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Molecule Parameter List for inact-GEF

The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by color.
Statistics
inact-GEF participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1002022

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Synaptic_
    Network
  • 16Network
    Shared_Object_Synaptic_Network PKC PLA2 
    PLCbeta Gq MAPK 
    Ras EGFR Sos 
    PLC_g CaMKII CaM 
    PP1 PP2B PKA 
    AC CaRegulation 
    This model is an annotated version of the synaptic signaling network.
    The primary reference is Bhalla US and Iyengar R. Science (1999) 283(5400):381-7 but several of the model pathways have been updated.
    Bhalla US Biophys J. 2002 Aug;83(2):740-52
    Bhalla US J Comput Neurosci. 2002 Jul-Aug;13(1):49-62

    inact-GEF acting as a Molecule in  
    Synaptic_Network Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    inact-GEF
  • Synaptic_
    Network

    Accession No. : 16
  • Ras
    Pathway No. : 76
    0.11000No
    This is the amount of inactive GEF available to the system. The value is the same as the estimated amount of SoS, though I treat it here as a different pool. Probably several molecules can function as GEFs and this is a simplification. Orita et al JBC 268(34):25542-25546 Gulbins et al 1994 Mol Cell Biol 14(2):906-913

    inact-GEF acting as a Substrate for an Enzyme in  
    Synaptic_Network Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1PKC-active  /
    PKC-act-GEF
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 3.3333344explicit E-S complexSubstrate
    inact-GEF

    Product
    GEF*
        Rate constants are generic PKC rates. See Chen et al 1993 Biochem 32:1032 This reaction activates GEF. Gives >= 2X stim of ras, and a 2X stim of MAPK over amount from direct phosph of c-raf. Note that it is a push-pull reaction, and also get effect through phosph and inact of GAPs.
    2PKA-active  /
    PKA-phosph-GEF
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 7.594explicit E-S complexSubstrate
    inact-GEF

    Product
    inact-GEF*
        This pathway inhibits Ras when cAMP is elevated. See: Hordijk et al JBC 269:5 3534-3538 1994 Burgering et al EMBO J 12:11 4211-4220 1993 The rates are the same as used in PKA-phosph-I1

    inact-GEF acting as a Substrate in a reaction in  
    Synaptic_Network Network
    Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reaction are not consider.
     NameAccession NamePathway NameKfKbKdtauReagents
    1bg-act-GEF
  • Synaptic_
    Network

    Accession No. : 16
  • Ras
    Pathway No. : 76
    6
    (uM^-1 s^-1)
    1
    (s^-1)
    Kd(bf) = 0.1667(uM)-Substrate
    BetaGamma
    inact-GEF

    Product
    GEF-Gprot-bg
      SoS/GEF is present at 50 nM ie 3e4/cell. BetaGamma maxes out at 9e4. Assume we have 1/3 of the GEF active when the BetaGamma is 1.5e4. so 1e4 * kb = 2e4 * 1.5e4 * kf, so kf/kb = 3e-5. The rate of this equil should be reasonably fast, say 1/sec
    2CaM-bind-GEF
  • Synaptic_
    Network

    Accession No. : 16
  • Ras
    Pathway No. : 76
    60
    (uM^-1 s^-1)
    1
    (s^-1)
    Kd(bf) = 0.0167(uM)-Substrate
    CaM-Ca4
    inact-GEF

    Product
    CaM-GEF
      We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995

    inact-GEF acting as a Product in a reaction in  
    Synaptic_Network Network
    Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reaction are not consider.
     NameAccession NamePathway NameKfKbKdtauReagents
    1dephosph-GEF
  • Synaptic_
    Network

    Accession No. : 16
  • Ras
    Pathway No. : 76
    1
    (s^-1)
    0
    (s^-1)
    --Substrate
    GEF*

    Product
    inact-GEF
      This rate is based on the known ratio of GDP-Ras to GTP-Ras. Basal: Ras.GTP = 7% Stimulated 15% Time course is within 10 min, probably much faster as not all early data points are there. See Gibbs et al JBC 265(33):20437-20422
    2
  • dephosph-inact-G
    EF*
  • Synaptic_
    Network

    Accession No. : 16
  • Ras
    Pathway No. : 76
    1
    (s^-1)
    0
    (s^-1)
    --Substrate
    inact-GEF*

    Product
    inact-GEF



    Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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