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Database: UniProt
Entry: KCNA1_MOUSE
LinkDB: KCNA1_MOUSE
Original site: KCNA1_MOUSE 
ID   KCNA1_MOUSE             Reviewed;         495 AA.
AC   P16388;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   22-NOV-2017, entry version 159.
DE   RecName: Full=Potassium voltage-gated channel subfamily A member 1;
DE   AltName: Full=MBK1 {ECO:0000303|PubMed:2451788};
DE   AltName: Full=MKI;
DE   AltName: Full=Voltage-gated potassium channel subunit Kv1.1;
GN   Name=Kcna1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2305265; DOI=10.1126/science.2305265;
RA   Chandy K.G., Williams C.B., Spencer R.H., Aguilar B.A., Ghanshani S.,
RA   Tempel B.L., Gutman G.A.;
RT   "A family of three mouse potassium channel genes with intronless
RT   coding regions.";
RL   Science 247:973-975(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=2451788; DOI=10.1038/332837a0;
RA   Tempel B.L., Jan Y.N., Jan L.Y.;
RT   "Cloning of a probable potassium channel gene from mouse brain.";
RL   Nature 332:837-839(1988).
RN   [3]
RP   SUBUNIT, INTERACTION WITH KCNA2, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=8361541; DOI=10.1038/365075a0;
RA   Wang H., Kunkel D.D., Martin T.M., Schwartzkroin P.A., Tempel B.L.;
RT   "Heteromultimeric K+ channels in terminal and juxtaparanodal regions
RT   of neurons.";
RL   Nature 365:75-79(1993).
RN   [4]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=8046438;
RA   Wang H., Kunkel D.D., Schwartzkroin P.A., Tempel B.L.;
RT   "Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic
RT   terminals, somata, and dendrites in the mouse brain.";
RL   J. Neurosci. 14:4588-4599(1994).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND ENZYME REGULATION.
RX   PubMed=7517498;
RA   Grissmer S., Nguyen A.N., Aiyar J., Hanson D.C., Mather R.J.,
RA   Gutman G.A., Karmilowicz M.J., Auperin D.D., Chandy K.G.;
RT   "Pharmacological characterization of five cloned voltage-gated K+
RT   channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in
RT   mammalian cell lines.";
RL   Mol. Pharmacol. 45:1227-1234(1994).
RN   [6]
RP   DISEASE, AND FUNCTION.
RX   PubMed=8995755; DOI=10.1007/s003359900259;
RA   Donahue L.R., Cook S.A., Johnson K.R., Bronson R.T., Davisson M.T.;
RT   "Megencephaly: a new mouse mutation on chromosome 6 that causes
RT   hypertrophy of the brain.";
RL   Mamm. Genome 7:871-876(1996).
RN   [7]
RP   DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=9736643;
RA   Zhou L., Zhang C.L., Messing A., Chiu S.Y.;
RT   "Temperature-sensitive neuromuscular transmission in Kv1.1 null mice:
RT   role of potassium channels under the myelin sheath in young nerves.";
RL   J. Neurosci. 18:7200-7215(1998).
RN   [8]
RP   DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=9581771; DOI=10.1016/S0896-6273(00)81018-1;
RA   Smart S.L., Lopantsev V., Zhang C.L., Robbins C.A., Wang H.,
RA   Chiu S.Y., Schwartzkroin P.A., Messing A., Tempel B.L.;
RT   "Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.";
RL   Neuron 20:809-819(1998).
RN   [9]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=10191303;
RA   Zhang C.L., Messing A., Chiu S.Y.;
RT   "Specific alteration of spontaneous GABAergic inhibition in cerebellar
RT   Purkinje cells in mice lacking the potassium channel Kv1. 1.";
RL   J. Neurosci. 19:2852-2864(1999).
RN   [10]
RP   DISEASE, FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=14686897; DOI=10.1111/j.1460-9568.2003.03044.x;
RA   Petersson S., Persson A.S., Johansen J.E., Ingvar M., Nilsson J.,
RA   Klement G., Arhem P., Schalling M., Lavebratt C.;
RT   "Truncation of the Shaker-like voltage-gated potassium channel, Kv1.1,
RT   causes megencephaly.";
RL   Eur. J. Neurosci. 18:3231-3240(2003).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=12611922; DOI=10.1113/jphysiol.2002.035568;
RA   Brew H.M., Hallows J.L., Tempel B.L.;
RT   "Hyperexcitability and reduced low threshold potassium currents in
RT   auditory neurons of mice lacking the channel subunit Kv1.1.";
RL   J. Physiol. (Lond.) 548:1-20(2003).
