KCNQ2_HUMAN
ID KCNQ2_HUMAN Reviewed; 872 AA.
AC O43526; O43796; O75580; O95845; Q4VXP4; Q4VXR6; Q5VYT8; Q96J59; Q99454;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Potassium voltage-gated channel subfamily KQT member 2 {ECO:0000305};
DE AltName: Full=KQT-like 2;
DE AltName: Full=Neuroblastoma-specific potassium channel subunit alpha KvLQT2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv7.2;
GN Name=KCNQ2 {ECO:0000312|HGNC:HGNC:6296};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RC TISSUE=Neuroblastoma;
RX PubMed=9039501; DOI=10.1093/dnares/3.5.311;
RA Yokoyama M., Nishi Y., Yoshii J., Okubo K., Matsubara K.;
RT "Identification and cloning of neuroblastoma-specific and nerve tissue-
RT specific genes through compiled expression profiles.";
RL DNA Res. 3:311-320(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS BFNS1 CYS-284 AND
RP THR-306.
RC TISSUE=Brain, Fetal brain, and Temporal cortex;
RX PubMed=9425895; DOI=10.1038/ng0198-25;
RA Singh N.A., Charlier C., Stauffer D., DuPont B.R., Leach R.J., Melis R.,
RA Ronen G.M., Bjerre I., Quattlebaum T., Murphy J.V., McHarg M.L., Gagnon D.,
RA Rosales T.O., Peiffer A., Anderson V.E., Leppert M.;
RT "A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy
RT of newborns.";
RL Nat. Genet. 18:25-29(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Fetal brain;
RX PubMed=9430594; DOI=10.1126/science.279.5349.403;
RA Biervert C., Schroeder B.C., Kubisch C., Berkovic S.F., Propping P.,
RA Jentsch T.J., Steinlein O.K.;
RT "A potassium channel mutation in neonatal human epilepsy.";
RL Science 279:403-406(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBUNIT, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9836639; DOI=10.1126/science.282.5395.1890;
RA Wang H.-S., Pan Z., Shi W., Brown B.S., Wymore R.S., Cohen I.S.,
RA Dixon J.E., McKinnon D.;
RT "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-
RT channel.";
RL Science 282:1890-1893(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 5).
RX PubMed=9827540; DOI=10.1016/s0014-5793(98)01296-4;
RA Tinel N., Lauritzen I., Chouabe C., Lazdunski M., Borsotto M.;
RT "The KCNQ2 potassium channel: splice variants, functional and developmental
RT expression. Brain localization and comparison with KCNQ3.";
RL FEBS Lett. 438:171-176(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC TISSUE=Brain, and Fetal brain;
RX PubMed=9677360; DOI=10.1074/jbc.273.31.19419;
RA Yang W.-P., Levesque P.C., Little W.A., Conder M.L., Ramakrishnan P.,
RA Neubauer M.G., Blanar M.A.;
RT "Functional expression of two KvLQT1-related potassium channels responsible
RT for an inherited idiopathic epilepsy.";
RL J. Biol. Chem. 273:19419-19423(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11160379; DOI=10.1523/jneurosci.21-04-01096.2001;
RA Smith J.S., Iannotti C.A., Dargis P.G., Christian E.P., Aiyar J.;
RT "Differential expression of KCNQ2 splice variants: implications to M
RT current function during neuronal development.";
RL J. Neurosci. 21:1096-1103(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP MUTAGENESIS OF SER-52 AND GLY-279, PHOSPHORYLATION AT SER-52, AND
RP CHARACTERIZATION OF VARIANTS CYS-284 AND THR-306.
RX PubMed=9872318; DOI=10.1038/25367;
RA Schroeder B.C., Kubisch C., Stein V., Jentsch T.J.;
RT "Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels
RT causes epilepsy.";
RL Nature 396:687-690(1998).
RN [11]
RP INVOLVEMENT IN M-LIKE CURRENT.
RX PubMed=10479678; DOI=10.1523/jneurosci.19-18-07742.1999;
RA Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Delmas P.,
RA Buckley N.J., London B., Brown D.A.;
RT "Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-
RT like current in a mammalian neuronal cell.";
RL J. Neurosci. 19:7742-7756(1999).
RN [12]
RP ASSOCIATION WITH KCNE2.
RX PubMed=11034315; DOI=10.1016/s0014-5793(00)01918-9;
RA Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M.;
RT "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2
RT subunit.";
RL FEBS Lett. 480:137-141(2000).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=10788442; DOI=10.1074/jbc.275.18.13343;
RA Schwake M., Pusch M., Kharkovets T., Jentsch T.J.;
RT "Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+
RT channels involved in epilepsy.";
RL J. Biol. Chem. 275:13343-13348(2000).
RN [14]
RP FUNCTION, AND INHIBITION BY M1 MUSCARINIC RECEPTORS.
RX PubMed=10684873; DOI=10.1523/jneurosci.20-05-01710.2000;
RA Shapiro M.S., Roche J.P., Kaftan E.J., Cruzblanca H., Mackie K., Hille B.;
RT "Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels
RT that underlie the neuronal M current.";
RL J. Neurosci. 20:1710-1721(2000).
RN [15]
RP INHIBITION BY M1 MUSCARINIC RECEPTORS.
