ID KCNA1_RAT Reviewed; 495 AA. AC P10499; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 27-MAR-2024, entry version 196. DE RecName: Full=Potassium voltage-gated channel subfamily A member 1 {ECO:0000305}; DE AltName: Full=RBKI {ECO:0000303|PubMed:2539643}; DE AltName: Full=RCK1 {ECO:0000303|PubMed:2348860, ECO:0000303|PubMed:8038169}; DE AltName: Full=Voltage-gated potassium channel subunit Kv1.1; GN Name=Kcna1 {ECO:0000312|RGD:2949}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=3191911; DOI=10.1002/j.1460-2075.1988.tb03092.x; RA Baumann A., Grupe A., Ackermann A., Pongs O.; RT "Structure of the voltage-dependent potassium channel is highly conserved RT from Drosophila to vertebrate central nervous systems."; RL EMBO J. 7:2457-2463(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR RP LOCATION, AND ACTIVITY REGULATION. RC TISSUE=Brain; RX PubMed=2539643; DOI=10.1126/science.2539643; RA Christie M.J., Adelman J.P., Douglass J., North R.A.; RT "Expression of a cloned rat brain potassium channel in Xenopus oocytes."; RL Science 244:221-224(1989). RN [3] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND ACTIVITY RP REGULATION. RX PubMed=2348860; DOI=10.1038/345535a0; RA Ruppersberg J.P., Schroeter K.H., Sakmann B., Stocker M., Sewing S., RA Pongs O.; RT "Heteromultimeric channels formed by rat brain potassium-channel RT proteins."; RL Nature 345:535-537(1990). RN [4] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, RP PHOSPHORYLATION AT SER-446, AND MUTAGENESIS OF ARG-443 AND SER-446. RX PubMed=8038169; DOI=10.1021/bi00195a021; RA Ivanina T., Perets T., Thornhill W.B., Levin G., Dascal N., Lotan I.; RT "Phosphorylation by protein kinase A of RCK1 K+ channels expressed in RT Xenopus oocytes."; RL Biochemistry 33:8786-8792(1994). RN [5] 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 [6] RP INTERACTION WITH KCNAB1 AND KCNAB2, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=9334400; DOI=10.1523/jneurosci.17-21-08246.1997; RA Rhodes K.J., Strassle B.W., Monaghan M.M., Bekele-Arcuri Z., Matos M.F., RA Trimmer J.S.; RT "Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits RT with Kv1 alpha-subunits in mammalian brain K+ channel complexes."; RL J. Neurosci. 17:8246-8258(1997). RN [7] RP SUBUNIT, INTERACTION WITH KCNA2 AND KCNA4, SUBCELLULAR LOCATION, AND RP GLYCOSYLATION. RX PubMed=10896669; DOI=10.1074/jbc.m005010200; RA Manganas L.N., Trimmer J.S.; RT "Subunit composition determines Kv1 potassium channel surface expression."; RL J. Biol. Chem. 275:29685-29693(2000). RN [8] RP INTERACTION WITH KCNA2 AND KCNA4, SUBUNIT, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. 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 [9] RP INTERACTION WITH STX1A; GNB1 AND GNG2, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12114518; DOI=10.1074/jbc.m203943200; RA Michaelevski I., Chikvashvili D., Tsuk S., Fili O., Lohse M.J., RA Singer-Lahat D., Lotan I.; RT "Modulation of a brain voltage-gated K+ channel by syntaxin 1A requires the RT physical interaction of Gbetagamma with the channel."; RL J. Biol. Chem. 277:34909-34917(2002). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12177193; DOI=10.1523/jneurosci.22-16-06953.2002; RA Dodson P.D., Barker M.C., Forsythe I.D.; RT "Two heteromeric Kv1 potassium channels differentially regulate action RT potential firing."; RL J. Neurosci. 22:6953-6961(2002). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12777451; DOI=10.1113/jphysiol.2003.046250; RA Dodson P.D., Billups B., Rusznak Z., Szucs G., Barker M.C., Forsythe I.D.; RT "Presynaptic rat Kv1.2 channels suppress synaptic terminal RT hyperexcitability following action potential invasion."; RL J. Physiol. (Lond.) 550:27-33(2003). