KCND2_RAT
ID KCND2_RAT Reviewed; 630 AA.
AC Q63881; Q00090; Q99249;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Potassium voltage-gated channel subfamily D member 2;
DE AltName: Full=RK5 {ECO:0000303|PubMed:1705709, ECO:0000303|PubMed:1722463};
DE AltName: Full=Shal1 {ECO:0000303|PubMed:1840649};
DE AltName: Full=Voltage-gated potassium channel subunit Kv4.2 {ECO:0000303|PubMed:9093524};
GN Name=Kcnd2;
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], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Hippocampus;
RX PubMed=1840649; DOI=10.1016/0896-6273(91)90299-f;
RA Baldwin T.J., Tsaur M.-L., Lopez G.A., Jan Y.N., Jan L.Y.;
RT "Characterization of a mammalian cDNA for an inactivating voltage-sensitive
RT K+ channel.";
RL Neuron 7:471-483(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RX PubMed=1705709; DOI=10.1073/pnas.88.5.1798;
RA Roberds S.L., Tamkun M.M.;
RT "Cloning and tissue-specific expression of five voltage-gated potassium
RT channel cDNAs expressed in rat heart.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1798-1802(1991).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=1722463; DOI=10.1016/0014-5793(91)81420-d;
RA Blair T.A., Roberds S.L., Tamkun M.M., Hartshorne R.P.;
RT "Functional characterization of RK5, a voltage-gated K+ channel cloned from
RT the rat cardiovascular system.";
RL FEBS Lett. 295:211-213(1991).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=9093524; DOI=10.1016/s0008-6363(96)00221-0;
RA Yeola S.W., Snyders D.J.;
RT "Electrophysiological and pharmacological correspondence between Kv4.2
RT current and rat cardiac transient outward current.";
RL Cardiovasc. Res. 33:540-547(1997).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=9058605;
RA Sanguinetti M.C., Johnson J.H., Hammerland L.G., Kelbaugh P.R.,
RA Volkmann R.A., Saccomano N.A., Mueller A.L.;
RT "Heteropodatoxins: peptides isolated from spider venom that block Kv4.2
RT potassium channels.";
RL Mol. Pharmacol. 51:491-498(1997).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9070739; DOI=10.1016/s0306-4522(96)00561-1;
RA Alonso G., Widmer H.;
RT "Clustering of KV4.2 potassium channels in postsynaptic membrane of rat
RT supraoptic neurons: an ultrastructural study.";
RL Neuroscience 77:617-621(1997).
RN [7]
RP PHOSPHORYLATION AT THR-38 AND SER-552 BY PKACA.
RX PubMed=10681507; DOI=10.1074/jbc.275.8.5337;
RA Anderson A.E., Adams J.P., Qian Y., Cook R.G., Pfaffinger P.J.,
RA Sweatt J.D.;
RT "Kv4.2 phosphorylation by cyclic AMP-dependent protein kinase.";
RL J. Biol. Chem. 275:5337-5346(2000).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10860776; DOI=10.1006/jmcc.2000.1172;
RA Takeuchi S., Takagishi Y., Yasui K., Murata Y., Toyama J., Kodama I.;
RT "Voltage-gated K(+)Channel, Kv4.2, localizes predominantly to the
RT transverse-axial tubular system of the rat myocyte.";
RL J. Mol. Cell. Cardiol. 32:1361-1369(2000).
RN [9]
RP PHOSPHORYLATION AT THR-602; THR-607 AND SER-616.
RX PubMed=11080179; DOI=10.1046/j.1471-4159.2000.0752277.x;
RA Adams J.P., Anderson A.E., Varga A.W., Dineley K.T., Cook R.G.,
RA Pfaffinger P.J., Sweatt J.D.;
RT "The A-type potassium channel Kv4.2 is a substrate for the mitogen-
RT activated protein kinase ERK.";
RL J. Neurochem. 75:2277-2287(2000).
RN [10]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH FILAMIN.
RX PubMed=11102480; DOI=10.1523/jneurosci.20-23-08736.2000;
RA Petrecca K., Miller D.M., Shrier A.;
RT "Localization and enhanced current density of the Kv4.2 potassium channel
RT by interaction with the actin-binding protein filamin.";
RL J. Neurosci. 20:8736-8744(2000).
RN [11]
RP INTERACTION WITH KCNIP1; KCNIP2 AND KCNIP3, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=10676964; DOI=10.1038/35000592;
RA An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G.,
RA Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J.;
RT "Modulation of A-type potassium channels by a family of calcium sensors.";
RL Nature 403:553-556(2000).
RN [12]
RP INTERACTION WITH KCNIP3, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP SER-552, PHOSPHORYLATION AT SER-552, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12451113; DOI=10.1523/jneurosci.22-23-10123.2002;
RA Schrader L.A., Anderson A.E., Mayne A., Pfaffinger P.J., Sweatt J.D.;
RT "PKA modulation of Kv4.2-encoded A-type potassium channels requires
RT formation of a supramolecular complex.";
RL J. Neurosci. 22:10123-10133(2002).
RN [13]
RP INTERACTION WITH KCNIP4, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11847232; DOI=10.1074/jbc.m200897200;
RA Morohashi Y., Hatano N., Ohya S., Takikawa R., Watabiki T., Takasugi N.,
RA Imaizumi Y., Tomita T., Iwatsubo T.;
RT "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand
RT protein interacting with presenilin 2 and voltage-gated potassium channel
RT subunit Kv4.";
RL J. Biol. Chem. 277:14965-14975(2002).
RN [14]
RP MUTAGENESIS OF 627-VAL--LEU-630, INTERACTION WITH DLG4, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11923279; DOI=10.1074/jbc.m109412200;
RA Wong W., Newell E.W., Jugloff D.G.M., Jones O.T., Schlichter L.C.;
RT "Cell surface targeting and clustering interactions between heterologously
RT expressed PSD-95 and the Shal voltage-gated potassium channel, Kv4.2.";
RL J. Biol. Chem. 277:20423-20430(2002).
RN [15]
RP INTERACTION WITH KCNIP4.