RX PubMed=10713961; DOI=10.1111/j.1469-7793.2000.t01-2-00349.x;
RA Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Jentsch T.J.,
RA Brown D.A.;
RT "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via
RT M1 muscarinic acetylcholine receptors.";
RL J. Physiol. (Lond.) 522:349-355(2000).
RN [16]
RP ACTIVATION BY RETICABINE.
RX PubMed=10908292; DOI=10.1124/mol.58.2.253;
RA Main M.J., Cryan J.E., Dupere J.R., Cox B., Clare J.J., Burbidge S.A.;
RT "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant
RT retigabine.";
RL Mol. Pharmacol. 58:253-262(2000).
RN [17]
RP ACTIVATION BY RETICABINE.
RX PubMed=10953053; DOI=10.1124/mol.58.3.591;
RA Wickenden A.D., Yu W., Zou A., Jegla T., Wagoner P.K.;
RT "Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3
RT potassium channels.";
RL Mol. Pharmacol. 58:591-600(2000).
RN [18]
RP ACTIVATION BY RETICABINE.
RX PubMed=10713399; DOI=10.1016/s0304-3940(00)00866-1;
RA Rundfeldt C., Netzer R.;
RT "The novel anticonvulsant retigabine activates M-currents in Chinese
RT hamster ovary-cells transfected with human KCNQ2/3 subunits.";
RL Neurosci. Lett. 282:73-76(2000).
RN [19]
RP TISSUE SPECIFICITY, AND BIOCHEMICAL CHARACTERIZATION.
RX PubMed=10781098; DOI=10.1073/pnas.090092797;
RA Cooper E.C., Aldape K.D., Abosch A., Barbaro N.M., Berger M.S.,
RA Peacock W.S., Jan Y.N., Jan L.Y.;
RT "Colocalization and coassembly of two human brain M-type potassium channel
RT subunits that are mutated in epilepsy.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:4914-4919(2000).
RN [20]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [21]
RP PHOSPHORYLATION AT THR-217, AND MUTAGENESIS OF THR-217.
RX PubMed=16319223; DOI=10.1073/pnas.0509122102;
RA Surti T.S., Huang L., Jan Y.N., Jan L.Y., Cooper E.C.;
RT "Identification by mass spectrometry and functional characterization of two
RT phosphorylation sites of KCNQ2/KCNQ3 channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17828-17833(2005).
RN [22]
RP UBIQUITINATION BY NEDD4L.
RX PubMed=27445338; DOI=10.1074/jbc.m116.722637;
RA Anta B., Martin-Rodriguez C., Gomis-Perez C., Calvo L., Lopez-Benito S.,
RA Calderon-Garcia A.A., Vicente-Garcia C., Villarroel A., Arevalo J.C.;
RT "Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-
RT expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the
RT Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3
RT (Kv7.2/3).";
RL J. Biol. Chem. 291:19132-19145(2016).
RN [23] {ECO:0007744|PDB:5J03}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 530-557 IN COMPLEX WITH
RP CALMODULIN, SUBUNIT, INTERACTION WITH CALMODULIN, AND REGION.
RX PubMed=27564677; DOI=10.1021/acs.biochem.6b00477;
RA Strulovich R., Tobelaim W.S., Attali B., Hirsch J.A.;
RT "Structural insights into the M-channel proximal C-terminus/calmodulin
RT complex.";
RL Biochemistry 55:5353-5365(2016).
RN [24]
RP VARIANT THR-780.
RX PubMed=10323247; DOI=10.1007/pl00008713;
RA Biervert C., Steinlein O.K.;
RT "Structural and mutational analysis of KCNQ2, the major gene locus for
RT benign familial neonatal convulsions.";
RL Hum. Genet. 104:234-240(1999).
RN [25]
RP VARIANT BFNS1 TRP-214.
RX PubMed=11175290; DOI=10.1038/sj.ejhg.5200570;
RA Miraglia del Giudice E., Coppola G., Scuccimarra G., Cirillo G.,
RA Bellini G., Pascotto A.;
RT "Benign familial neonatal convulsions (BFNC) resulting from mutation of the
RT KCNQ2 voltage sensor.";
RL Eur. J. Hum. Genet. 8:994-997(2000).
RN [26]
RP VARIANT BFNS1 TRP-207, CHARACTERIZATION OF VARIANT BFNS1 TRP-207, AND
RP FUNCTION.
RX PubMed=11572947; DOI=10.1073/pnas.211431298;
RA Dedek K., Kunath B., Kananura C., Reuner U., Jentsch T.J., Steinlein O.K.;
RT "Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor
RT of the KCNQ2 K+ channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12272-12277(2001).
RN [27]
RP VARIANTS BFNS1 VAL-208; GLN-228; PHE-243; CYS-284; THR-306 AND GLN-333,
RP CHARACTERIZATION OF VARIANTS BFNS1 VAL-208 AND GLN-333, AND FUNCTION.
RX PubMed=14534157; DOI=10.1093/brain/awg286;
RG The BFNC physician consortium;
RA Singh N.A., Westenskow P., Charlier C., Pappas C., Leslie J., Dillon J.,
RA Anderson V.E., Sanguinetti M.C., Leppert M.F.;
RT "KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal
RT convulsions: expansion of the functional and mutation spectrum.";
RL Brain 126:2726-2737(2003).
RN [28]
RP VARIANT DEE7 TRP-247, CHARACTERIZATION OF VARIANT DEE7 TRP-247, AND
RP FUNCTION.
