Calmodulin- a multigene family promoting multitudes of cellular activities

Calmodulin- a multigene family promoting multitudes of cellular activities

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The importance of calcium as a second messenger probably can’t be emphasized enough. Ca2+-signalling through Ca2+-sensors such as calmodulin regulates a variety of vital functions in cells in response to stimuli. Calmodulin is a small evolutionally conserved Ca2+-binding pro-tein of the EF-hand superfamily that participates in many different cellular pathways through regulation of a diverse group of targets. Its function has shown to depend hugely on the way it is distributed throughout the cell and pools probably allow for CaM to be activated at the right time and place.

Gene organization and evolutionary history
The three genes encoding human Calmodulin, CALM 1-3, are non-allelic and thus localized on different chromosomes, 14q24-q31, 2p21.1-p21.3 and 19q13.2-q13.3 respectively [1]. These CaM-genes show identical intron-exon boundaries, consist of six exons and code for an identi-cal monomeric CaM-protein of 148 amino acids (fig. 1), but transcribes to at least 7 different major mRNAs differentiating relative to alternative polyadenylation among transcripts of each gene [2]. In addition to the three known CALM-genes the human family of CaM/CaM-like genes holds numerous pseudogenes and calmodulin-like proteins [1].

CaM is a highly evolutionally conserved protein found in all eukaryotic cells (fig. 2). Since CaM belongs to the superfamily of EF-hand proteins (fig. 1) its main structure originated before the branching into plants, fungi, invertebrates and vertebrates. It’s probable that this happened as two gene duplications followed by fusion led to the joining of four EF-hands into one struc-ture. Further modifications that account for the invariant CaM in vertebrates [2] and later the three bona fide CaM-genes of mamma...

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...n of Long-Term Potentiation
[12]Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique
[13] Novel aspects of calmodulin target recognition and activation
[14] Solution NMR Structure of Apo-Calmodulin in Complex with the IQ Motif of Human Car-diac Sodium Channel NaV1.5
[15]Modulation of Calmodulin Plasticity in Molecular Recognitionon the Basis of X-ray Struc-ture
[16] Structural Basis for Calmodulin as a Dynamic Calcium Sensor
[17] Tyrosine phosphorylation modulates the interaction of calmodulin with its target pro-teins
[18] Berchtold, M. W. and Villalobo, A. (2013): The many faces of calmodulin in cell prolifera-tion, programmed cell death, autophagy, and cancer
[19] The alterations of Ca2+/calmodulin/CaMKII/CaV1.2 signaling in experimental models of Alzheimer's disease and vascular dementia

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