RX PubMed=11805342; DOI=10.1073/pnas.022509299;
RA Holmqvist M.H., Cao J., Hernandez-Pineda R., Jacobson M.D., Carroll K.I.,
RA Sung M.A., Betty M., Ge P., Gilbride K.J., Brown M.E., Jurman M.E.,
RA Lawson D., Silos-Santiago I., Xie Y., Covarrubias M., Rhodes K.J.,
RA Distefano P.S., An W.F.;
RT "Elimination of fast inactivation in Kv4 A-type potassium channels by an
RT auxiliary subunit domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1035-1040(2002).
RN [16]
RP PHOSPHORYLATION AT SER-552, AND SUBCELLULAR LOCATION.
RX PubMed=12829703; DOI=10.1074/jbc.m306142200;
RA Shibata R., Misonou H., Campomanes C.R., Anderson A.E., Schrader L.A.,
RA Doliveira L.C., Carroll K.I., Sweatt J.D., Rhodes K.J., Trimmer J.S.;
RT "A fundamental role for KChIPs in determining the molecular properties and
RT trafficking of Kv4.2 potassium channels.";
RL J. Biol. Chem. 278:36445-36454(2003).
RN [17]
RP SUBCELLULAR LOCATION, DENDRITIC TARGETING REGION, MUTAGENESIS OF
RP 481-LEU--LEU-482, AND FUNCTION.
RX PubMed=12592409; DOI=10.1038/nn1020;
RA Rivera J.F., Ahmad S., Quick M.W., Liman E.R., Arnold D.B.;
RT "An evolutionarily conserved dileucine motif in Shal K+ channels mediates
RT dendritic targeting.";
RL Nat. Neurosci. 6:243-250(2003).
RN [18]
RP INTERACTION WITH DPP6.
RX PubMed=12575952; DOI=10.1016/s0896-6273(02)01185-6;
RA Nadal M.S., Ozaita A., Amarillo Y., Vega-Saenz de Miera E., Ma Y., Mo W.,
RA Goldberg E.M., Misumi Y., Ikehara Y., Neubert T.A., Rudy B.;
RT "The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical
RT component of neuronal A-type K+ channels.";
RL Neuron 37:449-461(2003).
RN [19]
RP SUBUNIT, ZINC-BINDING, SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF
RP HIS-105; CYS-111; CYS-132 AND CYS-133.
RX PubMed=12754210; DOI=10.1074/jbc.m304268200;
RA Strang C., Kunjilwar K., DeRubeis D., Peterson D., Pfaffinger P.J.;
RT "The role of Zn2+ in Shal voltage-gated potassium channel formation.";
RL J. Biol. Chem. 278:31361-31371(2003).
RN [20]
RP MUTAGENESIS OF 627-VAL--LEU-630, INTERACTION WITH DLG4, AND SUBCELLULAR
RP LOCATION.
RX PubMed=14559911; DOI=10.1074/jbc.m304675200;
RA Wong W., Schlichter L.C.;
RT "Differential recruitment of Kv1.4 and Kv4.2 to lipid rafts by PSD-95.";
RL J. Biol. Chem. 279:444-452(2004).
RN [21]
RP FUNCTION, INTERACTION WITH KCNIP3, AND SUBCELLULAR LOCATION.
RX PubMed=15485870; DOI=10.1074/jbc.m409721200;
RA Kunjilwar K., Strang C., DeRubeis D., Pfaffinger P.J.;
RT "KChIP3 rescues the functional expression of Shal channel tetramerization
RT mutants.";
RL J. Biol. Chem. 279:54542-54551(2004).
RN [22]
RP INTERACTION WITH KCNIP1 AND KCNIP3.
RX PubMed=15356203; DOI=10.1523/jneurosci.0776-04.2004;
RA Rhodes K.J., Carroll K.I., Sung M.A., Doliveira L.C., Monaghan M.M.,
RA Burke S.L., Strassle B.W., Buchwalder L., Menegola M., Cao J., An W.F.,
RA Trimmer J.S.;
RT "KChIPs and Kv4 alpha subunits as integral components of A-type potassium
RT channels in mammalian brain.";
RL J. Neurosci. 24:7903-7915(2004).
RN [23]
RP INTERACTION WITH KCNIP1, AND MUTAGENESIS OF 7-ALA--PHE-11; GLU-71; ASP-73;
RP PHE-74 AND GLU-79.
RX PubMed=14980207; DOI=10.1016/s0896-6273(04)00049-2;
RA Scannevin R.H., Wang K., Jow F., Megules J., Kopsco D.C., Edris W.,
RA Carroll K.C., Lu Q., Xu W., Xu Z., Katz A.H., Olland S., Lin L., Taylor M.,
RA Stahl M., Malakian K., Somers W., Mosyak L., Bowlby M.R., Chanda P.,
RA Rhodes K.J.;
RT "Two N-terminal domains of Kv4 K(+) channels regulate binding to and
RT modulation by KChIP1.";
RL Neuron 41:587-598(2004).
RN [24]
RP DOMAIN, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KCNIP2.
RX PubMed=15452711; DOI=10.1007/s00424-004-1328-8;
RA Pourrier M., Herrera D., Caballero R., Schram G., Wang Z., Nattel S.;
RT "The Kv4.2 N-terminal restores fast inactivation and confers KChlP2
RT modulatory effects on N-terminal-deleted Kv1.4 channels.";
RL Pflugers Arch. 449:235-247(2004).
RN [25]
RP REVIEW.
RX PubMed=15858231; DOI=10.1385/cbb:42:2:167;
RA Cox R.H.;
RT "Molecular determinants of voltage-gated potassium currents in vascular
RT smooth muscle.";
RL Cell Biochem. Biophys. 42:167-195(2005).
RN [26]
RP INTERACTION WITH DPP6 AND DPP10, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15671030; DOI=10.1074/jbc.m410613200;
RA Zagha E., Ozaita A., Chang S.Y., Nadal M.S., Lin U., Saganich M.J.,
RA McCormack T., Akinsanya K.O., Qi S.Y., Rudy B.;
RT "DPP10 modulates Kv4-mediated A-type potassium channels.";
RL J. Biol. Chem. 280:18853-18861(2005).
