#beuke30

FIX: p65_mRNA

#reactions
Complex_association_c:
 {1.0}p65_cytoplasm + {1.0}IkBa_cytoplasm = {1.0}s19
  default * (IkBa_p65_association_k * IkBa_cytoplasm * p65_cytoplasm - IkBa_p65_dissociation_k * s19)
Complex_degradation_IkBa_c:
 {1.0}s19 = {1.0}p65_cytoplasm
  default * IkBa_deg_complex_cyt_k * s19
Complex_degradation_IkBa_n:
 {1.0}p65_IkBa_nucleus = {1.0}p65_nucleus
  c1 * IkBa_deg_complex_nuc_k * p65_IkBa_nucleus
Complex_degradation_p65_c:
 {1.0}s19 = {1.0}IkBa_cytoplasm
  default * p65_degradation_k * s19
Complex_degradation_p65_n:
 {1.0}p65_IkBa_nucleus = {1.0}s11
  c1 * p65_degradation_k * p65_IkBa_nucleus
Complex_nuclear_shuttle:
 {1.0}p65_IkBa_nucleus = {1.0}s19
  IkBa_p65_nuclear_export_k * p65_IkBa_nucleus - IkBa_p65_nuclear_import_k * s19
IKK_phosphorylation:
 {1.0}s14 = {1.0}s15
  default * Catalytic_activation__irrev(s14, TNFa_TNFR1_EL, IKKb_active_phosphorylation_kM, IKKb_active_phosphorylation_vmax, IKKb_active_phosphorylation_kA)
IkBa_degradation_c:
 {1.0}IkBa_cytoplasm = $pool
  default * IkBa_deg_cyt_k * IkBa_cytoplasm
IkBa_degradation_n:
 {1.0}s11 = $pool
  c1 * IkBa_deg_nuc_k * s11
IkBa_mRNA_degradation_c:
 {1.0}IkBa_mRNA_cytoplasm = $pool
  default * IkBa_mRNA_deg_cyt_k * IkBa_mRNA_cytoplasm
IkBa_mRNA_degradation_n:
 {1.0}IkBa_mRNA_nucleus = $pool
  c1 * IkBa_mRNA_deg_nuc_k * IkBa_mRNA_nucleus
IkBa_mRNA_transport:
 {1.0}IkBa_mRNA_nucleus = {1.0}IkBa_mRNA_cytoplasm
  IkBa_mRNA_transport_k * IkBa_mRNA_nucleus
IkBa_nuclear_shuttle:
 {1.0}IkBa_cytoplasm = {1.0}s11
  IkBa_nuclear_import_k * IkBa_cytoplasm - IkBa_nuclear_export_k * s11
IkBa_phosphorylation:
 {1.0}IkBa_cytoplasm = {1.0}s5
  default * Henri_Michaelis_Menten__irreversible(IkBa_cytoplasm, IkBa_phosphorylation_kM, IkBa_phosphorylation_vmax)
IkBa_transcription_elongation_1:
 {1.0}IkBa_pre_mRNA_1 = {1.0}IkBa_pre_mRNA_2
  c1 * IkBa_transcription_elongation_kbasal * IkBa_pre_mRNA_1
IkBa_transcription_elongation_2:
 {1.0}IkBa_pre_mRNA_2 = {1.0}IkBa_mRNA_nucleus
  c1 * IkBa_transcription_elongation_kbasal * IkBa_pre_mRNA_2
IkBa_translation:
 {1.0}IkBa_mRNA_cytoplasm = {1.0}IkBa_mRNA_cytoplasm + {1.0}IkBa_cytoplasm
  default * Henri_Michaelis_Menten__irreversible(IkBa_mRNA_cytoplasm, IkBa_translation_Km, IkBa_translation_vmax)
JNK_active_phosphorylation:
 {1.0}JNK = {1.0}JNK_P
  default * Henri_Michaelis_Menten__irreversible(JNK, JNK_active_phoshorylation_Km, JNK_active_phosphorylation_vmax)
JNK_basal_phosphorylation:
 {1.0}JNK = {1.0}JNK_P
  default * JNK_basal_phosphorylation_k * JNK
JNK_dephosphorylation:
 {1.0}JNK_P = {1.0}JNK
  default * JNK_dephosphorylation_k * JNK_P
LPS_LSEC_degradation:
 {1.0}LPS = $pool
  EL * LPS_LSEC_degradation_k * LPS
LPS_MC_degradation:
