metaid_0000058
kinetic law: 040130
reactant: 040118
is version of: GO:0030163
fast: false
reversible: false
name: pRB degradation
type: Reaction

metaid_0000070
kinetic law: 040634
reactant: 040622
is version of: GO:0030163
fast: false
reversible: false
name: pRBpp degradation
type: Reaction

040034
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

metaid_0000023
constant: true
value: 0.04
name: k34
type: Parameter

metaid_0000068
modifier: 040550
reactant: 040526
kinetic law: 040574
is version of: GO:0006468
fast: false
product: 040538
modifier: 040562
name: pRBp phosphorylation
type: Reaction
reversible: false

metaid_0000004
unit: 039937
name: norm. volume
type: SBMLUnitsDef

040442
stoichiometry: 1.0
species: metaid_0000051
type: SpeciesReference

metaid_0000018
constant: true
value: 0.1
name: phi_E2F1
type: Parameter

040622
stoichiometry: 1.0
species: metaid_0000052
type: SpeciesReference

metaid_0000037
constant: true
value: 0.06
name: k28
type: Parameter

metaid_0000042
constant: true
value: 0.01
name: k98
type: Parameter

metaid_0000060
kinetic law: 040214
reactant: 040202
is version of: GO:0030163
fast: false
reversible: false
name: E2F1 degradation
type: Reaction

metaid_0000059
fast: false
reversible: false
product: 040142
name: E2F1 synthesis
type: Reaction
modifier: 040178
kinetic law: 040190
is version of: GO:0006412
modifier: 040154
modifier: 040166

039925
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

040850
stoichiometry: 1.0
species: metaid_0000054
type: SpeciesReference

metaid_0000022
constant: true
value: 2.0
name: J63
type: Parameter

metaid_0000050
initial amount: NaN
has part: P11802
has part: P30281
boundary condition: false
has part: Q00534
type: Species
has only substance units: false
constant: false
name: CycD/cdk4,6(a)
in compartment: metaid_0000045
initial concentration: 0.1

040394
stoichiometry: 1.0
species: metaid_0000049
type: SpeciesReference

metaid_0000069
kinetic law: 040610
product: 040598
reactant: 040586
is version of: GO:0006470
fast: false
reversible: false
name: pRBpp dephosphorylation
type: Reaction

metaid_0000003
unit: 039925
name: norm. time
type: SBMLUnitsDef

metaid_0000019
constant: true
value: 0.05
name: k3
type: Parameter

metaid_0000005
constant: true
value: 1.0
name: k1
type: Parameter

metaid_0000021
constant: true
value: 0.002
name: J13
type: Parameter

040526
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

metaid_0000036
constant: true
value: 0.06
name: phi_pRBp
type: Parameter

040094
stoichiometry: 1.0
species: metaid_0000046
type: SpeciesReference

metaid_0000041
constant: true
value: 0.005
name: Km9
type: Parameter

metaid_0000011
constant: true
value: 0.005
name: phi_pRB
type: Parameter

metaid_0000061
fast: false
kinetic law: 040286
is version of: GO:0006412
modifier: 040274
type: Reaction
reversible: false
name: CycD synthesis
modifier: 040238
product: 040226
modifier: 040250
modifier: 040262

metaid_0000056
kinetic law: 040070
modifier: 040046
type: Reaction
reversible: false
product: 040034
name: pRB phosphorylation
is version of: GO:0006468
modifier: 040058
fast: false
reactant: 040022

040586
stoichiometry: 1.0
species: metaid_0000052
type: SpeciesReference

039950
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

040022
stoichiometry: 1.0
species: metaid_0000046
type: SpeciesReference

metaid_0000006
constant: true
value: 0.5
name: Km1
type: Parameter

metaid_0000020
constant: true
value: 0.3
name: k23
type: Parameter

metaid_0000049
has part: P11802
constant: false
name: CycD/cdk4,6(i)
in compartment: metaid_0000045
has part: P30281
has part: Q00534
boundary condition: false
has only substance units: false
initial concentration: 0.1
type: Species
initial amount: NaN

