<ReactionScheme>
<!-- First version of merges Gq Gs coupled pathway reactions
when reactions differ between the models, notes indicate which was source.
Either StriatumCRCNS/StochasticSP1/MSPNfinalxml/MSPNreactions_4spine_new50.xml for Gs
or MURI/BoHung/FinalMarch2012/mglu_2ag_reac12mar20desens025.xml for Gq
phosphatase reactions take from revision of Gs to improve Ca dep dphos of Dp32-->
<!-- Molecules species and diffusion constants -->
<Specie name="ERK" id="ERK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="pERK" id="pERK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="ppERK" id="ppERK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="MKP1" id="MKP1" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="pERKMKP1" id="pERKMKP1" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="ppERKMKP1" id="ppERKMKP1" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="ppMEKERK" id="ppMEKERK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="ppMEKpERK" id="ppMEKpERK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="MEK" id="MEK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="pMEK" id="pMEK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="ppMEK" id="ppMEK" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="PP2A" id="PP2A" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="pMEKPP2A" id="pMEKPP2A" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="ppMEKPP2A" id="ppMEKPP2A" kdiff="7" kdiffunit="mu2/s"/>
<Specie name="bRaf" id="bRaf" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="bRafRap1MEK" id="bRafRap1MEK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="bRafRap1pMEK" id="bRafRap1pMEK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="bRafRap1" id="bRafRap1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Raf1Rap1" id="Raf1Rap1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Rap1GTP" id="Rap1GTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Rap1GDP" id="Rap1GDP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Epac" id="Epac" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="EpacRap1" id="EpacRap1" kdiff="0.6" kdiffunit="mu2/s"/>
<Specie name="EpacAMP" id="EpacAMP" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="cAMP" id="cAMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="PDE2" id="PDE2" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="PDE2cAMP" id="PDE2cAMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="PDE2cAMP2" id="PDE2cAMP2" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="PDE4" id="PDE4" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="PDE4cAMP" id="PDE4cAMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="AMP" id="AMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="PKAcAMP2" id="PKAcAMP2" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="PKAcAMP4" id="PKAcAMP4" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="PKA" id="PKA" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="PKAc" id="PKAc" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="PKAr" id="PKAr" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="Src" id="Src" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="PKAcSrc" id="PKAcSrc" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="pSrc" id="pSrc" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="Cbl" id="Cbl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CblpSrc" id="CblpSrc" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pCbl" id="pCbl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CRKC3G" id="CRKC3G" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CRKC3GpCbl" id="CRKC3GpCbl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CRKC3GpCblRap1" id="CRKC3GpCblRap1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Rap1SynGap" id="Rap1SynGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Rap1pSynGap" id="Rap1pSynGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="rap1Gap" id="rap1Gap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Rap1GTPGap" id="Rap1GTPGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="SynGap" id="SynGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pSynGap" id="pSynGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pSynden" id="pSynden" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CK" id="CK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKp" id="CKp" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CamCa4" id="CamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKCamCa4" id="CKCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKpCamCa4" id="CKpCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKpCamCa4SynGap" id="CKpCamCa4SynGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP1" id="PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKpPP1" id="CKpPP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKpCamCa4PP1" id="CKpCamCa4PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip35" id="Ip35" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip35PP1" id="Ip35PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ng" id="Ng" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="NgCam" id="NgCam" