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Protein

Potassium voltage-gated channel subfamily A member 2

Gene

Kcna2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:12527813, PubMed:21233214). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20696761). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:23864368). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:23864368). Contributes to the regulation of action potentials in neurons (PubMed:12527813, PubMed:17925011). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:17634333, PubMed:17925011). Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). KCNA2-containing channels play a role in GABAergic transmission from basket cells to Purkinje cells in the cerebellum, and thereby play an import role in motor coordination (PubMed:20696761). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (PubMed:23981714). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21233214). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (PubMed:17925011).By similarityCurated7 Publications

Enzyme regulationi

Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (PubMed:12527813). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity).By similarity1 Publication

Kineticsi

Homotetrameric channels activate rapidly, i.e within a few msec, but inactivation is very slow, with only a marginal decrease in conductance over several seconds. The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, post-translational modifications and the presence or absence of ancillary subunits. For the activation of homotetrameric channels expressed in Chinese hamster ovary (CHO) cells, the voltage at half-maximal amplitude is about -37 mV.1 Publication

      Sites

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Sitei252 – 2521Important for normal, slow channel gatingBy similarity

      GO - Molecular functioni

      GO - Biological processi

      • neuronal action potential Source: UniProtKB
      • optic nerve structural organization Source: MGI
      • potassium ion transmembrane transport Source: UniProtKB
      • protein homooligomerization Source: InterPro
      • regulation of circadian sleep/wake cycle, non-REM sleep Source: UniProtKB
      • regulation of dopamine secretion Source: UniProtKB
      • sensory perception of pain Source: UniProtKB
      Complete GO annotation...

      Keywords - Molecular functioni

      Ion channel, Potassium channel, Voltage-gated channel

      Keywords - Biological processi

      Ion transport, Potassium transport, Transport

      Keywords - Ligandi

      Potassium

      Enzyme and pathway databases

      ReactomeiREACT_287159. Voltage gated Potassium channels.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium voltage-gated channel subfamily A member 2
      Alternative name(s):
      MK21 Publication
      Voltage-gated potassium channel subunit Kv1.2
      Gene namesi
      Name:Kcna2
      OrganismiMus musculus (Mouse)
      Taxonomic identifieri10090 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
      ProteomesiUP000000589 Componenti: Chromosome 3

      Organism-specific databases

      MGIiMGI:96659. Kcna2.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 160160CytoplasmicBy similarityAdd
      BLAST
      Transmembranei161 – 18222Helical; Name=Segment S1By similarityAdd
      BLAST
      Topological domaini183 – 22139ExtracellularBy similarityAdd
      BLAST
      Transmembranei222 – 24322Helical; Name=Segment S2By similarityAdd
      BLAST
      Topological domaini244 – 25411CytoplasmicBy similarityAdd
      BLAST
      Transmembranei255 – 27521Helical; Name=Segment S3By similarityAdd
      BLAST
      Topological domaini276 – 28914ExtracellularBy similarityAdd
      BLAST
      Transmembranei290 – 31021Helical; Voltage-sensor; Name=Segment S4By similarityAdd
      BLAST
      Topological domaini311 – 32515CytoplasmicBy similarityAdd
      BLAST
      Transmembranei326 – 34722Helical; Name=Segment S5By similarityAdd
      BLAST
      Topological domaini348 – 36114ExtracellularBy similarityAdd
      BLAST
      Intramembranei362 – 37312Helical; Name=Pore helixBy similarityAdd
      BLAST
      Intramembranei374 – 3818By similarity
      Topological domaini382 – 3887ExtracellularBy similarity
      Transmembranei389 – 41729Helical; Name=Segment S6By similarityAdd
      BLAST
      Topological domaini418 – 49982CytoplasmicBy similarityAdd
      BLAST

      GO - Cellular componenti

      • axon Source: UniProtKB
      • axon terminus Source: UniProtKB
      • cell junction Source: UniProtKB-KW
      • dendrite Source: UniProtKB
      • endoplasmic reticulum membrane Source: UniProtKB-SubCell
      • integral component of plasma membrane Source: UniProtKB
      • juxtaparanode region of axon Source: BHF-UCL
      • lamellipodium Source: UniProtKB
      • lamellipodium membrane Source: UniProtKB-SubCell
      • neuronal cell body membrane Source: UniProtKB
      • perikaryon Source: UniProtKB
      • presynaptic membrane Source: UniProtKB-SubCell
      • voltage-gated potassium channel complex Source: BHF-UCL
      Complete GO annotation...

