CALM1/A0008

Calmodulin-1 (CALM1), also known as A0008, is extensively conserved in evolution and appears to play an important part in mechanisms underlying calcium signaling.

Calmodulin-1 (CALM1), also known as A0008, is extensively conserved in evolution and appears to play an important part in mechanisms underlying calcium signaling. The gene encoding CALM1 is located on chromosome four and is made up of six exons. The protein itself is composed of 149 amino acids and possesses four calcium-binding domains, all of which appear to be pertinent to the efficacy of signal transduction. Methionine 124, within the C-terminal and the N-terminal hydrophilic amino acids, appears to be important for its function. Many proteins have CALM1 binding sites, such as K-Ras and Munc-13. Calmodulin-mediated signaling mechanisms have been conserved across species in evolution, showing that it is universally fundamental to life. Munc-13 has a very conserved calmodulin-binding domain, which appears to be essential for the regulation of synaptic vesicle priming and synaptic efficiency. Calmodulin has also been implicated in the localization of K-Ras to the cytosol for K-Ras mutants (serine 181 to Asparagine, which mimics serine 81 phosphorylation) designed to possess little to no calmodulin affinity. Farensylation of K-Ras appears to be essential for calmodulin binding but this interaction is not essential for localization of the former to the plasma membrane and calmodulin may make this process even more efficient. Drosophila melanogaster mutants, hemizygous for the first calcium-binding site in CALM1 showed defects in locomotion, coordination and flight. The defect in calcium ion binding is linked to pronounced effects at the behavioral and physiological levels. There is ongoing research into what interactions are performed by CALM1, particularly with calmodulin-2 and -3, why there are three isoforms in eukaryotic species.