Putative PP1-binding motifs within NCX1. Topology model of Na+/Ca2+ exchanger 1 (NCX1) consisting of 10 transmembrane domains (TMs) and a large cytosolic loop between TM5 and TM6 (11, 12) is shown. Within the TMs are two α repeats (α1 and α2) that face opposite sides of the membrane and catalyze ion translocation (36) (TMs involved in ion translocation are shown in black). The cytosolic loop mediates regulation of the exchanger and contains the two Ca2+-binding domains (CBD1 and CBD2). In silico screening of human, rat, and mouse NCX1 primary sequences identified three putative PP1-binding motifs. The first site, RVFF, is localized within the membrane loop connecting TM3 and -4. The second site, KIFF/KVFF (human and mouse/rat), is localized in CBD1, and the third site, KVLF, is localized at the end of the intracellular loop.