KCNA2_RAT
ID KCNA2_RAT Reviewed; 499 AA.
AC P63142; P15386; Q02010;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 2;
DE AltName: Full=RAK;
DE AltName: Full=RBK2 {ECO:0000303|PubMed:2722779};
DE AltName: Full=RCK5 {ECO:0000303|PubMed:2555158};
DE AltName: Full=Voltage-gated potassium channel subunit Kv1.2;
GN Name=Kcna2;
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], AND TISSUE SPECIFICITY.
RX PubMed=2722779; DOI=10.1016/s0021-9258(18)83173-8;
RA McKinnon D.;
RT "Isolation of a cDNA clone coding for a putative second potassium channel
RT indicates the existence of a gene family.";
RL J. Biol. Chem. 264:8230-8236(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Brain;
RX PubMed=2555158; DOI=10.1002/j.1460-2075.1989.tb08483.x;
RA Stuehmer W., Ruppersberg J.P., Schroerter K.H., Sakmann B., Stocker M.,
RA Giese K.P., Perschke A., Baumann A., Pongs O.;
RT "Molecular basis of functional diversity of voltage-gated potassium
RT channels in mammalian brain.";
RL EMBO J. 8:3235-3244(1989).
RN [3]
RP SEQUENCE REVISION.
RA Ludwig J.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Heart atrium;
RX PubMed=1715584; DOI=10.1073/pnas.88.17.7892;
RA Paulmichl M., Nasmith P., Herllmiss R., Reed K., Boyle W.A., Nerbonne J.M.,
RA Peralta E.G., Clapham D.E.;
RT "Cloning and expression of a rat cardiac delayed rectifier potassium
RT channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7892-7895(1991).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH KCNA4, AND
RP ACTIVITY REGULATION.
RX PubMed=8495559; DOI=10.1161/01.res.72.6.1326;
RA Po S., Roberds S., Snyders D.J., Tamkun M.M., Bennett P.B.;
RT "Heteromultimeric assembly of human potassium channels. Molecular basis of
RT a transient outward current?";
RL Circ. Res. 72:1326-1336(1993).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=8355670;
RA Werkman T.R., Gustafson T.A., Rogowski R.S., Blaustein M.P., Rogawski M.A.;
RT "Tityustoxin-K alpha, a structurally novel and highly potent K+ channel
RT peptide toxin, interacts with the alpha-dendrotoxin binding site on the
RT cloned Kv1.2 K+ channel.";
RL Mol. Pharmacol. 44:430-436(1993).
RN [7]
RP SUBUNIT, INTERACTION WITH KCNA4, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8361540; DOI=10.1038/365072a0;
RA Sheng M., Liao Y.J., Jan Y.N., Jan L.Y.;
RT "Presynaptic A-current based on heteromultimeric K+ channels detected in
RT vivo.";
RL Nature 365:72-75(1993).
RN [8]
RP INTERACTION WITH DLG1; DLG2 AND DLG4, AND TISSUE SPECIFICITY.
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RC TISSUE=Brain;
RX PubMed=7544443; DOI=10.1038/376737a0;
RA Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J.M.,
RA Plowman G.D., Rudy B., Schlessinger J.;
RT "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion
RT channel and MAP kinase functions.";
RL Nature 376:737-745(1995).
RN [10]
RP FUNCTION, AND INTERACTION WITH RHOA.
RX PubMed=9635436; DOI=10.1016/s0092-8674(00)81212-x;
RA Cachero T.G., Morielli A.D., Peralta E.G.;
RT "The small GTP-binding protein RhoA regulates a delayed rectifier potassium
RT channel.";
RL Cell 93:1077-1085(1998).
RN [11]
RP INTERACTION WITH CNTNAP2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10624965; DOI=10.1016/s0896-6273(00)81049-1;
RA Poliak S., Gollan L., Martinez R., Custer A., Einheber S., Salzer J.L.,
RA Trimmer J.S., Shrager P., Peles E.;
RT "Caspr2, a new member of the neurexin superfamily, is localized at the
RT juxtaparanodes of myelinated axons and associates with K+ channels.";
RL Neuron 24:1037-1047(1999).
RN [12]
RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH KCNAB2; KCNA1 AND KCNA4,
RP AND 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 [13]
RP SUBCELLULAR LOCATION, INTERACTION WITH KCNA1 AND KCNAB2, SUBUNIT, AND
RP TISSUE SPECIFICITY.
RX PubMed=11086297;
RX DOI=10.1002/1096-9861(20000101)429:1<166::aid-cne13>3.0.co;2-y;
RA Rasband M.N., Trimmer J.S.;
RT "Subunit composition and novel localization of K+ channels in spinal
RT cord.";
RL J. Comp. Neurol. 429:166-176(2001).
RN [14]
RP INTERACTION WITH PTK2B, AND PHOSPHORYLATION.
RX PubMed=11739373; DOI=10.1074/jbc.m104726200;
RA Byron K.L., Lucchesi P.A.;
RT "Signal transduction of physiological concentrations of vasopressin in A7r5
RT vascular smooth muscle cells. A role for PYK2 and tyrosine phosphorylation
RT of K+ channels in the stimulation of Ca2+ spiking.";
RL J. Biol. Chem. 277:7298-7307(2002).
RN [15]
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH CTTN, SUBCELLULAR LOCATION,
RP TOPOLOGY, AND MUTAGENESIS OF TYR-415 AND TYR-417.