RN [27]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15736227; DOI=10.1002/cne.20443;
RA Strassle B.W., Menegola M., Rhodes K.J., Trimmer J.S.;
RT "Light and electron microscopic analysis of KChIP and Kv4 localization in
RT rat cerebellar granule cells.";
RL J. Comp. Neurol. 484:144-155(2005).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16207878; DOI=10.1523/jneurosci.2858-05.2005;
RA Yuan W., Burkhalter A., Nerbonne J.M.;
RT "Functional role of the fast transient outward K+ current IA in pyramidal
RT neurons in (rat) primary visual cortex.";
RL J. Neurosci. 25:9185-9194(2005).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=16123112; DOI=10.1113/jphysiol.2005.087858;
RA Jerng H.H., Kunjilwar K., Pfaffinger P.J.;
RT "Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel
RT complexes with ISA-like properties.";
RL J. Physiol. (Lond.) 568:767-788(2005).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH KCNIP2, AND DOMAIN.
RX PubMed=16820361; DOI=10.1074/jbc.m604843200;
RA Han W., Nattel S., Noguchi T., Shrier A.;
RT "C-terminal domain of Kv4.2 and associated KChIP2 interactions regulate
RT functional expression and gating of Kv4.2.";
RL J. Biol. Chem. 281:27134-27144(2006).
RN [31]
RP FUNCTION.
RX PubMed=17026528; DOI=10.1111/j.1471-4159.2006.04185.x;
RA Lauver A., Yuan L.L., Jeromin A., Nadin B.M., Rodriguez J.J., Davies H.A.,
RA Stewart M.G., Wu G.Y., Pfaffinger P.J.;
RT "Manipulating Kv4.2 identifies a specific component of hippocampal
RT pyramidal neuron A-current that depends upon Kv4.2 expression.";
RL J. Neurochem. 99:1207-1223(2006).
RN [32]
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 [33]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17582333; DOI=10.1016/j.neuron.2007.05.026;
RA Kim J., Jung S.C., Clemens A.M., Petralia R.S., Hoffman D.A.;
RT "Regulation of dendritic excitability by activity-dependent trafficking of
RT the A-type K+ channel subunit Kv4.2 in hippocampal neurons.";
RL Neuron 54:933-947(2007).
RN [34]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18371079; DOI=10.1111/j.1460-9568.2008.06141.x;
RA Kollo M., Holderith N., Antal M., Nusser Z.;
RT "Unique clustering of A-type potassium channels on different cell types of
RT the main olfactory bulb.";
RL Eur. J. Neurosci. 27:1686-1699(2008).
RN [35]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-552, AND MUTAGENESIS OF
RP SER-552.
RX PubMed=18650329; DOI=10.1523/jneurosci.1951-08.2008;
RA Hammond R.S., Lin L., Sidorov M.S., Wikenheiser A.M., Hoffman D.A.;
RT "Protein kinase A mediates activity-dependent Kv4.2 channel trafficking.";
RL J. Neurosci. 28:7513-7519(2008).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MISCELLANEOUS.
RX PubMed=18276729; DOI=10.1113/jphysiol.2007.150540;
RA Amarillo Y., De Santiago-Castillo J.A., Dougherty K., Maffie J., Kwon E.,
RA Covarrubias M., Rudy B.;
RT "Ternary Kv4.2 channels recapitulate voltage-dependent inactivation
RT kinetics of A-type K+ channels in cerebellar granule neurons.";
RL J. Physiol. (Lond.) 586:2093-2106(2008).
RN [37]
RP REVIEW.
RX PubMed=18357523; DOI=10.1007/s11064-008-9650-8;
RA Covarrubias M., Bhattacharji A., De Santiago-Castillo J.A., Dougherty K.,
RA Kaulin Y.A., Na-Phuket T.R., Wang G.;
RT "The neuronal Kv4 channel complex.";
RL Neurochem. Res. 33:1558-1567(2008).
RN [38]
RP SUBCELLULAR LOCATION, INTERACTION WITH DPP6 AND KCNIP2, PHOSPHORYLATION AT
RP SER-548; SER-552; SER-572 AND SER-575, IDENTIFICATION BY MASS SPECTROMETRY,
RP AND MUTAGENESIS OF SER-552.
RX PubMed=19441798; DOI=10.1021/bi802316m;
RA Seikel E., Trimmer J.S.;
RT "Convergent modulation of Kv4.2 channel alpha subunits by structurally
RT distinct DPPX and KChIP auxiliary subunits.";
RL Biochemistry 48:5721-5730(2009).
RN [39]
RP FUNCTION, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19901547; DOI=10.4161/chan.3.6.10216;
RA Jerng H.H., Dougherty K., Covarrubias M., Pfaffinger P.J.;
RT "A novel N-terminal motif of dipeptidyl peptidase-like proteins produces
RT rapid inactivation of KV4.2 channels by a pore-blocking mechanism.";
RL Channels 3:448-461(2009).
RN [40]
RP INTERACTION WITH DLG1.
RX PubMed=19213956; DOI=10.1161/circresaha.108.191007;
RA El-Haou S., Balse E., Neyroud N., Dilanian G., Gavillet B., Abriel H.,
RA Coulombe A., Jeromin A., Hatem S.N.;
RT "Kv4 potassium channels form a tripartite complex with the anchoring
RT protein SAP97 and CaMKII in cardiac myocytes.";
RL Circ. Res. 104:758-769(2009).
RN [41]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19279261; DOI=10.1523/jneurosci.4767-08.2009;
RA Kaulin Y.A., De Santiago-Castillo J.A., Rocha C.A., Nadal M.S., Rudy B.,
RA Covarrubias M.;
RT "The dipeptidyl-peptidase-like protein DPP6 determines the unitary
RT conductance of neuronal Kv4.2 channels.";
RL J. Neurosci. 29:3242-3251(2009).
RN [42]
RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH PKA; CAV3; AKAP6 AND KCND3,
RP AND TISSUE SPECIFICITY.
RX PubMed=20224290; DOI=10.4161/chan.4.3.11479;
RA Alday A., Urrutia J., Gallego M., Casis O.;
RT "Alpha1-adrenoceptors regulate only the caveolae-located subpopulation of
RT cardiac K(V)4 channels.";
RL Channels 4:168-178(2010).
RN [43]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=20045463; DOI=10.1016/j.mcn.2009.12.005;
RA Lin L., Sun W., Wikenheiser A.M., Kung F., Hoffman D.A.;
RT "KChIP4a regulates Kv4.2 channel trafficking through PKA phosphorylation.";
RL Mol. Cell. Neurosci. 43:315-325(2010).
