KCNA2_MOUSE
ID KCNA2_MOUSE Reviewed; 499 AA.
AC P63141; B2RS05; P15386; Q02010; Q8C8W4;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 2;
DE AltName: Full=MK2 {ECO:0000303|PubMed:16141072};
DE AltName: Full=Voltage-gated potassium channel subunit Kv1.2;
GN Name=Kcna2;
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 [GENOMIC DNA].
RX PubMed=2305265; DOI=10.1126/science.2305265;
RA Chandy K.G., Williams C.B., Spencer R.H., Aguilar B.A., Ghanshani S.,
RA Tempel B.L., Gutman G.A.;
RT "A family of three mouse potassium channel genes with intronless coding
RT regions.";
RL Science 247:973-975(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI38651.1};
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 338-394.
RX PubMed=1691985; DOI=10.1016/0014-5793(90)80719-y;
RA Betsholtz C., Baumann A., Kenna S., Ashcroft F.M., Ashcroft S.J.H.,
RA Berggren P.-O., Grupe A., Pongs O., Rorsman P., Sandblom J., Welsh M.;
RT "Expression of voltage-gated K+ channels in insulin-producing cells.
RT Analysis by polymerase chain reaction.";
RL FEBS Lett. 263:121-126(1990).
RN [6]
RP SUBUNIT, INTERACTION WITH KCNA1, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=8361541; DOI=10.1038/365075a0;
RA Wang H., Kunkel D.D., Martin T.M., Schwartzkroin P.A., Tempel B.L.;
RT "Heteromultimeric K+ channels in terminal and juxtaparanodal regions of
RT neurons.";
RL Nature 365:75-79(1993).
RN [7]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=8046438; DOI=10.1523/jneurosci.14-08-04588.1994;
RA Wang H., Kunkel D.D., Schwartzkroin P.A., Tempel B.L.;
RT "Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic
RT terminals, somata, and dendrites in the mouse brain.";
RL J. Neurosci. 14:4588-4599(1994).
RN [8]
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 [9]
RP INTERACTION WITH KCNA5, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9852577; DOI=10.1523/jneurosci.18-24-10398.1998;
RA Sobko A., Peretz A., Shirihai O., Etkin S., Cherepanova V., Dagan D.,
RA Attali B.;
RT "Heteromultimeric delayed-rectifier K+ channels in Schwann cells:
RT developmental expression and role in cell proliferation.";
RL J. Neurosci. 18:10398-10408(1998).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=12527813; DOI=10.1124/mol.63.2.409;
RA Castle N.A., London D.O., Creech C., Fajloun Z., Stocker J.W.,
RA Sabatier J.-M.;
RT "Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated
RT potassium channels.";
RL Mol. Pharmacol. 63:409-418(2003).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17925011; DOI=10.1186/1741-7007-5-42;
RA Douglas C.L., Vyazovskiy V., Southard T., Chiu S.-Y., Messing A.,
RA Tononi G., Cirelli C.;
RT "Sleep in Kcna2 knockout mice.";
RL BMC Biol. 5:42-42(2007).
RN [12]
RP DISRUPTION PHENOTYPE, FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE
RP SPECIFICITY.
RX PubMed=17634333; DOI=10.1152/jn.00640.2006;
RA Brew H.M., Gittelman J.X., Silverstein R.S., Hanks T.D., Demas V.P.,
RA Robinson L.C., Robbins C.A., McKee-Johnson J., Chiu S.Y., Messing A.,
RA Tempel B.L.;
RT "Seizures and reduced life span in mice lacking the potassium channel
RT subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory
RT neurons.";
RL J. Neurophysiol. 98:1501-1525(2007).
RN [13]
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 [14]
RP SUBCELLULAR LOCATION.
