Many β-subunits of voltage-gated K⁺ channels (VIC superfamily, TC #1.A.1.2.1-3) have been sequenced and functionally characterized. The one from rat has been crystallized, and a 2.1 Å resolution structure is available (Gulbis, 2000). The mammalian β-subunits are 350-410 residues in length. They exhibit extensive sequence similarity with many ubiquitous oxidoreductases, with bacterial stress response proteins and with plant auxin-induced proteins. These β-subunits are to some extent interchangeable, and a variety of alternative splice variants are found. They regulate various aspects of the voltage-gated mammalian channels as well as the Drosophila Shaker K⁺ channel. Thus they affect the voltage-dependence of the activation process, the rate of deactivation and both N-type and C-type inactivation. The conserved C-terminal domain of the β-subunit interacts with the conserved N-terminal hydrophilic domain of the Shaker α-subunit, the same region that determines the compatibility of α-subunits. The hyperkinetic gene of Drosophila encodes a β-subunit of 546 amino acyl residues that when defective produces the Shaker-like, ether-sensitive leg shaking.

Regulatory β-subunits of other channel proteins of the VIC superfamily (TC #1.A.1) function in distinct regulatory capacities, and some are non-homologous to members of the Kvβ family.