RX PubMed=12742592; DOI=10.1016/s0920-1211(03)00037-8;
RA Dedek K., Fusco L., Teloy N., Steinlein O.K.;
RT "Neonatal convulsions and epileptic encephalopathy in an Italian family
RT with a missense mutation in the fifth transmembrane region of KCNQ2.";
RL Epilepsy Res. 54:21-27(2003).
RN [29]
RP VARIANT BFNS1 ASN-554, VARIANT DEE7 ASN-554, AND CHARACTERIZATION OF
RP VARIANT BFNS1 ASN-554.
RX PubMed=15249611; DOI=10.1212/01.wnl.0000132979.08394.6d;
RA Borgatti R., Zucca C., Cavallini A., Ferrario M., Panzeri C., Castaldo P.,
RA Soldovieri M.V., Baschirotto C., Bresolin N., Dalla Bernardina B.,
RA Taglialatela M., Bassi M.T.;
RT "A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy,
RT and mental retardation.";
RL Neurology 63:57-65(2004).
RN [30]
RP VARIANT GLN-207, CHARACTERIZATION OF VARIANT GLN-207, AND FUNCTION.
RX PubMed=17872363; DOI=10.1212/01.wnl.0000275523.95103.36;
RA Wuttke T.V., Jurkat-Rott K., Paulus W., Garncarek M., Lehmann-Horn F.,
RA Lerche H.;
RT "Peripheral nerve hyperexcitability due to dominant-negative KCNQ2
RT mutations.";
RL Neurology 69:2045-2053(2007).
RN [31]
RP VARIANTS BFNS1 ASP-154; GLU-159; VAL-196; 448-ARG--LYS-872 DEL AND TRP-547,
RP AND VARIANT ALA-217.
RX PubMed=23360469; DOI=10.1111/epi.12089;
RA Zara F., Specchio N., Striano P., Robbiano A., Gennaro E., Paravidino R.,
RA Vanni N., Beccaria F., Capovilla G., Bianchi A., Caffi L., Cardilli V.,
RA Darra F., Bernardina B.D., Fusco L., Gaggero R., Giordano L., Guerrini R.,
RA Incorpora G., Mastrangelo M., Spaccini L., Laverda A.M., Vecchi M.,
RA Vanadia F., Veggiotti P., Viri M., Occhi G., Budetta M., Taglialatela M.,
RA Coviello D.A., Vigevano F., Minetti C.;
RT "Genetic testing in benign familial epilepsies of the first year of life:
RT clinical and diagnostic significance.";
RL Epilepsia 54:425-436(2013).
RN [32]
RP VARIANT DEE7 ILE-276.
RX PubMed=24463883; DOI=10.1093/hmg/ddu030;
RG WGS500 Consortium;
RA Martin H.C., Kim G.E., Pagnamenta A.T., Murakami Y., Carvill G.L.,
RA Meyer E., Copley R.R., Rimmer A., Barcia G., Fleming M.R., Kronengold J.,
RA Brown M.R., Hudspith K.A., Broxholme J., Kanapin A., Cazier J.B.,
RA Kinoshita T., Nabbout R., Bentley D., McVean G., Heavin S., Zaiwalla Z.,
RA McShane T., Mefford H.C., Shears D., Stewart H., Kurian M.A.,
RA Scheffer I.E., Blair E., Donnelly P., Kaczmarek L.K., Taylor J.C.;
RT "Clinical whole-genome sequencing in severe early-onset epilepsy reveals
RT new genes and improves molecular diagnosis.";
RL Hum. Mol. Genet. 23:3200-3211(2014).
RN [33]
RP VARIANTS DEE7 CYS-210; PRO-234 AND 578-MET-LEU-579 DELINS ILE-MET.
RX PubMed=25818041; DOI=10.1111/epi.12954;
RA Mercimek-Mahmutoglu S., Patel J., Cordeiro D., Hewson S., Callen D.,
RA Donner E.J., Hahn C.D., Kannu P., Kobayashi J., Minassian B.A., Moharir M.,
RA Siriwardena K., Weiss S.K., Weksberg R., Snead O.C. III;
RT "Diagnostic yield of genetic testing in epileptic encephalopathy in
RT childhood.";
RL Epilepsia 56:707-716(2015).
RN [34]
RP VARIANTS BFNS1 ALA-114; ARG-159; 204-GLN--LYS-872 DEL; GLN-213; GLY-353;
RP PHE-358; 448-ARG--LYS-872 DEL; VAL-578; 581-ARG--LYS-872 DEL; SER-588 AND
RP ARG-637.
RX PubMed=25982755; DOI=10.1111/epi.13020;
RA Grinton B.E., Heron S.E., Pelekanos J.T., Zuberi S.M., Kivity S., Afawi Z.,
RA Williams T.C., Casalaz D.M., Yendle S., Linder I., Lev D., Lerman-Sagie T.,
RA Malone S., Bassan H., Goldberg-Stern H., Stanley T., Hayman M., Calvert S.,
RA Korczyn A.D., Shevell M., Scheffer I.E., Mulley J.C., Berkovic S.F.;
RT "Familial neonatal seizures in 36 families: Clinical and genetic features
RT correlate with outcome.";
RL Epilepsia 56:1071-1080(2015).
RN [35]
RP CHARACTERIZATION OF VARIANT DEE7 CYS-201, AND FUNCTION.
