Physiology

Reaction Diagram

reactionDiagram

Cross-References

Annotations

Reactions

Reactions
Name
Structure
Kinetics
Depiction
Ca_C+Fura4F_CCa_Fura4F_C Cabind_Fura4F C MassAction
IP3_C+LIBRAvIII_CIP3_LIBRAvIII_C IP3_LibraVIII C MassAction
PI4P_MDAG_M PLC_on_PI4P M GeneralKinetics
RG_GDP_MGaGTP_M+RGbeta_M NE_RG M MassAction
R_M+oxoM_EXRL_M L1 M MassAction
noninactiveIP3RinactiveIP3R h_reaction_IP3Rinactivation ERM GeneralKinetics
PI4P_MPIP2_M PIP5K_5Pase M MassAction
G_GDP_MGaGTP_M+Gbeta_M NE_G M MassAction
GaGTP_MGa_GDP_M GTPase_Ga M GeneralKinetics
IP3_C IP3deg_Palk C MassAction
Palk_C1Palk_C2 r12 C MassAction
Palk_C2Palk_C3 r23 C MassAction
Palk_C2Palk_O4 r24 C MassAction
PIP2_MboundPIP2_M PIP2_buffering M MassAction
RGbeta_M+oxoM_EXRLGbeta_M L2beta M MassAction
RLG_GDP_MGaGTP_M+RLGbeta_M NE_RLG M GeneralKinetics
GaGDP_PLC_MGaGTP_PLC_M NE_GaP M GeneralKinetics
PIP2_M+PH_YFP_CPH_YFP_PIP2_M PH_YFP_PIP2 M MassAction
PIP2_MPI4P_M VSP M MassAction
R_M+Gbeta_MRGbeta_M G1beta M MassAction
DAG_MPA_2AG_M DAGPase M GeneralKinetics
PI_MPI4P_M PI4K_4Pase_M M MassAction
PH_YFP_C+IP3_CIP3_PH_YFP_C PH_YFP_IP3 C MassAction
IP3_C IP3Pase_FDH C GeneralKinetics
RL_M+Gbeta_MRLGbeta_M G2beta M MassAction
GaGDP_PLC_MPLC_M+Ga_GDP_M PLCdiss M MassAction
RG_GDP_M+oxoM_EXRLG_GDP_M L2 M MassAction
GaGTP_M+PLC_MGaGTP_PLC_M PLCassoc M MassAction
G_GDP_M+R_MRG_GDP_M G1 M MassAction
PIP2_M+KCNQ_MKCNQ_PIP2_M PIP2bindKCNQ M GeneralKinetics
PIP2_MDAG_M+IP3_C PIP2hydr M GeneralKinetics
IP3_pipetteIP3_C IP3_dialysis M MassAction
GaGTP_PLC_MGaGDP_PLC_M GTPase_GaP M GeneralKinetics
OxoM_conc_EXoxoM_EX Oxo_appl EX MassAction
G_GDP_M+RL_MRLG_GDP_M G2 M MassAction
Ga_GDP_M+Gbeta_MG_GDP_M reconstitution M GeneralKinetics
DAG_M+C1_dom_CC1_DAG_M C1bindDAG M MassAction
PI_GPI4P_G PI4K_4Pase_G Golgi_Vesicle_M MassAction
PI4P_GPIP2_M PIP5K_5Pase_G M MassAction
PI_EPI_M PI_EX_M M MassAction
PI_EPI_G PI_EX_G Golgi_Vesicle_M MassAction
P4M_C+PI4P_GP4M_PI4P_G PI4P_P4M_G Golgi_Vesicle_M MassAction
PI4P_M+P4M_CP4M_PI4P_M PI4P_P4M_M M MassAction
PI4P_G+FAPP1_CFAPP1_PI4P_G PI4P_FAPP1_G Golgi_Vesicle_M MassAction
PI4P_GPI_G Sac1_G Golgi_Vesicle_M MassAction

Structures

Name
Type
Electrical
M Membrane C(+)   EX(-)
ERM Membrane Ca_store(+)   C(-)
Golgi_Vesicle_M Membrane (+)   (-)
EX Compartment (+)   (-)
Ca_store Compartment (+)   (-)
C Compartment (+)   (-)