RX PubMed=18509034; DOI=10.1523/jneurosci.4431-07.2008;
RA Ogawa Y., Horresh I., Trimmer J.S., Bredt D.S., Peles E., Rasband M.N.;
RT "Postsynaptic density-93 clusters Kv1 channels at axon initial segments
RT independently of Caspr2.";
RL J. Neurosci. 28:5731-5739(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-429, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=18760366; DOI=10.1016/j.mcn.2008.07.025;
RA Savvaki M., Panagiotaropoulos T., Stamatakis A., Sargiannidou I.,
RA Karatzioula P., Watanabe K., Stylianopoulou F., Karagogeos D., Kleopa K.A.;
RT "Impairment of learning and memory in TAG-1 deficient mice associated with
RT shorter CNS internodes and disrupted juxtaparanodes.";
RL Mol. Cell. Neurosci. 39:478-490(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434; SER-440 AND SER-468, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 [18]
RP FUNCTION, MUTAGENESIS OF ILE-402, SUBCELLULAR LOCATION, MISCELLANEOUS,
RP TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=20696761; DOI=10.1074/jbc.m110.153676;
RA Xie G., Harrison J., Clapcote S.J., Huang Y., Zhang J.Y., Wang L.Y.,
RA Roder J.C.;
RT "A new Kv1.2 channelopathy underlying cerebellar ataxia.";
RL J. Biol. Chem. 285:32160-32173(2010).
RN [19]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP DRD2.
RX PubMed=21233214; DOI=10.1074/jbc.m110.153262;
RA Fulton S., Thibault D., Mendez J.A., Lahaie N., Tirotta E., Borrelli E.,
RA Bouvier M., Tempel B.L., Trudeau L.E.;
RT "Contribution of Kv1.2 voltage-gated potassium channel to D2 autoreceptor
RT regulation of axonal dopamine overflow.";
RL J. Biol. Chem. 286:9360-9372(2011).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=22649228; DOI=10.1523/jneurosci.0719-12.2012;
RA Zenker J., Poirot O., de Preux Charles A.S., Arnaud E., Medard J.J.,
RA Lacroix C., Kuntzer T., Chrast R.;
RT "Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral
RT nerve hyperexcitability in type 2 diabetes mellitus.";
RL J. Neurosci. 32:7493-7498(2012).
RN [21]
RP INTERACTION WITH SIGMAR1, AND SUBCELLULAR LOCATION.
RX PubMed=23332758; DOI=10.1016/j.cell.2012.12.004;
RA Kourrich S., Hayashi T., Chuang J.Y., Tsai S.Y., Su T.P., Bonci A.;
RT "Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and
RT behavioral responses to cocaine.";
RL Cell 152:236-247(2013).
RN [22]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=23864368; DOI=10.1152/jn.00290.2013;
RA Wang W., Kim H.J., Lv P., Tempel B., Yamoah E.N.;
RT "Association of the Kv1 family of K+ channels and their functional
RT blueprint in the properties of auditory neurons as revealed by genetic and
RT functional analyses.";
RL J. Neurophysiol. 110:1751-1764(2013).
RN [23]
RP FUNCTION.
RX PubMed=23981714; DOI=10.1113/jphysiol.2013.259002;
RA Hyun J.H., Eom K., Lee K.H., Ho W.K., Lee S.H.;
RT "Activity-dependent downregulation of D-type K+ channel subunit Kv1.2 in
RT rat hippocampal CA3 pyramidal neurons.";
RL J. Physiol. (Lond.) 591:5525-5540(2013).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=25378149; DOI=10.1523/jneurosci.3369-14.2014;
RA Gordon A., Adamsky K., Vainshtein A., Frechter S., Dupree J.L.,
RA Rosenbluth J., Peles E.;
RT "Caspr and caspr2 are required for both radial and longitudinal
RT organization of myelinated axons.";
RL J. Neurosci. 34:14820-14826(2014).
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:12527813, PubMed:21233214). Can form functional homotetrameric
CC channels and heterotetrameric channels that contain variable
CC proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly
CC other family members as well; channel properties depend on the type of
CC alpha subunits that are part of the channel (PubMed:20696761). Channel
CC properties are modulated by cytoplasmic beta subunits that regulate the
CC subcellular location of the alpha subunits and promote rapid
CC inactivation of delayed rectifier potassium channels (By similarity).
CC In vivo, membranes probably contain a mixture of heteromeric potassium
CC channel complexes, making it difficult to assign currents observed in
CC intact tissues to any particular potassium channel family member.
CC Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that
CC opens in response to membrane depolarization, followed by slow
CC spontaneous channel closure (PubMed:23864368). In contrast, a
CC heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation
CC (PubMed:23864368). Contributes to the regulation of action potentials
CC in neurons (PubMed:12527813, PubMed:17925011). KCNA2-containing
CC channels play a presynaptic role and prevent hyperexcitability and
CC aberrant action potential firing (PubMed:17634333, PubMed:17925011).
