| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
8.A.10.1.1 | Slow voltage-dependent K+ channel auxiliary protein (β-subunit), MinK or K2NE1. KCNQ1-KCNE1 complexes may interact intermittently with the actin cytoskeleton via the C-terminal region (Mashanov et al., 2010; Coey et al., 2011). The transmembrane region and the C-terminal cytoplasmic domains that abuts the KCNE1 TMS both interact with and regulate the KCNQ1 channel (Lvov et al. 2010; Zheng et al. 2010). Mutations in KCNE1 can cause Meniere's disease (Doi et al. 2005). MinK-related peptides, MiRPs, confer changes in Kv channel conductance, gating kinetics and pharmacology, and are fundamental to recapitulation of the properties of some native currents. Inherited mutations in KCNE genes are associated with diseases of cardiac and skeletal muscle as well as the inner ear (McCrossan and Abbott 2004). | Eukaryota |
Metazoa, Chordata | MinK of Rattus norvegicus (130 aas; P15383) |
|
8.A.10.1.2 | Potassium voltage-gated channel Isk-related family member 1, of 129 aas and one TMS, KCNE1 (Sahu et al. 2015). Mutations can give rise to hearing disorders including chronic tinitus (Sand et al. 2010). KCNE proteins modulate both homomeric Kv.2.1 and heteromeric Kv2.1/Kv6.4 channels (David et al. 2015). Slow-activating channel complexes formed by KCNQ1 and KCNE1 are essential for human ventricular myocyte repolarization, while constitutively active KCNQ1-KCNE3 channels are important in the intestine. Inherited sequence variants in human KCNE1 and KCNE3 cause cardiac arrhythmias by different mechanisms (Abbott 2015). KCNE confers pH sensitivity to KCNQ1 (Heitzmann et al. 2007). State-dependent interactions between KCNE1 and KCNQ1 have been demonstrated (Westhoff et al. 2017). KCNE1 and KCNE3 exhibit similar functional properties (Law and Sanders 2019). The proximal C-terminal regions of KCNQ1 and KCNE1 participate in a physical and functional interaction during channel opening that is sensitive to perturbation (Chen et al. 2019). | Eukaryota |
Metazoa, Chordata | KCNE1 of Homo sapiens |
|
8.A.10.2.1 | K+ voltage-gated channel subfamily E member 2 (KCNE2) or minimum K+ channel-related peptide (MinK; MiRP1) (β-subunit) [associates with KCNH2/ERG1 and KCNQ1/KVLQT1 (McCrossan et al. 2009), as well as KCNQ2 and KCNQ3] (Eldstrom and Fedida, 2011; Roepke et al., 2006). Regulated by PKCδ phosphorylation (O'Mahony et al., 2007). A mutation (hERG T473P) in the transmembrane non-pore region causes clinical manifestations of long QT syndrome (Liu et al. 2012). Exhibits an array of functions in the heart, stomach, thyroid and choroid plexus. A variety of interconnected disease manifestations caused by KCNE2 disruption involve both excitable cells such as cardiomyocytes, and non-excitable, polarized epithelia (Abbott 2015). It's secondary structure has been determined (Abbott et al. 2008). Deletion of the Kcne2 structural gene in mice and humans gives rise to impaired insulin secretion as well as type 2 diabetes mellitus (Lee et al. 2017). The KCNE2 beta subunit is required for normal lung function and resilience to ischemia and reperfusion injury (Zhou et al. 2019). | Eukaryota |
Metazoa, Chordata | KCNE2 of Mus musculus (123 aas; Q9D808) |
|
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). | Eukaryota |
Metazoa, Chordata | KCNE3 of Mus musculus (103 aas; AAH04629) |
|
8.A.10.3.2 | Potassium voltage-gated channel subfamily E regulatory subunit 5, KCNE5 of 142 aas and 1 TMS. It is a potassium channel ancillary subunit of that is essential for the generation of some native K+ currents by virtue of the formation of heteromeric ion channel complexes with voltage-gated potassium (Kv) channel pore-forming alpha subunits. It functions as an inhibitory beta-subunit of the repolarizing cardiac potassium ion channel KCNQ1 (Angelo et al. 2002). | Eukaryota |
Metazoa, Chordata | KCNE5 of Homo sapiens |
|
8.A.10.3.3 | KCNE3 or MinK-related peptide 2 of 103 aas with 1 C-terminal TMS. It modulates the gating kinetics and enhances stability of the channel complex. It assembles with KCNB1 and modulates its gating characteristics of the delayed rectifier voltage-dependent response (McCrossan et al. 2003). It can associate with KCNC4/Kv3.4 to form the subthreshold voltage-gated potassium channel in skeletal muscle and establish the resting membrane potential in muscle cells. Its association with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion that produces a current with nearly instantaneous activation with a linear current-voltage relationship (Schroeder et al. 2000). Campbell et al. 2022 provided guidelines for detailed structural studies of KCNE3 in a native membrane environment, comparing lipid bilayer results to the isotropic bicelle structure and to the KCNQ1-bound cryo-EM structure. It has been implicated in autism spectrum disease (Ben-Mahmoud et al. 2024). | Eukaryota |
Metazoa, Chordata | KCNE3B auxilary protein of Homo sapiens |
|
8.A.10.4.1 | MinK-related peptide 3 (MiRK3) or KCNE4 (β-subunit). KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry (Sun et al. 2024). | Eukaryota |
Metazoa, Chordata | MiRP3 or KCNE4 of Mus musculus (170 aas; Q9WTW3) |