metaid_0000075
kinetic law: 040838
reactant: 040826
is version of: GO:0030163
fast: false
reversible: false
name: CycE degradation
type: Reaction

metaid_0000030
constant: true
value: 0.001
name: J15
type: Parameter

metaid_0000040
constant: true
value: 0.07
name: k89
type: Parameter

metaid_0000010
constant: true
value: 0.3
name: k61
type: Parameter

metaid_0000039
constant: true
value: 7.0
name: J68
type: Parameter

metaid_0000016
constant: true
value: 5.0
name: J12
type: Parameter

metaid_0000062
kinetic law: 040322
product: 040310
reactant: 040298
is version of: GO:0031658
fast: false
reversible: false
name: CycD inibition
type: Reaction

metaid_0000057
kinetic law: 040106
product: 040094
reactant: 040082
is version of: GO:0006470
fast: false
reversible: false
name: pRBp dephosphorylation
type: Reaction

040802
stoichiometry: 1.0
species: metaid_0000053
type: SpeciesReference

039937
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

metaid_0000077
unit: 039950
name: norm substance
type: SBMLUnitsDef

metaid_0000076
kinetic law: 040862
reactant: 040850
is version of: GO:0030163
fast: false
reversible: false
name: CycE degradation2
type: Reaction

metaid_0000048
name: E2F1
has only substance units: false
initial concentration: 0.1
type: Species
initial amount: NaN
constant: false
boundary condition: false
in compartment: metaid_0000045
is homolog to: Q01094
notes: dimers of E2F1-6 and DP1,2

metaid_0000007
constant: true
value: 0.5
name: J11
type: Parameter

040310
stoichiometry: 1.0
species: metaid_0000049
type: SpeciesReference

metaid_0000038
constant: true
value: 0.6
name: J18
type: Parameter

metaid_0000017
constant: true
value: 8.0
name: J62
type: Parameter

metaid_0000028
notes: mitogenic stimulation
constant: true
value: 0.005
name: Fm
type: Parameter

040670
stoichiometry: 1.0
species: metaid_0000053
type: SpeciesReference

metaid_0000027
constant: true
value: 0.03
name: phi_CycDa
type: Parameter

metaid_0000053
has part: P24864
initial concentration: 0.1
initial amount: NaN
name: CycE/cdk2(i)
has part: O96020
has only substance units: false
type: Species
constant: false
has part: P24941
boundary condition: false
in compartment: metaid_0000045

metaid_0000063
reversible: false
kinetic law: 040382
name: CycD activation
is version of: GO:0031659
type: Reaction
modifier: 040358
fast: false
modifier: 040370
reactant: 040334
product: 040346

