Top ▲
Gene and Protein Information  |
|||||||
| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 6 | 1 | 872 | 8q24.22 | KCNQ3 | potassium voltage-gated channel subfamily Q member 3 | 2,24 |
| Mouse | 6 | 1 | 873 | 15 29.16 cM | Kcnq3 | potassium voltage-gated channel, subfamily Q, member 3 | 17 |
| Rat | 6 | 1 | 873 | 7q34 | Kcnq3 | potassium voltage-gated channel subfamily Q member 3 | 31 |
| Previous and Unofficial Names |
| EBN2 | potassium channel subunit alpha KvLQT3 | potassium voltage-gated channel, KQT-like subfamily, member 3 | potassium channel, voltage gated KQT-like subfamily Q, member 3 | potassium channel, voltage-gated KQT-like subfamily Q, member 3 | potassium voltage-gated channel |
| Database Links |
|
| Alphafold | O43525 (Hs), Q8K3F6 (Mm), O88944 (Rn) |
| ChEMBL Target | CHEMBL2684 (Hs), CHEMBL5531 (Rn) |
| DrugBank Target | O43525 (Hs) |
| Ensembl Gene | ENSG00000184156 (Hs), ENSMUSG00000056258 (Mm), ENSRNOG00000005206 (Rn) |
| Entrez Gene | 3786 (Hs), 110862 (Mm), 29682 (Rn) |
| Human Protein Atlas | ENSG00000184156 (Hs) |
| KEGG Gene | hsa:3786 (Hs), mmu:110862 (Mm), rno:29682 (Rn) |
| OMIM | 602232 (Hs) |
| Orphanet | ORPHA122817 (Hs) |
| Pharos | O43525 (Hs) |
| RefSeq Nucleotide | NM_004519 (Hs), NM_152923 (Mm), NM_031597 (Rn) |
| RefSeq Protein | NP_004510 (Hs), NP_690887 (Mm), NP_113785 (Rn) |
| UniProtKB | O43525 (Hs), Q8K3F6 (Mm), O88944 (Rn) |
| Wikipedia | KCNQ3 (Hs) |
| Associated Proteins |
||||||||||||||||||||||
|
|
|
||||||||||||||||||||
| Associated Protein Comments | ||||||||||||||||||||||
| Gating and modulation: PIP2 exhibits high affinity to KCNQ3 (≈ 2.6 µM) and stabilizes the channel in the open state by increasing the open probability [8,26]. In contrast to KCNQ2, KCNQ4 and KCNQ5, Ca2+-calmodulin does not reduce the currents produced by KCNQ3 [27]. Src tyrosine kinase reduces KCNQ3 current amplitude and slows the activation kinetics [5]. | ||||||||||||||||||||||
| Functional Characteristics |
|
| M current as heteromeric KV7.2/KV7.3 or KV7.3/KV7.5 | |
| Ion Selectivity and Conductance |
||||||
|
||||||
| Ion Selectivity and Conductance Comments | ||||||
| Ion selectivity rank: K+ > Rb+ > Cs+ > NH4+ [21]. |
| Voltage Dependence |
||||||||||||||||
|
||||||||||||||||
|
Download all structure-activity data for this target as a CSV file 
| Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Heteromeric specific affinities are listed below :
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Heteromeric specific affinities are listed below : | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Distribution
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
| Physiological Functions
|
||||||||
|
| Phenotypes, Alleles and Disease Models
|
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinically-Relevant Mutations and Pathophysiology
|
||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
| General Comments |
| The M current is a slowly activating and deactivating potassium conductance that plays a critical role in determining the sub-threshold excitability of neurones as well as the responsiveness to synaptic inputs. The M current was first described in peripheral sympathetic neurones, and differential expression of this conductance produces subtypes of sympathetic neurones with distinct firing patterns. The M current is also expressed in many neurons in the central nervous system. The M-current is mediated by members of the Kv7 family, which form a heterotetrameric channel consisting of KCNQ3 subunits associated with either KCNQ2 or KCNQ5 subunits. Expression of KCNQ2, KCNQ3 and KCNQ5 proteins mostly overlaps with distribution of M current. |
1. Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA. (2001) MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell, 104 (2): 217-31. [PMID:11207363]
2. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach RJ, Leppert M. (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet, 18 (1): 53-5. [PMID:9425900]
3. Coghlan MJ, Carroll WA, Gopalakrishnan M. (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J Med Chem, 44 (11): 1627-53. [PMID:11356099]
4. Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY. (2000) Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci USA, 97 (9): 4914-9. [PMID:10781098]
5. Gamper N, Li Y, Shapiro MS. (2005) Structural requirements for differential sensitivity of KCNQ K+ channels to modulation by Ca2+/calmodulin. Mol Biol Cell, 16 (8): 3538-51. [PMID:15901836]
6. Gamper N, Stockand JD, Shapiro MS. (2003) Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase. J Neurosci, 23 (1): 84-95. [PMID:12514204]
7. Gao Z, Zhang T, Wu M, Xiong Q, Sun H, Zhang Y, Zu L, Wang W, Li M. (2010) Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions. J Biol Chem, 285 (36): 28322-32. [PMID:20584905]
8. Gilling M, Rasmussen HB, Calloe K, Sequeira AF, Baretto M, Oliveira G, Almeida J, Lauritsen MB, Ullmann R, Boonen SE et al.. (2013) Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders. Front Genet, 4: 54. [PMID:23596459]
