begin name
beuke4
end name

begin reactions
Complexassociationc {1.0}p65cytoplasm + {1.0}IkBacytoplasm = {1.0}s19
ComplexdegradationIkBac {1.0}s19 = {1.0}p65cytoplasm
ComplexdegradationIkBan {1.0}p65IkBanucleus = {1.0}p65nucleus
Complexdegradationp65c {1.0}s19 = {1.0}IkBacytoplasm
Complexdegradationp65n {1.0}p65IkBanucleus = {1.0}s11
Complexnuclearshuttle {1.0}p65IkBanucleus = {1.0}s19
IKKphosphorylation {1.0}s14 = {1.0}s15
IkBadegradationc {1.0}IkBacytoplasm = {1.0}$EXTERNAL
IkBadegradationn {1.0}s11 = {1.0}$EXTERNAL
IkBamRNAdegradationc {1.0}IkBamRNAcytoplasm = {1.0}$EXTERNAL
IkBamRNAdegradationn {1.0}IkBamRNAnucleus = {1.0}$EXTERNAL
IkBamRNAtransport {1.0}IkBamRNAnucleus = {1.0}IkBamRNAcytoplasm
IkBanuclearshuttle {1.0}IkBacytoplasm = {1.0}s11
IkBaphosphorylation {1.0}IkBacytoplasm = {1.0}s5
IkBatranscriptionelongation1 {1.0}IkBapremRNA1 = {1.0}IkBapremRNA2
IkBatranscriptionelongation2 {1.0}IkBapremRNA2 = {1.0}IkBamRNAnucleus
IkBatranslation {1.0}IkBamRNAcytoplasm = {1.0}IkBamRNAcytoplasm + {1.0}IkBacytoplasm
JNKactivephosphorylation {1.0}JNK = {1.0}JNKP
JNKbasalphosphorylation {1.0}JNK = {1.0}JNKP
JNKdephosphorylation {1.0}JNKP = {1.0}JNK
LPSLSECdegradation {1.0}LPS = {1.0}$EXTERNAL
LPSMCdegradation {1.0}LPS = {1.0}$EXTERNAL
MSK1activation {1.0}MSK1 = {1.0}MSK1P
MSK1deactivation {1.0}MSK1P = {1.0}MSK1
TNFR1shuttle {1.0}TNFR1cytoplasm = {1.0}TNFR1EL
TNFaLSECtranscriptionelongation {1.0}TNFapremRNALSEC = {1.0}TNFamRNALSEC
TNFaLSECtranscriptioninitiation {1.0}$EXTERNAL = {2.0}TNFapremRNALSEC
TNFaLSECtranslation {1.0}TNFamRNALSEC = {1.0}TNFamRNALSEC + {1.0}s16
TNFaMCtranscriptionelongation {1.0}TNFapremRNAMC = {1.0}TNFamRNAMC
TNFaMCtranscriptioninitiation {1.0}$EXTERNAL = {2.0}TNFapremRNAMC
TNFaMCtranslation {1.0}TNFamRNAMC = {1.0}TNFamRNAMC + {1.0}s16
TNFaTNFR1association {1.0}TNFR1EL + {1.0}s16 = {1.0}TNFaTNFR1EL
TNFaTNFR1internalisation {1.0}TNFaTNFR1EL = {1.0}TNFaTNFR1cytoplasm
TNFadegradation {1.0}s16 = {1.0}$EXTERNAL
TNFainternaldegradation {1.0}TNFaTNFR1cytoplasm = {1.0}TNFR1cytoplasm
TNFamRNALSECdegradation {1.0}TNFamRNALSEC = {1.0}$EXTERNAL
TNFamRNAMCdegradation {1.0}TNFamRNAMC = {1.0}$EXTERNAL
basalIKKbphosphorylation {1.0}s14 = {1.0}s15
p38activephosphorylation {1.0}p38 = {1.0}p38P
p38basalphosphorylation {1.0}p38 = {1.0}p38P
p38dephosphorylation {1.0}p38P = {1.0}p38
p652Pdegradation {1.0}p652P = {1.0}$EXTERNAL
p652Pdephosphorylation0 {1.0}p652P = {1.0}p65nucleus
p65Pdegradationc {1.0}s3 = {1.0}$EXTERNAL
p65Pdegradationn {1.0}s8 = {1.0}$EXTERNAL
p65Pdephosphorylationc {1.0}s8 = {1.0}p65nucleus
p65Pdephosphorylationn {1.0}s3 = {1.0}p65cytoplasm
p65PphosphorylationMSK1 {1.0}s8 = {1.0}p652P
p65nuclearshuttle {1.0}p65cytoplasm = {1.0}p65nucleus
p65phosphorylationMSK1 {1.0}p65nucleus = {1.0}p652P
p65translation {1.0}$p65mRNA = {1.0}$p65mRNA + {1.0}p65cytoplasm
re10 {1.0}$EXTERNAL = {1.0}IkBapremRNA1
re14 {1.0}s5 = {1.0}$EXTERNAL
re15 {1.0}s19 = {1.0}s3 + {1.0}s5
re17 {1.0}s15 = {1.0}s14
re19 {1.0}p65nucleus + {1.0}s11 = {1.0}p65IkBanucleus
re3 {1.0}s3 = {1.0}s8
end reactions

