ID KCNA1_HUMAN Reviewed; 495 AA. AC Q09470; A6NM83; Q3MIQ9; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 2. DT 27-MAR-2024, entry version 222. DE RecName: Full=Potassium voltage-gated channel subfamily A member 1 {ECO:0000305}; DE AltName: Full=Voltage-gated K(+) channel HuKI {ECO:0000303|PubMed:19912772}; DE AltName: Full=Voltage-gated potassium channel HBK1 {ECO:0000303|PubMed:2128063}; DE AltName: Full=Voltage-gated potassium channel subunit Kv1.1; GN Name=KCNA1 {ECO:0000312|HGNC:HGNC:6218}; 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], FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR RP LOCATION, AND ACTIVITY REGULATION. RC TISSUE=Brain; RX PubMed=19912772; DOI=10.1016/1044-7431(90)90004-n; RA Ramaswami M., Gautam M., Kamb A., Rudy B., Tanouye M.A., Mathew M.K.; RT "Human potassium channel genes: molecular cloning and functional RT expression."; RL Mol. Cell. Neurosci. 1:214-223(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain cortex; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 263-315. RX PubMed=2128063; DOI=10.1042/bst0180891; RA Freeman S.N., Conley E.C., Brennand J.C., Russell N.J.W., Brammar W.J.; RT "Cloning and characterization of a cDNA encoding a human brain potassium RT channel."; RL Biochem. Soc. Trans. 18:891-892(1990). RN [6] RP INTERACTION WITH KCNA2 AND KCNAB2, SUBUNIT, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RX PubMed=11086297; RX DOI=10.1002/1096-9861(20000101)429:1<166::aid-cne13>3.0.co;2-y; RA Rasband M.N., Trimmer J.S.; RT "Subunit composition and novel localization of K+ channels in spinal RT cord."; RL J. Comp. Neurol. 429:166-176(2001). RN [7] RP RNA EDITING OF POSITION 400. RX PubMed=12907802; DOI=10.1126/science.1086763; RA Hoopengardner B., Bhalla T., Staber C., Reenan R.; RT "Nervous system targets of RNA editing identified by comparative RT genomics."; RL Science 301:832-836(2003). RN [8] RP PALMITOYLATION AT CYS-243, MUTAGENESIS OF 35-CYS--CYS-36 AND CYS-243, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15837928; DOI=10.1073/pnas.0501999102; RA Gubitosi-Klug R.A., Mancuso D.J., Gross R.W.; RT "The human Kv1.1 channel is palmitoylated, modulating voltage sensing: RT Identification of a palmitoylation consensus sequence."; RL Proc. Natl. Acad. Sci. U.S.A. 102:5964-5968(2005). RN [9] RP REVIEW. RX PubMed=17917103; DOI=10.1007/s12035-007-8001-0; RA Baranauskas G.; RT "Ionic channel function in action potential generation: current RT perspective."; RL Mol. Neurobiol. 35:129-150(2007). RN [10] RP INTERACTION WITH KCNRG, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19968958; DOI=10.1016/j.bbrc.2009.11.143; RA Usman H., Mathew M.K.; RT "Potassium channel regulator KCNRG regulates surface expression of Shaker- RT type potassium channels."; RL Biochem. Biophys. Res. Commun. 391:1301-1305(2010). RN [11] RP FUNCTION. RX PubMed=21106501; DOI=10.1093/brain/awq318; RA Tomlinson S.E., Tan S.V., Kullmann D.M., Griggs R.C., Burke D., Hanna M.G., RA Bostock H.; RT "Nerve excitability studies characterize Kv1.1 fast potassium channel RT dysfunction in patients with episodic ataxia type 1."; RL Brain 133:3530-3540(2010). RN [12] RP TISSUE SPECIFICITY. RX PubMed=21483673; DOI=10.1371/journal.pone.0018213; RA Ma Z., Lavebratt C., Almgren M., Portwood N., Forsberg L.E., Branstrom R., RA Berglund E., Falkmer S., Sundler F., Wierup N., Bjorklund A.; RT "Evidence for presence and functional effects of Kv1.1 channels in beta- RT cells: general survey and results from mceph/mceph mice."; RL PLoS ONE 6:E18213-E18213(2011). RN [13] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-446, AND MUTAGENESIS OF RP SER-446. RX PubMed=23774215; DOI=10.1158/0008-5472.can-12-3690; RA Lallet-Daher H., Wiel C., Gitenay D., Navaratnam N., Augert A., RA Le Calve B., Verbeke S., Carling D., Aubert S., Vindrieux D., Bernard D.; RT "Potassium channel KCNA1 modulates oncogene-induced senescence and RT transformation."; RL Cancer Res. 73:5253-5265(2013). RN [14] RP INTERACTION WITH ANK3, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=23903368; DOI=10.1038/ki.2013.280; RA San-Cristobal P., Lainez S., Dimke H., de Graaf M.J., Hoenderop J.G., RA Bindels R.J.; RT "Ankyrin-3 is a novel binding partner of the voltage-gated potassium RT channel Kv1.1 implicated in renal magnesium handling."; RL Kidney Int. 85:94-102(2014). RN [15] RP VARIANTS EA1 PHE-174; SER-239; ILE-249 AND ALA-408. RX PubMed=7842011; DOI=10.1038/ng1094-136; RA Browne D.L., Gancher S.T., Nutt J.G., Brunt E.R.P., Smith E.A., Kramer P., RA Litt M.; RT "Episodic ataxia/myokymia syndrome is associated with point mutations in RT the human potassium channel gene, KCNA1."; RL Nat. Genet. 