      Keywords - Cellular componenti

      Cell junction, Cell membrane, Cell projection, Endoplasmic reticulum, Membrane, Synapse, Synaptosome

      Pathology & Biotechi

      Disruption phenotypei

      Pups are born at the expected Mendelian rate and appear normal during the first 14 days after birth. Starting at 14 to 17 days after birth, mice exhibit susceptibility to generalized seizures, followed by full tonic extension, which in mice often results in fatal apne. The average lifespan is 17 days; none survive more than 28 days (PubMed:17925011, PubMed:17634333). At P17 seizures are very rare and abnormal electroencephalograph activity is only present during the seizure. P17 pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than wild-type siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes (PubMed:17925011). Auditory neurons from the medial nucleus of the trapezoid body in brain stem are hypoexcitable and fire fewer action potentials than wild-type neurons with significantly smaller threshold current amplitudes (PubMed:17634333). In the inner ear, spiral ganglion neurons display a hyperpolarized resting membrane potential, increased excitability and increased outward potassium currents; this might be because normally channels there are heterotetramers formed by KCNA2 and KCNA4, so the loss of KCNA2 changes channel characteristics (PubMed:23864368).3 Publications

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi402 – 4021I → T in Pgu; chronic motor incoordination; decreases the number of functional channels at the cell surface. 1 Publication

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 499499Potassium voltage-gated channel subfamily A member 2PRO_0000053973Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Glycosylationi207 – 2071N-linked (GlcNAc...)Sequence Analysis
      Lipidationi244 – 2441S-palmitoyl cysteineSequence Analysis
      Modified residuei429 – 4291Phosphotyrosine1 Publication
      Modified residuei440 – 4401PhosphoserineBy similarity
      Modified residuei441 – 4411PhosphoserineBy similarity
      Modified residuei449 – 4491PhosphoserineBy similarity
      Modified residuei458 – 4581PhosphotyrosineBy similarity

      Post-translational modificationi

      Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (By similarity). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (By similarity). Phosphorylation on tyrosine residues suppresses ion channel activity (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN. This is probably due to endocytosis of the phosphorylated channnel subunits (By similarity). Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (By similarity).By similarity
      N-glycosylated, with complex, sialylated N-glycans.By similarity

      Keywords - PTMi

      Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

      Proteomic databases

      MaxQBiP63141.
      PaxDbiP63141.
      PRIDEiP63141.

      Expressioni

      Tissue specificityi

      Detected in brain (PubMed:17634333). Detected in cerebellum (PubMed:20696761). Detected in mitral cells in the olfactory bulb (PubMed:8046438). Detected in cochlea (PubMed:23864368). Detected in cerebellum, particularly in the basket cell axon plexus and in the terminal regions around Purkinje cells (PubMed:8361541, PubMed:8046438, PubMed:18760366). Detected in juxtaparanodal regions in sciatic nerve (PubMed:22649228). Detected in Schwann cells from sciatic nerve (PubMed:9852577). Detected in dopamine neurons in substantia nigra (PubMed:21233214). Detected in large myelinated fibers in juxtaparanodes in the CA3 and CA1 areas of the hippocampus (PubMed:8046438, PubMed:18760366). Detected in brain, in punctae on fiber tracts in brain stem and spinal cord, and on axons in the juxtaparanodal regions of the node of Ranvier (at protein level) (PubMed:8361541). Detected in dopamine neurons in the midbrain (PubMed:21233214).8 Publications

      Developmental stagei

      Detected at low levels in brainstem from neonates; increases tenfold during the first 29 days after birth.1 Publication

      Gene expression databases

      BgeeiP63141.
      ExpressionAtlasiP63141. baseline and differential.
      GenevisibleiP63141. MM.

