Ca2Calmodulin

Ca2+/calmodulin (Ca2+/CaM) is the calcium-bound form of calmodulin, a ubiquitous intracellular calcium sensor and signal transducer. Calmodulin is a small, acidic protein (~17 kDa); in humans, the CALM1, CALM2, and CALM3 genes encode nearly identical proteins. The molecule has two globular domains, each containing two EF-hand calcium-binding motifs, connected by a flexible central linker.

When Ca2+ binds, conformational changes reveal hydrophobic surfaces, enabling interactions with diverse targets. A single calmodulin can bind up to four Ca2+ ions, with binding governed by calcium concentration and target presence.

Ca2+/CaM modulates many enzymes and signaling proteins, notably calcium/calmodulin-dependent protein kinases (CaMKs), calcineurin, and various nitric oxide synthases; it also regulates some adenylyl cyclases and myosin light-chain kinases. In neurons, Ca2+/CaM links calcium signals to synaptic plasticity via CaMKII and related effectors.

Physiological role: Ca2+/CaM acts as a versatile network hub; its activity is primarily controlled by calcium fluctuations and subcellular localization. Malfunction or dysregulation of Ca2+/CaM signaling has been implicated in diverse processes and diseases. The term Ca2-calmodulin is sometimes used to denote the calcium-saturated form of calmodulin.