CC Response to toxins that are selective for KCNA1, respectively for
CC KCNA2, suggests that heteromeric potassium channels composed of both
CC KCNA1 and KCNA2 play a role in pacemaking and regulate the output of
CC deep cerebellar nuclear neurons (By similarity). Response to toxins
CC that are selective for KCNA2-containing potassium channels suggests
CC that in Purkinje cells, dendritic subthreshold KCNA2-containing
CC potassium channels prevent random spontaneous calcium spikes,
CC suppressing dendritic hyperexcitability without hindering the
CC generation of somatic action potentials, and thereby play an important
CC role in motor coordination (By similarity). KCNA2-containing channels
CC play a role in GABAergic transmission from basket cells to Purkinje
CC cells in the cerebellum, and thereby play an import role in motor
CC coordination (PubMed:20696761). Plays a role in the induction of long-
CC term potentiation of neuron excitability in the CA3 layer of the
CC hippocampus (PubMed:23981714). May function as down-stream effector for
CC G protein-coupled receptors and inhibit GABAergic inputs to basolateral
CC amygdala neurons (By similarity). May contribute to the regulation of
CC neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By
CC similarity). Contributes to the regulation of the axonal release of the
CC neurotransmitter dopamine (PubMed:21233214). Reduced KCNA2 expression
CC plays a role in the perception of neuropathic pain after peripheral
CC nerve injury, but not acute pain (By similarity). Plays a role in the
CC regulation of the time spent in non-rapid eye movement (NREM) sleep
CC (PubMed:17925011). {ECO:0000250, ECO:0000269|PubMed:12527813,
CC ECO:0000269|PubMed:17634333, ECO:0000269|PubMed:17925011,
CC ECO:0000269|PubMed:20696761, ECO:0000269|PubMed:21233214,
CC ECO:0000269|PubMed:23864368, ECO:0000269|PubMed:23981714, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Inhibited by 4-aminopyridine (4-AP), dendrotoxin
CC (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By
CC similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin
CC that is highly specific for KCNA2 (By similarity). Inhibited by
CC maurotoxin (PubMed:12527813). Inhibited by kappaM conotoxins kappaM-
CC RIIIJ and kappaM-RIIIK (By similarity). {ECO:0000250|UniProtKB:P16389,
CC ECO:0000250|UniProtKB:P63142, ECO:0000269|PubMed:12527813}.
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 Chinese hamster ovary (CHO) cells, the voltage at half-
CC maximal amplitude is about -37 mV. {ECO:0000269|PubMed:20696761};
CC -!- SUBUNIT: Homotetramer and heterotetramer with other channel-forming
CC alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7
CC (PubMed:8361541, PubMed:9852577, PubMed:23864368). Channel activity is
CC regulated by interaction with beta subunits, including KCNAB1 and
CC KCNAB2 (By similarity). Identified in a complex with KCNA1 and KCNAB2
CC (By similarity). Identified in a complex with KCNA5 and KCNAB1 (By
CC similarity). Identified in a complex with KCNA4 and FYN (By
CC similarity). Interacts with PTK2B (By similarity). Interacts (via C-
CC terminus) with CTTN (By similarity). Interacts with ADAM22 (By
CC similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-
CC terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity).
CC Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound
CC form); this regulates channel activity by reducing location at the cell
CC surface in response to CHRM1 activation (PubMed:9635436). Interacts
CC with DRD2 (PubMed:21233214). Interacts with SIGMAR1; cocaine
CC consumption leads to increased interaction (PubMed:23332758).
CC {ECO:0000250|UniProtKB:P16389, ECO:0000250|UniProtKB:P63142,
CC ECO:0000250|UniProtKB:Q09081, ECO:0000269|PubMed:17634333,
CC ECO:0000269|PubMed:21233214, ECO:0000269|PubMed:23332758,
CC ECO:0000269|PubMed:8361541, ECO:0000269|PubMed:9635436,
CC ECO:0000269|PubMed:9852577, ECO:0000305, ECO:0000305|PubMed:23864368}.
