KCNE3
Description
The KCNE3 (potassium voltage-gated channel subfamily E regulatory subunit 3) is a protein-coding gene located on chromosome 11.
KCNE3, also known as MinK-related peptide 2 (MiRP2), is a protein encoded by the KCNE3 gene in humans. It is a member of the KCNE family of voltage-gated potassium (Kv) channel ancillary or β subunits. KCNE3 primarily regulates the KCNQ1 Kv α subunit but also interacts with hERG, Kv2.1, Kv3.x, Kv4.x, and Kv12.2 in various experiments. By combining with KCNE3, KCNQ1 transitions from a voltage-dependent delayed rectifier K+ channel to a constitutively open K+ channel with a nearly linear current/voltage (I/V) relationship. KCNQ1-KCNE3 channels are found in the basolateral membrane of mouse small intestinal crypts, regulating Cl- secretion. Specific amino acids within KCNE3, including V72, D54, and D55, control its influence on KCNQ1 voltage dependence. D54 and D55 interact with R237 in the S4 segment of the KCNQ1 voltage sensor, stabilizing the activated state of S4, which keeps the channel open unless the cell is under strongly hyperpolarizing (negative) membrane potential. The ability of KCNQ1-KCNE3 channels to remain open at weakly negative membrane potentials allows them to function in non-excitable, polarized epithelial cells like those in the intestine.
KCNE3 is an ancillary protein that forms a beta subunit with voltage-gated potassium channel complexes composed of pore-forming alpha subunits. It regulates the gating kinetics and improves the stability of these channel complexes. When paired with KCNB1, KCNE3 modifies the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Its association with KCNC4/Kv3.4 is believed to form the subthreshold voltage-gated potassium channel in skeletal muscle, playing a role in establishing the resting membrane potential (RMP) in these cells. Additionally, KCNE3's association with KCNQ1/KCLQT1 might form the intestinal cAMP-stimulated potassium channel involved in chloride secretion. This channel exhibits nearly instantaneous activation with a linear current-voltage relationship.
KCNE3 is also known as BRGDA6, HOKPP, HYPP, MiRP2.
