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notes: This a model from the article: Modelling the response of FOXO transcription factors to multiple post-translational modifications made by ageing-related signalling pathways. Smith GR, Shanley DP. PLoS One. 2010 Jun 14;5(6):e11092. 20567500 , Abstract: FOXO transcription factors are an important, conserved family of regulators of cellular processes including metabolism, cell-cycle progression, apoptosis and stress resistance. They are required for the efficacy of several of the genetic interventions that modulate lifespan. FOXO activity is regulated by multiple post-translational modifications (PTMs) that affect its subcellular localization, half-life, DNA binding and transcriptional activity. Here, we show how a mathematical modelling approach can be used to simulate the effects, singly and in combination, of these PTMs. Our model is implemented using the Systems Biology Markup Language (SBML), generated by an ancillary program and simulated in a stochastic framework. The use of the ancillary program to generate the SBML is necessary because the possibility that many regulatory PTMs may be added, each independently of the others, means that a large number of chemically distinct forms of the FOXO molecule must be taken into account, and the program is used to generate them. Although the model does not yet include detailed representations of events upstream and downstream of FOXO, we show how it can qualitatively, and in some cases quantitatively, reproduce the known effects of certain treatments that induce various single and multiple PTMs, and allows for a complex spatiotemporal interplay of effects due to the activation of multiple PTM-inducing treatments. Thus, it provides an important framework to integrate current knowledge about the behaviour of FOXO. The approach should be generally applicable to other proteins experiencing multiple regulations. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomode…
name: Smith2010_Foxo_PTMs_AgeingRelatedSignallingPathway_B
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is described by: http://identifiers.org/pubmed/20567500
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value: 5.0E-5

111775
type: SpeciesReference
stoichiometry: 1.0
species: 106860

111763
type: SpeciesReference
stoichiometry: 1.0
species: 107007

112259
type: Reaction
kinetic law: 112307
modifier: 112296
product: 112283
reactant: 112271
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa0_Ac0_pUb0 to dnabound_Foxo1_Pa0_Ac1_pUb0 by CBPP300

112319
type: LocalParameter
value: 1.0E-4

112283
type: SpeciesReference
stoichiometry: 1.0
species: 106885

112271
type: SpeciesReference
stoichiometry: 1.0
species: 106812

109400
type: Reaction
kinetic law: 109437
product: 109425
reactant: 109413
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa1_Ac1_pUb1 to cytoplasm_Foxo1_Pa1_Ac1_pUb1

109449
type: LocalParameter
value: 0.55

109425
type: SpeciesReference
stoichiometry: 1.0
species: 107043

107043
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

109413
type: SpeciesReference
stoichiometry: 1.0
species: 107055

108179
type: Reaction
kinetic law: 108215
product: 108203
reactant: 108191
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa0_Ac1_pUb0 to cytoplasm_Foxo1_Pa0_Ac1_pUb0

108227
type: LocalParameter
value: 0.055

108203
type: SpeciesReference
stoichiometry: 1.0
species: 106860

108191
type: SpeciesReference
stoichiometry: 1.0
species: 106872

110231
type: Reaction
kinetic law: 110279
modifier: 110267
product: 110255
reactant: 110243
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac1_pUb1 to cytoplasm_Foxo1_Pa1_Ac1_pUb1 by Akt

110291
type: LocalParameter
value: 5.0E-5

110255
type: SpeciesReference
stoichiometry: 1.0
species: 107043

110243
type: SpeciesReference
stoichiometry: 1.0
species: 106897

116032
type: Reaction
kinetic law: 116068
product: 116056
reactant: 116044
fast: false
reversible: false
name: export of sod2 RNA

116080
type: LocalParameter
value: 0.22

116056
type: SpeciesReference
stoichiometry: 1.0
species: 107250

116044
type: SpeciesReference
stoichiometry: 1.0
species: 107238

110593
type: Reaction
kinetic law: 110642
modifier: 110629
product: 110617
reactant: 110605
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa0_Ac0_pUb0 to dnabound_Foxo1_Pa1_Ac0_pUb0 by SGK

110654
type: LocalParameter
value: 5.0E-5

110617
type: SpeciesReference
stoichiometry: 1.0
species: 106958

110605
type: SpeciesReference
stoichiometry: 1.0
species: 106812

108117
type: Reaction
kinetic law: 108154
product: 108142
reactant: 108129
fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa0_Ac1_pUb0 to nucleus_Foxo1_Pa0_Ac1_pUb0

108167
type: LocalParameter
value: 0.181818181818

108142
type: SpeciesReference
stoichiometry: 1.0
species: 106872

108129
type: SpeciesReference
stoichiometry: 1.0
species: 106860

112547
type: Reaction
kinetic law: 112596
modifier: 112584
product: 112572
reactant: 112560
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa0_Ac1_pUb0 to dnabound_Foxo1_Pa0_Ac0_pUb0 by SIRT1