RN   [12]
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   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH KCNAB1.
RX   PubMed=15361858; DOI=10.1038/nsmb825;
RA   Bhalla T., Rosenthal J.J., Holmgren M., Reenan R.;
RT   "Control of human potassium channel inactivation by editing of a small
RT   mRNA hairpin.";
RL   Nat. Struct. Mol. Biol. 11:950-956(2004).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=16452087; DOI=10.1074/mcp.T500041-MCP200;
RA   Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R.,
RA   Burlingame A.L.;
RT   "Comprehensive identification of phosphorylation sites in postsynaptic
RT   density preparations.";
RL   Mol. Cell. Proteomics 5:914-922(2006).
RN   [15]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=17250763; DOI=10.1186/1471-2202-8-10;
RA   Persson A.S., Westman E., Wang F.H., Khan F.H., Spenger C.,
RA   Lavebratt C.;
RT   "Kv1.1 null mice have enlarged hippocampus and ventral cortex.";
RL   BMC Neurosci. 8:10-10(2007).
RN   [16]
RP   DISEASE, AND FUNCTION.
RX   PubMed=17315199; DOI=10.1002/hipo.20268;
RA   Almgren M., Persson A.S., Fenghua C., Witgen B.M., Schalling M.,
RA   Nyengaard J.R., Lavebratt C.;
RT   "Lack of potassium channel induces proliferation and survival causing
RT   increased neurogenesis and two-fold hippocampus enlargement.";
RL   Hippocampus 17:292-304(2007).
RN   [17]
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   [18]
RP   TISSUE SPECIFICITY.
RX   PubMed=19307729; DOI=10.1172/JCI36948;
RA   Glaudemans B., van der Wijst J., Scola R.H., Lorenzoni P.J.,
RA   Heister A., van der Kemp A.W., Knoers N.V., Hoenderop J.G.,
RA   Bindels R.J.;
RT   "A missense mutation in the Kv1.1 voltage-gated potassium channel-
RT   encoding gene KCNA1 is linked to human autosomal dominant
RT   hypomagnesemia.";
RL   J. Clin. Invest. 119:936-942(2009).
RN   [19]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [20]
RP   DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=20392939; DOI=10.1523/JNEUROSCI.5591-09.2010;
RA   Glasscock E., Yoo J.W., Chen T.T., Klassen T.L., Noebels J.L.;
RT   "Kv1.1 potassium channel deficiency reveals brain-driven cardiac
RT   dysfunction as a candidate mechanism for sudden unexplained death in
RT   epilepsy.";
RL   J. Neurosci. 30:5167-5175(2010).
RN   [21]
RP   DISEASE, FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=21966978; DOI=10.1111/j.1460-9568.2011.07834.x;
RA   Fisahn A., Lavebratt C., Canlon B.;
RT   "Acoustic startle hypersensitivity in Mceph mice and its effect on
RT   hippocampal excitability.";
RL   Eur. J. Neurosci. 34:1121-1130(2011).
RN   [22]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=21233214; DOI=10.1074/jbc.M110.153262;
RA   Fulton S., Thibault D., Mendez J.A., Lahaie N., Tirotta E.,
RA   Borrelli E., Bouvier M., Tempel B.L., Trudeau L.E.;
RT   "Contribution of Kv1.2 voltage-gated potassium channel to D2
RT   autoreceptor regulation of axonal dopamine overflow.";
RL   J. Biol. Chem. 286:9360-9372(2011).
RN   [23]
RP   TISSUE SPECIFICITY, DISEASE, AND DISRUPTION PHENOTYPE.
RX   PubMed=21483673; DOI=10.1371/journal.pone.0018213;
RA   Ma Z., Lavebratt C., Almgren M., Portwood N., Forsberg L.E.,
RA   Branstrom R., Berglund E., Falkmer S., Sundler F., Wierup N.,
RA   Bjorklund A.;
RT   "Evidence for presence and functional effects of Kv1.1 channels in
RT   beta-cells: general survey and results from mceph/mceph mice.";
RL   PLoS ONE 6:E18213-E18213(2011).
RN   [24]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=22396426; DOI=10.1523/JNEUROSCI.1958-11.2012;
RA   Allen P.D., Ison J.R.;
RT   "Kcna1 gene deletion lowers the behavioral sensitivity of mice to
RT   small changes in sound location and increases asynchronous brainstem
RT   auditory evoked potentials but does not affect hearing thresholds.";
RL   J. Neurosci. 32:2538-2543(2012).
