Info! This is a derivative of the model beuke13-user-1900
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beuke13

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Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
1e-06 litre
1e-12 mole
Id Name Spatial dimensions Size
EL EL 3.0 0.00000259
LSEC LSEC 3.0 0.00000047
MC MC 3.0 0.00000035
c1 nucleus 3.0 0.0000008
default cytoplasm 3.0 0.000013
Id Name Initial quantity Compartment Fixed
IkBa_cytoplasm IkBa 0.564988584462963 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 2.79615255717589 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.0000866748867250049 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 5.33067431606035 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 5.33067431606035 c1 (nucleus)
JNK JNK 0.610494254930111 default (cytoplasm)
JNK_P JNK_P 0.38950574506989 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9534172138408 c1 (nucleus)
MSK1_P MSK1_P 0.0465827861591864 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669316 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511923 default (cytoplasm)
TNFa_TNFR1_EL TNFa:TNFR1 0.0 EL (EL)
TNFa_TNFR1_cytoplasm TNFa:TNFR1 0.0 default (cytoplasm)
TNFa_mRNA_LSEC TNFa_mRNA 0.0 LSEC (LSEC)
TNFa_mRNA_MC TNFa_mRNA 0.0 MC (MC)
TNFa_pre_mRNA_LSEC TNFa_pre_mRNA 0.0 LSEC (LSEC)
TNFa_pre_mRNA_MC TNFa_pre_mRNA 0.0 MC (MC)
p38 p38 0.573949218303294 default (cytoplasm)
p38_P p38_P 0.426050781696706 default (cytoplasm)
p65_2P p65_2P 0.228927278358454 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.84799128781868 c1 (nucleus)
p65_cytoplasm p65 0.000334685105954136 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0167298646806817 c1 (nucleus)
s11 IkBa 1.12997707322809 c1 (nucleus)
s14 IKKb 0.299976297560879 default (cytoplasm)
s15 IKKb_p 0.0000237024391214021 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.042399452680612 default (cytoplasm)
s3 p65_P 0.00435353355955181 default (cytoplasm)
s5 IkBa_p 0.073948097360867 default (cytoplasm)
s8 p65_P 0.217657350208359 c1 (nucleus)

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
Complex_association_c Complex_association_c p65_cytoplasm + IkBa_cytoplasm = s19

default * (IkBa_p65_association_k * IkBa_cytoplasm * p65_cytoplasm - IkBa_p65_dissociation_k * s19)
Complex_degradation_IkBa_c Complex_degradation_IkBa_c s19 > p65_cytoplasm

default * IkBa_deg_complex_cyt_k * s19
Complex_degradation_IkBa_n Complex_degradation_IkBa_n p65_IkBa_nucleus > p65_nucleus

c1 * IkBa_deg_complex_nuc_k * p65_IkBa_nucleus
Complex_degradation_p65_c Complex_degradation_p65_c s19 > IkBa_cytoplasm

default * p65_degradation_k * s19
Complex_degradation_p65_n Complex_degradation_p65_n p65_IkBa_nucleus > s11

c1 * p65_degradation_k * p65_IkBa_nucleus
Complex_nuclear_shuttle Complex_nuclear_shuttle p65_IkBa_nucleus = s19

IkBa_p65_nuclear_export_k * p65_IkBa_nucleus - IkBa_p65_nuclear_import_k * s19
IKK_phosphorylation IKK_phosphorylation s14 > s15

default * Catalytic_activation__irrev(s14, TNFa_TNFR1_EL, IKKb_active_phosphorylation_kM, IKKb_active_phosphorylation_vmax, IKKb_active_phosphorylation_kA)
IkBa_degradation_c IkBa_degradation_c IkBa_cytoplasm > ∅

default * IkBa_deg_cyt_k * IkBa_cytoplasm
IkBa_degradation_n IkBa_degradation_n s11 > ∅

c1 * IkBa_deg_nuc_k * s11
IkBa_mRNA_degradation_c IkBa_mRNA_degradation_c IkBa_mRNA_cytoplasm > ∅

default * IkBa_mRNA_deg_cyt_k * IkBa_mRNA_cytoplasm
IkBa_mRNA_degradation_n IkBa_mRNA_degradation_n IkBa_mRNA_nucleus > ∅

c1 * IkBa_mRNA_deg_nuc_k * IkBa_mRNA_nucleus
IkBa_mRNA_transport IkBa_mRNA_transport IkBa_mRNA_nucleus > IkBa_mRNA_cytoplasm

