Penta-EF hand, calcium binding motifs, found in Group I PEF proteins
The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.
Comment:Due to the presence of unfavorable residues at the Ca2+-coordinating positions, the EF5 hand of some family members may not be able to bind Ca2+ ion.
Structure:2ZN9; Homo sapiens ALG-2 binds three Ca2+ ions through its EF1, EF3 and EF5 hands.
Structure:1Y1X; Leishmania major Friedlin PDCD6-like protein binds two Ca2+ ions through its EF1 and EF2 hands.
Jiyao W et al.(2023). "The conserved domain database in 2023.",