| Structural highlights
Function
KCC2D_CAEEL Acts in the signaling of a variety of pathways and processes. Phosphorylates 'Ser-319' of daf-16 in response to stress signals, such as heat, starvation and oxidation, which plays a role in prolonging lifespan. Required for viability under chronic osmotic stress in which it acts downstream of osr-1. Has roles in locomotion, oocyte maturation, brood size, egg laying, defecation, meiotic maturation and neuronal cell fate specification. Required for the regulation of synaptic density and neuromuscular junction morphology. Regulates the synaptic trafficking of glr-1. Bidirectional modulator of neurotransmitter release with negative modulatory effects mainly mediated via slo-1 activation. Involved in activation of ADF neurons and increased tph-1 transcription following exposure to pathogenic bacteria which leads to learned olfactory aversion to the bacteria. Implicated in the muscle regulation of spicule protraction. In conjunction with egl-2 has a role in the suppression of mating behavior under food deprivation to encourage foraging. Involved in restricting str-2 expression to only one of the two AWC neurons. May suppress the functional response to an internal pacemaker, perhaps by modulating the activity of the IP3 receptor.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ca2+/calmodulin-dependent protein kinase-II (CaMKII) is unique among protein kinases for its dodecameric assembly and its complex response to Ca2+. The crystal structure of the autoinhibited kinase domain of CaMKII, determined at 1.8 A resolution, reveals an unexpected dimeric organization in which the calmodulin-responsive regulatory segments form a coiled-coil strut that blocks peptide and ATP binding to the otherwise intrinsically active kinase domains. A threonine residue in the regulatory segment, which when phosphorylated renders CaMKII calmodulin independent, is held apart from the catalytic sites by the organization of the dimer. This ensures a strict Ca2+ dependence for initial activation. The structure of the kinase dimer, when combined with small-angle X-ray scattering data for the holoenzyme, suggests that inactive CaMKII forms tightly packed autoinhibited assemblies that convert upon activation into clusters of loosely tethered and independent kinase domains.
Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme.,Rosenberg OS, Deindl S, Sung RJ, Nairn AC, Kuriyan J Cell. 2005 Dec 2;123(5):849-60. PMID:16325579[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Troemel ER, Sagasti A, Bargmann CI. Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans. Cell. 1999 Nov 12;99(4):387-98. PMID:10571181
- ↑ Bandyopadhyay J, Lee J, Lee J, Lee JI, Yu JR, Jee C, Cho JH, Jung S, Lee MH, Zannoni S, Singson A, Kim DH, Koo HS, Ahnn J. Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is involved in movement, fertility, egg laying, and growth in Caenorhabditis elegans. Mol Biol Cell. 2002 Sep;13(9):3281-93. PMID:12221132 doi:http://dx.doi.org/10.1091/mbc.E02-01-0005
- ↑ Solomon A, Bandhakavi S, Jabbar S, Shah R, Beitel GJ, Morimoto RI. Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to hyperosmotic environments. Genetics. 2004 May;167(1):161-70. PMID:15166144
- ↑ Umemura T, Rapp P, Rongo C. The role of regulatory domain interactions in UNC-43 CaMKII localization and trafficking. J Cell Sci. 2005 Aug 1;118(Pt 15):3327-38. PMID:16079277 doi:10.1242/jcs.02457
- ↑ Corrigan C, Subramanian R, Miller MA. Eph and NMDA receptors control Ca2+/calmodulin-dependent protein kinase II activation during C. elegans oocyte meiotic maturation. Development. 2005 Dec;132(23):5225-37. Epub 2005 Nov 2. PMID:16267094 doi:http://dx.doi.org/10.1242/dev.02083
- ↑ Liu Q, Chen B, Ge Q, Wang ZW. Presynaptic Ca2+/calmodulin-dependent protein kinase II modulates neurotransmitter release by activating BK channels at Caenorhabditis elegans neuromuscular junction. J Neurosci. 2007 Sep 26;27(39):10404-13. PMID:17898212 doi:10.1523/JNEUROSCI.5634-06.2007
- ↑ LeBoeuf B, Gruninger TR, Garcia LR. Food deprivation attenuates seizures through CaMKII and EAG K+ channels. PLoS Genet. 2007 Sep;3(9):1622-32. Epub 2007 Jul 30. PMID:17941711 doi:http://dx.doi.org/10.1371/journal.pgen.0030156
- ↑ Nehrke K, Denton J, Mowrey W. Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate execution of a rhythmic motor program. Am J Physiol Cell Physiol. 2008 Jan;294(1):C333-44. Epub 2007 Oct 17. PMID:17942636 doi:10.1152/ajpcell.00303.2007
- ↑ LeBoeuf B, Guo X, Garcia LR. The effects of transient starvation persist through direct interactions between CaMKII and ether-a-go-go K+ channels in C. elegans males. Neuroscience. 2011 Feb 23;175:1-17. doi: 10.1016/j.neuroscience.2010.12.002. Epub, 2010 Dec 9. PMID:21145946 doi:http://dx.doi.org/10.1016/j.neuroscience.2010.12.002
- ↑ Chang C, Hsieh YW, Lesch BJ, Bargmann CI, Chuang CF. Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans. Development. 2011 Aug;138(16):3509-18. doi: 10.1242/dev.069740. Epub 2011 Jul 19. PMID:21771813 doi:http://dx.doi.org/10.1242/dev.069740
- ↑ Wani KA, Catanese M, Normantowicz R, Herd M, Maher KN, Chase DL. D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16 and the R7 binding protein RSBP-1 in Caenoerhabditis elegans motor neurons. PLoS One. 2012;7(5):e37831. doi: 10.1371/journal.pone.0037831. Epub 2012 May 21. PMID:22629462 doi:http://dx.doi.org/10.1371/journal.pone.0037831
- ↑ Qin Y, Zhang X, Zhang Y. A neuronal signaling pathway of CaMKII and Gqalpha regulates experience-dependent transcription of tph-1. J Neurosci. 2013 Jan 16;33(3):925-35. doi: 10.1523/JNEUROSCI.2355-12.2013. PMID:23325232 doi:http://dx.doi.org/10.1523/JNEUROSCI.2355-12.2013
- ↑ Caylor RC, Jin Y, Ackley BD. The Caenorhabditis elegans voltage-gated calcium channel subunits UNC-2 and UNC-36 and the calcium-dependent kinase UNC-43/CaMKII regulate neuromuscular junction morphology. Neural Dev. 2013 May 10;8:10. doi: 10.1186/1749-8104-8-10. PMID:23663262 doi:http://dx.doi.org/10.1186/1749-8104-8-10
- ↑ Tao L, Xie Q, Ding YH, Li ST, Peng S, Zhang YP, Tan D, Yuan Z, Dong MQ. CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16. Elife. 2013 Jun 25;2:e00518. doi: 10.7554/eLife.00518. PMID:23805378 doi:http://dx.doi.org/10.7554/eLife.00518
- ↑ Rosenberg OS, Deindl S, Sung RJ, Nairn AC, Kuriyan J. Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme. Cell. 2005 Dec 2;123(5):849-60. PMID:16325579 doi:10.1016/j.cell.2005.10.029
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