RX PubMed=12151401; DOI=10.1074/jbc.m205005200;
RA Hattan D., Nesti E., Cachero T.G., Morielli A.D.;
RT "Tyrosine phosphorylation of Kv1.2 modulates its interaction with the
RT actin-binding protein cortactin.";
RL J. Biol. Chem. 277:38596-38606(2002).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND SUBUNIT.
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 [17]
RP INDUCTION BY HYPOXIA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=14713306; DOI=10.1046/j.1471-4159.2003.02110.x;
RA Qiu M.H., Zhang R., Sun F.Y.;
RT "Enhancement of ischemia-induced tyrosine phosphorylation of Kv1.2 by
RT vascular endothelial growth factor via activation of phosphatidylinositol
RT 3-kinase.";
RL J. Neurochem. 87:1509-1517(2003).
RN [18]
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 [19]
RP SUBUNIT, INTERACTION WITH KCNA4, AND TISSUE SPECIFICITY.
RX PubMed=12632190; DOI=10.1007/s00424-002-0994-7;
RA Fergus D.J., Martens J.R., England S.K.;
RT "Kv channel subunits that contribute to voltage-gated K+ current in renal
RT vascular smooth muscle.";
RL Pflugers Arch. 445:697-704(2003).
RN [20]
RP INDUCTION BY HYPOXIA.
RX PubMed=15151918; DOI=10.1165/rcmb.2003-0386oc;
RA Hong Z., Weir E.K., Nelson D.P., Olschewski A.;
RT "Subacute hypoxia decreases voltage-activated potassium channel expression
RT and function in pulmonary artery myocytes.";
RL Am. J. Respir. Cell Mol. Biol. 31:337-343(2004).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=15618540; DOI=10.1161/01.res.0000154070.06421.25;
RA Plane F., Johnson R., Kerr P., Wiehler W., Thorneloe K., Ishii K., Chen T.,
RA Cole W.;
RT "Heteromultimeric Kv1 channels contribute to myogenic control of arterial
RT diameter.";
RL Circ. Res. 96:216-224(2005).
RN [22]
RP FUNCTION.
RX PubMed=16210348; DOI=10.1113/jphysiol.2005.098053;
RA Khavandgar S., Walter J.T., Sageser K., Khodakhah K.;
RT "Kv1 channels selectively prevent dendritic hyperexcitability in rat
RT Purkinje cells.";
RL J. Physiol. (Lond.) 569:545-557(2005).
RN [23]
RP FUNCTION.
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 [24]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-207, AND
RP MUTAGENESIS OF ASN-207; SER-356; SER-360 AND THR-383.
RX PubMed=16770729; DOI=10.1007/s11064-006-9056-4;
RA Fujita T., Utsunomiya I., Ren J., Matsushita Y., Kawai M., Sasaki S.,
RA Hoshi K., Miyatake T., Taguchi K.;
RT "Glycosylation and cell surface expression of Kv1.2 potassium channel are
RT regulated by determinants in the pore region.";
RL Neurochem. Res. 31:589-596(2006).
RN [25]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17324383; DOI=10.1016/j.brainres.2007.01.092;
RA Watanabe I., Zhu J., Sutachan J.J., Gottschalk A., Recio-Pinto E.,
RA Thornhill W.B.;
RT "The glycosylation state of Kv1.2 potassium channels affects trafficking,
RT gating, and simulated action potentials.";
RL Brain Res. 1144:1-18(2007).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-252.
RX PubMed=17766348; DOI=10.1529/biophysj.107.116160;
RA Rezazadeh S., Kurata H.T., Claydon T.W., Kehl S.J., Fedida D.;
RT "An activation gating switch in Kv1.2 is localized to a threonine residue
RT in the S2-S3 linker.";
RL Biophys. J. 93:4173-4186(2007).
RN [27]
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 [28]
RP FUNCTION.
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 [29]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-440 AND SER-449,
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH KCNAB2, AND
RP MUTAGENESIS OF THR-46; SER-440 AND SER-449.
RX PubMed=18003609; DOI=10.1074/jbc.m708875200;
RA Connors E.C., Ballif B.A., Morielli A.D.;
RT "Homeostatic regulation of Kv1.2 potassium channel trafficking by cyclic
RT AMP.";
RL J. Biol. Chem. 283:3445-3453(2008).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 267-PHE--PHE-302.
RX PubMed=18638484; DOI=10.1016/j.jmb.2008.06.085;
RA Tao X., MacKinnon R.;
RT "Functional analysis of Kv1.2 and paddle chimera Kv channels in planar
RT lipid bilayers.";
RL J. Mol. Biol. 382:24-33(2008).
RN [31]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH KCNAB1.
RX PubMed=19713757; DOI=10.4161/chan.3.5.9558;
RA Peters C.J., Vaid M., Horne A.J., Fedida D., Accili E.A.;
RT "The molecular basis for the actions of Kvbeta1.2 on the opening and
RT closing of the Kv1.2 delayed rectifier channel.";
RL Channels 3:314-322(2009).
RN [32]
RP SUBCELLULAR LOCATION.
RX PubMed=19403695; DOI=10.1091/mbc.e08-10-1074;
RA Stirling L., Williams M.R., Morielli A.D.;
RT "Dual roles for RHOA/RHO-kinase in the regulated trafficking of a voltage-
RT sensitive potassium channel.";
RL Mol. Biol. Cell 20:2991-3002(2009).
RN [33]
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 [34]
RP FUNCTION, INTERACTION WITH ADAM22 AND DLG4, SUBCELLULAR LOCATION,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=20089912; DOI=10.1523/jneurosci.4661-09.2010;
RA Ogawa Y., Oses-Prieto J., Kim M.Y., Horresh I., Peles E., Burlingame A.L.,
RA Trimmer J.S., Meijer D., Rasband M.N.;
RT "ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated
RT guanylate kinases to juxtaparanodes of myelinated axons.";
RL J. Neurosci. 30:1038-1048(2010).
