Info! This is a derivative of the model bertram1
Info! This is a derivative of the model beuke27
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beuke27

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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 0.611053712242544 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 3.26595422991691 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.0000951547638540396 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 4.79369903738158 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 4.79369903738158 c1 (nucleus)
JNK JNK 0.859884281111124 default (cytoplasm)
JNK_P JNK_P 0.140115718888876 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9994524333736 c1 (nucleus)
MSK1_P MSK1_P 0.000547566626418636 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645670331 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905516488 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 0.976459418393607 default (cytoplasm)
p38_P p38_P 0.0235405816063926 default (cytoplasm)
p65_2P p65_2P 0.000000388970886222327 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.963320879667655 c1 (nucleus)
p65_cytoplasm p65 0.000830760491415635 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0415319258827991 c1 (nucleus)
s11 IkBa 1.22210731520188 c1 (nucleus)
s14 IKKb 0.299999438744 default (cytoplasm)
s15 IKKb_p 0.000000561256000466064 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.048165916121202 default (cytoplasm)
s3 p65_P 0.00465381558406888 default (cytoplasm)
s5 IkBa_p 0.0793163226564784 default (cytoplasm)
s8 p65_P 0.232670033938962 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 0.00162641923316831
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 120.298693229773
IKKb_basal_phosphoylation_k 0.00000626723248619685
IKKb_dephopshorylation_k 3.34992628454065
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 0.000224118181219206
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 0.00714676388441979
IkBa_p65_dissociation_k 0.0000214402916532594
IkBa_p65_nuclear_export_k 0.000100000000000222
IkBa_p65_nuclear_import_k 0.00199999999999978
IkBa_p65_phosphorylation_kM 0.5
IkBa_p65_phosphorylation_kcat 428.757821334368
IkBa_p65_phosphorylation_vmax 0.000240642899970671
IkBa_p_active_degradation_k 0.00287386529993596
IkBa_phosphorylation_kM 0.1
IkBa_phosphorylation_kcat 428.757821334368
IkBa_phosphorylation_vmax 0.000240642899970671
IkBa_transcription_elongation_kbasal 0.00248124676721259
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.399168332635982
IkBa_transcription_kA_p65 0.285802493357409
IkBa_translation_Km 6.34631360280143
IkBa_translation_vmax 0.000766177503129199
JNK_active_phoshorylation_Km 0.00100000000000022
JNK_active_phosphorylation_kcat 45535.7748105975
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.000101527696945163
JNK_dephosphorylation_k 0.000623071211372505
LPS_LSEC_degradation_k 0.000286638034022634
LPS_MC_degradation_k 0.000134500305240297
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.00000559692932024681
MSK1_dephosphorylation_k 0.00999999999999978
MSK1_phosphorylation_kcat 0.000237756628694634
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 1.01916477342579
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000119443999592431
TNFa_LSEC_translation_k 0.000021202626544429
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.774346576767653
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000558744259731383
TNFa_MC_translation_k 0.00000204736878958735
TNFa_degradation_k 0.000122938827241653
TNFa_mRNA_LSEC_degradation_k 0.606307267866555
TNFa_mRNA_MC_degradation_k 0.0542635500675031
k_IkBa 113282.217963726
k_IkBa_P 476417.796825599
k_IkBa_mRNA 8583.08101303565
k_JNK_P 374333.578541148
k_MSK_P 1486911091.21308
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 0.0000709248366671094
k_p38_P 2689396.80342838
k_p65 0.102372088824604
k_p65_P 2270088.87799786
p38_active_phoshorylation_Km 8.5004296173332
p38_active_phosphorylation_kcat 76703.9303427224
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.0000271934689367164
p38_dephosphorylation_k 0.00112798057864535
p65_2P_dephosphorylation 0.00110123102082084
p65_MSK1_phosphorylation_kM 10.0
p65_MSK1_phosphrylation_kcat 0.0000294602313133692
p65_MSK1_phosphrylation_vmax 0.0000000161314394737742
p65_P_MSK1_phosphrylation_kM 10.0
p65_P_MSK1_phosphrylation_kcat 0.0000294602313133692
p65_P_MSK1_phosphrylation_vmax 0.0000000161314394737742
p65_P_dephosphorylation_k 0.00110123102082084
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 0.491240200000001
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.68185024
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000172750338677516
scaled_p65_P 0.559884800000001
unscaled_IkBa 0.0000113493099191586
unscaled_IkBa_P 0.00000103111219453422
unscaled_IkBa_mRNA 0.0000424574811127309
unscaled_JNK_P 0.00000182150434555539
unscaled_MSK_P 0.000000000438053301134909
unscaled_p38_P 0.000000306027560883103
unscaled_p65 0.00000168747498132517
unscaled_p65_P 0.000000246635629744065

Local parameters

Id Value Reaction

Assignment rules

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

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
Henri_Michaelis_Menten__irreversible(substrate, Km, V) = V * substrate / (Km + substrate)
Catalytic_activation__irrev(substrate, Activator, Kms, V, Ka) = V * substrate * Activator / ((Kms + substrate) * (Ka + Activator))
Trigger Assignments