IkBa_mRNA_transport_k * IkBa_mRNA_nucleus
IkBa_nuclear_shuttle IkBa_nuclear_shuttle IkBa_cytoplasm = s11

IkBa_nuclear_import_k * IkBa_cytoplasm - IkBa_nuclear_export_k * s11
IkBa_phosphorylation IkBa_phosphorylation IkBa_cytoplasm > s5

default * Henri_Michaelis_Menten__irreversible(IkBa_cytoplasm, IkBa_phosphorylation_kM, IkBa_phosphorylation_vmax)
IkBa_transcription_elongation_1 IkBa_transcription_elongation_1 IkBa_pre_mRNA_1 > IkBa_pre_mRNA_2

c1 * IkBa_transcription_elongation_kbasal * IkBa_pre_mRNA_1
IkBa_transcription_elongation_2 IkBa_transcription_elongation_2 IkBa_pre_mRNA_2 > IkBa_mRNA_nucleus

c1 * IkBa_transcription_elongation_kbasal * IkBa_pre_mRNA_2
IkBa_translation IkBa_translation IkBa_mRNA_cytoplasm > IkBa_mRNA_cytoplasm + IkBa_cytoplasm

default * Henri_Michaelis_Menten__irreversible(IkBa_mRNA_cytoplasm, IkBa_translation_Km, IkBa_translation_vmax)
JNK_active_phosphorylation JNK_active_phosphorylation JNK > JNK_P

default * Henri_Michaelis_Menten__irreversible(JNK, JNK_active_phoshorylation_Km, JNK_active_phosphorylation_vmax)
JNK_basal_phosphorylation JNK_basal_phosphorylation JNK > JNK_P

default * JNK_basal_phosphorylation_k * JNK
JNK_dephosphorylation JNK_dephosphorylation JNK_P > JNK

default * JNK_dephosphorylation_k * JNK_P
LPS_LSEC_degradation LPS_LSEC_degradation LPS > ∅

EL * LPS_LSEC_degradation_k * LPS
LPS_MC_degradation LPS_MC_degradation LPS > ∅

EL * LPS_MC_degradation_k * LPS
MSK1_activation MSK1_activation MSK1 > MSK1_P

c1 * Henri_Michaelis_Menten__irreversible(MSK1, MSK1_activation_kM, MSK1_activation_vmax)
MSK1_deactivation MSK1_deactivation MSK1_P > MSK1

c1 * MSK1_dephosphorylation_k * MSK1_P
TNFR1_shuttle TNFR1_shuttle TNFR1_cytoplasm = TNFR1_EL

k_TNFR1_vessicle2outer_membrane_shuttle * TNFR1_cytoplasm - k_TNFR1_outer_membrane2vessicle_shuttle * TNFR1_EL
TNFa_LSEC_transcription_elongation TNFa_LSEC_transcription_elongation TNFa_pre_mRNA_LSEC > TNFa_mRNA_LSEC

LSEC * TNFa_LSEC_transcription_elongation_k * TNFa_pre_mRNA_LSEC
TNFa_LSEC_transcription_initiation TNFa_LSEC_transcription_initiation ∅ > {2.0}TNFa_pre_mRNA_LSEC

LSEC * TNFa_transcription_initiation(TNFa_LSEC_transcription_initiation_kbasal, TNFa_LSEC_transcription_initiation_vA_LPS, LPS, TNFa_LSEC_transcription_initiation_kA_LPS)
TNFa_LSEC_translation TNFa_LSEC_translation TNFa_mRNA_LSEC > TNFa_mRNA_LSEC + s16

TNFa_LSEC_translation_k * TNFa_mRNA_LSEC
TNFa_MC_transcription_elongation TNFa_MC_transcription_elongation TNFa_pre_mRNA_MC > TNFa_mRNA_MC

MC * TNFa_MC_transcription_elongation_k * TNFa_pre_mRNA_MC
TNFa_MC_transcription_initiation TNFa_MC_transcription_initiation ∅ > {2.0}TNFa_pre_mRNA_MC

MC * TNFa_transcription_initiation(TNFa_MC_transcription_initiation_kbasal, TNFa_MC_transcription_initiation_vA_LPS, LPS, TNFa_MC_transcription_initiation_kA_LPS)
TNFa_MC_translation TNFa_MC_translation TNFa_mRNA_MC > TNFa_mRNA_MC + s16

