begin name
strasen5
end name

begin reactions
reaction1 {1.0}TGFb = {1.0}$EXTERNAL
reaction10 {1.0}ActiveRecendo = {1.0}TGFbR2endo + {1.0}TGFbIn
reaction11 {1.0}ActiveRecendo = {1.0}TGFbR1endo + {1.0}TGFbR2endo
reaction12 {1.0}TGFbR1endo = {1.0}$EXTERNAL
reaction13 {1.0}TGFbR2endo = {1.0}$EXTERNAL
reaction14 {1.0}ActiveRec + {1.0}S7 = {1.0}InactiveRec
reaction15 {1.0}InactiveRec = {1.0}ActiveRec + {1.0}S7
reaction16 {1.0}InactiveRec = {1.0}TGFbR1surface + {1.0}TGFbR2surface + {1.0}S7
reaction17 {1.0}InactiveRec = {1.0}TGFbR1surface + {1.0}TGFbIn + {1.0}S7
reaction18 {1.0}TGFbR1surface = {1.0}TGFbR1endo
reaction19 {1.0}TGFbR2surface = {1.0}TGFbR2endo
reaction2 {1.0}TGFbR2surface = {1.0}$EXTERNAL
reaction20 {1.0}TGFbR1endo = {1.0}TGFbR1surface
reaction21 {1.0}TGFbR2endo = {1.0}TGFbR2surface
reaction22 {1.0}ActiveRec = {1.0}ActiveRecendo
reaction23 {1.0}ActiveRecendo = {1.0}TGFbR1endo + {1.0}TGFbR2endo + {1.0}TGFbIn
reaction24 {1.0}TGFbIn = {1.0}$EXTERNAL
reaction25 {1.0}S2c = {1.0}pS2c
reaction26 {2.0}pS2c + {1.0}S4c = {1.0}pS2pS2S4c
reaction27 {1.0}pS2pS2S4c = {2.0}pS2c + {1.0}S4c
reaction28 {2.0}pS2n + {1.0}S4n = {1.0}pS2pS2S4n
reaction29 {1.0}pS2pS2S4n = {2.0}pS2n + {1.0}S4n
reaction3 {1.0}$EXTERNAL = {1.0}ActiveR2
reaction30 {3.0}pS2c = {1.0}pS2pS2pS2c
reaction31 {3.0}pS2n = {1.0}pS2pS2pS2n
reaction32 {1.0}pS2pS2pS2n = {3.0}pS2n
reaction33 {1.0}pS2pS2pS2c = {3.0}pS2c
reaction34 {1.0}S2c = {1.0}S2n
reaction35 {1.0}S2n = {1.0}S2c
reaction36 {1.0}S4c = {1.0}S4n
reaction37 {1.0}S4n = {1.0}S4c
reaction38 {1.0}pS2c = {1.0}pS2n
reaction39 {1.0}pS2n = {1.0}pS2c
reaction4 {1.0}ActiveR2 = {1.0}$EXTERNAL
reaction40 {1.0}pS2pS2S4c = {1.0}pS2pS2S4n
reaction41 {1.0}pS2pS2pS2c = {1.0}pS2pS2pS2n
reaction42 {1.0}pS2n = {1.0}S2n
reaction43 {1.0}pS2pS2S4n = {1.0}pS2n + {1.0}S2n + {1.0}S4n
reaction44 {1.0}$EXTERNAL = {1.0}S2c
reaction45 {1.0}$EXTERNAL = {1.0}S4c
reaction46 {1.0}$EXTERNAL = {1.0}TGFbR1surface
reaction47 {1.0}$EXTERNAL = {1.0}TGFbR2surface
reaction5 {1.0}$EXTERNAL = {1.0}TGFbR2surface
reaction50 {1.0}$EXTERNAL = {1.0}Smad7mRNA1
reaction51 {1.0}Smad7mRNA1 = {1.0}Smad7mRNA
reaction52 {1.0}$EXTERNAL = {1.0}S7
reaction53 {1.0}S2c = {1.0}$EXTERNAL
reaction54 {1.0}S2n = {1.0}$EXTERNAL
reaction55 {1.0}pS2n = {1.0}$EXTERNAL
reaction56 {1.0}pS2c = {1.0}$EXTERNAL
reaction57 {1.0}S4c = {1.0}$EXTERNAL
reaction58 {1.0}S4n = {1.0}$EXTERNAL
reaction59 {1.0}pS2pS2S4c = {1.0}pS2c + {1.0}S4c
reaction6 {1.0}$EXTERNAL = {1.0}TGFb
reaction60 {1.0}pS2pS2S4c = {2.0}pS2c
reaction61 {1.0}pS2pS2pS2c = {2.0}pS2c
reaction62 {1.0}pS2pS2S4n = {1.0}pS2n + {1.0}S4n
reaction63 {1.0}pS2pS2S4n = {2.0}pS2n
reaction64 {1.0}pS2pS2pS2n = {2.0}pS2n
reaction65 {1.0}Smad7mRNA1 = {1.0}$EXTERNAL
reaction66 {1.0}Smad7mRNA = {1.0}$EXTERNAL
reaction67 {1.0}S7 = {1.0}$EXTERNAL
reaction7 {1.0}TGFbR1surface + {1.0}ActiveR2 = {1.0}ActiveRec
reaction8 {1.0}ActiveRec = {1.0}TGFbR1surface + {1.0}ActiveR2
reaction9 {1.0}ActiveRecendo = {1.0}TGFbR1endo + {1.0}TGFbIn
end reactions