RX PubMed=25740509; DOI=10.1523/jneurosci.4423-14.2015;
RA Miceli F., Soldovieri M.V., Ambrosino P., De Maria M., Migliore M.,
RA Migliore R., Taglialatela M.;
RT "Early-onset epileptic encephalopathy caused by gain-of-function mutations
RT in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits.";
RL J. Neurosci. 35:3782-3793(2015).
RN [36]
RP VARIANT DEE7 THR-306.
RX PubMed=26138355; DOI=10.1111/cge.12636;
RA Dimassi S., Labalme A., Ville D., Calender A., Mignot C., Boutry-Kryza N.,
RA de Bellescize J., Rivier-Ringenbach C., Bourel-Ponchel E., Cheillan D.,
RA Simonet T., Maincent K., Rossi M., Till M., Mougou-Zerelli S., Edery P.,
RA Saad A., Heron D., des Portes V., Sanlaville D., Lesca G.;
RT "Whole-exome sequencing improves the diagnosis yield in sporadic infantile
RT spasm syndrome.";
RL Clin. Genet. 89:198-204(2016).
RN [37]
RP VARIANTS DEE7 CYS-201; GLN-213 AND SER-561, AND VARIANTS BFNS1 TRP-213 AND
RP 581-ARG--LYS-872 DEL.
RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263;
RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A.,
RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A.,
RA Scott R.H.;
RT "Improving diagnosis and broadening the phenotypes in early-onset seizure
RT and severe developmental delay disorders through gene panel analysis.";
RL J. Med. Genet. 53:310-317(2016).
RN [38]
RP VARIANTS DEE7 GLU-266; PHE-268; SER-291; VAL-294; SER-301 AND GLN-581, AND
RP VARIANT SER-777.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: Associates with KCNQ3 to form a potassium channel with
CC essentially identical properties to the channel underlying the native
CC M-current, a slowly activating and deactivating potassium conductance
CC which plays a critical role in determining the subthreshold electrical
CC excitability of neurons as well as the responsiveness to synaptic
CC inputs. Therefore, it is important in the regulation of neuronal
CC excitability. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991,
CC and activated by the anticonvulsant retigabine (PubMed:9836639,
CC PubMed:11572947, PubMed:14534157, PubMed:12742592, PubMed:17872363). As
CC the native M-channel, the potassium channel composed of KCNQ2 and KCNQ3
CC is also suppressed by activation of the muscarinic acetylcholine
CC receptor CHRM1 (PubMed:10684873). {ECO:0000269|PubMed:10684873,
CC ECO:0000269|PubMed:11572947, ECO:0000269|PubMed:12742592,
CC ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:17872363,
CC ECO:0000269|PubMed:25740509, ECO:0000269|PubMed:9836639}.
CC -!- SUBUNIT: Heterotetramer with KCNQ3; form the heterotetrameric M
CC potassium channel (PubMed:9836639, PubMed:27564677). Interacts with
CC calmodulin; the interaction is calcium-independent, constitutive and
CC participates in the proper assembly of a functional heterotetrameric M
CC channel (PubMed:27564677). May associate with KCNE2 (PubMed:11034315).
CC Interacts with IQCJ-SCHIP1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z351, ECO:0000269|PubMed:11034315,
CC ECO:0000269|PubMed:27564677, ECO:0000269|PubMed:9836639}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10788442,
CC ECO:0000269|PubMed:9836639}; Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=O43526-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43526-2; Sequence=VSP_000988;
CC Name=3;
CC IsoId=O43526-3; Sequence=VSP_000985, VSP_000988;
CC Name=4;
CC IsoId=O43526-4; Sequence=VSP_000989, VSP_000990;
CC Name=5;
CC IsoId=O43526-5; Sequence=VSP_000984, VSP_000988;
CC Name=6; Synonyms=HNSPC;
CC IsoId=O43526-6; Sequence=VSP_000986, VSP_000987;
CC -!- TISSUE SPECIFICITY: In adult and fetal brain. Highly expressed in areas
CC containing neuronal cell bodies, low in spinal cord and corpus
CC callosum. Isoform 2 is preferentially expressed in differentiated
CC neurons. Isoform 6 is prominent in fetal brain, undifferentiated
CC neuroblastoma cells and brain tumors. {ECO:0000269|PubMed:10781098}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. {ECO:0000250}.
CC -!- PTM: KCNQ2/KCNQ3 heteromeric current can be increased by intracellular
CC cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the
CC N-terminal region. {ECO:0000269|PubMed:16319223,
CC ECO:0000269|PubMed:9872318}.
CC -!- PTM: KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to
CC protein degradation (Probable). Degradation induced by NEDD4L is
CC inhibited by USP36 (PubMed:27445338). {ECO:0000269|PubMed:27445338,
CC ECO:0000305|PubMed:27445338}.
CC -!- DISEASE: Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200]: A
CC disorder characterized by clusters of seizures occurring in the first
CC days of life. Most patients have spontaneous remission by 12 months of
CC age and show normal psychomotor development. Some rare cases manifest
CC an atypical severe phenotype associated with epileptic encephalopathy
CC and psychomotor retardation. The disorder is distinguished from benign
CC familial infantile seizures by an earlier age at onset. In some
CC patients, neonatal convulsions are followed later in life by myokymia,
CC a benign condition characterized by spontaneous involuntary
CC contractions of skeletal muscles fiber groups that can be observed as
CC vermiform movement of the overlying skin. Electromyography typically
CC shows continuous motor unit activity with spontaneous oligo- and
CC multiplet-discharges of high intraburst frequency (myokymic
CC discharges). Some patients may have isolated myokymia.