begin rate equations
Complexassociationc = default*(IkBap65associationk*IkBacytoplasm[t]*p65cytoplasm[t] - IkBap65dissociationk*s19[t])
ComplexdegradationIkBac = default*IkBadegcomplexcytk*s19[t]
ComplexdegradationIkBan = c1*IkBadegcomplexnuck*p65IkBanucleus[t]
Complexdegradationp65c = default*p65degradationk*s19[t]
Complexdegradationp65n = c1*p65degradationk*p65IkBanucleus[t]
Complexnuclearshuttle = IkBap65nuclearexportk*p65IkBanucleus[t] - IkBap65nuclearimportk*s19[t]
IKKphosphorylation = default*Catalyticactivationirrev[s14[t], TNFaTNFR1EL[t], IKKbactivephosphorylationkM, IKKbactivephosphorylationvmax, IKKbactivephosphorylationkA]
IkBadegradationc = default*IkBadegcytk*IkBacytoplasm[t]
IkBadegradationn = c1*IkBadegnuck*s11[t]
IkBamRNAdegradationc = default*IkBamRNAdegcytk*IkBamRNAcytoplasm[t]
IkBamRNAdegradationn = c1*IkBamRNAdegnuck*IkBamRNAnucleus[t]
IkBamRNAtransport = IkBamRNAtransportk*IkBamRNAnucleus[t]
IkBanuclearshuttle = IkBanuclearimportk*IkBacytoplasm[t] - IkBanuclearexportk*s11[t]
IkBaphosphorylation = default*HenriMichaelisMentenirreversible[IkBacytoplasm[t], IkBaphosphorylationkM, IkBaphosphorylationvmax]
IkBatranscriptionelongation1 = c1*IkBatranscriptionelongationkbasal*IkBapremRNA1[t]
IkBatranscriptionelongation2 = c1*IkBatranscriptionelongationkbasal*IkBapremRNA2[t]
IkBatranslation = default*HenriMichaelisMentenirreversible[IkBamRNAcytoplasm[t], IkBatranslationKm, IkBatranslationvmax]
JNKactivephosphorylation = default*HenriMichaelisMentenirreversible[JNK[t], JNKactivephoshorylationKm, JNKactivephosphorylationvmax]
JNKbasalphosphorylation = default*JNKbasalphosphorylationk*JNK[t]
JNKdephosphorylation = default*JNKdephosphorylationk*JNKP[t]
LPSLSECdegradation = EL*LPSLSECdegradationk*LPS[t]
LPSMCdegradation = EL*LPSMCdegradationk*LPS[t]
MSK1activation = c1*HenriMichaelisMentenirreversible[MSK1[t], MSK1activationkM, MSK1activationvmax]
MSK1deactivation = c1*MSK1dephosphorylationk*MSK1P[t]
TNFR1shuttle = kTNFR1vessicle2outermembraneshuttle*TNFR1cytoplasm[t] - kTNFR1outermembrane2vessicleshuttle*TNFR1EL[t]
TNFaLSECtranscriptionelongation = LSEC*TNFaLSECtranscriptionelongationk*TNFapremRNALSEC[t]
TNFaLSECtranscriptioninitiation = LSEC*TNFatranscriptioninitiation[TNFaLSECtranscriptioninitiationkbasal, TNFaLSECtranscriptioninitiationvALPS, LPS[t], TNFaLSECtranscriptioninitiationkALPS]
TNFaLSECtranslation = TNFaLSECtranslationk*TNFamRNALSEC[t]
TNFaMCtranscriptionelongation = MC*TNFaMCtranscriptionelongationk*TNFapremRNAMC[t]
TNFaMCtranscriptioninitiation = MC*TNFatranscriptioninitiation[TNFaMCtranscriptioninitiationkbasal, TNFaMCtranscriptioninitiationvALPS, LPS[t], TNFaMCtranscriptioninitiationkALPS]
TNFaMCtranslation = TNFaMCtranslationk*TNFamRNAMC[t]
TNFaTNFR1association = EL*(-(kTNFaTNFR1dissociation*TNFaTNFR1EL[t]) + kTNFaTNFR1association*s16[t]*TNFR1EL[t])
TNFaTNFR1internalisation = kTNFaTNFR1internalisation*TNFaTNFR1EL[t]
TNFadegradation = EL*TNFadegradationk*s16[t]
TNFainternaldegradation = default*kTNFainternaldegradation*TNFaTNFR1cytoplasm[t]
TNFamRNALSECdegradation = LSEC*TNFamRNALSECdegradationk*TNFamRNALSEC[t]
TNFamRNAMCdegradation = MC*TNFamRNAMCdegradationk*TNFamRNAMC[t]
basalIKKbphosphorylation = default*IKKbbasalphosphoylationk*s14[t]
p38activephosphorylation = default*HenriMichaelisMentenirreversible[p38[t], p38activephoshorylationKm, p38activephosphorylationvmax]
p38basalphosphorylation = default*p38basalphosphorylationk*p38[t]
p38dephosphorylation = default*p38dephosphorylationk*p38P[t]
p652Pdegradation = c1*p65degradationk*p652P[t]
p652Pdephosphorylation0 = c1*p652Pdephosphorylation*p652P[t]
p65Pdegradationc = default*p65degradationk*s3[t]
p65Pdegradationn = c1*p65degradationk*s8[t]
p65Pdephosphorylationc = c1*p65Pdephosphorylationk*s8[t]
p65Pdephosphorylationn = default*p65Pdephosphorylationk*s3[t]
p65PphosphorylationMSK1 = c1*HenriMichaelisMentenirreversible[s8[t], p65PMSK1phosphrylationkM, p65PMSK1phosphrylationvmax]
p65nuclearshuttle = p65nuclearimportk*p65cytoplasm[t] - p65nuclearexportk*p65nucleus[t]
p65phosphorylationMSK1 = c1*HenriMichaelisMentenirreversible[p65nucleus[t], p65MSK1phosphorylationkM, p65MSK1phosphrylationvmax]
p65translation = default*p65mRNA*p65translationk
re10 = c1*activatedTranscription1[IkBatranscriptioninitiationkbasal, IkBatranscriptionkA2p65P, s8[t], IkBatranscriptionkAp65, p65nucleus[t], p652P[t], IkBatranscriptionkA3p652P]
re14 = default*IkBapactivedegradationk*s5[t]
re15 = default*HenriMichaelisMentenirreversible[s19[t], IkBap65phosphorylationkM, IkBap65phosphorylationvmax]
re17 = default*IKKbdephopshorylationk*s15[t]
re19 = c1*(-(IkBap65dissociationk*p65IkBanucleus[t]) + IkBap65associationk*p65nucleus[t]*s11[t])
re3 = p65nuclearimportk*s3[t] - p65nuclearexportk*s8[t]
end rate equations

