#strasen8



#reactions
reaction1:
 {1.0}TGFb = $pool
  cyt * Function_for_reaction1_0(TGFb, TGFb_R2_surface, k_medium, kf_R2_activation)
reaction10:
 {1.0}Active_Rec_endo = {1.0}TGFb_R2_endo + {1.0}TGFb_In
  cyt * kdeg_R1 * Active_Rec_endo
reaction11:
 {1.0}Active_Rec_endo = {1.0}TGFb_R1_endo + {1.0}TGFb_R2_endo
  cyt * kin_deg_Ligand * Active_Rec_endo
reaction12:
 {1.0}TGFb_R1_endo = $pool
  cyt * kdeg_R1 * TGFb_R1_endo
reaction13:
 {1.0}TGFb_R2_endo = $pool
  cyt * kdeg_R2 * TGFb_R2_endo
reaction14:
 {1.0}Active_Rec + {1.0}S7 = {1.0}Inactive_Rec
  cyt * kf_Seq_S7_Rec * Active_Rec * S7
reaction15:
 {1.0}Inactive_Rec = {1.0}Active_Rec + {1.0}S7
  cyt * Function_for_reaction15_0(Inactive_Rec, index_seq_kb, kf_Seq_S7_Rec)
reaction16:
 {1.0}Inactive_Rec = {1.0}TGFb_R1_endo + {1.0}TGFb_R2_endo + {1.0}S7
  cyt * Function_for_reaction16_0(Inactive_Rec, index_induced_ligand_deg, kin_deg_Ligand)
reaction17:
 {1.0}Inactive_Rec = {1.0}TGFb_R1_endo + {1.0}TGFb_In + {1.0}S7
  cyt * Function_for_reaction17_0(Inactive_Rec, index_induced_R2_deg, kdeg_R2)
reaction18:
 {1.0}TGFb_R1_surface = {1.0}TGFb_R1_endo
  cyt * k_in_R1_C3 * TGFb_R1_surface
reaction19:
 {1.0}TGFb_R2_surface = {1.0}TGFb_R2_endo
  cyt * k_in_R2_C3 * TGFb_R2_surface
reaction2:
 {1.0}TGFb_R2_surface = $pool
  cyt * Function_for_reaction2_0(TGFb, TGFb_R2_surface, kf_R2_activation)
reaction20:
 {1.0}TGFb_R1_endo = {1.0}TGFb_R1_surface
  cyt * Function_for_reaction20_2_0(TGFb_R1_endo, index_k_out_1_relative_speed_C3, k_in_R1_C3)
reaction21:
 {1.0}TGFb_R2_endo = {1.0}TGFb_R2_surface
  cyt * Function_for_reaction21_2_0(TGFb_R2_endo, index_k_out_2_relative_speed_C3, k_in_R2_C3)
reaction22:
 {1.0}Active_Rec = {1.0}Active_Rec_endo
  cyt * Function_for_reaction22_2_0(Active_Rec, index_active_Rec_internalize_C3, k_in_R1_C3)
reaction23:
 {1.0}Active_Rec_endo = {1.0}TGFb_R1_endo + {1.0}TGFb_R2_endo + {1.0}TGFb_In
  cyt * k_disso_Active_Rec * Active_Rec_endo
reaction24:
 {1.0}TGFb_In = $pool
  cyt * kin_deg_Ligand * TGFb_In
reaction25:
 {1.0}TGFb = $pool
  cyt * kout_deg_Ligand_100pM * TGFb
reaction26:
 {1.0}S2_c = {1.0}pS2_c
  cyt * Function_for_reaction26(Active_Rec_endo, S2_c, k_phosphorylation)
reaction27:
 {2.0}pS2_c + {1.0}S4_c = {1.0}pS2_pS2_S4_c
  cyt * kf_trimmer * pow(pS2_c, 2) * S4_c
reaction28:
 {1.0}pS2_pS2_S4_c = {2.0}pS2_c + {1.0}S4_c
  cyt * kb_trimmer * pS2_pS2_S4_c
reaction29:
 {2.0}pS2_n + {1.0}S4_n = {1.0}pS2_pS2_S4_n
  nuc * kf_trimmer * pow(pS2_n, 2) * S4_n
reaction3:
 $pool = {1.0}Active_R2
  cyt * Function_for_reaction3_0(TGFb, TGFb_R2_surface, kf_R2_activation)
reaction30:
 {1.0}pS2_pS2_S4_n = {2.0}pS2_n + {1.0}S4_n
  nuc * kb_trimmer * pS2_pS2_S4_n
reaction31:
 {3.0}pS2_c = {1.0}pS2_pS2_pS2_c
  cyt * Function_for_reaction31_2(index_kf_homotrimer, kf_trimmer, pS2_c)
reaction32:
 {1.0}pS2_pS2_pS2_c = {3.0}pS2_c
  cyt * Function_for_reaction32_3_0(index_kb_homotrimer, kb_trimmer, pS2_pS2_pS2_c)
reaction33:
 {3.0}pS2_n = {1.0}pS2_pS2_pS2_n
  nuc * Function_for_reaction33_2(index_kf_homotrimer, kf_trimmer, pS2_n)
reaction34:
 {1.0}pS2_pS2_pS2_n = {3.0}pS2_n
  nuc * Function_for_reaction34_2_0(index_kb_homotrimer, kb_trimmer, pS2_pS2_pS2_n)
reaction35:
 {1.0}S2_c = {1.0}S2_n
  Function_for_reaction35_3_0(S2_c, S2_import_to_nuc_C3, cyt)
reaction36:
 {1.0}S2_n = {1.0}S2_c
  Function_for_reaction36_3_0(S2_export_from_nuc_C3, S2_n, nuc)
reaction37:
 {1.0}S4_c = {1.0}S4_n
  Function_for_reaction37_3_0(S4_c, S4_import_to_nuc_C3, cyt)
reaction38:
 {1.0}S4_n = {1.0}S4_c
  Function_for_reaction38_3_0(S4_export_from_nuc_C3, S4_n, nuc)
reaction39:
 {1.0}pS2_c = {1.0}pS2_n
  Function_for_reaction39_3_0(S2_import_to_nuc_C3, cyt, pS2_c)
reaction4:
 {1.0}Active_R2 = $pool
  cyt * Function_for_reaction4_0(Active_R2, index_kb_R2, kf_R2_activation)
reaction40:
 {1.0}pS2_n = {1.0}pS2_c
  Function_for_reaction40_3_0(S2_export_from_nuc_C3, nuc, pS2_n)
reaction41:
 {1.0}pS2_pS2_S4_c = {1.0}pS2_pS2_S4_n
  Function_for_reaction41_2_0(Trimer_import_to_nuc, cyt, pS2_pS2_S4_c)
reaction42:
 {1.0}pS2_pS2_pS2_c = {1.0}pS2_pS2_pS2_n
  Function_for_reaction42(Trimer_import_to_nuc, cyt, pS2_pS2_pS2_c)
reaction43:
 {1.0}pS2_n = {1.0}S2_n
  nuc * k_Dephos_C3 * pS2_n
reaction44:
 {1.0}pS2_pS2_S4_n = {1.0}pS2_n + {1.0}S2_n + {1.0}S4_n
  nuc * Function_for_reaction44_4_0(index_trimer_dephos, k_Dephos_C3, pS2_pS2_S4_n)
reaction45:
 $pool = {1.0}S2_c
  cyt * Function_for_reaction45_3(S2_export_from_nuc_C3, S2_import_to_nuc_C3, S2_total_C3, kdeg_S2)
reaction46:
 $pool = {1.0}S4_c
  cyt * Function_for_reaction46_3(S4_export_from_nuc_C3, S4_import_to_nuc_C3, S4_total_C3, kdeg_S4)
reaction47:
 $pool = {1.0}TGFb_R1_surface