RN [35]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP TYR-458, AND MUTAGENESIS OF TYR-458.
RX PubMed=21602278; DOI=10.1074/jbc.m111.219113;
RA Gu C., Gu Y.;
RT "Clustering and activity tuning of Kv1 channels in myelinated hippocampal
RT axons.";
RL J. Biol. Chem. 286:25835-25847(2011).
RN [36]
RP FUNCTION.
RX PubMed=21647367; DOI=10.1371/journal.pone.0020402;
RA Martel P., Leo D., Fulton S., Berard M., Trudeau L.E.;
RT "Role of Kv1 potassium channels in regulating dopamine release and
RT presynaptic D2 receptor function.";
RL PLoS ONE 6:E20402-E20402(2011).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440; SER-441 AND SER-468, 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 [38]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-381.
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 [39]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND IDENTIFICATION IN A COMPLEX
RP WITH KCNA1 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 [40]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=24472174; DOI=10.1186/1744-8069-10-8;
RA Fan L., Guan X., Wang W., Zhao J.Y., Zhang H., Tiwari V., Hoffman P.N.,
RA Li M., Tao Y.X.;
RT "Impaired neuropathic pain and preserved acute pain in rats overexpressing
RT voltage-gated potassium channel subunit Kv1.2 in primary afferent
RT neurons.";
RL Mol. Pain 10:8-8(2014).
RN [41]
RP SITE 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 [42]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 33-119 OF WILD-TYPE AND MUTANT
RP VAL-46, FUNCTION, SUBUNIT, REGION, DOMAIN, AND MUTAGENESIS OF ARG-34;
RP ASN-38; SER-40; GLY-41; LEU-42; ARG-43; PHE-44; GLU-45; THR-46; GLN-47;
RP THR-50; ASP-70; ARG-73; GLU-75; PHE-77; ASP-79; ASN-81; ARG-82; ASP-86;
RP LEU-89; TYR-90; GLN-93; ARG-97; ARG-99; VAL-102; ASN-103; PRO-105; ASP-107;
RP ILE-108 AND GLU-111.
RX PubMed=11007484; DOI=10.1016/s0092-8674(00)00088-x;
RA Minor D.L. Jr., Lin Y.-F., Mobley B.C., Avelar A., Jan Y.N., Jan L.Y.,
RA Berger J.M.;
RT "The polar T1 interface is linked to conformational changes that open the
RT voltage-gated potassium channel.";
RL Cell 102:657-670(2000).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH KCNAB2, SUBCELLULAR
RP LOCATION, TOPOLOGY, SUBUNIT, AND INTERACTION WITH KCNAB2.
RX PubMed=16002581; DOI=10.1126/science.1116269;
RA Long S.B., Campbell E.B., Mackinnon R.;
RT "Crystal structure of a mammalian voltage-dependent Shaker family K+
RT channel.";
RL Science 309:897-903(2005).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH KCNAB2, AND DOMAIN.
RX PubMed=16002579; DOI=10.1126/science.1116270;
RA Long S.B., Campbell E.B., Mackinnon R.;
RT "Voltage sensor of Kv1.2: structural basis of electromechanical coupling.";
RL Science 309:903-908(2005).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF PADDLE CHIMERA MUTANT IN COMPLEX
RP WITH KCNAB2, FUNCTION, SUBUNIT, INTERACTION WITH KCNAB2, SUBCELLULAR
RP LOCATION, AND TOPOLOGY.
RX PubMed=18004376; DOI=10.1038/nature06265;
RA Long S.B., Tao X., Campbell E.B., MacKinnon R.;
RT "Atomic structure of a voltage-dependent K+ channel in a lipid membrane-
RT like environment.";
RL Nature 450:376-382(2007).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH KCNAB2, INTERACTION
RP WITH KCNAB2, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=20534430; DOI=10.1073/pnas.1000142107;
RA Chen X., Wang Q., Ni F., Ma J.;
RT "Structure of the full-length Shaker potassium channel Kv1.2 by normal-
RT mode-based X-ray crystallographic refinement.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11352-11357(2010).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-266 AND 303-499 IN COMPLEX WITH
RP KCNAB2, SUBUNIT, INTERACTION WITH KCNAB2, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RX PubMed=20360102; DOI=10.1126/science.1185954;
RA Tao X., Lee A., Limapichat W., Dougherty D.A., MacKinnon R.;
RT "A gating charge transfer center in voltage sensors.";
RL Science 328:67-73(2010).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF PADDLE CHIMERA MUTANT IN COMPLEX
RP WITH KCNAB2 AND CHARYBDOTOXIN, INTERACTION WITH KCNAB2, SUBUNIT,
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=23705070; DOI=10.7554/elife.00594;
RA Banerjee A., Lee A., Campbell E., Mackinnon R.;
RT "Structure of a pore-blocking toxin in complex with a eukaryotic voltage-
RT dependent K(+) channel.";
RL Elife 2:E00594-E00594(2013).
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 cardiovascular system.
CC Prevents aberrant action potential firing and regulates neuronal
CC output. Forms tetrameric potassium-selective channels through which
CC potassium ions pass in accordance with their electrochemical gradient.
CC The channel alternates between opened and closed conformations in
CC response to the voltage difference across the membrane
CC (PubMed:12151401, PubMed:21602278, PubMed:24472174). Can form
CC functional homotetrameric channels and heterotetrameric channels that
CC contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6,
CC KCNA7, and possibly other family members as well; channel properties
CC depend on the type of alpha subunits that are part of the channel
CC (PubMed:8495559, PubMed:15618540, PubMed:20805574, PubMed:23725331).