begin rate equations
reaction1 = cyt*Functionforreaction1[TGFb[t], TGFbR2surface[t], kmedium, kfR2activation]
reaction10 = cyt*kdegR1*ActiveRecendo[t]
reaction11 = cyt*kindegLigand*ActiveRecendo[t]
reaction12 = cyt*kdegR1*TGFbR1endo[t]
reaction13 = cyt*kdegR2*TGFbR2endo[t]
reaction14 = cyt*kfSeqS7Rec*ActiveRec[t]*S7[t]
reaction15 = cyt*Functionforreaction15[InactiveRec[t], indexseqkb, kfSeqS7Rec]
reaction16 = cyt*Functionforreaction16[InactiveRec[t], indexinducedliganddeg, kindegLigand]
reaction17 = cyt*Functionforreaction17[InactiveRec[t], indexinducedR2deg, kdegR2]
reaction18 = cyt*kin1*TGFbR1surface[t]
reaction19 = cyt*kin2*TGFbR2surface[t]
reaction2 = cyt*Functionforreaction2[TGFb[t], TGFbR2surface[t], kfR2activation]
reaction20 = cyt*Functionforreaction20[TGFbR1endo[t], indexkout1relativespeed, kin1]
reaction21 = cyt*Functionforreaction21[TGFbR2endo[t], indexkout2relativespeed, kin2]
reaction22 = cyt*Functionforreaction22[ActiveRec[t], indexactiveRecinternalize, kin1]
reaction23 = cyt*kdissoActiveRec*ActiveRecendo[t]
reaction24 = cyt*kindegLigand*TGFbIn[t]
reaction25 = cyt*Functionforreaction25[ActiveRecendo[t], S2c[t], kphosphorylation]
reaction26 = cyt*kftrimmer*pS2c[t]^2*S4c[t]
reaction27 = cyt*kbtrimmer*pS2pS2S4c[t]
reaction28 = kftrimmer*nuc*pS2n[t]^2*S4n[t]
reaction29 = kbtrimmer*nuc*pS2pS2S4n[t]
reaction3 = cyt*Functionforreaction3[TGFb[t], TGFbR2surface[t], kfR2activation]
reaction30 = cyt*Functionforreaction30[indexkfhomotrimer, kftrimmer, pS2c[t]]
reaction31 = nuc*Functionforreaction310[indexkfhomotrimer, kftrimmer, pS2n[t]]
reaction32 = nuc*Functionforreaction32[indexkbhomotrimer, kbtrimmer, pS2pS2pS2n[t]]
reaction33 = cyt*Functionforreaction33[indexkbhomotrimer, kbtrimmer, pS2pS2pS2c[t]]
reaction34 = Functionforreaction34[S2c[t], S2importtonuc, cyt]
reaction35 = Functionforreaction35[S2exportfromnuc, S2n[t], nuc]
reaction36 = Functionforreaction36[S4c[t], S4importtonuc, cyt]
reaction37 = Functionforreaction37[S4exportfromnuc, S4n[t], nuc]
reaction38 = Functionforreaction38[S2importtonuc, cyt, pS2c[t]]
reaction39 = Functionforreaction39[S2exportfromnuc, nuc, pS2n[t]]
reaction4 = cyt*Functionforreaction4[ActiveR2[t], indexkbR2, kfR2activation]
reaction40 = Functionforreaction40[Trimerimporttonuc, cyt, pS2pS2S4c[t]]
reaction41 = Functionforreaction41[Trimerimporttonuc, cyt, pS2pS2pS2c[t]]
reaction42 = kDephos*nuc*pS2n[t]
reaction43 = nuc*Functionforreaction43[indextrimerdephos, kDephos, pS2pS2S4n[t]]
reaction44 = cyt*Functionforreaction440[S2exportfromnuc, S2importtonuc, S2total, kdegS2]
reaction45 = cyt*Functionforreaction450[S4exportfromnuc, S4importtonuc, S4total, kdegS4]
reaction46 = cyt*Functionforreaction460[R1total, indexkout1relativespeed, kin1, kdegR1]
reaction47 = cyt*Functionforreaction470[R2total, indexkout2relativespeed, kin2, kdegR2]
reaction5 = cyt*Functionforreaction5[ActiveR2[t], indexkbR2, kfR2activation]
reaction50 = nuc*Functionforreaction5010[DRB, Kmran, hillfact1, kinducedS7production, mRNAprod, pS2pS2S4n[t]]
reaction51 = Functionforreaction51[Smad7mRNA1[t], exportcytoplasm, nuc]
reaction52 = cyt*Functionforreaction52[Smad7mRNA[t], kS7protein]
reaction53 = cyt*kdegS2*S2c[t]
reaction54 = kdegS2*nuc*S2n[t]
reaction55 = kdegS2*nuc*pS2n[t]
reaction56 = cyt*kdegS2*pS2c[t]
reaction57 = cyt*kdegS4*S4c[t]
reaction58 = kdegS4*nuc*S4n[t]
reaction59 = cyt*kdegS2*pS2pS2S4c[t]
reaction6 = cyt*Functionforreaction6[ActiveR2[t], indexkbR2, kmedium, kfR2activation]
reaction60 = cyt*kdegS4*pS2pS2S4c[t]
reaction61 = cyt*kdegS2*pS2pS2pS2c[t]
reaction62 = kdegS2*nuc*pS2pS2S4n[t]
reaction63 = kdegS4*nuc*pS2pS2S4n[t]
reaction64 = kdegS2*nuc*pS2pS2pS2n[t]
reaction65 = kmRNA1degS7*nuc*Smad7mRNA1[t]
reaction66 = cyt*kmRNAdegS7*Smad7mRNA[t]
reaction67 = cyt*kdegS7*S7[t]
reaction7 = cyt*kfR1activation*ActiveR2[t]*TGFbR1surface[t]
reaction8 = cyt*Functionforreaction8[ActiveRec[t], indexkbR1, kfR1activation]
reaction9 = cyt*kdegR2*ActiveRecendo[t]
end rate equations

