// Created by libAntimony v2.13.0
model *Zi2011_TGFbeta_Pathway()

  // Compartments and Species:
  compartment default, Vmed, Vcyt, Vnuc;
  species TGF_beta_ex in Vmed, T1R_surf in Vcyt, T1R_endo in Vcyt, T2R_surf in Vcyt;
  species T2R_endo in Vcyt, LRC_surf in Vcyt, LRC_endo in Vcyt, Smad2c in Vcyt;
  species Smad2n in Vnuc, Smad4c in Vcyt, Smad4n in Vnuc, PSmad2c in Vcyt;
  species PSmad2_PSmad2_c in Vcyt, PSmad2_Smad4_c in Vcyt, PSmad2n in Vnuc;
  species PSmad2_PSmad2_n in Vnuc, PSmad2_Smad4_n in Vnuc, TGF_beta_endo in Vcyt;
  species TGF_beta_ns in Vmed, $AA in Vcyt, $empty_degraded in Vcyt;

  // Assignment Rules:
  Vmed := 2e-3/(1e6*exp(ln(1.45)*time/1440));
  totalNumT1R := (T1R_surf + T1R_endo + LRC_surf + LRC_endo)*2.3*602;
  totalNumT2R := (T2R_surf + T2R_endo + LRC_surf + LRC_endo)*2.3*602;
  totalNumLRC := (LRC_surf + LRC_endo)*2.3*602;
  totalNumPSmad2 := (PSmad2c + PSmad2_PSmad2_c*2 + PSmad2_Smad4_c)*2.3*602 + (PSmad2n + PSmad2_PSmad2_n*2 + PSmad2_Smad4_n)*602;
  totalNuclearPSmad2 := PSmad2n + 2*PSmad2_PSmad2_n + PSmad2_Smad4_n;
  totalSmad2c := Smad2c + PSmad2c + 2*PSmad2_PSmad2_c + PSmad2_Smad4_c;
  totalSmad2n := Smad2n + PSmad2n + 2*PSmad2_PSmad2_n + PSmad2_Smad4_n;
  medium_TGF_beta_amount := TGF_beta_ex*1e-9*Vmed*6e23;
  koff_ns := kon_ns*KD_ns;

  // Reactions:
  re1: $AA => T1R_surf; Vcyt*k_T1R;
  re2: T1R_surf => T1R_endo; Vcyt*ki*T1R_surf;
  re3: T1R_endo => T1R_surf; Vcyt*kr*T1R_endo;
  re4: T1R_endo => $empty_degraded; Vcyt*kdeg_T1R*T1R_endo;
  re5: $AA => T2R_surf; Vcyt*k_T2R;
  re6: T2R_surf => T2R_endo; Vcyt*ki*T2R_surf;
  re7: T2R_endo => T2R_surf; Vcyt*kr*T2R_endo;
  re8: T2R_endo => $empty_degraded; Vcyt*kdeg_T2R*T2R_endo;
  re9: TGF_beta_ex + T2R_surf + T1R_surf => LRC_surf; Vcyt*ka_LRC*TGF_beta_ex*T2R_surf*T1R_surf;
  re10: LRC_surf => LRC_endo; Vcyt*ki*LRC_surf;
  re11: LRC_endo => $empty_degraded; Vcyt*kdeg_LRC*LRC_endo;
  re12: LRC_endo => T1R_endo + T2R_endo + TGF_beta_endo; Vcyt*kdiss_LRC*LRC_endo;
  re13: TGF_beta_endo => $empty_degraded; Vcyt*kdeg_TGF_beta*TGF_beta_endo;
  re14: Smad2c => Smad2n; Vcyt*kimp_Smad2*Smad2c;
  re15: Smad2n => Smad2c; Vnuc*kexp_Smad2*Smad2n;
  re16: Smad4c => Smad4n; Vcyt*kimp_Smad4*Smad4c;
  re17: Smad4n => Smad4c; Vnuc*kexp_Smad4*Smad4n;
  re18: Smad2c => PSmad2c; Vcyt*kpho_Smad2*Smad2c*LRC_endo;
  re19: PSmad2c => PSmad2n; Vcyt*kimp_Smad2*PSmad2c;
  re20: PSmad2n => PSmad2c; Vnuc*kexp_Smad2*PSmad2n;
  re21: PSmad2c + Smad4c -> PSmad2_Smad4_c; Vcyt*(kon_Smads*PSmad2c*Smad4c - koff_Smads*PSmad2_Smad4_c);
  re22: PSmad2_Smad4_c => PSmad2_Smad4_n; Vcyt*kimp_Smads*PSmad2_Smad4_c;
  re23: PSmad2_Smad4_n -> PSmad2n + Smad4n; Vnuc*(koff_Smads*PSmad2_Smad4_n - kon_Smads*PSmad2n*Smad4n);
  re24: PSmad2n => Smad2n; Vnuc*kdepho_Smad2*PSmad2n;
  re25: 2 PSmad2c -> PSmad2_PSmad2_c; Vcyt*(kon_Smads*PSmad2c^2 - koff_Smads*PSmad2_PSmad2_c);
  re26: PSmad2_PSmad2_c => PSmad2_PSmad2_n; Vcyt*kimp_Smads*PSmad2_PSmad2_c;
  re27: PSmad2_PSmad2_n -> 2 PSmad2n; Vnuc*(koff_Smads*PSmad2_PSmad2_n - kon_Smads*PSmad2n^2);
  re28: LRC_surf => $empty_degraded; Vcyt*klid*LRC_surf*totalNuclearPSmad2;
  re29: TGF_beta_ex -> TGF_beta_ns; Vmed*(kon_ns*TGF_beta_ex - koff_ns*TGF_beta_ns);