  cyt * Function_for_reaction47_3(R1_total_C3, index_k_out_1_relative_speed_C3, k_in_R1_C3, kdeg_R1)
reaction48:
 $pool = {1.0}TGFb_R2_surface
  cyt * Function_for_reaction48_1(R2_total_C3, index_k_out_2_relative_speed_C3, k_in_R2_C3, kdeg_R2)
reaction5:
 $pool = {1.0}TGFb_R2_surface
  cyt * Function_for_reaction5_0(Active_R2, index_kb_R2, kf_R2_activation)
reaction51:
 $pool = {1.0}Smad7mRNA1
  nuc * Function_for_reaction51_3_0(DRB, K_mran, S7KD, hill_fact1, k_induced_S7_production_C3, mRNA_prod_C3, pS2_pS2_S4_n)
reaction52:
 {1.0}Smad7mRNA1 = {1.0}Smad7mRNA
  Function_for_reaction52_3_0(Smad7mRNA1, export_cytoplasm, nuc)
reaction53:
 $pool = {1.0}S7
  cyt * Function_for_reaction53_1_0(Smad7mRNA, k_S7_protein_C3)
reaction54:
 {1.0}S2_c = $pool
  cyt * kdeg_S2 * S2_c
reaction55:
 {1.0}S2_n = $pool
  nuc * kdeg_S2 * S2_n
reaction56:
 {1.0}pS2_n = $pool
  nuc * kdeg_S2 * pS2_n
reaction57:
 {1.0}pS2_c = $pool
  cyt * kdeg_S2 * pS2_c
reaction58:
 {1.0}S4_c = $pool
  cyt * kdeg_S4 * S4_c
reaction59:
 {1.0}S4_n = $pool
  nuc * kdeg_S4 * S4_n
reaction6:
 $pool = {1.0}TGFb
  cyt * Function_for_reaction6_0(Active_R2, index_kb_R2, k_medium, kf_R2_activation)
reaction60:
 {1.0}pS2_pS2_S4_c = {1.0}pS2_c + {1.0}S4_c
  cyt * kdeg_S2 * pS2_pS2_S4_c
reaction61:
 {1.0}pS2_pS2_S4_c = {2.0}pS2_c
  cyt * kdeg_S4 * pS2_pS2_S4_c
reaction62:
 {1.0}pS2_pS2_pS2_c = {2.0}pS2_c
  cyt * kdeg_S2 * pS2_pS2_pS2_c
reaction63:
 {1.0}pS2_pS2_S4_n = {1.0}pS2_n + {1.0}S4_n
  nuc * kdeg_S2 * pS2_pS2_S4_n
reaction64:
 {1.0}pS2_pS2_S4_n = {2.0}pS2_n
  nuc * kdeg_S4 * pS2_pS2_S4_n
reaction65:
 {1.0}pS2_pS2_pS2_n = {2.0}pS2_n
  nuc * kdeg_S2 * pS2_pS2_pS2_n
reaction66:
 {1.0}Smad7mRNA1 = $pool
  nuc * kmRNA1deg_S7 * Smad7mRNA1
reaction67:
 {1.0}Smad7mRNA = $pool
  cyt * kmRNAdeg_S7 * Smad7mRNA
reaction68:
 {1.0}S7 = $pool
  cyt * kdeg_S7 * S7
reaction7:
 {1.0}TGFb_R1_surface + {1.0}Active_R2 = {1.0}Active_Rec
  cyt * kf_R1_activation * TGFb_R1_surface * Active_R2
reaction8:
 {1.0}Active_Rec = {1.0}TGFb_R1_surface + {1.0}Active_R2
  cyt * Function_for_reaction8_0(Active_Rec, index_kb_R1, kf_R1_activation)
reaction9:
 {1.0}Active_Rec_endo = {1.0}TGFb_R1_endo + {1.0}TGFb_In
  cyt * kdeg_R2 * Active_Rec_endo


#parameters
DRB = 1.0
K_mran = 223.586
R1_total_C3 = 69.7199989056023
R2_total_C3 = 49.1925438819563
