BIOMD0000000243
type: SBMLModel
parameter: metaid_0000005
species: metaid_0000036
reaction: metaid_0000068
species: metaid_0000029
parameter: metaid_0000021
reaction: metaid_0000059
species: metaid_0000043
species: metaid_0000033
parameter: metaid_0000020
is part of: GO:0051092
species: metaid_0000026
parameter: metaid_0000017
parameter: metaid_0000011
length unit: length
parameter: metaid_0000009
species: metaid_0000030
species: metaid_0000040
reaction: metaid_0000065
species: metaid_0000023
substance units: metaid_0000004
reaction: metaid_0000064
reaction: metaid_0000050
units def: metaid_0000004
reaction: metaid_0000054
is part of: REACT 1619
reaction: metaid_0000057
reaction: metaid_0000049
occurs in: http://identifiers.org/taxonomy/9606
parameter: metaid_0000018
is described by: http://identifiers.org/pubmed/20212524
species: metaid_0000037
reaction: metaid_0000048
reaction: metaid_0000067
species: metaid_0000034
species: metaid_0000044
reaction: metaid_0000058
species: metaid_0000027
parameter: metaid_0000008
is: MODEL1003100001
volume units: metaid_0000003
species: metaid_0000031
species: metaid_0000041
reaction: metaid_0000053
parameter: metaid_0000016
parameter: metaid_0000010
species: metaid_0000024
parameter: metaid_0000013
parameter: metaid_0000015
area units: metaid_0000005
units def: metaid_0000003
is part of: GO:0008624
reaction: metaid_0000063
species: metaid_0000038
reaction: metaid_0000056
reaction: metaid_0000062
time units: metaid_0000003
reaction: metaid_0000066
reaction: metaid_0000047
species: metaid_0000035
species: metaid_0000045
notes: This is the reduced model (model 8) described in: Dynamics within the CD95 death-inducing signaling complex decide life and death of cells. Leo Neumann, Carina Pforr, Joel Beaudouin, Alexander Golks, Peter H. Krammer, Inna N. Lavrik and Roland Eils (German Cancer Research Center (DKFZ), http://www.dkfz.de ); Mol Sys Biol 2010; 6 :352. doi: 10.1038/msb.2010.6 ; Abstract: This study explores the dilemma in cellular signaling that triggering of CD95 (Fas/APO-1) in some situations results in cell death and in others leads to the activation of NF-κB. We established an integrated kinetic mathematical model for CD95-mediated apoptotic and NF-κB signaling. Systematic model reduction resulted in a surprisingly simple model well approximating experimentally observed dynamics. The model postulates a new link between c-FLIP L cleavage in the death-inducing signaling complex (DISC) and the NF-κB pathway. We validated experimentally that CD95 stimulation resulted in an interaction of p43-FLIP with the IKK complex followed by its activation. Furthermore, we showed that the apoptotic and NF-κB pathways diverge already at the DISC. Model and experimental analysis of DISC formation showed that a subtle balance of c-FLIP L and procaspase-8 determines life/death decisions in a nonlinear manner. We present an integrated model describing the complex dynamics of CD95-mediated apoptosis and NF-κB signaling. The original was taken from the MSB article supplementary material site msb20106-s2.xml . All the species ids were changed since the model was not a valid SBML with its original ids - Lukas. Notes added to the species [L] (the initial concentration of Anti-CD95), regarding changes to be made in the initial concentration of [L], to obtain figure 5D. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team. For more information see the terms of use . To cite BioModels Database, please use Le Novère N., Bornst…
reaction: metaid_0000046
species: metaid_0000028
reaction: metaid_0000061
species: metaid_0000042
species: metaid_0000032
parameter: metaid_0000007
species: metaid_0000025
reaction: metaid_0000060
parameter: metaid_0000006
compartment: metaid_0000022
reaction: metaid_0000052
is part of: REACT_21281
parameter: metaid_0000012
curated: true
reaction: metaid_0000051
parameter: metaid_0000014
reaction: metaid_0000055
species: metaid_0000039