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gbg" id="Gbg" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="SrcGbg" id="SrcGbg" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Grb2" id="Grb2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Sos" id="Sos" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pSos" id="pSos" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Grb2Sos" id="Grb2Sos" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ppERKpShcGrb2Sos" id="ppERKpShcGrb2Sos" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pShcGrb2" id="pShcGrb2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="SrcGbgShc" id="SrcGbgShc" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Shc" id="Shc" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pShc" id="pShc" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pShcGrb2Sos" id="pShcGrb2Sos" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pShcGrb2SosRas" id="pShcGrb2SosRas" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RasGRF" id="RasGRF" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CamCa4GRF" id="CamCa4GRF" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CamCa4GRFRas" id="CamCa4GRFRas" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Raf1" id="Raf1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Raf1Ras" id="Raf1Ras" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="dRaf1Ras" id="dRaf1Ras" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="dRaf1RasMEK" id="dRaf1RasMEK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="dRaf1RaspMEK" id="dRaf1RaspMEK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="bRafRas" id="bRafRas" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="bRafRasMEK" id="bRafRasMEK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="bRafRaspMEK" id="bRafRaspMEK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RasGTP" id="RasGTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RasGDP" id="RasGDP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RasSynGap" id="RasSynGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="rasGap" id="rasGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RasGTPGap" id="RasGTPGap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RaspSynGap" id="RaspSynGap" kdiff="0" kdiffunit="mu2/s"/>
<!-- calcium reaction subset, to adjust for proper basal calcium -->
<!-- calcium stuff first -->
<Specie name="Ca" id="Ca" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="Caext" id="Caext" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="CaextLeak" id="CaextLeak" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Leak" id="Leak" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pmca" id="pmca" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ncx" id="ncx" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pmcaCa" id="pmcaCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ncxCa" id="ncxCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Calbin" id="Calbin" kdiff="9.3" kdiffunit="mu2/s"/>
<Specie name="CalbinC" id="CalbinC" kdiff="9.3" kdiffunit="mu2/s"/>
<Specie name="CB" id="CB" kdiff="9.3" kdiffunit="mu2/s"/>
<Specie name="CaB" id="CaB" kdiff="9.3" kdiffunit="mu2/s"/>
<Specie name="Cabuff" id="Cabuff" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="Cbuff" id="Cbuff" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="Cbuffslow" id="Cbuffslow" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="Caextbuffslow" id="Caextbuffslow" kdiff="174.3" kdiffunit="mu2/s"/>
<!-- CaM from Gq files, with either C or N site binding first -->
<Specie name="Cam" id="Cam" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CamCa2C" id="CamCa2C" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CamCa2N" id="CamCa2N" kdiff="11" kdiffunit="mu2/s"/>
<!--****************************************************************************
Now, the reactions themselves
****************************************************************************-->
<!--ERK ACTIVATION BY ppMAPKK-->
<!--(ERK phos by ppMAPKK) ppMAPKK+ERK <-> ppMAPKKERK <-> pERK+ppMAPKK-->
<Reaction name = "ppMAPKK+ERK--ppMAPKKERK" id="ppMAPKK+ERK--ppMAPKKERK">
<Reactant specieID="ppMEK" />
<Reactant specieID="ERK" />
<Product specieID="ppMEKERK" />
<forwardRate> 0.032e-3 </forwardRate>
<reverseRate> 1.200e-3 </reverseRate>
</Reaction>
<Reaction name = "ppMEKERK--pERK+ppMAPKK" id="ppMAPKKERK--pERK+ppMAPKK">
<Reactant specieID="ppMEKERK" />
<Product specieID="pERK" />
<Product specieID="ppMEK" />
<forwardRate> 0.3e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(pERK phos by ppMAPKK) ppMAPKK+pERK <-> ppMAPKKpERK <-> ppERK+ppMAPKK-->
<Reaction name = "ppMAPKK+pERK--ppMAPKKpERK" id="ppMAPKK+pERK--ppMAPKKpERK">
<Reactant specieID="ppMEK" />
<Reactant specieID="pERK" />
<Product specieID="ppMEKpERK" />
<forwardRate> 0.032e-3 </forwardRate>
<reverseRate> 1.200e-3 </reverseRate>
</Reaction>
<Reaction name = "ppMAPKKpERK--ppERK+ppMAPKK" id="ppMAPKKpERK--ppERK+ppMAPKK">
<Reactant specieID="ppMEKpERK" />
<Product specieID="ppERK" />
<Product specieID="ppMEK" />
<forwardRate> 0.3e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--ERK INACTIVATION BY MKP1-->