S2_export_from_nuc_C3 = 3.00430865315074
S2_import_to_nuc_C3 = 0.248774260500559
S2_total_C3 = 1335.77950850425
S4_export_from_nuc_C3 = 0.0984718694215043
S4_import_to_nuc_C3 = 0.0730474752631315
S4_total_C3 = 347.505766824434
S7KD = 1.0
Trimer_import_to_nuc = 0.144035002432848
export_cytoplasm = 0.0304372961307751
hill_fact1 = 3.98630224594983
index_active_Rec_internalize_C3 = 1.0379108128956
index_induced_R2_deg = 1.00037776866312
index_induced_ligand_deg = 2.72106513634098
index_k_out_1_relative_speed_C3 = 1.13287434679021
index_k_out_2_relative_speed_C3 = 0.450697494637432
index_kb_R1 = 1.61290474569122
index_kb_R2 = 8.70498854136694
index_kb_homotrimer = 0.0163921522930962
index_kf_homotrimer = 4.4857919268227
index_seq_kb = 0.000865131944828012
index_trimer_dephos = 2.61013820571304
k_Dephos_C3 = 0.0707018316477647
k_S7_protein_C3 = 0.123149764012103
k_disso_Active_Rec = 0.00103940411358367
k_in_R1_C3 = 0.397836393488341
k_in_R2_C3 = 0.396038887562465
k_induced_S7_production_C3 = 2.9510868497
k_medium = 2000000.0
k_phosphorylation = 0.0701560191772152
kb_trimmer = 1.6077346670684
kdeg_R1 = 0.0586584495713968
kdeg_R2 = 0.0010003937382472
kdeg_S2 = 0.000514084012175461
kdeg_S4 = 0.00480202699360057
kdeg_S7 = 0.00102401829734485
kf_R1_activation = 4.98548548076033
kf_R2_activation = 4.95559496701657
kf_Seq_S7_Rec = 0.882455038106022
kf_trimmer = 4.81424700307387
kin_deg_Ligand = 0.720182234635314
kmRNA1deg_S7 = 0.00523181439900629
kmRNAdeg_S7 = 0.0990158065483902
kout_deg_Ligand_100pM = 0.00036189622
mRNA_prod_C3 = 0.0239754962469105
cyt = 2.0
nuc = 1.0


#initial values
Active_R2 = 0.0
Active_Rec = 0.0
Active_Rec_endo = 0.0
Inactive_Rec = 0.0
S2_c = 1146.0180383886332
S2_n = 189.76147011561696
S4_c = 143.91643145030181
S4_n = 203.58933537413213
S7 = 12.424323107678699
Smad7mRNA = 0.1033110724689415
Smad7mRNA1 = 0.6721641187798199
TGFb = 100.0
TGFb_In = 0.0
TGFb_R1_endo = 30.57468258089889
TGFb_R1_surface = 39.145316324703415
TGFb_R2_endo = 33.85063901424163
TGFb_R2_surface = 15.341904867714664
pS2_c = 0.0
pS2_n = 0.0
pS2_pS2_S4_c = 0.0
pS2_pS2_S4_n = 0.0
pS2_pS2_pS2_c = 0.0
pS2_pS2_pS2_n = 0.0


#assignment rules
!F NUC_CYT_SMAD2 = (2.0 * pS2_pS2_S4_n + pS2_n + S2_n + 3.0 * pS2_pS2_pS2_n) / (2.0 * pS2_pS2_S4_c + pS2_c + S2_c + 3.0 * pS2_pS2_pS2_c)