begin parameters
DRB = 1.0
Kmran = 223.595257238238
R1total = 34.8728125404976
R2total = 34.9992000511296
S2exportfromnuc = 1.99869955250212
S2importtonuc = 0.371577202544786
S2total = 876.042139372642
S4exportfromnuc = 0.196810731388947
S4importtonuc = 0.0370885363056236
S4total = 629.893021850583
TGFbLIGANDDose = 100.0
Trimerimporttonuc = 0.14403262974308
exportcytoplasm = 0.030437091663097
hillfact1 = 3.98592596228747
indexactiveRecinternalize = 0.537380811093942
indexinducedR2deg = 1.00037810941361
indexinducedliganddeg = 2.7210717377255
indexkout1relativespeed = 0.566651645025112
indexkout2relativespeed = 0.245785368672998
indexkbR1 = 1.61229612947783
indexkbR2 = 8.70467633794271
indexkbhomotrimer = 0.0164056196749139
indexkfhomotrimer = 4.48445616275042
indexseqkb = 0.000881183442123411
indextrimerdephos = 2.60999282198359
k5 = 47.0
kDephos = 0.139418263062769
kS7protein = 0.218269773101254
kdissoActiveRec = 0.00103714944572345
kin1 = 0.20092069321314
kin2 = 0.62580495280349
kinducedS7production = 4.99901466408568
kmedium = 2018.93290162616
kphosphorylation = 0.0701273900652988
kbtrimmer = 1.60762398289129
kdegR1 = 0.0586554820930934
kdegR2 = 0.00100039445581987
kdegS2 = 0.000514148278553222
kdegS4 = 0.00480202730242853
kdegS7 = 0.00102253743337089
kfR1activation = 4.98547574132432
kfR2activation = 4.95555330964476
kfSeqS7Rec = 0.882166671316411
kftrimmer = 4.81430089969474
kindegLigand = 0.720198437381795
kmRNA1degS7 = 0.0052188859785782
kmRNAdegS7 = 0.0990155435421535
mRNAprod = 0.0130886858359441
offsetDRB = 0.0286195
scaleDRB = 1.0205
cyt = 2.0
nuc = 1.0
end parameters

