begin name strasen8 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}$EXTERNAL reaction14 {1.0}ActiveRec + {1.0}S7 = {1.0}InactiveRec reaction15 {1.0}InactiveRec = {1.0}ActiveRec + {1.0}S7 reaction16 {1.0}InactiveRec = {1.0}TGFbR1endo + {1.0}TGFbR2endo + {1.0}S7 reaction17 {1.0}InactiveRec = {1.0}TGFbR1endo + {1.0}TGFbIn + {1.0}S7 reaction18 {1.0}TGFbR1surface = {1.0}TGFbR1endo reaction19 {1.0}TGFbR2surface = {1.0}TGFbR2endo reaction2 {1.0}TGFbR2surface = {1.0}$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}$EXTERNAL reaction25 {1.0}TGFb = {1.0}$EXTERNAL reaction26 {1.0}S2c = {1.0}pS2c reaction27 {2.0}pS2c + {1.0}S4c = {1.0}pS2pS2S4c reaction28 {1.0}pS2pS2S4c = {2.0}pS2c + {1.0}S4c reaction29 {2.0}pS2n + {1.0}S4n = {1.0}pS2pS2S4n reaction3 {1.0}$EXTERNAL = {1.0}ActiveR2 reaction30 {1.0}pS2pS2S4n = {2.0}pS2n + {1.0}S4n reaction31 {3.0}pS2c = {1.0}pS2pS2pS2c reaction32 {1.0}pS2pS2pS2c = {3.0}pS2c reaction33 {3.0}pS2n = {1.0}pS2pS2pS2n reaction34 {1.0}pS2pS2pS2n = {3.0}pS2n reaction35 {1.0}S2c = {1.0}S2n reaction36 {1.0}S2n = {1.0}S2c reaction37 {1.0}S4c = {1.0}S4n reaction38 {1.0}S4n = {1.0}S4c reaction39 {1.0}pS2c = {1.0}pS2n reaction4 {1.0}ActiveR2 = {1.0}$EXTERNAL reaction40 {1.0}pS2n = {1.0}pS2c reaction41 {1.0}pS2pS2S4c = {1.0}pS2pS2S4n reaction42 {1.0}pS2pS2pS2c = {1.0}pS2pS2pS2n reaction43 {1.0}pS2n = {1.0}S2n reaction44 {1.0}pS2pS2S4n = {1.0}pS2n + {1.0}S2n + {1.0}S4n reaction45 {1.0}$EXTERNAL = {1.0}S2c reaction46 {1.0}$EXTERNAL = {1.0}S4c reaction47 {1.0}$EXTERNAL = {1.0}TGFbR1surface reaction48 {1.0}$EXTERNAL = {1.0}TGFbR2surface reaction5 {1.0}$EXTERNAL = {1.0}TGFbR2surface reaction51 {1.0}$EXTERNAL = {1.0}Smad7mRNA1 reaction52 {1.0}Smad7mRNA1 = {1.0}Smad7mRNA reaction53 {1.0}$EXTERNAL = {1.0}S7 reaction54 {1.0}S2c = {1.0}$EXTERNAL reaction55 {1.0}S2n = {1.0}$EXTERNAL reaction56 {1.0}pS2n = {1.0}$EXTERNAL reaction57 {1.0}pS2c = {1.0}$EXTERNAL reaction58 {1.0}S4c = {1.0}$EXTERNAL reaction59 {1.0}S4n = {1.0}$EXTERNAL reaction6 {1.0}$EXTERNAL = {1.0}TGFb reaction60 {1.0}pS2pS2S4c = {1.0}pS2c + {1.0}S4c reaction61 {1.0}pS2pS2S4c = {2.0}pS2c reaction62 {1.0}pS2pS2pS2c = {2.0}pS2c reaction63 {1.0}pS2pS2S4n = {1.0}pS2n + {1.0}S4n reaction64 {1.0}pS2pS2S4n = {2.0}pS2n reaction65 {1.0}pS2pS2pS2n = {2.0}pS2n reaction66 {1.0}Smad7mRNA1 = {1.0}$EXTERNAL reaction67 {1.0}Smad7mRNA = {1.0}$EXTERNAL reaction68 {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*Functionforreaction10[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*Functionforreaction150[InactiveRec[t], indexseqkb, kfSeqS7Rec] reaction16 = cyt*Functionforreaction160[InactiveRec[t], indexinducedliganddeg, kindegLigand] reaction17 = cyt*Functionforreaction170[InactiveRec[t], indexinducedR2deg, kdegR2] reaction18 = cyt*kinR1C3*TGFbR1surface[t] reaction19 = cyt*kinR2C3*TGFbR2surface[t] reaction2 = cyt*Functionforreaction20[TGFb[t], TGFbR2surface[t], kfR2activation] reaction20 = cyt*Functionforreaction2020[TGFbR1endo[t], indexkout1relativespeedC3, kinR1C3] reaction21 = cyt*Functionforreaction2120[TGFbR2endo[t], indexkout2relativespeedC3, kinR2C3] reaction22 = cyt*Functionforreaction2220[ActiveRec[t], indexactiveRecinternalizeC3, kinR1C3] reaction23 = cyt*kdissoActiveRec*ActiveRecendo[t] reaction24 = cyt*kindegLigand*TGFbIn[t] reaction25 = cyt*koutdegLigand100pM*TGFb[t] reaction26 = cyt*Functionforreaction26[ActiveRecendo[t], S2c[t], kphosphorylation] reaction27 = cyt*kftrimmer*pS2c[t]^2*S4c[t] reaction28 = cyt*kbtrimmer*pS2pS2S4c[t] reaction29 = kftrimmer*nuc*pS2n[t]^2*S4n[t] reaction3 = cyt*Functionforreaction30[TGFb[t], TGFbR2surface[t], kfR2activation] reaction30 = kbtrimmer*nuc*pS2pS2S4n[t] reaction31 = cyt*Functionforreaction312[indexkfhomotrimer, kftrimmer, pS2c[t]] reaction32 = cyt*Functionforreaction3230[indexkbhomotrimer, kbtrimmer, pS2pS2pS2c[t]] reaction33 = nuc*Functionforreaction332[indexkfhomotrimer, kftrimmer, pS2n[t]] reaction34 = nuc*Functionforreaction3420[indexkbhomotrimer, kbtrimmer, pS2pS2pS2n[t]] reaction35 = Functionforreaction3530[S2c[t], S2importtonucC3, cyt] reaction36 = Functionforreaction3630[S2exportfromnucC3, S2n[t], nuc] reaction37 = Functionforreaction3730[S4c[t], S4importtonucC3, cyt] reaction38 = Functionforreaction3830[S4exportfromnucC3, S4n[t], nuc] reaction39 = Functionforreaction3930[S2importtonucC3, cyt, pS2c[t]] reaction4 = cyt*Functionforreaction40[ActiveR2[t], indexkbR2, kfR2activation] reaction40 = Functionforreaction4030[S2exportfromnucC3, nuc, pS2n[t]] reaction41 = Functionforreaction4120[Trimerimporttonuc, cyt, pS2pS2S4c[t]] reaction42 = Functionforreaction42[Trimerimporttonuc, cyt, pS2pS2pS2c[t]] reaction43 = kDephosC3*nuc*pS2n[t] reaction44 = nuc*Functionforreaction4440[indextrimerdephos, kDephosC3, pS2pS2S4n[t]] reaction45 = cyt*Functionforreaction453[S2exportfromnucC3, S2importtonucC3, S2totalC3, kdegS2] reaction46 = cyt*Functionforreaction463[S4exportfromnucC3, S4importtonucC3, S4totalC3, kdegS4] reaction47 = cyt*Functionforreaction473[R1totalC3, indexkout1relativespeedC3, kinR1C3, kdegR1] reaction48 = cyt*Functionforreaction481[R2totalC3, indexkout2relativespeedC3, kinR2C3, kdegR2] reaction5 = cyt*Functionforreaction50[ActiveR2[t], indexkbR2, kfR2activation] reaction51 = nuc*Functionforreaction5130[DRB, Kmran, S7KD, hillfact1, kinducedS7productionC3, mRNAprodC3, pS2pS2S4n[t]] reaction52 = Functionforreaction5230[Smad7mRNA1[t], exportcytoplasm, nuc] reaction53 = cyt*Functionforreaction5310[Smad7mRNA[t], kS7proteinC3] reaction54 = cyt*kdegS2*S2c[t] reaction55 = kdegS2*nuc*S2n[t] reaction56 = kdegS2*nuc*pS2n[t] reaction57 = cyt*kdegS2*pS2c[t] reaction58 = cyt*kdegS4*S4c[t] reaction59 = kdegS4*nuc*S4n[t] reaction6 = cyt*Functionforreaction60[ActiveR2[t], indexkbR2, kmedium, kfR2activation] reaction60 = cyt*kdegS2*pS2pS2S4c[t] reaction61 = cyt*kdegS4*pS2pS2S4c[t] reaction62 = cyt*kdegS2*pS2pS2pS2c[t] reaction63 = kdegS2*nuc*pS2pS2S4n[t] reaction64 = kdegS4*nuc*pS2pS2S4n[t] reaction65 = kdegS2*nuc*pS2pS2pS2n[t] reaction66 = kmRNA1degS7*nuc*Smad7mRNA1[t] reaction67 = cyt*kmRNAdegS7*Smad7mRNA[t] reaction68 = cyt*kdegS7*S7[t] reaction7 = cyt*kfR1activation*ActiveR2[t]*TGFbR1surface[t] reaction8 = cyt*Functionforreaction80[ActiveRec[t], indexkbR1, kfR1activation] reaction9 = cyt*kdegR2*ActiveRecendo[t] end rate equations begin parameters DRB = 1.0 Kmran = 223.586 R1totalC3 = 69.7199989056023 R2totalC3 = 49.1925438819563 S2exportfromnucC3 = 3.00430865315074 S2importtonucC3 = 0.248774260500559 S2totalC3 = 1335.77950850425 S4exportfromnucC3 = 0.0984718694215043 S4importtonucC3 = 0.0730474752631315 S4totalC3 = 347.505766824434 S7KD = 1.0 Trimerimporttonuc = 0.144035002432848 exportcytoplasm = 0.0304372961307751 hillfact1 = 3.98630224594983 indexactiveRecinternalizeC3 = 1.0379108128956 indexinducedR2deg = 1.00037776866312 indexinducedliganddeg = 2.72106513634098 indexkout1relativespeedC3 = 1.13287434679021 indexkout2relativespeedC3 = 0.450697494637432 indexkbR1 = 1.61290474569122 indexkbR2 = 8.70498854136694 indexkbhomotrimer = 0.0163921522930962 indexkfhomotrimer = 4.4857919268227 indexseqkb = 0.000865131944828012 indextrimerdephos = 2.61013820571304 kDephosC3 = 0.0707018316477647 kS7proteinC3 = 0.123149764012103 kdissoActiveRec = 0.00103940411358367 kinR1C3 = 0.397836393488341 kinR2C3 = 0.396038887562465 kinducedS7productionC3 = 2.9510868497 kmedium = 2000000.0 kphosphorylation = 0.0701560191772152 kbtrimmer = 1.6077346670684 kdegR1 = 0.0586584495713968 kdegR2 = 0.0010003937382472 kdegS2 = 0.000514084012175461 kdegS4 = 0.00480202699360057 kdegS7 = 0.00102401829734485 kfR1activation = 4.98548548076033 kfR2activation = 4.95559496701657 kfSeqS7Rec = 0.882455038106022 kftrimmer = 4.81424700307387 kindegLigand = 0.720182234635314 kmRNA1degS7 = 0.00523181439900629 kmRNAdegS7 = 0.0990158065483902 koutdegLigand100pM = 0.00036189622 mRNAprodC3 = 0.0239754962469105 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 = 1146.0180383886332 S2ni = 189.76147011561696 S4ci = 143.91643145030181 S4ni = 203.58933537413213 S7i = 12.424323107678699 Smad7mRNAi = 0.1033110724689415 Smad7mRNA1i = 0.6721641187798199 TGFbi = 100.0 TGFbIni = 0.0 TGFbR1endoi = 30.57468258089889 TGFbR1surfacei = 39.145316324703415 TGFbR2endoi = 33.85063901424163 TGFbR2surfacei = 15.341904867714664 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 := (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 Functionforreaction4030[S2exportfromnucC3_,nuc_,pS2n_] := nuc*pS2n*S2exportfromnucC3 Functionforreaction150[InactiveRec_,indexseqkb_,kfSeqS7Rec_] := InactiveRec*indexseqkb*kfSeqS7Rec Functionforreaction80[ActiveRec_,indexkbR1_,kfR1activation_] := ActiveRec*indexkbR1*kfR1activation Functionforreaction30[TGFb_,TGFbR2surface_,kfR2activation_] := kfR2activation*TGFb*TGFbR2surface Functionforreaction160[InactiveRec_,indexinducedliganddeg_,kindegLigand_] := InactiveRec*indexinducedliganddeg*kindegLigand Functionforreaction50[ActiveR2_,indexkbR2_,kfR2activation_] := ActiveR2*indexkbR2*kfR2activation Functionforreaction3530[S2c_,S2importtonucC3_,cyt_] := cyt*S2c*S2importtonucC3 Functionforreaction4120[Trimerimporttonuc_,cyt_,pS2pS2S4c_] := cyt*pS2pS2S4c*Trimerimporttonuc Functionforreaction5230[Smad7mRNA1_,exportcytoplasm_,nuc_] := exportcytoplasm*nuc*Smad7mRNA1 Functionforreaction3230[indexkbhomotrimer_,kbtrimmer_,pS2pS2pS2c_] := indexkbhomotrimer*kbtrimmer*pS2pS2pS2c