KCND2_MOUSE
ID KCND2_MOUSE Reviewed; 630 AA.
AC Q9Z0V2; Q8BSK3; Q8CHB7; Q9JJ60;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Potassium voltage-gated channel subfamily D member 2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv4.2;
GN Name=Kcnd2; Synonyms=Kiaa1044; ORFNames=MNCb-7013;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster; TISSUE=Heart ventricle;
RA Tanaka H., Janzen K., Winkfein R.J., Fiset C., Clark R.B., Giles W.R.;
RT "Cloning and functional characterization of mouse heart K+ channel alpha
RT subunits, Kv1.5, Kv4.2 and Kv4.3.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from mouse brain cDNA library made by
RT oligo-capping method.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12465718; DOI=10.1093/dnares/9.5.179;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I.
RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 9:179-188(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mesonephros, and Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH KCND3, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP TRP-362, AND TISSUE SPECIFICITY.
RX PubMed=9734479; DOI=10.1161/01.res.83.5.560;
RA Barry D.M., Xu H., Schuessler R.B., Nerbonne J.M.;
RT "Functional knockout of the transient outward current, long-QT syndrome,
RT and cardiac remodeling in mice expressing a dominant-negative Kv4 alpha
RT subunit.";
RL Circ. Res. 83:560-567(1998).
RN [7]
RP MUTAGENESIS OF TRP-362, AND FUNCTION.
RX PubMed=10601491; DOI=10.1111/j.1469-7793.1999.00587.x;
RA Guo W., Xu H., London B., Nerbonne J.M.;
RT "Molecular basis of transient outward K+ current diversity in mouse
RT ventricular myocytes.";
RL J. Physiol. (Lond.) 521:587-599(1999).
RN [8]
RP FUNCTION.
RX PubMed=10818150; DOI=10.1523/jneurosci.20-11-04145.2000;
RA Shibata R., Nakahira K., Shibasaki K., Wakazono Y., Imoto K., Ikenaka K.;
RT "A-type K+ current mediated by the Kv4 channel regulates the generation of
RT action potential in developing cerebellar granule cells.";
RL J. Neurosci. 20:4145-4155(2000).
RN [9]
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11040264; DOI=10.1101/lm.35300;
RA Varga A.W., Anderson A.E., Adams J.P., Vogel H., Sweatt J.D.;
RT "Input-specific immunolocalization of differentially phosphorylated Kv4.2
RT in the mouse brain.";
RL Learn. Memory 7:321-332(2000).
RN [10]
RP INTERACTION WITH KCNIP1 AND NCS1, FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11606724; DOI=10.1073/pnas.221168498;
RA Nakamura T.Y., Pountney D.J., Ozaita A., Nandi S., Ueda S., Rudy B.,
RA Coetzee W.A.;
RT "A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-
RT currents.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12808-12813(2001).
RN [11]
RP FUNCTION, INTERACTION WITH KCND3 AND KCNIP2, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=11909823; DOI=10.1161/01.res.0000012664.05949.e0;
RA Guo W., Li H., Aimond F., Johns D.C., Rhodes K.J., Trimmer J.S.,
RA Nerbonne J.M.;
RT "Role of heteromultimers in the generation of myocardial transient outward
RT K+ currents.";
RL Circ. Res. 90:586-593(2002).
RN [12]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16293790; DOI=10.1161/01.res.0000196559.63223.aa;
RA Guo W., Jung W.E., Marionneau C., Aimond F., Xu H., Yamada K.A.,
RA Schwarz T.L., Demolombe S., Nerbonne J.M.;
RT "Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical
RT and molecular remodeling, with no evidence of ventricular hypertrophy or
RT myocardial dysfunction.";
RL Circ. Res. 97:1342-1350(2005).
RN [13]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16009497; DOI=10.1016/j.neuroscience.2005.04.065;
RA Jinno S., Jeromin A., Kosaka T.;
RT "Postsynaptic and extrasynaptic localization of Kv4.2 channels in the mouse
RT hippocampal region, with special reference to targeted clustering at
RT gabaergic synapses.";
RL Neuroscience 134:483-494(2005).