112608
type: LocalParameter
value: 1.0E-4

112572
type: SpeciesReference
stoichiometry: 1.0
species: 106812

112560
type: SpeciesReference
stoichiometry: 1.0
species: 106885

114862
type: Reaction
kinetic law: 114910
modifier: 114898
product: 114886
reactant: 114874
fast: false
reversible: false
name: transcription of sod2 by dnabound_Foxo1_Pa0_Ac1_pUb0

114922
type: LocalParameter
value: 0.3

114886
type: SpeciesReference
stoichiometry: 1.0
species: 107238

114874
type: SpeciesReference
stoichiometry: 1.0
species: 106763

107346
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

113558
type: Reaction
kinetic law: 113606
modifier: 113595
product: 113582
reactant: 113570
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac1_pUb0 to cytoplasm_Foxo1_Pa0_Ac1_pUb1 by SCF

113618
type: LocalParameter
value: 3.33333333333E-8

113582
type: SpeciesReference
stoichiometry: 1.0
species: 106897

113570
type: SpeciesReference
stoichiometry: 1.0
species: 106860

110954
type: Reaction
kinetic law: 111003
modifier: 110990
product: 110978
reactant: 110966
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa0_Ac1_pUb0 to nucleus_Foxo1_Pa1_Ac1_pUb0 by SGK

111015
type: LocalParameter
value: 5.0E-5

110978
type: SpeciesReference
stoichiometry: 1.0
species: 107019

110966
type: SpeciesReference
stoichiometry: 1.0
species: 106872

108797
type: Reaction
kinetic law: 108833
product: 108821
reactant: 108809
fast: false
reversible: false
name: transport dnabound_Foxo1_Pa1_Ac0_pUb0 to nucleus_Foxo1_Pa1_Ac0_pUb0

108845
type: LocalParameter
value: 0.125

108821
type: SpeciesReference
stoichiometry: 1.0
species: 106946

108809
type: SpeciesReference
stoichiometry: 1.0
species: 106958

108977
type: Reaction
kinetic law: 109013
product: 109001
reactant: 108989
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa1_Ac0_pUb1 to dnabound_Foxo1_Pa1_Ac0_pUb1

109025
type: LocalParameter
value: 0.125

109001
type: SpeciesReference
stoichiometry: 1.0
species: 106995

108989
type: SpeciesReference
stoichiometry: 1.0
species: 106982

107334
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

109280
type: Reaction
kinetic law: 109316
product: 109304
reactant: 109292
fast: false
reversible: false
name: transport dnabound_Foxo1_Pa1_Ac1_pUb0 to nucleus_Foxo1_Pa1_Ac1_pUb0

109328
type: LocalParameter
value: 0.125

109304
type: SpeciesReference
stoichiometry: 1.0
species: 107019

109292
type: SpeciesReference
stoichiometry: 1.0
species: 107031

109798
type: Reaction
kinetic law: 109846
modifier: 109834
product: 109821
reactant: 109810
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac0_pUb1 to cytoplasm_Foxo1_Pa1_Ac0_pUb1 by Akt

109858
type: LocalParameter
value: 5.0E-5

109821
type: SpeciesReference
stoichiometry: 1.0
species: 106970

109810
type: SpeciesReference
stoichiometry: 1.0
species: 106824

112764
type: Reaction
kinetic law: 112812
modifier: 112799
product: 112787
reactant: 112775
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa1_Ac0_pUb0 to nucleus_Foxo1_Pa1_Ac1_pUb0 by CBPP300

112825
type: LocalParameter
value: 1.0E-4

112787
type: SpeciesReference
stoichiometry: 1.0
species: 107019

112775
type: SpeciesReference
stoichiometry: 1.0
species: 106946

112113
type: Reaction
kinetic law: 112163
modifier: 112150
product: 112139
reactant: 112126
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa1_Ac1_pUb1 to dnabound_Foxo1_Pa0_Ac1_pUb1 by PP2A

112176
type: LocalParameter
value: 5.0E-5

112139
type: SpeciesReference
stoichiometry: 1.0
species: 106922

112126
type: SpeciesReference
stoichiometry: 1.0
species: 107067

114135
type: Reaction
kinetic law: 114184
modifier: 114172
product: 114160
reactant: 114148
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa1_Ac1_pUb0 to dnabound_Foxo1_Pa1_Ac1_pUb1 by SCF

114196
type: LocalParameter
value: 1.0E-7

114160
type: SpeciesReference
stoichiometry: 1.0
species: 107067

114148
type: SpeciesReference
stoichiometry: 1.0
species: 107031

108617
type: Reaction
kinetic law: 108653
product: 108641
reactant: 108629
fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa1_Ac0_pUb0 to nucleus_Foxo1_Pa1_Ac0_pUb0