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=12681381; DOI=10.1016/s0028-3908(03)00070-4; RA Winklhofer M., Matthias K., Seifert G., Stocker M., Sewing S., Herget T., RA Steinhaeuser C., Saaler-Reinhardt S.; RT "Analysis of phosphorylation-dependent modulation of Kv1.1 potassium RT channels."; RL Neuropharmacology 44:829-842(2003). RN [13] RP INTERACTION WITH DLG1; DLG2 AND DLG4. RX PubMed=7477295; DOI=10.1038/378085a0; RA Kim E., Niethammer M., Rothschild A., Jan Y.N., Sheng M.; RT "Clustering of Shaker-type K+ channels by interaction with a family of RT membrane-associated guanylate kinases."; RL Nature 378:85-88(1995). RN [14] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=16306173; DOI=10.1152/jn.01004.2005; RA Finnegan T.F., Chen S.R., Pan H.L.; RT "Mu opioid receptor activation inhibits GABAergic inputs to basolateral RT amygdala neurons through Kv1.1/1.2 channels."; RL J. Neurophysiol. 95:2032-2041(2006). RN [15] RP INTERACTION WITH LGI1; KCNA4 AND KCNAB1. RX PubMed=16504945; DOI=10.1016/j.neuron.2006.01.033; RA Schulte U., Thumfart J.-O., Kloecker N., Sailer C.A., Bildl W., RA Biniossek M., Dehn D., Deller T., Eble S., Abbass K., Wangler T., RA Knaus H.-G., Fakler B.; RT "The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels RT and inhibits inactivation by Kvbeta1."; RL Neuron 49:697-706(2006). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17855588; DOI=10.1152/jn.00437.2007; RA Chi X.X., Nicol G.D.; RT "Manipulation of the potassium channel Kv1.1 and its effect on neuronal RT excitability in rat sensory neurons."; RL J. Neurophysiol. 98:2683-2692(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 FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17869444; DOI=10.1016/j.neuroscience.2007.08.007; RA Yang Q., Chen S.R., Li D.P., Pan H.L.; RT "Kv1.1/1.2 channels are downstream effectors of nitric oxide on synaptic RT GABA release to preautonomic neurons in the paraventricular nucleus."; RL Neuroscience 149:315-327(2007). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION. RX PubMed=20805574; DOI=10.1085/jgp.200910398; RA Al-Sabi A., Shamotienko O., Dhochartaigh S.N., Muniyappa N., Le Berre M., RA Shaban H., Wang J., Sack J.T., Dolly J.O.; RT "Arrangement of Kv1 alpha subunits dictates sensitivity to RT tetraethylammonium."; RL J. Gen. Physiol. 136:273-282(2010). RN [20] 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 [21] RP FUNCTION, TRANSPORTER ACTIVITY, MUTAGENESIS OF SER-309, SUBCELLULAR RP LOCATION, AND MISCELLANEOUS. RX PubMed=22206926; DOI=10.1016/j.brainres.2011.11.023; RA Ishida S., Sakamoto Y., Nishio T., Baulac S., Kuwamura M., Ohno Y., RA Takizawa A., Kaneko S., Serikawa T., Mashimo T.; RT "Kcna1-mutant rats dominantly display myokymia, neuromyotonia and RT spontaneous epileptic seizures."; RL Brain Res. 1435:154-166(2012). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-437 AND SER-439, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [23] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND ACTIVITY RP REGULATION. RX PubMed=23725331; DOI=10.1042/bj20130297; RA Al-Sabi A., Kaza S.K., Dolly J.O., Wang J.; RT "Pharmacological characteristics of Kv1.1- and Kv1.2-containing channels RT are influenced by the stoichiometry and positioning of their alpha RT subunits."; RL Biochem. J. 454:101-108(2013). