Potassium voltage-gated channel subfamily KQT member 2

NamePotassium voltage-gated channel subfamily KQT member 2
Synonyms
  • KQT-like 2
  • Neuroblastoma-specific potassium channel subunit alpha KvLQT2
  • Voltage-gated potassium channel subunit Kv7.2
Gene NameKCNQ2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001787|Potassium voltage-gated channel subfamily KQT member 2
MVQKSRNGGVYPGPSGEKKLKVGFVGLDPGAPDSTRDGALLIAGSEAPKRGSILSKPRAG
GAGAGKPPKRNAFYRKLQNFLYNVLERPRGWAFIYHAYVFLLVFSCLVLSVFSTIKEYEK
SSEGALYILEIVTIVVFGVEYFVRIWAAGCCCRYRGWRGRLKFARKPFCVIDIMVLIASI
AVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLLGSVVYAHSKELVTAWYIGF
LCLILASFLVYLAEKGENDHFDTYADALWWGLITLTTIGYGDKYPQTWNGRLLAATFTLI
GVSFFALPAGILGSGFALKVQEQHRQKHFEKRRNPAAGLIQSAWRFYATNLSRTDLHSTW
QYYERTVTVPMYSSQTQTYGASRLIPPLNQLELLRNLKSKSGLAFRKDPPPEPSPSKGSP
CRGPLCGCCPGRSSQKVSLKDRVFSSPRGVAAKGKGSPQAQTVRRSPSADQSLEDSPSKV
PKSWSFGDRSRARQAFRIKGAASRQNSEEASLPGEDIVDDKSCPCEFVTEDLTPGLKVSI
RAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAGHLDMLSRIKSLQSRVDQIVGRGPAIT
DKDRTKGPAEAELPEDPSMMGRLGKVEKQVLSMEKKLDFLVNIYMQRMGIPPTETEAYFG
AKEPEPAPPYHSPEDSREHVDRHGCIVKIVRSSSSTGQKNFSAPPAAPPVQCPPSTSWQP
QSHPRQGHGTSPVGDHGSLVRIPPPPAHERSLSAYGGGNRASMEFLRQEDTPGCRPPEGN
LRDSDTSISIPSVDHEELERSFSGFSISQSKENLDALNSCYAAVAPCAKVRPYIAEGESD
TDSDLCTPCGPPPRSATGEGPFGDVGWAGPRK
Number of residues872
Molecular Weight95846.575
Theoretical pI9.59
GO Classification
Functions
  • ankyrin binding
  • delayed rectifier potassium channel activity
  • voltage-gated potassium channel activity
  • potassium channel activity
Processes
  • synaptic transmission
  • axon guidance
  • nervous system development
  • potassium ion transmembrane transport
  • potassium ion transport
  • transmission of nerve impulse
Components
  • integral component of membrane
  • axon initial segment
  • node of Ranvier
  • plasma membrane
  • voltage-gated potassium channel complex
General FunctionVoltage-gated potassium channel activity
Specific FunctionProbably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors.
Pfam Domain Function
Transmembrane Regions92-112 123-143 167-187 196-218 232-252 292-312
GenBank Protein ID1841342
UniProtKB IDO43526
UniProtKB Entry NameKCNQ2_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0010632|Potassium voltage-gated channel subfamily KQT member 2 (KCNQ2)
ATGGTGCAGAAGTCGCGCAACGGCGGCGTATACCCCGGCCCGAGCGGGGAGAAGAAGCTG
AAGGTGGGCTTCGTGGGGCTGGACCCCGGCGCGCCCGACTCCACCCGGGACGGGGCGCTG
CTGATCGCCGGCTCCGAGGCCCCCAAGCGCGGCAGCATCCTCAGCAAACCTCGCGCGGGC
GGCGCGGGCGCCGGGAAGCCCCCCAAGCGCAACGCCTTCTACCGCAAGCTGCAGAATTTC
CTCTACAACGTGCTGGAGCGGCCGCGCGGCTGGGCGTTCATCTACCACGCCTACGTGTTC
CTCCTGGTTTTCTCCTGCCTCGTGCTGTCTGTGTTTTCCACCATCAAGGAGTATGAGAAG
AGCTCGGAGGGGGCCCTCTACATCCTGGAAATCGTGACTATCGTGGTGTTTGGCGTGGAG
TACTTCGTGCGGATCTGGGCCGCAGGCTGCTGCTGCCGGTACCGTGGCTGGAGGGGGCGG
CTCAAGTTTGCCCGGAAACCGTTCTGTGTGATTGACATCATGGTGCTCATCGCCTCCATT
GCGGTGCTGGCCGCCGGCTCCCAGGGCAACGTCTTTGCCACATCTGCGCTCCGGAGCCTG
CGCTTCCTGCAGATTCTGCGGATGATCCGCATGGACCGGCGGGGAGGCACCTGGAAGCTG
CTGGGCTCTGTGGTCTATGCCCACAGCAAGGAGCTGGTCACTGCCTGGTACATCGGCTTC
CTTTGTCTCATCCTGGCCTCGTTCCTGGTGTACTTGGCAGAGAAGGGGGAGAACGACCAC
TTTGACACCTACGCGGATGCACTCTGGTGGGGCCTGATCACGCTGACCACCATTGGCTAC