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

metaid_0000036
type: Species
is: SBO:0000296
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000022
name: p43-FLIP:IKK*

metaid_0000022
type: Compartment
is: GO:0005623
constant: true
size: 1.0
spatial dimensions: 3.0
name: default

metaid_0000068
type: Reaction
kinetic law: 762761
reactant: 762749
is version of: GO:0030163
fast: false
reversible: false
name: reaction_23

762749
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000037

metaid_0000037
type: Species
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initial amount: NaN
is: SBO:0000245
name: NF-kB*
is version of: P19838
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boundary condition: false
constant: false
is version of: GO:0071159

metaid_0000029
type: Species
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is: SBO:0000245
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name: C3
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is version of: P42574

metaid_0000021
type: Parameter
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value: 0.0064182
name: k17

metaid_0000059
type: Reaction
kinetic law: 762398
product: 762385
reactant: 762373
reactant: 762361
fast: false
reversible: false
name: reaction_14

762385
type: SpeciesReference
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species: metaid_0000031

metaid_0000031
type: Species
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is version of: Q14790
is: SBO:0000245

762373
type: SpeciesReference
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metaid_0000028
type: Species
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is: SBO:0000245
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boundary condition: false
constant: false

762361
type: SpeciesReference
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species: metaid_0000028

metaid_0000043
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has part: Q13158
name: L:RF:FL:FL
in compartment: metaid_0000022
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metaid_0000033
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initial concentration: 0.0
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metaid_0000020
type: Parameter
constant: true
value: 0.02229912
name: k16

metaid_0000026
type: Species
is: SBO:0000296
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initial amount: NaN
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name: L:RF:FL
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has only substance units: false
boundary condition: false

metaid_0000017
type: Parameter
constant: true
value: 7.204261E-4
name: k13

metaid_0000011
type: Parameter
constant: true
value: 0.8875063
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metaid_0000009
type: Parameter
constant: true
value: 5.946569E-4
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metaid_0000030
type: Species
initial concentration: 64.47652
initial amount: NaN
constant: false
is: SBO:0000245
name: C8
has only substance units: false
in compartment: metaid_0000022
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is version of: Q14790

metaid_0000040
type: Species
initial concentration: 5.083923
is version of: O15519
boundary condition: false
constant: false
in compartment: metaid_0000022
is: SBO:0000245
has only substance units: false
name: FS
initial amount: NaN

metaid_0000065
type: Reaction
reversible: false
fast: false
kinetic law: 762676
name: reaction_20
reactant: 762628
product: 762664
is version of: GO:0006468
is version of: GO:0008384
reactant: 762640
product: 762652
is version of: http://identifiers.org/ec-code/2.7.11.10

762628
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000034

metaid_0000034
type: Species
name: NF-kB:IkB
has only substance units: false
constant: false
boundary condition: false
is: SBO:0000296
initial amount: NaN
has part: P19838
has part: P25963
initial concentration: 4.739546
is version of: REACT 7272
in compartment: metaid_0000022

762664
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000036

762640
type: SpeciesReference
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species: metaid_0000036

762652
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000035

metaid_0000035
type: Species
has part: P25963
has version: REACT 7108
initial concentration: 0.0
constant: false
has version: REACT 7645
is: SBO:0000296
initial amount: NaN
in compartment: metaid_0000022
boundary condition: false
has only substance units: false
name: NF-kB:IkB:P
has part: P19838

metaid_0000023
type: Species
is: SBO:0000245
initial amount: NaN
constant: false
is version of: Q0VHD7
name: L
has only substance units: false
in compartment: metaid_0000022
initial concentration: 113.22
notes: Initial concentration of anti-CD95 = 113.22nM is equivalent to 1500ng/ml. The model as such reproduces the figure 5D (black plot: i.e. anti-CD95=1500ng/ml). To obtain the blue (anti-CD95=500ng/ml) and red (250ng/ml) plot of figure 5D, the model parameter [L] (initial concentration of anti-CD95 [L]) should be set as 37.74nM and 18.87nM respectively.
boundary condition: false

761707
type: SBMLUnit
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE

metaid_0000064
type: Reaction
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reversible: false
product: 762603
reactant: 762579
fast: false
reactant: 762591
name: reaction_19
is version of: GO:0006461
is: SBO:0000526