begin initial conditions
ActiveR2[0] = ActiveR2i
ActiveRec[0] = ActiveReci
ActiveRecendo[0] = ActiveRecendoi
InactiveRec[0] = InactiveReci
S2c[0] = S2ci
S2n[0] = S2ni
S4c[0] = S4ci
S4n[0] = S4ni
S7[0] = S7i
Smad7mRNA[0] = Smad7mRNAi
Smad7mRNA1[0] = Smad7mRNA1i
TGFb[0] = TGFbi
TGFbIn[0] = TGFbIni
TGFbR1endo[0] = TGFbR1endoi
TGFbR1surface[0] = TGFbR1surfacei
TGFbR2endo[0] = TGFbR2endoi
TGFbR2surface[0] = TGFbR2surfacei
pS2c[0] = pS2ci
pS2n[0] = pS2ni
pS2pS2S4c[0] = pS2pS2S4ci
pS2pS2S4n[0] = pS2pS2S4ni
pS2pS2pS2c[0] = pS2pS2pS2ci
pS2pS2pS2n[0] = pS2pS2pS2ni
end initial conditions

begin initial values
ActiveR2i = 0.0
ActiveReci = 0.0
ActiveRecendoi = 0.0
InactiveReci = 0.0
S2ci = 638.6434569983527
S2ni = 237.39868237428928
S4ci = 460.47553390898076
S4ni = 169.41748794160233
S7i = 12.043365220732587
Smad7mRNAi = 0.05642005114580563
Smad7mRNA1i = 0.3670825118716101
TGFbi = 100
TGFbIni = 0.0
TGFbR1endoi = 18.76309651441349
TGFbR1surfacei = 16.109716026084108
TGFbR2endoi = 28.058081318683687
TGFbR2surfacei = 6.941118732445909
pS2ci = 0.0
pS2ni = 0.0
pS2pS2S4ci = 0.0
pS2pS2S4ni = 0.0
pS2pS2pS2ci = 0.0
pS2pS2pS2ni = 0.0
end initial values

begin assignment rules
NUCCYTSMAD2 := offsetDRB + (scaleDRB*(pS2n[t] + 3*pS2pS2pS2n[t] + 2*pS2pS2S4n[t] + S2n[t]))/(pS2c[t] + 3*pS2pS2pS2c[t] + 2*pS2pS2S4c[t] + S2c[t])
end assignment rules