CC {ECO:0000269|PubMed:11175290, ECO:0000269|PubMed:11572947,
CC ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:15249611,
CC ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:25982755,
CC ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:9425895}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 7 (DEE7)
CC [MIM:613720]: An autosomal dominant seizure disorder characterized by
CC infantile onset of refractory seizures with resultant delayed
CC neurologic development and persistent neurologic abnormalities.
CC {ECO:0000269|PubMed:12742592, ECO:0000269|PubMed:15249611,
CC ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:25740509,
CC ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355,
CC ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Inclusion of isoform 6 in heteromultimers results in
CC attenuation of potassium current. Prominent expression of isoform 6 in
CC the developing brain may alter firing repertoires of immature neurons
CC excitability to provide cues for proliferation rather than
CC differentiation.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15)
CC subfamily. Kv7.2/KCNQ2 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; D82346; BAA11557.1; -; mRNA.
DR EMBL; AF033348; AAB97315.1; -; mRNA.
DR EMBL; Y15065; CAA75348.1; -; mRNA.
DR EMBL; AF110020; AAD16988.1; -; mRNA.
DR EMBL; AF074247; AAC25921.1; -; mRNA.
DR EMBL; AL121827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000699; AAH00699.1; -; mRNA.
DR CCDS; CCDS13518.1; -. [O43526-3]
DR CCDS; CCDS13519.1; -. [O43526-2]
DR CCDS; CCDS13520.1; -. [O43526-1]
DR CCDS; CCDS13521.1; -. [O43526-6]
DR CCDS; CCDS46629.1; -. [O43526-4]
DR PIR; JC5275; JC5275.
DR RefSeq; NP_004509.2; NM_004518.5. [O43526-3]
DR RefSeq; NP_742104.1; NM_172106.2. [O43526-2]
DR RefSeq; NP_742105.1; NM_172107.3. [O43526-1]
DR RefSeq; NP_742106.1; NM_172108.4. [O43526-4]
DR RefSeq; NP_742107.1; NM_172109.2. [O43526-6]
DR PDB; 5J03; X-ray; 2.00 A; A=530-557.
DR PDB; 6FEG; NMR; -; A=326-372.
DR PDB; 6FEH; NMR; -; A=326-372.
DR PDB; 7CR0; EM; 3.10 A; A/B/C/D=64-702.
DR PDB; 7CR1; EM; 3.40 A; A/B/C/D=64-702.
DR PDB; 7CR2; EM; 3.20 A; A/B/C/D=64-702.
DR PDB; 7CR3; EM; 3.60 A; A/B/D/G=64-702.
DR PDB; 7CR4; EM; 3.90 A; A/B/D/F=64-702.
DR PDB; 7CR7; EM; 3.70 A; A/B/D/G=64-702.
DR PDBsum; 5J03; -.
DR PDBsum; 6FEG; -.
DR PDBsum; 6FEH; -.
DR PDBsum; 7CR0; -.
DR PDBsum; 7CR1; -.
DR PDBsum; 7CR2; -.
DR PDBsum; 7CR3; -.
DR PDBsum; 7CR4; -.
DR PDBsum; 7CR7; -.
DR AlphaFoldDB; O43526; -.
DR SMR; O43526; -.
DR BioGRID; 109986; 9.
DR CORUM; O43526; -.
DR IntAct; O43526; 3.
DR STRING; 9606.ENSP00000352035; -.
DR BindingDB; O43526; -.
DR ChEMBL; CHEMBL2476; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB04953; Ezogabine.
DR DrugBank; DB06089; ICA-105665.
DR DrugBank; DB00939; Meclofenamic acid.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; O43526; -.
DR GuidetoPHARMACOLOGY; 561; -.
DR TCDB; 1.A.1.15.2; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; O43526; -.
DR PhosphoSitePlus; O43526; -.
DR BioMuta; KCNQ2; -.
DR jPOST; O43526; -.
DR MassIVE; O43526; -.
DR PaxDb; O43526; -.
DR PeptideAtlas; O43526; -.
DR PRIDE; O43526; -.
DR ProteomicsDB; 49031; -. [O43526-1]
DR ProteomicsDB; 49032; -. [O43526-2]
DR ProteomicsDB; 49033; -. [O43526-3]
DR ProteomicsDB; 49034; -. [O43526-4]
DR ProteomicsDB; 49035; -. [O43526-5]
DR ProteomicsDB; 49036; -. [O43526-6]
DR ABCD; O43526; 1 sequenced antibody.
DR Antibodypedia; 15101; 287 antibodies from 31 providers.
DR DNASU; 3785; -.
DR Ensembl; ENST00000344425.8; ENSP00000345523.5; ENSG00000075043.20. [O43526-6]
DR Ensembl; ENST00000344462.8; ENSP00000339611.4; ENSG00000075043.20. [O43526-4]
DR Ensembl; ENST00000359125.7; ENSP00000352035.2; ENSG00000075043.20. [O43526-1]
DR Ensembl; ENST00000360480.7; ENSP00000353668.3; ENSG00000075043.20. [O43526-3]
DR Ensembl; ENST00000626839.2; ENSP00000486706.1; ENSG00000075043.20. [O43526-2]
DR GeneID; 3785; -.