RN   [25]
RP   FUNCTION.
RX   PubMed=22411008; DOI=10.1113/jphysiol.2012.228486;
RA   Yang S.B., Mclemore K.D., Tasic B., Luo L., Jan Y.N., Jan L.Y.;
RT   "Kv1.1-dependent control of hippocampal neuron number as revealed by
RT   mosaic analysis with double markers.";
RL   J. Physiol. (Lond.) 590:2645-2658(2012).
RN   [26]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=22641786; DOI=10.1113/jphysiol.2012.235606;
RA   Glasscock E., Qian J., Kole M.J., Noebels J.L.;
RT   "Transcompartmental reversal of single fibre hyperexcitability in
RT   juxtaparanodal Kv1.1-deficient vagus nerve axons by activation of
RT   nodal KCNQ channels.";
RL   J. Physiol. (Lond.) 590:3913-3926(2012).
RN   [27]
RP   FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=22158511; DOI=10.1038/nn.3006;
RA   Li K.X., Lu Y.M., Xu Z.H., Zhang J., Zhu J.M., Zhang J.M., Cao S.X.,
RA   Chen X.J., Chen Z., Luo J.H., Duan S., Li X.M.;
RT   "Neuregulin 1 regulates excitability of fast-spiking neurons through
RT   Kv1.1 and acts in epilepsy.";
RL   Nat. Neurosci. 15:267-273(2012).
RN   [28]
RP   FUNCTION.
RX   PubMed=23466697; DOI=10.1016/j.nbd.2013.02.009;
RA   Simeone T.A., Simeone K.A., Samson K.K., Kim D.Y., Rho J.M.;
RT   "Loss of the Kv1.1 potassium channel promotes pathologic sharp waves
RT   and high frequency oscillations in in vitro hippocampal slices.";
RL   Neurobiol. Dis. 54:68-81(2013).
RN   [29]
RP   FUNCTION, DISEASE, AND TISSUE SPECIFICITY.
RX   PubMed=23473320; DOI=10.1016/j.neuron.2012.12.035;
RA   Hao J., Padilla F., Dandonneau M., Lavebratt C., Lesage F., Noel J.,
RA   Delmas P.;
RT   "Kv1.1 channels act as mechanical brake in the senses of touch and
RT   pain.";
RL   Neuron 77:899-914(2013).
RN   [30]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=25377007; DOI=10.1111/epi.12793;
RA   Moore B.M., Jerry Jou C., Tatalovic M., Kaufman E.S., Kline D.D.,
RA   Kunze D.L.;
RT   "The Kv1.1 null mouse, a model of sudden unexpected death in epilepsy
RT   (SUDEP).";
RL   Epilepsia 55:1808-1816(2014).
RN   [31]
RP   INTERACTION WITH ANK3, AND INDUCTION BY MAGNESIUM.
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).
CC   -!- FUNCTION: Voltage-gated potassium channel that mediates
CC       transmembrane potassium transport in excitable membranes,
CC       primarily in the brain and the central nervous system, but also in
CC       the kidney. Contributes to the regulation of the membrane
CC       potential and nerve signaling, and prevents neuronal
CC       hyperexcitability (PubMed:9736643, PubMed:9581771 PubMed:10191303,
CC       PubMed:12611922, PubMed:21966978, PubMed:22158511,
CC       PubMed:23473320). Forms tetrameric potassium-selective channels
CC       through which potassium ions pass in accordance with their
CC       electrochemical gradient. The channel alternates between opened
CC       and closed conformations in response to the voltage difference
CC       across the membrane (PubMed:15361858). Can form functional
CC       homotetrameric channels and heterotetrameric channels that contain
CC       variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7,
CC       and possibly other family members as well; channel properties
CC       depend on the type of alpha subunits that are part of the channel.
CC       Channel properties are modulated by cytoplasmic beta subunits that
CC       regulate the subcellular location of the alpha subunits and
CC       promote rapid inactivation of delayed rectifier potassium channels
CC       (PubMed:15361858). In vivo, membranes probably contain a mixture
CC       of heteromeric potassium channel complexes, making it difficult to
CC       assign currents observed in intact tissues to any particular
CC       potassium channel family member. Homotetrameric KCNA1 forms a
CC       delayed-rectifier potassium channel that opens in response to
CC       membrane depolarization, followed by slow spontaneous channel
CC       closure (PubMed:7517498, PubMed:15361858). In contrast, a
CC       heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid
CC       inactivation (By similarity). Regulates neuronal excitability in
CC       hippocampus, especially in mossy fibers and medial perforant path
CC       axons, preventing neuronal hyperexcitability (PubMed:23466697).
