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 03-AUG-2022, entry version 184.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 coding
RT 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 of
RT neurons.";
RL Nature 365:75-79(1993).
RN [4]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=8046438; DOI=10.1523/jneurosci.14-08-04588.1994;
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 ACTIVITY REGULATION.
RX PubMed=7517498;
RA Grissmer S., Nguyen A.N., Aiyar J., Hanson D.C., Mather R.J., Gutman G.A.,
RA Karmilowicz M.J., Auperin D.D., Chandy K.G.;
RT "Pharmacological characterization of five cloned voltage-gated K+ channels,
RT types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell
RT 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 hypertrophy
RT 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; DOI=10.1523/jneurosci.18-18-07200.1998;
RA Zhou L., Zhang C.L., Messing A., Chiu S.Y.;
RT "Temperature-sensitive neuromuscular transmission in Kv1.1 null mice: role
RT 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., Chiu S.Y.,
RA 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; DOI=10.1523/jneurosci.19-08-02852.1999;
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 auditory
RT 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 mRNA
RT 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., 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., 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., 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 [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 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., Borrelli E.,
RA Bouvier M., Tempel B.L., Trudeau L.E.;
RT "Contribution of Kv1.2 voltage-gated potassium channel to D2 autoreceptor
RT 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., 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 [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 small
RT changes in sound location and increases asynchronous brainstem auditory
RT 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 mosaic
RT 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 nodal
RT KCNQ channels.";
RL J. Physiol. (Lond.) 590:3913-3926(2012).
RN [27]
RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND TISSUE 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 Kv1.1
RT 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 and
RT 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 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 transmembrane
CC potassium transport in excitable membranes, primarily in the brain and
CC the central nervous system, but also in the kidney. Contributes to the
CC regulation of the membrane potential and nerve signaling, and prevents
CC neuronal hyperexcitability (PubMed:9736643, PubMed:9581771
CC PubMed:10191303, PubMed:12611922, PubMed:21966978, PubMed:22158511,
CC PubMed:23473320). Forms tetrameric potassium-selective channels through
CC which potassium ions pass in accordance with their electrochemical
CC gradient. The channel alternates between opened and closed
CC conformations in response to the voltage difference across the membrane
CC (PubMed:15361858). Can form functional homotetrameric channels and
CC heterotetrameric channels that contain variable proportions of KCNA1,
CC KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as
CC well; channel properties depend on the type of alpha subunits that are
CC part of the channel. Channel properties are modulated by cytoplasmic
CC beta subunits that regulate the subcellular location of the alpha
CC subunits and promote rapid inactivation of delayed rectifier potassium
CC channels (PubMed:15361858). In vivo, membranes probably contain a
CC mixture of heteromeric potassium channel complexes, making it difficult
CC to assign currents observed in intact tissues to any particular
CC potassium channel family member. Homotetrameric KCNA1 forms a delayed-
CC rectifier potassium channel that opens in response to membrane
CC depolarization, followed by slow spontaneous channel closure
CC (PubMed:7517498, PubMed:15361858). In contrast, a heterotetrameric
CC channel formed by KCNA1 and KCNA4 shows rapid inactivation (By
CC similarity). Regulates neuronal excitability in hippocampus, especially
CC in mossy fibers and medial perforant path axons, preventing neuronal
CC hyperexcitability (PubMed:23466697). May function as down-stream
CC effector for G protein-coupled receptors and inhibit GABAergic inputs
CC to basolateral amygdala neurons (By similarity). May contribute to the
CC regulation of neurotransmitter release, such as gamma-aminobutyric acid
CC (GABA) release (By similarity). Plays a role in regulating the
CC generation of action potentials and preventing hyperexcitability in
CC myelinated axons of the vagus nerve, and thereby contributes to the
CC regulation of heart contraction (PubMed:20392939, PubMed:22641786,
CC PubMed:25377007). Required for normal neuromuscular responses
CC (PubMed:9736643). Regulates the frequency of neuronal action potential
CC firing in response to mechanical stimuli, and plays a role in the
CC perception of pain caused by mechanical stimuli, but does not play a
CC role in the perception of pain due to heat stimuli (PubMed:23473320).