8:136-140(1994). RN [16] RP VARIANTS EA1 PHE-174; CYS-184 AND ASP-325. RX PubMed=8541859; DOI=10.1093/hmg/4.9.1671; RA Browne D.L., Brunt E.R.P., Griggs R.C., Nutt J.G., Gancher S.T., RA Smith E.A., Litt M.; RT "Identification of two new KCNA1 mutations in episodic ataxia/myokymia RT families."; RL Hum. Mol. Genet. 4:1671-1672(1995). RN [17] RP CHARACTERIZATION OF VARIANTS EA1 CYS-184; ASP-325 AND ALA-408, FUNCTION, RP AND TRANSPORTER ACTIVITY. RX PubMed=8845167; DOI=10.1016/0896-6273(95)90022-5; RA Adelman J.P., Bond C.T., Pessia M., Maylie J.; RT "Episodic ataxia results from voltage-dependent potassium channels with RT altered functions."; RL Neuron 15:1449-1454(1995). RN [18] RP VARIANT EA1 MET-226. RX PubMed=8871592; DOI=10.1002/ana.410400422; RA Comu S., Giuliani M., Narayanan V.; RT "Episodic ataxia and myokymia syndrome: a new mutation of potassium channel RT gene Kv1.1."; RL Ann. Neurol. 40:684-687(1996). RN [19] RP VARIANTS EA1 ARG-177; ALA-226 AND ILE-404. RX PubMed=9600245; DOI=10.1007/s004390050722; RA Scheffer H., Brunt E.R.P., Mol G.J.J., van der Vlies P., Stulp R.P., RA Verlind E., Mantel G., Averyanov Y.N., Hofstra R.M.W., Buys C.H.C.M.; RT "Three novel KCNA1 mutations in episodic ataxia type I families."; RL Hum. Genet. 102:464-466(1998). RN [20] RP VARIANT EA1 ARG-226, AND CHARACTERIZATION OF VARIANT EA1 ARG-226. RX PubMed=10355668; DOI=10.1093/brain/122.5.817; RA Zuberi S.M., Eunson L.H., Spauschus A., De Silva R., Tolmie J., Wood N.W., RA McWilliam R.C., Stephenson J.P.B., Kullmann D.M., Hanna M.G.; RT "A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) RT associates with episodic ataxia type 1 and sometimes with partial RT epilepsy."; RL Brain 122:817-825(1999). RN [21] RP VARIANTS MK1 PRO-242 AND HIS-244, VARIANT EA1 ILE-404, CHARACTERIZATION OF RP VARIANTS MK1 PRO-242 AND HIS-244, CHARACTERIZATION OF VARIANT EA1 ILE-404, RP AND FUNCTION. RX PubMed=11026449; RX DOI=10.1002/1531-8249(200010)48:4<647::aid-ana12>3.3.co;2-h; RA Eunson L.H., Rea R., Zuberi S.M., Youroukos S., Panayiotopoulos C.P., RA Liguori R., Avoni P., McWilliam R.C., Stephenson J.B.P., Hanna M.G., RA Kullmann D.M., Spauschus A.; RT "Clinical, genetic, and expression studies of mutations in the potassium RT channel gene KCNA1 reveal new phenotypic variability."; RL Ann. Neurol. 48:647-656(2000). RN [22] RP VARIANT EA1 ILE-329. RX PubMed=11013453; RX DOI=10.1002/1098-1004(200010)16:4<374::aid-humu15>3.0.co;2-4; RA Knight M.A., Storey E., McKinlay Gardner R.J., Hand P., Forrest S.M.; RT "Identification of a novel missense mutation L329I in the episodic ataxia RT type 1 gene KCNA1 -- a challenging problem."; RL Hum. Mutat. 16:374-374(2000). RN [23] RP CHARACTERIZATION OF VARIANTS EA1 ASP-325 AND ALA-408, FUNCTION, SUBCELLULAR RP LOCATION, SUBUNIT, AND INTERACTION WITH KCNAB1. RX PubMed=12077175; DOI=10.1523/jneurosci.22-12-04786.2002; RA Maylie B., Bissonnette E., Virk M., Adelman J.P., Maylie J.G.; RT "Episodic ataxia type 1 mutations in the human Kv1.1 potassium channel RT alter hKvbeta 1-induced N-type inactivation."; RL J. Neurosci. 22:4786-4793(2002). RN [24] RP VARIANT EA1 ILE-342. RX PubMed=15532032; DOI=10.1002/humu.9295; RA Lee H., Wang H., Jen J.C., Sabatti C., Baloh R.W., Nelson S.F.; RT "A novel mutation in KCNA1 causes episodic ataxia without myokymia."; RL Hum. Mutat. 24:536-536(2004). RN [25] RP CHARACTERIZATION OF VARIANTS EA1 ASP-325; ILE-404 AND ALA-408, MUTAGENESIS RP OF ILE-177, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17156368; DOI=10.1111/j.1460-9568.2006.05186.x; RA Imbrici P., D'Adamo M.C., Kullmann D.M., Pessia M.; RT "Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast RT inactivation properties of the human potassium channels Kv1.4-1.1/Kvbeta1.1 RT and Kv1.4-1.1/Kvbeta1.2."; RL Eur. J. Neurosci. 24:3073-3083(2006). RN [26] RP VARIANT MK1 LYS-226, CHARACTERIZATION OF VARIANT MK1 LYS-226, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=17136396; DOI=10.1007/s10048-006-0071-z; RA Chen H., von Hehn C., Kaczmarek L.K., Ment L.R., Pober B.R., Hisama F.M.; RT "Functional analysis of a novel potassium channel (KCNA1) mutation in RT hereditary myokymia."; RL Neurogenetics 8:131-135(2007). RN [27] RP VARIANT MK1 ASP-255, CHARACTERIZATION OF VARIANT MK1 ASP-255, FUNCTION, RP TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION. RX PubMed=19307729; DOI=10.1172/jci36948; RA Glaudemans B., van der Wijst J., Scola R.H., Lorenzoni P.J., Heister A., RA van der Kemp A.W., Knoers N.V., Hoenderop J.G., Bindels R.J.; RT "A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding RT gene KCNA1 is linked to human autosomal dominant hypomagnesemia."; RL J. Clin. Invest. 