begin name
hatakeyama1
end name

begin reactions
reaction0000001 {1.0}R + {1.0}HRG = {1.0}RHRG
reaction0000002 {2.0}RHRG = {1.0}RHRG2
reaction0000003 {1.0}RHRG2 = {1.0}RP
reaction0000004 {1.0}RP = {1.0}RHRG2
reaction0000005 {1.0}RP + {1.0}Shc = {1.0}RShc
reaction0000006 {1.0}RShc = {1.0}RShP
reaction0000007 {1.0}RShP + {1.0}GS = {1.0}RShGS
reaction0000008 {1.0}RShGS = {1.0}ShGS + {1.0}RP
reaction0000009 {1.0}ShGS = {1.0}GS + {1.0}ShP
reaction0000010 {1.0}ShP = {1.0}Shc
reaction0000011 {1.0}RasGDP = {1.0}RasGTP
reaction0000012 {1.0}RasGTP = {1.0}RasGDP
reaction0000013 {1.0}Raf = {1.0}Rafstar
reaction0000014 {1.0}Rafstar = {1.0}Raf
reaction0000015 {1.0}MEK = {1.0}MEKP
reaction0000016 {1.0}MEKP = {1.0}MEK
reaction0000017 {1.0}MEKP = {1.0}MEKPP
reaction0000018 {1.0}MEKPP = {1.0}MEKP
reaction0000019 {1.0}ERK = {1.0}ERKP
reaction0000020 {1.0}ERKP = {1.0}ERK
reaction0000021 {1.0}ERKP = {1.0}ERKPP
reaction0000022 {1.0}ERKPP = {1.0}ERKP
reaction0000023 {1.0}RP + {1.0}PI3K = {1.0}RPI3K
reaction0000024 {1.0}RPI3K = {1.0}RPI3Kstar
reaction0000025 {1.0}RPI3Kstar = {1.0}RP + {1.0}PI3Kstar
reaction0000026 {1.0}PI3Kstar = {1.0}PI3K
reaction0000027 {1.0}PI = {1.0}PIP3
reaction0000028 {1.0}PIP3 = {1.0}PI
reaction0000029 {1.0}PIP3 + {1.0}Akt = {1.0}AktPIP3
reaction0000030 {1.0}AktPIP3 = {1.0}AktPIP
reaction0000031 {1.0}AktPIP = {1.0}AktPIP3
reaction0000032 {1.0}AktPIP = {1.0}AktPIPP
reaction0000033 {1.0}AktPIPP = {1.0}AktPIP
reaction0000034 {1.0}RP = {1.0}internalization
end reactions

begin rate equations
reaction0000001 = compartment0000001*(k1*HRG[t]*R[t] - k1*RHRG[t])
reaction0000002 = compartment0000001*(k2*RHRG[t]^2 - k2*RHRG2[t])
reaction0000003 = compartment0000001*(k3*RHRG2[t] - k3*RP[t])
reaction0000004 = (compartment0000001*V4*RP[t])/(K4 + RP[t])
reaction0000005 = compartment0000001*(-(k5*RShc[t]) + k5*RP[t]*Shc[t])
reaction0000006 = compartment0000001*(k6*RShc[t] - k6*RShP[t])
reaction0000007 = compartment0000001*(-(k7*RShGS[t]) + k7*GS[t]*RShP[t])
reaction0000008 = compartment0000001*(k8*RShGS[t] - k8*RP[t]*ShGS[t])
reaction0000009 = compartment0000001*(k9*ShGS[t] - k9*GS[t]*ShP[t])
reaction0000010 = (compartment0000001*V10*ShP[t])/(K10 + ShP[t])
reaction0000011 = (compartment0000001*k11*RasGDP[t]*ShGS[t])/(K11 + RasGDP[t])
reaction0000012 = (compartment0000001*V12*RasGTP[t])/(K12 + RasGTP[t])
reaction0000013 = (compartment0000001*k13*Raf[t]*RasGTP[t])/(K13 + Raf[t])
reaction0000014 = (compartment0000001*k14*(AktPIPP[t] + E[t])*Rafstar[t])/(K14 + Rafstar[t])
reaction0000015 = (compartment0000001*k15*MEK[t]*Rafstar[t])/(MEK[t] + K15*(1 + MEKP[t]/K17))
reaction0000016 = (compartment0000001*k16*MEKP[t]*PP2A[t])/(MEKP[t] + K16*(1 + AktPIP[t]/K31 + AktPIPP[t]/K33 + MEKPP[t]/K18))
reaction0000017 = (compartment0000001*k17*MEKP[t]*Rafstar[t])/(K17*(1 + MEK[t]/K15) + MEKP[t])
reaction0000018 = (compartment0000001*k18*MEKPP[t]*PP2A[t])/(K18*(1 + AktPIPP[t]/K31 + AktPIPP[t]/K33 + MEKP[t]/K16) + MEKPP[t])
reaction0000019 = (compartment0000001*k19*ERK[t]*MEKPP[t])/(ERK[t] + K19*(1 + ERKP[t]/K21))
reaction0000020 = (compartment0000001*k20*ERKP[t]*MKP3[t])/(ERKP[t] + K20*(1 + ERKPP[t]/K22))
reaction0000021 = (compartment0000001*k21*ERKP[t]*MEKPP[t])/(K21*(1 + ERK[t]/K19) + ERKP[t])
reaction0000022 = (compartment0000001*k22*ERKPP[t]*MKP3[t])/(K22*(1 + ERKP[t]/K20) + ERKPP[t])
reaction0000023 = compartment0000001*(k23*PI3K[t]*RP[t] - k23*RPI3K[t])
reaction0000024 = compartment0000001*(k24*RPI3K[t] - k24*RPI3Kstar[t])
reaction0000025 = compartment0000001*(-(k25*PI3Kstar[t]*RP[t]) + k25*RPI3Kstar[t])
reaction0000026 = (compartment0000001*V26*PI3Kstar[t])/(K26 + PI3Kstar[t])
reaction0000027 = (compartment0000001*k27*PI3Kstar[t]*PI[t])/(K27 + PI[t])
reaction0000028 = (compartment0000001*V28*PIP3[t])/(K28 + PIP3[t])
reaction0000029 = compartment0000001*(-(k29*AktPIP3[t]) + k29*Akt[t]*PIP3[t])
reaction0000030 = (compartment0000001*V30*AktPIP3[t])/(K30*(1 + AktPIP[t]/K32) + AktPIP3[t])
reaction0000031 = (compartment0000001*k31*AktPIP[t]*PP2A[t])/(AktPIP[t] + K31*(1 + AktPIPP[t]/K33 + MEKP[t]/K16 + MEKPP[t]/K18))
reaction0000032 = (compartment0000001*V32*AktPIP[t])/(AktPIP[t] + K32*(1 + AktPIP3[t]/K30))
reaction0000033 = (compartment0000001*k33*AktPIPP[t]*PP2A[t])/(AktPIPP[t] + K33*(1 + AktPIP[t]/K31 + MEKP[t]/K16 + MEKPP[t]/K18))
reaction0000034 = compartment0000001*(-(k34*internalization[t]) + k34*RP[t])
end rate equations

