KCNA1_HUMAN
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 03-AUG-2022, entry version 213.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 1;
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;
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, SUBCELLULAR LOCATION, AND ACTIVITY
RP 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.
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>3.0.co;2-q;
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 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 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:19903818).
CC Contributes to the regulation of the membrane potential and nerve
CC signaling, and prevents neuronal hyperexcitability (PubMed:17156368).
CC Forms tetrameric potassium-selective channels through which potassium
CC ions pass in accordance with their electrochemical gradient. The
CC channel alternates between opened and closed conformations in response
CC to the voltage difference across the membrane (PubMed:19912772). Can
CC form functional homotetrameric channels and heterotetrameric channels
CC that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6,
CC KCNA7, and possibly other family members as well; channel properties
CC depend on the type of alpha subunits that are part of the channel
CC (PubMed:12077175, PubMed:17156368). Channel properties are modulated by
CC cytoplasmic beta subunits that regulate the subcellular location of the
CC alpha subunits and promote rapid inactivation of delayed rectifier
CC potassium channels (PubMed:12077175, PubMed:17156368). In vivo,
CC membranes probably contain a mixture of heteromeric potassium channel
CC complexes, making it difficult to assign currents observed in intact
CC tissues to any particular potassium channel family member.
CC Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that
CC opens in response to membrane depolarization, followed by slow
CC spontaneous channel closure (PubMed:19912772, PubMed:19968958,
CC PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric
CC channel formed by KCNA1 and KCNA4 shows rapid inactivation
CC (PubMed:17156368). Regulates neuronal excitability in hippocampus,
CC especially in mossy fibers and medial perforant path axons, preventing
CC neuronal hyperexcitability. Response to toxins that are selective for
CC KCNA1, respectively for KCNA2, suggests that heteromeric potassium
CC channels composed of both KCNA1 and KCNA2 play a role in pacemaking and
CC regulate the output of deep cerebellar nuclear neurons (By similarity).
CC May function as down-stream effector for G protein-coupled receptors
CC and inhibit GABAergic inputs to basolateral amygdala neurons (By
CC similarity). May contribute to the regulation of neurotransmitter
CC release, such as gamma-aminobutyric acid (GABA) release (By
CC similarity). Plays a role in regulating the generation of action
CC potentials and preventing hyperexcitability in myelinated axons of the
CC 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 -!- 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).
CC {ECO:0000250|UniProtKB:P10499, 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 voltage-sensor and is
CC 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) (TC
CC 1.A.1.2) subfamily. Kv1.1/KCNA1 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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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 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; Q09470; -.
DR PeptideAtlas; Q09470; -.
DR PRIDE; Q09470; -.
DR ProteomicsDB; 58722; -.
DR ABCD; Q09470; 2 sequenced antibodies.
DR Antibodypedia; 22315; 448 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 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; PQEGSYP; -.
DR OrthoDB; 695337at2759; -.
DR PhylomeDB; Q09470; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q09470; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q09470; -.
DR BioGRID-ORCS; 3736; 10 hits in 1073 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 tissues.
DR ExpressionAtlas; Q09470; baseline and differential.
DR Genevisible; Q09470; HS.
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:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; 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; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0005267; F:potassium channel activity; TAS:ProtInc.
DR GO; GO:0015079; F:potassium ion transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR GO; GO:0099508; F:voltage-gated 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:0010644; P:cell communication by electrical coupling; ISS:UniProtKB.
DR GO; GO:0071286; P:cellular response to magnesium ion; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
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: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:1903818; P:positive regulation of voltage-gated potassium channel activity; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
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; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 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; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01508; KV11CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01496; SHAKERCHANEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
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 wild-
FT 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 (probable disease-associated variant found in
FT a patient with neonatal onset epileptic encephalopathy;
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