119:936-942(2009). RN [28] RP CHARACTERIZATION OF VARIANT MK1 ASP-255, MUTAGENESIS OF ASN-255, FUNCTION, RP TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=19903818; DOI=10.1074/jbc.m109.041517; RA van der Wijst J., Glaudemans B., Venselaar H., Nair A.V., Forst A.L., RA Hoenderop J.G., Bindels R.J.; RT "Functional analysis of the Kv1.1 N255D mutation associated with autosomal RT dominant hypomagnesemia."; RL J. Biol. Chem. 285:171-178(2010). RN [29] RP VARIANT LEU-405. 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: Voltage-gated potassium channel that mediates transmembrane CC potassium transport in excitable membranes, primarily in the brain and CC the central nervous system, but also in the kidney (PubMed:8845167, CC PubMed:19903818). Contributes to the regulation of the membrane CC potential and nerve signaling, and prevents neuronal hyperexcitability CC (PubMed:17156368). Forms tetrameric potassium-selective channels CC through which potassium ions pass in accordance with their CC electrochemical gradient. The channel alternates between opened and CC closed conformations in response to the voltage difference across the CC membrane (PubMed:19912772). Can form functional homotetrameric channels CC and heterotetrameric channels that contain variable proportions of CC KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family CC members as well; channel properties depend on the type of alpha CC subunits that are part of the channel (PubMed:12077175, CC PubMed:17156368). Channel properties are modulated by cytoplasmic beta CC subunits that regulate the subcellular location of the alpha subunits CC and promote rapid inactivation of delayed rectifier potassium channels CC (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain CC a mixture of heteromeric potassium channel complexes, making it CC difficult to assign currents observed in intact tissues to any CC particular potassium channel family member. Homotetrameric KCNA1 forms CC a delayed-rectifier potassium channel that opens in response to CC membrane depolarization, followed by slow spontaneous channel closure CC (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). CC In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows CC rapid inactivation (PubMed:17156368). Regulates neuronal excitability CC in hippocampus, especially in mossy fibers and medial perforant path CC axons, preventing neuronal hyperexcitability. Response to toxins that CC are selective for KCNA1, respectively for KCNA2, suggests that CC heteromeric potassium channels composed of both KCNA1 and KCNA2 play a CC role in pacemaking and regulate the output of deep cerebellar nuclear CC neurons (By similarity). May function as down-stream effector for G CC protein-coupled receptors and inhibit GABAergic inputs to basolateral CC amygdala neurons (By similarity). May contribute to the regulation of CC neurotransmitter release, such as gamma-aminobutyric acid (GABA) CC release (By similarity). Plays a role in regulating the generation of CC action potentials and preventing hyperexcitability in myelinated axons CC of the vagus nerve, and thereby contributes to the regulation of heart CC contraction (By similarity). Required for normal neuromuscular CC responses (PubMed:11026449, PubMed:17136396). Regulates the frequency CC of neuronal action potential firing in response to mechanical stimuli, CC and plays a role in the perception of pain caused by mechanical CC stimuli, but does not play a role in the perception of pain due to heat CC stimuli (By similarity). Required for normal responses to auditory CC stimuli and precise location of sound sources, but not for sound CC perception (By similarity). The use of toxins that block specific CC channels suggest that it contributes to the regulation of the axonal CC release of the neurotransmitter dopamine (By similarity). Required for CC normal postnatal brain development and normal proliferation of neuronal CC precursor cells in the brain (By similarity). Plays a role in the CC reabsorption of Mg(2+) in the distal convoluted tubules in the kidney CC and in magnesium ion homeostasis, probably via its effect on the CC membrane potential (PubMed:23903368, PubMed:19307729). CC {ECO:0000250|UniProtKB:P10499, ECO:0000269|PubMed:11026449, CC ECO:0000269|PubMed:12077175, ECO:0000269|PubMed:15837928, CC ECO:0000269|PubMed:17136396, ECO:0000269|PubMed:17156368, CC ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818, CC ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:19968958, CC ECO:0000269|PubMed:21106501, ECO:0000269|PubMed:23903368, CC ECO:0000269|PubMed:8845167}. CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818, CC ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:8845167}; CC -!