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Molecule Parameter List for CaMKII

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

*CaMKII* participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	1	0	0	0	2	2	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
MAPK_network_ 2003	50	Network	Shared_Object_MAPK_network_2003, PKC, PLA2, PLCbeta, Gq, MAPK, Ras, EGFR, Sos, PLC_g, CaMKII, CaM, PP1, PP2B, PKA, AC
This is a network model of many pathways present at the neuronal synapse. The network has properties of temporal tuning as well as steady-state computational properties. In its default form the network is bistable.Bhalla US Biophys J. 2004 Aug;87(2):745-53

CaMKII acting as a Molecule in MAPK_network_2003 Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
CaMKII	MAPK_network_ 2003 Accession No. : 50	CaMKII Pathway No. : 216	70	1000	No
Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around 2.5% of protein in spine as a whole. This level is so high it is unlikely to matter much if we are off a bit. This comes to about 70 uM.

CaMKII acting as a Product of an Enzyme in MAPK_network_2003 Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PP1-active / Deph-thr306	MAPK_network_ 2003 Accession No. : 50	Shared_Object_ MAPK_network_ 2003 Pathway No. : 206	5.09907	0.35	4	explicit E-S complex	Substrate CaMK-thr306 Product CaMKII
	See Cohen et al
2	PP1-active / Deph_thr286b	MAPK_network_ 2003 Accession No. : 50	Shared_Object_ MAPK_network_ 2003 Pathway No. : 206	5.09907	0.35	4	explicit E-S complex	Substrate CaMKII-thr286 Product CaMKII

CaMKII acting as a Substrate in a reaction in MAPK_network_2003 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
1	CaMKII-bind-CaM	MAPK_network_ 2003 Accession No. : 50	CaMKII Pathway No. : 216	49.9998 (uM^-1 s^-1)	5 (s^-1)	Kd(bf) = 0.1(uM)	-	Substrate CaM-Ca4 CaMKII Product CaMKII-CaM
	This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994) so lets say kb = 10. This gives kf = 1.6667e-4 H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol.
2	basal-activity	MAPK_network_ 2003 Accession No. : 50	CaMKII Pathway No. : 216	0.003 (s^-1)	0 (s^-1)	-	-	Substrate CaMKII Product CaMKII-thr286
	This reaction represents one of the big unknowns in CaMK-II biochemistry: what maintains the basal level of phosphorylation on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992 61:559-601, specially pg 580, for review. I have not been able to find any compelling mechanism in the literature, but fortunately the level of basal activity is well documented.

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