CC       May function as down-stream effector for G protein-coupled
CC       receptors and inhibit GABAergic inputs to basolateral amygdala
CC       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
CC       of action potentials and preventing hyperexcitability in
CC       myelinated axons of the vagus nerve, and thereby contributes to
CC       the regulation of heart contraction (PubMed:20392939,
CC       PubMed:22641786, PubMed:25377007). Required for normal
CC       neuromuscular responses (PubMed:9736643). Regulates the frequency
CC       of neuronal action potential firing in response to mechanical
CC       stimuli, and plays a role in the perception of pain caused by
CC       mechanical stimuli, but does not play a role in the perception of
CC       pain due to heat stimuli (PubMed:23473320). Required for normal
CC       responses to auditory stimuli and precise location of sound
CC       sources, but not for sound perception (PubMed:21966978,
CC       PubMed:22396426). The use of toxins that block specific channels
CC       suggest that it contributes to the regulation of the axonal
CC       release of the neurotransmitter dopamine (PubMed:21233214).
CC       Required for normal postnatal brain development and normal
CC       proliferation of neuronal precursor cells in the brain
CC       (PubMed:8995755, PubMed:17250763, PubMed:17315199,
CC       PubMed:22411008). Plays a role in the reabsorption of Mg(2+) in
CC       the distal convoluted tubules in the kidney and in magnesium ion
CC       homeostasis, probably via its effect on the membrane potential (By
CC       similarity). {ECO:0000250|UniProtKB:P10499,
CC       ECO:0000250|UniProtKB:Q09470, ECO:0000269|PubMed:10191303,
CC       ECO:0000269|PubMed:12611922, ECO:0000269|PubMed:15361858,
CC       ECO:0000269|PubMed:17250763, ECO:0000269|PubMed:17315199,
CC       ECO:0000269|PubMed:20392939, ECO:0000269|PubMed:21233214,
CC       ECO:0000269|PubMed:21966978, ECO:0000269|PubMed:22158511,
CC       ECO:0000269|PubMed:22396426, ECO:0000269|PubMed:22411008,
CC       ECO:0000269|PubMed:22641786, ECO:0000269|PubMed:23466697,
CC       ECO:0000269|PubMed:23473320, ECO:0000269|PubMed:25377007,
CC       ECO:0000269|PubMed:7517498, ECO:0000269|PubMed:8995755,
CC       ECO:0000269|PubMed:9581771, ECO:0000269|PubMed:9736643}.
CC   -!- ENZYME REGULATION: Inhibited by 4-aminopyridine (4-AP),
CC       tetraethylammonium (TEA) and dendrotoxin (DTX), but not by
CC       charybdotoxin (CTX). {ECO:0000269|PubMed:7517498}.
CC   -!- SUBUNIT: Homotetramer and heterotetramer with other channel-
CC       forming alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and
CC       KCNA7 (PubMed:8361541). Channel activity is regulated by
CC       interaction with the beta subunits KCNAB1 and KCNAB2
CC       (PubMed:15361858). Identified in a complex with KCNA2 and KCNAB2.
CC       Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and
CC       DLG4 (By similarity). Interacts with LGI1 within a complex
CC       containing LGI1, KCNA4 and KCNAB1 (By similarity). Interacts (via
CC       N-terminus) with STX1A; this promotes channel inactivation (By
CC       similarity). Interacts (via N-terminus) with the heterodimer
CC       formed by GNB1 and GNG2; this promotes channel inactivation (By
CC       similarity). Can interact simultaneously with STX1A and the
CC       heterodimer formed by GNB1 and GNG2 (By similarity). Interacts
CC       (via cytoplasmic N-terminal domain) with KCNRG; this inhibits
CC       channel activity (By similarity). Interacts with ANK3; this
CC       inhibits channel activity (PubMed:23903368).