RN [44]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22098631; DOI=10.1111/j.1460-9568.2011.07907.x;
RA Kerti K., Lorincz A., Nusser Z.;
RT "Unique somato-dendritic distribution pattern of Kv4.2 channels on
RT hippocampal CA1 pyramidal cells.";
RL Eur. J. Neurosci. 35:66-75(2012).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548; SER-552; SER-572 AND
RP SER-575, AND 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 [46]
RP INDUCTION BY HYPOXIA, FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=25352783; DOI=10.3389/fncel.2014.00329;
RA Liu Y.Q., Huang W.X., Sanchez R.M., Min J.W., Hu J.J., He X.H., Peng B.W.;
RT "Regulation of Kv4.2 A-type potassium channels in HEK-293 cells by
RT hypoxia.";
RL Front. Cell. Neurosci. 8:329-329(2014).
RN [47]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24037673; DOI=10.1002/cne.23435;
RA Rainnie D.G., Hazra R., Dabrowska J., Guo J.D., Li C.C., Dewitt S.,
RA Muly E.C.;
RT "Distribution and functional expression of Kv4 family alpha subunits and
RT associated KChIP beta subunits in the bed nucleus of the stria
RT terminalis.";
RL J. Comp. Neurol. 522:609-625(2014).
RN [48]
RP INTERACTION WITH KCNIP4.
RX PubMed=24811166; DOI=10.1074/jbc.m114.563452;
RA Kitazawa M., Kubo Y., Nakajo K.;
RT "The stoichiometry and biophysical properties of the Kv4 potassium channel
RT complex with K+ channel-interacting protein (KChIP) subunits are variable,
RT depending on the relative expression level.";
RL J. Biol. Chem. 289:17597-17609(2014).
RN [49]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24793047; DOI=10.1007/s00424-014-1521-3;
RA Rudakova E., Wagner M., Frank M., Volk T.;
RT "Localization of Kv4.2 and KChIP2 in lipid rafts and modulation of outward
RT K(+) currents by membrane cholesterol content in rat left ventricular
RT myocytes.";
RL Pflugers Arch. 467:299-309(2015).
RN [50]
RP FUNCTION, PHOSPHORYLATION AT SER-438, AND SUBCELLULAR LOCATION.
RX PubMed=24404150; DOI=10.1371/journal.pone.0084086;
RA Labno A., Warrier A., Wang S., Zhang X.;
RT "Local plasticity of dendritic excitability can be autonomous of synaptic
RT plasticity and regulated by activity-based phosphorylation of Kv4.2.";
RL PLoS ONE 9:E84086-E84086(2014).
RN [51]
RP SPECIFIC INHIBITION BY SCORPION TOXIN.
RX PubMed=27346450; DOI=10.1016/j.toxicon.2016.06.014;
RA Pucca M.B., Cerni F.A., Cordeiro F.A., Peigneur S., Cunha T.M., Tytgat J.,
RA Arantes E.C.;
RT "Ts8 scorpion toxin inhibits the Kv4.2 channel and produces nociception in
RT vivo.";
RL Toxicon 119:244-252(2016).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 42-146 IN COMPLEX WITH ZINC IONS,
RP AND MUTAGENESIS OF LEU-66 AND ARG-93.
RX PubMed=12835418; DOI=10.1073/pnas.1432840100;
RA Nanao M.H., Zhou W., Pfaffinger P.J., Choe S.;
RT "Determining the basis of channel-tetramerization specificity by X-ray
RT crystallography and a sequence-comparison algorithm: family values
RT (FamVal).";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8670-8675(2003).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-30, FUNCTION, INTERACTION WITH
RP KCNIP1; KCNIP2 AND KCNIP3, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP TRP-8 AND PHE-11, AND DOMAIN.
RX PubMed=14980206; DOI=10.1016/s0896-6273(04)00045-5;
RA Zhou W., Qian Y., Kunjilwar K., Pfaffinger P.J., Choe S.;
RT "Structural insights into the functional interaction of KChIP1 with Shal-
RT type K(+) channels.";
RL Neuron 41:573-586(2004).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes, primarily in the brain, but
CC also in rodent heart (PubMed:1840649, PubMed:1722463, PubMed:9093524,
CC PubMed:9058605, PubMed:10676964, PubMed:12592409, PubMed:12754210,
CC PubMed:16207878, PubMed:16123112, PubMed:19279261, PubMed:25352783,
CC PubMed:14980206). Mediates the major part of the dendritic A-type
CC current I(SA) in brain neurons (PubMed:16207878, PubMed:17026528). This
CC current is activated at membrane potentials that are below the
CC threshold for action potentials. It regulates neuronal excitability,
CC prolongs the latency before the first spike in a series of action
CC potentials, regulates the frequency of repetitive action potential
CC firing, shortens the duration of action potentials and regulates the
CC back-propagation of action potentials from the neuronal cell body to
CC the dendrites. Contributes to the regulation of the circadian rhythm of
CC action potential firing in suprachiasmatic nucleus neurons, which
CC regulates the circadian rhythm of locomotor activity (By similarity).
CC Functions downstream of the metabotropic glutamate receptor GRM5 and
CC plays a role in neuronal excitability and in nociception mediated by
CC activation of GRM5 (By similarity). Mediates the transient outward
CC current I(to) in rodent heart left ventricle apex cells, but not in
CC human heart, where this current is mediated by another family member
CC (PubMed:9093524, PubMed:9058605). Forms tetrameric potassium-selective
CC channels through which potassium ions pass in accordance with their
CC electrochemical gradient. The channel alternates between opened and
CC closed conformations in response to the voltage difference across the
CC membrane (PubMed:1840649, PubMed:1722463, PubMed:9093524,
CC PubMed:10676964, PubMed:12451113, PubMed:12592409, PubMed:12754210,
CC PubMed:15452711, PubMed:16207878, PubMed:16820361, PubMed:25352783,
CC PubMed:14980206). Can form functional homotetrameric channels and
CC heterotetrameric channels that contain variable proportions of KCND2
CC and KCND3; channel properties depend on the type of pore-forming alpha
CC subunits that are part of the channel (PubMed:25352783). In vivo,
CC membranes probably contain a mixture of heteromeric potassium channel
CC complexes (PubMed:12451113, PubMed:16123112). Interaction with specific
CC isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4
CC strongly increases expression at the cell surface and thereby increases
CC channel activity; it modulates the kinetics of channel activation and
CC inactivation, shifts the threshold for channel activation to more
CC negative voltage values, shifts the threshold for inactivation to less
CC negative voltages and accelerates recovery after inactivation
CC (PubMed:12451113, PubMed:15452711, PubMed:16123112, PubMed:16820361,
CC PubMed:20045463, PubMed:14980206). Likewise, interaction with DPP6 or
CC DPP10 promotes expression at the cell membrane and regulates both
CC channel characteristics and activity (PubMed:15671030, PubMed:16123112,
CC PubMed:19441798, PubMed:19901547, PubMed:19279261).
