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 27-MAR-2024, entry version 169. 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 CC half-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). Interacts with ADAM11 (By CC similarity). Intercts with LYNX1 (By similarity). CC {ECO:0000250|UniProtKB:P16389, 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 neurons of the medial nucleus of the CC trapezoid body (PubMed:12177193). Detected in neurons in the brain CC cortex (PubMed:14713306). Detected in axon tracts of the corpus CC callosum, specific terminal fields of the brain cortex neuropil, CC neurons in the medial entorhinal cortex, and in puncta representing CC mossy fiber terminals in the hippocampus mossy fiber tract; these CC puncta correspond to synapses made by dentate granule cells CC (PubMed:8361540). Detected in paranodal and juxtanodal zones in the CC central nervous system, including myelinated spinal cord CC (PubMed:11086297, PubMed:20089912). Detected in the juxtaparanodal CC region in optic nerve (PubMed:10624965). Detected at nerve terminal CC plexuses of basket cells in the cerebellum (at protein level) CC (PubMed:7477295, PubMed:20089912). Detected in brain (PubMed:2722779). CC Detected in heart atrium and ventricle (PubMed:1715584). Detected in CC renal arteries (PubMed:12632190). {ECO:0000269|PubMed:10624965, CC ECO:0000269|PubMed:11086297, ECO:0000269|PubMed:12177193, CC ECO:0000269|PubMed:12632190, ECO:0000269|PubMed:14713306, CC ECO:0000269|PubMed:1715584, ECO:0000269|PubMed:20089912, CC ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:24472174, CC ECO:0000269|PubMed:2722779, ECO:0000269|PubMed:7477295, CC 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 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: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) CC (TC 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 PDB; 7SIT; X-ray; 3.32 A; B/D=1-499. DR PDB; 7SIZ; X-ray; 3.10 A; B/D=1-499. 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 PDBsum; 7SIT; -. DR PDBsum; 7SIZ; -. DR AlphaFoldDB; P63142; -. DR EMDB; EMD-9024; -. DR EMDB; EMD-9025; -. DR EMDB; EMD-9026; -. DR SMR; P63142; -. DR BioGRID; 247501; 5. DR CORUM; P63142; -. DR IntAct; P63142; 4. DR STRING; 10116.ENSRNOP00000075852; -. DR BindingDB; P63142; -. DR ChEMBL; CHEMBL4105982; -. DR DrugCentral; P63142; -. DR GuidetoPHARMACOLOGY; 539; -. DR GlyCosmos; P63142; 1 site, No reported glycans. DR GlyGen; P63142; 1 site. DR iPTMnet; P63142; -. DR PhosphoSitePlus; P63142; -. DR PaxDb; 10116-ENSRNOP00000042653; -. DR ABCD; P63142; 3 sequenced antibodies. DR Ensembl; ENSRNOT00000092450.2; ENSRNOP00000075852.1; ENSRNOG00000018285.7. DR Ensembl; ENSRNOT00000100022.1; ENSRNOP00000089201.1; ENSRNOG00000018285.7. DR Ensembl; ENSRNOT00000108979.1; ENSRNOP00000079590.1; ENSRNOG00000018285.7. DR Ensembl; ENSRNOT00000116262.1; ENSRNOP00000090952.1; ENSRNOG00000018285.7. DR Ensembl; ENSRNOT00055034634; ENSRNOP00055028059; ENSRNOG00055020280. DR Ensembl; ENSRNOT00055034637; ENSRNOP00055028062; ENSRNOG00055020280. DR Ensembl; ENSRNOT00055034641; ENSRNOP00055028065; ENSRNOG00055020280. DR Ensembl; ENSRNOT00055034645; ENSRNOP00055028070; ENSRNOG00055020280. DR Ensembl; ENSRNOT00060051941; ENSRNOP00060043198; ENSRNOG00060029911. DR Ensembl; ENSRNOT00060051956; ENSRNOP00060043210; ENSRNOG00060029911. DR Ensembl; ENSRNOT00060051963; ENSRNOP00060043217; ENSRNOG00060029911. DR Ensembl; ENSRNOT00060051970; ENSRNOP00060043223; ENSRNOG00060029911. DR Ensembl; ENSRNOT00065039166; ENSRNOP00065031816; ENSRNOG00065022931. DR Ensembl; ENSRNOT00065039168; ENSRNOP00065031817; ENSRNOG00065022931. DR Ensembl; ENSRNOT00065039175; ENSRNOP00065031822; ENSRNOG00065022931. DR Ensembl; ENSRNOT00065039180; ENSRNOP00065031826; ENSRNOG00065022931. DR GeneID; 25468; -. DR KEGG; rno:25468; -. DR AGR; RGD:2950; -. 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; VNHSTED; -. DR OrthoDB; 1478695at2759; -. 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 cell types or tissues. DR ExpressionAtlas; P63142; baseline and differential. 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:0098978; C:glutamatergic synapse; 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:0005886; C:plasma membrane; IMP: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:SynGO. 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: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:0021987; P:cerebral cortex development; IEP:RGD. DR GO; GO:0022038; P:corpus callosum development; IEP:RGD. DR GO; GO:0019228; P:neuronal action potential; IMP:UniProtKB. DR GO; GO:0021554; P:optic nerve development; IEP:RGD. 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:0019233; P:sensory perception of pain; 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; IPR004049; K_chnl_volt-dep_Kv1.2. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR003131; T1-type_BTB. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR11537:SF23; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY A MEMBER 2; 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; PR01509; KV12CHANNEL. 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; P63142; RN. 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 STRAND 242..245 FT /evidence="ECO:0007829|PDB:7SIT" FT TURN 249..252 FT /evidence="ECO:0007829|PDB:4JTA" FT HELIX 254..261 FT /evidence="ECO:0007829|PDB:4JTA" FT HELIX 264..268 FT /evidence="ECO:0007829|PDB:7SIZ" FT HELIX 279..282 FT /evidence="ECO:0007829|PDB:3LUT" 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 //