CC       {ECO:0000250|UniProtKB:P10499, ECO:0000250|UniProtKB:Q09470,
CC       ECO:0000269|PubMed:15361858, ECO:0000269|PubMed:23903368,
CC       ECO:0000269|PubMed:8361541, ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15361858,
CC       ECO:0000269|PubMed:7517498}; Multi-pass membrane protein
CC       {ECO:0000305}. Cell projection, axon {ECO:0000269|PubMed:20392939,
CC       ECO:0000269|PubMed:21233214, ECO:0000269|PubMed:8046438,
CC       ECO:0000269|PubMed:8361541, ECO:0000269|PubMed:9581771,
CC       ECO:0000269|PubMed:9736643}. Membrane
CC       {ECO:0000269|PubMed:22158511}. Perikaryon
CC       {ECO:0000269|PubMed:12611922, ECO:0000269|PubMed:8046438}. Cell
CC       projection, dendrite {ECO:0000269|PubMed:8046438}. Cell junction
CC       {ECO:0000269|PubMed:8046438}. Cell junction, synapse
CC       {ECO:0000269|PubMed:8046438}. Cytoplasmic vesicle
CC       {ECO:0000269|PubMed:12611922}. Endoplasmic reticulum
CC       {ECO:0000250|UniProtKB:P10499}. Cell junction, synapse,
CC       presynaptic cell membrane {ECO:0000250|UniProtKB:P10499}.
CC       Note=Homotetrameric KCNA1 is primarily located in the endoplasmic
CC       reticulum. Interaction with KCNA2 and KCNAB2 or with KCNA4 and
CC       KCNAB2 promotes expression at the cell membrane (By similarity).
CC       Detected at axon terminals (PubMed:21233214).
CC       {ECO:0000250|UniProtKB:P10499, ECO:0000269|PubMed:21233214}.
CC   -!- TISSUE SPECIFICITY: Detected in brain (PubMed:21483673,
CC       PubMed:22158511). Detected in the juxtaparanodal regions of the
CC       nodes of Ranvier in myelinated axons (PubMed:8361541,
CC       PubMed:8046438). Detected in the paranodal region in sciatic nerve
CC       (PubMed:9736643). Detected on cell bodies in cerebellum, dorsal
CC       and ventral cochlear nucleus, pontine reticular nucleus,
CC       mesencephalic trigeminal nucleus, motor trigeminal nucleus and the
CC       pricipal sensory trigeminal nucleus (PubMed:8046438). Detected in
CC       terminal fields of basket cells in the cerebellum corpus medullare
CC       (PubMed:8361541, PubMed:8046438, PubMed:9581771). Detected in
CC       hippocampus CA3 pyramidal neurons and in the hilus and stratum
CC       moleculare of the dentate gyrus (PubMed:8046438, PubMed:9581771,
CC       PubMed:14686897). Detected in the central nucleus and the external
CC       nucleus of the inferior colliculus (PubMed:8046438,
CC       PubMed:21966978). Detected in fiber tracts in the optic tract,
CC       external medullary lamina, stria terminalis, medulla, ventral
CC       pallidum and substantia nigra (PubMed:8046438). Detected in
CC       neurons from dorsal root ganglion (PubMed:23473320). Detected in
CC       neurons in the medial nucleus of the trapezoid body
CC       (PubMed:12611922). Detected in midbrain dopamine neuron axon
CC       terminals (PubMed:21233214). Detected in brain cortex
CC       (PubMed:8046438, PubMed:14686897). Detected in brainstem
CC       (PubMed:8361541). Detected in juxtaparanodal regions of the nodes
CC       of Ranvier in the vagus nerve, but only at very low levels in the
CC       heart (PubMed:20392939, PubMed:22641786). Detected in the islet of
CC       Langerhans (PubMed:21483673). Detected at the luminal membrane in
CC       distal convoluted tubules in the kidney (at protein level)
CC       (PubMed:19307729). Detected in brain (PubMed:2451788,
CC       PubMed:9581771). Detected in hippocampus, thalamus, neocortex and
CC       ventral brain cortex, including the piriform and entorhinal cortex
CC       and the amygdala (PubMed:14686897). Detected in midbrain dopamine
CC       neurons (PubMed:21233214). Detected in heart atrium, ventricle,
CC       sinoatrial node and atrioventricular node (PubMed:20392939).
CC       Detected in the islet of Langerhans (PubMed:21483673).
CC       {ECO:0000269|PubMed:12611922, ECO:0000269|PubMed:14686897,
CC       ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:20392939,
CC       ECO:0000269|PubMed:21233214, ECO:0000269|PubMed:21483673,
CC       ECO:0000269|PubMed:21966978, ECO:0000269|PubMed:22158511,
CC       ECO:0000269|PubMed:22641786, ECO:0000269|PubMed:23473320,
CC       ECO:0000269|PubMed:2451788, ECO:0000269|PubMed:8046438,
CC       ECO:0000269|PubMed:8361541, ECO:0000269|PubMed:9581771,
CC       ECO:0000269|PubMed:9736643}.