9. Hadley JK, Noda M, Selyanko AA, Wood IC, Abogadie FC, Brown DA. (2000) Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels. Br J Pharmacol, 129 (3): 413-5. [PMID:10711337]
10. Hadley JK, Passmore GM, Tatulian L, Al-Qatari M, Ye F, Wickenden AD, Brown DA. (2003) Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium. J Neurosci, 23 (12): 5012-9. [PMID:12832524]
11. Haitin Y, Attali B. (2008) The C-terminus of Kv7 channels: a multifunctional module. J Physiol (Lond.), 586 (7): 1803-10. [PMID:18218681]
12. Lerche C, Scherer CR, Seebohm G, Derst C, Wei AD, Busch AE, Steinmeyer K. (2000) Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J Biol Chem, 275 (29): 22395-400. [PMID:10787416]
13. Li Y, Gamper N, Shapiro MS. (2004) Single-channel analysis of KCNQ K+ channels reveals the mechanism of augmentation by a cysteine-modifying reagent. J Neurosci, 24 (22): 5079-90. [PMID:15175377]
14. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA. (2000) Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol, 58 (2): 253-62. [PMID:10908292]
15. Manville RW, Abbott GW. (2018) Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels. Mol Pharmacol, 94 (4): 1155-1163. [PMID:30021858]
16. Martire M, Castaldo P, D'Amico M, Preziosi P, Annunziato L, Taglialatela M. (2004) M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals. J Neurosci, 24 (3): 592-7. [PMID:14736843]
17. McCormack T, Rudy B, Seldin MF. (1999) Chromosomal mapping of the potassium channel genes Kcnq2 and Kcnq3 in mouse. Genomics, 56 (3): 360-1. [PMID:10087209]
18. Padilla K, Wickenden AD, Gerlach AC, McCormack K. (2009) The KCNQ2/3 selective channel opener ICA-27243 binds to a novel voltage-sensor domain site. Neurosci Lett, 465 (2): 138-42. [PMID:19733209]
19. Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, Bennett V, Scherer SS, Cooper EC. (2006) A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci, 26 (10): 2599-613. [PMID:16525039]
20. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B. (2005) Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol, 67 (4): 1053-66. [PMID:15598972]
21. Prole DL, Marrion NV. (2004) Ionic permeation and conduction properties of neuronal KCNQ2/KCNQ3 potassium channels. Biophys J, 86 (3): 1454-69. [PMID:14990473]
22. Punke MA, Friederich P. (2007) Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg, 104 (5): 1256-64, tables of contents. [PMID:17456683]
23. Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ. (2000) KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J Biol Chem, 275 (31): 24089-95. [PMID:10816588]
24. Schroeder BC, Kubisch C, Stein V, Jentsch TJ. (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature, 396 (6712): 687-90. [PMID:9872318]
25. Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Jentsch TJ, Brown DA. (2000) Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors. J Physiol (Lond.), 522 Pt 3: 349-55. [PMID:10713961]
26. Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B. (2000) Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current. J Neurosci, 20 (5): 1710-21. [PMID:10684873]
27. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, Anderson VE, Sanguinetti MC, Leppert MF. (2003) KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain, 126 (Pt 12): 2726-37. [PMID:14534157]
28. Soldovieri MV, Boutry-Kryza N, Milh M, Doummar D, Heron B, Bourel E, Ambrosino P, Miceli F, De Maria M, Dorison N et al.. (2014) Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A. Hum Mutat, 35 (3): 356-67. [PMID:24375629]
29. Tatulian L, Delmas P, Abogadie FC, Brown DA. (2001) Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J Neurosci, 21 (15): 5535-45. [PMID:11466425]
30. Vernier JM, De La Rosa MA, Chen H, Wu JZ, Larson GL, Cheney IW. (2008) Derivatives of 4-(n-azacycloalkyl) anilides as potassium channel modulators. Patent number: WO2008024398A2. Assignee: Valeant Pharmaceuticals International. Priority date: 22/08/2007. Publication date: 28/02/2008.
31. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D. (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science, 282 (5395): 1890-3. [PMID:9836639]
32. Wickenden AD, Zou A, Wagoner PK, Jegla T. (2001) Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. Br J Pharmacol, 132 (2): 381-4. [PMID:11159685]
33. Wua YJ, Dworetzky SI. (2005) Recent developments on KCNQ potassium channel openers. Curr Med Chem, 12 (4): 453-60. [PMID:15720253]
34. Xiong Q, Sun H, Li M. (2007) Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol, 3 (5): 287-96. [PMID:17435769]
35. Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA. (1998) Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J Biol Chem, 273 (31): 19419-23. [PMID:9677360]
36. Zhang F, Mi Y, Qi JL, Li JW, Si M, Guan BC, Du XN, An HL, Zhang HL. (2013) Modulation of K(v)7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58. Br J Pharmacol, 168 (4): 1030-42. [PMID:23013484]