762603
type: SpeciesReference
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762579
type: SpeciesReference
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762591
type: SpeciesReference
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species: metaid_0000041

metaid_0000041
type: Species
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is version of: O14920
is version of: O15111
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is version of: Q9Y6K9
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name: IKK
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initial concentration: 5.772825
in compartment: metaid_0000022

metaid_0000050
type: Reaction
kinetic law: 761960
product: 761948
product: 761936
reactant: 761924
reactant: 761912
fast: false
reversible: false
name: reaction_5

761948
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species: metaid_0000028

761936
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species: metaid_0000028

761924
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species: metaid_0000030

761912
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000025

metaid_0000025
type: Species
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constant: false
has part: Q0VHD7
is: SBO:0000296
name: L:RF:C8
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metaid_0000054
type: Reaction
name: reaction_9
reactant: 762130
reactant: 762118
is: SBO:0000526
fast: false
reversible: false
product: 762143
kinetic law: 762155
is version of: GO:0006461

762130
type: SpeciesReference
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species: metaid_0000039

metaid_0000039
type: Species
boundary condition: false
name: FL
initial concentration: 7.398562
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762118
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species: metaid_0000026

762143
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species: metaid_0000043

metaid_0000057
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kinetic law: 762299
is: SBO:0000526
reactant: 762263
is version of: GO:0006461
fast: false
product: 762287
reactant: 762275
reversible: false
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762263
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species: metaid_0000027

metaid_0000027
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762287
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species: metaid_0000044

metaid_0000044
type: Species
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is: SBO:0000296
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name: L:RF:FL:FS
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boundary condition: false
has part: Q0VHD7

762275
type: SpeciesReference
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species: metaid_0000039

metaid_0000049
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fast: false
kinetic law: 761900
is version of: GO:0006461
reversible: false
product: 761888
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reactant: 761876
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761888
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761864
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species: metaid_0000024

metaid_0000024
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is: SBO:0000296
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name: L:RF
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initial concentration: 0.0

761876
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000040

metaid_0000018
type: Parameter
constant: true
value: 0.3588224
name: k14

metaid_0000048
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product: 761840
reversible: false
kinetic law: 761852
name: reaction_3
reactant: 761828
reactant: 761816
is version of: GO:0006461
is: SBO:0000526
fast: false

761840
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species: metaid_0000026

761828
type: SpeciesReference
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species: metaid_0000039

761816
type: SpeciesReference
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species: metaid_0000024

metaid_0000067
type: Reaction
kinetic law: 762737
reactant: 762725
is version of: GO:0030163
fast: false
reversible: false
name: reaction_22

762725
type: SpeciesReference
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species: metaid_0000036

metaid_0000058
type: Reaction
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reactant: 762324
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reactant: 762311
is: SBO:0000526
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product: 762336
fast: false

762324
type: SpeciesReference
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species: metaid_0000040

762311
type: SpeciesReference
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species: metaid_0000027

762336
type: SpeciesReference
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species: metaid_0000045

metaid_0000045
type: Species
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initial concentration: 0.0
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has part: P25445
name: L:RF:FS:FS
constant: false
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has part: O15519
is: SBO:0000296
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metaid_0000008
type: Parameter
constant: true
value: 1.0E-5
name: k4

metaid_0000053
type: Reaction
kinetic law: 762105
product: 762093
reactant: 762081
reactant: 762069
fast: false
reversible: false
name: reaction_8

762093
type: SpeciesReference
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species: metaid_0000033

762081
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000030

762069
type: SpeciesReference
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species: metaid_0000026

metaid_0000016
type: Parameter
constant: true
value: 0.1502914
name: k12

metaid_0000010
type: Parameter
constant: true
value: 0.9999999
name: k6

metaid_0000013
type: Parameter
constant: true
value: 0.002249759
name: k9

metaid_0000015
type: Parameter
constant: true
value: 0.02891451
name: k11

761695
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND

metaid_0000063
type: Reaction
kinetic law: 762567
reactant: 762555
is version of: GO:0030163
fast: false
reversible: false
name: reaction_18