DR KEGG; hsa:3785; -.
DR MANE-Select; ENST00000359125.7; ENSP00000352035.2; NM_172107.4; NP_742105.1.
DR UCSC; uc002yey.2; human. [O43526-1]
DR CTD; 3785; -.
DR DisGeNET; 3785; -.
DR GeneCards; KCNQ2; -.
DR GeneReviews; KCNQ2; -.
DR HGNC; HGNC:6296; KCNQ2.
DR HPA; ENSG00000075043; Tissue enriched (brain).
DR MalaCards; KCNQ2; -.
DR MIM; 121200; phenotype.
DR MIM; 602235; gene.
DR MIM; 613720; phenotype.
DR neXtProt; NX_O43526; -.
DR OpenTargets; ENSG00000075043; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 306; Benign familial infantile epilepsy.
DR Orphanet; 1949; Benign familial neonatal epilepsy.
DR Orphanet; 140927; Benign familial neonatal-infantile seizures.
DR Orphanet; 439218; KCNQ2-related epileptic encephalopathy.
DR Orphanet; 293181; Malignant migrating focal seizures of infancy.
DR PharmGKB; PA30074; -.
DR VEuPathDB; HostDB:ENSG00000075043; -.
DR eggNOG; KOG1419; Eukaryota.
DR GeneTree; ENSGT00940000160093; -.
DR HOGENOM; CLU_011722_1_6_1; -.
DR InParanoid; O43526; -.
DR OMA; TSWQPQG; -.
DR OrthoDB; 1168835at2759; -.
DR PhylomeDB; O43526; -.
DR TreeFam; TF315186; -.
DR PathwayCommons; O43526; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR SignaLink; O43526; -.
DR SIGNOR; O43526; -.
DR BioGRID-ORCS; 3785; 25 hits in 1072 CRISPR screens.
DR ChiTaRS; KCNQ2; human.
DR GeneWiki; KvLQT2; -.
DR GenomeRNAi; 3785; -.
DR Pharos; O43526; Tclin.
DR PRO; PR:O43526; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O43526; protein.
DR Bgee; ENSG00000075043; Expressed in right hemisphere of cerebellum and 135 other tissues.
DR ExpressionAtlas; O43526; baseline and differential.
DR Genevisible; O43526; HS.
DR GO; GO:0043194; C:axon initial segment; ISS:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0030506; F:ankyrin binding; IPI:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR InterPro; IPR020969; Ankyrin-G_BS.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003937; K_chnl_volt-dep_KCNQ.
DR InterPro; IPR003947; K_chnl_volt-dep_KCNQ2.
DR InterPro; IPR013821; K_chnl_volt-dep_KCNQ_C.
DR InterPro; IPR028325; VG_K_chnl.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF6; PTHR11537:SF6; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03520; KCNQ_channel; 1.
DR Pfam; PF11956; KCNQC3-Ank-G_bd; 1.
DR PRINTS; PR01461; KCNQ2CHANNEL.
DR PRINTS; PR01459; KCNQCHANNEL.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW Epilepsy; Intellectual disability; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..872
FT /note="Potassium voltage-gated channel subfamily KQT member
FT 2"
FT /id="PRO_0000054030"
FT TOPO_DOM 1..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..112
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..122
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..218
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 265..285
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..291
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..872
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 317..539
FT /note="Mediates interaction with calmodulin"
FT /evidence="ECO:0000269|PubMed:27564677"
FT REGION 402..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..488
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 659..680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 693..757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 838..872
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 277..282
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 459..479
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9872318"
FT MOD_RES 217
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16319223"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88943"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88943"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88943"
FT MOD_RES 803
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88943"
FT VAR_SEQ 310..320
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:9827540"
FT /id="VSP_000984"
FT VAR_SEQ 373..393
FT /note="SSQTQTYGASRLIPPLNQLEL -> RYRRRAPATKQLFHFLFSICS (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9039501"
FT /id="VSP_000986"
FT VAR_SEQ 373..382
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9430594"
FT /id="VSP_000985"
FT VAR_SEQ 394..872
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9039501"
FT /id="VSP_000987"
FT VAR_SEQ 417..446
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9836639"
FT /id="VSP_000989"
FT VAR_SEQ 417..434
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11160379,
FT ECO:0000303|PubMed:9430594, ECO:0000303|PubMed:9827540"
FT /id="VSP_000988"
FT VAR_SEQ 509
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9836639"
