1mxe

Structural highlights

Function

[CALM_DROME] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. [KCC1A_RAT] Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-516', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation (By similarity). Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-275' and 'Ser-294'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.^{[1] [2] [3] [4] [5] [6] [7] [8]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Calmodulin 3D structures

References

1. ↑ Sheng M, Thompson MA, Greenberg ME. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991 Jun 7;252(5011):1427-30. PMID:1646483
2. ↑ Sun P, Lou L, Maurer RA. Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV. J Biol Chem. 1996 Feb 9;271(6):3066-73. PMID:8621702
3. ↑ Suizu F, Fukuta Y, Ueda K, Iwasaki T, Tokumitsu H, Hosoya H. Characterization of Ca2+/calmodulin-dependent protein kinase I as a myosin II regulatory light chain kinase in vitro and in vivo. Biochem J. 2002 Oct 15;367(Pt 2):335-45. PMID:12081505 doi:10.1042/BJ20020536
4. ↑ Wayman GA, Kaech S, Grant WF, Davare M, Impey S, Tokumitsu H, Nozaki N, Banker G, Soderling TR. Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I. J Neurosci. 2004 Apr 14;24(15):3786-94. PMID:15084659 doi:10.1523/JNEUROSCI.3294-03.2004
5. ↑ Schmitt JM, Guire ES, Saneyoshi T, Soderling TR. Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase-dependent long-term potentiation. J Neurosci. 2005 Feb 2;25(5):1281-90. PMID:15689566 doi:10.1523/JNEUROSCI.4086-04.2005
6. ↑ Tokumitsu H, Hatano N, Yokokura S, Sueyoshi Y, Nozaki N, Kobayashi R. Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2. FEBS Lett. 2006 Oct 16;580(24):5797-801. Epub 2006 Sep 27. PMID:17022975 doi:10.1016/j.febslet.2006.09.043
7. ↑ Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, Soderling TR. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006 Jun 15;50(6):897-909. PMID:16772171 doi:10.1016/j.neuron.2006.05.008
8. ↑ Davare MA, Saneyoshi T, Soderling TR. Calmodulin-kinases regulate basal and estrogen stimulated medulloblastoma migration via Rac1. J Neurooncol. 2011 Aug;104(1):65-82. doi: 10.1007/s11060-010-0472-6. Epub 2010, Nov 24. PMID:21107644 doi:10.1007/s11060-010-0472-6
9. ↑ Clapperton JA, Martin SR, Smerdon SJ, Gamblin SJ, Bayley PM. Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism. Biochemistry. 2002 Dec 17;41(50):14669-79. PMID:12475216