CC   -!- INDUCTION: Down-regulated by high dietary Mg(2+) levels.
CC       {ECO:0000269|PubMed:23903368}.
CC   -!- DOMAIN: The cytoplasmic N-terminus is important for
CC       tetramerization and for interaction with the beta subunits that
CC       promote rapid channel closure. {ECO:0000250|UniProtKB:P10499}.
CC   -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor
CC       and is characterized by a series of positively charged amino acids
CC       at every third position. Channel opening and closing is effected
CC       by a conformation change that affects the position and orientation
CC       of the voltage-sensor paddle formed by S3 and S4 within the
CC       membrane. A transmembrane electric field that is positive inside
CC       would push the positively charged S4 segment outwards, thereby
CC       opening the pore, while a field that is negative inside would pull
CC       the S4 segment inwards and close the pore. Changes in the position
CC       and orientation of S4 are then transmitted to the activation gate
CC       formed by the inner helix bundle via the S4-S5 linker region.
CC       {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:0000250|UniProtKB:Q09470}.
CC   -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation
CC       increases in response to NRG1; this inhibits channel activity
CC       (PubMed:22158511). Phosphorylation at Ser-446 regulates channel
CC       activity by down-regulating expression at the cell membrane (By
CC       similarity). {ECO:0000250|UniProtKB:Q09470,
CC       ECO:0000269|PubMed:22158511}.
CC   -!- RNA EDITING: Modified_positions=400 {ECO:0000269|PubMed:12907802};
CC       Note=Partially edited. RNA editing varies from 35% in the frontal
CC       cortex to 75% in the spinal chord.;
CC   -!- DISEASE: Note=A spontaneous mutation leading to a frameshift and
CC       truncation of Kcna2 causes megencephaly with a 25% increase of
CC       brain weight relative to wild-type. Especially the hippocampus
CC       shows increased proliferation of neurons and astrocytes, leading
CC       to increased brain volume (PubMed:17315199). Mutant mice appear
CC       normal at birth. After 3-4 weeks, they display low body weight, a
CC       subtle shakiness in their gait, a preference for a strange sitting
CC       position that is maintained for periods ranging from 30 seconds to
CC       several minutes, excessive lacrimation and acoustic startle
CC       hypersensitivity (PubMed:8995755, PubMed:21966978). The increase
CC       in the acoustic startle response is down-regulated by treatment
CC       with the anti-epileptic drug valproate (PubMed:21966978). Mutant
CC       mice display an abnormal electro-encephalogram with single spikes
CC       and waves, when anesthesized (PubMed:21966978). The electric
CC       activity of mossy cells from the dentate hilus region is altered
CC       and shows increased firing of action potentials, probably due to
CC       the absence of functional Kcna1 channels (PubMed:14686897).
CC       Heterozygotes show mechanical allodynia, but no increased
CC       sensitivity to heat (PubMed:23473320). Homozygotes show no
CC       alteration of the islet of Langerhans structure, of the basal
CC       levels of insulin secretion and blood glucose levels
CC       (PubMed:21483673). Compared to wild-type, they display moderately
CC       increased insulin secretion in response to a glucose stimulus
CC       (PubMed:21483673). Besides, the frequency of beta cell action
CC       potentials is increased (PubMed:21483673).
CC       {ECO:0000269|PubMed:14686897, ECO:0000269|PubMed:17315199,
CC       ECO:0000269|PubMed:21483673, ECO:0000269|PubMed:21966978,
CC       ECO:0000269|PubMed:8995755}.
CC   -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian
CC       rate. After three weeks, mice begin to display episodic eye
CC       blinking, twitching of whiskers, forlimb padding, arrested motion
CC       and a hyperstartle response. About 50% of the homozygotes die
CC       between the third and the fifth week after birth. Surviving mice
CC       continue to display spontaneous seizures occurring once or twice
CC       every hour throughout adult life (PubMed:9581771). The fecundity
CC       of homozygotes is extremely low (PubMed:9581771). Mutant mice
CC       display interictal cardiac abnormalities, including a fivefold
CC       increase in atrioventricular conduction blocks, brachycardia and
CC       premature ventricular contractions; this may lead to sudden
CC       unexplained death in epilepsy (PubMed:20392939). Mutant mice have
CC       slightly elevated heart rates; they all have a reduced livespan
CC       and are subject to sudden death after presumed seizure activity
CC       and sinus bradycardia (PubMed:25377007). About 70% of the mutant
CC       mice have an enlarged hippocampus and ventral brain cortex
CC       (PubMed:17250763). Mutant mice show a temperature-sensitive
CC       alteration in neuromuscular transmission, causing nerve
CC       hyperexcitability when exposed to cold and delayed repetitive
CC       discharge after a single nerve stimulation (PubMed:9736643). After
CC       2 minutes of swimming in cold water, mutant mice have impaired
CC       motor control; they fall over when placed on dry ground and
CC       exhibit severe neuromyotonia with violent tremors that decrease
CC       with time, leading to full recovery after twenty minutes
CC       (PubMed:9736643). Mutant mice have an increased frequency of
CC       spontaneous postsynaptic currents in Purkinje cells, impaired
CC       ability to maintain their balance on a thin stationary rod, but
CC       perform as well as wild-type on a rotarod (PubMed:10191303).
