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beuke8

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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 0.241634452762376 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 6.01172521418603 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.000164221156411386 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 8.03887879197844 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 8.03887879197844 c1 (nucleus)
JNK JNK 0.729275694992988 default (cytoplasm)
JNK_P JNK_P 0.270724305007012 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9997455500515 c1 (nucleus)
MSK1_P MSK1_P 0.000254449948512746 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669215 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511468 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 0.739915161796727 default (cytoplasm)
p38_P p38_P 0.260084838203273 default (cytoplasm)
p65_2P p65_2P 0.00000000199645168379983 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.000539612968448037 c1 (nucleus)
p65_cytoplasm p65 0.000705283722934093 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0352130805415481 c1 (nucleus)
s11 IkBa 0.483268359476626 c1 (nucleus)
s14 IKKb 0.299986138101811 default (cytoplasm)
s15 IKKb_p 0.0000138618981889868 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.107777930651562 default (cytoplasm)
s3 p65_P 0.00456552780808916 default (cytoplasm)
s5 IkBa_p 0.0141499687497891 default (cytoplasm)
s8 p65_P 0.22819112785393 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 0.480113006649611
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 430.793686266021
IKKb_basal_phosphoylation_k 0.000000100000807653583
IKKb_dephopshorylation_k 0.00216412324532414
IkBa_deg_complex_cyt_k 0.00001
IkBa_deg_complex_nuc_k 0.0000100000000002221
IkBa_deg_cyt_k 0.0000242377808963832
IkBa_deg_nuc_k 0.00001
IkBa_mRNA_deg_cyt_k 0.000210129308924844
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 0.00199984177455124
IkBa_p65_nuclear_import_k 0.0000100000000002221
IkBa_p65_phosphorylation_kM 0.1
IkBa_p65_phosphorylation_kcat 12.086972022643
IkBa_p65_phosphorylation_vmax 0.000167548375591009
IkBa_p_active_degradation_k 0.00999999999999978
IkBa_phosphorylation_kM 0.5
IkBa_phosphorylation_kcat 12.086972022643
IkBa_phosphorylation_vmax 0.000167548375591009
IkBa_transcription_elongation_kbasal 0.00255354674372806
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.669306846091184
IkBa_transcription_kA_p65 0.582278857689383
IkBa_translation_Km 9.55643725141526
IkBa_translation_vmax 0.000385160990150945
JNK_active_phoshorylation_Km 0.00100000000000022
JNK_active_phosphorylation_kcat 87809.2408373703
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.000194360077507406
JNK_dephosphorylation_k 0.000523566144530142
LPS_LSEC_degradation_k 0.000333722673467154
LPS_MC_degradation_k 0.0001446522471925
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.00000260084838209048
MSK1_dephosphorylation_k 0.00999999999999978
MSK1_phosphorylation_kcat 0.0000100000000002221
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 0.977587844536314
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000120273735155731
TNFa_LSEC_translation_k 0.000021355383976935
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.754112302722779
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000546629532381917
TNFa_MC_translation_k 0.00000200299958028451
TNFa_degradation_k 0.000107694856083586
TNFa_mRNA_LSEC_degradation_k 0.608781957704734
TNFa_mRNA_MC_degradation_k 0.0555227961557056
k_IkBa 251434.627201244
k_IkBa_P 2670515.27536911
k_IkBa_mRNA 4662.87993522611
k_JNK_P 193739.599627673
k_MSK_P 3199776202.58475
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 0.0000676703660423514
k_p38_P 243420.436809916
k_p65 0.102372088824604
k_p65_P 2314484.39142756
p38_active_phoshorylation_Km 0.0100000000000002
p38_active_phosphorylation_kcat 87400.2446760506
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.000297895867031184
p38_dephosphorylation_k 0.000847483729446398
p65_2P_dephosphorylation 0.00465727753760888
p65_MSK1_phosphorylation_kM 9.73849564081927
p65_MSK1_phosphrylation_kcat 0.00000138295892142743
p65_MSK1_phosphrylation_vmax 0.000000000351893826352454
p65_P_MSK1_phosphrylation_kM 9.73849564081927
p65_P_MSK1_phosphrylation_kcat 0.00000138295892142743
p65_P_MSK1_phosphrylation_vmax 0.000000000351893826352454
p65_P_dephosphorylation_k 0.00465727753760888
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 0.491240199999995
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.68185024
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000172065850814733
scaled_p65_P 0.559884799999997
unscaled_IkBa 0.00000511335695608452
unscaled_IkBa_P 0.000000183949593747258
unscaled_IkBa_mRNA 0.0000781525591613436
unscaled_JNK_P 0.00000351941596509116
unscaled_MSK_P 0.000000000203559958810197
unscaled_p38_P 0.00000338110289664255
unscaled_p65 0.00000168078870706191
unscaled_p65_P 0.000000241904763788303

Local parameters

Id Value Reaction

Assignment rules

Definition
IkBa_p65_phosphorylation_vmax = IkBa_p65_phosphorylation_kcat * s15
unscaled_MSK_P = c1 * MSK1_P
p65_2P_dephosphorylation = p65_P_dephosphorylation_k * 1.0
scaled_MSK_P = k_MSK_P * unscaled_MSK_P
p65_nuclear_export_k = p65_nuclear_import_k * 0.02
p65_P_MSK1_phosphrylation_kcat = p65_MSK1_phosphrylation_kcat * 1.0
unscaled_p38_P = default * p38_P
p65_P_MSK1_phosphrylation_kM = p65_MSK1_phosphorylation_kM * 1.0
JNK_active_phosphorylation_vmax = JNK_active_phosphorylation_kcat * TNFa_TNFR1_EL
scaled_p65 = k_p65 * unscaled_p65
IkBa_nuclear_export_k = IkBa_nuclear_import_k * 0.5
scaled_IkBa_mRNA = k_IkBa_mRNA * unscaled_IkBa_mRNA
unscaled_JNK_P = default * JNK_P
scaled_JNK_P = k_JNK_P * unscaled_JNK_P
scaled_IkBa = k_IkBa * unscaled_IkBa
IkBa_p65_dissociation_k = IkBa_p65_association_k * 0.003
unscaled_IkBa_P = s5 * default
unscaled_p65_P = c1 * s8 + default * s3
IkBa_phosphorylation_kcat = IkBa_p65_phosphorylation_kcat
IkBa_phosphorylation_vmax = IkBa_phosphorylation_kcat * s15
scaled_p65_P = k_p65_P * unscaled_p65_P
scaled_IkBa_P = k_IkBa_P * unscaled_IkBa_P
unscaled_IkBa = (s11 + p65_IkBa_nucleus) * c1 + (s5 + s19 + IkBa_cytoplasm) * default
k_TNFa_TNFR1_dissociation = k_TNFa_TNFR1_association * 1.9e-5
unscaled_IkBa_mRNA = IkBa_mRNA_cytoplasm * default + c1 * IkBa_mRNA_nucleus
unscaled_p65 = (s3 + s19 + p65_cytoplasm) * default + c1 * (s8 + p65_IkBa_nucleus + p65_nucleus + p65_2P)
scaled_p38_P = k_p38_P * unscaled_p38_P
p38_active_phosphorylation_vmax = p38_active_phosphorylation_kcat * TNFa_TNFR1_EL
p65_P_MSK1_phosphrylation_vmax = p65_P_MSK1_phosphrylation_kcat * MSK1_P
MSK1_activation_vmax = MSK1_phosphorylation_kcat * p38_P
p65_MSK1_phosphrylation_vmax = p65_MSK1_phosphrylation_kcat * MSK1_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
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