InterPro domain: IPR003938
General Information
- Identifier IPR003938
- Description Potassium channel, voltage-dependent, EAG/ELK/ERG
- Number of genes 1388
- Gene duplication stats Loading...
- Associated GO terms GO:0006813 GO:0005249 GO:0016020
Abstract
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 [ 1 ].
Potassium channels are the most diverse group of the ion channel family [ 2 , 3 ]. They are important in shaping the action potential, and in neuronal excitability and plasticity [ 4 ]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [ 5 ]: 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 [ 6 ]. 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 [ 7 ]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [ 8 ].
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) [ 9 ]. 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.
1. Ion channels and synaptic organization: analysis of the Drosophila genome. Neuron 26, 35-43
2. The molecular biology of K+ channels. Curr. Opin. Cell Biol. 3, 663-70
3. Shaw-like rat brain potassium channel cDNA's with divergent 3' ends. FEBS Lett. 288, 163-7
4. Cloning of a probable potassium channel gene from mouse brain. Nature 332, 837-9
5. Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J. 8, 3235-44
6. Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila. Nature 331, 137-42
7. Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes. J. Biol. Chem. 267, 8650-7
8. An overview of the potassium channel family. Genome Biol. 1, REVIEWS0004