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beuke10

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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 0.24615354235788 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 6.25168191520823 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.000170870057152887 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 8.4396878325918 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 8.4396878325918 c1 (nucleus)
JNK JNK 0.982009456703999 default (cytoplasm)
JNK_P JNK_P 0.0179905432960006 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9998313157222 c1 (nucleus)
MSK1_P MSK1_P 0.000168684277806875 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669284 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511779 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 0.829034372153804 default (cytoplasm)
p38_P p38_P 0.170965627846196 default (cytoplasm)
p65_2P p65_2P 0.000000397559152543905 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.000570886877218979 c1 (nucleus)
p65_cytoplasm p65 0.000696598456889738 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0347787246987784 c1 (nucleus)
s11 IkBa 0.492306535300222 c1 (nucleus)
s14 IKKb 0.299986251897689 default (cytoplasm)
s15 IKKb_p 0.0000137481023113396 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.107747249215877 default (cytoplasm)
s3 p65_P 0.0045725866204645 default (cytoplasm)
s5 IkBa_p 0.0143429657251615 default (cytoplasm)
s8 p65_P 0.228543326011228 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 1.12012501519371
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 999.999747666759
IKKb_basal_phosphoylation_k 0.000000100000000221985
IKKb_dephopshorylation_k 0.00218201934907053
IkBa_deg_complex_cyt_k 0.00001
IkBa_deg_complex_nuc_k 0.0000100784831509279
IkBa_deg_cyt_k 0.0000263184315126283
IkBa_deg_nuc_k 0.00001
IkBa_mRNA_deg_cyt_k 0.000210245030513269
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 0.0999999999999998
IkBa_p65_dissociation_k 0.000299999999999999
IkBa_p65_nuclear_export_k 0.00199999999048107
IkBa_p65_nuclear_import_k 0.0000105840674496221
IkBa_p65_phosphorylation_kM 0.1
IkBa_p65_phosphorylation_kcat 12.2948323895773
IkBa_p65_phosphorylation_vmax 0.000169030613592681
IkBa_p_active_degradation_k 0.00999999999999978
IkBa_phosphorylation_kM 0.5
IkBa_phosphorylation_kcat 12.2948323895773
IkBa_phosphorylation_vmax 0.000169030613592681
IkBa_transcription_elongation_kbasal 0.00253075304576218
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000129463705141222
IkBa_transcription_kA_p65 0.61344720050337
IkBa_translation_Km 9.86262014219756
IkBa_translation_vmax 0.000389961249687994
JNK_active_phoshorylation_Km 1.40482967455377
JNK_active_phosphorylation_kcat 14242.2772650189
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.0000129042787872645
JNK_dephosphorylation_k 0.000704376938069221
LPS_LSEC_degradation_k 0.000333538717101295
LPS_MC_degradation_k 0.000144691531716043
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.00000172419833147535
MSK1_dephosphorylation_k 0.00999999999999978
MSK1_phosphorylation_kcat 0.0000100850583429932
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 0.978126286843748
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.000012024024024793
TNFa_LSEC_translation_k 0.0000213500321684928
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.754012694494756
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000546584093798564
TNFa_MC_translation_k 0.00000200280657450139
TNFa_degradation_k 0.000107644105772485
TNFa_mRNA_LSEC_degradation_k 0.608933606390876
TNFa_mRNA_MC_degradation_k 0.0555247609448968
k_IkBa 248129.354373767
k_IkBa_P 2634581.18888326
k_IkBa_mRNA 4483.90580831975
k_JNK_P 2915421.59670066
k_MSK_P 4826667313.54863
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 0.0000679015845264866
k_p38_P 370308.147436699
k_p65 0.102372088824604
k_p65_P 2310916.12550826
p38_active_phoshorylation_Km 1.0884807748579
p38_active_phosphorylation_kcat 139948.704840381
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.00019306790829154
p38_dephosphorylation_k 0.000936211179697006
p65_2P_dephosphorylation 0.00469068413708133
p65_MSK1_phosphorylation_kM 0.00190442700767811
p65_MSK1_phosphrylation_kcat 0.00000571518737470576
p65_MSK1_phosphrylation_vmax 0.000000000964062254833211
p65_P_MSK1_phosphrylation_kM 0.00190442700767811
p65_P_MSK1_phosphrylation_kcat 0.00000571518737470576
p65_P_MSK1_phosphrylation_vmax 0.000000000964062254833211
p65_P_dephosphorylation_k 0.00469068413708133
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 0.491240200000003
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.68185024
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000172018719408048
scaled_p65_P 0.559884800000002
unscaled_IkBa 0.0000051814707826279
unscaled_IkBa_P 0.0000001864585544271
unscaled_IkBa_mRNA 0.0000812720015937527
unscaled_JNK_P 0.000000233877062848008
unscaled_MSK_P 0.0000000001349474222455
unscaled_p38_P 0.00000222255316200055
unscaled_p65 0.00000168032831392911
unscaled_p65_P 0.000000242278286875021

Local parameters

Id Value Reaction

Assignment rules

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

Rate rules

Definition

Algebraic rules

Definition
Definition
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)
activated_Transcription__1(k1, k2, Modifier, k3, Modifier2, Modifier3, k4) = k1 + k2 * Modifier + k3 * Modifier2 + k4 * Modifier3
TNFa_transcription_initiation(kbasal, vA, A, kA) = kbasal + vA * A / (A + kA)
Trigger Assignments