RN [14]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17122039; DOI=10.1523/jneurosci.2667-06.2006;
RA Chen X., Yuan L.L., Zhao C., Birnbaum S.G., Frick A., Jung W.E.,
RA Schwarz T.L., Sweatt J.D., Johnston D.;
RT "Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances
RT induction of long-term potentiation in hippocampal CA1 pyramidal neurons.";
RL J. Neurosci. 26:12143-12151(2006).
RN [15]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17122053; DOI=10.1523/jneurosci.2599-06.2006;
RA Burkhalter A., Gonchar Y., Mellor R.L., Nerbonne J.M.;
RT "Differential expression of I(A) channel subunits Kv4.2 and Kv4.3 in mouse
RT visual cortical neurons and synapses.";
RL J. Neurosci. 26:12274-12282(2006).
RN [16]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-616, MUTAGENESIS OF
RP THR-602; THR-607 AND SER-616, AND TISSUE SPECIFICITY.
RX PubMed=18045912; DOI=10.1523/jneurosci.0269-07.2007;
RA Hu H.J., Alter B.J., Carrasquillo Y., Qiu C.S., Gereau R.W.;
RT "Metabotropic glutamate receptor 5 modulates nociceptive plasticity via
RT extracellular signal-regulated kinase-Kv4.2 signaling in spinal cord dorsal
RT horn neurons.";
RL J. Neurosci. 27:13181-13191(2007).
RN [17]
RP REVIEW.
RX PubMed=17917103; DOI=10.1007/s12035-007-8001-0;
RA Baranauskas G.;
RT "Ionic channel function in action potential generation: current
RT perspective.";
RL Mol. Neurobiol. 35:129-150(2007).
RN [18]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18187474; DOI=10.1113/jphysiol.2007.146597;
RA Nerbonne J.M., Gerber B.R., Norris A., Burkhalter A.;
RT "Electrical remodelling maintains firing properties in cortical pyramidal
RT neurons lacking KCND2-encoded A-type K+ currents.";
RL J. Physiol. (Lond.) 586:1565-1579(2008).
RN [19]
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 [20]
RP SUBUNIT.
RX PubMed=19713751; DOI=10.4161/chan.3.4.9553;
RA Marionneau C., LeDuc R.D., Rohrs H.W., Link A.J., Townsend R.R.,
RA Nerbonne J.M.;
RT "Proteomic analyses of native brain K(V)4.2 channel complexes.";
RL Channels 3:284-294(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-552; SER-572 AND SER-575, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20371829; DOI=10.1523/jneurosci.5890-09.2010;
RA Norris A.J., Nerbonne J.M.;
RT "Molecular dissection of I(A) in cortical pyramidal neurons reveals three
RT distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits.";
RL J. Neurosci. 30:5092-5101(2010).
RN [23]
RP INTERACTION WITH KCND3; KCNIP2; KCNIP3 AND KCNIP4.
RX PubMed=20943905; DOI=10.1523/jneurosci.2487-10.2010;
RA Norris A.J., Foeger N.C., Nerbonne J.M.;
RT "Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in
RT the generation of Kv4-encoded IA channels in cortical pyramidal neurons.";
RL J. Neurosci. 30:13644-13655(2010).
RN [24]
RP DISRUPTION PHENOTYPE.
RX PubMed=20857488; DOI=10.1002/hipo.20877;
RA Lockridge A., Yuan L.L.;
RT "Spatial learning deficits in mice lacking A-type K(+) channel subunits.";
RL Hippocampus 21:1152-1156(2011).
RN [25]
RP DISRUPTION PHENOTYPE.
RX PubMed=22738428; DOI=10.1186/2045-5380-2-5;
RA Kiselycznyk C., Hoffman D.A., Holmes A.;
RT "Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel
RT on murine anxiety-, fear- and stress-related behaviors.";
RL Biol. Mood Anxiety Disord. 2:5-5(2012).
RN [26]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22612819; DOI=10.1111/j.1528-1167.2012.03485.x;
RA Menegola M., Clark E., Trimmer J.S.;
RT "The importance of immunohistochemical analyses in evaluating the phenotype
RT of Kv channel knockout mice.";
RL Epilepsia 53:142-149(2012).