CC Channel properties are modulated by cytoplasmic beta subunits that
CC regulate the subcellular location of the alpha subunits and promote
CC rapid inactivation of delayed rectifier potassium channels
CC (PubMed:18003609, PubMed:19713757). In vivo, membranes probably contain
CC a mixture of heteromeric potassium channel complexes, making it
CC difficult to assign currents observed in intact tissues to a particular
CC potassium channel family member. Homotetrameric KCNA2 forms a delayed-
CC rectifier potassium channel that opens in response to membrane
CC depolarization, followed by slow spontaneous channel closure
CC (PubMed:1715584, PubMed:16770729, PubMed:17766348, PubMed:18003609,
CC PubMed:18638484, PubMed:19713757, PubMed:20089912). In contrast, a
CC heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation
CC (PubMed:8495559). Response to toxins that are selective for KCNA1,
CC respectively for KCNA2, suggests that heteromeric potassium channels
CC composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate
CC the output of deep cerebellar nuclear neurons (PubMed:23318870). KCNA2-
CC containing channels play a presynaptic role and prevent
CC hyperexcitability and aberrant action potential firing
CC (PubMed:12777451). Response to toxins that are selective for KCNA2-
CC containing potassium channels suggests that in Purkinje cells,
CC dendritic subthreshold KCNA2-containing potassium channels prevent
CC random spontaneous calcium spikes, suppressing dendritic
CC hyperexcitability without hindering the generation of somatic action
CC potentials, and thereby play an important role in motor coordination
CC (PubMed:16210348). Plays a role in the induction of long-term
CC potentiation of neuron excitability in the CA3 layer of the hippocampus
CC (By similarity). May function as down-stream effector for G protein-
CC coupled receptors and inhibit GABAergic inputs to basolateral amygdala
CC neurons (PubMed:16306173). May contribute to the regulation of
CC neurotransmitter release, such as gamma-aminobutyric acid (GABA)
CC (PubMed:17869444). Contributes to the regulation of the axonal release
CC of the neurotransmitter dopamine (PubMed:21647367). Reduced KCNA2
CC expression plays a role in the perception of neuropathic pain after
CC peripheral nerve injury, but not acute pain (PubMed:24472174). Plays a
CC role in the regulation of the time spent in non-rapid eye movement
CC (NREM) sleep (By similarity). {ECO:0000250|UniProtKB:P63141,
CC ECO:0000269|PubMed:11007484, ECO:0000269|PubMed:12151401,
CC ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:12777451,
CC ECO:0000269|PubMed:15618540, ECO:0000269|PubMed:16210348,
CC ECO:0000269|PubMed:16770729, ECO:0000269|PubMed:1715584,
CC ECO:0000269|PubMed:17766348, ECO:0000269|PubMed:18003609,
CC ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:18638484,
CC ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20805574,
CC ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:23318870,
CC ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2555158,
CC ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8495559, ECO:0000305,
CC ECO:0000305|PubMed:12177193, ECO:0000305|PubMed:16306173,
CC ECO:0000305|PubMed:17869444, ECO:0000305|PubMed:21647367}.
CC -!- ACTIVITY REGULATION: Inhibited by 4-aminopyridine (4-AP), dendrotoxin
CC (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA)
CC (PubMed:2555158, PubMed:8495559, PubMed:18638484). Inhibited by
CC tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for
CC KCNA2 (PubMed:8355670). Inhibited by maurotoxin (PubMed:24472174).
CC Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By
CC similarity). {ECO:0000250|UniProtKB:P16389,
CC ECO:0000269|PubMed:18638484, ECO:0000269|PubMed:20805574,
CC ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2555158,
CC ECO:0000269|PubMed:8355670, ECO:0000269|PubMed:8495559}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=Homotetrameric channels activate rapidly, i.e within a few msec,
CC but inactivation is very slow, with only a marginal decrease in
CC conductance over several seconds. The voltage-dependence of
CC activation and inactivation and other channel characteristics vary
CC depending on the experimental conditions, the expression system,
CC post-translational modifications and the presence or absence of
CC ancillary subunits. For the activation of homotetrameric channels
CC expressed in xenopus oocytes, the voltage at half-maximal amplitude
CC is about -34 mV (PubMed:2555158). Unit channel conductance is about
CC 10 pS (PubMed:2555158). For the activation of homotetrameric channels
CC expressed in Chinese hamster ovary (CHO) cells, the voltage at half-
CC maximal amplitude is about -10 mV (PubMed:17324383).
CC {ECO:0000269|PubMed:17324383, ECO:0000269|PubMed:2555158};
CC -!- SUBUNIT: Homotetramer and heterotetramer with other channel-forming
CC alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7
CC (PubMed:8495559, PubMed:8361540, PubMed:10896669, PubMed:12777451,
CC PubMed:12632190, PubMed:15618540, PubMed:11007484, PubMed:16002581,
CC PubMed:18004376, PubMed:20534430). Channel activity is regulated by
CC interaction with beta subunits, including KCNAB1 and KCNAB2
CC (PubMed:18003609, PubMed:19713757, PubMed:16002581, PubMed:18004376,
CC PubMed:20534430, PubMed:20360102, PubMed:23705070). Identified in a
CC complex with KCNA1 and KCNAB2 (PubMed:11086297, PubMed:23318870).
CC Identified in a complex with KCNA5 and KCNAB1 (By similarity).
