Calmodulin (CaM) is the most important calcium-binding protein, which is related to calretinin and calbindin. Calmodulin belongs to the group of so-called EF-Hand proteins (Note: EF-Hand is the structure of the calcium-binding region that forms a typical helix-loop-helix structure: see also Calretinin).
In the resting state only little Ca2+ is bound to calmodulin; the Ca2+ concentration in the cytosol is very low. If the Ca2+ concentration increases, the 4 binding sites of calmodulin are occupied and the so-called Ca2+/calmodulin complex (CaM) is increasingly bound. This complex can activate a multitude of enzymes, receptors and ion channels. These include: phospholipase A2, phosphodiesterase, adenylate cyclase, guanylate cyclase, Ca-Mg-ATPase, calcineurin, and protein kinases. In humans, calmodulin is found bound to actin in the smooth muscle where it regulates contraction.
In the brain, in which CaM-kinase II is very strongly enriched, calmodulin plays an important role as regulator of CaM-kinase II.