begin name
beuke11
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 = 0.691393057063674
IKKbactivephosphorylationkM = 5.0
IKKbactivephosphorylationvmax = 617.88403458051
IKKbbasalphosphoylationk = "1.00000000222045e-07"
IKKbdephopshorylationk = 0.002175755740092
IkBadegcomplexcytk = "1e-05"
IkBadegcomplexnuck = "1.00000000002221e-05"
IkBadegcytk = "2.30544221016227e-05"
IkBadegnuck = "1e-05"
IkBamRNAdegcytk = 0.000210154567719939
IkBamRNAdegnuck = "5e-05"
IkBamRNAtransportk = 0.0001
IkBanuclearimportk = 0.005
IkBap65associationk = 0.0999999999999998
IkBap65nuclearexportk = 0.00199999999999978
IkBap65nuclearimportk = "1.00000000002221e-05"
IkBap65phosphorylationkM = 0.1
IkBap65phosphorylationkcat = 12.161193049696
IkBapactivedegradationk = 0.00999999999999978
IkBaphosphorylationkM = 0.5
IkBatranscriptionelongationkbasal = 0.00255279471616561
IkBatranscriptioninitiationkbasal = "1e-06"
IkBatranscriptionkA2p65P = 0.000100000000000222
IkBatranscriptionkA3p652P = 0.000100157903696224
IkBatranscriptionkAp65 = 0.406192446600196
IkBatranslationKm = 6.66471342708503
IkBatranslationvmax = 0.000385531368765079
JNKactivephoshorylationKm = 10.0
JNKactivephosphorylationkcat = 267839.122269674
JNKbasalphosphorylationk = "4.82691427381975e-05"
JNKdephosphorylationk = 0.000662033343347143
LPSLSECdegradationk = 0.000335742036350122
LPSMCdegradationk = 0.000144664368083339
MSK1activationkM = 0.332175
MSK1dephosphorylationk = 0.00999999999999978
MSK1phosphorylationkcat = "1.00000000002221e-05"
TNFaLSECtranscriptionelongationk = "1.00000000022204e-06"
TNFaLSECtranscriptioninitiationkALPS = 0.976432788282717
TNFaLSECtranscriptioninitiationkbasal = 0.0
TNFaLSECtranscriptioninitiationvALPS = "1.2028208130262e-05"
TNFaLSECtranslationk = "2.13601072370864e-05"
TNFaMCtranscriptionelongationk = "1.00000000022204e-06"
TNFaMCtranscriptioninitiationkALPS = 0.764641819804591
TNFaMCtranscriptioninitiationkbasal = 0.0
TNFaMCtranscriptioninitiationvALPS = "5.46031437939905e-06"
TNFaMCtranslationk = "2.00078139757655e-06"
TNFadegradationk = 0.000107080098427041
TNFamRNALSECdegradationk = 0.608833029655888
TNFamRNAMCdegradationk = 0.055509931610376
kIkBa = 250865.381604027
kIkBaP = 2666296.84529316
kIkBamRNA = 6699.67997447578
kJNKP = 771825.982295121
kMSKP = 15106750507.0978
kTNFR1outermembrane2vessicleshuttle = "1.8e-05"
kTNFR1vessicle2outermembraneshuttle = 0.0004
kTNFaTNFR1association = 16.833
kTNFaTNFR1internalisation = 0.00077
kTNFainternaldegradation = "6.80175820099816e-05"
kp38P = 1149234.39629039
kp65 = 0.102372088824604
kp65P = 2314129.4681712
p38activephoshorylationKm = 2.61750530711309
p38activephosphorylationkcat = 70186.2120794266
p38basalphosphorylationk = "6.27623531922627e-05"
p38dephosphorylationk = 0.0010765315189227
p65MSK1phosphorylationkM = 10.0
p65MSK1phosphrylationkcat = 0.000461090709390465
p65Pdephosphorylationk = 0.00466001858611242
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 = 0.242411784115408
IkBamRNAcytoplasmi = 4.18407341521561
IkBamRNAnucleusi = 0.000114309278184806
IkBapremRNA1i = 5.59726381368684
IkBapremRNA2i = 5.59726381368684
JNKi = 0.932044243566961
JNKPi = 0.0679557564330392
LPSi = 5.0
MSK1i = 14.9999461046974
MSK1Pi = 5.38953026077621e-05
TNFR1ELi = 0.0012283464566929
TNFR1cytoplasmi = 5.52755905511804e-05
TNFaTNFR1ELi = 0.0
TNFaTNFR1cytoplasmi = 0.0
TNFamRNALSECi = 0.0
TNFamRNAMCi = 0.0
TNFapremRNALSECi = 0.0
TNFapremRNAMCi = 0.0
p38i = 0.944911181628887
p38Pi = 0.0550888183711128
p652Pi = 1.37261889488584e-07
p65IkBanucleusi = 0.000539556338524618
p65cytoplasmi = 0.000703390958527773
p65nucleusi = 0.0351184345815313
s11i = 0.484823021894256
s14i = 0.299986212321197
s15i = 1.3787678803245e-05
s16i = 0.0
s19i = 0.10777507185251
s3i = 0.00456622878939381
s5i = 0.0141723558496553
s8i = 0.22822611375682
end initial values

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

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