Calcium binding proteins are subdivided into two major families: the EF-family and the Annexin family. The EF-hand family is distinguished by the characteristic helix-loop-helix motif which consists of two alpha-helices separated by a loop. The EF-hand Ca2+(-)binding protein family contain subfamilies rich in proline, glutamic acid, serine and threonine residues (called PEST sequences) and non PEST-containing subfamilies. A few of the Ca2+(-)binding proteins contain KFERQ-like sequences which are thought to be possible signals for lysosomal degradation. Arginine pairs (RR) which have also been suggested to act as signals for proteolysis were found to be few or absent. However, most EF-hand proteins were found to possess lysine pairs (KK) which may also act as signals for proteolysis.