CC Required for normal responses to auditory stimuli and precise location
CC of sound 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 release of
CC the neurotransmitter dopamine (PubMed:21233214). Required for normal
CC postnatal brain development and normal proliferation of neuronal
CC precursor cells in the brain (PubMed:8995755, PubMed:17250763,
CC PubMed:17315199, PubMed:22411008). Plays a role in the reabsorption of
CC Mg(2+) in the distal convoluted tubules in the kidney and in magnesium
CC ion 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 -!- ACTIVITY 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-forming
CC alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7
CC (PubMed:8361541). Channel activity is regulated by interaction with the
CC beta subunits KCNAB1 and KCNAB2 (PubMed:15361858). Identified in a
CC complex with KCNA2 and KCNAB2. Interacts (via C-terminus) with the PDZ
CC domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with LGI1
CC within a complex containing LGI1, KCNA4 and KCNAB1 (By similarity).
CC Interacts (via N-terminus) with STX1A; this promotes channel
CC inactivation (By similarity). Interacts (via N-terminus) with the
CC heterodimer formed by GNB1 and GNG2; this promotes channel inactivation
CC (By similarity). Can interact simultaneously with STX1A and the
CC heterodimer formed by GNB1 and GNG2 (By similarity). Interacts (via
CC cytoplasmic N-terminal domain) with KCNRG; this inhibits channel
CC activity (By similarity). Interacts with ANK3; this inhibits channel
CC activity (PubMed:23903368). {ECO:0000250|UniProtKB:P10499,
CC ECO:0000250|UniProtKB:Q09470, ECO:0000269|PubMed:15361858,
CC ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:8361541, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15361858,
CC ECO:0000269|PubMed:7517498}; Multi-pass membrane protein {ECO:0000305}.
CC 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 {ECO:0000269|PubMed:22158511}.
CC Perikaryon {ECO:0000269|PubMed:12611922, ECO:0000269|PubMed:8046438}.
CC Cell projection, dendrite {ECO:0000269|PubMed:8046438}. Cell junction
CC {ECO:0000269|PubMed:8046438}. Synapse {ECO:0000269|PubMed:8046438}.
CC Cytoplasmic vesicle {ECO:0000269|PubMed:12611922}. Endoplasmic
CC reticulum {ECO:0000250|UniProtKB:P10499}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:P10499}. Presynapse
CC {ECO:0000269|PubMed:21233214}. 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:0000269|PubMed:21233214}.
CC -!- TISSUE SPECIFICITY: Detected in brain (PubMed:21483673,
CC PubMed:22158511). Detected in the juxtaparanodal regions of the nodes
CC of Ranvier in myelinated axons (PubMed:8361541, PubMed:8046438).
CC Detected in the paranodal region in sciatic nerve (PubMed:9736643).
CC Detected on cell bodies in cerebellum, dorsal and ventral cochlear
CC nucleus, pontine reticular nucleus, mesencephalic trigeminal nucleus,
CC motor trigeminal nucleus and the pricipal sensory trigeminal nucleus
CC (PubMed:8046438). Detected in terminal fields of basket cells in the
CC cerebellum corpus medullare (PubMed:8361541, PubMed:8046438,
CC PubMed:9581771). Detected in hippocampus CA3 pyramidal neurons and in
CC the hilus and stratum moleculare of the dentate gyrus (PubMed:8046438,
CC PubMed:9581771, PubMed:14686897). Detected in the central nucleus and
CC the external nucleus of the inferior colliculus (PubMed:8046438,
CC PubMed:21966978). Detected in fiber tracts in the optic tract, external
CC medullary lamina, stria terminalis, medulla, ventral pallidum and
CC substantia nigra (PubMed:8046438). Detected in neurons from dorsal root
CC ganglion (PubMed:23473320). Detected in neurons in the medial nucleus
CC of the trapezoid body (PubMed:12611922). Detected in midbrain dopamine
CC neuron axon 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 of
CC Ranvier in the vagus nerve, but only at very low levels in the heart
CC (PubMed:20392939, PubMed:22641786). Detected in the islet of Langerhans
CC (PubMed:21483673). Detected at the luminal membrane in distal
CC convoluted tubules in the kidney (at protein level) (PubMed:19307729).