- ACTIVITY REGULATION: Inhibited by 1.1 mM 4-aminopyridine (4-AP) and by CC 20 mM tetraethylammonium (TEA), but not by charybdotoxin CC (CTX)(PubMed:19912772). Inhibited by dendrotoxin (DTX) CC (PubMed:19307729). {ECO:0000269|PubMed:19307729, CC ECO:0000269|PubMed:19912772}. CC -!- SUBUNIT: Homotetramer and heterotetramer with other channel-forming CC alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 CC (PubMed:12077175, PubMed:17156368). Channel activity is regulated by CC interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:12077175, CC PubMed:17156368). Identified in a complex with KCNA2 and KCNAB2 CC (PubMed:11086297). Interacts (via C-terminus) with the PDZ domains of CC DLG1, DLG2 and DLG4 (By similarity). Interacts with LGI1 within a CC complex containing LGI1, KCNA4 and KCNAB1 (By similarity). Interacts CC (via N-terminus) with STX1A; this promotes channel inactivation (By CC similarity). Interacts (via N-terminus) with the heterodimer formed by CC GNB1 and GNG2; this promotes channel inactivation (By similarity). Can CC interact simultaneously with STX1A and the heterodimer formed by GNB1 CC and GNG2 (By similarity). Interacts (via cytoplasmic N-terminal domain) CC with KCNRG; this inhibits channel activity (PubMed:19968958). Interacts CC with ANK3; this inhibits channel activity (PubMed:23903368). Interacts CC with ADAM11 (By similarity). {ECO:0000250|UniProtKB:P10499, CC ECO:0000250|UniProtKB:P16388, ECO:0000269|PubMed:11086297, CC ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19968958, CC ECO:0000269|PubMed:23903368, ECO:0000305}. CC -!- INTERACTION: CC Q09470; Q9BQE5: APOL2; NbExp=3; IntAct=EBI-8286599, EBI-4290634; CC Q09470; P78352: DLG4; NbExp=2; IntAct=EBI-8286599, EBI-80389; CC Q09470; Q9UPQ8: DOLK; NbExp=7; IntAct=EBI-8286599, EBI-8645574; CC Q09470; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-8286599, EBI-13345167; CC Q09470; O15529: GPR42; NbExp=3; IntAct=EBI-8286599, EBI-18076404; CC Q09470; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-8286599, EBI-725665; CC Q09470; Q8N5M9: JAGN1; NbExp=5; IntAct=EBI-8286599, EBI-10266796; CC Q09470; Q16322: KCNA10; NbExp=3; IntAct=EBI-8286599, EBI-12265328; CC Q09470; P22001: KCNA3; NbExp=3; IntAct=EBI-8286599, EBI-8627664; CC Q09470; P21145: MAL; NbExp=3; IntAct=EBI-8286599, EBI-3932027; CC Q09470; O43765: SGTA; NbExp=3; IntAct=EBI-8286599, EBI-347996; CC Q09470; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-8286599, EBI-8638294; CC Q09470; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-8286599, EBI-12015604; CC Q09470; Q62936: Dlg3; Xeno; NbExp=2; IntAct=EBI-8286599, EBI-349596; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12077175, CC ECO:0000269|PubMed:15837928, ECO:0000269|PubMed:17136396, CC ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19307729, CC ECO:0000269|PubMed:19903818, ECO:0000269|PubMed:19912772, CC ECO:0000269|PubMed:19968958, ECO:0000269|PubMed:23903368}; Multi-pass CC membrane protein {ECO:0000305}. Membrane {ECO:0000269|PubMed:11086297}. CC Cell projection, axon {ECO:0000269|PubMed:11086297}. Cytoplasmic CC vesicle {ECO:0000269|PubMed:23774215}. Perikaryon CC {ECO:0000250|UniProtKB:P10499}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:P10499}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:P16388}. Cell junction CC {ECO:0000250|UniProtKB:P16388}. Synapse {ECO:0000250|UniProtKB:P16388}. CC Presynaptic cell membrane {ECO:0000250|UniProtKB:P10499}. Presynapse CC {ECO:0000250|UniProtKB:P16388}. Note=Homotetrameric KCNA1 is primarily CC located in the endoplasmic reticulum. Interaction with KCNA2 and KCNAB2 CC or with KCNA4 and KCNAB2 promotes expression at the cell membrane (By CC similarity). {ECO:0000250|UniProtKB:P10499, CC ECO:0000250|UniProtKB:P16388}. CC -!- TISSUE SPECIFICITY: Detected adjacent to nodes of Ranvier in CC juxtaparanodal zones in spinal cord nerve fibers, but also in paranodal CC regions in some myelinated spinal cord axons (at protein level) CC (PubMed:11086297). Detected in the islet of Langerhans CC (PubMed:21483673). {ECO:0000269|PubMed:11086297, CC ECO:0000269|PubMed:21483673}. CC -!- DOMAIN: The cytoplasmic N-terminus is important for tetramerization and CC for interaction with the beta subunits that promote rapid channel CC closure. {ECO:0000250|UniProtKB:P10499}. CC -!