begin function definitions
Functionforreaction25[ActiveRecendo_,S2c_,kphosphorylation_] := ActiveRecendo*kphosphorylation*S2c
Functionforreaction41[Trimerimporttonuc_,cyt_,pS2pS2pS2c_] := cyt*pS2pS2pS2c*Trimerimporttonuc
Functionforreaction52[Smad7mRNA_,kS7protein_] := kS7protein*Smad7mRNA
Functionforreaction39[S2exportfromnuc_,nuc_,pS2n_] := nuc*pS2n*S2exportfromnuc
Functionforreaction1[TGFb_,TGFbR2surface_,kmedium_,kfR2activation_] := (kfR2activation*TGFb*TGFbR2surface)/kmedium
Functionforreaction35[S2exportfromnuc_,S2n_,nuc_] := nuc*S2exportfromnuc*S2n
Functionforreaction6[ActiveR2_,indexkbR2_,kmedium_,kfR2activation_] := (ActiveR2*indexkbR2*kfR2activation)/kmedium
Functionforreaction43[indextrimerdephos_,kDephos_,pS2pS2S4n_] := indextrimerdephos*kDephos*pS2pS2S4n
Functionforreaction33[indexkbhomotrimer_,kbtrimmer_,pS2pS2pS2c_] := indexkbhomotrimer*kbtrimmer*pS2pS2pS2c
Functionforreaction310[indexkfhomotrimer_,kftrimmer_,pS2n_] := indexkfhomotrimer*kftrimmer*pS2n^3
Functionforreaction51[Smad7mRNA1_,exportcytoplasm_,nuc_] := exportcytoplasm*nuc*Smad7mRNA1
Functionforreaction30[indexkfhomotrimer_,kftrimmer_,pS2c_] := indexkfhomotrimer*kftrimmer*pS2c^3
Functionforreaction38[S2importtonuc_,cyt_,pS2c_] := cyt*pS2c*S2importtonuc
Functionforreaction37[S4exportfromnuc_,S4n_,nuc_] := nuc*S4exportfromnuc*S4n
Functionforreaction36[S4c_,S4importtonuc_,cyt_] := cyt*S4c*S4importtonuc
Functionforreaction34[S2c_,S2importtonuc_,cyt_] := cyt*S2c*S2importtonuc
Functionforreaction3[TGFb_,TGFbR2surface_,kfR2activation_] := kfR2activation*TGFb*TGFbR2surface
Functionforreaction40[Trimerimporttonuc_,cyt_,pS2pS2S4c_] := cyt*pS2pS2S4c*Trimerimporttonuc
Functionforreaction5[ActiveR2_,indexkbR2_,kfR2activation_] := ActiveR2*indexkbR2*kfR2activation
Functionforreaction8[ActiveRec_,indexkbR1_,kfR1activation_] := ActiveRec*indexkbR1*kfR1activation
Functionforreaction15[InactiveRec_,indexseqkb_,kfSeqS7Rec_] := InactiveRec*indexseqkb*kfSeqS7Rec
Functionforreaction470[R2total_,indexkout2relativespeed_,kin2_,kdegR2_] := (kdegR2^2*kin2*R2total)/(kdegR2^2 + kdegR2*kin2 + indexkout2relativespeed*kdegR2*kin2)
Functionforreaction5010[DRB_,Kmran_,hillfact1_,kinducedS7production_,mRNAprod_,pS2pS2S4n_] := DRB*(mRNAprod + (kinducedS7production*pS2pS2S4n^hillfact1)/(Kmran^hillfact1 + pS2pS2S4n^hillfact1))
Functionforreaction32[indexkbhomotrimer_,kbtrimmer_,pS2pS2pS2n_] := indexkbhomotrimer*kbtrimmer*pS2pS2pS2n
Functionforreaction17[InactiveRec_,indexinducedR2deg_,kdegR2_] := InactiveRec*indexinducedR2deg*kdegR2
Functionforreaction16[InactiveRec_,indexinducedliganddeg_,kindegLigand_] := InactiveRec*indexinducedliganddeg*kindegLigand
Functionforreaction460[R1total_,indexkout1relativespeed_,kin1_,kdegR1_] := (kdegR1^2*kin1*R1total)/(kdegR1^2 + kdegR1*kin1 + indexkout1relativespeed*kdegR1*kin1)
Functionforreaction4[ActiveR2_,indexkbR2_,kfR2activation_] := ActiveR2*indexkbR2*kfR2activation
Functionforreaction22[ActiveRec_,indexactiveRecinternalize_,kin1_] := ActiveRec*indexactiveRecinternalize*kin1
Functionforreaction21[TGFbR2endo_,indexkout2relativespeed_,kin2_] := indexkout2relativespeed*kin2*TGFbR2endo
Functionforreaction2[TGFb_,TGFbR2surface_,kfR2activation_] := kfR2activation*TGFb*TGFbR2surface
Functionforreaction450[S4exportfromnuc_,S4importtonuc_,S4total_,kdegS4_] := ((kdegS4^2 + kdegS4*S4exportfromnuc + kdegS4*S4importtonuc)*S4total)/(kdegS4 + S4exportfromnuc + 2*S4importtonuc)
Functionforreaction440[S2exportfromnuc_,S2importtonuc_,S2total_,kdegS2_] := ((kdegS2^2 + kdegS2*S2exportfromnuc + kdegS2*S2importtonuc)*S2total)/(kdegS2 + S2exportfromnuc + 2*S2importtonuc)
Functionforreaction20[TGFbR1endo_,indexkout1relativespeed_,kin1_] := indexkout1relativespeed*kin1*TGFbR1endo
end function definitions

begin events
end events

begin process annotations
end process annotations

begin species annotations
end species annotations

begin units
end units