  // Events:
  single_pulse_TGF_beta_washout: at 0 after (stimulation_type == 2) && (time == single_pulse_duration): TGF_beta_ex = 0;

  // Species initializations:
  TGF_beta_ex = 0.05;
  TGF_beta_ex has nM_per_volume;
  T1R_surf = (k_T1R*kdeg_T1R + k_T1R*kr)/(kdeg_T1R*ki);
  T1R_surf has nM_per_volume;
  T1R_endo = k_T1R/kdeg_T1R;
  T1R_endo has nM_per_volume;
  T2R_surf = (k_T2R*kdeg_T2R + k_T2R*kr)/(kdeg_T2R*ki);
  T2R_surf has nM_per_volume;
  T2R_endo = k_T2R/kdeg_T2R;
  T2R_endo has nM_per_volume;
  LRC_surf = 0;
  LRC_surf has nM_per_volume;
  LRC_endo = 0;
  LRC_endo has nM_per_volume;
  Smad2c = 60.6;
  Smad2c has nM_per_volume;
  Smad2n = 28.5;
  Smad2n has nM_per_volume;
  Smad4c = 50.8;
  Smad4c has nM_per_volume;
  Smad4n = 50.8;
  Smad4n has nM_per_volume;
  PSmad2c = 0;
  PSmad2c has nM_per_volume;
  PSmad2_PSmad2_c = 0;
  PSmad2_PSmad2_c has nM_per_volume;
  PSmad2_Smad4_c = 0;
  PSmad2_Smad4_c has nM_per_volume;
  PSmad2n = 0;
  PSmad2n has nM_per_volume;
  PSmad2_PSmad2_n = 0;
  PSmad2_PSmad2_n has nM_per_volume;
  PSmad2_Smad4_n = 0;
  PSmad2_Smad4_n has nM_per_volume;
  TGF_beta_endo = 0;
  TGF_beta_endo has nM_per_volume;
  TGF_beta_ns = 0;
  TGF_beta_ns has nM_per_volume;
  AA = 0;
  AA has nM_per_volume;
  empty_degraded = 0;
  empty_degraded has nM_per_volume;

  // Compartment initializations:
  default = 1;
  default has volume;
  Vmed has volume;
  Vcyt = 2.3e-12;
  Vcyt has volume;
  Vnuc = 1e-12;
  Vnuc has volume;

