Potassium voltage-gated channel subfamily KQT member 2

Details

Name
Potassium 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 Name
KCNQ2
Organism
Humans
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 residues
872
Molecular Weight
95846.575
Theoretical pI
9.59
GO Classification
Functions
ankyrin binding / delayed rectifier potassium channel activity / potassium channel activity / voltage-gated potassium channel activity
Processes
axon guidance / nervous system development / potassium ion transmembrane transport / potassium ion transport / synaptic transmission / transmission of nerve impulse
Components
axon initial segment / integral component of membrane / node of Ranvier / plasma membrane / voltage-gated potassium channel complex
General Function
Voltage-gated potassium channel activity
Specific Function
Probably 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 Regions
92-112 123-143 167-187 196-218 232-252 292-312
Cellular Location
Membrane
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
Chromosome Location
20
Locus
20q13.3
External Identifiers
ResourceLink
UniProtKB IDO43526
UniProtKB Entry NameKCNQ2_HUMAN
GenBank Protein ID1841342
GenBank Gene IDD82346
GenAtlas IDKCNQ2
HGNC IDHGNC:6296
General 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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:11160379]
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  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10713399]
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  20. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:17872363]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00321AmitriptylineapprovednoinhibitorDetails
DB04953Ezogabineapproved, investigationalunknownDetails
DB06089ICA-105665investigationalunknownDetails
DB00939Meclofenamic acidapproved, vet_approvedunknownotherDetails
DB00586Diclofenacapproved, vet_approvedunknownagonistDetails