8.A.10.3.1
KCNE3 (β-subunit) constitutively opens outwardly rectifying KCNQ1 (Kv7.1) K⁺ channels by abolishing their voltage-dependent gating. KCNQ1/KCNE3 heteromers are present in basolateral membranes of intestinal and tracheal epithelial cells where they may facilitate transepithelial Cl^- secretion (Preston et al., 2010).  Mutations cause Meniere's disease and tinnitus.  KCNE3 regulates Kv4.2 in spiral gangion neurons (Wang et al. 2014) and other voltage-gated ion channels (Kroncke et al. 2016). KCNE3 induces the constitutive activation of KCNQ1 in a process involving interactions in both sides of the membrane (Kroncke et al. 2016). The human ortholog (KCNE3; Q9Y6H6) is 93% identical to the mouse protein. The TMS of KCNE3 is less flexible and more stable than its N- and C-termini in different membrane environments. The conformational flexibility of N- and C-termini varies across the lipid environment. The TMS of KCNE3 spans the membrane width, having residue A69 close to the center of the lipid bilayer, and residues S57 and S82 close to the lipid bilayer membrane surfaces (Asare et al. 2022). This mouse protein is 93% identical to the human ortholog (Q9Y6H6).