Functionforreaction4440[indextrimerdephos_,kDephosC3_,pS2pS2S4n_] := indextrimerdephos*kDephosC3*pS2pS2S4n Functionforreaction2020[TGFbR1endo_,indexkout1relativespeedC3_,kinR1C3_] := indexkout1relativespeedC3*kinR1C3*TGFbR1endo Functionforreaction332[indexkfhomotrimer_,kftrimmer_,pS2n_] := indexkfhomotrimer*kftrimmer*pS2n^3 Functionforreaction5310[Smad7mRNA_,kS7proteinC3_] := kS7proteinC3*Smad7mRNA Functionforreaction3830[S4exportfromnucC3_,S4n_,nuc_] := nuc*S4exportfromnucC3*S4n Functionforreaction10[TGFb_,TGFbR2surface_,kmedium_,kfR2activation_] := (kfR2activation*TGFb*TGFbR2surface)/kmedium Functionforreaction170[InactiveRec_,indexinducedR2deg_,kdegR2_] := InactiveRec*indexinducedR2deg*kdegR2 Functionforreaction60[ActiveR2_,indexkbR2_,kmedium_,kfR2activation_] := (ActiveR2*indexkbR2*kfR2activation)/kmedium Functionforreaction2220[ActiveRec_,indexactiveRecinternalizeC3_,kinR1C3_] := ActiveRec*indexactiveRecinternalizeC3*kinR1C3 Functionforreaction26[ActiveRecendo_,S2c_,kphosphorylation_] := ActiveRecendo*kphosphorylation*S2c Functionforreaction3630[S2exportfromnucC3_,S2n_,nuc_] := nuc*S2exportfromnucC3*S2n Functionforreaction312[indexkfhomotrimer_,kftrimmer_,pS2c_] := indexkfhomotrimer*kftrimmer*pS2c^3 Functionforreaction3730[S4c_,S4importtonucC3_,cyt_] := cyt*S4c*S4importtonucC3 Functionforreaction2120[TGFbR2endo_,indexkout2relativespeedC3_,kinR2C3_] := indexkout2relativespeedC3*kinR2C3*TGFbR2endo Functionforreaction3930[S2importtonucC3_,cyt_,pS2c_] := cyt*pS2c*S2importtonucC3 Functionforreaction453[S2exportfromnucC3_,S2importtonucC3_,S2totalC3_,kdegS2_] := ((kdegS2^2 + kdegS2*S2exportfromnucC3 + kdegS2*S2importtonucC3)*S2totalC3)/(kdegS2 + S2exportfromnucC3 + 2*S2importtonucC3) Functionforreaction463[S4exportfromnucC3_,S4importtonucC3_,S4totalC3_,kdegS4_] := ((kdegS4^2 + kdegS4*S4exportfromnucC3 + kdegS4*S4importtonucC3)*S4totalC3)/(kdegS4 + S4exportfromnucC3 + 2*S4importtonucC3) Functionforreaction20[TGFb_,TGFbR2surface_,kfR2activation_] := kfR2activation*TGFb*TGFbR2surface Functionforreaction473[R1totalC3_,indexkout1relativespeedC3_,kinR1C3_,kdegR1_] := (kdegR1^2*kinR1C3*R1totalC3)/(kdegR1^2 + kdegR1*kinR1C3 + indexkout1relativespeedC3*kdegR1*kinR1C3) Functionforreaction481[R2totalC3_,indexkout2relativespeedC3_,kinR2C3_,kdegR2_] := (kdegR2^2*kinR2C3*R2totalC3)/(kdegR2^2 + kdegR2*kinR2C3 + indexkout2relativespeedC3*kdegR2*kinR2C3) Functionforreaction3420[indexkbhomotrimer_,kbtrimmer_,pS2pS2pS2n_] := indexkbhomotrimer*kbtrimmer*pS2pS2pS2n Functionforreaction42[Trimerimporttonuc_,cyt_,pS2pS2pS2c_] := cyt*pS2pS2pS2c*Trimerimporttonuc Functionforreaction5130[DRB_,Kmran_,S7KD_,hillfact1_,kinducedS7productionC3_,mRNAprodC3_,pS2pS2S4n_] := DRB*(mRNAprodC3 + (kinducedS7productionC3*pS2pS2S4n^hillfact1)/(Kmran^hillfact1 + pS2pS2S4n^hillfact1))*S7KD Functionforreaction40[ActiveR2_,indexkbR2_,kfR2activation_] := ActiveR2*indexkbR2*kfR2activation end function definitions begin events end events begin process annotations end process annotations begin species annotations end species annotations begin units end units