Species

Name
Structure
BioNetGen Definition
Depiction
IP3_pipette EX EX
PI4P_M M M
PH_YFP_PIP2_M M M
KCNQ_M M M
inactiveIP3R ERM ERM
IP3_PH_YFP_C C C
RLG_GDP_M M M
RL_M M M
GaGTP_PLC_M M M
GaGTP_M M M
RLGbeta_M M M
Gbeta_M M M
C1_dom_C C C
K_C C C
Ca_C C C
RGbeta_M M M
R_M M M
noninactiveIP3R ERM ERM
boundPIP2_M M M
IP3_LIBRAvIII_C C C
LIBRAvIII_C C C
G_GDP_M M M
RG_GDP_M M M
Ga_GDP_M M M
DAG_M M M
oxoM_EX EX EX
PA_2AG_M M M
PLC_M M M
PH_YFP_C C C
PIP2_M M M
OxoM_conc_EX EX EX
Ca_Fura4F_C C C
Ca_Ca_store Ca_store Ca_store
Fura4F_C C C
IP3_C C C
Palk_C1 C C
Palk_C2 C C
Palk_C3 C C
Palk_O4 C C
C1_DAG_M M M
GaGDP_PLC_M M M
K_EX EX EX
KCNQ_PIP2_M M M
PI4P_G Golgi_Vesicle_M Golgi_Vesicle_M
PI_E ERM ERM
PI_M M M
PI_G Golgi_Vesicle_M Golgi_Vesicle_M
P4M_C C C
P4M_PI4P_M M M
P4M_PI4P_G Golgi_Vesicle_M Golgi_Vesicle_M
FAPP1_C C C
FAPP1_PI4P_G Golgi_Vesicle_M Golgi_Vesicle_M

Molecules

Name
BioNetGen Definition
DEPICTION

Observables

Name
Structure
Count
BNGL Definition
Sequence Type
DEPICTION

Applications

Name
Properties Math Type
Annotation
Modeling PI cycle Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental cloned from 'Modeling PI cycle' owned by user cherubim0521 cloned from 'modelinOct2010' owned by user hillelab cloned from 'modelinOct2010' owned by user bfalken (copied from PBio519 talk) (copied from M1R activation, manuscript 1) (copied from M1R activation) (copied from PipDecay) cloned from 'PipDecay' owned by user hillelab cloned from 'PipDecay' owned by user bfalken cloned from 'PipDecay' owned by user hillelab cloned from 'PipDecay' owned by user bfalken cloned from 'PipDecay' owned by user hillelab

Specifications (Species) - Modeling PI cycle go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
IP3_pipette 0.0 [uM] 0.0 [um2/s] EX
oxoM_EX 0.0 [uM] 0.0 [um2/s] EX
OxoM_conc_EX 10.0 [uM] 0.0 [um2/s] EX
K_EX 0.0 [uM] 0.0 [um2/s] EX
Ca_Ca_store 400.0 [uM] 0.0 [um2/s] Ca_store
IP3_PH_YFP_C 0.0 [uM] 0.0 [um2/s] C
C1_dom_C 0.0 [uM] 0.0 [um2/s] C
K_C 100000.0 [uM] 0.0 [um2/s] C
Ca_C 0.13 [uM] 0.0 [um2/s] C
IP3_LIBRAvIII_C 0.0 [uM] 0.0 [um2/s] C
LIBRAvIII_C 0.0 [uM] 0.0 [um2/s] C
PH_YFP_C 0.0 [uM] 0.0 [um2/s] C
Ca_Fura4F_C 0.0 [uM] 0.0 [um2/s] C
Fura4F_C 0.0 [uM] 0.0 [um2/s] C
IP3_C 0.033 [uM] 0.0 [um2/s] C
Palk_C1 1.0 [uM] 0.0 [um2/s] C
Palk_C2 0.0 [uM] 0.0 [um2/s] C
Palk_C3 0.0 [uM] 0.0 [um2/s] C
Palk_O4 0.0 [uM] 0.0 [um2/s] C
P4M_C 0.0 [uM] 0.0 [um2/s] C
FAPP1_C 0.0 [uM] 0.0 [um2/s] C
PI4P_M 2000.0 [uM] 0.0 [um2/s] M
PH_YFP_PIP2_M 0.0 [uM] 0.0 [um2/s] M
KCNQ_M 4.0 [uM] 0.0 [um2/s] M
RLG_GDP_M 0.0 [uM] 0.0 [um2/s] M
RL_M 0.0 [uM] 0.0 [um2/s] M
GaGTP_PLC_M 0.0 [uM] 0.0 [um2/s] M
GaGTP_M 0.0 [uM] 0.0 [um2/s] M
RLGbeta_M 0.0 [uM] 0.0 [um2/s] M
Gbeta_M 0.0 [uM] 0.0 [um2/s] M
RGbeta_M 0.0 [uM] 0.0 [um2/s] M
R_M 500.0 [uM] 0.0 [um2/s] M
boundPIP2_M (( - 1.0 + foldPIP2) * PIP2_M) [uM] 0.0 [um2/s] M
G_GDP_M 40.0 [uM] 0.0 [um2/s] M
RG_GDP_M 0.0 [uM] 0.0 [um2/s] M
Ga_GDP_M 0.0 [uM] 0.0 [um2/s] M
DAG_M 13.0 [uM] 0.0 [um2/s] M
PA_2AG_M 0.0 [uM] 0.0 [um2/s] M
PLC_M 10.0 [uM] 0.0 [um2/s] M
PIP2_M 5000.0 [uM] 0.0 [um2/s] M
C1_DAG_M 0.0 [uM] 0.0 [um2/s] M
GaGDP_PLC_M 0.0 [uM] 0.0 [um2/s] M
KCNQ_PIP2_M 0.0 [uM] 0.0 [um2/s] M
PI_M 1400.0 [uM] 0.0 [um2/s] M
P4M_PI4P_M 0.0 [uM] 0.0 [um2/s] M
inactiveIP3R 0.0 [uM] 0.0 [um2/s] ERM
noninactiveIP3R 1.0 [uM] 0.0 [um2/s] ERM
PI_E 14000.0 [uM] 0.0 [um2/s] ERM
PI4P_G 1000.0 [uM] 0.0 [um2/s] Golgi_Vesicle_M
PI_G 35000.0 [uM] 0.0 [um2/s] Golgi_Vesicle_M
P4M_PI4P_G 0.0 [uM] 0.0 [um2/s] Golgi_Vesicle_M
FAPP1_PI4P_G 0.0 [uM] 0.0 [um2/s] Golgi_Vesicle_M