CC {ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10676964,
CC ECO:0000269|PubMed:11847232, ECO:0000269|PubMed:12451113,
CC ECO:0000269|PubMed:12592409, ECO:0000269|PubMed:12754210,
CC ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:15452711,
CC ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:16123112,
CC ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:16820361,
CC ECO:0000269|PubMed:17026528, ECO:0000269|PubMed:1722463,
CC ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:1840649,
CC ECO:0000269|PubMed:19279261, ECO:0000269|PubMed:19441798,
CC ECO:0000269|PubMed:19901547, ECO:0000269|PubMed:24404150,
CC ECO:0000269|PubMed:25352783, ECO:0000269|PubMed:9058605,
CC ECO:0000269|PubMed:9093524, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Inhibited by 5 mM 4-aminopyridine (4-AP)
CC (PubMed:1840649, PubMed:1722463, PubMed:9093524). Not inhibited by
CC dendrotoxins and by tetraethylammonium (TEA) (PubMed:1722463).
CC Inhibited by 10 mM flecainide and 20 mM quinidine (PubMed:9093524).
CC Inhibited by the heteropodatoxins HpTx(1), HpTx(2), and HpTx(3)
CC (PubMed:9058605). {ECO:0000269|PubMed:1722463,
CC ECO:0000269|PubMed:1840649, ECO:0000269|PubMed:9058605,
CC ECO:0000269|PubMed:9093524}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=Homotetrameric channels activate rapidly, i.e within a few msec
CC (PubMed:1722463, PubMed:9093524). After that, they inactivate
CC rapidly, i.e within about 50-100 msec (PubMed:1722463,
CC PubMed:9093524). The voltage-dependence of activation and
CC inactivation and other channel characteristics vary depending on the
CC experimental conditions, the expression system and the presence or
CC absence of ancillary subunits (PubMed:19901547, PubMed:19279261).
CC Homotetrameric channels have a unitary conductance of about 4 pS when
CC expressed in a heterologous system (PubMed:19279261). For the
CC activation of homotetrameric channels expressed in xenopus oocytes,
CC the voltage at half-maximal amplitude is about -10 mV
CC (PubMed:12451113). The time constant for inactivation is about 20
CC msec (PubMed:12451113). For inactivation, the voltage at half-maximal
CC amplitude is -62 mV (PubMed:12451113). The time constant for recovery
CC after inactivation is about 70 msec (PubMed:12451113).
CC {ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:1722463,
CC ECO:0000269|PubMed:19279261, ECO:0000269|PubMed:19901547,
CC ECO:0000269|PubMed:9093524, ECO:0000305|PubMed:15858231};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCND1 or KCND3
CC (PubMed:12754210, PubMed:15485870, PubMed:20224290, PubMed:25352783).
CC Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and
CC KCNIP4 (PubMed:10676964, PubMed:12451113, PubMed:11847232,
CC PubMed:11805342, PubMed:15485870, PubMed:15356203, PubMed:15452711,
CC PubMed:16820361, PubMed:20045463, PubMed:24811166, PubMed:14980206).
CC Interacts with DPP6, DPP10, DLG4 and DLG1 (PubMed:11923279,
CC PubMed:12575952, PubMed:14559911, PubMed:15671030, PubMed:19213956). In
CC vivo, probably exists as heteromeric complex containing variable
CC proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4,
CC DPP6 and DPP10 (PubMed:16123112, PubMed:19901547). The tetrameric
CC channel can associate with up to four regulatory subunits, such as
CC KCNIP2 or KCNIP4 (By similarity). Interaction with KCNIP3 promotes
CC tetramerization and formation of a functional potassium channel
CC (PubMed:15485870). Interaction with four KCNIP4 chains does not reduce
CC interaction with DPP10 (By similarity). Probably part of a complex
CC consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity).