CC Identified in a complex with KCNA4 and FYN (By similarity). Interacts
CC (via C-terminus) with the PDZ domains of DLG1 and DLG2
CC (PubMed:7477295). Interacts with DLG4 (via PDZ domain) (PubMed:7477295,
CC PubMed:20089912). Interacts with PTK2B (PubMed:11739373). Interacts
CC (via C-terminus) with CTTN (PubMed:12151401). Interacts (via N-terminal
CC cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel
CC activity by reducing location at the cell surface in response to CHRM1
CC activation (PubMed:9635436). Interacts with DRD2 (By similarity).
CC Interacts with SIGMAR1; cocaine consumption leads to increased
CC interaction (By similarity). Interacts with CNTNAP2 (PubMed:10624965).
CC Interacts with ADAM22 (PubMed:20089912). {ECO:0000250|UniProtKB:P63141,
CC ECO:0000250|UniProtKB:Q09081, ECO:0000269|PubMed:10624965,
CC ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:11007484,
CC ECO:0000269|PubMed:11086297, ECO:0000269|PubMed:11739373,
CC ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:12632190,
CC ECO:0000269|PubMed:15618540, ECO:0000269|PubMed:16002581,
CC ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:19713757,
CC ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20360102,
CC ECO:0000269|PubMed:20534430, ECO:0000269|PubMed:23318870,
CC ECO:0000269|PubMed:23705070, ECO:0000269|PubMed:7477295,
CC ECO:0000269|PubMed:8361540, ECO:0000269|PubMed:8495559,
CC ECO:0000269|PubMed:9635436, ECO:0000305}.
CC -!- INTERACTION:
CC P63142; P78352: DLG4; Xeno; NbExp=2; IntAct=EBI-631446, EBI-80389;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10896669,
CC ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:14713306,
CC ECO:0000269|PubMed:15618540, ECO:0000269|PubMed:16770729,
CC ECO:0000269|PubMed:1715584, ECO:0000269|PubMed:17766348,
CC ECO:0000269|PubMed:18003609, ECO:0000269|PubMed:20089912,
CC ECO:0000269|PubMed:20805574, ECO:0000269|PubMed:21602278,
CC ECO:0000269|PubMed:23318870, ECO:0000269|PubMed:23725331,
CC ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2555158,
CC ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:9635436,
CC ECO:0000305|PubMed:11086297}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:16002581,
CC ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:20360102,
CC ECO:0000269|PubMed:20534430, ECO:0000269|PubMed:23705070, ECO:0000305}.
CC Membrane {ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:16002581,
CC ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:18638484,
CC ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20360102,
CC ECO:0000269|PubMed:20534430, ECO:0000269|PubMed:23705070,
CC ECO:0000269|PubMed:8361540}. Cell projection, axon
CC {ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:12177193,
CC ECO:0000269|PubMed:12777451, ECO:0000269|PubMed:20089912,
CC ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:8361540}. Synapse
CC {ECO:0000269|PubMed:8361540}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:P63141}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:P63141}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P63141}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10896669}. Cell projection, lamellipodium membrane
CC {ECO:0000269|PubMed:12151401}. Endosome {ECO:0000269|PubMed:19403695}.
CC Perikaryon {ECO:0000269|PubMed:23318870}. Cell junction, paranodal
CC septate junction {ECO:0000250|UniProtKB:P63141}. Note=KCNA2 by itself
CC is detected both at the endoplasmic reticulum and at the cell membrane.
CC Coexpression with KCNA4 or with beta subunits promotes expression at
CC the cell membrane (PubMed:10896669, PubMed:16770729, PubMed:18003609).
CC Coexpression with KCNA1 inhibits cell surface expression
CC (PubMed:10896669). Surface levels are regulated both by steady-state
CC and stimulus-induced clathrin-dependent endocytosis (PubMed:19403695).
CC Expression at the cell surface is down-regulated in response to CHRM1
CC activation (PubMed:9635436). Expression at the cell surface is
CC increased in response to the activation of beta-adrenergic receptors
CC and increased cAMP levels (PubMed:18003609). Detected on presynaptic
CC and postsynaptic axon segments (PubMed:12777451). In myelinated
CC peripheral axons, clustered in the juxtaparadonal region and at an
CC internodal line located along the mesaxon and below the Schmidt-
CC Lanterman incisures (By similarity). {ECO:0000250|UniProtKB:P63141,
CC ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:12777451,
CC ECO:0000269|PubMed:16770729, ECO:0000269|PubMed:18003609,
CC ECO:0000269|PubMed:19403695, ECO:0000269|PubMed:9635436}.
CC -!- TISSUE SPECIFICITY: Detected in neurons in dorsal root ganglion
CC (PubMed:24472174). Detected in hippocampus neurons (PubMed:21602278).
CC Detected on neurons of the anteroventral cochlear nucleus
CC (PubMed:12777451). Detected in renal arteries (PubMed:12632190).
CC Detected in neurons of the medial nucleus of the trapezoid body
CC (PubMed:12177193). Detected in neurons in the brain cortex
CC (PubMed:14713306). Detected in axon tracts of the corpus callosum,
CC specific terminal fields of the brain cortex neuropil, neurons in the
CC medial entorhinal cortex, and in puncta representing mossy fiber
CC terminals in the hippocampus mossy fiber tract; these puncta correspond
CC to synapses made by dentate granule cells (PubMed:8361540). Detected in
CC paranodal and juxtanodal zones in the central nervous system, including
CC myelinated spinal cord (PubMed:11086297, PubMed:20089912). Detected in
CC the juxtaparanodal region in optic nerve (PubMed:10624965). Detected at
CC nerve terminal plexuses of basket cells in the cerebellum (at protein
CC level) (PubMed:7477295, PubMed:20089912). Detected in brain
CC (PubMed:2722779). Detected in heart atrium and ventricle
CC (PubMed:1715584). Detected in renal arteries (PubMed:12632190).