762555
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000032

metaid_0000032
type: Species
is: SBO:0000245
name: C3*
is version of: P42574
initial concentration: 0.0
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boundary condition: false
initial amount: NaN
constant: false

metaid_0000038
type: Species
constant: false
has only substance units: false
name: RF
initial concentration: 91.26592
is: SBO:0000296
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metaid_0000056
type: Reaction
name: reaction_11
is version of: GO:0006461
fast: false
kinetic law: 762251
reversible: false
reactant: 762227
reactant: 762215
product: 762239
is: SBO:0000526

762227
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000030

762215
type: SpeciesReference
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species: metaid_0000027

762239
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000042

metaid_0000042
type: Species
initial amount: NaN
constant: false
name: L:RF:C8:FS
has part: O15519
has part: Q13158
initial concentration: 0.0
is: SBO:0000296
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boundary condition: false
has part: Q14790
has part: Q0VHD7

metaid_0000062
type: Reaction
kinetic law: 762543
reactant: 762531
is version of: GO:0030163
fast: false
reversible: false
name: reaction_17

762531
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000031

metaid_0000066
type: Reaction
kinetic law: 762713
product: 762701
reactant: 762688
fast: false
reversible: false
name: reaction_21

762701
type: SpeciesReference
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species: metaid_0000037

762688
type: SpeciesReference
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species: metaid_0000035

metaid_0000047
type: Reaction
name: reaction_2
is version of: GO:0006461
product: 761791
is: SBO:0000526
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kinetic law: 761803
reversible: false
reactant: 761767

761791
type: SpeciesReference
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species: metaid_0000025

761779
type: SpeciesReference
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761767
type: SpeciesReference
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species: metaid_0000024

metaid_0000046
type: Reaction
fast: false
name: reaction_1
product: 761743
reactant: 761731
is version of: GO:0006461
kinetic law: 761755
reactant: 761719
is: SBO:0000526
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761743
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species: metaid_0000024

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species: metaid_0000038

761719
type: SpeciesReference
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species: metaid_0000023

metaid_0000061
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kinetic law: 762519
product: 762506
product: 762494
reactant: 762482
reactant: 762470
fast: false
reversible: false
name: reaction_16

762506
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000032

762494
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000028

762482
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000032

762470
type: SpeciesReference
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species: metaid_0000030

metaid_0000007
type: Parameter
constant: true
value: 0.6693316
name: k3

metaid_0000060
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kinetic law: 762458
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reactant: 762422
reactant: 762410
fast: false
reversible: false
name: reaction_15

762446
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species: metaid_0000031

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type: SpeciesReference
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species: metaid_0000031

762410
type: SpeciesReference
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species: metaid_0000029

metaid_0000006
type: Parameter
constant: true
value: 1.277248E-4
name: k2

metaid_0000052
type: Reaction
name: reaction_7
reversible: false
reactant: 762033
reactant: 762021
kinetic law: 762057
fast: false
is version of: GO:0006461
product: 762045
is: SBO:0000526

762033
type: SpeciesReference
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species: metaid_0000040

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type: SpeciesReference
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species: metaid_0000025

762045
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000042

metaid_0000012
type: Parameter
constant: true
value: 8.044378E-4
name: k8

metaid_0000051
type: Reaction
kinetic law: 762009
product: 761997
reactant: 761984
reactant: 761972
fast: false
reversible: false
name: reaction_6

761997
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species: metaid_0000033

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type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000039

761972
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000025

metaid_0000014
type: Parameter
constant: true
value: 0.1205258
name: k10

metaid_0000055
type: Reaction
reactant: 762167
is version of: GO:0006461
product: 762191
reactant: 762179
is: SBO:0000526
fast: false
kinetic law: 762203
reversible: false
name: reaction_10

762167
type: SpeciesReference
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species: metaid_0000026

762191
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000044

762179
type: SpeciesReference
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species: metaid_0000040

metaid_0000019
type: Parameter
constant: true
value: 3.684162
name: k15

W3 CDTF: Fri Mar 12 12:09:20 GMT 2010

ORG:
  orgname: German Cancer Research Centre, University of Heidelberg, Heidelberg.
n:
  given: Leo
  family: Neumann

ORG:
  orgname: EMBL-EBI
n:
  given: Vijayalakshmi
  family: Chelliah

W3 CDTF: Thu Jun 03 11:14:03 BST 2010