TNFa_MC_translation_k * TNFa_mRNA_MC
TNFa_TNFR1_association TNFa:TNFR1_association TNFR1_EL + s16 = TNFa_TNFR1_EL

EL * (k_TNFa_TNFR1_association * TNFR1_EL * s16 - k_TNFa_TNFR1_dissociation * TNFa_TNFR1_EL)
TNFa_TNFR1_internalisation TNFa:TNFR1_internalisation TNFa_TNFR1_EL > TNFa_TNFR1_cytoplasm

k_TNFa_TNFR1_internalisation * TNFa_TNFR1_EL
TNFa_degradation TNFa degradation s16 > ∅

EL * TNFa_degradation_k * s16
TNFa_internal_degradation TNFa_internal_degradation TNFa_TNFR1_cytoplasm > TNFR1_cytoplasm

default * k_TNFa_internal_degradation * TNFa_TNFR1_cytoplasm
TNFa_mRNA_LSEC_degradation TNFa_mRNA_LSEC_degradation TNFa_mRNA_LSEC > ∅

LSEC * TNFa_mRNA_LSEC_degradation_k * TNFa_mRNA_LSEC
TNFa_mRNA_MC_degradation TNFa_mRNA_MC_degradation TNFa_mRNA_MC > ∅

MC * TNFa_mRNA_MC_degradation_k * TNFa_mRNA_MC
basal_IKKb_phosphorylation basal_IKKb_phosphorylation s14 > s15

default * IKKb_basal_phosphoylation_k * s14
p38_active_phosphorylation p38_active_phosphorylation p38 > p38_P

default * Henri_Michaelis_Menten__irreversible(p38, p38_active_phoshorylation_Km, p38_active_phosphorylation_vmax)
p38_basal_phosphorylation p38_basal_phosphorylation p38 > p38_P

default * p38_basal_phosphorylation_k * p38
p38_dephosphorylation p38_dephosphorylation p38_P > p38

default * p38_dephosphorylation_k * p38_P
p65_2P_degradation p65_2P_degradation p65_2P > ∅

c1 * p65_degradation_k * p65_2P
p65_2P_dephosphorylation_0 p65_2P_dephosphorylation p65_2P > p65_nucleus

c1 * p65_2P_dephosphorylation * p65_2P
p65_P_degradation_c p65_P_degradation_c s3 > ∅

default * p65_degradation_k * s3
p65_P_degradation_n p65_P_degradation_n s8 > ∅

c1 * p65_degradation_k * s8
p65_P_dephosphorylation_c p65_P_dephosphorylation_c s8 > p65_nucleus

c1 * p65_P_dephosphorylation_k * s8
p65_P_dephosphorylation_n p65_P_dephosphorylation_n s3 > p65_cytoplasm

default * p65_P_dephosphorylation_k * s3
p65_P_phosphorylation_MSK1 p65_P_phosphorylation_MSK1 s8 > p65_2P

c1 * Henri_Michaelis_Menten__irreversible(s8, p65_P_MSK1_phosphrylation_kM, p65_P_MSK1_phosphrylation_vmax)
p65_nuclear_shuttle p65_nuclear_shuttle p65_cytoplasm = p65_nucleus

p65_nuclear_import_k * p65_cytoplasm - p65_nuclear_export_k * p65_nucleus
p65_phosphorylation_MSK1 p65_phosphorylation_MSK1 p65_nucleus > p65_2P

c1 * Henri_Michaelis_Menten__irreversible(p65_nucleus, p65_MSK1_phosphorylation_kM, p65_MSK1_phosphrylation_vmax)
p65_translation p65_translation p65_mRNA > p65_mRNA + p65_cytoplasm

default * p65_translation_k * p65_mRNA
re10 IkBa_transcription_initiation ∅ > IkBa_pre_mRNA_1

c1 * activated_Transcription__1(IkBa_transcription_initiation_kbasal, IkBa_transcription_kA2_p65_P, s8, IkBa_transcription_kA_p65, p65_nucleus, p65_2P, IkBa_transcription_kA3_p65_2P)
re14 IkBa_p_active_degradation s5 > ∅

default * IkBa_p_active_degradation_k * s5
re15 Complex_phosphorylation s19 > s3 + s5

