The two small and similar viral K+ channels Kcv and Kesv are sorted in mammalian cells and yeast to different
destinations. Analysis of the sorting pathways shows that Kcv is trafficking via the secretory pathway
to the plasma membrane, while Kesv is inserted via the TIM/TOM complex to the inner membrane of
mitochondria. Studies with Kesv mutants show that an N-terminal mitochondrial targeting sequence in
this channel is neither necessary nor sufficient for sorting of Kesv the mitochondria. Instead the sorting
of Kesv can be redirected from the mitochondria to the plasma membrane by an insertion of
≥2 amino
acids in a position sensitive manner into the C-terminal transmembrane domain (TMD2) of this channel.
The available data advocate the presence of a C-terminal sorting signal in TMD2 of Kesv channel, which
is presumably not determined by the length of this domain.