CC {ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:11086297,
CC ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:12632190,
CC ECO:0000269|PubMed:14713306, ECO:0000269|PubMed:1715584,
CC ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:21602278,
CC ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2722779,
CC ECO:0000269|PubMed:7477295, ECO:0000269|PubMed:8361540}.
CC -!- INDUCTION: Up-regulated in brain cortex in response to ischemia (at
CC protein level) (PubMed:14713306). Down-regulated in dorsal root
CC ganglion neurons after peripheral nerve injury (at protein level)
CC (PubMed:24472174). Down-regulated in pulmonary artery myocytes in
CC response to chronic moderate hypoxia. {ECO:0000269|PubMed:14713306,
CC ECO:0000269|PubMed:15151918, ECO:0000269|PubMed:24472174}.
CC -!- DOMAIN: The cytoplasmic N-terminus is important for tetramerization.
CC Interactions between the different subunits modulate the gating
CC characteristics (PubMed:11007484). Besides, the cytoplasmic N-terminal
CC domain mediates interaction with RHOA and thus is required for RHOA-
CC mediated endocytosis (PubMed:9635436). {ECO:0000269|PubMed:11007484,
CC ECO:0000269|PubMed:19403695, ECO:0000269|PubMed:9635436}.
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:0000305|PubMed:16002579,
CC ECO:0000305|PubMed:20360102}.
CC -!- PTM: Phosphorylated on tyrosine residues; phosphorylation increases in
CC response to ischemia (PubMed:14713306). Phosphorylated on tyrosine
CC residues by activated PTK2B/PYK2 (PubMed:7544443). Phosphorylation on
CC tyrosine residues suppresses ion channel activity (PubMed:7544443).
CC Phosphorylated on tyrosine residues in response to CHRM1 activation;
CC this abolishes interaction with CTTN (PubMed:12151401). This is
CC probably due to endocytosis of the phosphorylated channel subunits.
CC Phosphorylated on serine residues in response to increased cAMP levels;
CC phosphorylation is apparently not catalyzed by PKA (PubMed:18003609).
CC {ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:14713306,
CC ECO:0000269|PubMed:18003609, ECO:0000269|PubMed:7544443}.
CC -!- PTM: N-glycosylated, with complex, sialylated N-glycans.
CC {ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:16770729}.
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. Kv1.2/KCNA2 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; J04731; AAA40819.1; -; mRNA.
DR EMBL; X16003; CAA34134.1; -; mRNA.
DR EMBL; M74449; AAA19867.1; -; mRNA.
DR PIR; A33814; A33814.
DR RefSeq; NP_037102.1; NM_012970.3.
DR RefSeq; XP_006233194.1; XM_006233132.3.
DR RefSeq; XP_006233195.1; XM_006233133.3.
DR RefSeq; XP_006233196.1; XM_006233134.3.
DR RefSeq; XP_006233197.1; XM_006233135.3.
DR RefSeq; XP_008759593.1; XM_008761371.2.
DR PDB; 1DSX; X-ray; 1.60 A; A/B/C/D/E/F/G/H=33-119.
DR PDB; 1QDV; X-ray; 1.60 A; A/B/C/D=33-131.
DR PDB; 1QDW; X-ray; 2.10 A; A/B/C/D/E/F/G/H=33-119.
DR PDB; 2A79; X-ray; 2.90 A; B=1-499.
DR PDB; 2R9R; X-ray; 2.40 A; B/H=1-499.
DR PDB; 3LNM; X-ray; 2.90 A; B/D=1-266, B/D=303-499.
DR PDB; 3LUT; X-ray; 2.90 A; B=1-499.
DR PDB; 4JTA; X-ray; 2.50 A; B/Q=1-266, B/Q=304-499.
DR PDB; 4JTC; X-ray; 2.56 A; B/H=1-266, B/H=304-499.
DR PDB; 4JTD; X-ray; 2.54 A; B/H=1-266, B/H=304-499.
DR PDB; 5WIE; X-ray; 3.30 A; B/H=1-42.
DR PDB; 6EBK; EM; 3.30 A; B/D/F/H=1-266, B/D/F/H=305-499.
DR PDB; 6EBL; EM; 3.00 A; B/D/F/H=1-266, B/D/F/H=305-499.
DR PDB; 6EBM; EM; 4.00 A; B/D/F/H=1-266, B/D/F/H=305-499.
DR PDBsum; 1DSX; -.
DR PDBsum; 1QDV; -.
DR PDBsum; 1QDW; -.
DR PDBsum; 2A79; -.
DR PDBsum; 2R9R; -.
DR PDBsum; 3LNM; -.
DR PDBsum; 3LUT; -.
DR PDBsum; 4JTA; -.
DR PDBsum; 4JTC; -.
DR PDBsum; 4JTD; -.
DR PDBsum; 5WIE; -.
DR PDBsum; 6EBK; -.
DR PDBsum; 6EBL; -.
DR PDBsum; 6EBM; -.
DR AlphaFoldDB; P63142; -.
DR SMR; P63142; -.
DR BioGRID; 247501; 5.
DR CORUM; P63142; -.
DR IntAct; P63142; 4.
DR STRING; 10116.ENSRNOP00000042653; -.
DR BindingDB; P63142; -.
