#hatakeyama1



#reactions
reaction_0000001:
 {1.0}R + {1.0}HRG = {1.0}RHRG
  compartment_0000001 * (k1 * R * HRG - k_1 * RHRG)
reaction_0000002:
 {2.0}RHRG = {1.0}RHRG2
  compartment_0000001 * (k2 * pow(RHRG, 2) - k_2 * RHRG2)
reaction_0000003:
 {1.0}RHRG2 = {1.0}RP
  compartment_0000001 * (k3 * RHRG2 - k_3 * RP)
reaction_0000004:
 {1.0}RP = {1.0}RHRG2
  compartment_0000001 * V4 * RP / (K4 + RP)
reaction_0000005:
 {1.0}RP + {1.0}Shc = {1.0}RShc
  compartment_0000001 * (k5 * RP * Shc - k_5 * RShc)
reaction_0000006:
 {1.0}RShc = {1.0}RShP
  compartment_0000001 * (k6 * RShc - k_6 * RShP)
reaction_0000007:
 {1.0}RShP + {1.0}GS = {1.0}RShGS
  compartment_0000001 * (k7 * RShP * GS - k_7 * RShGS)
reaction_0000008:
 {1.0}RShGS = {1.0}ShGS + {1.0}RP
  compartment_0000001 * (k8 * RShGS - k_8 * ShGS * RP)
reaction_0000009:
 {1.0}ShGS = {1.0}GS + {1.0}ShP
  compartment_0000001 * (k9 * ShGS - k_9 * GS * ShP)
reaction_0000010:
 {1.0}ShP = {1.0}Shc
  compartment_0000001 * V10 * ShP / (K10 + ShP)
reaction_0000011:
 {1.0}RasGDP = {1.0}RasGTP
  compartment_0000001 * (k11 * ShGS * RasGDP / (K11 + RasGDP))
reaction_0000012:
 {1.0}RasGTP = {1.0}RasGDP
  compartment_0000001 * (V12 * RasGTP / (K12 + RasGTP))
reaction_0000013:
 {1.0}Raf = {1.0}Rafstar
  compartment_0000001 * (k13 * RasGTP * Raf / (K13 + Raf))
reaction_0000014:
 {1.0}Rafstar = {1.0}Raf
  compartment_0000001 * k14 * (AktPIPP + E) * Rafstar / (K14 + Rafstar)
reaction_0000015:
 {1.0}MEK = {1.0}MEKP
  compartment_0000001 * k15 * Rafstar * MEK / (K15 * (1 + MEKP / K17) + MEK)
reaction_0000016:
 {1.0}MEKP = {1.0}MEK
  compartment_0000001 * k16 * PP2A * MEKP / (K16 * (1 + MEKPP / K18 + AktPIP / K31 + AktPIPP / K33) + MEKP)
reaction_0000017:
 {1.0}MEKP = {1.0}MEKPP
  compartment_0000001 * k17 * Rafstar * MEKP / (K17 * (1 + MEK / K15) + MEKP)
reaction_0000018:
 {1.0}MEKPP = {1.0}MEKP
  compartment_0000001 * k18 * PP2A * MEKPP / (K18 * (1 + MEKP / K16 + AktPIPP / K31 + AktPIPP / K33) + MEKPP)
reaction_0000019:
 {1.0}ERK = {1.0}ERKP
  compartment_0000001 * k19 * MEKPP * ERK / (K19 * (1 + ERKP / K21) + ERK)
reaction_0000020:
 {1.0}ERKP = {1.0}ERK
  compartment_0000001 * k20 * MKP3 * ERKP / (K20 * (1 + ERKPP / K22) + ERKP)
reaction_0000021:
 {1.0}ERKP = {1.0}ERKPP
  compartment_0000001 * k21 * MEKPP * ERKP / (K21 * (1 + ERK / K19) + ERKP)
reaction_0000022:
 {1.0}ERKPP = {1.0}ERKP
  compartment_0000001 * k22 * MKP3 * ERKPP / (K22 * (1 + ERKP / K20) + ERKPP)
reaction_0000023:
 {1.0}RP + {1.0}PI3K = {1.0}RPI3K
  compartment_0000001 * (k23 * RP * PI3K - k_23 * RPI3K)
reaction_0000024:
 {1.0}RPI3K = {1.0}RPI3Kstar
  compartment_0000001 * (k24 * RPI3K - k_24 * RPI3Kstar)
reaction_0000025:
 {1.0}RPI3Kstar = {1.0}RP + {1.0}PI3Kstar
  compartment_0000001 * (k25 * RPI3Kstar - k_25 * RP * PI3Kstar)
reaction_0000026:
 {1.0}PI3Kstar = {1.0}PI3K
  compartment_0000001 * V26 * PI3Kstar / (K26 + PI3Kstar)
reaction_0000027:
 {1.0}P_I = {1.0}PIP3
  compartment_0000001 * k27 * PI3Kstar * P_I / (K27 + P_I)
reaction_0000028:
 {1.0}PIP3 = {1.0}P_I
  compartment_0000001 * (V28 * PIP3 / (K28 + PIP3))
reaction_0000029:
 {1.0}PIP3 + {1.0}Akt = {1.0}AktPIP3
  compartment_0000001 * (k29 * PIP3 * Akt - k_29 * AktPIP3)
reaction_0000030:
 {1.0}AktPIP3 = {1.0}AktPIP
  compartment_0000001 * V30 * AktPIP3 / (K30 * (1 + AktPIP / K32) + AktPIP3)
reaction_0000031:
 {1.0}AktPIP = {1.0}AktPIP3
  compartment_0000001 * k31 * PP2A * AktPIP / (K31 * (1 + MEKP / K16 + MEKPP / K18 + AktPIPP / K33) + AktPIP)
reaction_0000032:
 {1.0}AktPIP = {1.0}AktPIPP
  compartment_0000001 * V32 * AktPIP / (K32 * (1 + AktPIP3 / K30) + AktPIP)
reaction_0000033:
 {1.0}AktPIPP = {1.0}AktPIP
  compartment_0000001 * k33 * PP2A * AktPIPP / (K33 * (1 + MEKP / K16 + MEKPP / K18 + AktPIP / K31) + AktPIPP)
reaction_0000034:
 {1.0}RP = {1.0}internalization
  compartment_0000001 * (k34 * RP - k_34 * internalization)