 {1.0}LPS = $pool
  EL * LPS_MC_degradation_k * LPS
MSK1_activation:
 {1.0}MSK1 = {1.0}MSK1_P
  c1 * Henri_Michaelis_Menten__irreversible(MSK1, MSK1_activation_kM, MSK1_activation_vmax)
MSK1_deactivation:
 {1.0}MSK1_P = {1.0}MSK1
  c1 * MSK1_dephosphorylation_k * MSK1_P
TNFR1_shuttle:
 {1.0}TNFR1_cytoplasm = {1.0}TNFR1_EL
  k_TNFR1_vessicle2outer_membrane_shuttle * TNFR1_cytoplasm - k_TNFR1_outer_membrane2vessicle_shuttle * TNFR1_EL
TNFa_LSEC_transcription_elongation:
 {1.0}TNFa_pre_mRNA_LSEC = {1.0}TNFa_mRNA_LSEC
  LSEC * TNFa_LSEC_transcription_elongation_k * TNFa_pre_mRNA_LSEC
TNFa_LSEC_transcription_initiation:
 $pool = {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:
 {1.0}TNFa_mRNA_LSEC = {1.0}TNFa_mRNA_LSEC + {1.0}s16
  TNFa_LSEC_translation_k * TNFa_mRNA_LSEC
TNFa_MC_transcription_elongation:
 {1.0}TNFa_pre_mRNA_MC = {1.0}TNFa_mRNA_MC
  MC * TNFa_MC_transcription_elongation_k * TNFa_pre_mRNA_MC
TNFa_MC_transcription_initiation:
 $pool = {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:
 {1.0}TNFa_mRNA_MC = {1.0}TNFa_mRNA_MC + {1.0}s16
  TNFa_MC_translation_k * TNFa_mRNA_MC
TNFa_TNFR1_association:
 {1.0}TNFR1_EL + {1.0}s16 = {1.0}TNFa_TNFR1_EL
  EL * (k_TNFa_TNFR1_association * TNFR1_EL * s16 - k_TNFa_TNFR1_dissociation * TNFa_TNFR1_EL)
TNFa_TNFR1_internalisation:
 {1.0}TNFa_TNFR1_EL = {1.0}TNFa_TNFR1_cytoplasm
  k_TNFa_TNFR1_internalisation * TNFa_TNFR1_EL
TNFa_degradation:
 {1.0}s16 = $pool
  EL * TNFa_degradation_k * s16
TNFa_internal_degradation:
 {1.0}TNFa_TNFR1_cytoplasm = {1.0}TNFR1_cytoplasm
  default * k_TNFa_internal_degradation * TNFa_TNFR1_cytoplasm
TNFa_mRNA_LSEC_degradation:
 {1.0}TNFa_mRNA_LSEC = $pool
  LSEC * TNFa_mRNA_LSEC_degradation_k * TNFa_mRNA_LSEC
TNFa_mRNA_MC_degradation:
 {1.0}TNFa_mRNA_MC = $pool
  MC * TNFa_mRNA_MC_degradation_k * TNFa_mRNA_MC
basal_IKKb_phosphorylation:
 {1.0}s14 = {1.0}s15
  default * IKKb_basal_phosphoylation_k * s14
p38_active_phosphorylation:
 {1.0}p38 = {1.0}p38_P
  default * Henri_Michaelis_Menten__irreversible(p38, p38_active_phoshorylation_Km, p38_active_phosphorylation_vmax)
p38_basal_phosphorylation:
 {1.0}p38 = {1.0}p38_P
  default * p38_basal_phosphorylation_k * p38
p38_dephosphorylation:
 {1.0}p38_P = {1.0}p38
  default * p38_dephosphorylation_k * p38_P
p65_2P_degradation:
 {1.0}p65_2P = $pool
  c1 * p65_degradation_k * p65_2P
p65_2P_dephosphorylation_0:
 {1.0}p65_2P = {1.0}p65_nucleus
  c1 * p65_2P_dephosphorylation * p65_2P
p65_P_degradation_c:
 {1.0}s3 = $pool
  default * p65_degradation_k * s3
p65_P_degradation_n:
 {1.0}s8 = $pool
  c1 * p65_degradation_k * s8
p65_P_dephosphorylation_c:
 {1.0}s8 = {1.0}p65_nucleus
  c1 * p65_P_dephosphorylation_k * s8
p65_P_dephosphorylation_n:
 {1.0}s3 = {1.0}p65_cytoplasm
  default * p65_P_dephosphorylation_k * s3
p65_P_phosphorylation_MSK1:
 {1.0}s8 = {1.0}p65_2P
  c1 * Henri_Michaelis_Menten__irreversible(s8, p65_P_MSK1_phosphrylation_kM, p65_P_MSK1_phosphrylation_vmax)
p65_nuclear_shuttle:
 {1.0}p65_cytoplasm = {1.0}p65_nucleus
  p65_nuclear_import_k * p65_cytoplasm - p65_nuclear_export_k * p65_nucleus
p65_phosphorylation_MSK1:
 {1.0}p65_nucleus = {1.0}p65_2P
  c1 * Henri_Michaelis_Menten__irreversible(p65_nucleus, p65_MSK1_phosphorylation_kM, p65_MSK1_phosphrylation_vmax)
p65_translation:
 {1.0}p65_mRNA = {1.0}p65_mRNA + {1.0}p65_cytoplasm
  default * p65_translation_k * p65_mRNA
re10:
 $pool = {1.0}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:
 {1.0}s5 = $pool
  default * IkBa_p_active_degradation_k * s5
re15:
 {1.0}s19 = {1.0}s3 + {1.0}s5
  default * Henri_Michaelis_Menten__irreversible(s19, IkBa_p65_phosphorylation_kM, IkBa_p65_phosphorylation_vmax)
re17:
 {1.0}s15 = {1.0}s14
  default * IKKb_dephopshorylation_k * s15
re19:
 {1.0}p65_nucleus + {1.0}s11 = {1.0}p65_IkBa_nucleus
  c1 * (IkBa_p65_association_k * p65_nucleus * s11 - IkBa_p65_dissociation_k * p65_IkBa_nucleus)
re3:
 {1.0}s3 = {1.0}s8
  p65_nuclear_import_k * s3 - p65_nuclear_export_k * s8


#parameters
IKKb_active_phosphorylation_kA = 0.00100000000000022
IKKb_active_phosphorylation_kM = 5.0
IKKb_active_phosphorylation_vmax = 1000.0
IKKb_basal_phosphoylation_k = 8.50405639506259e-05
IKKb_dephopshorylation_k = 5.24031174643618
IkBa_deg_complex_cyt_k = 1e-05
IkBa_deg_complex_nuc_k = 1.00000000002221e-05
IkBa_deg_cyt_k = 4.9999999999778e-05
IkBa_deg_nuc_k = 1e-05
IkBa_mRNA_deg_cyt_k = 0.000224716979510694
IkBa_mRNA_deg_nuc_k = 5e-05
IkBa_mRNA_transport_k = 0.0001
IkBa_nuclear_import_k = 0.005
IkBa_p65_association_k = 0.00717358486800796
IkBa_p65_nuclear_export_k = 0.000100000000000222
IkBa_p65_nuclear_import_k = 0.00199999999999978
IkBa_p65_phosphorylation_kM = 0.5
IkBa_p65_phosphorylation_kcat = 49.4377608001032
IkBa_p_active_degradation_k = 0.00287394120561127
IkBa_phosphorylation_kM = 0.1
IkBa_transcription_elongation_kbasal = 0.00247372765740391
IkBa_transcription_initiation_kbasal = 1e-06
IkBa_transcription_kA2_p65_P = 0.000100000000000222
IkBa_transcription_kA3_p65_2P = 0.000345477406826646
IkBa_transcription_kA_p65 = 0.114429380979452
IkBa_translation_Km = 2.52747529861618
IkBa_translation_vmax = 0.000765158501957606
JNK_active_phoshorylation_Km = 0.488925805517754
JNK_active_phosphorylation_kcat = 66609.298097084
JNK_basal_phosphorylation_k = 9.14614546565897e-05
JNK_dephosphorylation_k = 0.000626077589491631
LPS_LSEC_degradation_k = 0.000286708655476603
LPS_MC_degradation_k = 0.00013440385436684
MSK1_activation_kM = 0.332175
