584

c177

c177

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
706.0, 251.7075489304051

c178

c178

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
657.0, 249.0

c179

c179

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
464.0, 1094.0

c18

c18

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
642.0, 316.00570813538206

c180

c180

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
874.0, 771.0

c181

c181

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1022.0, 451.91816295637074

c182

c182

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1034.998729508888, 900.1008083069468

c183

c183

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1032.519207833685, 703.0

c184

c184

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1027.6961833112434, 589.0

c185

c185

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1038.2744631916617, 908.3289916300824

c186

c186

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
853.0, 321.0

c187

c187

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
850.0, 321.0

c188

c188

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
848.0, 321.0

c189

c189

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
467.0, 1141.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
847.0, 321.0

c190

c190

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
845.0, 321.0

c191

c191

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
845.0, 321.0

c192

c192

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
844.0, 321.0

c193

c193

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
843.0, 321.0

c194

c194

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
843.0, 321.0

c195

c195

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
842.0, 321.0

c196

c196

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
842.0, 321.0

c197

c197

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
842.0, 321.0

c198

c198

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
841.0, 321.0

c199

c199

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
160.0, 239.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
297.0, 1100.0

c20

c20

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
861.0, 490.02212513718734

c200

c200

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 521.762420271769

c201

c201

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 551.403844417527

c202

c202

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 583.8629857313305

c203

c203

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 620.072069779996

c204

c204

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 645.3862463034083

c205

c205

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 661.0

c206

c206

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 664.0

c207

c207

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 667.0

c208

c208

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
863.0, 670.0

c209

c209

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
440.0, 992.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
863.0, 674.0

c210

c210

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
861.0, 675.0

c211

c211

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
859.0, 675.0

c212

c212

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
530.0, 1003.0

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
533.7585526044338, 1082.0

c23

c23

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
541.884613462592, 1002.0745671513299

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
481.4376015698018, 1119.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
287.0, 1306.1103343325483

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
467.0, 1306.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
466.1554175279993, 1315.5777087639997

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
459.0, 1267.748021039078

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
119.13194536189366, 231.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
488.0, 1256.0

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
467.1738719632737, 1204.9981103105913

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
811.0, 1348.762860105874

c32

c32

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
815.0, 1499.0536785982254

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
902.0, 1480.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
894.0, 1452.8308170454445

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
901.0, 1328.0

c36

c36

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
893.0, 1339.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
792.0, 1360.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
797.5240571578818, 1370.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
36.0, 368.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
489.68571346272915, 1189.220317222566

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
792.0, 1371.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
798.9955592558332, 1401.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
854.7462185896749, 1365.9990241521741

c43

c43

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
855.5894663844041, 1407.5298221281348

c44

c44

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
734.0, 1490.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
741.0831832227035, 1465.7186711919194

c46

c46

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
734.0, 1463.7825416385167

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
742.0, 1454.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
805.5121497996619, 1398.0

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
118.0, 368.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
806.6731636398415, 1445.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
618.8993262705642, 1395.0496045501138

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
546.0953126733358, 1355.6954753506957

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
727.9382230137094, 1353.9922778767136

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
708.0, 1300.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
559.3531602401445, 1212.1513543886333

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
482.0, 1182.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
884.0, 1115.0

c57

c57

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
859.8262546692157, 1043.1716000756319

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
840.0, 994.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
104.0, 331.0

c6

c6

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
873.3042819623698, 918.9887054413853

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
856.0, 778.9996975596846

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
877.0, 758.0

c62

c62

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1109.0, 381.94257241545523

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1011.0, 451.79219152338226

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
767.0, 428.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
744.0, 443.0

c66

c66

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
744.0, 573.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
749.0, 671.0

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
776.0, 757.0

c69

c69

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
295.0, 1138.1538177138507

c7

c7

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
776.0, 819.0

c70

c70

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
788.0, 913.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
692.0, 804.0

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
672.0, 816.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1165.0, 327.99609660869663

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
851.9999188389918, 427.0

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
891.0, 1107.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
923.0, 1114.3225202593821

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
855.0, 983.0

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
912.0, 986.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
290.0, 1182.1583847918305

c8

c8

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1111.0, 427.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1095.0, 385.0

c81

c81

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1108.061148983219, 349.19554444497504

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
953.0, 866.5777087639997

c83

c83

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1103.9463531699773, 246.3517178529796

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1106.0, 228.0

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1034.0, 228.0

c86

c86

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.7385488374939, 913.0

c87

c87

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
687.9226461262386, 806.7828456861378

c88

c88

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1024.1121980852033, 784.5128117873124

c89

c89

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
286.0, 1218.3665869935685

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1022.5625247654788, 589.0

c90

c90

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
611.0, 807.9514749175171

c91

c91

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
614.0, 792.0

c92

c92

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1027.99808533945, 227.89393378356044

c93

c93

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
684.6117584882778, 241.0

c94

c94

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1028.7285416995237, 777.0663114960532

c95

c95

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
687.9872611141445, 805.3189808891316

c96

c96

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1024.653207544305, 700.0

c97

c97

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
877.0, 763.0

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1011.0, 451.83239983666766

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back