Potassium channel, voltage-dependent, beta subunit, KCNE3 (IPR005426)
Short name: K_chnl_volt-dep_bsu_KCNE3
Overlapping homologous superfamilies
- Potassium channel, voltage-dependent, beta subunit, KCNE (IPR000369)
- Potassium channel, voltage-dependent, beta subunit, KCNE3 (IPR005426)
Potassium channels are the most diverse group of the ion channel family [PMID: 1772658, PMID: 1879548]. They are important in shaping the action potential, and in neuronal excitability and plasticity [PMID: 2451788]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [PMID: 2555158]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.
These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers [PMID: 2448635]. In eukaryotic cells, K+ channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [PMID: 1373731]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [PMID: 11178249].
All K+ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+ channels; and three types of calcium (Ca)-activated K+ channels (BK, IK and SK) [PMID: 11178249]. The 2TM domain family comprises inward-rectifying K+ channels. In addition, there are K+ channel alpha-subunits that possess two P-domains. These are usually highly regulated K+ selective leak channels.
Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2).
KCNE3 is known to associate with the pore forming subunits KCNQ1, KCNQ4, HERG and Kv3.4. KCNE3 forms complexes with Kv3.4 in skeletal muscle - KCNE3 mutations have been identified in families with skeletal muscle disorders [PMID: 11207363]. In the intestine, KCNE3 associates with KCNQ1 to form channels that are stimulated by cAMP and are thought to be involved in secretory diarrhoea and cystic fibrosis [PMID: 10646604].