- DOMAIN: The transmembrane segment S4 functions as a voltage-sensor and CC is characterized by a series of positively charged amino acids at every CC third position. Channel opening and closing is effected by a CC conformation change that affects the position and orientation of the CC voltage-sensor paddle formed by S3 and S4 within the membrane. A CC transmembrane electric field that is positive inside would push the CC positively charged S4 segment outwards, thereby opening the pore, while CC a field that is negative inside would pull the S4 segment inwards and CC close the pore. Changes in the position and orientation of S4 are then CC transmitted to the activation gate formed by the inner helix bundle via CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P10499}. CC -!- PTM: Palmitoylated on Cys-243; which may be required for membrane CC targeting. {ECO:0000269|PubMed:15837928}. CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation increases in CC response to NRG1; this inhibits channel activity (By similarity). CC Phosphorylation at Ser-446 regulates channel activity by down- CC regulating expression at the cell membrane (PubMed:23774215). CC {ECO:0000250|UniProtKB:P16388, ECO:0000269|PubMed:23774215}. CC -!- RNA EDITING: Modified_positions=400 {ECO:0000269|PubMed:12907802}; CC Note=Partially edited. RNA editing varies from 17% in the caudate CC nucleus to 68% in the spinal cord and to 77% in the medulla.; CC -!- DISEASE: Episodic ataxia 1 (EA1) [MIM:160120]: An autosomal dominant CC disorder characterized by brief episodes of ataxia and dysarthria. CC Neurological examination during and between the attacks demonstrates CC spontaneous, repetitive discharges in the distal musculature (myokymia) CC that arise from peripheral nerve. Nystagmus is absent. CC {ECO:0000269|PubMed:10355668, ECO:0000269|PubMed:11013453, CC ECO:0000269|PubMed:11026449, ECO:0000269|PubMed:12077175, CC ECO:0000269|PubMed:15532032, ECO:0000269|PubMed:17156368, CC ECO:0000269|PubMed:7842011, ECO:0000269|PubMed:8541859, CC ECO:0000269|PubMed:8845167, ECO:0000269|PubMed:8871592, CC ECO:0000269|PubMed:9600245}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myokymia isolated 1 (MK1) [MIM:160120]: A condition CC characterized by spontaneous involuntary contraction of muscle fiber CC groups that can be observed as vermiform movement of the overlying CC skin. Electromyography typically shows continuous motor unit activity CC with spontaneous oligo- and multiplet-discharges of high intraburst CC frequency (myokymic discharges). Isolated spontaneous muscle twitches CC occur in many persons and have no grave significance. CC {ECO:0000269|PubMed:11026449, ECO:0000269|PubMed:17136396, CC ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: The delay or D-type current observed in hippocampus CC pyramidal neurons is probably mediated by potassium channels containing CC KCNA2 plus KCNA1 or other family members. It is activated at about -50 CC mV, i.e. below the action potential threshold, and is characterized by CC slow inactivation, extremely slow recovery from inactivation, CC sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP). CC {ECO:0000305|PubMed:17917103}. CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) CC (TC 1.A.1.2) subfamily. Kv1.1/KCNA1 sub-subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L02750; AAA36139.1; -; mRNA. DR EMBL; AC006063; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471116; EAW88833.1; -; Genomic_DNA. DR EMBL; BC101733; AAI01734.1; -; mRNA. DR EMBL; BC112180; AAI12181.1; -; mRNA. DR CCDS; CCDS8535.1; -. DR PIR; I57680; I57680. DR RefSeq; NP_000208.2; NM_000217.2. DR AlphaFoldDB; Q09470; -. DR SMR; Q09470; -. DR BioGRID; 109939; 21. DR CORUM; Q09470; -. DR IntAct; Q09470; 15. DR MINT; Q09470; -. DR STRING; 9606.ENSP00000371985; -. DR BindingDB; Q09470; -. DR ChEMBL; CHEMBL2309; -. DR DrugBank; DB11640; Amifampridine. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB06637; Dalfampridine. DR DrugBank; DB01189; Desflurane. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB00753; Isoflurane. