EF-hand, calcium binding motif, found in calbindin (CB)
CB, also termed calbindin D28, or D-28K, or avian-type vitamin D-dependent calcium-binding protein, is a unique intracellular calcium binding protein that functions as both a calcium sensor and buffer in eukaryotic cells, which undergoes a conformational change upon calcium binding and protects cells against insults of high intracellular calcium concentration. CB is highly expressed in brain and sensory neurons. It plays essential roles in neural functioning, altering synaptic interactions in the hippocampus, modulating calcium channel activity, calcium transients, and intrinsic neuronal firing activity. It prevents a neuronal death, as well as maintains and controls calcium homeostasis. CB also modulates the activity of proteins participating in the development of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and bipolar disorder. Moreover, CB interacts with Ran-binding protein M, a protein known to involve in microtubule function. It also interacts with alkaline phosphatase and myo-inositol monophosphatase, as well as caspase 3, an enzyme that plays an important role in the regulation of apoptosis. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity.
Comment:The consensus sequence of the EF-hand calcium-binding loop is D#x#D/N#G#D/S/N#G#x#I/L/V#x#x#x#E/D, where the uppercase letters represent residues that occur with more than 50% frequency and #x# stands in positions with less defined preference.
Comment:Due to the lack of key residues involved in Ca2+ coordination, the EF-hand motifs 2 and 6 are non-canonical, low-affinity Ca2+-binding motifs.
Structure:2G9B; Rattus norvegicus Calbindin D28k binds four Ca2+ ions through its EF-hand motifs 1, 3, 4, and 5.
Jiyao W et al.(2023). "The conserved domain database in 2023.",