  // Variable initializations:
  k_T1R = 0.0167;
  k_T1R has nM_per_min;
  kdeg_T1R = 0.00256;
  kdeg_T1R has per_min;
  kr = 0.0333;
  kr has per_min;
  ki = 0.333;
  ki has per_min;
  k_T2R = 0.0190076;
  k_T2R has nM_per_min;
  kdeg_T2R = 0.0132;
  kdeg_T2R has per_min;
  stimulation_type = 1;
  stimulation_type has dimensionless;
  single_pulse_duration = 0.5;
  single_pulse_duration has min;
  totalNumT1R has molecules_per_cell;
  totalNumT2R has molecules_per_cell;
  totalNumLRC has molecules_per_cell;
  totalNumPSmad2 has molecules_per_cell;
  totalNuclearPSmad2 has nM;
  totalSmad2c has nM;
  totalSmad2n has nM;
  medium_TGF_beta_amount has molecules_per_cell;
  TGF_beta_dose_mol_per_cell = TGF_beta_ex*1e-9*Vmed*6e23;
  TGF_beta_dose_mol_per_cell has molecules_per_cell;
  kdeg_LRC = 0.00256;
  kdeg_LRC has per_min;
  kdeg_TGF_beta = 0.347;
  kdeg_TGF_beta has per_min;
  klid = 0.0233678;
  klid has per_min;
  ka_LRC = 117.897;
  ka_LRC has third_order;
  kdiss_LRC = 0.0438111;
  kdiss_LRC has per_min;
  kimp_Smad2 = 0.156;
  kimp_Smad2 has per_min;
  kexp_Smad2 = 0.763;
  kexp_Smad2 has per_min;
  kimp_Smad4 = 0.156;
  kimp_Smad4 has per_min;
  kexp_Smad4 = 0.359;
  kexp_Smad4 has per_min;
  kpho_Smad2 = 0.0488268;
  kpho_Smad2 has second_order;
  kon_Smads = 0.198472;
  kon_Smads has second_order;
  koff_Smads = 1;
  koff_Smads has per_min;
  kimp_Smads = 0.889;
  kimp_Smads has per_min;
  kdepho_Smad2 = 0.394;
  kdepho_Smad2 has per_min;
  kon_ns = 0.0505413;
  kon_ns has per_min;
  koff_ns has per_min;
  KD_ns = 40.2257;
  KD_ns has dimensionless;

  // Other declarations:
  var Vmed, totalNumT1R, totalNumT2R, totalNumLRC, totalNumPSmad2, totalNuclearPSmad2;
  var totalSmad2c, totalSmad2n, medium_TGF_beta_amount, TGF_beta_dose_mol_per_cell;
  var koff_ns;
  const default, Vcyt, Vnuc, k_T1R, kdeg_T1R, kr, ki, k_T2R, kdeg_T2R, stimulation_type;
  const single_pulse_duration, kdeg_LRC, kdeg_TGF_beta, klid, ka_LRC, kdiss_LRC;
  const kimp_Smad2, kexp_Smad2, kimp_Smad4, kexp_Smad4, kpho_Smad2, kon_Smads;
  const koff_Smads, kimp_Smads, kdepho_Smad2, kon_ns, KD_ns;

  // Unit definitions:
  unit substance = 1e-9 mole;
  unit volume = litre;
  unit area = metre^2;
  unit length = metre;
  unit time_unit = 60 second;
  unit per_min = 1 / 60 second;
  unit nM_per_min = 1e-9 mole / 60 second;
  unit third_order = 1 / ((1e-9 mole)^2 * 60 second);
  unit second_order = 1 / (1e-9 mole * 60 second);
  unit min = 60 second;
  unit nM = 1e-9 mole;
  unit molecules_per_cell = dimensionless;
  unit nM_per_volume = 1e-9 mole / litre;