begin parameters
IKKbactivephosphorylationkA = 0.719768509273427
IKKbactivephosphorylationkM = 5.0
IKKbactivephosphorylationvmax = 992.489864002052
IKKbbasalphosphoylationk = "1.00000000222045e-07"
IKKbdephopshorylationk = 0.00407406675412333
IkBadegcomplexcytk = "1e-05"
IkBadegcomplexnuck = "1.00000000002221e-05"
IkBadegcytk = "1.52811252693767e-05"
IkBadegnuck = "1e-05"
IkBamRNAdegcytk = 0.000204295016355302
IkBamRNAdegnuck = "5e-05"
IkBamRNAtransportk = 0.0001
IkBanuclearimportk = 0.005
IkBap65associationk = 0.0323167309116097
IkBap65nuclearexportk = 0.000100000000000222
IkBap65nuclearimportk = 0.00199999999999978
IkBap65phosphorylationkM = 0.5
IkBap65phosphorylationkcat = 35.4633298809972
IkBapactivedegradationk = 0.00329668590741014
IkBaphosphorylationkM = 0.109722103897208
IkBatranscriptionelongationkbasal = 0.00216351669101177
IkBatranscriptioninitiationkbasal = "1e-06"
IkBatranscriptionkA2p65P = 0.000100000000000222
IkBatranscriptionkA3p652P = 0.000100000000000222
IkBatranscriptionkAp65 = 0.888503709645383
IkBatranslationKm = 9.80157474422967
IkBatranslationvmax = 0.000830201042958578
JNKactivephoshorylationKm = 0.00100000000000022
JNKactivephosphorylationkcat = 791828.514880157
JNKbasalphosphorylationk = 0.000999999999999778
JNKdephosphorylationk = 0.000971808407241833
LPSLSECdegradationk = 0.000230610474560969
LPSMCdegradationk = 0.000117891832873459
MSK1activationkM = 0.332175
MSK1dephosphorylationk = 0.00961219681165222
MSK1phosphorylationkcat = "1.06928110615404e-05"
TNFaLSECtranscriptionelongationk = "1.00000000022204e-06"
TNFaLSECtranscriptioninitiationkALPS = 1.07890107243052
TNFaLSECtranscriptioninitiationkbasal = 0.0
TNFaLSECtranscriptioninitiationvALPS = "1.22197303679613e-05"
TNFaLSECtranslationk = "2.17056328697255e-05"
TNFaMCtranscriptionelongationk = "1.00000000022204e-06"
TNFaMCtranscriptioninitiationkALPS = 0.826687919847419
TNFaMCtranscriptioninitiationkbasal = 0.0
TNFaMCtranscriptioninitiationvALPS = "5.90149401714897e-06"
TNFaMCtranslationk = "2.16243947067119e-06"
TNFadegradationk = 0.000161877075794809
TNFamRNALSECdegradationk = 0.590975155351609
TNFamRNAMCdegradationk = 0.0513700937478488
kIkBa = 141486.09791093
kIkBaP = 534775.710753531
kIkBamRNA = 6962.47635118251
kJNKP = 103421.387362462
kMSKP = 2507839664.71384
kTNFR1outermembrane2vessicleshuttle = "1.8e-05"
kTNFR1vessicle2outermembraneshuttle = 0.0004
kTNFaTNFR1association = 16.833
kTNFaTNFR1internalisation = 0.00077
kTNFainternaldegradation = "8.15877575483622e-05"
kp38P = 212229.814667102
kp65 = 0.102372088824604
kp65P = 2736942.70014217
p38activephoshorylationKm = 5.63943100353927
p38activephosphorylationkcat = 1000000.0
p38basalphosphorylationk = 0.000254830975439548
p38dephosphorylationk = 0.000599422075477218
p65MSK1phosphorylationkM = 0.972449055455997
p65MSK1phosphrylationkcat = 2.74002381945741
p65Pdephosphorylationk = 0.000746701258489332
p65degradationk = "1.328912101e-05"
p65nuclearimportk = 0.0005
p65translationk = "1.68e-06"
p65mRNA = 1.0
EL = "2.59e-06"
LSEC = "4.7e-07"
MC = "3.5e-07"
c1 = "8e-07"
default = "1.3e-05"
end parameters