metaid_0000032
constant: true
value: 0.01
name: phi_AP1
type: Parameter

040538
stoichiometry: 1.0
species: metaid_0000052
type: SpeciesReference

040646
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

metaid_0000013
constant: true
value: 1.6
name: k2
type: Parameter

039962
stoichiometry: 1.0
species: metaid_0000046
type: SpeciesReference

metaid_0000008
constant: true
value: 5.0
name: J61
type: Parameter

metaid_0000033
constant: true
value: 0.7
name: k67
type: Parameter

BIOMD0000000228
parameter: metaid_0000032
reaction: metaid_0000075
parameter: metaid_0000036
parameter: metaid_0000016
is version of: GO:0000083
type: SBMLModel
reaction: metaid_0000060
parameter: metaid_0000008
volume units: metaid_0000004
parameter: metaid_0000039
reaction: metaid_0000070
parameter: metaid_0000040
parameter: metaid_0000007
parameter: metaid_0000020
reaction: metaid_0000063
parameter: metaid_0000044
parameter: metaid_0000024
reaction: metaid_0000067
reaction: metaid_0000069
reaction: metaid_0000071
species: metaid_0000046
species: metaid_0000054
parameter: metaid_0000012
reaction: metaid_0000057
reaction: metaid_0000055
compartment: metaid_0000045
parameter: metaid_0000043
is part of: REACT 1783
parameter: metaid_0000027
parameter: metaid_0000031
reaction: metaid_0000074
units def: metaid_0000004
parameter: metaid_0000035
parameter: metaid_0000015
parameter: metaid_0000019
parameter: metaid_0000038
species: metaid_0000048
parameter: metaid_0000018
parameter: metaid_0000006
is described by: http://identifiers.org/pubmed/15231543
reaction: metaid_0000062
species: metaid_0000051
reaction: metaid_0000068
parameter: metaid_0000023
reaction: metaid_0000066
occurs in: http://identifiers.org/taxonomy/40674
curated: true
notes: This is the extended model described the article: Bifurcation analysis of the regulatory modules of the mammalian G1/S transition. Swat M, Kel A, Herzel H. Bioinformatics 2004 Jul 10;20(10):1506-11. PMID: 15231543 , doi: 10.1093/bioinformatics/bth110 Abstract: MOTIVATION: Mathematical models of the cell cycle can contribute to an understanding of its basic mechanisms. Modern simulation tools make the analysis of key components and their interactions very effective. This paper focuses on the role of small modules and feedbacks in the gene-protein network governing the G1/S transition in mammalian cells. Mutations in this network may lead to uncontrolled cell proliferation. Bifurcation analysis helps to identify the key components of this extremely complex interaction network. RESULTS: We identify various positive and negative feedback loops in the network controlling the G1/S transition. It is shown that the positive feedback regulation of E2F1 and a double activator-inhibitor module can lead to bistability. Extensions of the core module preserve the essential features such as bistability. The complete model exhibits a transcritical bifurcation in addition to bistability. We relate these bifurcations to the cell cycle checkpoint and the G1/S phase transition point. Thus, core modules can explain major features of the complex G1/S network and have a robust decision taking function. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or …
parameter: metaid_0000011
reaction: metaid_0000056
parameter: metaid_0000029
parameter: metaid_0000042
reaction: metaid_0000065
species: metaid_0000047
time units: metaid_0000003
parameter: metaid_0000026
area units: metaid_0000005
parameter: metaid_0000030
parameter: metaid_0000010
reaction: metaid_0000073
parameter: metaid_0000034
parameter: metaid_0000014
name: Swat2004_Mammalian_G1_S_Transition
species: metaid_0000050
reaction: metaid_0000059
reaction: metaid_0000076
parameter: metaid_0000037
parameter: metaid_0000017
parameter: metaid_0000005
species: metaid_0000049
reaction: metaid_0000061
parameter: metaid_0000009
parameter: metaid_0000022
is: MODEL3897709120
species: metaid_0000052
parameter: metaid_0000028
parameter: metaid_0000041
parameter: metaid_0000021
reaction: metaid_0000064
units def: metaid_0000003

metaid_0000047
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: metaid_0000045
type: Species
notes: monophosphorlyated pRB
is homolog to: P06400
name: pRBp
constant: false
boundary condition: false

metaid_0000073
type: Reaction
reactant: 040730
product: 040742
name: CycE activation
kinetic law: 040778
fast: false
modifier: 040754
reversible: false
modifier: 040766
is version of: GO:0031659

040598
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

040730
stoichiometry: 1.0
species: metaid_0000053
type: SpeciesReference

040346
stoichiometry: 1.0
species: metaid_0000050
type: SpeciesReference

metaid_0000054
has part: P24941
boundary condition: false
has part: P24864
has only substance units: false
type: Species
constant: false
in compartment: metaid_0000045
initial concentration: 0.1
initial amount: NaN
has part: O96020
name: CycEa/cdk2(a)

metaid_0000026
constant: true
value: 0.01
name: k43
type: Parameter

040502
stoichiometry: 1.0
species: metaid_0000051
type: SpeciesReference

metaid_0000029
constant: true
value: 0.9
name: k25
type: Parameter

metaid_0000064
kinetic law: 040406
reactant: 040394
is version of: GO:0030163
fast: false
reversible: false
name: CycD degradation
type: Reaction