MSK1_dephosphorylation_k = 0.00999999999999978
MSK1_phosphorylation_kcat = 1.20575858380321e-05
TNFa_LSEC_transcription_elongation_k = 1.00000000022204e-06
TNFa_LSEC_transcription_initiation_kA_LPS = 1.01909414363877
TNFa_LSEC_transcription_initiation_kbasal = 0.0
TNFa_LSEC_transcription_initiation_vA_LPS = 1.1946674450075e-05
TNFa_LSEC_translation_k = 2.12126907719036e-05
TNFa_MC_transcription_elongation_k = 1.00000000022204e-06
TNFa_MC_transcription_initiation_kA_LPS = 0.776929437245413
TNFa_MC_transcription_initiation_kbasal = 0.0
TNFa_MC_transcription_initiation_vA_LPS = 5.58761538599797e-06
TNFa_MC_translation_k = 2.04743502269246e-06
TNFa_degradation_k = 0.000122908799477538
TNFa_mRNA_LSEC_degradation_k = 0.606716817898513
TNFa_mRNA_MC_degradation_k = 0.0542730608777408
k_IkBa = 113249.646560924
k_IkBa_P = 476325.258024042
k_IkBa_mRNA = 21500.5919579352
k_JNK_P = 411484.119225489
k_MSK_P = 3399673029.87478
k_TNFR1_outer_membrane2vessicle_shuttle = 1.8e-05
k_TNFR1_vessicle2outer_membrane_shuttle = 0.0004
k_TNFa_TNFR1_association = 16.833
k_TNFa_TNFR1_internalisation = 0.00077
k_TNFa_internal_degradation = 7.09894916654482e-05
k_p38_P = 311842.249743014
k_p65 = 0.102372088824604
k_p65_P = 2273699.96038902
p38_active_phoshorylation_Km = 0.764708862864952
p38_active_phosphorylation_kcat = 142404.415096322
p38_basal_phosphorylation_k = 0.000231053288338233
p38_dephosphorylation_k = 0.000907032593299214
p65_MSK1_phosphorylation_kM = 0.00196384100934669
p65_MSK1_phosphrylation_kcat = 3.08754864462186e-06
p65_P_dephosphorylation_k = 0.00110346502106112
p65_degradation_k = 1.328912101e-05
p65_nuclear_import_k = 0.0005
p65_translation_k = 1.68e-06
p65_mRNA = 1.0
EL = 2.59e-06
LSEC = 4.7e-07
MC = 3.5e-07
c1 = 8e-07
default = 1.3e-05


#initial values
IkBa_cytoplasm = 0.611236783151804
IkBa_mRNA_cytoplasm = 1.3037757128177
IkBa_mRNA_nucleus = 3.80874702186936e-05
IkBa_pre_mRNA_1 = 1.92459977049642
IkBa_pre_mRNA_2 = 1.92459977049642
JNK = 0.87253452560876
JNK_P = 0.12746547439124
LPS = 5.0
MSK1 = 14.9997605114131
MSK1_P = 0.000239488586945077
TNFR1_EL = 0.00122834645669291
TNFR1_cytoplasm = 5.52755905511807e-05
TNFa_TNFR1_EL = 0.0
TNFa_TNFR1_cytoplasm = 0.0
TNFa_mRNA_LSEC = 0.0
TNFa_mRNA_MC = 0.0
TNFa_pre_mRNA_LSEC = 0.0
TNFa_pre_mRNA_MC = 0.0
p38 = 0.796980797261275
p38_P = 0.203019202738725
p65_2P = 1.28871252075337e-06
p65_IkBa_nucleus = 0.963590525843699
p65_cytoplasm = 0.000828004765590007
p65_nucleus = 0.0413941344971436
s11 = 1.22247345696318
s14 = 0.299995131634069
s15 = 4.86836593144912e-06
s16 = 0.0
s19 = 0.0481793983610179
s3 = 0.0046464250373966
s5 = 0.0793317319536317
s8 = 0.232300498007703


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