DR ChEMBL; CHEMBL4105982; -.
DR DrugCentral; P63142; -.
DR GuidetoPHARMACOLOGY; 539; -.
DR GlyGen; P63142; 1 site.
DR iPTMnet; P63142; -.
DR PhosphoSitePlus; P63142; -.
DR PaxDb; P63142; -.
DR PRIDE; P63142; -.
DR ABCD; P63142; 3 sequenced antibodies.
DR Ensembl; ENSRNOT00000092450; ENSRNOP00000075852; ENSRNOG00000018285.
DR Ensembl; ENSRNOT00000100022; ENSRNOP00000089201; ENSRNOG00000018285.
DR Ensembl; ENSRNOT00000108979; ENSRNOP00000079590; ENSRNOG00000018285.
DR Ensembl; ENSRNOT00000116262; ENSRNOP00000090952; ENSRNOG00000018285.
DR GeneID; 25468; -.
DR KEGG; rno:25468; -.
DR CTD; 3737; -.
DR RGD; 2950; Kcna2.
DR eggNOG; KOG1545; Eukaryota.
DR GeneTree; ENSGT00940000158688; -.
DR HOGENOM; CLU_011722_4_0_1; -.
DR InParanoid; P63142; -.
DR OMA; HPLDYDP; -.
DR OrthoDB; 695337at2759; -.
DR PhylomeDB; P63142; -.
DR TreeFam; TF313103; -.
DR Reactome; R-RNO-1296072; Voltage gated Potassium channels.
DR EvolutionaryTrace; P63142; -.
DR PRO; PR:P63142; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000018285; Expressed in cerebellum and 12 other tissues.
DR ExpressionAtlas; P63142; baseline and differential.
DR Genevisible; P63142; RN.
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:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
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:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0033010; C:paranodal junction; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0034705; C:potassium channel complex; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IMP:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; IPI:RGD.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IMP:RGD.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; IMP:UniProtKB.
DR GO; GO:0021633; P:optic nerve structural organization; ISO:RGD.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; IMP:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0045188; P:regulation of circadian sleep/wake cycle, non-REM sleep; ISO:RGD.
DR GO; GO:0014059; P:regulation of dopamine secretion; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; 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; IPR004049; K_chnl_volt-dep_Kv1.2.
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 PANTHER; PTHR11537:SF23; PTHR11537:SF23; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01509; KV12CHANNEL.
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 Endoplasmic reticulum; Endosome; Glycoprotein; Ion channel; Ion transport;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Synapse;
KW Synaptosome; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..499
FT /note="Potassium voltage-gated channel subfamily A member
FT 2"
FT /id="PRO_0000053975"
FT TOPO_DOM 1..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TRANSMEM 161..182
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TOPO_DOM 183..221
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430,
FT ECO:0000305|PubMed:12151401"
FT TRANSMEM 222..243
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TOPO_DOM 244..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TRANSMEM 255..275
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20534430"
FT TOPO_DOM 276..289
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TRANSMEM 290..310
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20534430"
FT TOPO_DOM 311..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TRANSMEM 326..347
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TOPO_DOM 348..361
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT INTRAMEM 362..373
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT INTRAMEM 374..381
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TOPO_DOM 382..388
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TRANSMEM 389..417
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000269|PubMed:18004376,
FT ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430"
FT TOPO_DOM 418..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:12151401, ECO:0000305"
FT REGION 1..125
FT /note="Tetramerization domain"
FT /evidence="ECO:0000305|PubMed:11007484"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..325
FT /note="S4-S5 linker"
FT /evidence="ECO:0000305|PubMed:16002579"
FT MOTIF 374..379
FT /note="Selectivity filter"
FT /evidence="ECO:0000305"
FT MOTIF 497..499
FT /note="PDZ-binding"
FT /evidence="ECO:0000269|PubMed:7477295"
FT SITE 252
FT /note="Important for normal, slow channel gating"
FT /evidence="ECO:0000269|PubMed:17766348"
FT SITE 381
FT /note="Important for binding with the scorpion
FT mesomartoxin; when the scorpion mesomartoxin-rKv1.2/KCNA2
FT interaction is modeled, this residue is close to the 'Y-57'
FT residue of the toxin"
FT /evidence="ECO:0000305|PubMed:25514171"
FT MOD_RES 429
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P63141"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63141"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18003609,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18003609,
FT ECO:0000269|PubMed:21602278"
FT MOD_RES 458
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:21602278"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 244
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:16770729"
FT MUTAGEN 34
FT /note="R->L: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 38
FT /note="N->A: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 40
FT /note="S->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 41
FT /note="G->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 42
FT /note="L->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 43
FT /note="R->L: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 44
FT /note="F->A: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 45
FT /note="E->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 46
FT /note="T->D: Impairs protein folding. Loss of
FT tetramerization."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 46
FT /note="T->V,A: No effect on tetramerization. Alters
FT voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 46
FT /note="T->V: Abolishes interaction with KCNAB2 and strongly
FT reduces cell surface expression. No effect phosphorylation
FT in response to increased cAMP levels."
FT /evidence="ECO:0000269|PubMed:18003609"
FT MUTAGEN 47
FT /note="Q->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 50
FT /note="T->A: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 70
FT /note="D->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 73
FT /note="R->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 75
FT /note="E->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 77
FT /note="F->W: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 79
FT /note="D->N: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 81
FT /note="N->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 82
FT /note="R->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 86
FT /note="D->A: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 89
FT /note="L->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 90
FT /note="Y->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 93
FT /note="Q->A: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 97
FT /note="R->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 99
FT /note="R->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 102
FT /note="V->T: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 103
FT /note="N->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 105
FT /note="P->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 107
FT /note="D->A: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 108
FT /note="I->A: No effect on channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 111
FT /note="E->A: Alters voltage-sensitive channel opening."