RN [27]
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 [28]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH DPP6 AND DPP10.
RX PubMed=22311982; DOI=10.1074/jbc.m111.324574;
RA Foeger N.C., Norris A.J., Wren L.M., Nerbonne J.M.;
RT "Augmentation of Kv4.2-encoded currents by accessory dipeptidyl peptidase 6
RT and 10 subunits reflects selective cell surface Kv4.2 protein
RT stabilization.";
RL J. Biol. Chem. 287:9640-9650(2012).
RN [29]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=22815518; DOI=10.1523/jneurosci.0174-12.2012;
RA Granados-Fuentes D., Norris A.J., Carrasquillo Y., Nerbonne J.M.,
RA Herzog E.D.;
RT "I(A) channels encoded by Kv1.4 and Kv4.2 regulate neuronal firing in the
RT suprachiasmatic nucleus and circadian rhythms in locomotor activity.";
RL J. Neurosci. 32:10045-10052(2012).
RN [30]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23713033; DOI=10.1113/jphysiol.2013.255836;
RA Foeger N.C., Wang W., Mellor R.L., Nerbonne J.M.;
RT "Stabilization of Kv4 protein by the accessory K(+) channel interacting
RT protein 2 (KChIP2) subunit is required for the generation of native
RT myocardial fast transient outward K(+) currents.";
RL J. Physiol. (Lond.) 591:4149-4166(2013).
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. Mediates the major part of the dendritic A-type
CC current I(SA) in brain neurons (PubMed:10818150, PubMed:17122039,
CC PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518).
CC This 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 (PubMed:10818150, PubMed:17122039, PubMed:22815518).
CC Contributes to the regulation of the circadian rhythm of action
CC potential firing in suprachiasmatic nucleus neurons, which regulates
CC the circadian rhythm of locomotor activity (PubMed:22815518). Functions
CC downstream of the metabotropic glutamate receptor GRM5 and plays a role
CC in neuronal excitability and in nociception mediated by activation of
CC GRM5 (PubMed:18045912). Mediates the transient outward current I(to) in
CC rodent heart left ventricle apex cells, but not in human heart, where
CC this current is mediated by another family member (PubMed:9734479,
CC PubMed:10601491, PubMed:11909823, PubMed:23713033). Forms tetrameric
CC potassium-selective channels through which potassium ions pass in
CC accordance with their electrochemical gradient. The channel alternates
CC between opened and closed conformations in response to the voltage
CC difference across the membrane (PubMed:9734479, PubMed:22311982). Can
CC form functional homotetrameric channels and heterotetrameric channels
CC that contain variable proportions of KCND2 and KCND3; channel
CC properties depend on the type of pore-forming alpha subunits that are
CC part of the channel (PubMed:11909823). In vivo, membranes probably
CC contain a mixture of heteromeric potassium channel complexes
CC (PubMed:11909823). Interaction with specific isoforms of the regulatory
CC subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression
CC at the cell surface and thereby increases channel activity; it
CC modulates the kinetics of channel activation and inactivation, shifts
CC the threshold for channel activation to more negative voltage values,
CC shifts the threshold for inactivation to less negative voltages and
CC accelerates recovery after inactivation (By similarity). Likewise,
CC interaction with DPP6 or DPP10 promotes expression at the cell membrane
CC and regulates both channel characteristics and activity
CC (PubMed:22311982). {ECO:0000250|UniProtKB:Q63881,
CC ECO:0000269|PubMed:10601491, ECO:0000269|PubMed:10818150,
CC ECO:0000269|PubMed:11909823, ECO:0000269|PubMed:17122039,
CC ECO:0000269|PubMed:18187474, ECO:0000269|PubMed:20371829,
CC ECO:0000269|PubMed:22311982, ECO:0000269|PubMed:23713033,
CC ECO:0000269|PubMed:9734479}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=Homotetrameric channels activate rapidly, i.e within a few msec.
CC After that, they inactivate rapidly, i.e within about 50-100 msec.
