Potassium channels are the most diverse group of the ion channel family [[cite:PUB00001055], [cite:PUB00001622]]. They are important in shaping the action potential, and in neuronal excitability and plasticity [[cite:PUB00004020]]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [[cite:PUB00006577]]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.
\r\nThese 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 [[cite:PUB00004011]]. 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 [[cite:PUB00002771]]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [[cite:PUB00009378]].
\r\nAll 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) [[cite:PUB00009378]]. 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.
","llm":false,"checked":false,"updated":false},{"text":"The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screening 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 [[cite:PUB00007312]].
","llm":false,"checked":false,"updated":false},{"text":"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 [[cite:PUB00008904]]. 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 [[cite:PUB00008906]].
","llm":false,"checked":false,"updated":false},{"text":"This entry also includes the nematode homologue Potassium voltage-gated channel unc-103 from Caenorhabditis elegans which is involved in the movements of the male's copulatory spicules before and during male mating behaviour [[cite:PUB00155000]].
","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00007312":{"PMID":10798390,"ISBN":null,"volume":"26","issue":"1","year":2000,"title":"Ion channels and synaptic organization: analysis of the Drosophila genome.","URL":null,"raw_pages":"35-43","medline_journal":"Neuron","ISO_journal":"Neuron","authors":["Littleton JT","Ganetzky B."],"DOI_URL":"http://dx.doi.org/10.1016/S0896-6273(00)81135-6"},"PUB00009378":{"PMID":11178249,"ISBN":null,"volume":"1","issue":"4","year":2000,"title":"An overview of the potassium channel family.","URL":null,"raw_pages":"REVIEWS0004","medline_journal":"Genome Biol","ISO_journal":"Genome Biol.","authors":["Miller C."],"DOI_URL":"http://ukpmc.ac.uk/picrender.cgi?tool=EBI&pubmedid=11178249&action=stream&blobtype=pdf"},"PUB00001622":{"PMID":1879548,"ISBN":null,"volume":"288","issue":"1-2","year":1991,"title":"Shaw-like rat brain potassium channel cDNA's with divergent 3' ends.","URL":null,"raw_pages":"163-7","medline_journal":"FEBS Lett","ISO_journal":"FEBS Lett.","authors":["Luneau C","Wiedmann R","Smith JS","Williams JB."],"DOI_URL":"http://dx.doi.org/10.1016/0014-5793(91)81026-5"},"PUB00006577":{"PMID":2555158,"ISBN":null,"volume":"8","issue":"11","year":1989,"title":"Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain.","URL":null,"raw_pages":"3235-44","medline_journal":"EMBO J","ISO_journal":"EMBO J.","authors":["Stuhmer W","Ruppersberg JP","Schroter KH","Sakmann B","Stocker M","Giese KP","Perschke A","Baumann A","Pongs O."],"DOI_URL":"http://ukpmc.ac.uk/articlerender.cgi?tool=EBI&pubmedid=2555158"},"PUB00002771":{"PMID":1373731,"ISBN":null,"volume":"267","issue":"12","year":1992,"title":"Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes.","URL":null,"raw_pages":"8650-7","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Attali B","Romey G","Honore E","Schmid-Alliana A","Mattei MG","Lesage F","Ricard P","Barhanin J","Lazdunski M."],"DOI_URL":"http://intl.jbc.org/cgi/content/abstract/267/12/8650"},"PUB00008906":{"PMID":10187793,"ISBN":null,"volume":"274","issue":"15","year":1999,"title":"Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation.","URL":null,"raw_pages":"10113-8","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Chen J","Zou A","Splawski I","Keating MT","Sanguinetti MC."],"DOI_URL":"http://dx.doi.org/10.1074/jbc.274.15.10113"},"PUB00004020":{"PMID":2451788,"ISBN":null,"volume":"332","issue":"6167","year":1988,"title":"Cloning of a probable potassium channel gene from mouse brain.","URL":null,"raw_pages":"837-9","medline_journal":"Nature","ISO_journal":"Nature","authors":["Tempel BL","Jan YN","Jan LY."],"DOI_URL":"http://dx.doi.org/10.1038/332837a0"},"PUB00004011":{"PMID":2448635,"ISBN":null,"volume":"331","issue":"6152","year":1988,"title":"Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila.","URL":null,"raw_pages":"137-42","medline_journal":"Nature","ISO_journal":"Nature","authors":["Schwarz TL","Tempel BL","Papazian DM","Jan YN","Jan LY."],"DOI_URL":"http://dx.doi.org/10.1038/331137a0"},"PUB00008904":{"PMID":7604285,"ISBN":null,"volume":"269","issue":"5220","year":1995,"title":"HERG, a human inward rectifier in the voltage-gated potassium channel family.","URL":null,"raw_pages":"92-5","medline_journal":"Science","ISO_journal":"Science","authors":["Trudeau MC","Warmke JW","Ganetzky B","Robertson GA."],"DOI_URL":"http://www.sciencemag.org/cgi/content/abstract/269/5220/92"},"PUB00001055":{"PMID":1772658,"ISBN":null,"volume":"3","issue":"4","year":1991,"title":"The molecular biology of K+ channels.","URL":null,"raw_pages":"663-70","medline_journal":"Curr Opin Cell Biol","ISO_journal":"Curr. Opin. Cell Biol.","authors":["Perney TM","Kaczmarek LK."],"DOI_URL":"http://dx.doi.org/10.1016/0955-0674(91)90039-2"},"PUB00155000":{"PMID":12684455,"ISBN":null,"volume":"23","issue":"7","year":2003,"title":"Caenorhabditis elegans UNC-103 ERG-like potassium channel regulates contractile behaviors of sex muscles in males before and during mating.","URL":null,"raw_pages":"2696-705","medline_journal":"J Neurosci","ISO_journal":"J Neurosci","authors":["Garcia LR","Sternberg PW."],"DOI_URL":null}},"set_info":null,"overlaps_with":[{"accession":"IPR014710","name":"RmlC-like jelly roll fold","type":"homologous_superfamily"},{"accession":"IPR018490","name":"Cyclic nucleotide-binding domain superfamily","type":"homologous_superfamily"}],"counters":{"subfamilies":0,"domain_architectures":0,"interactions":0,"matches":25286,"pathways":10,"proteins":5432,"proteomes":1140,"sets":0,"structural_models":{"alphafold":4537,"bfvd":0},"structures":21,"taxa":3836},"entry_annotations":{},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}