108665
type: LocalParameter
value: 0.0181818181818

108641
type: SpeciesReference
stoichiometry: 1.0
species: 106946

108629
type: SpeciesReference
stoichiometry: 1.0
species: 106934

106934
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

114426
type: Reaction
kinetic law: 114474
modifier: 114462
product: 114450
reactant: 114438
fast: false
reversible: false
name: degradation of cytoplasm_Foxo1_Pa1_Ac1_pUb1

114486
type: LocalParameter
value: 1.0E-4

114450
type: SpeciesReference
stoichiometry: 1.0
species: 106775

114438
type: SpeciesReference
stoichiometry: 1.0
species: 107043

112619
type: Reaction
kinetic law: 112668
modifier: 112655
product: 112644
reactant: 112631
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa0_Ac1_pUb1 to nucleus_Foxo1_Pa0_Ac0_pUb1 by SIRT1

112679
type: LocalParameter
value: 1.0E-4

112644
type: SpeciesReference
stoichiometry: 1.0
species: 106836

112631
type: SpeciesReference
stoichiometry: 1.0
species: 106910

107394
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

108496
type: Reaction
kinetic law: 108532
product: 108520
reactant: 108508
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa0_Ac1_pUb1 to dnabound_Foxo1_Pa0_Ac1_pUb1

108545
type: LocalParameter
value: 0.125

108520
type: SpeciesReference
stoichiometry: 1.0
species: 106922

108508
type: SpeciesReference
stoichiometry: 1.0
species: 106910

109098
type: Reaction
kinetic law: 109134
product: 109123
reactant: 109110
fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa1_Ac1_pUb0 to nucleus_Foxo1_Pa1_Ac1_pUb0

109146
type: LocalParameter
value: 0.0181818181818

109123
type: SpeciesReference
stoichiometry: 1.0
species: 107019

109110
type: SpeciesReference
stoichiometry: 1.0
species: 107007

109220
type: Reaction
kinetic law: 109256
product: 109244
reactant: 109232
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa1_Ac1_pUb0 to dnabound_Foxo1_Pa1_Ac1_pUb0

109268
type: LocalParameter
value: 0.0625

109244
type: SpeciesReference
stoichiometry: 1.0
species: 107031

109232
type: SpeciesReference
stoichiometry: 1.0
species: 107019

107756
type: Reaction
kinetic law: 107792
product: 107780
reactant: 107768
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa0_Ac0_pUb0 to dnabound_Foxo1_Pa0_Ac0_pUb0

107805
type: LocalParameter
value: 0.25

107780
type: SpeciesReference
stoichiometry: 1.0
species: 106812

107768
type: SpeciesReference
stoichiometry: 1.0
species: 106800

111606
type: Reaction
kinetic law: 111654
modifier: 111642
product: 111630
reactant: 111619
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa1_Ac0_pUb1 to nucleus_Foxo1_Pa0_Ac0_pUb1 by PP2A

111666
type: LocalParameter
value: 5.0E-5

111630
type: SpeciesReference
stoichiometry: 1.0
species: 106836

111619
type: SpeciesReference
stoichiometry: 1.0
species: 106982

107177
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106702

112332
type: Reaction
kinetic law: 112380
modifier: 112368
product: 112356
reactant: 112344
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa0_Ac0_pUb1 to nucleus_Foxo1_Pa0_Ac1_pUb1 by CBPP300

112392
type: LocalParameter
value: 1.0E-4

112356
type: SpeciesReference
stoichiometry: 1.0
species: 106910

112344
type: SpeciesReference
stoichiometry: 1.0
species: 106836

113918
type: Reaction
kinetic law: 113967
modifier: 113955
product: 113943
reactant: 113931
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa1_Ac0_pUb0 to dnabound_Foxo1_Pa1_Ac0_pUb1 by SCF

113979
type: LocalParameter
value: 3.0E-6

113943
type: SpeciesReference
stoichiometry: 1.0
species: 106995

113931
type: SpeciesReference
stoichiometry: 1.0
species: 106958

114789
type: Reaction
kinetic law: 114838
modifier: 114825
product: 114813
reactant: 114801
fast: false
reversible: false
name: transcription of inr by dnabound_Foxo1_Pa0_Ac1_pUb0

114850
type: LocalParameter
value: 0.3

114813
type: SpeciesReference
stoichiometry: 1.0
species: 107201

114801
type: SpeciesReference
stoichiometry: 1.0
species: 106763

107165
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106702

110086
type: Reaction
kinetic law: 110135
modifier: 110123
product: 110111
reactant: 110098
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa0_Ac1_pUb0 to nucleus_Foxo1_Pa1_Ac1_pUb0 by Akt

110147
type: LocalParameter
value: 5.0E-5

110111
type: SpeciesReference
stoichiometry: 1.0
species: 107019

110098
type: SpeciesReference
stoichiometry: 1.0
species: 106872

116224
type: Reaction
kinetic law: 116261
product: 116249
reactant: 116236
fast: false
reversible: false
name: degradation of Sod2 protein