CC -!- INTERACTION:
CC P63141; Q60598: Cttn; NbExp=3; IntAct=EBI-644033, EBI-397955;
CC P63141; O55242: Sigmar1; NbExp=3; IntAct=EBI-644033, EBI-1557700;
CC P63141; Q9R0C9: Sigmar1; Xeno; NbExp=3; IntAct=EBI-644033, EBI-1557826;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12527813,
CC ECO:0000269|PubMed:18509034, ECO:0000269|PubMed:20696761,
CC ECO:0000269|PubMed:23332758, ECO:0000269|PubMed:23864368}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P63142}. Membrane
CC {ECO:0000269|PubMed:23332758, ECO:0000269|PubMed:8361541,
CC ECO:0000269|PubMed:9852577}. Cell projection, axon
CC {ECO:0000269|PubMed:18509034, ECO:0000269|PubMed:21233214,
CC ECO:0000269|PubMed:8046438, ECO:0000269|PubMed:8361541}. Synapse
CC {ECO:0000250|UniProtKB:P63142}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P63142}. Cell projection, lamellipodium membrane
CC {ECO:0000250|UniProtKB:P63142}. Synapse, synaptosome
CC {ECO:0000269|PubMed:21233214}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:21233214}. Cell projection, dendrite
CC {ECO:0000269|PubMed:8046438}. Perikaryon {ECO:0000269|PubMed:8046438}.
CC Cell junction, paranodal septate junction
CC {ECO:0000269|PubMed:25378149}. Note=KCNA2 by itself is detected both at
CC the endoplasmic reticulum and at the cell membrane. Coexpression with
CC KCNA4 or with beta subunits promotes expression at the cell membrane.
CC Coexpression with KCNA1 inhibits cell surface expression (By
CC similarity). Cocaine-induced interaction with SIGMAR1 increases
CC expression at the cell surface (PubMed:23332758). 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 (PubMed:25378149). {ECO:0000250|UniProtKB:P63142,
CC ECO:0000269|PubMed:23332758, ECO:0000269|PubMed:25378149}.
CC -!- TISSUE SPECIFICITY: Detected in brain (PubMed:17634333). Detected in
CC cerebellum (PubMed:20696761). Detected in mitral cells in the olfactory
CC bulb (PubMed:8046438). Detected in cochlea (PubMed:23864368). Detected
CC in cerebellum, particularly in the basket cell axon plexus and in the
CC terminal regions around Purkinje cells (PubMed:8361541, PubMed:8046438,
CC PubMed:18760366). Detected in juxtaparanodal regions in sciatic nerve
CC (PubMed:22649228). Detected in Schwann cells from sciatic nerve
CC (PubMed:9852577). Detected in dopamine neurons in substantia nigra
CC (PubMed:21233214). Detected in large myelinated fibers in
CC juxtaparanodes in the CA3 and CA1 areas of the hippocampus
CC (PubMed:8046438, PubMed:18760366). Detected in brain, in punctae on
CC fiber tracts in brain stem and spinal cord, and on axons in the
CC juxtaparanodal regions of the node of Ranvier (at protein level)
CC (PubMed:8361541). Detected in dopamine neurons in the midbrain
CC (PubMed:21233214). {ECO:0000269|PubMed:17634333,
CC ECO:0000269|PubMed:18760366, ECO:0000269|PubMed:20696761,
CC ECO:0000269|PubMed:22649228, ECO:0000269|PubMed:23864368,
CC ECO:0000269|PubMed:8046438, ECO:0000269|PubMed:8361541,
CC ECO:0000269|PubMed:9852577}.
CC -!- DEVELOPMENTAL STAGE: Detected at low levels in brainstem from neonates;
CC increases tenfold during the first 29 days after birth.
CC {ECO:0000269|PubMed:17634333}.
CC -!- DOMAIN: The cytoplasmic N-terminus is important for tetramerization.
CC Interactions between the different subunits modulate the gating
CC characteristics (By similarity). Besides, the cytoplasmic N-terminal
CC domain mediates interaction with RHOA and thus is required for RHOA-
CC mediated endocytosis (By similarity). {ECO:0000250|UniProtKB:P63142}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- PTM: Phosphorylated on tyrosine residues; phosphorylation increases in
CC response to ischemia (By similarity). Phosphorylated on tyrosine
CC residues by activated PTK2B/PYK2 (By similarity). Phosphorylation on
CC tyrosine residues suppresses ion channel activity (By similarity).
