EF-hand, calcium binding motif, found in calretinin (CR)
CR, also termed 29 kDa calbindin, is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t specific neurons of the central and peripheral nervous system. It possibly functions as a calcium buffer, calcium sensor, and apoptosis regulator, which may be implicated in many biological processes, including cell proliferation, differentiation, and cell death. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. CR I-II consists of EF-hand motifs 1 and 2, and CR III-VI consists of EF-hand motifs 3-6. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. Thus, CR has two pairs of cooperative binding sites (I-II and III-IV), which display high affinity calcium-binding sites, and one independent calcium ion-binding site (V), which displays lower affinity binding.
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:Calretinin binds five Ca2+ ions through its EF-hand motifs 1, 2, 3, 4, and 5. Due to the lack of key residues involved in Ca2+ coordination, the EF-hand motif 6 is a non-canonical, low-affinity Ca2+-binding motif.
Jiyao W et al.(2023). "The conserved domain database in 2023.",