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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 |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | Ajay_Bhalla_
2004_Feedback_
Tuning | 78 | Network |
Shared_Object_Ajay_Bhalla_2004_Feedback_Tuning, PKC, PLA2,
PLCbeta, Gq, MAPK,
Ras, EGFR, Sos,
PLC_g, CaMKII, CaM,
PP1, PP2B, PKA,
AC | | This model is taken from Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedback model from Figure 8a. |
craf-1* acting as a Molecule in Ajay_Bhalla_2004_Feedback_Tuning Network
craf-1* acting as a Substrate for an Enzyme in Ajay_Bhalla_2004_Feedback_Tuning Network
craf-1* acting as a Product of an Enzyme in Ajay_Bhalla_2004_Feedback_Tuning Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | PKC-active /
PKC-act-raf | Ajay_Bhalla_
2004_Feedback_
Tuning
Accession No. : 78 | Shared_Object_
Ajay_Bhalla_
2004_Feedback_
Tuning
Pathway No. : 347 | 66.6673 | 4 | 4 | explicit E-S complex | Substrate
craf-1
Product
craf-1*
| | | Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC | | 2 | PPhosphatase2A /
craf**-deph | Ajay_Bhalla_
2004_Feedback_
Tuning
Accession No. : 78 | Shared_Object_
Ajay_Bhalla_
2004_Feedback_
Tuning
Pathway No. : 347 | 15.6568 | 6 | 4 | explicit E-S complex | Substrate
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 not known to me, but it may be PP2A like the rest, so I have made it so. |
craf-1* acting as a Substrate in a reaction in Ajay_Bhalla_2004_Feedback_Tuning 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. |
| Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | Ras-act-craf | Ajay_Bhalla_
2004_Feedback_
Tuning
Accession No. : 78 | Shared_Object_
Ajay_Bhalla_
2004_Feedback_
Tuning
Pathway No. : 347 | 9.9999
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.05(uM) | - | Substrate
GTP-Ras
craf-1*
Product
Raf*-GTP-Ras
| | Assume the binding is fast and limited only by the amount of Ras* available. 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 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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