GGGGACAAGTACCCCCAGACCTGGAACGGCAGGCTCCTTGCGGCAACCTTCACCCTCATC
GGTGTCTCCTTCTTCGCGCTGCCTGCAGGCATCTTGGGGTCTGGGTTTGCCCTGAAGGTT
CAGGAGCAGCACAGGCAGAAGCACTTTGAGAAGAGGCGGAACCCGGCAGCAGGCCTGATC
CAGTCGGCCTGGAGATTCTACGCCACCAACCTCTCGCGCACAGACCTGCACTCCACGTGG
CAGTACTACGAGCGAACGGTCACCGTGCCCATGTACAGACTTATCCCCCCGCTGAACCAG
CTGGAGCTGCTGAGGAACCTCAAGAGTAAATCTGGACTCGCTTTCAGGAAGGACCCCCCG
CCGGAGCCGTCTCCAAGCCAGAAGGTCAGTTTGAAAGATCGTGTCTTCTCCAGCCCCCGA
GGCGTGGCTGCCAAGGGGAAGGGGTCCCCGCAGGCCCAGACTGTGAGGCGGTCACCCAGC
GCCGACCAGAGCCTCGAGGACAGCCCCAGCAAGGTGCCCAAGAGCTGGAGCTTCGGGGAC
CGCAGCCGGGCACGCCAGGCTTTCCGCATCAAGGGTGCCGCGTCACGGCAGAACTCAGAA
GAAGCAAGCCTCCCCGGAGAGGACATTGTGGATGACAAGAGCTGCCCCTGCGAGTTTGTG
ACCGAGGACCTGACCCCGGGCCTCAAAGTCAGCATCAGAGCCGTGTGTGTCATGCGGTTC
CTGGTGTCCAAGCGGAAGTTCAAGGAGAGCCTGCGGCCCTACGACGTGATGGACGTCATC
GAGCAGTACTCAGCCGGCCACCTGGACATGCTGTCCCGAATTAAGAGCCTGCAGTCCAGA
GTGGACCAGATCGTGGGGCGGGGCCCAGCGATCACGGACAAGGACCGCACCAAGGGCCCG
GCCGAGGCGGAGCTGCCCGAGGACCCCAGCATGATGGGACGGCTCGGGAAGGTGGAGAAG
CAGGTCTTGTCCATGGAGAAGAAGCTGGACTTCCTGGTGAATATCTACATGCAGCGGATG
GGCATCCCCCCGACAGAGACCGAGGCCTACTTTGGGGCCAAAGAGCCGGAGCCGGCGCCG
CCGTACCACAGCCCGGAAGACAGCCGGGAGCATGTCGACAGGCACGGCTGCATTGTCAAG
ATCGTGCGCTCCAGCAGCTCCACGGGCCAGAAGAACTTCTCGGCGCCCCCGGCCGCGCCC
CCTGTCCAGTGTCCGCCCTCCACCTCCTGGCAGCCACAGAGCCACCCGCGCCAGGGCCAC
GGCACCTCCCCCGTGGGGGACCACGGCTCCCTGGTGCGCATCCCGCCGCCGCCTGCCCAC
GAGCGGTCGCTGTCCGCCTACGGCGGGGGCAACCGCGCCAGCATGGAGTTCCTGCGGCAG
GAGGACACCCCGGGCTGCAGGCCCCCCGAGGGGAACCTGCGGGACAGCGACACGTCCATC
TCCATCCCGTCCGTGGACCACGAGGAGCTGGAGCGTTCCTTCAGCGGCTTCAGCATCTCC
CAGTCCAAGGAGAACCTGGATGCTCTCAACAGCTGCTACGCGGCCGTGGCGCCTTGTGCC
AAAGTCAGGCCCTACATTGCGGAGGGAGAGTCAGACACCGACTCCGACCTCTGTACCCCG
TGCGGGCCCCCGCCACGCTCGGCCACCGGCGAGGGTCCCTTTGGTGACGTGGGCTGGGCC
GGGCCCAGGAAGTGA
GenBank Gene IDD82346
GeneCard IDNot Available
GenAtlas IDKCNQ2
HGNC IDHGNC:6296
Chromosome Location20
Locus20q13.3
References
  1. Yokoyama M, Nishi Y, Yoshii J, Okubo K, Matsubara K: Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles. DNA Res. 1996 Oct 31;3(5):311-20. 9039501
  2. Singh NA, Charlier C, Stauffer D, DuPont BR, Leach RJ, Melis R, Ronen GM, Bjerre I, Quattlebaum T, Murphy JV, McHarg ML, Gagnon D, Rosales TO, Peiffer A, Anderson VE, Leppert M: A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet. 1998 Jan;18(1):25-9. 9425895
  3. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK: A potassium channel mutation in neonatal human epilepsy. Science. 1998 Jan 16;279(5349):403-6. 9430594
  4. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D: KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998 Dec 4;282(5395):1890-3. 9836639
  5. Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M: The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS Lett. 1998 Nov 6;438(3):171-6. 9827540
  6. Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA: Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J Biol Chem. 1998 Jul 31;273(31):19419-23. 9677360
  7. Smith JS, Iannotti CA, Dargis P, Christian EP, Aiyar J: Differential expression of kcnq2 splice variants: implications to m current function during neuronal development. J Neurosci. 2001 Feb 15;21(4):1096-103. 11160379