116273
type: LocalParameter
value: 0.0019

116249
type: SpeciesReference
stoichiometry: 1.0
species: 106763

116236
type: SpeciesReference
stoichiometry: 1.0
species: 107262

107262
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

115296
type: Reaction
kinetic law: 115345
modifier: 115333
product: 115321
reactant: 115308
fast: false
reversible: false
name: transcription of sod2 by dnabound_Foxo1_Pa1_Ac0_pUb1

115357
type: LocalParameter
value: 0.3

115321
type: SpeciesReference
stoichiometry: 1.0
species: 107238

115308
type: SpeciesReference
stoichiometry: 1.0
species: 106763

107406
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 1000.0
in compartment: 106726

111459
type: Reaction
kinetic law: 111508
modifier: 111495
product: 111483
reactant: 111471
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa1_Ac0_pUb0 to dnabound_Foxo1_Pa0_Ac0_pUb0 by PP2A

111520
type: LocalParameter
value: 5.0E-5

111483
type: SpeciesReference
stoichiometry: 1.0
species: 106812

111471
type: SpeciesReference
stoichiometry: 1.0
species: 106958

108677
type: Reaction
kinetic law: 108713
product: 108701
reactant: 108689
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa1_Ac0_pUb0 to cytoplasm_Foxo1_Pa1_Ac0_pUb0

108725
type: LocalParameter
value: 0.55

108701
type: SpeciesReference
stoichiometry: 1.0
species: 106934

108689
type: SpeciesReference
stoichiometry: 1.0
species: 106946

108239
type: Reaction
kinetic law: 108275
product: 108263
reactant: 108251
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa0_Ac1_pUb0 to dnabound_Foxo1_Pa0_Ac1_pUb0

108288
type: LocalParameter
value: 0.125

108263
type: SpeciesReference
stoichiometry: 1.0
species: 106885

108251
type: SpeciesReference
stoichiometry: 1.0
species: 106872

107877
type: Reaction
kinetic law: 107913
product: 107901
reactant: 107889
fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa0_Ac0_pUb1 to nucleus_Foxo1_Pa0_Ac0_pUb1

107925
type: LocalParameter
value: 0.181818181818

107901
type: SpeciesReference
stoichiometry: 1.0
species: 106836

107889
type: SpeciesReference
stoichiometry: 1.0
species: 106824

114643
type: Reaction
kinetic law: 114692
modifier: 114680
product: 114668
reactant: 114655
fast: false
reversible: false
name: transcription of inr by dnabound_Foxo1_Pa0_Ac0_pUb1

114704
type: LocalParameter
value: 0.3

114668
type: SpeciesReference
stoichiometry: 1.0
species: 107201

114655
type: SpeciesReference
stoichiometry: 1.0
species: 106763

108301
type: Reaction
kinetic law: 108340
product: 108327
reactant: 108314
fast: false
reversible: false
name: transport dnabound_Foxo1_Pa0_Ac1_pUb0 to nucleus_Foxo1_Pa0_Ac1_pUb0

108353
type: LocalParameter
value: 0.125

108327
type: SpeciesReference
stoichiometry: 1.0
species: 106872

108314
type: SpeciesReference
stoichiometry: 1.0
species: 106885

115839
type: Reaction
kinetic law: 115887
modifier: 115875
product: 115863
reactant: 115851
fast: false
reversible: false
name: translation of inr

115899
type: LocalParameter
value: 1.23

115863
type: SpeciesReference
stoichiometry: 1.0
species: 107225

115851
type: SpeciesReference
stoichiometry: 1.0
species: 106763

107274
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

110447
type: Reaction
kinetic law: 110496
modifier: 110484
product: 110472
reactant: 110459
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac0_pUb0 to cytoplasm_Foxo1_Pa1_Ac0_pUb0 by SGK

110508
type: LocalParameter
value: 5.0E-5

110472
type: SpeciesReference
stoichiometry: 1.0
species: 106934

110459
type: SpeciesReference
stoichiometry: 1.0
species: 106788

115080
type: Reaction
kinetic law: 115128
modifier: 115116
product: 115104
reactant: 115092
fast: false
reversible: false
name: transcription of inr by dnabound_Foxo1_Pa1_Ac0_pUb0

115140
type: LocalParameter
value: 0.3

115104
type: SpeciesReference
stoichiometry: 1.0
species: 107201

115092
type: SpeciesReference
stoichiometry: 1.0
species: 106763

115224
type: Reaction
kinetic law: 115272
modifier: 115260
product: 115248
reactant: 115236
fast: false
reversible: false
name: transcription of inr by dnabound_Foxo1_Pa1_Ac0_pUb1

115284
type: LocalParameter
value: 0.3

115248
type: SpeciesReference
stoichiometry: 1.0
species: 107201

115236
type: SpeciesReference
stoichiometry: 1.0
species: 106763

109461
type: Reaction
kinetic law: 109497
product: 109485
reactant: 109473
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa1_Ac1_pUb1 to dnabound_Foxo1_Pa1_Ac1_pUb1