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB08837; Tetraethylammonium. DR DrugCentral; Q09470; -. DR GuidetoPHARMACOLOGY; 538; -. DR TCDB; 1.A.1.2.12; the voltage-gated ion channel (vic) superfamily. DR TCDB; 8.B.31.1.1; the shaker-like peptide inhibitor, kappa-actitoxin-ate1a (ate1a) family. DR GlyCosmos; Q09470; 1 site, No reported glycans. DR GlyGen; Q09470; 1 site. DR iPTMnet; Q09470; -. DR PhosphoSitePlus; Q09470; -. DR SwissPalm; Q09470; -. DR BioMuta; KCNA1; -. DR DMDM; 223590092; -. DR jPOST; Q09470; -. DR MassIVE; Q09470; -. DR MaxQB; Q09470; -. DR PaxDb; 9606-ENSP00000371985; -. DR PeptideAtlas; Q09470; -. DR ProteomicsDB; 58722; -. DR ABCD; Q09470; 2 sequenced antibodies. DR Antibodypedia; 22315; 513 antibodies from 35 providers. DR DNASU; 3736; -. DR Ensembl; ENST00000382545.5; ENSP00000371985.3; ENSG00000111262.6. DR GeneID; 3736; -. DR KEGG; hsa:3736; -. DR MANE-Select; ENST00000382545.5; ENSP00000371985.3; NM_000217.3; NP_000208.2. DR UCSC; uc001qnh.4; human. DR AGR; HGNC:6218; -. DR CTD; 3736; -. DR DisGeNET; 3736; -. DR GeneCards; KCNA1; -. DR GeneReviews; KCNA1; -. DR HGNC; HGNC:6218; KCNA1. DR HPA; ENSG00000111262; Tissue enriched (brain). DR MalaCards; KCNA1; -. DR MIM; 160120; phenotype. DR MIM; 176260; gene. DR neXtProt; NX_Q09470; -. DR OpenTargets; ENSG00000111262; -. DR Orphanet; 1934; Early infantile epileptic encephalopathy. DR Orphanet; 37612; Episodic ataxia type 1. DR Orphanet; 972; Hereditary continuous muscle fiber activity. DR Orphanet; 199326; Isolated autosomal dominant hypomagnesemia, Glaudemans type. DR Orphanet; 98809; Paroxysmal kinesigenic dyskinesia. DR PharmGKB; PA30019; -. DR VEuPathDB; HostDB:ENSG00000111262; -. DR eggNOG; KOG1545; Eukaryota. DR GeneTree; ENSGT00940000158576; -. DR HOGENOM; CLU_011722_4_0_1; -. DR InParanoid; Q09470; -. DR OMA; IATQNCV; -. DR OrthoDB; 1478695at2759; -. DR PhylomeDB; Q09470; -. DR TreeFam; TF313103; -. DR PathwayCommons; Q09470; -. DR Reactome; R-HSA-1296072; Voltage gated Potassium channels. DR SignaLink; Q09470; -. DR SIGNOR; Q09470; -. DR BioGRID-ORCS; 3736; 13 hits in 1160 CRISPR screens. DR ChiTaRS; KCNA1; human. DR GeneWiki; Kv1.1; -. DR GenomeRNAi; 3736; -. DR Pharos; Q09470; Tclin. DR PRO; PR:Q09470; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q09470; Protein. DR Bgee; ENSG00000111262; Expressed in endothelial cell and 114 other cell types or tissues. DR ExpressionAtlas; Q09470; baseline and differential. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0043194; C:axon initial segment; IEA:Ensembl. DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB. DR GO; GO:0044305; C:calyx of Held; IEA:Ensembl. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB. DR GO; GO:0033270; C:paranode region of axon; IDA:UniProtKB. DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB. DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB. DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA. DR GO; GO:1905030; F:voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl. DR GO; GO:0099508; F:voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB. DR GO; GO:0061564; P:axon development; IEA:Ensembl. DR GO; GO:0010644; P:cell communication by electrical coupling; ISS:UniProtKB. DR GO; GO:0071286; P:cellular response to magnesium ion; ISS:UniProtKB. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0022038; P:corpus callosum development; IEA:Ensembl. DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISS:UniProtKB. DR GO; GO:0050976; P:detection of mechanical stimulus involved in sensory perception of touch; ISS:UniProtKB. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0010960; P:magnesium ion homeostasis; IMP:UniProtKB. DR GO; GO:0086011; P:membrane repolarization during action potential; IMP:UniProtKB. DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl. DR GO; GO:0050905; P:neuromuscular process; IMP:UniProtKB. DR GO; GO:0019228; P:neuronal action potential; ISS:UniProtKB. DR GO; GO:0023041; P:neuronal signal transduction; ISS:UniProtKB. DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl. DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro. DR GO; GO:0008104; P:protein localization; IEA:Ensembl. DR GO; GO:0042391; P:regulation of membrane potential; IMP:UniProtKB. DR GO; GO:0006937; P:regulation of muscle contraction; ISS:UniProtKB. DR GO; GO:0001964; P:startle response; IEA:Ensembl. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 1. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR003968; K_chnl_volt-dep_Kv. DR InterPro; IPR003972; K_chnl_volt-dep_Kv1. DR InterPro; IPR004048; K_chnl_volt-dep_Kv1.1. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR003131; T1-type_BTB. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR11537:SF24; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY A MEMBER 1; 1. DR PANTHER; PTHR11537; VOLTAGE-GATED POTASSIUM CHANNEL; 1. DR Pfam; PF02214; BTB_2; 1. DR Pfam; PF00520; Ion_trans; 1. DR PRINTS; PR00169; KCHANNEL. DR PRINTS; PR01508; KV11CHANNEL. DR PRINTS; PR01491; KVCHANNEL. DR PRINTS; PR01496; SHAKERCHANEL. DR SMART; SM00225; BTB; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; Q09470; HS. PE 1: Evidence at protein level; KW Cell junction; Cell membrane; Cell projection; Cytoplasmic vesicle; KW Disease variant; Endoplasmic reticulum; Glycoprotein; Ion channel; KW Ion transport; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Potassium; KW Potassium channel; Potassium transport; Reference proteome; RNA editing; KW Synapse; Transmembrane; Transmembrane helix; Transport; KW Voltage-gated channel. FT CHAIN 1..495 FT /note="Potassium voltage-gated channel subfamily A member FT 1" FT /id="PRO_0000053968" FT TOPO_DOM 1..164 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TRANSMEM 165..186 FT /note="Helical; Name=Segment S1" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 187..220 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TRANSMEM 221..242 FT /note="Helical; Name=Segment S2" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 243..253 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TRANSMEM 254..274 FT /note="Helical; Name=Segment S3" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 275..287 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TRANSMEM 288..308 FT /note="Helical; Voltage-sensor; Name=Segment S4" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 309..323 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TRANSMEM 324..345 FT /note="Helical; Name=Segment S5" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 346..359 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P63142" FT INTRAMEM 360..371 FT /note="Helical; Name=Pore helix" FT /evidence="ECO:0000250|UniProtKB:P63142" FT INTRAMEM 372..379 FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 380..386 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TRANSMEM 387..415 FT /note="Helical; Name=Segment S6" FT /evidence="ECO:0000250|UniProtKB:P63142" FT TOPO_DOM 416..495 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P63142" FT REGION 1..128 FT /note="Tetramerization domain" FT /evidence="ECO:0000250|UniProtKB:P10499" FT REGION 1..30 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 310..323 FT /note="S4-S5 linker" FT /evidence="ECO:0000250|UniProtKB:P63142" FT MOTIF 372..377 FT /note="Selectivity filter" FT /evidence="ECO:0000250|UniProtKB:P63142" FT MOTIF 493..495 FT /note="PDZ-binding" FT /evidence="ECO:0000250" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P10499" FT MOD_RES 322 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 437 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P10499" FT MOD_RES 439 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P10499" FT MOD_RES 446 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000305|PubMed:23774215" FT LIPID 243 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:15837928" FT CARBOHYD 207 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 174 FT /note="V -> F (in EA1; dbSNP:rs104894349)" FT /evidence="ECO:0000269|PubMed:7842011, FT ECO:0000269|PubMed:8541859" FT /id="VAR_001508" FT VARIANT 177 FT /note="I -> R (in EA1)" FT /evidence="ECO:0000269|PubMed:9600245" FT /id="VAR_001509" FT VARIANT 184 FT /note="F -> C (in EA1; alters voltage dependence and FT kinetics of activation though not of C-type inactivation; FT dbSNP:rs104894357)" FT /evidence="ECO:0000269|PubMed:8541859, FT ECO:0000269|PubMed:8845167" FT /id="VAR_020830" FT VARIANT 204 FT /note="R -> H (in dbSNP:rs2229000)" FT /id="VAR_020051" FT VARIANT 226 FT /note="T -> A (in EA1; dbSNP:rs104894354)" FT /evidence="ECO:0000269|PubMed:9600245" FT /id="VAR_001510" FT VARIANT 226 FT /note="T -> K (in MK1; induces a reduced efflux of FT potassium ions during depolarization which results in FT increased muscle cell activity; coexpression studies of the FT mutant protein with the wild-type protein produces FT significantly reduced currents suggesting a severe effect FT of the mutation; dbSNP:rs28933383)" FT /evidence="ECO:0000269|PubMed:17136396" FT /id="VAR_037100" FT VARIANT 226 FT /note="T -> M (in EA1; dbSNP:rs28933383)" FT /evidence="ECO:0000269|PubMed:8871592" FT /id="VAR_020831" FT VARIANT 226 FT /note="T -> R (in EA1; yields currents with a largely FT reduced amplitude; dbSNP:rs28933383)" FT /evidence="ECO:0000269|PubMed:10355668" FT /id="VAR_037101" FT VARIANT 239 FT /note="R -> S (in EA1; dbSNP:rs104894348)" FT /evidence="ECO:0000269|PubMed:7842011" FT /id="VAR_001511" FT VARIANT 242 FT /note="A -> P (in MK1; 10% reduction of mean peak current FT amplitudes compared to wil-dtype; mutant and wild-type FT expression together is consistent with