KCNA1_RAT
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 03-AUG-2022, entry version 188.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 1;
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;
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, SUBCELLULAR LOCATION, AND ACTIVITY
RP 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, SUBCELLULAR LOCATION, AND ACTIVITY 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, SUBCELLULAR LOCATION, GLYCOSYLATION, PHOSPHORYLATION AT SER-446,
RP 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, MUTAGENESIS OF SER-309, SUBCELLULAR 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, SUBCELLULAR LOCATION, AND ACTIVITY 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 -!- 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). {ECO:0000250, 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). Detected in the islet of Langerhans
CC (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 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: 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) (TC
CC 1.A.1.2) subfamily. Kv1.1/KCNA1 sub-subfamily. {ECO:0000305}.
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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 GlyGen; P10499; 1 site.
DR iPTMnet; P10499; -.
DR PhosphoSitePlus; P10499; -.
DR PaxDb; P10499; -.
DR PRIDE; P10499; -.
DR ABCD; P10499; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000101523; ENSRNOP00000081659; ENSRNOG00000064052.
DR GeneID; 24520; -.
DR KEGG; rno:24520; -.
DR UCSC; RGD:2949; rat.
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; PQEGSYP; -.
DR OrthoDB; 695337at2759; -.
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 tissues.
DR Genevisible; P10499; RN.
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:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; 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; IEA:UniProtKB-SubCell.
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 ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR GO; GO:0099508; F:voltage-gated 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: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: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: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:1903818; P:positive regulation of voltage-gated potassium channel activity; IDA: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; 1.20.120.350; -; 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 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