109509
type: LocalParameter
value: 0.0625

109485
type: SpeciesReference
stoichiometry: 1.0
species: 107067

109473
type: SpeciesReference
stoichiometry: 1.0
species: 107055

110159
type: Reaction
kinetic law: 110207
modifier: 110195
product: 110183
reactant: 110171
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa0_Ac1_pUb0 to dnabound_Foxo1_Pa1_Ac1_pUb0 by Akt

110219
type: LocalParameter
value: 5.0E-5

110183
type: SpeciesReference
stoichiometry: 1.0
species: 107031

110171
type: SpeciesReference
stoichiometry: 1.0
species: 106885

107322
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106726

115441
type: Reaction
kinetic law: 115490
modifier: 115478
product: 115466
reactant: 115454
fast: false
reversible: false
name: transcription of sod2 by dnabound_Foxo1_Pa1_Ac1_pUb0

115502
type: LocalParameter
value: 0.3

115466
type: SpeciesReference
stoichiometry: 1.0
species: 107238

115454
type: SpeciesReference
stoichiometry: 1.0
species: 106763

107997
type: Reaction
kinetic law: 108033
product: 108021
reactant: 108009
fast: false
reversible: false
name: transport nucleus_Foxo1_Pa0_Ac0_pUb1 to dnabound_Foxo1_Pa0_Ac0_pUb1

108045
type: LocalParameter
value: 0.25

108021
type: SpeciesReference
stoichiometry: 1.0
species: 106848

108009
type: SpeciesReference
stoichiometry: 1.0
species: 106836

107128
type: Species
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: 106702

112837
type: Reaction
kinetic law: 112885
modifier: 112873
product: 112860
reactant: 112848
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa1_Ac0_pUb0 to dnabound_Foxo1_Pa1_Ac1_pUb0 by CBPP300

112896
type: LocalParameter
value: 1.0E-4

112860
type: SpeciesReference
stoichiometry: 1.0
species: 107031

112848
type: SpeciesReference
stoichiometry: 1.0
species: 106958

107817
type: Reaction
kinetic law: 107853
product: 107841
reactant: 107829
fast: false
reversible: false
name: transport dnabound_Foxo1_Pa0_Ac0_pUb0 to nucleus_Foxo1_Pa0_Ac0_pUb0

107865
type: LocalParameter
value: 0.125

107841
type: SpeciesReference
stoichiometry: 1.0
species: 106800

107829
type: SpeciesReference
stoichiometry: 1.0
species: 106812

114354
type: Reaction
kinetic law: 114402
modifier: 114390
product: 114378
reactant: 114366
fast: false
reversible: false
name: degradation of cytoplasm_Foxo1_Pa1_Ac0_pUb1

114414
type: LocalParameter
value: 1.0E-4

114378
type: SpeciesReference
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species: 106775

114366
type: SpeciesReference
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species: 106970

106665
type: SBMLUnit
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scale: 0
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kind: ITEM

111099
type: Reaction
kinetic law: 111147
modifier: 111135
product: 111123
reactant: 111111
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac1_pUb1 to cytoplasm_Foxo1_Pa1_Ac1_pUb1 by SGK

111159
type: LocalParameter
value: 5.0E-5

111123
type: SpeciesReference
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species: 107043

111111
type: SpeciesReference
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species: 106897

115514
type: Reaction
kinetic law: 115562
modifier: 115550
product: 115538
reactant: 115526
fast: false
reversible: false
name: transcription of inr by dnabound_Foxo1_Pa1_Ac1_pUb1

115574
type: LocalParameter
value: 0.3

115538
type: SpeciesReference
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species: 107201

115526
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species: 106763

113052
type: Reaction
kinetic law: 113100
modifier: 113088
product: 113076
reactant: 113064
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa1_Ac1_pUb0 to nucleus_Foxo1_Pa1_Ac0_pUb0 by SIRT1

113112
type: LocalParameter
value: 1.0E-4

113076
type: SpeciesReference
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species: 106946

113064
type: SpeciesReference
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species: 107019

112042
type: Reaction
kinetic law: 112090
modifier: 112078
product: 112066
reactant: 112054
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa1_Ac1_pUb1 to nucleus_Foxo1_Pa0_Ac1_pUb1 by PP2A

112102
type: LocalParameter
value: 5.0E-5

112066
type: SpeciesReference
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species: 106910

112054
type: SpeciesReference
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species: 107055

107564
type: Reaction
kinetic law: 107612
modifier: 107600
product: 107588
reactant: 107576
fast: false
reversible: false
name: Synthesis

107624
type: LocalParameter
value: 0.0055

107588
type: SpeciesReference
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species: 106788

107576
type: SpeciesReference
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112404
type: Reaction
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modifier: 112440
product: 112428
reactant: 112416
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name: conversion of dnabound_Foxo1_Pa0_Ac0_pUb1 to dnabound_Foxo1_Pa0_Ac1_pUb1 by CBPP300