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND IDENTIFICATION IN A COMPLEX RP WITH KCNA2 AND KCNAB2. RX PubMed=23318870; DOI=10.1113/jphysiol.2012.249706; RA Ovsepian S.V., Steuber V., Le Berre M., O'Hara L., O'Leary V.B., RA Dolly J.O.; RT "A defined heteromeric KV1 channel stabilizes the intrinsic pacemaking and RT regulates the output of deep cerebellar nuclear neurons to thalamic RT targets."; RL J. Physiol. (Lond.) 591:1771-1791(2013). RN [25] RP MUTAGENESIS OF ALA-352; HIS-355; SER-357; TYR-379 AND VAL-381. RX PubMed=25514171; DOI=10.1016/j.bcp.2014.12.002; RA Wang X., Umetsu Y., Gao B., Ohki S., Zhu S.; RT "Mesomartoxin, a new K(v)1.2-selective scorpion toxin interacting with the RT channel selectivity filter."; RL Biochem. Pharmacol. 93:232-239(2015). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 29-128, INTERACTION WITH KCNAB2, RP TETRAMERIZATION, SUBUNIT, AND DOMAIN. RX PubMed=10884227; DOI=10.1126/science.289.5476.123; RA Gulbis J.M., Zhou M., Mann S., MacKinnon R.; RT "Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent RT K+ channels."; RL Science 289:123-127(2000). 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:12177193, PubMed:17855588, CC PubMed:22206926). Forms tetrameric potassium-selective channels through CC which potassium ions pass in accordance with their electrochemical CC gradient (PubMed:23725331). The channel alternates between opened and CC closed conformations in response to the voltage difference across the CC membrane (PubMed:2539643). Can form functional homotetrameric channels CC and heterotetrameric channels that contain variable proportions of CC KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family CC members as well; channel properties depend on the type of alpha CC subunits that are part of the channel (PubMed:2348860, PubMed:12177193, CC PubMed:10896669, PubMed:23725331). 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:10896669, PubMed:12114518). 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:2348860, PubMed:8038169, CC PubMed:12681381, PubMed:22206926, PubMed:23725331). In contrast, a CC heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid CC inactivation (PubMed:2348860). Regulates neuronal excitability in CC hippocampus, especially in mossy fibers and medial perforant path CC axons, preventing neuronal hyperexcitability. Response to toxins that CC are selective for KCNA1, respectively for KCNA2, suggests that CC heteromeric potassium channels composed of both KCNA1 and KCNA2 play a CC role in pacemaking and regulate the output of deep cerebellar nuclear CC neurons (PubMed:12177193, PubMed:23318870). May function as down-stream CC effector for G protein-coupled receptors and inhibit GABAergic inputs CC to basolateral amygdala neurons (PubMed:16306173). May contribute to CC the regulation of neurotransmitter release, such as gamma-aminobutyric CC acid (GABA) release (PubMed:17869444). 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 (By similarity). Required for normal CC neuromuscular responses (PubMed:22206926). Regulates the frequency of CC neuronal action potential firing in response to mechanical stimuli, and CC plays a role in the perception of pain caused by mechanical stimuli, CC but does not play a role in the perception of pain due to heat stimuli CC (By similarity). Required for normal responses to auditory stimuli and CC precise location of sound sources, but not for sound perception (By CC similarity). The use of toxins that block specific channels suggest CC that it contributes to the regulation of the axonal release of the CC neurotransmitter dopamine (By similarity). Required for normal CC 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 (By similarity). {ECO:0000250|UniProtKB:P16388, CC ECO:0000250|UniProtKB:Q09470, ECO:0000269|PubMed:10896669, CC ECO:0000269|PubMed:12114518, ECO:0000269|PubMed:12177193, CC ECO:0000269|PubMed:12681381, ECO:0000269|PubMed:17855588, CC ECO:0000269|PubMed:17869444, ECO:0000269|PubMed:22206926, CC ECO:0000269|PubMed:23318870, ECO:0000269|PubMed:2348860, CC ECO:0000269|PubMed:23725331, ECO:0000269|PubMed:2539643, CC ECO:0000269|PubMed:8038169, ECO:0000305|PubMed:16306173}. CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000269|PubMed:22206926, ECO:0000269|PubMed:2348860, CC ECO:0000269|PubMed:23725331, ECO:0000269|PubMed:2539643, CC ECO:0000269|PubMed:8038169}; CC -!