CC Detected in brain (PubMed:2451788, PubMed:9581771). Detected in
CC hippocampus, thalamus, neocortex and ventral brain cortex, including
CC the piriform and entorhinal cortex and the amygdala (PubMed:14686897).
CC Detected in midbrain dopamine neurons (PubMed:21233214). Detected in
CC heart atrium, ventricle, sinoatrial node and atrioventricular node
CC (PubMed:20392939). Detected in the islet of Langerhans
CC (PubMed:21483673). {ECO:0000269|PubMed:12611922,
CC ECO:0000269|PubMed:14686897, ECO:0000269|PubMed:19307729,
CC ECO:0000269|PubMed:20392939, ECO:0000269|PubMed:21233214,
CC ECO:0000269|PubMed:21483673, ECO:0000269|PubMed:21966978,
CC ECO:0000269|PubMed:22158511, ECO:0000269|PubMed:22641786,
CC ECO:0000269|PubMed:23473320, ECO:0000269|PubMed:2451788,
CC ECO:0000269|PubMed:8046438, ECO:0000269|PubMed:8361541,
CC ECO:0000269|PubMed:9581771, 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 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:0000250|UniProtKB:Q09470}.
CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation increases in
CC response to NRG1; this inhibits channel activity (PubMed:22158511).
CC Phosphorylation at Ser-446 regulates channel activity by down-
CC regulating expression at the cell membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q09470, 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 brain
CC weight relative to wild-type. Especially the hippocampus shows
CC increased proliferation of neurons and astrocytes, leading to increased
CC brain volume (PubMed:17315199). Mutant mice appear normal at birth.
CC After 3-4 weeks, they display low body weight, a subtle shakiness in
CC their gait, a preference for a strange sitting position that is
CC maintained for periods ranging from 30 seconds to several minutes,
CC excessive lacrimation and acoustic startle hypersensitivity
CC (PubMed:8995755, PubMed:21966978). The increase in the acoustic startle
CC response is down-regulated by treatment with the anti-epileptic drug
CC valproate (PubMed:21966978). Mutant mice display an abnormal electro-
CC encephalogram with single spikes and waves, when anesthesized
CC (PubMed:21966978). The electric activity of mossy cells from the
CC dentate hilus region is altered and shows increased firing of action
CC potentials, probably due to the absence of functional Kcna1 channels
CC (PubMed:14686897). Heterozygotes show mechanical allodynia, but no
CC increased sensitivity to heat (PubMed:23473320). Homozygotes show no
CC alteration of the islet of Langerhans structure, of the basal levels of
CC insulin secretion and blood glucose levels (PubMed:21483673). Compared
CC to wild-type, they display moderately increased insulin secretion in
CC response to a glucose stimulus (PubMed:21483673). Besides, the
CC frequency of beta cell action potentials is increased
CC (PubMed:21483673). {ECO:0000269|PubMed:14686897,
CC ECO:0000269|PubMed:17315199, ECO:0000269|PubMed:21483673,
CC ECO:0000269|PubMed:21966978, ECO:0000269|PubMed:8995755}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate.
