Info! This is a derivative of the model beuke11
Info! This is a derivative of the model beuke15
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beuke15

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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 0.553759259425354 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 3.22913423763466 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.000100039184381124 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 6.0918417093312 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 6.0918417093312 c1 (nucleus)
JNK JNK 0.927842435336309 default (cytoplasm)
JNK_P JNK_P 0.0721575646636914 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.999279347004 c1 (nucleus)
MSK1_P MSK1_P 0.000720652995965723 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669291 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511811 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 0.808627081500007 default (cytoplasm)
p38_P p38_P 0.191372918499993 default (cytoplasm)
p65_2P p65_2P 0.216927924797993 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.854435434176943 c1 (nucleus)
p65_cytoplasm p65 0.000344111747718407 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.01720113644126 c1 (nucleus)
s11 IkBa 1.10751842391647 c1 (nucleus)
s14 IKKb 0.299979368938256 default (cytoplasm)
s15 IKKb_p 0.0000206310617440954 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.0427216608889609 default (cytoplasm)
s3 p65_P 0.00435834985769916 default (cytoplasm)
s5 IkBa_p 0.0726048407784883 default (cytoplasm)
s8 p65_P 0.217898409179996 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 0.00100000000000022
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 1000.0
IKKb_basal_phosphoylation_k 0.0000749782205031676
IKKb_dephopshorylation_k 1.09019688611586
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 0.000238309135178843
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 0.018010806454204
IkBa_p65_dissociation_k 0.000054032419362612
IkBa_p65_nuclear_export_k 0.000100000000000222
IkBa_p65_nuclear_import_k 0.00199999999999978
IkBa_p65_phosphorylation_kM 0.5
IkBa_p65_phosphorylation_kcat 10.5774114674864
IkBa_p65_phosphorylation_vmax 0.000218223229078414
IkBa_p_active_degradation_k 0.00278247907207367
IkBa_phosphorylation_kM 0.1
IkBa_phosphorylation_kcat 10.5774114674864
IkBa_phosphorylation_vmax 0.000218223229078414
IkBa_transcription_elongation_kbasal 0.00205272947759711
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000100000000000222
IkBa_transcription_kA_p65 0.724395185094474
IkBa_translation_Km 9.86301142075893
IkBa_translation_vmax 0.0008481509538929
JNK_active_phoshorylation_Km 0.568966840627525
JNK_active_phosphorylation_kcat 38785.8630052268
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.0000544709009923005
JNK_dephosphorylation_k 0.000700417394450816
LPS_LSEC_degradation_k 0.000237811878843816
LPS_MC_degradation_k 0.000119976428327166
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.00000734955782406374
MSK1_dephosphorylation_k 0.00997750729678741
MSK1_phosphorylation_kcat 0.0000384043775977844
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 1.066831184478
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000121839556946101
TNFa_LSEC_translation_k 0.0000216224881777563
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.820812703471533
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000585014238232532
TNFa_MC_translation_k 0.00000214362891215152
TNFa_degradation_k 0.000155188593113988
TNFa_mRNA_LSEC_degradation_k 0.595382327452443
TNFa_mRNA_MC_degradation_k 0.0518515375370093
k_IkBa 125215.750086731
k_IkBa_P 520457.138768405
k_IkBa_mRNA 8680.94804828611
k_JNK_P 726881.771938882
k_MSK_P 1129784923.61492
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 0.0000890147601567767
k_p38_P 330819.874720568
k_p65 0.102372088824604
k_p65_P 2423982.18094116
p38_active_phoshorylation_Km 0.704510353296192
p38_active_phosphorylation_kcat 111677.069964186
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.000167773486051032
p38_dephosphorylation_k 0.000708910045590036
p65_2P_dephosphorylation 0.000559909778156753
p65_MSK1_phosphorylation_kM 1.02705609273782
p65_MSK1_phosphrylation_kcat 0.901014753000316
p65_MSK1_phosphrylation_vmax 0.000649318981158994
p65_P_MSK1_phosphrylation_kM 1.02705609273782
p65_P_MSK1_phosphrylation_kcat 0.901014753000316
p65_P_MSK1_phosphrylation_vmax 0.000649318981158994
p65_P_dephosphorylation_k 0.000559909778156753
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 0.491240199999999
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.68185024
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000170110053457801
scaled_p65_P 0.5598848
unscaled_IkBa 0.0000102676779806812
unscaled_IkBa_P 0.000000943862930120348
unscaled_IkBa_mRNA 0.0000419788251205981
unscaled_JNK_P 0.000000938048340627988
unscaled_MSK_P 0.000000000576522396772579
unscaled_p38_P 0.0000024878479404999
unscaled_p65 0.00000166168391610387
unscaled_p65_P 0.000000230977275494086

Local parameters

Id Value Reaction

Assignment rules

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

Rate rules

Definition

Algebraic rules

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