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Molecule Parameter List for craf-1*

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
craf-1* participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1002210

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

    craf-1* acting as a Molecule in  
    Synaptic_Network Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    craf-1*
  • Synaptic_
    Network

    Accession No. : 16
  • MAPK
    Pathway No. : 75
    01000No
    Singly phosphorylated form of c-raf-1. This is the form that gets best activated by GTP.Ras.

    craf-1* acting as a Substrate for an Enzyme in  
    Synaptic_Network Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1MAPK*  /
    MAPK*-feedback
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 25.641104explicit E-S complexSubstrate
    craf-1*

    Product
    craf-1**
        Ueki et al JBC 269(22):15756-15761 show the presence of this step, but not the rate consts, which are derived from Sanghera et al JBC 265(1):52-57, 1990, see the deriv in the MAPK* notes.
    2PPhosphatase2A  /
    craf-deph
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 15.656664.16667explicit E-S complexSubstrate
    craf-1*

    Product
    craf-1
        See parent PPhosphatase2A for parms

    craf-1* acting as a Product of an Enzyme in  
    Synaptic_Network Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1PKC-active  /
    PKC-act-raf
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 66.666744explicit E-S complexSubstrate
    craf-1

    Product
    craf-1*
        Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = 4 Km for this substrate is trickier. Specific substrates are in the uM range, so we use a higher Km here. This may be too conservative in which case PKC would have a still higher effect on raf. The presence of this phosphorylation and activation step is from Kolch et al 1993 Nature 364:249
    2PPhosphatase2A  /
    craf**-deph
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 15.656664.16667explicit E-S complexSubstrate
    craf-1**

    Product
    craf-1*
        Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is assumed to be PP2A.

    craf-1* 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
    Ras-act-craf
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 24
    (uM^-1 s^-1)
    0.5
    (s^-1)
    Kd(bf) = 0.0208(uM)-Substrate
    GTP-Ras
    craf-1*

    Product
    Raf-GTP-Ras*
    Assume binding is fast and limited only by available Ras*. So kf = kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to about 1e-4, giving a Kf of 60 for Kb of 0.5 and a tau of approx 2 sec. Based on: Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414. Also see Koide et al 1993 PNAS USA 90(18):8683-8686



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