- ACTIVITY REGULATION: Inhibited by 4-aminopyridine (4-AP) and by CC tetraethylammonium (TEA) (PubMed:2539643). Inhibited by kaliotoxin CC (KTX) (PubMed:23725331). {ECO:0000269|PubMed:2348860, CC ECO:0000269|PubMed:23725331, ECO:0000269|PubMed:2539643}. CC -!- SUBUNIT: Homotetramer and heterotetramer with other channel-forming CC alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 CC (PubMed:10896669, PubMed:10884227). Channel activity is regulated by CC interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:9334400, CC PubMed:12114518). Identified in a complex with KCNA2 and KCNAB2 CC (PubMed:10896669, PubMed:11086297, PubMed:23318870, PubMed:10884227). CC Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4. CC Interacts with LGI1 within a complex containing LGI1, KCNA4 and KCNAB1. CC Interacts (via cytoplasmic N-terminal domain) with KCNRG; this inhibits CC channel activity (By similarity). Interacts with ANK3; this inhibits CC channel activity (By similarity). Interacts (via N-terminus) with CC STX1A; this promotes channel inactivation (PubMed:12114518). Interacts CC (via N-terminus) with the heterodimer formed by GNB1 and GNG2; this CC promotes channel inactivation (PubMed:12114518). Can interact CC simultaneously with STX1A and the heterodimer formed by GNB1 and GNG2 CC (PubMed:12114518). Interacts with ADAM11 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P16388, ECO:0000250|UniProtKB:Q09470, CC ECO:0000269|PubMed:10884227, ECO:0000269|PubMed:10896669, CC ECO:0000269|PubMed:11086297, ECO:0000269|PubMed:12114518, CC ECO:0000269|PubMed:16504945, ECO:0000269|PubMed:23318870, CC ECO:0000269|PubMed:7477295, ECO:0000269|PubMed:9334400}. CC -!- INTERACTION: CC P10499; P78352: DLG4; Xeno; NbExp=2; IntAct=EBI-631463, EBI-80389; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12114518, CC ECO:0000269|PubMed:12681381, ECO:0000269|PubMed:17855588, CC ECO:0000269|PubMed:22206926, ECO:0000269|PubMed:2348860, CC ECO:0000269|PubMed:23725331, ECO:0000269|PubMed:2539643, CC ECO:0000269|PubMed:8038169}; Multi-pass membrane protein {ECO:0000305}. CC Membrane {ECO:0000269|PubMed:11086297, ECO:0000269|PubMed:9334400}. CC Cell projection, axon {ECO:0000269|PubMed:11086297, CC ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:9334400}. Cytoplasmic CC vesicle {ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:8038169}. CC Perikaryon {ECO:0000269|PubMed:12177193}. Endoplasmic reticulum CC {ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:12681381}. Cell CC projection, dendrite {ECO:0000250|UniProtKB:P16388}. Cell junction CC {ECO:0000250|UniProtKB:P16388}. Synapse {ECO:0000250|UniProtKB:P16388}. CC Presynapse {ECO:0000250|UniProtKB:P16388}. Presynaptic cell membrane CC {ECO:0000269|PubMed:17869444}. 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 CC (PubMed:10896669). {ECO:0000250|UniProtKB:P16388, CC ECO:0000269|PubMed:10896669}. CC -!