CC The voltage-dependence of activation and inactivation and other
CC channel characteristics vary depending on the experimental
CC conditions, the expression system and the presence or absence of
CC ancillary subunits. Homotetrameric channels have a unitary
CC conductance of about 4 pS when expressed in a heterologous system.
CC For the activation of homotetrameric channels expressed in xenopus
CC oocytes, the voltage at half-maximal amplitude is about -10 mV. The
CC time constant for inactivation is about 20 msec. For inactivation,
CC the voltage at half-maximal amplitude is -62 mV. The time constant
CC for recovery after inactivation is about 70 msec.
CC {ECO:0000305|PubMed:17917103};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCND3 or KCND1
CC (PubMed:9734479, PubMed:11909823, PubMed:19713751, PubMed:20943905).
CC Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and
CC KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905). In vivo,
CC probably exists as heteromeric complex containing variable proportions
CC of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10
CC (PubMed:19713751). The tetrameric channel can associate with up to four
CC regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity).
CC Interaction with four KCNIP4 chains does not reduce interaction with
CC DPP10 (By similarity). Interacts with DLG1 (By similarity). Interacts
CC with DLG4 (By similarity). Interacts with NCS1/FREQ (PubMed:11606724).
CC Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and
CC KCND2 (By similarity). Interacts with FLNA and FLNC (By similarity).
CC Interacts with DPP6 and DPP10 (PubMed:19713751, PubMed:22311982).
CC Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3,
CC AKAP6 and KCND3 in cardiac myocytes (By similarity).
CC {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9NZV8,
CC ECO:0000269|PubMed:11909823, ECO:0000269|PubMed:19713751,
CC ECO:0000269|PubMed:20943905, ECO:0000269|PubMed:22311982,
CC ECO:0000269|PubMed:9734479}.
CC -!- INTERACTION:
CC Q9Z0V2; Q99PW8: Kif17; NbExp=3; IntAct=EBI-959779, EBI-959754;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16009497,
CC ECO:0000269|PubMed:17122053, ECO:0000269|PubMed:22098631,
CC ECO:0000269|PubMed:22311982, ECO:0000269|PubMed:9734479}; Multi-pass
CC membrane protein {ECO:0000305}. Cell projection, dendrite
CC {ECO:0000269|PubMed:11040264, ECO:0000269|PubMed:17122053,
CC ECO:0000269|PubMed:22098631}. Synapse {ECO:0000269|PubMed:16009497,
CC ECO:0000269|PubMed:17122053}. Perikaryon {ECO:0000269|PubMed:11040264,
CC ECO:0000269|PubMed:16009497, ECO:0000269|PubMed:17122053,
CC ECO:0000269|PubMed:22098631}. Postsynaptic cell membrane
CC {ECO:0000269|PubMed:16009497}. Cell projection, dendritic spine
CC {ECO:0000269|PubMed:17122053}. Cell junction
CC {ECO:0000250|UniProtKB:Q63881}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q63881}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:Q63881}. Note=In neurons, primarily detected on
CC dendrites, dendritic spines and on the neuron cell body, but not on
CC axons (PubMed:17122053, PubMed:22098631). Localized preferentially at
CC the dendrites of pyramidal cells in the hippocampus CA1 layer. Detected
CC at GABAergic synapses (PubMed:16009497). Detected at cell junctions
CC that are distinct from synaptic cell contacts (By similarity). Detected
CC in lipid rafts (By similarity). Detected primarily at the endoplasmic
CC reticulum or Golgi when expressed by itself (By similarity).
CC Interaction with KCNIP1, KCNIP2, KCNIP3 or KCNIP4 promotes expression
CC at the cell membrane (PubMed:22311982). Interaction with DPP6 or DPP10
CC promotes expression at the cell membrane (By similarity). Internalized
CC from the cell membrane by clathrin-dependent endocytosis in response to
CC activation of AMPA-selective glutamate receptors and PKA-mediated
CC phosphorylation at Ser-552. Redistributed from dendritic spines to the
CC main dendritic shaft in response to activation of AMPA-selective
CC glutamate receptors and activation of PKA (By similarity).