  // Display Names:
  time_unit is "min";
  per_min is "per min";
  nM_per_min is "nM per min";
  third_order is "third order rate constant";
  second_order is "second order rate constant";
  min is "minute";
  nM is "nanomolar";
  molecules_per_cell is "molecules per cell";
  Vmed is "Medium";
  Vcyt is "Cytoplasm";
  Vnuc is "Nucleus";
  single_pulse_TGF_beta_washout is "TGF-beta washout in singel pulse stimulation";
  re1 is "T1R production";
  re2 is "T1R internalization to early endosome";
  re3 is "T1R recycling from early endosome";
  re4 is "T1R constitutive degradation";
  re5 is "T2R production";
  re6 is "T2R internalization to early endosome";
  re7 is "T2R recycling from early endosome";
  re8 is "T2R constitutive degradation";
  re9 is "LRC activation";
  re10 is "LRC internalization to early endosome";
  re11 is "LRC constitutive degradation";
  re12 is "dissociation of LRC in endosome";
  re13 is "TGF-beta constitutive degradation";
  re14 is "Smad2 nuclear import";
  re15 is "Smad2 nuclear export";
  re16 is "Smad4 nuclear import";
  re17 is "Smad4 nuclear export";
  re18 is "Smad2 phosphorylation";
  re19 is "PSmad2 nuclear import";
  re20 is "PSmad2 nuclear export";
  re21 is "Smad2-Smad4 complex formation";
  re22 is "Smad2-Smad4 nuclear import";
  re23 is "Smad2-Smad4 dissociation";
  re24 is "Smad2 dephosphorylation";
  re25 is "PSmad2 dimer formation";
  re26 is "PSmad2 dimer nuclear  import";
  re27 is "PSmad2 dimmer dissociation";
  re28 is "negative feedback induced LRC degradation";
  re29 is "non-specific binding of TGF-beta";

  // SBO terms:
  Vmed.sboTerm = 290
  Vcyt.sboTerm = 290
  Vnuc.sboTerm = 290
  TGF_beta_ex.sboTerm = 252
  T1R_surf.sboTerm = 244
  T1R_endo.sboTerm = 244
  T2R_surf.sboTerm = 244
  T2R_endo.sboTerm = 244
  LRC_surf.sboTerm = 297
  LRC_endo.sboTerm = 297
  Smad2c.sboTerm = 252
  Smad2n.sboTerm = 252
  Smad4c.sboTerm = 252
  Smad4n.sboTerm = 252
  PSmad2c.sboTerm = 252
  PSmad2_PSmad2_c.sboTerm = 286
  PSmad2_Smad4_c.sboTerm = 297
  PSmad2n.sboTerm = 252
  PSmad2_PSmad2_n.sboTerm = 286
  PSmad2_Smad4_n.sboTerm = 297
  TGF_beta_endo.sboTerm = 252
  TGF_beta_ns.sboTerm = 252
  AA.sboTerm = 291
  empty_degraded.sboTerm = 291