<!--(ppERK dephos by MKP1) ppERK+MKP1<-> ppERKMKP1 <-> pERK+MKP1-->
<Reaction name = "ppERK+MKP1--ppERKMKP1" id="ppERK+MKP1--ppERKMKP1">
<Reactant specieID="ppERK" />
<Reactant specieID="MKP1" />
<Product specieID="ppERKMKP1" />
<forwardRate> 0.150e-3 </forwardRate>
<reverseRate> 16e-3 </reverseRate>
</Reaction>
<Reaction name = "ppERKMKP1--pERK+MKP1" id="ppERKMKP1--pERK+MKP1">
<Reactant specieID="ppERKMKP1" />
<Product specieID="pERK" />
<Product specieID="MKP1" />
<forwardRate> 4e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(pERK dephos by MKP1) pERK+MKP1<-> pERKMKP1 <-> ERK+MKP1-->
<Reaction name = "pERK+MKP1--pERKMKP1" id="pERK+MKP1--pERKMKP1">
<Reactant specieID="pERK" />
<Reactant specieID="MKP1" />
<Product specieID="pERKMKP1" />
<forwardRate> 0.150e-3 </forwardRate>
<reverseRate> 16e-3 </reverseRate>
</Reaction>
<Reaction name = "pERKMKP1--ERK+MKP1" id="pERKMKP1--ERK+MKP1">
<Reactant specieID="pERKMKP1" />
<Product specieID="ERK" />
<Product specieID="MKP1" />
<forwardRate> 4e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--MAPKK ACTIVATION BY bRafRap1GTP-->
<!--(MAPKK phos by bRafRap1) MAPKK + bRafRap1GTP <-> bRafRap1GTPMAPKK <-> pMAPKK + bRafRap1GTP-->
<Reaction name = "MAPKK+bRafRap1--bRafRap1MAPKK" id="MAPKK+bRafRap1--bRafRap1MAPKK">
<Reactant specieID="MEK" />
<Reactant specieID="bRafRap1" />
<Product specieID="bRafRap1MEK" />
<forwardRate> 0.00942863e-3 </forwardRate>
<!-- forwardRate> 0 </forwardRate-->
<reverseRate> 1.2e-3 </reverseRate>
</Reaction>
<Reaction name = "bRafRap1MAPKK--pMAPKK+bRafRap1" id="bRafRap1MAPKK--pMAPKK+bRafRap1">
<Reactant specieID="bRafRap1MEK" />
<Product specieID="pMEK" />
<Product specieID="bRafRap1" />
<forwardRate> 0.3e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(pMAPKK phos by bRafRap1) pMAPKK + bRafRap1 <-> bRafRap1pMAPKK <-> ppMAPKK + bRafRap1-->
<Reaction name = "pMAPKK+bRafRap1--bRafRap1pMAPKK" id="pMAPKK+bRafRap1--bRafRap1pMAPKK">
<Reactant specieID="pMEK" />
<Reactant specieID="bRafRap1" />
<Product specieID="bRafRap1pMEK" />
<forwardRate> 0.00942863e-3 </forwardRate>
<!-- forwardRate> 0 </forwardRate-->
<reverseRate> 1.2e-3 </reverseRate>
</Reaction>
<Reaction name = "bRafRap1pMAPKK--ppMAPKK+bRafRap1" id="bRafRap1pMAPKK--ppMAPKK+bRafRap1">
<Reactant specieID="bRafRap1pMEK" />
<Product specieID="ppMEK" />
<Product specieID="bRafRap1" />
<forwardRate> 0.3e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--MAPKK INACTIVATION BY PP2A-->
<!--(ppMAPKK dephos by PP2A) ppMAPKK+PP2A <-> ppMAPKKPP2A <-> pMAPKK+PP2A-->
<Reaction name = "ppMAPKK+PP2A--ppMAPKKPP2A" id="ppMAPKK+PP2A--ppMAPKKPP2A">
<Reactant specieID="ppMEK" />
<Reactant specieID="PP2A" />
<Product specieID="ppMEKPP2A" />
<forwardRate> 0.0019168e-3 </forwardRate>
<reverseRate> 24.000000e-3 </reverseRate>
</Reaction>
<Reaction name = "ppMAPKKPP2A--pMAPKK+PP2A" id="ppMAPKKPP2A--pMAPKK+PP2A">
<Reactant specieID="ppMEKPP2A" />
<Product specieID="pMEK" />
<Product specieID="PP2A" />
<forwardRate> 6e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(pMAPKK dephos by PP2A) pMAPKK+PP2A <-> pMAPKKPP2A <-> MAPKK+PP2A-->
<Reaction name = "pMAPKK+PP2A--pMAPKKPP2A" id="pMAPKK+PP2A--pMAPKKPP2A">
<Reactant specieID="pMEK" />
<Reactant specieID="PP2A" />
<Product specieID="pMEKPP2A" />
<forwardRate> 0.0019168e-3 </forwardRate>
<reverseRate> 24.000000e-3 </reverseRate>
</Reaction>
<Reaction name = "pMAPKKPP2A--MAPKK+PP2A" id="pMAPKKPP2A--pMAPKK+PP2A">
<Reactant specieID="pMEKPP2A" />
<Product specieID="MEK" />
<Product specieID="PP2A" />
<forwardRate> 6e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Rap1GTP activates bRaf -->
<!-- (bRaf activation) Rap1GTP + bRaf <-> bRafRap1 -->
<Reaction name = "Rap1GTP+bRaf--bRafRap1" id="Rap1GTP+bRaf--bRafRap1">
<Reactant specieID="Rap1GTP" />
<Reactant specieID="bRaf" />
<Product specieID="bRafRap1" />
<forwardRate> 0.06e-3 </forwardRate>
<!--forwardRate> 0 </forwardRate-->
<reverseRate> 1e-3 </reverseRate>
</Reaction>
<!-- Rap1GTP forms an inactif complex with Raf1 -->
<!-- (Raf1 complex with Rap1) Rap1GTP + Raf1 <-> Raf1Rap1 -->
<Reaction name = "Rap1GTP+Raf1--Raf1Rap1" id="Rap1GTP+Raf1--Raf1Rap1">
<Reactant specieID="Rap1GTP" />
<Reactant specieID="Raf1" />
<Product specieID="Raf1Rap1" />
<forwardRate> 0.006e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<!--Two pathways to activate Rap1-->
<!--Epac pathway to activate Rap1-->
<!--(Epac binding) Epac + cAMP <-> EpacAMP-->
<Reaction name = "Epac+cAmp--EpacAMP" id="Epac+cAMP--EpacAMP">
<Reactant specieID="Epac" />
<Reactant specieID="cAMP" />
<Product specieID="EpacAMP" />
<forwardRate> 0 </forwardRate>
<reverseRate> 0 </reverseRate>
<!--forwardRate> 0.000121e-3 </forwardRate-->
<!--reverseRate> 0.1452e-3 </reverseRate-->
</Reaction>
<!--(Epac(GEF) activates Rap1) Epacamp + Rap1<-> EpacRap1 <-> Epacamp + Rap1GTP-->
<Reaction name = "EpacAMP+Rap1GDP--EpacRap1" id="EpacAMP+Rap1--EpacRap1">
<Reactant specieID="EpacAMP" />
<Reactant specieID="Rap1GDP" />
<Product specieID="EpacRap1" />
<forwardRate> 0 </forwardRate>
<reverseRate> 0 </reverseRate>
<!--forwardRate> 0.0012e-3 </forwardRate-->
<!--reverseRate> 0.960e-3 </reverseRate-->