CC Phosphorylated on tyrosine residues in response to CHRM1 activation;
CC this abolishes interaction with CTTN. This is probably due to
CC endocytosis of the phosphorylated channel subunits (By similarity).
CC Phosphorylated on serine residues in response to increased cAMP levels;
CC phosphorylation is apparently not catalyzed by PKA (By similarity).
CC {ECO:0000250|UniProtKB:P63142}.
CC -!- PTM: N-glycosylated, with complex, sialylated N-glycans.
CC {ECO:0000250|UniProtKB:P63142}.
CC -!- DISRUPTION PHENOTYPE: Pups are born at the expected Mendelian rate and
CC appear normal during the first 14 days after birth. Starting at 14 to
CC 17 days after birth, mice exhibit susceptibility to generalized
CC seizures, followed by full tonic extension, which in mice often results
CC in fatal apne. The average lifespan is 17 days; none survive more than
CC 28 days (PubMed:17925011, PubMed:17634333). At P17 seizures are very
CC rare and abnormal electroencephalograph activity is only present during
CC the seizure. P17 pups have significantly less non-rapid eye movement
CC (NREM) sleep (-23%) and significantly more waking (+21%) than wild-type
CC siblings with no change in rapid eye movement (REM) sleep time. The
CC decrease in NREM sleep is due to an increase in the number of waking
CC episodes, with no change in number or duration of sleep episodes
CC (PubMed:17925011). Auditory neurons from the medial nucleus of the
CC trapezoid body in brain stem are hypoexcitable and fire fewer action
CC potentials than wild-type neurons with significantly smaller threshold
CC current amplitudes (PubMed:17634333). In the inner ear, spiral ganglion
CC neurons display a hyperpolarized resting membrane potential, increased
CC excitability and increased outward potassium currents; this might be
CC because normally channels there are heterotetramers formed by KCNA2 and
CC KCNA4, so the loss of KCNA2 changes channel characteristics
CC (PubMed:23864368). {ECO:0000269|PubMed:17634333,
CC ECO:0000269|PubMed:17925011, ECO:0000269|PubMed:23864368}.
CC -!- MISCELLANEOUS: Mutagenesis with N-ethyl-N-nitrosourea (ENU) lead to the
CC discovery of the Pingu (Pgu) phenotype. At P21, heterozygous mice are
CC clearly smaller than wild-type and have abnormal gait with a higher
CC stance and splayed hind limbs. Homozygous mice are even smaller, and
CC about half of them die between P15 and P35. Mutant mice have difficulty
CC staing on a rotating rod and perform poorly in a beam-walking test,
CC where they display flattened posture, severe tremors, myoclonic jerks
CC and ataxic movement. These symptoms are alleviated by a drug used to
CC treat cerebellar ataxia. Measurements with Purkinje cells from
CC cerebellar brain slices show increased frequency and amplitude of
CC spontaneous inhibitory postsynaptic currents.
CC {ECO:0000269|PubMed:20696761}.
CC -!- MISCELLANEOUS: The delay or D-type current observed in hippocampus
CC pyramidal neurons is probably mediated by potassium channels containing
CC KCNA2 plus KCNA1 or other family members. It is activated at about -50
CC mV, i.e. below the action potential threshold, and is characterized by
CC slow inactivation, extremely slow recovery from inactivation,
CC sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).
CC {ECO:0000305|PubMed:17917103}.
CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) (TC
CC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; M30440; AAA39713.1; -; Genomic_DNA.
DR EMBL; AK044342; BAC31877.1; -; mRNA.
DR EMBL; CH466607; EDL01892.1; -; Genomic_DNA.
DR EMBL; BC138650; AAI38651.1; -; mRNA.
DR EMBL; BC138651; AAI38652.1; -; mRNA.
DR CCDS; CCDS17733.1; -.
DR PIR; B40090; I84204.
DR RefSeq; NP_032443.3; NM_008417.5.
DR RefSeq; XP_006501111.1; XM_006501048.3.
DR RefSeq; XP_006501112.1; XM_006501049.3.
DR RefSeq; XP_006501113.1; XM_006501050.3.
DR RefSeq; XP_006501114.1; XM_006501051.3.
DR RefSeq; XP_006501115.1; XM_006501052.3.
