Subfamily-specific assembly into functional Kv channels. (A) Each subfamily is represented in a different color, with the lighter and darker shades representing a different subunit within the same subfamily. The Kv1–Kv4 subunits form functional homo- and heterotetrameric channels within their own subfamilies. Members of the electrically silent Kv subfamilies (Kv5, Kv6, Kv8, and Kv9) do not form functional homotetramers but heterotetramerize with Kv2 subunits to form functional channels. (B) Subfamily-specific Kv2/KvS assembly is determined by interactions (represented in green) that involve both the N and C termini: an interaction between the Kv2 and KvS N terminus and an interaction between the C terminus of the KvS subunits and the N terminus of the Kv2 subunits. For clarity, both possible Kv2/KvS stoichiometries (2:2 and 3:1) are shown. (C) Kv2/KvS heterotetramerization can cause a shift in the voltage dependence of Kv2 activation and inactivation. (D) KvS subunits (partially) modulate the biophysical Kv2 properties by changing the gating mechanism. This figure is adapted from Fig. 3 in Bocksteins and Snyders (2012) and Fig. 5 in Bocksteins et al. (2014).