begin 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
k1 = 0.00076
k2 = 0.1
k23 = 2.0
k24 = 0.0985
k25 = 0.047
k29 = 234.0
k3 = 0.01
k34 = 0.0
k5 = 1.0
k6 = 5.0
k7 = 546.0
k8 = 15700.0
k9 = 0.0
compartment0000001 = 1.0
end parameters

begin initial conditions
Akt[0] = Akti
AktPIP[0] = AktPIPi
AktPIP3[0] = AktPIP3i
AktPIPP[0] = AktPIPPi
E[0] = Ei
ERK[0] = ERKi
ERKP[0] = ERKPi
ERKPP[0] = ERKPPi
GS[0] = GSi
HRG[0] = HRGi
MEK[0] = MEKi
MEKP[0] = MEKPi
MEKPP[0] = MEKPPi
MKP3[0] = MKP3i
PI3K[0] = PI3Ki
PI3Kstar[0] = PI3Kstari
PIP3[0] = PIP3i
PP2A[0] = PP2Ai
PI[0] = PIi
R[0] = Ri
RHRG[0] = RHRGi
RHRG2[0] = RHRG2i
RP[0] = RPi
RPI3K[0] = RPI3Ki
RPI3Kstar[0] = RPI3Kstari
RShGS[0] = RShGSi
RShP[0] = RShPi
RShc[0] = RShci
Raf[0] = Rafi
Rafstar[0] = Rafstari
RasGDP[0] = RasGDPi
RasGTP[0] = RasGTPi
ShGS[0] = ShGSi
ShP[0] = ShPi
Shc[0] = Shci
internalization[0] = internalizationi
end initial conditions

begin initial values
Akti = 10.0
AktPIPi = 0.0
AktPIP3i = 0.0
AktPIPPi = 0.0
Ei = 7.0
ERKi = 1000.0
ERKPi = 0.0
ERKPPi = 0.0
GSi = 10.0
HRGi = 330.0
MEKi = 120.0
MEKPi = 0.0
MEKPPi = 0.0
MKP3i = 2.4
PI3Ki = 10.0
PI3Kstari = 0.0
PIP3i = 0.0
PP2Ai = 11.4
PIi = 800.0
Ri = 80.0
RHRGi = 0.0
RHRG2i = 0.0
RPi = 0.0
RPI3Ki = 0.0
RPI3Kstari = 0.0
RShGSi = 0.0
RShPi = 0.0
RShci = 0.0
Rafi = 100.0
Rafstari = 0.0
RasGDPi = 120.0
RasGTPi = 0.0
ShGSi = 0.0
ShPi = 0.0
Shci = 1000.0
internalizationi = 0.0
end initial values

begin assignment rules
MEKPPpercent := (5*MEKPP[t])/6
AktPPpercent := 10*AktPIPP[t]
ERKPPpercent := ERKPP[t]/10
Rafstarpercent := Rafstar[t]
PI3Kstarpercent := 10*PI3Kstar[t]
ShPpercent := ShP[t]/10
RPpercent := (5*(RP[t] + RPI3K[t] + RPI3Kstar[t] + RShc[t] + RShGS[t] + RShP[t]))/2
end assignment rules

begin function definitions
end function definitions

begin events
end events

begin process annotations
end process annotations

begin species annotations
PIP3 http://identifiers.org/chebi/CHEBI:16618
P_I http://identifiers.org/chebi/CHEBI:26034
end species annotations

begin units
end units