DR RefSeq; XP_006501116.1; XM_006501053.3.
DR RefSeq; XP_006501117.1; XM_006501054.3.
DR RefSeq; XP_006501118.1; XM_006501055.3.
DR PDB; 5WIE; X-ray; 3.30 A; B/H=266-279.
DR PDBsum; 5WIE; -.
DR AlphaFoldDB; P63141; -.
DR SMR; P63141; -.
DR BioGRID; 200877; 5.
DR DIP; DIP-32239N; -.
DR IntAct; P63141; 7.
DR STRING; 10090.ENSMUSP00000041702; -.
DR GlyGen; P63141; 1 site.
DR iPTMnet; P63141; -.
DR PhosphoSitePlus; P63141; -.
DR SwissPalm; P63141; -.
DR EPD; P63141; -.
DR MaxQB; P63141; -.
DR PaxDb; P63141; -.
DR PeptideAtlas; P63141; -.
DR PRIDE; P63141; -.
DR ProteomicsDB; 263395; -.
DR ABCD; P63141; 3 sequenced antibodies.
DR Antibodypedia; 4539; 291 antibodies from 31 providers.
DR DNASU; 16490; -.
DR Ensembl; ENSMUST00000038695; ENSMUSP00000041702; ENSMUSG00000040724.
DR Ensembl; ENSMUST00000196403; ENSMUSP00000142873; ENSMUSG00000040724.
DR Ensembl; ENSMUST00000197470; ENSMUSP00000143798; ENSMUSG00000040724.
DR GeneID; 16490; -.
DR KEGG; mmu:16490; -.
DR UCSC; uc008qws.2; mouse.
DR CTD; 3737; -.
DR MGI; MGI:96659; Kcna2.
DR VEuPathDB; HostDB:ENSMUSG00000040724; -.
DR eggNOG; KOG1545; Eukaryota.
DR GeneTree; ENSGT00940000158688; -.
DR InParanoid; P63141; -.
DR OMA; HPLDYDP; -.
DR OrthoDB; 695337at2759; -.
DR PhylomeDB; P63141; -.
DR TreeFam; TF313103; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR BioGRID-ORCS; 16490; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Kcna2; mouse.
DR PRO; PR:P63141; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P63141; protein.
DR Bgee; ENSMUSG00000040724; Expressed in lateral geniculate body and 148 other tissues.
DR Genevisible; P63141; MM.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043194; C:axon initial segment; IDA:MGI.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0044305; C:calyx of Held; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:UniProtKB.
DR GO; GO:0033010; C:paranodal junction; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0034705; C:potassium channel complex; ISO:MGI.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; ISO:MGI.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; ISO:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; ISS:UniProtKB.
DR GO; GO:0021633; P:optic nerve structural organization; IMP:MGI.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0045188; P:regulation of circadian sleep/wake cycle, non-REM sleep; IMP:UniProtKB.
DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003972; K_chnl_volt-dep_Kv1.
DR InterPro; IPR004049; K_chnl_volt-dep_Kv1.2.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF23; PTHR11537:SF23; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01509; KV12CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01496; SHAKERCHANEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cell membrane; Cell projection;
KW Endoplasmic reticulum; 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_0000053973"
FT TOPO_DOM 1..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 161..182
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 183..221
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 222..243
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 244..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 255..275
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 276..289
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 290..310
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 311..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 326..347
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 348..361
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 362..373
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 374..381
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 382..388
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 389..417
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 418..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..125
FT /note="Tetramerization domain"
FT /evidence="ECO:0000250|UniProtKB:P63142"
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:0000250|UniProtKB:P63142"
FT MOTIF 374..379
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 497..499
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT SITE 252
FT /note="Important for normal, slow channel gating"
FT /evidence="ECO:0000250|UniProtKB:P63142"
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:0000250|UniProtKB:P63142"
FT MOD_RES 429
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q09081"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q09081"
FT MOD_RES 458
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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"
FT MUTAGEN 402
FT /note="I->T: In Pgu; chronic motor incoordination;
FT decreases the number of functional channels at the cell
FT surface."
FT /evidence="ECO:0000269|PubMed:20696761"
FT CONFLICT 33
FT /note="E -> G (in Ref. 2; BAC31877)"
FT /evidence="ECO:0000305"
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
