beuke5

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Title

Authors

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Abstract

Journal

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 0.522763709334491 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 2.63517227233744 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.0000673276010851041 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 3.1005818952741 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 3.1005818952741 c1 (nucleus)
JNK JNK 0.616670811976973 default (cytoplasm)
JNK_P JNK_P 0.383329188023027 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9999767369237 c1 (nucleus)
MSK1_P MSK1_P 0.0000232630763425564 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 0.976221762033416 default (cytoplasm)
p38_P p38_P 0.0237782379665834 default (cytoplasm)
p65_2P p65_2P 0.0000000244073607085619 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.995677006901286 c1 (nucleus)
p65_cytoplasm p65 0.000837832928890983 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0418838902101805 c1 (nucleus)
s11 IkBa 1.04552727286279 c1 (nucleus)
s14 IKKb 0.299986453439014 default (cytoplasm)
s15 IKKb_p 0.0000135465609861083 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.0497836762522615 default (cytoplasm)
s3 p65_P 0.00376873197835305 default (cytoplasm)
s5 IkBa_p 0.0710076786866834 default (cytoplasm)
s8 p65_P 0.188408277732023 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 0.165415506192632
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 250.87681998337
IKKb_basal_phosphoylation_k 0.000000131828904190415
IKKb_dephopshorylation_k 0.00291933026171174
IkBa_deg_complex_cyt_k 0.00001
IkBa_deg_complex_nuc_k 0.0000100000000002221
IkBa_deg_cyt_k 0.000049999999999778
IkBa_deg_nuc_k 0.00001
IkBa_mRNA_deg_cyt_k 0.000196535395111827
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 0.0112347785033669
IkBa_p65_dissociation_k 0.0000337043355101007
IkBa_p65_nuclear_export_k 0.000100000000000222
IkBa_p65_nuclear_import_k 0.00199999999999978
IkBa_p65_phosphorylation_kM 0.5
IkBa_p65_phosphorylation_kcat 23.5329180613935
IkBa_p65_phosphorylation_vmax 0.000318790109699757
IkBa_p_active_degradation_k 0.00392563699911632
IkBa_phosphorylation_kM 0.144154720921219
IkBa_phosphorylation_kcat 23.5329180613935
IkBa_phosphorylation_vmax 0.000318790109699757
IkBa_transcription_elongation_kbasal 0.0027143142114213
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000100000000000222
IkBa_transcription_kA_p65 0.200461624497413
IkBa_translation_Km 4.23640360791583
IkBa_translation_vmax 0.000799612745202467
JNK_active_phoshorylation_Km 0.00100000000000022
JNK_active_phosphorylation_kcat 124658.528432239
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.000275215741877753
JNK_dephosphorylation_k 0.000442746131302696
LPS_LSEC_degradation_k 0.000273789277266435
LPS_MC_degradation_k 0.000130836797364456
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.000000237782379671114
MSK1_dephosphorylation_k 0.00999999999999978
MSK1_phosphorylation_kcat 0.0000100000000002221
TNFa_LSEC_transcription_elongation_k 0.00000100000000019659
TNFa_LSEC_transcription_initiation_kA_LPS 1.02839948548981
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000119658064721131
TNFa_LSEC_translation_k 0.0000212429168000038
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.781991352895356
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000564407927057263
TNFa_MC_translation_k 0.00000206824343855873
TNFa_degradation_k 0.000129839671736531
TNFa_mRNA_LSEC_degradation_k 0.602429849586471
TNFa_mRNA_MC_degradation_k 0.0537532979025462
k_IkBa 128578.052923268
k_IkBa_P 532163.681325837
k_IkBa_mRNA 10637.6179728709
k_JNK_P 136827.614750765
k_MSK_P 34998934707.1252
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 0.0000675530979350756
k_p38_P 2662517.08861057
k_p65 0.102372088824604
k_p65_P 2803346.75248691
p38_active_phoshorylation_Km 1.5560380425359
p38_active_phosphorylation_kcat 20617.9840591781
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.0000272905345938646
p38_dephosphorylation_k 0.00112042001621386
p65_2P_dephosphorylation 0.00186568775565587
p65_MSK1_phosphorylation_kM 0.00100000000000022
p65_MSK1_phosphrylation_kcat 0.00000100000000022204
p65_MSK1_phosphrylation_vmax 0.0000000000232630763477219
p65_P_MSK1_phosphrylation_kM 0.00100000000000022
p65_P_MSK1_phosphrylation_kcat 0.00000100000000022204
p65_P_MSK1_phosphrylation_vmax 0.0000000000232630763477219
p65_P_dephosphorylation_k 0.00186568775565587
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 0.000000172788575998792
scaled_p65_P 0.559884799999999
unscaled_IkBa 0.00000999917925936593
unscaled_IkBa_P 0.000000923099822926884
unscaled_IkBa_mRNA 0.0000342572934024676
unscaled_JNK_P 0.00000498327944429935
unscaled_MSK_P 0.0000000000186104610740451
unscaled_p38_P 0.000000309117093565585
unscaled_p65 0.00000168784849447425
unscaled_p65_P 0.000000199720137904208