a loss-of-function FT effect of the mutation; dbSNP:rs28933381)" FT /evidence="ECO:0000269|PubMed:11026449" FT /id="VAR_037102" FT VARIANT 244 FT /note="P -> H (in MK1; does not affect channel activity; FT dbSNP:rs28933382)" FT /evidence="ECO:0000269|PubMed:11026449" FT /id="VAR_037103" FT VARIANT 249 FT /note="F -> I (in EA1; dbSNP:rs104894356)" FT /evidence="ECO:0000269|PubMed:7842011" FT /id="VAR_001512" FT VARIANT 255 FT /note="N -> D (in MK1; strongly reduces the activity of FT homomeric channels with dominant negative effects on FT wild-type channels; dbSNP:rs121918067)" FT /evidence="ECO:0000269|PubMed:19307729" FT /id="VAR_072397" FT VARIANT 325 FT /note="E -> D (in EA1; results in non-functional homomeric FT channels; accelerates recovery from N-type inactivation due FT to interaction with KCNAB1; slows down N-type inactivation FT of heteromeric channels formed by KCNA1 and KCNA4; FT dbSNP:rs104894353)" FT /evidence="ECO:0000269|PubMed:12077175, FT ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:8541859, FT ECO:0000269|PubMed:8845167" FT /id="VAR_020832" FT VARIANT 329 FT /note="L -> I (in EA1)" FT /evidence="ECO:0000269|PubMed:11013453" FT /id="VAR_020833" FT VARIANT 342 FT /note="S -> I (in EA1; phenotype without myokymia)" FT /evidence="ECO:0000269|PubMed:15532032" FT /id="VAR_020834" FT VARIANT 400 FT /note="I -> V (in RNA edited version)" FT /id="VAR_016805" FT VARIANT 404 FT /note="V -> I (in EA1; results in slower channel activation FT compared to wild-type; slows down N-type inactivation of FT heteromeric channels formed by KCNA1 and KCNA4; FT dbSNP:rs104894355)" FT /evidence="ECO:0000269|PubMed:11026449, FT ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:9600245" FT /id="VAR_001513" FT VARIANT 405 FT /note="P -> L (found in a patient with neonatal onset FT epileptic encephalopathy; likely pathogenic; FT dbSNP:rs1555085798)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078205" FT VARIANT 408 FT /note="V -> A (in EA1; channels have voltage dependence FT similar to that of wild-type channels but with faster FT kinetics and increased C-type inactivation; accelerates FT recovery from N-type inactivation due to interaction with FT KCNAB1; slows down N-type inactivation of heteromeric FT channels formed by KCNA1 and KCNA4; dbSNP:rs104894352)" FT /evidence="ECO:0000269|PubMed:12077175, FT ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:7842011, FT ECO:0000269|PubMed:8845167" FT /id="VAR_001514" FT MUTAGEN 35..36 FT /note="CC->AA: No effect on palmitoylation, no effect on FT current kinetics." FT /evidence="ECO:0000269|PubMed:15837928" FT MUTAGEN 177 FT /note="I->N: Slows down N-type inactivation of heteromeric FT channels formed by KCNA1 and KCNA4." FT /evidence="ECO:0000269|PubMed:17156368" FT MUTAGEN 243 FT /note="C->A: Strongly decreases palmitoylation and alters FT current kinetics." FT /evidence="ECO:0000269|PubMed:15837928" FT MUTAGEN 255 FT /note="N->A,H,T: Slightly increases channel activity, but FT does not affect expression at the cell membrane." FT /evidence="ECO:0000269|PubMed:19307729" FT MUTAGEN 255 FT /note="N->E: Abolishes channel activity, but does not FT affect expression at the cell membrane." FT /evidence="ECO:0000269|PubMed:19307729" FT MUTAGEN 255 FT /note="N->Q: Strongly reduces channel activity, but does FT not affect expression at the cell membrane." FT /evidence="ECO:0000269|PubMed:19307729" FT MUTAGEN 255 FT /note="N->V: No effect on channel activity." FT /evidence="ECO:0000269|PubMed:19307729" FT MUTAGEN 446 FT /note="S->A: Impairs phosphorylation by PKA." FT /evidence="ECO:0000269|PubMed:23774215" FT MUTAGEN 446 FT /note="S->E: Impairs expression at the cell membrane." FT /evidence="ECO:0000269|PubMed:23774215" FT CONFLICT 265 FT /note="Missing (in Ref. 5; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 315 FT /note="L -> R (in Ref. 5; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 452 FT /note="S -> Y (in Ref. 1; AAA36139)" FT /evidence="ECO:0000305" SQ SEQUENCE 495 AA; 56466 MW; 0A1B1AB87BCDDEBA CRC64; MTVMSGENVD EASAAPGHPQ DGSYPRQADH DDHECCERVV INISGLRFET QLKTLAQFPN TLLGNPKKRM RYFDPLRNEY FFDRNRPSFD AILYYYQSGG RLRRPVNVPL DMFSEEIKFY ELGEEAMEKF REDEGFIKEE ERPLPEKEYQ RQVWLLFEYP ESSGPARVIA IVSVMVILIS IVIFCLETLP ELKDDKDFTG TVHRIDNTTV IYNSNIFTDP FFIVETLCII WFSFELVVRF FACPSKTDFF KNIMNFIDIV AIIPYFITLG TEIAEQEGNQ KGEQATSLAI LRVIRLVRVF RIFKLSRHSK GLQILGQTLK ASMRELGLLI FFLFIGVILF SSAVYFAEAE EAESHFSSIP DAFWWAVVSM TTVGYGDMYP VTIGGKIVGS LCAIAGVLTI ALPVPVIVSN FNYFYHRETE GEEQAQLLHV SSPNLASDSD LSRRSSSTMS KSEYMEIEED MNNSIAHYRQ VNIRTANCTT ANQNCVNKSK LLTDV //