begin initial conditions
IkBacytoplasm[0] = IkBacytoplasmi
IkBamRNAcytoplasm[0] = IkBamRNAcytoplasmi
IkBamRNAnucleus[0] = IkBamRNAnucleusi
IkBapremRNA1[0] = IkBapremRNA1i
IkBapremRNA2[0] = IkBapremRNA2i
JNK[0] = JNKi
JNKP[0] = JNKPi
LPS[0] = LPSi
MSK1[0] = MSK1i
MSK1P[0] = MSK1Pi
TNFR1EL[0] = TNFR1ELi
TNFR1cytoplasm[0] = TNFR1cytoplasmi
TNFaTNFR1EL[0] = TNFaTNFR1ELi
TNFaTNFR1cytoplasm[0] = TNFaTNFR1cytoplasmi
TNFamRNALSEC[0] = TNFamRNALSECi
TNFamRNAMC[0] = TNFamRNAMCi
TNFapremRNALSEC[0] = TNFapremRNALSECi
TNFapremRNAMC[0] = TNFapremRNAMCi
p38[0] = p38i
p38P[0] = p38Pi
p652P[0] = p652Pi
p65IkBanucleus[0] = p65IkBanucleusi
p65cytoplasm[0] = p65cytoplasmi
p65nucleus[0] = p65nucleusi
s11[0] = s11i
s14[0] = s14i
s15[0] = s15i
s16[0] = s16i
s19[0] = s19i
s3[0] = s3i
s5[0] = s5i
s8[0] = s8i
end initial conditions