112464
type: LocalParameter
value: 1.0E-4

112428
type: SpeciesReference
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species: 106922

112416
type: SpeciesReference
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species: 106848

107310
type: Species
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109037
type: Reaction
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product: 109061
reactant: 109049
fast: false
reversible: false
name: transport dnabound_Foxo1_Pa1_Ac0_pUb1 to nucleus_Foxo1_Pa1_Ac0_pUb1

109085
type: LocalParameter
value: 0.125

109061
type: SpeciesReference
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species: 106982

109049
type: SpeciesReference
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species: 106995

108857
type: Reaction
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product: 108881
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fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa1_Ac0_pUb1 to nucleus_Foxo1_Pa1_Ac0_pUb1

108905
type: LocalParameter
value: 0.0181818181818

108881
type: SpeciesReference
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species: 106982

108869
type: SpeciesReference
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species: 106970

113991
type: Reaction
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modifier: 114027
product: 114015
reactant: 114003
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa1_Ac1_pUb0 to cytoplasm_Foxo1_Pa1_Ac1_pUb1 by SCF

114051
type: LocalParameter
value: 1.0E-7

114015
type: SpeciesReference
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species: 107043

114003
type: SpeciesReference
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species: 107007

109942
type: Reaction
kinetic law: 109990
modifier: 109978
product: 109966
reactant: 109954
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa0_Ac0_pUb1 to dnabound_Foxo1_Pa1_Ac0_pUb1 by Akt

110002
type: LocalParameter
value: 5.0E-5

109966
type: SpeciesReference
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species: 106995

109954
type: SpeciesReference
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species: 106848

113268
type: Reaction
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modifier: 113304
product: 113292
reactant: 113280
fast: false
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name: conversion of dnabound_Foxo1_Pa1_Ac1_pUb1 to dnabound_Foxo1_Pa1_Ac0_pUb1 by SIRT1

113328
type: LocalParameter
value: 1.0E-4

113292
type: SpeciesReference
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species: 106995

113280
type: SpeciesReference
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species: 107067

107153
type: Species
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111678
type: Reaction
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modifier: 111714
product: 111703
reactant: 111690
fast: false
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name: conversion of dnabound_Foxo1_Pa1_Ac0_pUb1 to dnabound_Foxo1_Pa0_Ac0_pUb1 by PP2A

111738
type: LocalParameter
value: 5.0E-5

111703
type: SpeciesReference
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species: 106848

111690
type: SpeciesReference
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109582
type: Reaction
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modifier: 109617
product: 109605
reactant: 109594
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac0_pUb0 to cytoplasm_Foxo1_Pa1_Ac0_pUb0 by Akt

109641
type: LocalParameter
value: 5.0E-5

109605
type: SpeciesReference
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species: 106934

109594
type: SpeciesReference
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species: 106788

111027
type: Reaction
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modifier: 111064
product: 111051
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fast: false
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name: conversion of dnabound_Foxo1_Pa0_Ac1_pUb0 to dnabound_Foxo1_Pa1_Ac1_pUb0 by SGK

111087
type: LocalParameter
value: 5.0E-5

111051
type: SpeciesReference
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species: 107031

111039
type: SpeciesReference
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species: 106885

111532
type: Reaction
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modifier: 111570
product: 111557
reactant: 111545
fast: false
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name: conversion of cytoplasm_Foxo1_Pa1_Ac0_pUb1 to cytoplasm_Foxo1_Pa0_Ac0_pUb1 by PP2A

111594
type: LocalParameter
value: 5.0E-5

111557
type: SpeciesReference
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species: 106824

111545
type: SpeciesReference
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species: 106970

110014
type: Reaction
kinetic law: 110062
modifier: 110050
product: 110038
reactant: 110026
fast: false
reversible: false
name: conversion of cytoplasm_Foxo1_Pa0_Ac1_pUb0 to cytoplasm_Foxo1_Pa1_Ac1_pUb0 by Akt

110074
type: LocalParameter
value: 5.0E-5

110038
type: SpeciesReference
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species: 107007

110026
type: SpeciesReference
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species: 106860

115658
type: Reaction
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product: 115682
reactant: 115670
fast: false
reversible: false
name: basal transcription of inr

115706
type: LocalParameter
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115682
type: SpeciesReference
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species: 107201

115670
type: SpeciesReference
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species: 106763

107091
type: Species
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in compartment: 106702

107141
type: Species
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111968
type: Reaction
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modifier: 112005
product: 111993
reactant: 111980
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reversible: false
name: conversion of cytoplasm_Foxo1_Pa1_Ac1_pUb1 to cytoplasm_Foxo1_Pa0_Ac1_pUb1 by PP2A

112030
type: LocalParameter
value: 5.0E-5

111993
type: SpeciesReference
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species: 106897

111980
type: SpeciesReference
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species: 107043

113630
type: Reaction
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modifier: 113666
product: 113654
reactant: 113642
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa0_Ac1_pUb0 to nucleus_Foxo1_Pa0_Ac1_pUb1 by SCF