Specifications (Reaction) - Modeling PI cycle go to Simulations

Name
Enabled?
Cabind_Fura4F included
IP3_LibraVIII included
PLC_on_PI4P included
NE_RG included
L1 included
h_reaction_IP3Rinactivation included
PIP5K_5Pase included
NE_G included
GTPase_Ga included
IP3deg_Palk excluded
r12 excluded
r23 excluded
r24 excluded
PIP2_buffering included
L2beta included
NE_RLG included
NE_GaP included
PH_YFP_PIP2 included
VSP included
G1beta included
DAGPase included
PI4K_4Pase_M included
PH_YFP_IP3 included
IP3Pase_FDH included
G2beta included
PLCdiss included
L2 included
PLCassoc included
G1 included
PIP2bindKCNQ included
PIP2hydr included
IP3_dialysis included
GTPase_GaP included
Oxo_appl included
G2 included
reconstitution included
C1bindDAG included
PI4K_4Pase_G included
PIP5K_5Pase_G included
PI_EX_M included
PI_EX_G included
PI4P_P4M_G included
PI4P_P4M_M included
PI4P_FAPP1_G included
Sac1_G included
RyR_Palk excluded
leak_Palk excluded
SERCA_Palk excluded
KCNQ2/3 included
ER_leak_flux_FDH included
IP3R_flux_FDH included
SERCA_flux_FDH included
IP3R_Palk excluded