  // CV terms:
  Vmed hypernym "http://identifiers.org/bto/BTO:0000316"
  Vcyt hypernym "http://identifiers.org/go/GO:0005737"
  Vnuc hypernym "http://identifiers.org/go/GO:0005634"
  TGF_beta_ex hypernym "http://identifiers.org/uniprot/P01137"
  TGF_beta_ex container "http://identifiers.org/bto/BTO:0000316"
  T1R_surf hypernym "http://identifiers.org/uniprot/P36897"
  T1R_surf container "http://identifiers.org/go/GO:0009986"
  T1R_endo hypernym "http://identifiers.org/uniprot/P36897"
  T1R_endo container "http://identifiers.org/go/GO:0005769"
  T2R_surf hypernym "http://identifiers.org/uniprot/P37173"
  T2R_surf container "http://identifiers.org/go/GO:0009986"
  T2R_endo hypernym "http://identifiers.org/uniprot/P37173"
  T2R_endo encodement "http://identifiers.org/go/GO:0005769"
  LRC_surf container "http://identifiers.org/go/GO:0009986"
  LRC_surf hypernym "http://identifiers.org/go/GO:0043235"
  LRC_surf part "http://identifiers.org/uniprot/P01137",
                "http://identifiers.org/uniprot/P36897"
  LRC_surf part "http://identifiers.org/uniprot/P01137",
                "http://identifiers.org/uniprot/P37173"
  LRC_endo container "http://identifiers.org/go/GO:0005769"
  LRC_endo hypernym "http://identifiers.org/go/GO:0043235"
  LRC_endo part "http://identifiers.org/uniprot/P01137",
                "http://identifiers.org/uniprot/P36897"
  LRC_endo part "http://identifiers.org/uniprot/P01137",
                "http://identifiers.org/uniprot/P37173"
  Smad2c hypernym "http://identifiers.org/uniprot/Q15796"
  Smad2n hypernym "http://identifiers.org/uniprot/Q15796"
  Smad4c hypernym "http://identifiers.org/uniprot/Q13485"
  Smad4n hypernym "http://identifiers.org/uniprot/Q13485"
  PSmad2c hypernym "http://identifiers.org/uniprot/Q15796",
                   "http://identifiers.org/kegg.compound/C00562"
  PSmad2_PSmad2_c part "http://identifiers.org/uniprot/Q15796"
  PSmad2_PSmad2_c hypernym "http://identifiers.org/kegg.compound/C00562"
  PSmad2_Smad4_c part "http://identifiers.org/uniprot/Q15796",
                      "http://identifiers.org/uniprot/Q13485"
  PSmad2_Smad4_c hypernym "http://identifiers.org/kegg.compound/C00562"
  PSmad2n hypernym "http://identifiers.org/uniprot/Q15796",
                   "http://identifiers.org/kegg.compound/C00562"
  PSmad2_PSmad2_n part "http://identifiers.org/uniprot/Q15796"
  PSmad2_PSmad2_n hypernym "http://identifiers.org/kegg.compound/C00562"
  PSmad2_Smad4_n part "http://identifiers.org/uniprot/Q15796",
                      "http://identifiers.org/uniprot/Q13485"
  PSmad2_Smad4_n version "http://identifiers.org/kegg.compound/C00562"
  TGF_beta_endo hypernym "http://identifiers.org/uniprot/P01137"
  TGF_beta_endo container "http://identifiers.org/go/GO:0005769"
  TGF_beta_ns hypernym "http://identifiers.org/uniprot/P01137"
  re1 hypernym "http://identifiers.org/go/GO:0032800"
  re2 hypernym "http://identifiers.org/go/GO:0031623"
  re3 hypernym "http://identifiers.org/go/GO:0032456"
  re4 hypernym "http://identifiers.org/go/GO:0032801"
  re5 hypernym "http://identifiers.org/go/GO:0032800"
  re6 hypernym "http://identifiers.org/go/GO:0031623"
  re7 hypernym "http://identifiers.org/go/GO:0032456"
  re8 hypernym "http://identifiers.org/go/GO:0032801"
  re9 hypernym "http://identifiers.org/go/GO:0005102"
  re10 hypernym "http://identifiers.org/go/GO:0031623"
  re11 hypernym "http://identifiers.org/go/GO:0032801"
  re12 hypernym "http://identifiers.org/go/GO:0043241"
  re13 hypernym "http://identifiers.org/go/GO:0030163"
  re14 hypernym "http://identifiers.org/go/GO:0051169"
  re15 hypernym "http://identifiers.org/go/GO:0051169"
  re16 hypernym "http://identifiers.org/go/GO:0051169"
  re17 hypernym "http://identifiers.org/go/GO:0051169"
  re18 hypernym "http://identifiers.org/go/GO:0006468"
  re19 hypernym "http://identifiers.org/go/GO:0051169"
  re20 hypernym "http://identifiers.org/go/GO:0051169"
  re21 hypernym "http://identifiers.org/go/GO:0006461"
  re23 hypernym "http://identifiers.org/go/GO:0051169"
  re24 hypernym "http://identifiers.org/go/GO:0006470"
  re25 hypernym "http://identifiers.org/go/GO:0006461"
  re26 hypernym "http://identifiers.org/go/GO:0051169"
  re27 hypernym "http://identifiers.org/go/GO:0043241"
  re28 hypernym "http://identifiers.org/go/GO:0009057"
  re29 hypernym "http://identifiers.org/go/GO:0005102"
end

Zi2011_TGFbeta_Pathway is "Zi2011_TGF-beta_Pathway"

Zi2011_TGFbeta_Pathway model_entity_is "http://identifiers.org/biomodels.db/MODEL1104050000"
Zi2011_TGFbeta_Pathway model_entity_is "http://identifiers.org/biomodels.db/BIOMD0000000342"
Zi2011_TGFbeta_Pathway description "http://identifiers.org/pubmed/21613981"
Zi2011_TGFbeta_Pathway taxon "http://identifiers.org/taxonomy/9606"
Zi2011_TGFbeta_Pathway container "http://identifiers.org/bto/BTO:0000312"
Zi2011_TGFbeta_Pathway parthood "http://identifiers.org/kegg.pathway/map04350",
                                "http://identifiers.org/reactome/REACT_6844"
Zi2011_TGFbeta_Pathway hypernym "http://identifiers.org/go/GO:0007179"
