Pathways & interactions
Potassium channel, voltage-dependent, ERG (IPR003967)
Short name: K_chnl_volt-dep_ERG
- Potassium channel, voltage-dependent, EAG/ELK/ERG (IPR003938)
- Potassium channel, voltage-dependent, ERG (IPR003967)
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.
The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [PMID: 10798390].
The human ether-a-go-go-related gene (HERG), cloned from hippocampus, shares 49% amino acid identity with EAG. It is also found in the heart, where it helps to control K+ efflux [PMID: 7604285]. Mutations in HERG result in the disruption of the repolarising current and the disease LQT2 syndrome, an inherited disorder of cardiac repolarisation that predisposes affected individuals to life-threatening arrhythmias [PMID: 10187793].
- PR01470 (ERGCHANNEL)