metaid_0000031
constant: true
value: 6.0
name: J65
type: Parameter

metaid_0000012
constant: true
value: 0.05
name: kp
type: Parameter

metaid_0000009
constant: true
value: 0.4
name: k16
type: Parameter

040226
stoichiometry: 1.0
species: metaid_0000049
type: SpeciesReference

metaid_0000046
type: Species
is homolog to: P06400
constant: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: metaid_0000045
name: pRB
boundary condition: false
notes: retinoblastoma tumor suppressor protein

metaid_0000055
modifier: 039974
modifier: 039986
modifier: 039998
kinetic law: 040010
type: Reaction
product: 039962
is version of: GO:0006412
fast: false
name: pRB synthesis
reversible: false

040142
stoichiometry: 1.0
species: metaid_0000048
type: SpeciesReference

metaid_0000074
kinetic law: 040814
product: 040802
reactant: 040790
is version of: GO:0031658
fast: false
reversible: false
name: CycE inibition
type: Reaction

metaid_0000051
name: AP1
constant: false
is homolog to: P01100
initial amount: NaN
notes: c-Jun/Fos dimers
has only substance units: false
type: Species
initial concentration: 0.1
boundary condition: false
in compartment: metaid_0000045

metaid_0000025
constant: true
value: 0.023
name: phi_CycDi
type: Parameter

040082
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

metaid_0000065
kinetic law: 040430
reactant: 040418
is version of: GO:0030163
fast: false
reversible: false
name: CycD degradation2
type: Reaction

metaid_0000015
constant: true
value: 4.0
name: Km2
type: Parameter

metaid_0000035
constant: true
value: 0.04
name: phi_pRBpp
type: Parameter

metaid_0000066
is version of: GO:0006412
kinetic law: 040490
modifier: 040454
fast: false
modifier: 040478
reversible: false
product: 040442
name: AP1 synthesis
type: Reaction
modifier: 040466

040202
stoichiometry: 1.0
species: metaid_0000048
type: SpeciesReference

040742
stoichiometry: 1.0
species: metaid_0000054
type: SpeciesReference

040298
stoichiometry: 1.0
species: metaid_0000050
type: SpeciesReference

040418
stoichiometry: 1.0
species: metaid_0000050
type: SpeciesReference

metaid_0000071
kinetic law: 040658
reactant: 040646
is version of: GO:0030163
fast: false
reversible: false
name: pRBp degradation
type: Reaction

metaid_0000045
constant: true
size: 1.0
spatial dimensions: 3.0
name: cell
type: Compartment

metaid_0000043
constant: true
value: 0.06
name: phi_CycEi
type: Parameter

metaid_0000052
initial amount: NaN
boundary condition: false
has only substance units: false
type: Species
name: pRBpp
initial concentration: 0.1
in compartment: metaid_0000045
is homolog to: P06400
constant: false
notes: diphosphorylated form of pRB

040118
stoichiometry: 1.0
species: metaid_0000046
type: SpeciesReference

metaid_0000024
constant: true
value: 0.3
name: Km4
type: Parameter

metaid_0000014
constant: true
value: 0.04
name: a
type: Parameter

040334
stoichiometry: 1.0
species: metaid_0000049
type: SpeciesReference

metaid_0000034
constant: true
value: 0.1
name: k76
type: Parameter

metaid_0000067
kinetic law: 040514
reactant: 040502
is version of: GO:0030163
fast: false
reversible: false
name: Ap1 degradation
type: Reaction

040790
stoichiometry: 1.0
species: metaid_0000054
type: SpeciesReference

040826
stoichiometry: 1.0
species: metaid_0000053
type: SpeciesReference

metaid_0000044
constant: true
value: 0.05
name: phi_CycEa
type: Parameter

metaid_0000072
kinetic law: 040718
reversible: false
fast: false
is version of: GO:0006412
modifier: 040694
modifier: 040706
modifier: 040682
name: CycE synthesis
type: Reaction
product: 040670

W3 CDTF: Mon Aug 17 15:15:15 BST 2009

orgname: EMBL-EBI

given: Lukas
family: Endler

W3 CDTF: Thu Aug 09 17:28:08 BST 2012