Evolutionary aspects of calmodulin

Calmodulin (CaM) is a major cellular sensor of calcium signaling, interacts with numerous proteins associated with cellular second messenger systems ( e.g., cyclic AMP, nitric oxide), and is associated with neurosecretory acti vity. An identical CaM protein consisting of four helix-loop-helix regions that arose by gene duplication is encoded by three nonallelic mammalian gen es that are some of the most highly conserved genes known. Differential tis sue and cellular expression of each CaM suggest unique functions that promo te strong selective preservation of these replicate, yet distinct, CaM gene s in mammals. Each gene displays the same exon-intron arrangement but is ch aracterized by distinct promoter elements and by unique 5'- and 3'-untransl ated regions that are highly conserved among human, rat, and mouse. These d istinct untranslated regions may permit regulation of CaM levels at discret e cellular sites during differentiation and in highly specialized cell type s such as neurons.