</Reaction>
<Reaction name = "EpacRap1--EpacAMP+Rap1GTP" id="EpacRap1--EpacAMP+Rap1GTP">
<Reactant specieID="EpacRap1" />
<Product specieID="EpacAMP" />
<Product specieID="Rap1GTP" />
<forwardRate> 0.24e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--PKA pathway to activate Rap1-->
<!--(activation of Src by PKAc) PKAc + Src <-> PKAcSrc <-> PKAc + pSrc-->
<Reaction name = "PKAc+Src--PKAcSrc" id="PKAc+Src--PKAcSrc">
<Reactant specieID="PKAc" />
<Reactant specieID="Src" />
<Product specieID="PKAcSrc" />
<forwardRate> 2.041e-3 </forwardRate>
<reverseRate> 80.00e-3 </reverseRate>
</Reaction>
<Reaction name = "PKAcSrc--PKAc+pSrc" id="PKAcSrc--PKAc+pSrc">
<Reactant specieID="PKAcSrc" />
<Product specieID="PKAc" />
<Product specieID="pSrc" />
<forwardRate> 20e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(inactivation of pSrc) pSrc<->Src-->
<Reaction name = "pSrc--Src" id="pSrc--Src">
<Reactant specieID="pSrc" />
<Product specieID="Src" />
<forwardRate> 100e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(activation of Cbl by pSrc) Cbl + pSrc <-> CblpSrc <-> pCbl + pSrc-->
<Reaction name = "Cbl+pSrc--CblpSrc" id="Cbl+pSrc--CblpSrc">
<Reactant specieID="Cbl" />
<Reactant specieID="pSrc" />
<Product specieID="CblpSrc" />
<forwardRate> 0.4e-3 </forwardRate>
<reverseRate> 160e-3 </reverseRate>
</Reaction>
<Reaction name = "CblpSrc--pCbl+pSrc" id="CblpSrc--pCbl+pSrc">
<Reactant specieID="CblpSrc" />
<Product specieID="pCbl" />
<Product specieID="pSrc" />
<forwardRate> 40e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(inactivation of pCbl) pCbl<->Cbl-->
<Reaction name = "pCbl--Cbl" id="pCbl--Cbl">
<Reactant specieID="pCbl" />
<Product specieID="Cbl" />
<forwardRate> 100e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(activation of CRKC3G by pCbl) CRKC3G + pCbl <=> CRKC3GpCbl -->
<Reaction name = "CRKC3G+pCbl--CRKC3GpCbl" id="CRKC3G+pCbl--CRKC3GpCbl">
<Reactant specieID="CRKC3G" />
<Reactant specieID="pCbl" />
<Product specieID="CRKC3GpCbl" />
<forwardRate> 0.001e-3 </forwardRate>
<reverseRate> 0.2e-3 </reverseRate>
</Reaction>
<!--(Rap activation by Crk (GEF)) Rap1GDP + CRKC3GpCbl <-> CRKC3GpCblRap1 <-> Rap1GTP + CRKC3GpCbl-->
<Reaction name = "Rap1GDP+CRKC3GpCbl--CRKC3GpCblRap1" id="Rap1GDP+CRKC3GpCbl--CRKC3GpCblRap1">
<Reactant specieID="Rap1GDP" />
<Reactant specieID="CRKC3GpCbl" />
<Product specieID="CRKC3GpCblRap1" />
<forwardRate> 0.0101e-3 </forwardRate>
<reverseRate> 0.0800e-3 </reverseRate>
</Reaction>
<Reaction name = "CRKC3GpCblRap1--Rap1GTP+CRKC3GpCbl" id="CRKC3GpCblRap1--Rap1GTP+CRKC3GpCbl">
<Reactant specieID="CRKC3GpCblRap1" />
<Product specieID="Rap1GTP" />
<Product specieID="CRKC3GpCbl" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(Inactivation of Rap by Rap1GAP) Rap1GTP+Rap1GAP <-> Rap1GTPGAP -> Rap1GAP + Rap1GDP -->
<Reaction name = "Rap1GTP+Rap1GAP--Rap1GTPGAP" id="Rap1GTP+Rap1GAP--Rap1GTPGAP">
<Reactant specieID="Rap1GTP" />
<Reactant specieID="rap1Gap" />
<Product specieID="Rap1GTPGap" />
<forwardRate> 0.2e-3 </forwardRate>
<reverseRate> 200e-3 </reverseRate>
</Reaction>
<Reaction name = "Rap1GTPGAP--Rap1GAP+Rap1GDP" id = "Rap1GTPGAP--Rap1GAP+Rap1GDP">
<Reactant specieID="Rap1GTPGap" />
<Product specieID="rap1Gap" />
<Product specieID="Rap1GDP" />
<forwardRate> 2e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(Inactivation of Rap by SynGAP) Rap1GTP+SynGap <-> Rap1GTPGap -> SynGap + Rap1GDP -->
<Reaction name = "Rap1GTP+SynGap--Rap1Gap" id="Rap1GTP+SynGap--Rap1Gap">
<Reactant specieID="Rap1GTP" />
<Reactant specieID="SynGap" />
<Product specieID="Rap1SynGap" />
<forwardRate> 0.0032e-3 </forwardRate>
<reverseRate> 3.2e-3 </reverseRate>
</Reaction>
<Reaction name = "Rap1Gap--SynGap+Rap1GDP" id = "Rap1Gap--SynGap+Rap1GDP">
<Reactant specieID="Rap1SynGap" />
<Product specieID="SynGap" />
<Product specieID="Rap1GDP" />
<forwardRate> 0.8e-3 </forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!--(Inactivation of RapGTP by pSynGAP) Rap1GTP+pSynGap <-> Rap1GTPpGap -> pSynGap + Rap1GDP -->
<Reaction name = "Rap1GTP+pSynGap--Rap1pGap" id="Rap1GTP+pSynGap--Rap1pGap">
<Reactant specieID="Rap1GTP" />
<Reactant specieID="pSynGap" />
<Product specieID="Rap1pSynGap"/>
<forwardRate> 0.00614e-3 </forwardRate>
<reverseRate> 6.14e-3 </reverseRate>
</Reaction>
<Reaction name = "Rap1pGap--pSynGap+Rap1GDP" id = "Rap1pGap--pSynGap+Rap1GDP">
<Reactant specieID="Rap1pSynGap" />
<Product specieID="pSynGap" />
<Product specieID="Rap1GDP" />
<forwardRate>1.53e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- (Phosphorylation of SynGAP by CaMKII) CKpCamCa4+SynGap <-> CKpCamCa4Gap -> CKpCamCa4+pSynGap -->
<Reaction name = "CKpCamCa4+SynGap--CKpCamCa4Gap" id="CKpCamCa4+SynGap--CKpCamCa4Gap">
<Reactant specieID="CKpCamCa4" />
<Reactant specieID="SynGap" />
<Product specieID="CKpCamCa4SynGap" />
<forwardRate> 0.3067258192987457e-3</forwardRate>
<reverseRate> 0.058715155531797236 </reverseRate>
</Reaction>
<Reaction name = "CKpCamCa4Gap--CKpCamCa4+pSynGap" id="CKpCamCa4Gap--CKpCamCa4+pSynGap">
<Reactant specieID="CKpCamCa4SynGap" />
<Product specieID="pSynGap" />
<Product specieID="CKpCamCa4" />