FT /evidence="ECO:0000269|PubMed:11007484"
FT MUTAGEN 207
FT /note="N->Q: Loss of glycosylation site."
FT /evidence="ECO:0000269|PubMed:16770729"
FT MUTAGEN 252
FT /note="T->R: Changes channel gating from a predominantly
FT slow mode to a much more rapid mode."
FT /evidence="ECO:0000269|PubMed:17766348"
FT MUTAGEN 267..302
FT /note="FITLGTELAEKPEDAQQGQQAMSLAILRVIRLVRVF->YVTIFLTESNKSVL
FT QFQNVRRVVQIFRIM: In paddle chimera; changes channel
FT activation to less negative voltage values and renders the
FT channel susceptible to inhibition by the spider toxin
FT VsTx1."
FT /evidence="ECO:0000269|PubMed:18638484"
FT MUTAGEN 356
FT /note="S->A: Impairs N-glycosylation and abolishes
FT expression at the cell surface."
FT /evidence="ECO:0000269|PubMed:16770729"
FT MUTAGEN 360
FT /note="S->A: No effect on N-glycosylation. Abolishes
FT channel activity of the homotetramer, but retains channel
FT activity in the presence of a beta subunit."
FT /evidence="ECO:0000269|PubMed:16770729"
FT MUTAGEN 381
FT /note="V->Y: Confers sensitivity to inhibition by
FT tetraethylammonium (TEA)."
FT /evidence="ECO:0000269|PubMed:23725331"
FT MUTAGEN 383
FT /note="T->A: Impairs N-glycosylation and abolishes
FT expression at the cell surface."
FT /evidence="ECO:0000269|PubMed:16770729"
FT MUTAGEN 415
FT /note="Y->F: Nearly abolishes interaction with CTTN; when
FT associated with F-417."
FT /evidence="ECO:0000269|PubMed:12151401"
FT MUTAGEN 417
FT /note="Y->F: Nearly abolishes interaction with CTTN; when
FT associated with F-415. Strongly reduces channel activity."
FT /evidence="ECO:0000269|PubMed:12151401"
FT MUTAGEN 440
FT /note="S->A: Strongly reduces cell surface expression.
FT Abolishes phosphorylation in response to increased cAMP
FT levels."
FT /evidence="ECO:0000269|PubMed:18003609"
FT MUTAGEN 449
FT /note="S->A: Strongly reduces cell surface expression.
FT Abolishes phosphorylation in response to increased cAMP
FT levels."
FT /evidence="ECO:0000269|PubMed:18003609"
FT MUTAGEN 458
FT /note="Y->A: Impairs clustering on axon membranes."
FT /evidence="ECO:0000269|PubMed:21602278"
FT CONFLICT 411
FT /note="S -> F (in Ref. 4; AAA19867)"
FT /evidence="ECO:0000305"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:1DSX"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:1DSX"
FT HELIX 48..52
FT /evidence="ECO:0007829|PDB:1DSX"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1DSX"
FT HELIX 62..66
FT /evidence="ECO:0007829|PDB:1DSX"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:1DSX"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:1DSX"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:1QDW"
FT HELIX 85..93
FT /evidence="ECO:0007829|PDB:1DSX"
FT HELIX 106..116
FT /evidence="ECO:0007829|PDB:1DSX"
FT HELIX 120..130
FT /evidence="ECO:0007829|PDB:1QDV"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:4JTA"
FT TURN 150..154
FT /evidence="ECO:0007829|PDB:4JTA"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:4JTC"
FT HELIX 160..182
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:4JTA"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:4JTA"
FT TURN 193..196
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 202..210
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 221..241
FT /evidence="ECO:0007829|PDB:4JTA"
FT TURN 249..252
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 254..261
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:3LUT"
FT HELIX 283..287
FT /evidence="ECO:0007829|PDB:5WIE"
FT HELIX 291..299
FT /evidence="ECO:0007829|PDB:2A79"
FT HELIX 305..309
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 312..323
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 325..351
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:4JTA"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 385..403
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 406..418
FT /evidence="ECO:0007829|PDB:4JTA"
SQ SEQUENCE 499 AA; 56701 MW; A8FEA6F3F59AF42A CRC64;
MTVATGDPVD EAAALPGHPQ DTYDPEADHE CCERVVINIS GLRFETQLKT LAQFPETLLG
DPKKRMRYFD PLRNEYFFDR NRPSFDAILY YYQSGGRLRR PVNVPLDIFS EEIRFYELGE
EAMEMFREDE GYIKEEERPL PENEFQRQVW LLFEYPESSG PARIIAIVSV MVILISIVSF
CLETLPIFRD ENEDMHGGGV TFHTYSNSTI GYQQSTSFTD PFFIVETLCI IWFSFEFLVR
FFACPSKAGF FTNIMNIIDI VAIIPYFITL GTELAEKPED AQQGQQAMSL AILRVIRLVR
VFRIFKLSRH SKGLQILGQT LKASMRELGL LIFFLFIGVI LFSSAVYFAE ADERDSQFPS
IPDAFWWAVV SMTTVGYGDM VPTTIGGKIV GSLCAIAGVL TIALPVPVIV SNFNYFYHRE
TEGEEQAQYL QVTSCPKIPS SPDLKKSRSA STISKSDYME IQEGVNNSNE DFREENLKTA
NCTLANTNYV NITKMLTDV