113690
type: LocalParameter
value: 3.33333333333E-8

113654
type: SpeciesReference
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species: 106910

113642
type: SpeciesReference
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species: 106872

113196
type: Reaction
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modifier: 113232
product: 113220
reactant: 113208
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa1_Ac1_pUb1 to nucleus_Foxo1_Pa1_Ac0_pUb1 by SIRT1

113256
type: LocalParameter
value: 1.0E-4

113220
type: SpeciesReference
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species: 106982

113208
type: SpeciesReference
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species: 107055

107079
type: Species
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initial concentration: NaN
initial amount: 0.0
in compartment: 106702

115152
type: Reaction
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modifier: 115188
product: 115176
reactant: 115164
fast: false
reversible: false
name: transcription of sod2 by dnabound_Foxo1_Pa1_Ac0_pUb0

115212
type: LocalParameter
value: 0.3

115176
type: SpeciesReference
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species: 107238

115164
type: SpeciesReference
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species: 106763

109158
type: Reaction
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product: 109183
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fast: false
reversible: false
name: transport nucleus_Foxo1_Pa1_Ac1_pUb0 to cytoplasm_Foxo1_Pa1_Ac1_pUb0

109207
type: LocalParameter
value: 0.55

109183
type: SpeciesReference
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species: 107007

109171
type: SpeciesReference
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species: 107019

115718
type: Reaction
kinetic law: 115754
product: 115742
reactant: 115730
fast: false
reversible: false
name: export of inr RNA

115766
type: LocalParameter
value: 0.22

115742
type: SpeciesReference
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species: 107213

115730
type: SpeciesReference
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species: 107201

109340
type: Reaction
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product: 109365
reactant: 109352
fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa1_Ac1_pUb1 to nucleus_Foxo1_Pa1_Ac1_pUb1

109388
type: LocalParameter
value: 0.0181818181818

109365
type: SpeciesReference
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species: 107055

109352
type: SpeciesReference
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species: 107043

113702
type: Reaction
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product: 113726
reactant: 113714
fast: false
reversible: false
name: conversion of dnabound_Foxo1_Pa0_Ac1_pUb0 to dnabound_Foxo1_Pa0_Ac1_pUb1 by SCF

113762
type: LocalParameter
value: 3.33333333333E-8

113726
type: SpeciesReference
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species: 106922

113714
type: SpeciesReference
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species: 106885

107696
type: Reaction
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product: 107720
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fast: false
reversible: false
name: transport nucleus_Foxo1_Pa0_Ac0_pUb0 to cytoplasm_Foxo1_Pa0_Ac0_pUb0

107744
type: LocalParameter
value: 0.055

107720
type: SpeciesReference
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species: 106788

107708
type: SpeciesReference
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species: 106800

112908
type: Reaction
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product: 112932
reactant: 112920
fast: false
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name: conversion of nucleus_Foxo1_Pa1_Ac0_pUb1 to nucleus_Foxo1_Pa1_Ac1_pUb1 by CBPP300

112968
type: LocalParameter
value: 1.0E-4

112932
type: SpeciesReference
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species: 107055

112920
type: SpeciesReference
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species: 106982

106714
type: Compartment
constant: true
size: 6.4E-14
spatial dimensions: 3.0

110303
type: Reaction
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modifier: 110339
product: 110327
reactant: 110315
fast: false
reversible: false
name: conversion of nucleus_Foxo1_Pa0_Ac1_pUb1 to nucleus_Foxo1_Pa1_Ac1_pUb1 by Akt

110363
type: LocalParameter
value: 5.0E-5

110327
type: SpeciesReference
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species: 107055

110315
type: SpeciesReference
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species: 106910

108057
type: Reaction
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product: 108081
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fast: false
reversible: false
name: transport dnabound_Foxo1_Pa0_Ac0_pUb1 to nucleus_Foxo1_Pa0_Ac0_pUb1

108105
type: LocalParameter
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108081
type: SpeciesReference
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species: 106836

108069
type: SpeciesReference
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species: 106848

107115
type: Species
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in compartment: 106702

108366
type: Reaction
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product: 108392
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fast: false
reversible: false
name: transport cytoplasm_Foxo1_Pa0_Ac1_pUb1 to nucleus_Foxo1_Pa0_Ac1_pUb1

108418
type: LocalParameter
value: 0.181818181818

108392
type: SpeciesReference
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species: 106910

108379
type: SpeciesReference
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115008
type: Reaction
kinetic law: 115056
modifier: 115044
product: 115032
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fast: false
reversible: false
name: transcription of sod2 by dnabound_Foxo1_Pa0_Ac1_pUb1

115068
type: LocalParameter
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115032
type: SpeciesReference
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species: 107238

115020
type: SpeciesReference
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species: 106763

116285
type: Event
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trigger: 116297
use values from trigger time: true