CC {ECO:0000250|UniProtKB:Q63881, ECO:0000269|PubMed:17122053,
CC ECO:0000269|PubMed:22098631, ECO:0000269|PubMed:22311982}.
CC -!- TISSUE SPECIFICITY: Detected in hippocampus, thalamus, medial habenular
CC nucleus, striatum, amygdala, brain cortex and cerebellum
CC (PubMed:11040264, PubMed:17122039, PubMed:18187474, PubMed:20371829,
CC PubMed:22612819). Detected in hippocampus CA1 and CA3 layer, in stratum
CC oriens, stratum radiatum and stratum lacunosum-moleculare and in
CC dentate gyrus (PubMed:16009497, PubMed:22098631). Detected in dorsal
CC horn neurons; colocalizes with GRM5 (PubMed:18045912). C-terminally
CC phosphorylated forms are detected in the stratum radiatum and in
CC basilar dendrites in stratum oriens in hippocampus CA1 and on cell
CC bodies in hippocampus CA3 layers, with lower levels in stratum
CC lacunosum-moleculare (PubMed:11040264). In contrast, N-terminally
CC phosphorylated forms are detected in stratum lacunosum moleculare in
CC the hippocampus CA1 layer (PubMed:11040264). Both C-terminally and N-
CC terminally phosphorylated forms are observed on cell bodies and
CC neuronal processes in the amygdala (PubMed:11040264). C-terminally
CC phosphorylated forms are detected in the dentate gyrus molecular layer,
CC while N-terminally phosphorylated forms are detected in the hilus of
CC the dentate gyrus (PubMed:11040264). Both N-terminally and C-terminally
CC phosphorylated forms are detected in the somatosensory cortex
CC (PubMed:11040264). C-terminally phosphorylated forms are detected in
CC the cerebellum granular layers (PubMed:11040264). Detected in heart
CC ventricle myocytes (at protein level) (PubMed:9734479, PubMed:11909823,
CC PubMed:16293790, PubMed:23713033). Detected in brain and heart
CC (PubMed:16293790). {ECO:0000269|PubMed:11040264,
CC ECO:0000269|PubMed:11909823, ECO:0000269|PubMed:16009497,
CC ECO:0000269|PubMed:16293790, ECO:0000269|PubMed:17122039,
CC ECO:0000269|PubMed:17122053, ECO:0000269|PubMed:18045912,
CC ECO:0000269|PubMed:18187474, ECO:0000269|PubMed:22098631,
CC ECO:0000269|PubMed:22612819, ECO:0000269|PubMed:23713033,
CC ECO:0000269|PubMed:9734479}.
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 (By similarity). This
CC probably does not happen in vivo, where the N-terminal region mediates
CC interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By
CC similarity). The zinc binding sites in the N-terminal domain are
CC important for tetramerization and assembly of a functional channel
CC complex (By similarity). Most likely, the channel undergoes closed-
CC state inactivation, where a subtle conformation change would render the
CC protein less sensitive to activation. {ECO:0000250|UniProtKB:Q63881,
CC ECO:0000250|UniProtKB:Q9NZV8, 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:0000250|UniProtKB:Q63881}.