<forwardRate> 0.0006484330410680531</forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- disperssion of pSynGAP) pSynGap -> pSynden -->
<Reaction name ="pSynGap--pSynden" id="pSynGap--Synden">
<Reactant specieID="pSynGap"/>
<Product specieID="pSynden"/>
<forwardRate> 0.025e-3 </forwardRate>
<reverseRate> 0.025e-3 </reverseRate>
</Reaction>
<!-- inactivation of pSynGAP) pSynGap -> SynGap -->
<Reaction name ="pSynGap--SynGap" id="pSynGap--SynGap">
<Reactant specieID="pSynGap"/>
<Product specieID="SynGap"/>
<forwardRate> 1e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- ******* PKA from Asia Hippo Model ********* -->
<!--1) PKA + 2camp <-> PKAcAMP2 -->
<Reaction name = "PKA_bind" id="PKA_bind">
<Reactant specieID="PKA"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP2"/>
<forwardRate> 0.261e-6 </forwardRate>
<reverseRate> 0.060e-3 </reverseRate>
</Reaction>
<!--2) PKAcAMP2 + 2cAMP <-> PKAcAMP4 -->
<Reaction name = "PKAcAMP2_bind" id="PKAcAMP2_bind">
<Reactant specieID="PKAcAMP2"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP4"/>
<forwardRate> 0.35e-6 </forwardRate>
<reverseRate> 0.6e-3 </reverseRate>
</Reaction>
<!--3) PKAcAMP4 <-> 2PKAr(as dimer) + 2PKAc(monomers) -->
<Reaction name = "PKAcAMP4_diss" id="PKAcAMP4_diss">
<Reactant specieID="PKAcAMP4"/>
<Product specieID="PKAr" />
<Product specieID="PKAc" n="2"/>
<forwardRate> 0.24e-3 </forwardRate>
<reverseRate> 0.0255e-3 </reverseRate>
</Reaction>
<!-- production of cAMP to mimic AC production -->
<Reaction name = "cAMP" id= "cAMP">
<Product specieID="cAMP" />
<forwardRate> 12e-3 </forwardRate>
</Reaction>
<!-- PDE2 buff for cAMP, two steps-->
<Reaction name = "PDE2+cAMP--PDE2cAMP" id="PDE2+cAMP--PDE2cAMP">
<Reactant specieID="PDE2" />
<Reactant specieID="cAMP" />
<Product specieID="PDE2cAMP" />
<forwardRate> 0.00002e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE2cAMP+cAMP--PDE2cAMP2" id="PDE2cAMP+cAMP--PDE2cAMP2">
<Reactant specieID="PDE2cAMP" />
<Reactant specieID="cAMP" />
<Product specieID="PDE2cAMP2" />
<forwardRate> 0.0059e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE2cAMP2--PDE2cAMP+AMP" id="PDE2cAMP2--PDE2cAMP+AMP">
<Reactant specieID="PDE2cAMP2" />
<Product specieID="PDE2cAMP" />
<Product specieID="AMP" />
<forwardRate> 5.4e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- PDE4 buff for cAMP cAMP + PDE4 <-> PDE4cAMP -->
<Reaction name = "PDE4 enzyme1" id="PDE4bind">
<Reactant specieID="PDE4" />
<Reactant specieID="cAMP" />
<Product specieID="PDE4cAMP" />
<forwardRate> 0.0216e-03 </forwardRate>
<reverseRate> 68.95e-03 </reverseRate>
</Reaction>
<!-- PDE4cAMP -> AMP + PDE4 -->
<Reaction name = "PDE4 actvcomp" id="PDE4cat">
<Reactant specieID="PDE4cAMP" />
<Product specieID="PDE4" />
<Product specieID="AMP" />
<forwardRate> 17.233e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Calcium binding -->
<!-- control Ca back to level on time -->
<Reaction name ="ca+cbuff--cabuff" id="ca+cbuff--cabuff">
<Reactant specieID="Ca"/>
<Reactant specieID="Cbuff"/>
<Product specieID="Cabuff"/>
<forwardRate> 0.1e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- remove exess buff -->
<Reaction name ="Cbuffslow+Caext--ext" id="Cbuffslow+Caext--ext">
<Reactant specieID="Cbuffslow"/>
<Reactant specieID="Caext"/>
<Product specieID="Caextbuffslow"/>
<forwardRate> 10e-6 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- i: Ca pump high affinity - Ca + pmca <-> pmcaCa SAME-->
<Reaction name = "Ca_pump1a" id="Ca_pump1a">
<Reactant specieID="Ca"/>
<Reactant specieID="pmca"/>
<Product specieID="pmcaCa"/>
<forwardRate>0.5e-4</forwardRate>
<reverseRate>0.007</reverseRate>
</Reaction>
<!-- ii: Ca pump high affinity - pmcaCa <-> pmca + CaOut SAME-->
<Reaction name = "Ca_pump1b" id="Ca_pump1b">
<Reactant specieID="pmcaCa"/>
<Product specieID="pmca"/>
<Product specieID="Caext"/>
<forwardRate>0.0035</forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!-- iii: Ca pump low affinity - 7 Ca + ncx <-> ncxCa SAME-->
<Reaction name = "Ca_pump2a" id="Ca_pump2a">
<Reactant specieID="Ca"/>
<Reactant specieID="ncx"/>
<Product specieID="ncxCa"/>
<forwardRate>1.68e-5</forwardRate>
<reverseRate>0.0112</reverseRate>
</Reaction>
<!-- iv: Ca pump low affinity - ncxCa <-> ncx + CaOut SAME-->
<Reaction name = "Ca_pump2b" id="Ca_pump2b">
<Reactant specieID="ncxCa"/>
<Product specieID="ncx"/>
<Product specieID="Caext"/>
<forwardRate>0.0056</forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!-- v: Ca leak - CaOut + Leak <-> CaOutLeak GQ RXN FILE, Leak is sm only-->
<Reaction name = "Ca_leak" id="Ca_leak">
<Reactant specieID="Caext"/>
<Reactant specieID="Leak"/>
<Product specieID="CaextLeak"/>
<forwardRate>1.5e-6</forwardRate>
<reverseRate>1.1e-3</reverseRate>
</Reaction>
<!-- vi: Ca leak - CaOutLeak <-> Ca (inside) + Leak -->
<Reaction name = "Ca_leak" id="Ca_leak">
<Reactant specieID="CaextLeak"/>
<Product specieID="Ca"/>
<Product specieID="Leak"/>
<forwardRate>1.1e-3</forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!-- vii: Ca Buffer Ca + Calbindin <-> calbinC SAME-->
<Reaction name = "Ca_buffer" id="Ca_Buffer">
<Reactant specieID="Ca"/>
<Reactant specieID="Calbin"/>
<Product specieID="CalbinC"/>