      Interactioni

      Subunit structurei

      Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8361541, PubMed:9852577, PubMed:23864368). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (By similarity). Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts with PTK2B (By similarity). Interacts (via C-terminus) with CTTN (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (PubMed:9635436). Interacts with DRD2 (PubMed:21233214). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (PubMed:23332758).By similarityCurated6 Publications

      Binary interactionsi

      WithEntry#Exp.IntActNotes
      Sigmar1O552423EBI-644033,EBI-1557700
      Sigmar1Q9R0C93EBI-644033,EBI-1557826From a different organism.

      Protein-protein interaction databases

      BioGridi200877. 3 interactions.
      DIPiDIP-32239N.
      IntActiP63141. 5 interactions.
      MINTiMINT-1659109.
      STRINGi10090.ENSMUSP00000041702.

      Structurei

      3D structure databases

      ProteinModelPortaliP63141.
      SMRiP63141. Positions 3-421.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni1 – 125125Tetramerization domainBy similarityAdd
      BLAST
      Regioni312 – 32514S4-S5 linkerBy similarityAdd
      BLAST

      Motif

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Motifi374 – 3796Selectivity filterBy similarity
      Motifi497 – 4993PDZ-bindingBy similarity

      Domaini

      The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (By similarity). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (By similarity).By similarity
      The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.By similarity

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiCOG1226.
      GeneTreeiENSGT00760000118846.
      HOGENOMiHOG000231015.
      HOVERGENiHBG052230.
      InParanoidiP63141.
      KOiK04875.
      OMAiMTFHTYS.
      OrthoDBiEOG7M0NRD.
      PhylomeDBiP63141.
      TreeFamiTF313103.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ-like.
      IPR011333. BTB/POZ_fold.
      IPR027359. Channel_four-helix_dom.
      IPR005821. Ion_trans_dom.
      IPR003091. K_chnl.
      IPR003968. K_chnl_volt-dep_Kv.
      IPR003972. K_chnl_volt-dep_Kv1.
      IPR004049. K_chnl_volt-dep_Kv1.2.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 1 hit.
      PfamiPF02214. BTB_2. 1 hit.
      PF00520. Ion_trans. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01509. KV12CHANNEL.
      PR01491. KVCHANNEL.
      PR01496. SHAKERCHANEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.

      Sequencei

      Sequence statusi: Complete.

      P63141-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MTVATGDPVD EAAALPGHPQ DTYDPEADHE CCERVVINIS GLRFETQLKT
      60 70 80 90 100
      LAQFPETLLG DPKKRMRYFD PLRNEYFFDR NRPSFDAILY YYQSGGRLRR
      110 120 130 140 150
      PVNVPLDIFS EEIRFYELGE EAMEMFREDE GYIKEEERPL PENEFQRQVW
      160 170 180 190 200
      LLFEYPESSG PARIIAIVSV MVILISIVSF CLETLPIFRD ENEDMHGGGV
      210 220 230 240 250
      TFHTYSNSTI GYQQSTSFTD PFFIVETLCI IWFSFEFLVR FFACPSKAGF
      260 270 280 290 300
      FTNIMNIIDI VAIIPYFITL GTELAEKPED AQQGQQAMSL AILRVIRLVR
      310 320 330 340 350
      VFRIFKLSRH SKGLQILGQT LKASMRELGL LIFFLFIGVI LFSSAVYFAE
      360 370 380 390 400
      ADERDSQFPS IPDAFWWAVV SMTTVGYGDM VPTTIGGKIV GSLCAIAGVL
      410 420 430 440 450
      TIALPVPVIV SNFNYFYHRE TEGEEQAQYL QVTSCPKIPS SPDLKKSRSA
      460 470 480 490
      STISKSDYME IQEGVNNSNE DFREENLKTA NCTLANTNYV NITKMLTDV
      Length:499
      Mass (Da):56,701
      Last modified:September 13, 2004 - v1
      Checksum:iA8FEA6F3F59AF42A
      GO