CC -!- PTM: Phosphorylation at Ser-438 in response to MAPK activation is
CC increased in stimulated dendrites. Interaction with KCNIP2 and DPP6
CC propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552
CC has no effect on interaction with KCNIP3, but is required for the
CC regulation of channel activity by KCNIP3. Phosphorylation at Ser-552
CC leads to KCND2 internalization (By similarity). Phosphorylated by MAPK
CC in response to signaling via the metabotropic glutamate receptor GRM5
CC (PubMed:18045912). Phosphorylation at Ser-616 is required for the down-
CC regulation of neuronal A-type currents in response to signaling via
CC GRM5 (PubMed:18045912). {ECO:0000250|UniProtKB:Q63881,
CC ECO:0000269|PubMed:18045912}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable, fertile and appear to be in good
CC health (PubMed:16293790, PubMed:22738428). The loss of KCND2 has only
CC minor functional consequences, probably due to an increase of the
CC activity of other potassium channels, even though there is no visible
CC change of their expression levels (PubMed:20371829). Mutant mice show
CC no sign of heart dysfunction, but the fast component of the rapidly
CC inactivating and rapidly recovering potassium current I(to) is lost in
CC their ventricular myocytes (PubMed:16293790). Instead, a slowly
CC inactivating current is expressed that is not observed in wild-type
CC (PubMed:16293790). Electrocardiograms of mutant hearts display no
CC significant differences relative to wild-type regarding their QT, PR,
CC QRS and RR intervals (PubMed:16293790). The neuronal A-type current is
CC reduced by about 80% in brain cortex and hippocampus CA1 pyramidal
CC neurons, by about 50% in suprachiasmatic nucleus neurons and by about
CC 60% in dorsal horn neurons (PubMed:17122039, PubMed:18045912,
CC PubMed:18187474, PubMed:20371829, PubMed:22815518). The dendritic A-
CC type current is abolished in pyramidal neurons from the hippocampus CA1
CC layer (PubMed:17122039). Concomitantly, the back-propagation of action
CC potential in dendrites is increased (PubMed:17122039). This may lower
CC the treshold for neuronal long-term potentiation (LTP)
CC (PubMed:17122039). Loss of KCND2 does not influence the levels of KCND3
CC or KCNA4, but leads to reduced KCNIP1, KCNIP2 and KCNIP3 protein levels
CC (PubMed:17122039, PubMed:18187474, PubMed:22612819). Mutant mice show
CC only minor differences in their behavior when compared to wild-type;
CC they display hyperactivity to some, but not all, novel stimuli
CC (PubMed:22738428). Mutant mice show subtle spatial learning deficits
CC (PubMed:20857488). Mutant mice display shorter periods of locomotor
CC activity that wild-type littermates, due to a corresponding change in
CC the circadian rhythm of repetitive firing in suprachiasmatic nucleus
CC neurons (PubMed:22815518). Mutant mice display loss of spontaneous
CC nociceptive behavior that is caused by the activation of GRM5
CC (PubMed:18045912). {ECO:0000269|PubMed:16293790,
CC ECO:0000269|PubMed:17122039, ECO:0000269|PubMed:18045912,
CC ECO:0000269|PubMed:18187474, ECO:0000269|PubMed:20371829,
CC ECO:0000269|PubMed:20857488, ECO:0000269|PubMed:22612819,
CC ECO:0000269|PubMed:22738428, ECO:0000269|PubMed:22815518}.
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:10601491, ECO:0000269|PubMed:16293790,
CC ECO:0000269|PubMed:17122039, ECO:0000269|PubMed:9734479,
CC ECO:0000305|PubMed:17917103, ECO:0000305|PubMed:18357523}.
CC -!- MISCELLANEOUS: Is specifically and reversibly inhibited by the scorpion
CC toxin Ts8 (AC P69940). {ECO:0000250|UniProtKB:Q63881}.
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=BAA97986.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC41464.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF107780; AAD16972.1; -; mRNA.
DR EMBL; AB045326; BAA97986.1; ALT_FRAME; mRNA.
DR EMBL; AB093280; BAC41464.1; ALT_INIT; mRNA.
DR EMBL; AK032268; BAC27787.1; -; mRNA.
DR EMBL; AK032772; BAC28015.1; -; mRNA.
DR EMBL; BC079667; AAH79667.1; -; mRNA.
DR CCDS; CCDS19934.1; -.
DR RefSeq; NP_062671.1; NM_019697.3.
DR AlphaFoldDB; Q9Z0V2; -.
DR SMR; Q9Z0V2; -.
DR BioGRID; 200890; 4.
DR ComplexPortal; CPX-3261; Kv4.2-KChIP2 channel complex.
DR IntAct; Q9Z0V2; 3.
DR STRING; 10090.ENSMUSP00000080257; -.
DR GuidetoPHARMACOLOGY; 553; -.
DR iPTMnet; Q9Z0V2; -.
DR PhosphoSitePlus; Q9Z0V2; -.
DR SwissPalm; Q9Z0V2; -.
DR MaxQB; Q9Z0V2; -.