<forwardRate>2.8e-5</forwardRate>
<reverseRate>0.0196</reverseRate>
</Reaction>
<!-- viii: Ca fixBuffer Ca + CB <-> CaB SAME-->
<Reaction name = "Ca_buffer" id="Ca_Buffer">
<Reactant specieID="Ca"/>
<Reactant specieID="CB"/>
<Product specieID="CaB"/>
<forwardRate>0.02e-3</forwardRate>
<reverseRate>1</reverseRate>
</Reaction>
<!--1A) Cam + 2Ca <-> CamCa2C GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamC_bind" id="CamC_bind">
<Reactant specieID="Cam"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa2C"/>
<forwardRate>6e-6</forwardRate>
<reverseRate>9.1e-3</reverseRate>
</Reaction>
<!--2A) CamCa2C + 2Ca <-> CamCa4 GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamCa2C_bind" id="CamCa2C_bind">
<Reactant specieID="CamCa2C"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa4"/>
<forwardRate>0.1e-3</forwardRate>
<reverseRate>1000e-3</reverseRate>
</Reaction>
<!--1B) Cam + 2Ca <-> CamCa2N GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamN_bind" id="CamN_bind">
<Reactant specieID="Cam"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa2N"/>
<forwardRate>0.1e-3</forwardRate>
<reverseRate>1000e-3</reverseRate>
</Reaction>
<!--2B) CamCa2N + 2Ca <-> CamCa4 GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamCa2N_bind" id="CamCa2N_bind">
<Reactant specieID="CamCa2N"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa4"/>
<forwardRate>6e-6</forwardRate>
<reverseRate>9.1e-3</reverseRate>
</Reaction>
<!-- New CamKII part -->
<!--1) CamCa4 + CK <-> CKCamCa4 -->
<Reaction name = "CK bind" id="CK-Cam_bind">
<Reactant specieID="CamCa4" />
<Reactant specieID="CK" />
<Product specieID="CKCamCa4" />
<forwardRate> 0.01e-3 </forwardRate>
<reverseRate> 1.5e-3 </reverseRate>
<!--0.8 from ode file
reverseRate> 0.8e-3 </reverseRate-->
</Reaction>
<!--2a) 2 CKCamCa4 <-> 1 CKCamCa4 + 1 CKpCamCa4 -->
<Reaction name = "CKCam bind" id="CKCam_pow2">
<Reactant specieID="CKCamCa4" power="2" />
<Product specieID="CKCamCa4" />
<Product specieID="CKpCamCa4" />
<forwardRate> 3.83119676007e-10 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2b) 3 CKCamCa4 <-> 2 CKCamCa4 + 1 CKpCamCa4 -->
<Reaction name = "CKCam bind" id="CKCam_pow3">
<Reactant specieID="CKCamCa4" power="3" />
<Product specieID="CKCamCa4" power="2" />
<Product specieID="CKpCamCa4" />
<forwardRate> 3.55792141502e-13 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2c) 4 CKCamCa4 <-> 3 CKCamCa4 + 1 CKpCamCa4 -->
<Reaction name = "CKCam bind" id="CKCam_pow4">
<Reactant specieID="CKCamCa4" power="4" />
<Product specieID="CKCamCa4" power="3" />
<Product specieID="CKpCamCa4" />
<forwardRate> 2.23694832822e-16 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2d) 2 CKpCamCa4 + 2 CKCamCa4 <-> 3 CKpCamCa4 + 1 CKCamCa4-->
<Reaction name = "CKCam bind" id="CK2_CKpCam_pow2">
<Reactant specieID="CKpCamCa4" power="2" />
<Reactant specieID="CKCamCa4" power="2" />
<Product specieID="CKCamCa4" />
<Product specieID="CKpCamCa4" power="3" />
<forwardRate> 1.10450093247e-18 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2e) 2 CKpCamCa4 + 2 CKCamCa4 <-> 3 CKpCamCa4 + 1 CKCamCa4-->
<Reaction name = "CKCam bind" id="CK1_CKpCam_pow2">
<Reactant specieID="CKpCamCa4" power="2" />
<Reactant specieID="CKCamCa4" />
<Product specieID="CKpCamCa4" power="3" />
<forwardRate> 3.0330636368e-13 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2f) 2 CKpCamCa4 + 2 CKCamCa4 <-> 3 CKpCamCa4 + 1 CKCamCa4-->
<Reaction name = "CKCam bind" id="CK2_CKpCam_pow1">
<Reactant specieID="CKpCamCa4" power="2" />
<Reactant specieID="CKCamCa4" power="2" />
<Product specieID="CKpCamCa4" power="3" />
<Product specieID="CKCamCa4" />
<forwardRate> 2.39399544094e-13 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!-- CKpCamCa4 <-> CKp + CamCa4 -->
<Reaction name = "CKp auto" id="CKp_auto">
<Reactant specieID="CKpCamCa4" />
<Product specieID="CamCa4" />
<Product specieID="CKp" />
<forwardRate> 0.0008e-3 </forwardRate>
<reverseRate> 0.01e-3 </reverseRate>
</Reaction>
<!-- Km=5.1 uM from foulkes et. al., et al., Eur. JBiochem.1983 132(309-313))
Vmax=5.7 umol/min gives kcat=3.5 sec-1 & kb=14 sec-1 -->
<!-- kf=0.000039,kb=0.34,kcat=0.086 /sec for CKp only from Myungs paper 2010 PloS -->
<!-- kf=0.6e-9,kb=0.34e-3,kcat=0.086e-3 /msec for CKp and CKpCam from Myungs Stoch sims-->
<!-- CKp + PP1 <-> CKpPP1 -->
<Reaction name = "CKp_bind" id="CKp_bind">
<Reactant specieID="CKp"/>
<Reactant specieID="PP1"/>
<Product specieID="CKpPP1"/>
<forwardRate> 0.04e-6 </forwardRate>
<reverseRate> 0.34e-3 </reverseRate>
</Reaction>
<!-- CKpPP1 -> PP1 + CK -->
<Reaction name = "CKpPP1_reac" id="CKpPP1_reac">
<Reactant specieID="CKpPP1"/>
<Product specieID="PP1"/>
<Product specieID="CK"/>
<forwardRate> 0.086e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- CKpCamCa4 + PP1 <-> CKpCamCa4PP1 -->
<Reaction name = "CKpCamPP1_bind" id="CKpCamPP1_bind">
<Reactant specieID="CKpCamCa4"/>
<Reactant specieID="PP1"/>
` <Product specieID="CKpCamCa4PP1"/>
<forwardRate> 0.04e-6 </forwardRate>
<reverseRate> 0.34e-3 </reverseRate>
</Reaction>
<!-- CKpCamCa4PP1 -> PP1 + CKCamCa4 -->
<Reaction name = "CKpCamPP1_reac" id="CKpCamPP1_reac">
<Reactant specieID="CKpCamCa4PP1"/>