#parameters
K10 = 340.0
K11 = 0.181
K12 = 0.0571
K13 = 11.7
K14 = 8.07
K15 = 317.0
K16 = 2200.0
K17 = 317.0
K18 = 60.0
K19 = 146000.0
K20 = 160.0
K21 = 146000.0
K22 = 60.0
K26 = 3680.0
K27 = 39.1
K28 = 9.02
K30 = 80000.0
K31 = 4.35
K32 = 80000.0
K33 = 12.0
K4 = 50.0
V10 = 0.0154
V12 = 0.289
V26 = 2620.0
V28 = 17000.0
V30 = 20000.0
V32 = 20000.0
V4 = 62.5
k1 = 0.0012
k11 = 0.222
k13 = 1.53
k14 = 0.00673
k15 = 3.5
k16 = 0.058
k17 = 2.9
k18 = 0.058
k19 = 9.5
k2 = 0.01
k20 = 0.3
k21 = 16.0
k22 = 0.27
k23 = 0.1
k24 = 9.85
k25 = 45.8
k27 = 16.9
k29 = 507.0
k3 = 1.0
k31 = 0.107
k33 = 0.211
k34 = 0.001
k5 = 0.1
k6 = 20.0
k7 = 60.0
k8 = 2040.0
k9 = 40.8
k_1 = 0.00076
k_2 = 0.1
k_23 = 2.0
k_24 = 0.0985
k_25 = 0.047
k_29 = 234.0
k_3 = 0.01
k_34 = 0.0
k_5 = 1.0
k_6 = 5.0
k_7 = 546.0
k_8 = 15700.0
k_9 = 0.0
compartment_0000001 = 1.0


#initial values
Akt = 10.0
AktPIP = 0.0
AktPIP3 = 0.0
AktPIPP = 0.0
E = 7.0
ERK = 1000.0
ERKP = 0.0
ERKPP = 0.0
GS = 10.0
HRG = 330.0
MEK = 120.0
MEKP = 0.0
MEKPP = 0.0
MKP3 = 2.4
PI3K = 10.0
PI3Kstar = 0.0
PIP3 = 0.0
PP2A = 11.4
P_I = 800.0
R = 80.0
RHRG = 0.0
RHRG2 = 0.0
RP = 0.0
RPI3K = 0.0
RPI3Kstar = 0.0
RShGS = 0.0
RShP = 0.0
RShc = 0.0
Raf = 100.0
Rafstar = 0.0
RasGDP = 120.0
RasGTP = 0.0
ShGS = 0.0
ShP = 0.0
Shc = 1000.0
internalization = 0.0


#assignment rules
!F MEKPP_percent = MEKPP * 100.0 / 120.0
!F AktPP_percent = AktPIPP * 100.0 / 10.0
!F ERKPP_percent = ERKPP * 100.0 / 1000.0
!F Rafstar_percent = Rafstar * 100.0 / 100.0
!F PI3Kstar_percent = PI3Kstar * 100.0 / 10.0
!F ShP_percent = ShP * 100.0 / 1000.0
!F RP_percent = (RP + RPI3K + RPI3Kstar + RShGS + RShP + RShc) * 200.0 / 80.0