DR PaxDb; Q9Z0V2; -.
DR PeptideAtlas; Q9Z0V2; -.
DR PRIDE; Q9Z0V2; -.
DR ProteomicsDB; 269261; -.
DR ABCD; Q9Z0V2; 2 sequenced antibodies.
DR Antibodypedia; 31683; 439 antibodies from 39 providers.
DR DNASU; 16508; -.
DR Ensembl; ENSMUST00000081542; ENSMUSP00000080257; ENSMUSG00000060882.
DR GeneID; 16508; -.
DR KEGG; mmu:16508; -.
DR UCSC; uc009baq.1; mouse.
DR CTD; 3751; -.
DR MGI; MGI:102663; Kcnd2.
DR VEuPathDB; HostDB:ENSMUSG00000060882; -.
DR eggNOG; KOG4390; Eukaryota.
DR GeneTree; ENSGT00940000155472; -.
DR HOGENOM; CLU_011722_9_1_1; -.
DR InParanoid; Q9Z0V2; -.
DR OMA; RTTVEKY; -.
DR OrthoDB; 469107at2759; -.
DR PhylomeDB; Q9Z0V2; -.
DR TreeFam; TF313103; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR Reactome; R-MMU-5576894; Phase 1 - inactivation of fast Na+ channels.
DR BioGRID-ORCS; 16508; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Kcnd2; mouse.
DR PRO; PR:Q9Z0V2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9Z0V2; protein.
DR Bgee; ENSMUSG00000060882; Expressed in cerebellum lobe and 152 other tissues.
DR Genevisible; Q9Z0V2; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
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; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR GO; GO:0034705; C:potassium channel complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; ISS: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; IMP:UniProtKB.
DR GO; GO:0005216; F:ion channel activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005267; F:potassium channel activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:0001508; P:action potential; ISO:MGI.
DR GO; GO:0086001; P:cardiac muscle cell action potential; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045475; P:locomotor rhythm; IMP:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; IMP:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
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; IMP:UniProtKB.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; 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 Cell junction; Cell membrane; Cell projection; Ion channel; Ion transport;
KW Membrane; Metal-binding; Phosphoprotein; Postsynaptic cell membrane;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel; Zinc.
FT CHAIN 1..630
FT /note="Potassium voltage-gated channel subfamily D member
FT 2"
FT /id="PRO_0000054065"
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:0000250|UniProtKB:Q63881"
FT REGION 71..90
FT /note="Interaction with KCNIP1"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
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:0000250|UniProtKB:Q63881"
FT REGION 474..489
FT /note="Required for dendritic targeting"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
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:0000250|UniProtKB:Q63881"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 575
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 607
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63881"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:18045912"
FT MUTAGEN 362
FT /note="W->F: Abolishes channel activity. Alters potassium
FT channel kinetics in heart myocytes. Abolishes the fast
FT component of I(to) in heart ventricle."
FT /evidence="ECO:0000269|PubMed:10601491,
FT ECO:0000269|PubMed:9734479"
FT MUTAGEN 602
FT /note="T->A: No effect on the regulation of neuronal A-type
FT current in response to activation of metabotropic glutamate
FT receptors."
FT /evidence="ECO:0000269|PubMed:18045912"
FT MUTAGEN 607
FT /note="T->A: No effect on the regulation of neuronal A-type
FT current in response to activation of metabotropic glutamate
FT receptors."
FT /evidence="ECO:0000269|PubMed:18045912"
FT MUTAGEN 616
FT /note="S->A: Abolishes regulation of neuronal A-type
FT current in response to activation of metabotropic glutamate
FT receptors."
FT /evidence="ECO:0000269|PubMed:18045912"
FT CONFLICT 22
FT /note="V -> A (in Ref. 2; BAA97986)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="S -> R (in Ref. 3; BAC41464)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 630 AA; 70577 MW; 7FB94277429E7683 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 EDEPAFISKS GSSFETQHHH
LLHCLEKTTN HEFVDEQVFE ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKTFRI
PNANVSGSHR GSVQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI
PTPPVTTPEG DDRPESPEYS GGNIVRVSAL