<Product specieID="PP1"/>
<Product specieID="CKCamCa4"/>
<forwardRate> 0.086e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- PP1 inhibitor -->
<!-- Ip35 + PP1 <-> Ip35PP1 -->
<Reaction name = "Ip35+PP1" id="Ip35+PP1">
<Reactant specieID="Ip35"/>
<Reactant specieID="PP1"/>
` <Product specieID="Ip35PP1"/>
<forwardRate> 1.00e-6 </forwardRate>
<reverseRate> 1.10e-6 </reverseRate>
</Reaction>
<!-- Ng binding to Cam -->
<!-- Ng+Cam <-> NgCam -->
<Reaction name = "Ng+Cam" id="Ng+Cam">
<Reactant specieID="Ng"/>
<Reactant specieID="Cam"/>
` <Product specieID="NgCam"/>
<forwardRate> 2.80e-5 </forwardRate>
<reverseRate> 3.60e-2 </reverseRate>
</Reaction>
<!--MAPKK ACTIVATION BY dRaf1RasGTP (dimer)-->
<!--(MAPKK phos by Raf1RasGTP) MAPKK + Raf1RasGTP <-> Raf1RasGTPMAPKK <-> pMAPKK + Raf1RasGTP-->
<Reaction name = "MAPKK+dRaf1Ras--dRaf1RasMAPKK" id="MAPKK+dRaf1Ras--dRaf1RasMAPKK">
<Reactant specieID="MEK" />
<Reactant specieID="dRaf1Ras" />
<Product specieID="dRaf1RasMEK" />
<forwardRate> 0.018857251e-3 </forwardRate>
<reverseRate> 2.4e-3 </reverseRate>
</Reaction>
<Reaction name = "dRaf1RasMAPKK--pMAPKK+dRaf1Ras" id="dRaf1RasMAPKK--pMAPKK+dRaf1Ras">
<Reactant specieID="dRaf1RasMEK" />
<Product specieID="pMEK" />
<Product specieID="dRaf1Ras" />
<forwardRate> 0.6e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(pMAPKK phos by Raf1RasGTP) pMAPKK + Raf1RasGTP <-> Raf1RasGTPMAPKK <-> ppMAPKK + Raf1RasGTP-->
<Reaction name = "pMAPKK+Raf1Ras--Raf1RaspMAPKK" id="pMAPKK+Raf1Ras--Raf1RaspMAPKK">
<Reactant specieID="pMEK" />
<Reactant specieID="dRaf1Ras" />
<Product specieID="dRaf1RaspMEK" />
<forwardRate> 0.018857251e-3 </forwardRate>
<reverseRate> 2.4e-3 </reverseRate>
</Reaction>
<Reaction name = "Raf1RaspMAPKK--ppMAPKK+Raf1Ras" id="Raf1RaspMAPKK--ppMAPKK+Raf1Ras">
<Reactant specieID="dRaf1RaspMEK" />
<Product specieID="ppMEK" />
<Product specieID="dRaf1Ras" />
<forwardRate> 0.6e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--MAPKK ACTIVATION BY bRafRasGTP-->
<!--(MAPKK phos by bRafRasGTP) MAPKK + bRafRasGTP <-> bRafRasGTPMAPKK <-> pMAPKK + bRafRasGTP-->
<Reaction name = "MAPKK+bRafRas--bRafRasMAPKK" id="MAPKK+bRafRas--bRafRasMAPKK">
<Reactant specieID="MEK" />
<Reactant specieID="bRafRas" />
<Product specieID="bRafRasMEK" />
<forwardRate> 0.00628575e-3 </forwardRate>
<reverseRate> 0.8e-3 </reverseRate>
</Reaction>
<Reaction name = "bRafRasMAPKK--pMAPKK+bRafRas" id="bRafRasMAPKK--pMAPKK+bRafRas">
<Reactant specieID="bRafRasMEK" />
<Product specieID="pMEK" />
<Product specieID="bRafRas" />
<forwardRate> 0.2e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(pMAPKK phos by bRaf1RasGTP) pMAPKK + bRafRasGTP <-> bRafRasGTPMAPKK <-> ppMAPKK + bRafRasGTP-->
<Reaction name = "pMAPKK+bRafRas--bRaf1RaspMAPKK" id="pMAPKK+bRafRasGTP--bRafRaspMAPKK">
<Reactant specieID="pMEK" />
<Reactant specieID="bRafRas" />
<Product specieID="bRafRaspMEK" />
<forwardRate> 0.00628575e-3 </forwardRate>
<reverseRate> 0.8e-3 </reverseRate>
</Reaction>
<Reaction name = "bRafRaspMAPKK--ppMAPKK+bRafRas" id="bRafRaspMAPKK--ppMAPKK+bRafRas">
<Reactant specieID="bRafRaspMEK" />
<Product specieID="ppMEK" />
<Product specieID="bRafRas" />
<forwardRate> 0.2e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- RasGTP activates Raf1 -->
<!-- (Raf1 binds to Ras, step 1) RasGTP + Raf1 <-> RasGTPRaf1 -->
<Reaction name = "Ras+Raf1--Raf1RasGTP" id="RasGTP+Raf1--Raf1Ras">
<Reactant specieID="RasGTP" />
<Reactant specieID="Raf1" />
<Product specieID="Raf1Ras" />
<forwardRate> 0.06e-3 </forwardRate>
<reverseRate> 1e-3 </reverseRate>
</Reaction>
<!-- (Raf1Ras dimerize) RasGTPRaf1*2 <-> dRasGTPRaf1 -->
<Reaction name = "Raf1Ras+Raf1Ras--2Raf1RasGTP" id="Raf1Ras+Raf1Ras--2Raf1RasGTP">
<Reactant specieID="Raf1Ras" n="2" />
<Product specieID="dRaf1Ras" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<!-- RasGTP binding to bRaf -->
<!-- (bRaf bind to RasGTP) RasGTP + bRaf <-> bRafRasGTP -->
<Reaction name = "RasGTP+Raf1--bRafRas" id="RasGTP+bRaf--bRafRas">
<Reactant specieID="RasGTP" />
<Reactant specieID="bRaf" />
<Product specieID="bRafRas" />
<forwardRate> 0.006e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<!--Two pathways to activate Ras-->
<!-- Calmodulin pathway to activate Ras -->
<!--(activaton of RasGRF) CamCa4+RasGRF->CamCa4RasGRF -->
<Reaction name = "CamCa4+RasGRF--CamCa4GRF" id="CamCa4+RasGRF--CamCa4GRF">
<Reactant specieID="CamCa4" />
<Reactant specieID="RasGRF" />
<Product specieID="CamCa4GRF" />
<forwardRate> 0.06e-3 </forwardRate>
<reverseRate> 0.924e-3 </reverseRate>
</Reaction>
<!--(active RasGRF activates Ras)CamCa4GRF +RasGDP <-> CamCa4GRFRasGDP <-> CamCa4GRF + RasGTP-->
<Reaction name = "CamCa4GRF+RasGDP--CamCa4GRFRasGDP" id="CamCa4GRF+RasGDP--CamCa4GRFRasGDP">
<Reactant specieID="CamCa4GRF" />
<Reactant specieID="RasGDP" />
<Product specieID="CamCa4GRFRas" />
<forwardRate> 0.0019e-3 </forwardRate>
<reverseRate> 0.08e-3 </reverseRate>
</Reaction>
<Reaction name = "CamCa4GRFRasGDP--CamCa4GRF+RasGTP" id="CamCa4GRFRasGDP--CamCa4GRF+RasGTP">
<Reactant specieID="CamCa4GRFRas" />
<Product specieID="CamCa4GRF" />