Local parameters

Id Value Reaction

Assignment rules

Definition
unscaled_IkBa = (s11 + p65_IkBa_nucleus) * c1 + (s5 + s19 + IkBa_cytoplasm) * default
unscaled_IkBa_P = s5 * default
unscaled_p65_P = c1 * s8 + default * s3
IkBa_nuclear_export_k = IkBa_nuclear_import_k * 0.5
IkBa_phosphorylation_kcat = IkBa_p65_phosphorylation_kcat
unscaled_MSK_P = c1 * MSK1_P
scaled_MSK_P = k_MSK_P * unscaled_MSK_P
unscaled_JNK_P = default * JNK_P
JNK_active_phosphorylation_vmax = JNK_active_phosphorylation_kcat * TNFa_TNFR1_EL
unscaled_p38_P = default * p38_P
IkBa_p65_phosphorylation_vmax = IkBa_p65_phosphorylation_kcat * s15
MSK1_activation_vmax = MSK1_phosphorylation_kcat * p38_P
p65_2P_dephosphorylation = p65_P_dephosphorylation_k * 1.0
p65_P_MSK1_phosphrylation_kM = p65_MSK1_phosphorylation_kM * 1.0
p65_MSK1_phosphrylation_vmax = p65_MSK1_phosphrylation_kcat * MSK1_P
scaled_p65 = k_p65 * unscaled_p65
scaled_IkBa = k_IkBa * unscaled_IkBa
scaled_p65_P = k_p65_P * unscaled_p65_P
scaled_IkBa_P = k_IkBa_P * unscaled_IkBa_P
scaled_IkBa_mRNA = k_IkBa_mRNA * unscaled_IkBa_mRNA
p65_P_MSK1_phosphrylation_vmax = p65_P_MSK1_phosphrylation_kcat * MSK1_P
p65_P_MSK1_phosphrylation_kcat = p65_MSK1_phosphrylation_kcat * 1.0
p65_nuclear_export_k = p65_nuclear_import_k * 0.02
scaled_p38_P = k_p38_P * unscaled_p38_P
p38_active_phosphorylation_vmax = p38_active_phosphorylation_kcat * TNFa_TNFR1_EL
scaled_JNK_P = k_JNK_P * unscaled_JNK_P
IkBa_phosphorylation_vmax = IkBa_phosphorylation_kcat * s15
k_TNFa_TNFR1_dissociation = k_TNFa_TNFR1_association * 1.900000e-05
IkBa_p65_dissociation_k = IkBa_p65_association_k * 0.003
unscaled_p65 = (s3 + s19 + p65_cytoplasm) * default + c1 * (s8 + p65_IkBa_nucleus + p65_nucleus + p65_2P)
unscaled_IkBa_mRNA = IkBa_mRNA_cytoplasm * default + c1 * IkBa_mRNA_nucleus

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)
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
Trigger Assignments