begin initial values
IkBacytoplasmi = 0.472516225018224
IkBamRNAcytoplasmi = 4.0261471309602
IkBamRNAnucleusi = 0.000106927833215887
IkBapremRNA1i = 6.17789756552652
IkBapremRNA2i = 6.17789756552652
JNKi = 0.492851335694075
JNKPi = 0.507148664305926
LPSi = 5.0
MSK1i = 14.9996753449188
MSK1Pi = 0.00032465508120628
TNFR1ELi = 0.00122834645669292
TNFR1cytoplasmi = 5.52755905511812e-05
TNFaTNFR1ELi = 0.0
TNFaTNFR1cytoplasmi = 0.0
TNFamRNALSECi = 0.0
TNFamRNAMCi = 0.0
TNFapremRNALSECi = 0.0
TNFapremRNAMCi = 0.0
p38i = 0.701691465817923
p38Pi = 0.298308534182077
p652Pi = 0.211595599589762
p65IkBanucleusi = 0.875592507158422
p65cytoplasmi = 0.000300053052727992
p65nucleusi = 0.0149965911371502
s11i = 0.945032331339863
s14i = 0.29999263653113
s15i = 7.36346887033862e-06
s16i = 0.0
s19i = 0.0437794842697899
s3i = 0.00386008654775653
s5i = 0.0706608526386937
s8i = 0.192980810254843
end initial values

begin assignment rules
unscaledJNKP := default*JNKP[t]
unscaledp38P := default*p38P[t]
p65nuclearexportk := 0.02*p65nuclearimportk
p652Pdephosphorylation := p65Pdephosphorylationk
unscaledMSKP := c1*MSK1P[t]
scaledMSKP := kMSKP*unscaledMSKP
IkBap65dissociationk := 0.003*IkBap65associationk
IkBanuclearexportk := 0.5*IkBanuclearimportk
unscaledIkBaP := default*s5[t]
scaledIkBaP := kIkBaP*unscaledIkBaP
p65MSK1phosphrylationvmax := p65MSK1phosphrylationkcat*MSK1P[t]
JNKactivephosphorylationvmax := JNKactivephosphorylationkcat*TNFaTNFR1EL[t]
scaledp65P := kp65P*unscaledp65P
scaledp65 := kp65*unscaledp65
p65PMSK1phosphrylationkcat := p65MSK1phosphrylationkcat
MSK1activationvmax := MSK1phosphorylationkcat*p38P[t]
IkBaphosphorylationvmax := IkBaphosphorylationkcat*s15[t]
p38activephosphorylationvmax := p38activephosphorylationkcat*TNFaTNFR1EL[t]
kTNFaTNFR1dissociation := 0.000019*kTNFaTNFR1association
IkBaphosphorylationkcat := IkBap65phosphorylationkcat
scaledJNKP := kJNKP*unscaledJNKP
unscaledp65P := default*s3[t] + c1*s8[t]
p65PMSK1phosphrylationvmax := p65PMSK1phosphrylationkcat*MSK1P[t]
scaledIkBamRNA := kIkBamRNA*unscaledIkBamRNA
scaledIkBa := kIkBa*unscaledIkBa
unscaledIkBa := c1*(p65IkBanucleus[t] + s11[t]) + default*(IkBacytoplasm[t] + s19[t] + s5[t])
unscaledIkBamRNA := default*IkBamRNAcytoplasm[t] + c1*IkBamRNAnucleus[t]
p65PMSK1phosphrylationkM := p65MSK1phosphorylationkM
scaledp38P := kp38P*unscaledp38P
unscaledp65 := default*(p65cytoplasm[t] + s19[t] + s3[t]) + c1*(p652P[t] + p65IkBanucleus[t] + p65nucleus[t] + s8[t])
IkBap65phosphorylationvmax := IkBap65phosphorylationkcat*s15[t]
end assignment rules

begin function definitions
TNFatranscriptioninitiation[kbasal_,vA_,A_,kA_] := kbasal + (A*vA)/(A + kA)
activatedTranscription1[k1_,k2_,Modifier_,k3_,Modifier2_,Modifier3_,k4_] := k1 + k2*Modifier + k3*Modifier2 + k4*Modifier3
HenriMichaelisMentenirreversible[substrate_,Km_,V_] := (substrate*V)/(Km + substrate)
Catalyticactivationirrev[substrate_,Activator_,Kms_,V_,Ka_] := (Activator*substrate*V)/((Activator + Ka)*(Kms + substrate))
end function definitions

begin events
end events

begin process annotations
end process annotations

begin species annotations
end species annotations

begin units
end units