default * Henri_Michaelis_Menten__irreversible(s19, IkBa_p65_phosphorylation_kM, IkBa_p65_phosphorylation_vmax)
re17 dephosphorylation IKK s15 > s14

default * IKKb_dephopshorylation_k * s15
re19 Complex_association_n p65_nucleus + s11 = p65_IkBa_nucleus

c1 * (IkBa_p65_association_k * p65_nucleus * s11 - IkBa_p65_dissociation_k * p65_IkBa_nucleus)
re3 p65_P_nuclear_shuttle s3 = s8

p65_nuclear_import_k * s3 - p65_nuclear_export_k * s8

Global parameters

Id Value
IKKb_active_phosphorylation_kA 0.00100000751793317
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 999.994251892825
IKKb_basal_phosphoylation_k 0.0000750988514561613
IKKb_dephopshorylation_k 0.950445449749497
IkBa_deg_complex_cyt_k 0.00001
IkBa_deg_complex_nuc_k 0.0000100000000002221
IkBa_deg_cyt_k 0.0000100000000002221
IkBa_deg_nuc_k 0.00001
IkBa_mRNA_deg_cyt_k 0.00023844546542126
IkBa_mRNA_deg_nuc_k 0.00005
IkBa_mRNA_transport_k 0.0001
IkBa_nuclear_export_k 0.0025
IkBa_nuclear_import_k 0.005
IkBa_p65_association_k 0.0182773778651534
IkBa_p65_dissociation_k 0.0000548321335954604
IkBa_p65_nuclear_export_k 0.000100000000000222
IkBa_p65_nuclear_import_k 0.00199999999999978
IkBa_p65_phosphorylation_kM 0.5
IkBa_p65_phosphorylation_kcat 9.35331903485181
IkBa_p65_phosphorylation_vmax 0.000221696475006626
IkBa_p_active_degradation_k 0.0027815203293068
IkBa_phosphorylation_kM 0.1
IkBa_phosphorylation_kcat 9.35331903485181
IkBa_phosphorylation_vmax 0.000221696475006626
IkBa_transcription_elongation_kbasal 0.00203245678351198
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000100000000000222
IkBa_transcription_kA_p65 0.644877105549519
IkBa_translation_Km 8.62022804518077
IkBa_translation_vmax 0.000869570552810696
JNK_active_phoshorylation_Km 0.00100000000000022
JNK_active_phosphorylation_kcat 128223.281718797
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.000297281217739997
JNK_dephosphorylation_k 0.000465945567751045
LPS_LSEC_degradation_k 0.000237613611887944
LPS_MC_degradation_k 0.000119938547034168
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.000426047912774491
MSK1_dephosphorylation_k 0.00894728276588594
MSK1_phosphorylation_kcat 0.000999993266243514
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 1.06727068122671
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000121773968583006
TNFa_LSEC_translation_k 0.0000216264815881264
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.820922917690253
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000585088364603215
TNFa_MC_translation_k 0.00000214389156706575
TNFa_degradation_k 0.000155294844602142
TNFa_mRNA_LSEC_degradation_k 0.595159854597121
TNFa_mRNA_MC_degradation_k 0.0518402782192837
k_IkBa 123151.961018769
k_IkBa_P 511003.109490479
k_IkBa_mRNA 10025.184947558
k_JNK_P 134657.881495759
k_MSK_P 17478192.2064024
k_TNFR1_outer_membrane2vessicle_shuttle 0.000018
k_TNFR1_vessicle2outer_membrane_shuttle 0.0004
k_TNFa_TNFR1_association 16.833
k_TNFa_TNFR1_dissociation 0.000319827
k_TNFa_TNFR1_internalisation 0.00077
k_TNFa_internal_degradation 0.0000899671747509247
k_p38_P 148597.227473568
k_p65 0.102372088824604
k_p65_P 2426666.054545
p38_active_phoshorylation_Km 0.10616767037577
p38_active_phosphorylation_kcat 166798.143477709
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.000370463577422213
p38_dephosphorylation_k 0.000499065580456255
p65_2P_dephosphorylation 0.000552351266083683
p65_MSK1_phosphorylation_kM 0.945158930722195
p65_MSK1_phosphrylation_kcat 0.0135882089748922
p65_MSK1_phosphrylation_vmax 0.00063297663296374
p65_P_MSK1_phosphrylation_kM 0.945158930722195
p65_P_MSK1_phosphrylation_kcat 0.0135882089748922
p65_P_MSK1_phosphrylation_vmax 0.00063297663296374
p65_P_dephosphorylation_k 0.000552351266083683
p65_degradation_k 0.00001328912101
p65_nuclear_export_k 0.00001
p65_nuclear_import_k 0.0005
p65_translation_k 0.00000168
scaled_IkBa 1.285675
scaled_IkBa_P 0.4912402
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.68185024
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000170058912073069
scaled_p65_P 0.5598848
unscaled_IkBa 0.0000104397444373952
unscaled_IkBa_P 0.00000096132526569127
unscaled_IkBa_mRNA 0.000036350052583196
unscaled_JNK_P 0.00000506357468590857
unscaled_MSK_P 0.0000000372662289273491
unscaled_p38_P 0.00000553866016205718
unscaled_p65 0.00000166118435235247
unscaled_p65_P 0.000000230721816440861