- TISSUE SPECIFICITY: Detected in hippocampus, in the middle third of the CC molecular layer of the dentate gyrus and in stratum radiatum and CC stratum oriens (PubMed:9334400). Detected in the mossy fiber zone in CC the hippocampus CA3 region, at or near axon terminals (PubMed:9334400). CC Detected in brain cortex, at basket cell terminals (PubMed:9334400). CC Detected adjacent to nodes of Ranvier in juxtaparanodal zones in spinal CC cord nerve fibers, but also in paranodal regions in some myelinated CC spinal cord axons (PubMed:11086297). Detected in juxtaparanodal regions CC adjacent to the nodes of Ranvier in myelinated axons in cerebellar CC white matter (PubMed:9334400). Detected in sensory neurons CC (PubMed:17855588). Detected in neurons from the medial nucleus of the CC trapezoid body (PubMed:12177193). Detected in basolateral amygdala CC (PubMed:16306173). Detected in the paraventricular nucleus of the CC hypothalamus (PubMed:17869444). Detected in the islet of Langerhans (at CC protein level) (PubMed:21483673). {ECO:0000269|PubMed:11086297, CC ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:16306173, CC ECO:0000269|PubMed:17855588, ECO:0000269|PubMed:21483673, CC ECO:0000269|PubMed:9334400}. 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:0000269|PubMed:10884227}. CC -!- DOMAIN: The transmembrane segment S4 functions as a voltage-sensor and CC is characterized by a series of positively charged amino acids at every CC third position. Channel opening and closing is effected by a CC conformation change that affects the position and orientation of the CC voltage-sensor paddle formed by S3 and S4 within the membrane. A CC transmembrane electric field that is positive inside would push the CC positively charged S4 segment outwards, thereby opening the pore, while CC a field that is negative inside would pull the S4 segment inwards and CC close the pore. Changes in the position and orientation of S4 are then CC transmitted to the activation gate formed by the inner helix bundle via CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}. CC -!- PTM: Palmitoylated on Cys-243; which may be required for membrane CC targeting. {ECO:0000250|UniProtKB:Q09470}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10896669, CC ECO:0000269|PubMed:8038169}. CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation increases in CC response to NRG1; this inhibits channel activity (By similarity). CC Phosphorylated by PKA (PubMed:8038169, PubMed:12681381). CC Phosphorylation at Ser-446 regulates channel activity by down- CC regulating expression at the cell membrane (By similarity). CC {ECO:0000250|UniProtKB:P16388, ECO:0000250|UniProtKB:Q09470, CC ECO:0000269|PubMed:12681381, ECO:0000269|PubMed:8038169}. CC -!- RNA EDITING: Modified_positions=400 {ECO:0000269|PubMed:12907802}; CC Note=Partially edited. RNA editing is at an average of 50% in the whole CC brain.; CC -!- MISCELLANEOUS: A missense mutation at Ser-309 is the cause of the CC autosomal dominant myokymia and seizures (ADMS) phenotype. Homozygous CC and heterozygous rats are born at the expected Mendelian rate. After 6 CC weeks, heterozygous rats begin to display muscle twitching, startle CC responses and spontaneous convulsive seizures; over 80% of the animals CC are dead after 30 weeks. After 16 weeks, they display lower body weight CC compared to wild-type. The rats exhibit severe periodic seizures with CC characteristic alterations in their cortical and hippocampal CC electroencephalogram, similar to rodent models of temporal lobe CC epilepsy. Homozygous rats display impaired development starting 14 days CC after birth, with reduced body weight, tremors, motor incoordination, CC spontaneous convulsive seizures; none survive past 18 days after birth. CC {ECO:0000269|PubMed:22206926}. CC -!