  8. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  9. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  10. Schroeder BC, Kubisch C, Stein V, Jentsch TJ: Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature. 1998 Dec 17;396(6712):687-90. 9872318
  11. Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Delmas P, Buckley NJ, London B, Brown DA: Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell. J Neurosci. 1999 Sep 15;19(18):7742-56. 10479678
  12. Tinel N, Diochot S, Lauritzen I, Barhanin J, Lazdunski M, Borsotto M: M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit. FEBS Lett. 2000 Sep 1;480(2-3):137-41. 11034315
  13. Schwake M, Pusch M, Kharkovets T, Jentsch TJ: Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. J Biol Chem. 2000 May 5;275(18):13343-8. 10788442
  14. Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B: Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current. J Neurosci. 2000 Mar 1;20(5):1710-21. 10684873
  15. Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Jentsch TJ, Brown DA: Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors. J Physiol. 2000 Feb 1;522 Pt 3:349-55. 10713961
  16. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. 10908292
  17. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. 10953053
  18. Rundfeldt C, Netzer R: The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits. Neurosci Lett. 2000 Mar 17;282(1-2):73-6. 10713399
  19. Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY: Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4914-9. 10781098
  20. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. 14759258
  21. Surti TS, Huang L, Jan YN, Jan LY, Cooper EC: Identification by mass spectrometry and functional characterization of two phosphorylation sites of KCNQ2/KCNQ3 channels. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17828-33. Epub 2005 Nov 30. 16319223
  22. Biervert C, Steinlein OK: Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions. Hum Genet. 1999 Mar;104(3):234-40. 10323247
  23. Miraglia del Giudice E, Coppola G, Scuccimarra G, Cirillo G, Bellini G, Pascotto A: Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor. Eur J Hum Genet. 2000 Dec;8(12):994-7. 11175290
  24. Dedek K, Kunath B, Kananura C, Reuner U, Jentsch TJ, Steinlein OK: Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12272-7. Epub 2001 Sep 25. 11572947
  25. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, Anderson VE, Sanguinetti MC, Leppert MF: KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain. 2003 Dec;126(Pt 12):2726-37. Epub 2003 Oct 8. 14534157
  26. Dedek K, Fusco L, Teloy N, Steinlein OK: Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2. Epilepsy Res. 2003 Apr;54(1):21-7. 12742592
  27. Borgatti R, Zucca C, Cavallini A, Ferrario M, Panzeri C, Castaldo P, Soldovieri MV, Baschirotto C, Bresolin N, Dalla Bernardina B, Taglialatela M, Bassi MT: A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology. 2004 Jul 13;63(1):57-65. 15249611
  28. Wuttke TV, Jurkat-Rott K, Paulus W, Garncarek M, Lehmann-Horn F, Lerche H: Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations. Neurology. 2007 Nov 27;69(22):2045-53. Epub 2007 Sep 13. 17872363