Fig. 4.
NaV1.2 and ENaC have similar regulatory elements suggestive of convergent evolution. β and γ ENaC and NaV1.2 do not share an evolutionary history; however, they share some regulatory motifs, including PY motifs (PXXY) which are required for binding of the E3 ubiqutin ligase NEDD4-2, as well as MAPK1/2-mediated phosphorylation sites (β ENaC T613), and a motif with similarity to the canonical ankyrin G binding motif, (V/A)P(I/L)AXXE(S/D)D. Both ENaC and NaV1.2 are phosphorylated by CK2 at a serine which is the penultimate residue in this putative ankyrin biding sequence.