CC Interacts with FLNA and FLNC (PubMed:11102480). Interacts with
CC NCS1/FREQ (By similarity). Identified in a complex with cAMP-dependent
CC protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes
CC (PubMed:20224290). {ECO:0000250|UniProtKB:Q9NZV8,
CC ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10676964,
CC ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:11805342,
CC ECO:0000269|PubMed:11847232, ECO:0000269|PubMed:11923279,
CC ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:12575952,
CC ECO:0000269|PubMed:12754210, ECO:0000269|PubMed:14559911,
CC ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:14980207,
CC ECO:0000269|PubMed:15356203, ECO:0000269|PubMed:15452711,
CC ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:15671030,
CC ECO:0000269|PubMed:16123112, ECO:0000269|PubMed:16207878,
CC ECO:0000269|PubMed:16820361, ECO:0000269|PubMed:19213956,
CC ECO:0000269|PubMed:20224290, ECO:0000269|PubMed:24811166,
CC ECO:0000269|PubMed:25352783, ECO:0000305|PubMed:19441798,
CC ECO:0000305|PubMed:19901547}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10676964,
CC ECO:0000269|PubMed:10860776, ECO:0000269|PubMed:11102480,
CC ECO:0000269|PubMed:11847232, ECO:0000269|PubMed:12451113,
CC ECO:0000269|PubMed:12592409, ECO:0000269|PubMed:12754210,
CC ECO:0000269|PubMed:12829703, ECO:0000269|PubMed:14559911,
CC ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:15452711,
CC ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:15671030,
CC ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:16123112,
CC ECO:0000269|PubMed:16820361, ECO:0000269|PubMed:1722463,
CC ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18371079,
CC ECO:0000269|PubMed:1840649, ECO:0000269|PubMed:18650329,
CC ECO:0000269|PubMed:20045463, ECO:0000269|PubMed:22098631,
CC ECO:0000269|PubMed:24793047, ECO:0000269|PubMed:25352783,
CC ECO:0000269|PubMed:9070739, ECO:0000269|PubMed:9093524}; Multi-pass
CC membrane protein {ECO:0000305}. Cell projection, dendrite
CC {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11102480,
CC ECO:0000269|PubMed:12592409, ECO:0000269|PubMed:15736227,
CC ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:17582333,
CC ECO:0000269|PubMed:18371079, ECO:0000269|PubMed:20224290,
CC ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24037673,
CC ECO:0000269|PubMed:24404150, ECO:0000269|PubMed:9070739}. Synapse
CC {ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:15736227,
CC ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:9070739}. Perikaryon
CC {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:15736227,
CC ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:18371079,
CC ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:9070739}. Postsynaptic
CC cell membrane {ECO:0000269|PubMed:15736227,
CC ECO:0000269|PubMed:9070739}. Cell projection, dendritic spine
CC {ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18650329,
CC ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24037673,
CC ECO:0000269|PubMed:9070739}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:10860776}. Cell junction
CC {ECO:0000269|PubMed:18371079}. Membrane, caveola
CC {ECO:0000269|PubMed:20224290}. Note=In neurons, primarily detected on
CC dendrites, dendritic spines and on the neuron cell body, but not on
CC axons (PubMed:9070739, PubMed:17582333, PubMed:16207878,
CC PubMed:22098631). Localized preferentially at the dendrites of
CC pyramidal cells in the hippocampus CA1 layer (PubMed:22098631).
CC Detected at GABAergic synapses (By similarity). Detected at cell
CC junctions that are distinct from synaptic cell contacts
CC (PubMed:18371079). Detected in lipid rafts (PubMed:14559911,
CC PubMed:20224290, PubMed:24793047). Detected primarily at the
CC endoplasmic reticulum or Golgi when expressed by itself
CC (PubMed:12829703, PubMed:12754210, PubMed:16820361, PubMed:19441798,
CC PubMed:14980206). Interaction with KCNIP1, KCNIP2, KCNIP3 or KCNIP4
CC promotes expression at the cell membrane (PubMed:12829703,
CC PubMed:15485870, PubMed:20045463, PubMed:14980206). Interaction with
CC DPP6 or DPP10 promotes expression at the cell membrane
CC (PubMed:19441798). Internalized from the cell membrane by clathrin-
CC dependent endocytosis in response to activation of AMPA-selective
CC glutamate receptors and PKA-mediated phosphorylation at Ser-552
CC (PubMed:17582333, PubMed:18650329). Redistributed from dendritic spines
CC to the main dendritic shaft in response to activation of AMPA-selective
CC glutamate receptors and activation of PKA (PubMed:17582333,
CC PubMed:18650329). {ECO:0000250|UniProtKB:Q9Z0V2,
CC ECO:0000269|PubMed:12754210, ECO:0000269|PubMed:14559911,
CC ECO:0000269|PubMed:14980206, ECO:0000269|PubMed:15485870,
CC ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:16820361,
CC ECO:0000269|PubMed:17582333, ECO:0000269|PubMed:18650329,
CC ECO:0000269|PubMed:19441798, ECO:0000269|PubMed:20045463,
CC ECO:0000269|PubMed:20224290, ECO:0000269|PubMed:22098631,
CC ECO:0000269|PubMed:24793047, ECO:0000269|PubMed:9070739, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in brain cortex, hippocampus, dentate
CC gyrus, thalamus and cerebellum (PubMed:16123112). Detected in neurons
CC from the primary visual cortex (PubMed:16207878). Detected in the
CC supraoptic nucleus in hypothalamus, in hippocampus and the habenular
CC nucleus of the thalamus (PubMed:9070739). Detected in the bed nucleus
CC of the stria terminalis (PubMed:24037673). Detected in dendritic fields
CC in the hippocampus CA1 layer, in stratum radiatum, stratum oriens,
CC stratum lacunosum-moleculare and stratum pyramidale (PubMed:10676964,
CC PubMed:22098631). Detected in dendritic fields in the hippocampus CA3
CC layer and in dentate gyrus (PubMed:10676964). Detected in the
CC cerebellum granule cell layer, where it localizes at synapses
CC (PubMed:11102480, PubMed:10676964, PubMed:15736227). Detected in the
CC main olfactory bulb, especially in the granule cell layer and the
CC external plexiform layer, but also the mitral layer (PubMed:18371079).
CC Detected in heart atrium and ventricle (PubMed:10860776). Detected in
CC heart left ventricle (at protein level) (PubMed:24793047). Highly
CC expressed in heart and throughout the brain, with similar levels in
CC cortex and hypothalamus, and much higher levels in hippocampus, dentate
CC gyrus and the habenular nucleus of the thalamus. Detected in brain, and
CC at lower levels in heart atrium and ventricle (PubMed:1705709).
CC Detected in neurons from the bed nucleus of the stria terminalis
CC (PubMed:24037673). Detected in aorta, cardiac and smooth muscle.
CC {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11102480,
CC ECO:0000269|PubMed:15736227, ECO:0000269|PubMed:16123112,
CC ECO:0000269|PubMed:16207878, ECO:0000269|PubMed:1705709,
CC ECO:0000269|PubMed:18371079, ECO:0000269|PubMed:1840649,
CC ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:24793047,
CC ECO:0000269|PubMed:9070739}.
CC -!- INDUCTION: Down-regulated in response to hypoxia lasting about 15 min,
CC a treatment that leads to spontaneous convulsive seizures in these
CC pups. {ECO:0000269|PubMed:25352783}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- DOMAIN: The N-terminal cytoplasmic region can mediate N-type
CC inactivation by physically blocking the channel (PubMed:15452711). This
CC probably does not happen in vivo, where the N-terminal region mediates
CC interaction with regulatory subunits, such as KCNIP1 and KCNIP2
CC (PubMed:16820361, PubMed:18357523, PubMed:14980206). The zinc binding
CC sites in the N-terminal domain are important for tetramerization and
CC assembly of a functional channel complex (PubMed:12754210). Most
CC likely, the channel undergoes closed-state inactivation, where a subtle
CC conformation change would render the protein less sensitive to
CC activation. {ECO:0000250|UniProtKB:Q9NZV8, ECO:0000269|PubMed:12754210,
CC ECO:0000269|PubMed:16820361, ECO:0000305|PubMed:14980206,
CC ECO:0000305|PubMed:15452711, ECO:0000305|PubMed:18357523}.