Simulations - Modeling PI cycle go to Specifications

Name
End Time
Output Options
S Figure 9A. PtdIns4P_M_P4M 720.0

OutputTimeStep 1.0

S Figure 9D. InsP3_LIBRA 720.0

OutputTimeStep 1.0

Backbone Figure 7 720.0

OutputTimeStep 1.0

S Figure 9E. DAG_C1A 720.0

OutputTimeStep 1.0

S Figure 9C. PH domain 720.0

OutputTimeStep 1.0

S Figure 9B. FAPP1 720.0

OutputTimeStep 1.0

Figure 6G. PtdIns4P_M_P4M Sac1 720.0

OutputTimeStep 1.0

Figure 6F. PH domain Sac1 720.0

OutputTimeStep 1.0

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1595765197

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment Golgi_Vesicle_M

Events

Name Variable Rate Expression

Global Parameters

Name
Expression
KfL1 (KrL1 / KL1)[uM-1.s-1]
KrL1 5.555555555555555[s-1]
KfG1 (0.1 * KfG2)[um2.molecules-1.s-1]
KfG2 0.0026666[um2.molecules-1.s-1]
KrG2 0.68[s-1]
KfL2 KfL1[uM-1.s-1]
KrL2 (KL2 * KfL2)[s-1]
allRL (RL_M + RLG_GDP_M + RLGbeta_M)[molecules.um-2]
KrG1 (KfG1 * KG1)[s-1]
alpha 100.0[1]
KL1 2.0[uM]
KL2 (KL1 / alpha)[uM]
KG1 (KG2 * alpha)[molecules.um-2]
KG2 (KrG2 / KfG2)[molecules.um-2]
allRGbeta (RG_GDP_M + RLG_GDP_M + RLGbeta_M + RGbeta_M)[molecules.um-2]
allGabg (G_GDP_M + RG_GDP_M + RLG_GDP_M)[molecules.um-2]
allGaPLC (GaGTP_PLC_M + GaGDP_PLC_M)[molecules.um-2]
allPIP2M (PIP2_M + KCNQ_PIP2_M + PH_YFP_PIP2_M + boundPIP2_M)[molecules.um-2]
allPH_cytoplasm (PH_YFP_C + IP3_PH_YFP_C)[uM]
speed_PH_PIP2 20.0[uM-1.s-1]
KD_PH_PIP2 2.0[uM]
speed_PH_IP3 10.0[uM-1.s-1]
KD_PH_IP3 2.0[uM]
K_plc 0.2[um2.molecules-1.s-1]
PLC_basal 0.0[s-1]
start 120.0[s]
end 720.0[s]
foldPIP2 3.0[1]
KD_act_Ca_IP3R 0.2[uM]
KD_IP3_IP3R 0.1[uM]
IP3R pow((h * IP3_C * Ca_C / (IP3_C + KD_IP3_IP3R) / (Ca_C + KD_act_Ca_IP3R)),3.0)[1]
KD_DAG_C1 0.2[uM]
speed_DAG_C1 0.2[uM-1.s-1]
activePKC (DAG_M * PIP2_M / ((DAG_M + (1000.0 * KD_DAG_C1)) * (PIP2_M + (1000.0 * KD_PH_PIP2))))[1]
h (noninactiveIP3R / (noninactiveIP3R + inactiveIP3R))[1]
stim_4k ((0.0023581 / (1.0 + exp( - (277.77777777777777 * ( - 0.0175 + OxoMforKinases))))) * stim_second)[s-1]
stim_4k_max 9.0[s-1]
stim_5K_max 0.03092299998[s-1]
stim_5k (stim_5K_max / (1.0 + exp( - (277.77777777777777 * ( - 0.0175 + OxoMforKinases)))))[s-1]
tau_stim_onset 1.0[s]
k5k_base 0.0117624[s-1]
OxoMforKinases 0.0[uM]
all_IP3 (IP3_C + IP3_LIBRAvIII_C + IP3_PH_YFP_C)[uM]
r_FDH 1.0[1]
r_Palk 0.0[1]
perms2pers 1000.0[s-1]
uM2nM 1000.0[uM-1]
removeuM 1.0[uM-1]
onset_second 20.0[s]
K4_base (2.41884E-4 * 6.0)[s-1]
scale4K 0.75[1]
K4_rest 0.00312[s-1]
K4_Oxo (K4_rest + ((stim_4k - K4_rest + K4_base) * (1.0 - exp(((start + tau_stim_onset - t) / tau_stim_onset)))))[s-1]
tau_second 300.0[s]
tau_Ga_PI4P_PLC 241.0[tbd]
tau_PM_PI4K 210.0[s]
star 120.0[s]
tau_PI4K 300.0[s]
speed_P4M_PI4P 0.01[um2.s-1.molecules-1]
KD_P4M_PI4P 1.5[uM]
stim_second (1.0 + ((((stim_4k_max / (1.0 + exp( - (277.77777777777777 * ( - 0.0175 + OxoMforKinases))))) - (0.0077419 * stim_4k_max)) * (1.0 - exp(((start + onset_second - t) / tau_second)))) * ((start + onset_second) < t) * (t <= end)))[s-1]
tau_PIP2_PLC 20.0[s]

Downloads

Model Format
Model Downloads
Virtual Cell Markup Language VCML File
PDF Report Report
COMBINE Archive OMEX File
SEDML SEDML File
File Format
Application Downloads
BNGL Modeling PI cycle.bngl
SBML Modeling PI cycle.sbml
Matlab Modeling PI cycle.m
NFSim XML Modeling PI cycle.xml