CC       Mutant mice have a normal hearing threshold, but altered brainstem
CC       responses to auditory stimuli and reduced sensitivity to small
CC       changes in sound location (PubMed:22396426). Mutant mice display
CC       no alteration of the islet of Langerhans, but have reduced blood
CC       glucose levels and increased insulin secretion in response to a
CC       glucose stimulus (PubMed:21483673). {ECO:0000269|PubMed:10191303,
CC       ECO:0000269|PubMed:17250763, ECO:0000269|PubMed:20392939,
CC       ECO:0000269|PubMed:21483673, ECO:0000269|PubMed:22396426,
CC       ECO:0000269|PubMed:25377007, ECO:0000269|PubMed:9581771,
CC       ECO:0000269|PubMed:9736643}.
CC   -!- MISCELLANEOUS: The delay or D-type current observed in hippocampus
CC       pyramidal neurons is probably mediated by potassium channels
CC       containing KCNA2 plus KCNA1 or other family members. It is
CC       activated at about -50 mV, i.e. below the action potential
CC       threshold, and is characterized by slow inactivation, extremely
CC       slow recovery from inactivation, sensitivity to dendrotoxin (DTX)
CC       and to 4-aminopyridine (4-AP). {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}.
DR   EMBL; M30439; AAA39711.1; -; Genomic_DNA.
DR   EMBL; Y00305; CAA68408.1; -; mRNA.
DR   CCDS; CCDS20555.1; -.
DR   PIR; A40090; A40090.
DR   PIR; S09042; S09042.
DR   RefSeq; NP_034725.3; NM_010595.3.
DR   UniGene; Mm.40424; -.
DR   ProteinModelPortal; P16388; -.
DR   SMR; P16388; -.
DR   BioGrid; 200876; 3.
DR   IntAct; P16388; 2.
DR   MINT; MINT-4099639; -.
DR   STRING; 10090.ENSMUSP00000055225; -.
DR   ChEMBL; CHEMBL2429705; -.
DR   GuidetoPHARMACOLOGY; 538; -.
DR   iPTMnet; P16388; -.
DR   PhosphoSitePlus; P16388; -.
DR   MaxQB; P16388; -.
DR   PaxDb; P16388; -.
DR   PeptideAtlas; P16388; -.
DR   PRIDE; P16388; -.
DR   Ensembl; ENSMUST00000055168; ENSMUSP00000055225; ENSMUSG00000047976.
DR   Ensembl; ENSMUST00000203094; ENSMUSP00000144947; ENSMUSG00000047976.
DR   GeneID; 16485; -.
DR   KEGG; mmu:16485; -.
DR   UCSC; uc009dvb.1; mouse.
DR   CTD; 3736; -.
DR   MGI; MGI:96654; Kcna1.
DR   eggNOG; KOG1545; Eukaryota.
DR   eggNOG; COG1226; LUCA.
DR   GeneTree; ENSGT00760000118846; -.
DR   HOGENOM; HOG000231015; -.
DR   HOVERGEN; HBG052230; -.
DR   InParanoid; P16388; -.
DR   KO; K04874; -.
DR   OMA; AHYRQAN; -.
DR   OrthoDB; EOG091G10NU; -.
DR   PhylomeDB; P16388; -.
DR   TreeFam; TF313103; -.
DR   Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR   PRO; PR:P16388; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   Bgee; ENSMUSG00000047976; -.
DR   Genevisible; P16388; MM.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR   GO; GO:0030424; C:axon; IDA:UniProtKB.
DR   GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR   GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR   GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR   GO; GO:0033270; C:paranode region of axon; IDA:UniProtKB.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; IDA: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; ISO:MGI.
