CALMLs

CALMLs, short for calmodulin-like proteins, constitute a family of calcium-binding proteins related to calmodulin. Like calmodulin, they contain EF-hand motifs that coordinately bind calcium ions and undergo conformational changes that enable interaction with target proteins. CALMLs are found across eukaryotes and are typically smaller, with sequence divergence that modulates calcium affinity and partner selectivity.

Structure and biophysics: Most CALMLs preserve the four EF-hand motifs characteristic of calmodulin, arranged in two globular domains. Some family members carry degenerate EF-hands or additional sequence extensions that influence calcium binding kinetics and localization. Calcium binding triggers exposure of hydrophobic surfaces that recruit interactors such as kinases, phosphatases, ion channels, and cytoskeletal regulators.

Function and localization: CALMLs function as calcium sensors and adaptors that translate fluctuations in intracellular Ca2+ into precise cellular responses. They can regulate enzymes and channels directly or serve as scaffolds that assemble signaling complexes. Subcellular distribution ranges from cytosol to nucleus, depending on family member and cellular context, and can be influenced by post-translational modifications or interacting partners.

Genomics and evolution: The CALML gene family is represented in many animal genomes and shows examples of gene duplication and divergence. In vertebrates, multiple CALML genes exist, often with tissue-preferential expression patterns, suggesting specialization of function while maintaining core calcium-binding capability.

Clinical and research notes: CALML family members are subjects of ongoing research to understand their specific roles in signaling networks, development, and disease. While they share heritage with calmodulin, their distinct binding partners and expression patterns mean they may have unique contributions in particular tissues.