116297
type: Trigger
persistant: true
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107103
type: Species
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108431
type: Reaction
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product: 108458
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fast: false
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name: transport nucleus_Foxo1_Pa0_Ac1_pUb1 to cytoplasm_Foxo1_Pa0_Ac1_pUb1

108484
type: LocalParameter
value: 0.055

108458
type: SpeciesReference
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species: 106897

108444
type: SpeciesReference
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species: 106910

113774
type: Reaction
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product: 113798
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fast: false
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name: conversion of cytoplasm_Foxo1_Pa1_Ac0_pUb0 to cytoplasm_Foxo1_Pa1_Ac0_pUb1 by SCF

113834
type: LocalParameter
value: 3.0E-6

113798
type: SpeciesReference
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species: 106970

113786
type: SpeciesReference
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species: 106934

113341
type: Reaction
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modifier: 113377
product: 113365
reactant: 113353
fast: false
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name: conversion of cytoplasm_Foxo1_Pa0_Ac0_pUb0 to cytoplasm_Foxo1_Pa0_Ac0_pUb1 by SCF

113401
type: LocalParameter
value: 1.0E-6

113365
type: SpeciesReference
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species: 106824

113353
type: SpeciesReference
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species: 106788

110667
type: Reaction
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product: 110691
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fast: false
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name: conversion of cytoplasm_Foxo1_Pa0_Ac0_pUb1 to cytoplasm_Foxo1_Pa1_Ac0_pUb1 by SGK

110727
type: LocalParameter
value: 5.0E-5

110691
type: SpeciesReference
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species: 106970

110679
type: SpeciesReference
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species: 106824

112476
type: Reaction
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fast: false
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name: conversion of nucleus_Foxo1_Pa0_Ac1_pUb0 to nucleus_Foxo1_Pa0_Ac0_pUb0 by SIRT1

112536
type: LocalParameter
value: 1.0E-4

112500
type: SpeciesReference
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species: 106800

112488
type: SpeciesReference
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species: 106872

111823
type: Reaction
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fast: false
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name: conversion of nucleus_Foxo1_Pa1_Ac1_pUb0 to nucleus_Foxo1_Pa0_Ac1_pUb0 by PP2A

111884
type: LocalParameter
value: 5.0E-5

111847
type: SpeciesReference
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species: 106872

111835
type: SpeciesReference
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species: 107019

115911
type: Reaction
kinetic law: 115947
product: 115935
reactant: 115923
fast: false
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name: degradation of Inr protein

115959
type: LocalParameter
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115935
type: SpeciesReference
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species: 106763

115923
type: SpeciesReference
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species: 107225

107937
type: Reaction
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fast: false
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name: transport nucleus_Foxo1_Pa0_Ac0_pUb1 to cytoplasm_Foxo1_Pa0_Ac0_pUb1

107985
type: LocalParameter
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107961
type: SpeciesReference
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species: 106824

107949
type: SpeciesReference
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species: 106836

116092
type: Reaction
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product: 116116
reactant: 116104
fast: false
reversible: false
name: cyto degr of sod2 RNA

116140
type: LocalParameter
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116116
type: SpeciesReference
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species: 106763

116104
type: SpeciesReference
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species: 107250

110811
type: Reaction
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product: 110835
reactant: 110823
fast: false
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name: conversion of dnabound_Foxo1_Pa0_Ac0_pUb1 to dnabound_Foxo1_Pa1_Ac0_pUb1 by SGK

110871
type: LocalParameter
value: 5.0E-5

110835
type: SpeciesReference
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species: 106995

110823
type: SpeciesReference
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species: 106848

108557
type: Reaction
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product: 108581
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fast: false
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name: transport dnabound_Foxo1_Pa0_Ac1_pUb1 to nucleus_Foxo1_Pa0_Ac1_pUb1

108605
type: LocalParameter
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108581
type: SpeciesReference
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species: 106910

108569
type: SpeciesReference
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species: 106922

111315
type: Reaction
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product: 111339
reactant: 111327
fast: false
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name: conversion of cytoplasm_Foxo1_Pa1_Ac0_pUb0 to cytoplasm_Foxo1_Pa0_Ac0_pUb0 by PP2A

111375
type: LocalParameter
value: 5.0E-5

111339
type: SpeciesReference
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species: 106788

111327
type: SpeciesReference
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110739
type: Reaction
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modifier: 110775
product: 110763
reactant: 110751
fast: false
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name: conversion of nucleus_Foxo1_Pa0_Ac0_pUb1 to nucleus_Foxo1_Pa1_Ac0_pUb1 by SGK

110799
type: LocalParameter
value: 5.0E-5

110763
type: SpeciesReference
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species: 106982

110751
type: SpeciesReference
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116152
type: Reaction
kinetic law: 116200
modifier: 116188
product: 116176
reactant: 116164
fast: false
reversible: false
name: translation of sod2

116212
type: LocalParameter
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116176
type: SpeciesReference
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116164
type: SpeciesReference
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species: 106763