CC -!- DOMAIN: The C-terminal cytoplasmic region is important for normal
CC expression at the cell membrane and modulates the voltage-dependence of
CC channel activation and inactivation. It is required for interaction
CC with KCNIP2, and probably other family members as well.
CC {ECO:0000269|PubMed:16820361}.
CC -!- PTM: Phosphorylation at Ser-438 in response to MAPK activation is
CC increased in stimulated dendrites (PubMed:24404150). Interaction with
CC KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552
CC (PubMed:19441798). Phosphorylation at Ser-552 has no effect on
CC interaction with KCNIP3, but is required for the regulation of channel
CC activity by KCNIP3 (PubMed:12451113). Phosphorylation at Ser-552 leads
CC to KCND2 internalization (PubMed:17582333). Phosphorylated by MAPK in
CC response to signaling via the metabotropic glutamate receptor GRM5 (By
CC similarity). Phosphorylation at Ser-616 is required for the down-
CC regulation of neuronal A-type currents in response to signaling via
CC GRM5 (By similarity). {ECO:0000250|UniProtKB:Q9Z0V2,
CC ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:17582333,
CC ECO:0000269|PubMed:19441798, ECO:0000269|PubMed:24404150}.
CC -!- MISCELLANEOUS: The transient neuronal A-type potassium current called
CC I(SA) is triggered at membrane potentials that are below the threshold
CC for action potentials. It inactivates rapidly and recovers rapidly from
CC inactivation. It regulates the firing of action potentials and plays a
CC role in synaptic integration and plasticity. Potassium channels
CC containing KCND2 account for about 80% of the neuronal A-type potassium
CC current. In contrast, the potassium channel responsible for the cardiac
CC I(to) current differs between species; it is mediated by KCND2 in
CC rodents. In human and other non-rodents KCND3 may play an equivalent
CC role. {ECO:0000269|PubMed:9093524, ECO:0000305|PubMed:17917103,
CC ECO:0000305|PubMed:18357523}.
CC -!- MISCELLANEOUS: Is specifically and reversibly inhibited by the scorpion
CC toxin Ts8 (AC P69940). {ECO:0000269|PubMed:27346450}.
CC -!- SIMILARITY: Belongs to the potassium channel family. D (Shal) (TC
CC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA40929.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; S64320; AAB19939.1; -; mRNA.
DR EMBL; M59980; AAA40929.1; ALT_FRAME; mRNA.
DR PIR; I57681; I57681.
DR PIR; JU0271; JU0271.
DR RefSeq; NP_113918.2; NM_031730.2.
DR PDB; 1NN7; X-ray; 2.10 A; A=42-146.
DR PDB; 1S6C; X-ray; 2.00 A; B=1-30.
DR PDBsum; 1NN7; -.
DR PDBsum; 1S6C; -.
DR AlphaFoldDB; Q63881; -.
DR SMR; Q63881; -.
DR BioGRID; 249292; 2.
DR CORUM; Q63881; -.
DR IntAct; Q63881; 3.
DR MINT; Q63881; -.
DR STRING; 10116.ENSRNOP00000039227; -.
DR BindingDB; Q63881; -.
DR ChEMBL; CHEMBL1075227; -.
DR DrugCentral; Q63881; -.
DR GuidetoPHARMACOLOGY; 553; -.
DR iPTMnet; Q63881; -.
DR PhosphoSitePlus; Q63881; -.
DR PaxDb; Q63881; -.
DR PRIDE; Q63881; -.
DR ABCD; Q63881; 3 sequenced antibodies.
DR GeneID; 65180; -.
DR KEGG; rno:65180; -.
DR UCSC; RGD:68393; rat.
DR CTD; 3751; -.
DR RGD; 68393; Kcnd2.
DR eggNOG; KOG4390; Eukaryota.
DR InParanoid; Q63881; -.
DR OrthoDB; 469107at2759; -.
DR PhylomeDB; Q63881; -.
DR Reactome; R-RNO-1296072; Voltage gated Potassium channels.
DR Reactome; R-RNO-5576894; Phase 1 - inactivation of fast Na+ channels.
DR EvolutionaryTrace; Q63881; -.
DR PRO; PR:Q63881; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:RGD.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; ISO:RGD.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB.
DR GO; GO:0034705; C:potassium channel complex; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005250; F:A-type (transient outward) potassium channel activity; IDA:UniProtKB.
DR GO; GO:0005216; F:ion channel activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005267; F:potassium channel activity; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; IMP:SynGO.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0001508; P:action potential; IMP:RGD.
DR GO; GO:0086001; P:cardiac muscle cell action potential; IMP:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0045475; P:locomotor rhythm; ISO:RGD.
DR GO; GO:0019228; P:neuronal action potential; ISO:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:RGD.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
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; IPR003975; K_chnl_volt-dep_Kv4.
DR InterPro; IPR004055; K_chnl_volt-dep_Kv4.2.
DR InterPro; IPR024587; K_chnl_volt-dep_Kv4_C.
DR InterPro; IPR021645; Shal-type_N.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF11879; DUF3399; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF11601; Shal-type; 1.
DR PRINTS; PR01517; KV42CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01497; SHALCHANNEL.
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; Ion channel;
KW Ion transport; Membrane; Metal-binding; Phosphoprotein;
KW Postsynaptic cell membrane; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel; Zinc.
