Calmodulin (CaM) (CaM)

Calmodulin (CaM) is a ubiquitous, highly conserved calcium-binding messenger protein that serves as a primary sensor of intracellular calcium levels in eukaryotic cells [3, 12]. Upon binding calcium ions, CaM undergoes a conformational change that allows it to interact with and regulate a wide array of target proteins, including kinases such as CaMKII and CaMKK, phosphatases like calcineurin, and various ion channels [3, 6, 14]. This signaling network, often referred to as Calmodulin-dependent signaling, is critical for diverse physiological processes including muscle contraction, synaptic plasticity, cell cycle progression, and inflammation [3, 18, 20]. Dysregulation of this pathway is implicated in various pathologies, notably cardiac arrhythmias and heart failure due to aberrant CaMKII activity, as well as several types of cancer where CaM-dependent kinases promote cell proliferation and survival [1, 5, 9, 13]. Pharmacological modulation has been explored using CaM antagonists like trifluoperazine and specific kinase inhibitors like KN-93, though the ubiquity of CaM presents significant challenges for achieving therapeutic selectivity and minimizing off-target effects [1, 12, 17]. In the heart, CaM-dependent signaling regulates excitation-contraction coupling, and its overactivation is a hallmark of maladaptive remodeling [5, 15, 19]. In the brain, it is essential for long-term potentiation and memory formation, making it a sensitive target for neurological side effects [3, 8, 14].

Other names

Calcium-modulated proteinCALM1CALM2CALM3Calmodulin-1Calmodulin-2Calmodulin-3Calmodulin-dependent signaling

Calmodulin inhibition, CaMKII inhibition, and calcium-dependent binding to target proteins.