- MISCELLANEOUS: The delay or D-type current observed in hippocampus CC pyramidal neurons is probably mediated by potassium channels containing CC KCNA2 plus KCNA1 or other family members. It is activated at about -50 CC mV, i.e. below the action potential threshold, and is characterized by CC slow inactivation, extremely slow recovery from inactivation, CC sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP). CC {ECO:0000305|PubMed:17917103}. CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) CC (TC 1.A.1.2) subfamily. Kv1.1/KCNA1 sub-subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X12589; CAA31102.1; -; mRNA. DR EMBL; M26161; AAA41982.1; -; mRNA. DR PIR; B39113; B39113. DR RefSeq; NP_775118.1; NM_173095.3. DR PDB; 1EXB; X-ray; 2.10 A; E=27-129. DR PDBsum; 1EXB; -. DR AlphaFoldDB; P10499; -. DR SMR; P10499; -. DR BioGRID; 246675; 4. DR CORUM; P10499; -. DR IntAct; P10499; 3. DR MINT; P10499; -. DR STRING; 10116.ENSRNOP00000026731; -. DR BindingDB; P10499; -. DR ChEMBL; CHEMBL5190; -. DR GuidetoPHARMACOLOGY; 538; -. DR GlyCosmos; P10499; 1 site, No reported glycans. DR GlyGen; P10499; 1 site. DR iPTMnet; P10499; -. DR PhosphoSitePlus; P10499; -. DR PaxDb; 10116-ENSRNOP00000026731; -. DR ABCD; P10499; 2 sequenced antibodies. DR Ensembl; ENSRNOT00000101523.1; ENSRNOP00000081659.1; ENSRNOG00000064052.1. DR Ensembl; ENSRNOT00055018095; ENSRNOP00055014537; ENSRNOG00055010711. DR Ensembl; ENSRNOT00060028402; ENSRNOP00060022866; ENSRNOG00060016588. DR Ensembl; ENSRNOT00065057508; ENSRNOP00065047349; ENSRNOG00065033451. DR GeneID; 24520; -. DR KEGG; rno:24520; -. DR UCSC; RGD:2949; rat. DR AGR; RGD:2949; -. DR CTD; 3736; -. DR RGD; 2949; Kcna1. DR eggNOG; KOG1545; Eukaryota. DR GeneTree; ENSGT00940000158576; -. DR HOGENOM; CLU_011722_4_0_1; -. DR InParanoid; P10499; -. DR OMA; IATQNCV; -. DR OrthoDB; 1478695at2759; -. DR PhylomeDB; P10499; -. DR TreeFam; TF313103; -. DR Reactome; R-RNO-1296072; Voltage gated Potassium channels. DR EvolutionaryTrace; P10499; -. DR PRO; PR:P10499; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000019750; Expressed in cerebellum and 4 other cell types or tissues. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD. DR GO; GO:0030424; C:axon; ISO:RGD. DR GO; GO:0043194; C:axon initial segment; ISO:RGD. DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB. DR GO; GO:0044305; C:calyx of Held; IDA:SynGO. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:RGD. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; IDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. 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; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO. DR GO; GO:0034705; C:potassium channel complex; IDA:UniProtKB. DR GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IMP:UniProtKB. DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB. DR GO; GO:0097718; F:disordered domain specific binding; ISO:RGD. DR GO; GO:1905030; F:voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO. DR GO; GO:0099508; F:voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IDA:SynGO. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB. DR GO; GO:0061564; P:axon development; IEP:RGD. DR GO; GO:0007420; P:brain development; ISO:RGD. DR GO; GO:0010644; P:cell communication by electrical coupling; IMP:UniProtKB. DR GO; GO:0071286; P:cellular response to magnesium ion; ISS:UniProtKB. DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD. DR GO; GO:0022038; P:corpus callosum development; IEP:RGD. 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; ISO:RGD. DR GO; GO:0010960; P:magnesium ion homeostasis; ISS:UniProtKB. DR GO; GO:0086011; P:membrane repolarization during action potential; IDA:UniProtKB. DR GO; GO:0007405; P:neuroblast proliferation; ISO:RGD. DR GO; GO:0050905; P:neuromuscular process; ISS:UniProtKB. DR GO; GO:0019228; P:neuronal action potential; IMP:UniProtKB. DR GO; GO:0023041; P:neuronal signal transduction; IMP:UniProtKB. DR GO; GO:0021554; P:optic nerve development; IEP:RGD. 