FT CHAIN 1..630
FT /note="Potassium voltage-gated channel subfamily D member
FT 2"
FT /id="PRO_0000054067"
FT TOPO_DOM 1..182
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 183..204
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 205..228
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 229..250
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 251..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 262..279
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 280..286
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 287..306
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 307..321
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 322..343
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 344..357
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 358..369
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 370..377
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 378..384
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 385..413
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 414..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 2..20
FT /note="Interaction with KCNIP1, KCNIP2, and other family
FT members"
FT /evidence="ECO:0000305|PubMed:14980206,
FT ECO:0000305|PubMed:14980207"
FT REGION 71..90
FT /note="Interaction with KCNIP1"
FT /evidence="ECO:0000305|PubMed:14980207"
FT REGION 308..321
FT /note="S4-S5 linker"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 474..630
FT /note="Important for normal channel activation and
FT inactivation, for interaction with KCNIP2, and probably
FT other family members as well"
FT /evidence="ECO:0000305|PubMed:16820361"
FT REGION 474..489
FT /note="Required for dendritic targeting"
FT /evidence="ECO:0000269|PubMed:12592409"
FT REGION 600..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 370..375
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 627..630
FT /note="PDZ-binding"
FT /evidence="ECO:0000269|PubMed:11923279,
FT ECO:0000269|PubMed:14559911"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0007744|PDB:1NN7"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0007744|PDB:1NN7"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0007744|PDB:1NN7"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:10681507"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:24404150"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19441798,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10681507,
FT ECO:0000269|PubMed:12451113, ECO:0000269|PubMed:12829703,
FT ECO:0000269|PubMed:18650329, ECO:0000269|PubMed:19441798,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19441798,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 575
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19441798,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11080179"
FT MOD_RES 607
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11080179"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11080179"
FT MUTAGEN 7..11
FT /note="Missing: Greatly reduces interaction with KCNIP1."
FT /evidence="ECO:0000269|PubMed:14980207"
FT MUTAGEN 8
FT /note="W->A: Abolishes interaction with KCNP1; when
FT associated with A-11."
FT /evidence="ECO:0000269|PubMed:14980206"
FT MUTAGEN 11
FT /note="F->A: Abolishes interaction with KCNP1; when
FT associated with A-8."
FT /evidence="ECO:0000269|PubMed:14980206"
FT MUTAGEN 66
FT /note="L->R: Abolishes expression."
FT /evidence="ECO:0000269|PubMed:12835418"
FT MUTAGEN 71
FT /note="E->K: Abolishes interaction with KCNIP1."
FT /evidence="ECO:0000269|PubMed:14980207"
FT MUTAGEN 73
FT /note="D->M: Abolishes interaction with KCNIP1."
FT /evidence="ECO:0000269|PubMed:14980207"
FT MUTAGEN 74
FT /note="F->R: Abolishes interaction with KCNIP1."
FT /evidence="ECO:0000269|PubMed:14980207"
FT MUTAGEN 79
FT /note="E->L,R: Abolishes interaction with KCNIP1."
FT /evidence="ECO:0000269|PubMed:14980207"
FT MUTAGEN 93
FT /note="R->A: Greatly reduces expression and changes
FT multimerization."
FT /evidence="ECO:0000269|PubMed:12835418"
FT MUTAGEN 105
FT /note="H->A: Abolishes tetramerization and assembly of a
FT functional channel."
FT /evidence="ECO:0000269|PubMed:12754210"
FT MUTAGEN 111
FT /note="C->A: Abolishes tetramerization and assembly of a
FT functional channel; when associated with A-105; A-132 and
FT A-133."
FT /evidence="ECO:0000269|PubMed:12754210"
FT MUTAGEN 132
FT /note="C->A: Abolishes tetramerization and assembly of a
FT functional channel; when associated with A-105; A-111 and
FT A-133."
FT /evidence="ECO:0000269|PubMed:12754210"
FT MUTAGEN 133
FT /note="C->A: Abolishes tetramerization and assembly of a
FT functional channel; when associated with A-105; A-111 and
FT A-132."
FT /evidence="ECO:0000269|PubMed:12754210"
FT MUTAGEN 481..482
FT /note="Missing: Loss of dendritic targeted expression."
FT /evidence="ECO:0000269|PubMed:12592409"
FT MUTAGEN 552
FT /note="S->A: Abolishes PKA-mediated modulation of cell
FT surface expression and channel activity."
FT /evidence="ECO:0000269|PubMed:12451113,
FT ECO:0000269|PubMed:18650329"
FT MUTAGEN 627..630
FT /note="Missing: Abolishes interaction with DLG4."
FT /evidence="ECO:0000269|PubMed:11923279,
FT ECO:0000269|PubMed:14559911"
FT HELIX 1..6
FT /evidence="ECO:0007829|PDB:1S6C"
FT HELIX 9..17
FT /evidence="ECO:0007829|PDB:1S6C"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:1NN7"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:1NN7"
FT HELIX 56..60
FT /evidence="ECO:0007829|PDB:1NN7"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1NN7"
FT HELIX 70..75
FT /evidence="ECO:0007829|PDB:1NN7"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1NN7"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:1NN7"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1NN7"
FT HELIX 92..101
FT /evidence="ECO:0007829|PDB:1NN7"
FT HELIX 112..122
FT /evidence="ECO:0007829|PDB:1NN7"
FT HELIX 131..145
FT /evidence="ECO:0007829|PDB:1NN7"
SQ SEQUENCE 630 AA; 70549 MW; FDE57E8A5113BABF CRC64;
MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE
RYPDTLLGSS ERDFFYHPET QQYFFDRDPD IFRHILNFYR TGKLHYPRHE CISAYDEELA
FFGLIPEIIG DCCYEEYKDR RRENAERLQD DADTDNTGES ALPTMTARQR VWRAFENPHT
STMALVFYYV TGFFIAVSVI ANVVETVPCG SSPGHIKELP CGERYAVAFF CLDTACVMIF
TVEYLLRLAA APSRYRFVRS VMSIIDVVAI LPYYIGLVMT DNEDVSGAFV TLRVFRVFRI
FKFSRHSQGL RILGYTLKSC ASELGFLLFS LTMAIIIFAT VMFYAEKGSS ASKFTSIPAA
FWYTIVTMTT LGYGDMVPKT IAGKIFGSIC SLSGVLVIAL PVPVIVSNFS RIYHQNQRAD
KRRAQKKARL ARIRAAKSGS ANAYMQSKRN GLLSNQLQSS EDEPAFVSKS GSSFETQHHH
LLHCLEKTTN HEFVDEQVFE ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKSFRI
PNANVSGSHR GSVQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI
PTPPVTTPEG DDRPESPEYS GGNIVRVSAL