<Product specieID="RasGTP" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Gbg pathway to activate Ras -->
<!-- Gbgext binding to Gbg to balance the baseline -->
<Reaction name ="Gbg--Gbgext" id="Gbg--Gbgext">
<Reactant specieID="Gbg"/>
<forwardRate> 1e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(Gbg binds to Src) Gbg+Src <->SrcGbg -->
<Reaction name = "Gbg+Src--SrcGbg" id="Gbg+Src--SrcGbg">
<Reactant specieID="Gbg" />
<Reactant specieID="Src" />
<Product specieID="SrcGbg" />
<forwardRate> 0.0002e-3 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction>
<!--(SrcGbg activates Shc) SrcGbg+Shc<->SrcGbgShc -->
<Reaction name = "SrcGbg+Shc--SrcGbgShc" id="SrcGbg+Shc--SrcGbgShc">
<Reactant specieID="SrcGbg" />
<Reactant specieID="Shc" />
<Product specieID="SrcGbgShc" />
<forwardRate> 0.008e-3 </forwardRate>
<reverseRate> 0.128e-3 </reverseRate>
</Reaction>
<Reaction name = "SrcGbgShc--SrcGbg+pShc" id="SrcGbgShc--SrcGbg+pShc">
<Reactant specieID="SrcGbgShc" />
<Product specieID="pShc" />
<Product specieID="SrcGbg" />
<forwardRate> 0.032e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(inactivation of pShc) pShc<->Shc-->
<Reaction name = "pShc--Shc" id="pShc--Shc">
<Reactant specieID="pShc" />
<Product specieID="Shc" />
<forwardRate> 0.2e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(Grb2 binds to Sos) Grb2+Sos<->Grb2Sos -->
<Reaction name = " Grb2+Sos--Grb2Sos" id="Grb2+Sos--Grb2Sos">
<Reactant specieID="Grb2" />
<Reactant specieID="Sos" />
<Product specieID="Grb2Sos" />
<forwardRate> 0.00025e-3 </forwardRate>
<reverseRate> 0.0168e-3 </reverseRate>
</Reaction>
<!--(Grb2Sos binds to pShc) Grb2Sos+pShc<->pShcGrb2Sos -->
<Reaction name = "Grb2Sos+pShc--pShcGrb2Sos" id="Grb2Sos+pShc--pShcGrb2Sos">
<Reactant specieID="Grb2Sos" />
<Reactant specieID="pShc" />
<Product specieID="pShcGrb2Sos" />
<forwardRate> 5e-3 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction>
<!--(pShcGrb2Sos activates Ras) pShcGrb2Sos+RasGDP<->pShcGrb2SosRasGDP -->
<Reaction name = "pShcGrb2Sos+RasGDP--pShcGrb2SosRasGDP" id="pShcGrb2Sos+RasGDP--pShcGrb2SosRasGDP">
<Reactant specieID="pShcGrb2Sos" />
<Reactant specieID="RasGDP" />
<Product specieID="pShcGrb2SosRas" />
<forwardRate> 0.0198e-3 </forwardRate>
<reverseRate> 0.8e-3 </reverseRate>
</Reaction>
<Reaction name = "pShcGrb2SosRasGDP--pShcGrb2Sos+RasGTP" id="pShcGrb2SosRasGDP--pShcGrb2Sos+RasGTP">
<Reactant specieID="pShcGrb2SosRas" />
<Product specieID="RasGTP" />
<Product specieID="pShcGrb2Sos" />
<forwardRate> 0.2e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Negative feedback ERK to SOS -->
<Reaction name = "ppERK+pShcGrb2Sos--ppERKpShcGrb2Sos" id="ppERK+pShcGrb2Sos--ppERKpShcGrb2Sos">
<Reactant specieID="pShcGrb2Sos" />
<Reactant specieID="ppERK" />
<Product specieID="ppERKpShcGrb2Sos" />
<forwardRate> 0.01953e-3 </forwardRate>
<reverseRate> 40e-3</reverseRate>
</Reaction>
<Reaction name = "ppERKpShcGrb2Sos--ppERK+pShcGrb2+Sos" id="ppERKpShcGrb2Sos--ppERK+pShcGrb2+Sos">
<Reactant specieID="ppERKpShcGrb2Sos" />
<Product specieID="ppERK" />
<Product specieID="pSos" />
<Product specieID="pShcGrb2" />
<forwardRate> 10e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(inactivation of pSos) pSos<->Sos-->
<Reaction name = "pSos--Sos" id="pSos--Sos">
<Reactant specieID="pSos" />
<Product specieID="Sos" />
<forwardRate> 1e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--Syngap activity on Ras -->
<!--(Inactivation of RasGTP by SynGAP) RasGTP+SynGap <-> RasGTPGap -> SynGap + RasGDP -->
<Reaction name = "RasGTP+SynGap--RasGap" id="RasGTP+SynGap--RasGap">
<Reactant specieID="RasGTP" />
<Reactant specieID="SynGap" />
<Product specieID="RasSynGap" />
<forwardRate>0.00082e-3 </forwardRate>
<reverseRate> 0.82e-3 </reverseRate>
</Reaction>
<Reaction name = "RasGap--SynGap+RasGDP" id = "RasGap--SynGap+RasGDP">
<Reactant specieID="RasSynGap" />
<Product specieID="SynGap" />
<Product specieID="RasGDP" />
<forwardRate> 0.205e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(Inactivation of Ras by pSynGAP) RasGTP+pSynGap <-> RasGTPGap -> pSynGap + RasGDP -->
<Reaction name = "RasGTP+pSynGap--RaspGap" id="RasGTP+pSynGap--RaspGap">
<Reactant specieID="RasGTP" />
<Reactant specieID="pSynGap" />
<Product specieID="RaspSynGap" />
<forwardRate> 0.00112e-3 </forwardRate>
<reverseRate> 1.112e-3 </reverseRate>
</Reaction>
<Reaction name = "RaspGap--pSynGap+RasGDP" id = "RaspGap--pSynGap+RasGDP">
<Reactant specieID="RaspSynGap" />
<Product specieID="pSynGap" />
<Product specieID="RasGDP" />
<forwardRate> 0.279e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--(Inactivation of Ras by RasGAP) RasGTP+RasGTPGAP <-> RasGTPGAP -> RasGAP + RasGDP -->
<Reaction name = "RasGTP+RasGTPGAP-- RasGTPGAP" id="RasGTP+RasGTPGAP-- RasGTPGAP">
<Reactant specieID="RasGTP" />
<Reactant specieID="rasGap" />
<Product specieID="RasGTPGap" />
<forwardRate> 0.0495e-3 </forwardRate>
<reverseRate> 40e-3 </reverseRate>
</Reaction>
<Reaction name = "RasGTPGAP--RasGAP+RasGDP" id = "RasGTPGAP--RasGAP+RasGDP">
<Reactant specieID="RasGTPGap" />
<Product specieID="rasGap" />
<Product specieID="RasGDP" />
<forwardRate> 10e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
</ReactionScheme>