FT /id="VSP_000990"
FT VARIANT 114
FT /note="T -> A (in BFNS1; dbSNP:rs1057516076)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078658"
FT VARIANT 154
FT /note="Y -> D (in BFNS1; with infantile seizures;
FT dbSNP:rs1057516078)"
FT /evidence="ECO:0000269|PubMed:23360469"
FT /id="VAR_078659"
FT VARIANT 159
FT /note="G -> E (in BFNS1; dbSNP:rs1057516081)"
FT /evidence="ECO:0000269|PubMed:23360469"
FT /id="VAR_078660"
FT VARIANT 159
FT /note="G -> R (in BFNS1; dbSNP:rs1057516080)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078661"
FT VARIANT 196
FT /note="A -> V (in BFNS1; with infantile seizures;
FT dbSNP:rs118192199)"
FT /evidence="ECO:0000269|PubMed:23360469"
FT /id="VAR_078662"
FT VARIANT 201
FT /note="R -> C (in DEE7; gain-of-function mutation; results
FT in loss of voltage-dependent channel gating and highly
FT increased potassium currents; dbSNP:rs796052623)"
FT /evidence="ECO:0000269|PubMed:25740509,
FT ECO:0000269|PubMed:26993267"
FT /id="VAR_078663"
FT VARIANT 204..872
FT /note="Missing (in BFNS1)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078664"
FT VARIANT 207
FT /note="R -> Q (found in a patient with isolated myokymia;
FT leads to a shift of voltage-dependent activation;
FT dbSNP:rs118192200)"
FT /evidence="ECO:0000269|PubMed:17872363"
FT /id="VAR_043819"
FT VARIANT 207
FT /note="R -> W (in BFNS1; phenotype manifestations include
FT myokymia in some patients; leads to a shift of voltage-
FT dependent activation of the channel and a dramatic slowing
FT of activation upon depolarization; dbSNP:rs74315391)"
FT /evidence="ECO:0000269|PubMed:11572947"
FT /id="VAR_026987"
FT VARIANT 208
FT /note="M -> V (in BFNS1; minor effect on maximal current
FT but clearly exhibits a faster rate of deactivation;
FT dbSNP:rs118192201)"
FT /evidence="ECO:0000269|PubMed:14534157"
FT /id="VAR_026988"
FT VARIANT 210
FT /note="R -> C (in DEE7; dbSNP:rs796052626)"
FT /evidence="ECO:0000269|PubMed:25818041"
FT /id="VAR_078665"
FT VARIANT 213
FT /note="R -> Q (in BFNS1 and DEE7; dbSNP:rs397514581)"
FT /evidence="ECO:0000269|PubMed:25982755,
FT ECO:0000269|PubMed:26993267"
FT /id="VAR_078666"
FT VARIANT 213
FT /note="R -> W (in BFNS1; unknown pathological significance;
FT dbSNP:rs118192203)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078667"
FT VARIANT 214
FT /note="R -> W (in BFNS1; dbSNP:rs28939684)"
FT /evidence="ECO:0000269|PubMed:11175290"
FT /id="VAR_010929"
FT VARIANT 217
FT /note="T -> A (in BFNS1; also in patients with infantile
FT seizures; dbSNP:rs1057516089)"
FT /evidence="ECO:0000269|PubMed:23360469"
FT /id="VAR_078668"
FT VARIANT 228
FT /note="H -> Q (in BFNS1; dbSNP:rs118192204)"
FT /evidence="ECO:0000269|PubMed:14534157"
FT /id="VAR_026989"
FT VARIANT 234
FT /note="T -> P (in DEE7; dbSNP:rs1057516091)"
FT /evidence="ECO:0000269|PubMed:25818041"
FT /id="VAR_078669"
FT VARIANT 243
FT /note="L -> F (in BFNS1; dbSNP:rs118192205)"
FT /evidence="ECO:0000269|PubMed:14534157"
FT /id="VAR_026990"
FT VARIANT 247
FT /note="S -> W (in DEE7; reduces channel currents by more
FT than 50% in homomeric channels; dbSNP:rs74315392)"
FT /evidence="ECO:0000269|PubMed:12742592"
FT /id="VAR_026991"
FT VARIANT 266
FT /note="D -> E (in DEE7; patient also manifests dyskinesia;
FT dbSNP:rs1057519536)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078207"
FT VARIANT 268
FT /note="L -> F (in DEE7; dbSNP:rs1057516094)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078208"
FT VARIANT 276
FT /note="T -> I (in DEE7; dbSNP:rs1057516095)"
FT /evidence="ECO:0000269|PubMed:24463883"
FT /id="VAR_078670"
FT VARIANT 284
FT /note="Y -> C (in BFNS1; 30%-60% reduction of wt current in
FT heteromeric channels; dbSNP:rs28939683)"
FT /evidence="ECO:0000269|PubMed:14534157,
FT ECO:0000269|PubMed:9425895, ECO:0000269|PubMed:9872318"
FT /id="VAR_010930"
FT VARIANT 291
FT /note="R -> S (in DEE7; dbSNP:rs1057519535)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078209"
FT VARIANT 294
FT /note="A -> V (in DEE7; dbSNP:rs118192211)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078210"
FT VARIANT 301
FT /note="G -> S (in DEE7; dbSNP:rs1057516099)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078211"
FT VARIANT 306
FT /note="A -> T (in BFNS1 and DEE7; 20%-40% reduction of wt
FT current in heteromeric channels; dbSNP:rs74315390)"
FT /evidence="ECO:0000269|PubMed:14534157,
FT ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:9425895,
FT ECO:0000269|PubMed:9872318"
FT /id="VAR_010931"
FT VARIANT 333
FT /note="R -> Q (in BFNS1; moderate effect; less than 50%
FT reduction in current compared with wt heteromeric channels;
FT dbSNP:rs118192216)"
FT /evidence="ECO:0000269|PubMed:14534157"
FT /id="VAR_026992"
FT VARIANT 353