DR   GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR   GO; GO:0010644; P:cell communication by electrical coupling; ISS:UniProtKB.
DR   GO; GO:0034613; P:cellular protein localization; IEA:Ensembl.
DR   GO; GO:0071286; P:cellular response to magnesium ion; IMP:UniProtKB.
DR   GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:UniProtKB.
DR   GO; GO:0050976; P:detection of mechanical stimulus involved in sensory perception of touch; IMP:UniProtKB.
DR   GO; GO:0021766; P:hippocampus development; IMP:UniProtKB.
DR   GO; GO:0010960; P:magnesium ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0007405; P:neuroblast proliferation; IMP:UniProtKB.
DR   GO; GO:0050905; P:neuromuscular process; IMP:UniProtKB.
DR   GO; GO:0019228; P:neuronal action potential; IMP: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; IDA:UniProtKB.
DR   GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR   GO; GO:0042391; P:regulation of membrane potential; ISS:UniProtKB.
DR   GO; GO:0006937; P:regulation of muscle contraction; ISS:UniProtKB.
DR   GO; GO:0001964; P:startle response; IMP:UniProtKB.
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   PANTHER; PTHR11537; PTHR11537; 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; SSF54695; 1.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Cell projection; Complete proteome;
KW   Cytoplasmic vesicle; Endoplasmic reticulum; Glycoprotein; Ion channel;
KW   Ion transport; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW   Potassium; Potassium channel; Potassium transport; Reference proteome;
KW   RNA editing; Synapse; Transmembrane; Transmembrane helix; Transport;
KW   Voltage-gated channel.
FT   CHAIN         1    495       Potassium voltage-gated channel subfamily
FT                                A member 1.
FT                                /FTId=PRO_0000053969.
FT   TOPO_DOM      1    164       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    165    186       Helical; Name=Segment S1.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    187    220       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    221    242       Helical; Name=Segment S2.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    243    253       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    254    274       Helical; Name=Segment S3.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    275    287       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    288    308       Helical; Voltage-sensor; Name=Segment S4.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    309    323       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    324    345       Helical; Name=Segment S5.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    346    359       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   INTRAMEM    360    371       Helical; Name=Pore helix.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   INTRAMEM    372    379       {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    380    386       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    387    415       Helical; Name=Segment S6.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    416    495       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   REGION        1    128       Tetramerization domain.
FT                                {ECO:0000250|UniProtKB:P10499}.
FT   REGION      310    323       S4-S5 linker.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   MOTIF       372    377       Selectivity filter.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   MOTIF       493    495       PDZ-binding. {ECO:0000250}.
FT   MOD_RES      23     23       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P10499}.
FT   MOD_RES     322    322       Phosphoserine; by PKA. {ECO:0000255}.
FT   MOD_RES     437    437       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P10499}.
FT   MOD_RES     439    439       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P10499}.
FT   MOD_RES     446    446       Phosphoserine; by PKA.
FT                                {ECO:0000250|UniProtKB:P10499}.
FT   LIPID       243    243       S-palmitoyl cysteine.
FT                                {ECO:0000250|UniProtKB:Q09470}.
FT   CARBOHYD    207    207       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VARIANT     400    400       I -> V (in RNA edited version).
SQ   SEQUENCE   495 AA;  56409 MW;  C9249F130E943D3D CRC64;
     MTVMSGENAD EASTAPGHPQ DGSYPRQADH DDHECCERVV INISGLRFET QLKTLAQFPN
     TLLGNPKKRM RYFDPLRNEY FFDRNRPSFD AILYYYQSGG RLRRPVNVPL DMFSEEIKFY
     ELGEEAMEKF REDEGFIKEE ERPLPEKEYQ RQVWLLFEYP ESSGPARVIA IVSVMVILIS
     IVIFCLETLP ELKDDKDFTG TIHRIDNTTV IYTSNIFTDP FFIVETLCII WFSFELVVRF
     FACPSKTDFF KNIMNFIDIV AIIPYFITLG TEIAEQEGNQ KGEQATSLAI LRVIRLVRVF
     RIFKLSRHSK GLQILGQTLK ASMRELGLLI FFLFIGVILF SSAVYFAEAE EAESHFSSIP
     DAFWWAVVSM TTVGYGDMYP VTIGGKIVGS LCAIAGVLTI ALPVPVIVSN FNYFYHRETE
     GEEQAQLLHV SSPNLASDSD LSRRSSSTIS KSEYMEIEED MNNSIAHYRQ ANIRTGNCTT
     ADQNCVNKSK LLTDV
//
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