Warning! Found 10 non-fixable id collusion: time, CIS, SOCS3, pSTAT5, p2EpoRpJAK2, init_EpoRJAK2, p12EpoRpJAK2, p1EpoRpJAK2, init_STAT5, task_bachmann_time
Info! Removed 19 unused DataGenerator from this document
Info! This is a derivative of the model beuke6-user-1701
 Edit

beuke6

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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 0.507019200945615 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 2.32465659746121 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.0000593117584186388 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 2.71761907781739 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 2.71761907781739 c1 (nucleus)
JNK JNK 0.994640290695112 default (cytoplasm)
JNK_P JNK_P 0.00535970930488779 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9996890652631 c1 (nucleus)
MSK1_P MSK1_P 0.000310934736947729 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669299 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511846 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 0.682179470574155 default (cytoplasm)
p38_P p38_P 0.317820529425844 default (cytoplasm)
p65_2P p65_2P 0.000000326668505834246 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.969088067881206 c1 (nucleus)
p65_cytoplasm p65 0.000841273703140653 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.042055782651398 c1 (nucleus)
s11 IkBa 1.01403825546669 c1 (nucleus)
s14 IKKb 0.299989533750916 default (cytoplasm)
s15 IKKb_p 0.0000104662490835518 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.0514360586910982 default (cytoplasm)
s3 p65_P 0.00376476893578587 default (cytoplasm)
s5 IkBa_p 0.06901470086292 default (cytoplasm)
s8 p65_P 0.188210099301579 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 0.433737796220232
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 505.111775275613
IKKb_basal_phosphoylation_k 0.000000100987402760599
IKKb_dephopshorylation_k 0.00289455789050888
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 0.000196263093665646
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 0.0115834748985079
IkBa_p65_dissociation_k 0.0000347504246955238
IkBa_p65_nuclear_export_k 0.000102691182488865
IkBa_p65_nuclear_import_k 0.00193476039888421
IkBa_p65_phosphorylation_kM 0.499969554377041
IkBa_p65_phosphorylation_kcat 29.5948052113158
IkBa_p65_phosphorylation_vmax 0.000309746602920829
IkBa_p_active_degradation_k 0.00394038080997718
IkBa_phosphorylation_kM 0.139132395762857
IkBa_phosphorylation_kcat 29.5948052113158
IkBa_phosphorylation_vmax 0.000309746602920829
IkBa_transcription_elongation_kbasal 0.00272811330639913
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000100000000000222
IkBa_transcription_kA_p65 0.175817717782383
IkBa_translation_Km 3.7375848293375
IkBa_translation_vmax 0.000779810447646675
JNK_active_phoshorylation_Km 10.0
JNK_active_phosphorylation_kcat 19256.1795467347
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.00000384084217469915
JNK_dephosphorylation_k 0.000712773055373148
LPS_LSEC_degradation_k 0.000273673403151409
LPS_MC_degradation_k 0.000130401203016782
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.00000317820529432902
MSK1_dephosphorylation_k 0.00999999999999978
MSK1_phosphorylation_kcat 0.0000100000000002221
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 1.02756459883434
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000119673224866826
TNFa_LSEC_translation_k 0.0000212549381121375
TNFa_MC_transcription_elongation_k 0.00000100000000019855
TNFa_MC_transcription_initiation_kA_LPS 0.789977345876892
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000564626209629571
TNFa_MC_translation_k 0.00000206871102970719
TNFa_degradation_k 0.000130126972446871
TNFa_mRNA_LSEC_degradation_k 0.602026595546492
TNFa_mRNA_MC_degradation_k 0.05370637376387
k_IkBa 131950.573561959
k_IkBa_P 547531.282753271
k_IkBa_mRNA 12058.5363091937
k_JNK_P 9785981.94004788
k_MSK_P 2618500904.69908
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 0.0000673727646011927
k_p38_P 199200.363291349
k_p65 0.102372088824604
k_p65_P 2806298.37013514
p38_active_phoshorylation_Km 0.0100000000000002
p38_active_phosphorylation_kcat 107282.81225467
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.000362958652246269
p38_dephosphorylation_k 0.00077906528466544
p65_2P_dephosphorylation 0.00186941158123724
p65_MSK1_phosphorylation_kM 0.00100072640681537
p65_MSK1_phosphrylation_kcat 0.00000100329669061444
p65_MSK1_phosphrylation_vmax 0.000000000311959792576729
p65_P_MSK1_phosphrylation_kM 0.00100072640681537
p65_P_MSK1_phosphrylation_kcat 0.00000100329669061444
p65_P_MSK1_phosphrylation_vmax 0.000000000311959792576729
p65_P_dephosphorylation_k 0.00186941158123724
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 0.000000172807232699613
scaled_p65_P 0.559884800000002
unscaled_IkBa 0.00000974361054517354
unscaled_IkBa_P 0.00000089719111121796
unscaled_IkBa_mRNA 0.0000302205832164025
unscaled_JNK_P 0.0000000696762209635413
unscaled_MSK_P 0.000000000248747789558184
unscaled_p38_P 0.00000413166688253598
unscaled_p65 0.00000168803073849247
unscaled_p65_P 0.000000199510075606479

Local parameters

Id Value Reaction

Assignment rules

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

Rate rules

Definition

Algebraic rules

Definition
Definition
Henri_Michaelis_Menten__irreversible(substrate, Km, V) = V * substrate / (Km + substrate)
TNFa_transcription_initiation(kbasal, vA, A, kA) = kbasal + vA * A / (A + kA)
Catalytic_activation__irrev(substrate, Activator, Kms, V, Ka) = V * substrate * Activator / ((Kms + substrate) * (Ka + Activator))
activated_Transcription__1(k1, k2, Modifier, k3, Modifier2, Modifier3, k4) = k1 + k2 * Modifier + k3 * Modifier2 + k4 * Modifier3
Trigger Assignments