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beuke7

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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 0.402845161595828 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 6.28632882916418 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.000157166190926943 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 7.18140328980903 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 7.18140328980903 c1 (nucleus)
JNK JNK 0.980466198972063 default (cytoplasm)
JNK_P JNK_P 0.019533801027937 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9999306731002 c1 (nucleus)
MSK1_P MSK1_P 0.0000693268997811892 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669288 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511796 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 0.929650735059334 default (cytoplasm)
p38_P p38_P 0.0703492649406657 default (cytoplasm)
p65_2P p65_2P 0.0000002189217886387 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.995652059221173 c1 (nucleus)
p65_cytoplasm p65 0.00082222617042193 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0411030139624838 c1 (nucleus)
s11 IkBa 0.805690176476432 c1 (nucleus)
s14 IKKb 0.299989869269092 default (cytoplasm)
s15 IKKb_p 0.0000101307309084452 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.0497846885277208 default (cytoplasm)
s3 p65_P 0.00376885551788092 default (cytoplasm)
s5 IkBa_p 0.0566777858683295 default (cytoplasm)
s8 p65_P 0.188414573904168 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 0.243146348449513
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 277.103899203292
IKKb_basal_phosphoylation_k 0.000000102344651825526
IKKb_dephopshorylation_k 0.00303061634929536
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 0.000192317445092793
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 0.0153889708315641
IkBa_p65_dissociation_k 0.0000461669124946923
IkBa_p65_nuclear_export_k 0.000100004543264477
IkBa_p65_nuclear_import_k 0.00199999999999978
IkBa_p65_phosphorylation_kM 0.372292128739572
IkBa_p65_phosphorylation_kcat 24.0559815899914
IkBa_p65_phosphorylation_vmax 0.000243704676226715
IkBa_p_active_degradation_k 0.00395159188864045
IkBa_phosphorylation_kM 0.10004489890377
IkBa_phosphorylation_kcat 24.0559815899914
IkBa_phosphorylation_vmax 0.000243704676226715
IkBa_transcription_elongation_kbasal 0.00273564663219183
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000100392930213726
IkBa_transcription_kA_p65 0.477481779382945
IkBa_translation_Km 10.0
IkBa_translation_vmax 0.00063658986783369
JNK_active_phoshorylation_Km 5.53631315145271
JNK_active_phosphorylation_kcat 42478.015487462
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.0000140201022425048
JNK_dephosphorylation_k 0.00070371538725355
LPS_LSEC_degradation_k 0.000281375430692567
LPS_MC_degradation_k 0.000133176015283507
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.000000708621510724562
MSK1_dephosphorylation_k 0.00999999999999978
MSK1_phosphorylation_kcat 0.0000100729056845474
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 1.02438212695228
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000119438296662267
TNFa_LSEC_translation_k 0.0000212090661254614
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.777847391047605
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.0000056070630385483
TNFa_MC_translation_k 0.00000205455299505843
TNFa_degradation_k 0.000125263672194682
TNFa_mRNA_LSEC_degradation_k 0.605694690908452
TNFa_mRNA_MC_degradation_k 0.0541021024827527
k_IkBa 159472.010610349
k_IkBa_P 666711.077600919
k_IkBa_mRNA 4459.19353465518
k_JNK_P 2685090.23853192
k_MSK_P 11744112207.0905
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 0.000069007617563905
k_p38_P 899937.831283299
k_p65 0.102372088824604
k_p65_P 2803253.51262869
p38_active_phoshorylation_Km 9.99601266623388
p38_active_phosphorylation_kcat 284561.328834224
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.0000804034531971613
p38_dephosphorylation_k 0.00106251471751828
p65_2P_dephosphorylation 0.00185771613858199
p65_MSK1_phosphorylation_kM 0.00550375653893175
p65_MSK1_phosphrylation_kcat 0.00000318759281450581
p65_MSK1_phosphrylation_vmax 0.000000000220985927594483
p65_P_MSK1_phosphrylation_kM 0.00550375653893175
p65_P_MSK1_phosphrylation_kcat 0.00000318759281450581
p65_P_MSK1_phosphrylation_vmax 0.000000000220985927594483
p65_P_dephosphorylation_k 0.00185771613858199
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 0.491240200000005
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.68185024
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000172703853998684
scaled_p65_P 0.559884800000003
unscaled_IkBa 0.00000806207305645249
unscaled_IkBa_P 0.000000736811216288283
unscaled_IkBa_mRNA 0.0000817224005120871
unscaled_JNK_P 0.000000253939413363181
unscaled_MSK_P 0.0000000000554615198249514
unscaled_p38_P 0.000000914540444228654
unscaled_p65 0.000001687020905616
unscaled_p65_P 0.000000199726780855787

Local parameters

Id Value Reaction

Assignment rules

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

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