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; IDA:UniProtKB. DR GO; GO:0042391; P:regulation of membrane potential; ISS:UniProtKB. DR GO; GO:0006937; P:regulation of muscle contraction; IMP:UniProtKB. DR GO; GO:0001964; P:startle response; IMP:UniProtKB. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 1. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR003968; K_chnl_volt-dep_Kv. DR InterPro; IPR003972; K_chnl_volt-dep_Kv1. DR InterPro; IPR004048; K_chnl_volt-dep_Kv1.1. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR003131; T1-type_BTB. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR11537:SF24; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY A MEMBER 1; 1. DR PANTHER; PTHR11537; VOLTAGE-GATED POTASSIUM CHANNEL; 1. DR Pfam; PF02214; BTB_2; 1. DR Pfam; PF00520; Ion_trans; 1. DR PRINTS; PR00169; KCHANNEL. DR PRINTS; PR01508; KV11CHANNEL. DR PRINTS; PR01491; KVCHANNEL. DR PRINTS; PR01496; SHAKERCHANEL. DR SMART; SM00225; BTB; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; P10499; RN. PE 1: Evidence at protein level; KW 3D-structure; Cell junction; Cell membrane; Cell projection; KW Cytoplasmic vesicle; 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_0000053970" 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:0000305" 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:0000305" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 322 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 437 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 439 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 446 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:8038169" 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)" FT MUTAGEN 309 FT /note="S->T: In ADMS: Dominant negative mutation that FT abolishes channel activity; leads to myokymia, FT neuromyotonia, spontaneous epileptic seizures and premature FT death." FT /evidence="ECO:0000269|PubMed:22206926" FT MUTAGEN 352 FT /note="A->R: Is not blocked by the scorpion mesomartoxin." FT /evidence="ECO:0000269|PubMed:25514171" FT MUTAGEN 355 FT /note="H->Q: Is not blocked by the scorpion mesomartoxin." FT /evidence="ECO:0000269|PubMed:25514171" FT MUTAGEN 357 FT /note="S->P: Is not blocked by the scorpion mesomartoxin." FT /evidence="ECO:0000269|PubMed:25514171" FT MUTAGEN 379 FT /note="Y->V: Is blocked by the scorpion mesomartoxin, with FT an IC(50)=16.60 nM." FT /evidence="ECO:0000269|PubMed:25514171" FT MUTAGEN 381 FT /note="V->T: Is not blocked by the scorpion mesomartoxin." FT /evidence="ECO:0000269|PubMed:25514171" FT MUTAGEN 443 FT /note="R->C: Abolishes phosphorylation by PKA; when FT associated with A-446." FT MUTAGEN 446 FT /note="S->A: Abolishes phosphorylation by PKA; when FT associated with C-443." FT STRAND 38..43 FT /evidence="ECO:0007829|PDB:1EXB" FT STRAND 46..51 FT /evidence="ECO:0007829|PDB:1EXB" FT HELIX 52..56 FT /evidence="ECO:0007829|PDB:1EXB" FT TURN 62..64 FT /evidence="ECO:0007829|PDB:1EXB" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:1EXB" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:1EXB" FT TURN 75..78 FT /evidence="ECO:0007829|PDB:1EXB" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:1EXB" FT HELIX 86..97 FT /evidence="ECO:0007829|PDB:1EXB" FT HELIX 110..119 FT /evidence="ECO:0007829|PDB:1EXB" SQ SEQUENCE 495 AA; 56379 MW; 29804463133F5D31 CRC64; MTVMSGENAD EASAAPGHPQ 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 ANIRTGNCTA TDQNCVNKSK LLTDV //