calmoduliiniin

Calmodulin is a small, highly conserved calcium-binding messenger protein that coordinates a wide range of intracellular signaling pathways in eukaryotic cells. In humans, it consists of about 149 amino acids and forms two globular domains connected by a flexible central linker. Each globular domain contains two EF-hand motifs, giving a total of four calcium-binding sites. When calcium levels rise, Ca2+ binds to these sites and induces a conformational change that exposes hydrophobic surfaces, enabling calmodulin to interact with a broad set of target proteins.

As a universal intracellular calcium sensor and signal transducer, calmodulin regulates the activity and localization of numerous enzymes and other proteins. Key targets include calcium/calmodulin-dependent kinases (such as CaMKII), the phosphatase calcineurin, myosin light-chain kinase (MLCK), and various phosphodiesterases and ion channels. Through these interactions, calmodulin influences processes such as muscle contraction, neurotransmitter release, metabolism, secretion, and gene expression. Target recognition typically depends on calcium-bound calmodulin binding to specific sequences or motifs within the partner proteins.

Genetics and evolution: The human genome contains three CALM genes (CALM1, CALM2, CALM3) that encode highly similar calmodulin proteins, underscoring the essential nature of its function. Calmodulin is one of the most highly conserved proteins across eukaryotes, from yeast to humans.

Clinical relevance: Mutations in CALM genes have been linked to congenital arrhythmias, including forms of long QT syndrome, highlighting the critical role of proper calmodulin signaling in cardiac electrical activity.