FT /note="R -> G (in BFNS1; dbSNP:rs118192218)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078671"
FT VARIANT 358
FT /note="S -> F (in BFNS1; dbSNP:rs1057516110)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078672"
FT VARIANT 448..872
FT /note="Missing (in BFNS1; with infantile seizures)"
FT /evidence="ECO:0000269|PubMed:23360469,
FT ECO:0000269|PubMed:25982755"
FT /id="VAR_078673"
FT VARIANT 547
FT /note="R -> W (in BFNS1; dbSNP:rs796052650)"
FT /evidence="ECO:0000269|PubMed:23360469"
FT /id="VAR_078674"
FT VARIANT 554
FT /note="K -> N (in BFNS1 and DEE7; decreases the voltage-
FT dependence of the channel; dbSNP:rs267607198)"
FT /evidence="ECO:0000269|PubMed:15249611"
FT /id="VAR_026993"
FT VARIANT 561
FT /note="P -> S (in DEE7)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078675"
FT VARIANT 578..579
FT /note="ML -> IM (in DEE7; dbSNP:rs796052665)"
FT /evidence="ECO:0000269|PubMed:25818041"
FT /id="VAR_078676"
FT VARIANT 578
FT /note="M -> V (in BFNS1; dbSNP:rs1057516123)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078677"
FT VARIANT 581..872
FT /note="Missing (in BFNS1)"
FT /evidence="ECO:0000269|PubMed:25982755,
FT ECO:0000269|PubMed:26993267"
FT /id="VAR_078678"
FT VARIANT 581
FT /note="R -> Q (in DEE7; dbSNP:rs118192235)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078212"
FT VARIANT 588
FT /note="R -> S (in BFNS1; dbSNP:rs118192237)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078679"
FT VARIANT 637
FT /note="L -> R (in BFNS1; dbSNP:rs118192240)"
FT /evidence="ECO:0000269|PubMed:25982755"
FT /id="VAR_078680"
FT VARIANT 777
FT /note="P -> S (found in a patient with continuous spikes
FT and waves during sleep; unknown pathological significance;
FT dbSNP:rs748400155)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078213"
FT VARIANT 780
FT /note="N -> T (in dbSNP:rs1801475)"
FT /evidence="ECO:0000269|PubMed:10323247"
FT /id="VAR_010932"
FT MUTAGEN 52
FT /note="S->E: 40% increase in potassium current amplitude.
FT Ratio of 1:1."
FT /evidence="ECO:0000269|PubMed:9872318"
FT MUTAGEN 52
FT /note="S->Q: Decrease of PKA stimulation. Ratio of 1:1."
FT /evidence="ECO:0000269|PubMed:9872318"
FT MUTAGEN 217
FT /note="T->A: No effect on current or expression."
FT /evidence="ECO:0000269|PubMed:16319223"
FT MUTAGEN 217
FT /note="T->D: Abolishes currents without reducing channel
FT protein expression."
FT /evidence="ECO:0000269|PubMed:16319223"
FT MUTAGEN 279
FT /note="G->S: More than 50% reduction of wt heteromeric
FT current. Ratio of 1:1 and 1:1:2."
FT /evidence="ECO:0000269|PubMed:9872318"
FT CONFLICT 699
FT /note="K -> E (in Ref. 4; AAD16988)"
FT /evidence="ECO:0000305"
FT CONFLICT 854
FT /note="R -> C (in Ref. 4; AAD16988)"
FT /evidence="ECO:0000305"
FT HELIX 71..85
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 92..113
FT /evidence="ECO:0007829|PDB:7CR0"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 119..147
FT /evidence="ECO:0007829|PDB:7CR0"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 157..164
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 167..182
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 196..210
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 216..227
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 229..253
FT /evidence="ECO:0007829|PDB:7CR0"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 264..275
FT /evidence="ECO:0007829|PDB:7CR0"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:7CR0"
FT HELIX 288..304
FT /evidence="ECO:0007829|PDB:7CR2"
FT HELIX 324..333
FT /evidence="ECO:0007829|PDB:5J03"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:6FEH"
FT HELIX 357..367
FT /evidence="ECO:0007829|PDB:6FEG"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:6FEG"
SQ SEQUENCE 872 AA; 95848 MW; 22E8A0880A27B58C CRC64;
MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG
GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK
SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI
AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF
LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI
GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW
QYYERTVTVP MYSSQTQTYG ASRLIPPLNQ LELLRNLKSK SGLAFRKDPP PEPSPSKGSP
CRGPLCGCCP GRSSQKVSLK DRVFSSPRGV AAKGKGSPQA QTVRRSPSAD QSLEDSPSKV
PKSWSFGDRS RARQAFRIKG AASRQNSEEA SLPGEDIVDD KSCPCEFVTE DLTPGLKVSI
RAVCVMRFLV SKRKFKESLR PYDVMDVIEQ YSAGHLDMLS RIKSLQSRVD QIVGRGPAIT
DKDRTKGPAE AELPEDPSMM GRLGKVEKQV LSMEKKLDFL VNIYMQRMGI PPTETEAYFG
AKEPEPAPPY HSPEDSREHV DRHGCIVKIV RSSSSTGQKN FSAPPAAPPV QCPPSTSWQP
QSHPRQGHGT SPVGDHGSLV RIPPPPAHER SLSAYGGGNR ASMEFLRQED TPGCRPPEGN
LRDSDTSISI PSVDHEELER SFSGFSISQS KENLDALNSC YAAVAPCAKV RPYIAEGESD
TDSDLCTPCG PPPRSATGEG PFGDVGWAGP RK