CC After three weeks, mice begin to display episodic eye blinking,
CC twitching of whiskers, forlimb padding, arrested motion and a
CC hyperstartle response. About 50% of the homozygotes die between the
CC third and the fifth week after birth. Surviving mice continue to
CC display spontaneous seizures occurring once or twice every hour
CC throughout adult life (PubMed:9581771). The fecundity of homozygotes is
CC extremely low (PubMed:9581771). Mutant mice display interictal cardiac
CC abnormalities, including a fivefold increase in atrioventricular
CC conduction blocks, brachycardia and premature ventricular contractions;
CC this may lead to sudden unexplained death in epilepsy
CC (PubMed:20392939). Mutant mice have slightly elevated heart rates; they
CC all have a reduced livespan and are subject to sudden death after
CC presumed seizure activity and sinus bradycardia (PubMed:25377007).
CC About 70% of the mutant mice have an enlarged hippocampus and ventral
CC brain cortex (PubMed:17250763). Mutant mice show a temperature-
CC sensitive alteration in neuromuscular transmission, causing nerve
CC hyperexcitability when exposed to cold and delayed repetitive discharge
CC after a single nerve stimulation (PubMed:9736643). After 2 minutes of
CC swimming in cold water, mutant mice have impaired motor control; they
CC fall over when placed on dry ground and exhibit severe neuromyotonia
CC with violent tremors that decrease with time, leading to full recovery
CC after twenty minutes (PubMed:9736643). Mutant mice have an increased
CC frequency of spontaneous postsynaptic currents in Purkinje cells,
CC impaired ability to maintain their balance on a thin stationary rod,
CC but perform as well as wild-type on a rotarod (PubMed:10191303). Mutant
CC mice have a normal hearing threshold, but altered brainstem responses
CC to auditory stimuli and reduced sensitivity to small changes in sound
CC location (PubMed:22396426). Mutant mice display no alteration of the
CC islet of Langerhans, but have reduced blood glucose levels and
CC increased insulin secretion in response to a glucose stimulus
CC (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 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 ---------------------------------------------------------------------------
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; 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 AlphaFoldDB; P16388; -.
DR SMR; P16388; -.
DR BioGRID; 200876; 10.
DR IntAct; P16388; 2.
DR STRING; 10090.ENSMUSP00000055225; -.
DR ChEMBL; CHEMBL2429705; -.
DR DrugCentral; P16388; -.
DR GuidetoPHARMACOLOGY; 538; -.
DR GlyGen; P16388; 1 site.
DR iPTMnet; P16388; -.
DR PhosphoSitePlus; P16388; -.
DR MaxQB; P16388; -.
DR PaxDb; P16388; -.
DR PeptideAtlas; P16388; -.
DR PRIDE; P16388; -.
DR ProteomicsDB; 269195; -.
DR ABCD; P16388; 3 sequenced antibodies.
DR Antibodypedia; 22315; 448 antibodies from 35 providers.
DR DNASU; 16485; -.
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 VEuPathDB; HostDB:ENSMUSG00000047976; -.
DR eggNOG; KOG1545; Eukaryota.
DR GeneTree; ENSGT00940000158576; -.
DR HOGENOM; CLU_011722_4_0_1; -.
DR InParanoid; P16388; -.
DR OMA; PQEGSYP; -.
DR OrthoDB; 695337at2759; -.
DR PhylomeDB; P16388; -.
DR TreeFam; TF313103; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR BioGRID-ORCS; 16485; 2 hits in 73 CRISPR screens.
DR PRO; PR:P16388; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P16388; protein.
DR Bgee; ENSMUSG00000047976; Expressed in sciatic nerve and 136 other tissues.
DR Genevisible; P16388; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043194; C:axon initial segment; IDA:MGI.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0044305; C:calyx of Held; ISO:MGI.
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:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
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:0034705; C:potassium channel complex; ISO:MGI.
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:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; ISO:MGI.
DR GO; GO:0099508; F:voltage-gated ion channel activity involved in regulation of presynaptic membrane potential; 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: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; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0008104; P:protein localization; ISO:MGI.
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 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 Endoplasmic reticulum; Glycoprotein; Ion channel; Ion transport;
KW 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_0000053969"
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:0000250|UniProtKB:Q09470"
FT LIPID 243
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q09470"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 400
FT /note="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