Local parameters

Id Value Reaction

Assignment rules

Definition
scaled_JNK_P = k_JNK_P * unscaled_JNK_P
p65_P_MSK1_phosphrylation_kcat = p65_MSK1_phosphrylation_kcat * 1.0
p65_nuclear_export_k = p65_nuclear_import_k * 0.02
unscaled_p38_P = default * p38_P
scaled_p65 = k_p65 * unscaled_p65
k_TNFa_TNFR1_dissociation = k_TNFa_TNFR1_association * 1.9e-5
scaled_IkBa = k_IkBa * unscaled_IkBa
p65_P_MSK1_phosphrylation_kM = p65_MSK1_phosphorylation_kM * 1.0
scaled_p38_P = k_p38_P * unscaled_p38_P
MSK1_activation_vmax = MSK1_phosphorylation_kcat * p38_P
unscaled_JNK_P = default * JNK_P
unscaled_MSK_P = c1 * MSK1_P
unscaled_IkBa_P = s5 * default
IkBa_nuclear_export_k = IkBa_nuclear_import_k * 0.5
IkBa_p65_dissociation_k = IkBa_p65_association_k * 0.003
scaled_MSK_P = k_MSK_P * unscaled_MSK_P
unscaled_p65_P = c1 * s8 + default * s3
IkBa_phosphorylation_kcat = IkBa_p65_phosphorylation_kcat
p65_2P_dephosphorylation = p65_P_dephosphorylation_k * 1.0
IkBa_p65_phosphorylation_vmax = IkBa_p65_phosphorylation_kcat * s15
JNK_active_phosphorylation_vmax = JNK_active_phosphorylation_kcat * TNFa_TNFR1_EL
scaled_IkBa_mRNA = k_IkBa_mRNA * unscaled_IkBa_mRNA
unscaled_p65 = (s3 + s19 + p65_cytoplasm) * default + c1 * (s8 + p65_IkBa_nucleus + p65_nucleus + p65_2P)
unscaled_IkBa = (s11 + p65_IkBa_nucleus) * c1 + (s5 + s19 + IkBa_cytoplasm) * default
p38_active_phosphorylation_vmax = p38_active_phosphorylation_kcat * TNFa_TNFR1_EL
p65_P_MSK1_phosphrylation_vmax = p65_P_MSK1_phosphrylation_kcat * MSK1_P
p65_MSK1_phosphrylation_vmax = p65_MSK1_phosphrylation_kcat * MSK1_P
scaled_IkBa_P = k_IkBa_P * unscaled_IkBa_P
unscaled_IkBa_mRNA = IkBa_mRNA_cytoplasm * default + c1 * IkBa_mRNA_nucleus
IkBa_phosphorylation_vmax = IkBa_phosphorylation_kcat * s15
scaled_p65_P = k_p65_P * unscaled_p65_P

Rate rules

Definition

Algebraic rules

Definition
Definition
Henri_Michaelis_Menten__irreversible(substrate, Km, V) = V * substrate / (Km + substrate)
TNFa_transcription_initiation(kbasal, vA, A, kA) = kbasal + vA * A / (A + kA)
Catalytic_activation__irrev(substrate, Activator, Kms, V, Ka) = V * substrate * Activator / ((Kms + substrate) * (Ka + Activator))
activated_Transcription__1(k1, k2, Modifier, k3, Modifier2, Modifier3, k4) = k1 + k2 * Modifier + k3 * Modifier2 + k4 * Modifier3
Trigger Assignments