      Experimental Info

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Sequence conflicti33 – 331E → G in BAC31877 (PubMed:16141072).Curated

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      M30440 Genomic DNA. Translation: AAA39713.1.
      AK044342 mRNA. Translation: BAC31877.1.
      CH466607 Genomic DNA. Translation: EDL01892.1.
      BC138650 mRNA. Translation: AAI38651.1.
      BC138651 mRNA. Translation: AAI38652.1.
      CCDSiCCDS17733.1.
      PIRiB40090. I84204.
      RefSeqiNP_032443.3. NM_008417.5.
      XP_006501111.1. XM_006501048.2.
      XP_006501112.1. XM_006501049.2.
      XP_006501113.1. XM_006501050.2.
      XP_006501114.1. XM_006501051.2.
      XP_006501115.1. XM_006501052.2.
      XP_006501116.1. XM_006501053.2.
      XP_006501117.1. XM_006501054.2.
      XP_006501118.1. XM_006501055.2.
      UniGeneiMm.39285.

      Genome annotation databases

      EnsembliENSMUST00000038695; ENSMUSP00000041702; ENSMUSG00000040724.
      ENSMUST00000196403; ENSMUSP00000142873; ENSMUSG00000040724.
      GeneIDi16490.
      KEGGimmu:16490.
      UCSCiuc008qws.2. mouse.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      M30440 Genomic DNA. Translation: AAA39713.1.
      AK044342 mRNA. Translation: BAC31877.1.
      CH466607 Genomic DNA. Translation: EDL01892.1.
      BC138650 mRNA. Translation: AAI38651.1.
      BC138651 mRNA. Translation: AAI38652.1.
      CCDSiCCDS17733.1.
      PIRiB40090. I84204.
      RefSeqiNP_032443.3. NM_008417.5.
      XP_006501111.1. XM_006501048.2.
      XP_006501112.1. XM_006501049.2.
      XP_006501113.1. XM_006501050.2.
      XP_006501114.1. XM_006501051.2.
      XP_006501115.1. XM_006501052.2.
      XP_006501116.1. XM_006501053.2.
      XP_006501117.1. XM_006501054.2.
      XP_006501118.1. XM_006501055.2.
      UniGeneiMm.39285.

      3D structure databases

      ProteinModelPortaliP63141.
      SMRiP63141. Positions 3-421.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi200877. 3 interactions.
      DIPiDIP-32239N.
      IntActiP63141. 5 interactions.
      MINTiMINT-1659109.
      STRINGi10090.ENSMUSP00000041702.

      Proteomic databases

      MaxQBiP63141.
      PaxDbiP63141.
      PRIDEiP63141.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENSMUST00000038695; ENSMUSP00000041702; ENSMUSG00000040724.
      ENSMUST00000196403; ENSMUSP00000142873; ENSMUSG00000040724.
      GeneIDi16490.
      KEGGimmu:16490.
      UCSCiuc008qws.2. mouse.

      Organism-specific databases

      CTDi3737.
      MGIiMGI:96659. Kcna2.

      Phylogenomic databases

      eggNOGiCOG1226.
      GeneTreeiENSGT00760000118846.
      HOGENOMiHOG000231015.
      HOVERGENiHBG052230.
      InParanoidiP63141.
      KOiK04875.
      OMAiMTFHTYS.
      OrthoDBiEOG7M0NRD.
      PhylomeDBiP63141.
      TreeFamiTF313103.

      Enzyme and pathway databases

      ReactomeiREACT_287159. Voltage gated Potassium channels.

      Miscellaneous databases

      ChiTaRSiKcna2. mouse.
      NextBioi289787.
      PROiP63141.
      SOURCEiSearch...

      Gene expression databases

      BgeeiP63141.
      ExpressionAtlasiP63141. baseline and differential.
      GenevisibleiP63141. MM.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ-like.
      IPR011333. BTB/POZ_fold.
      IPR027359. Channel_four-helix_dom.
      IPR005821. Ion_trans_dom.
      IPR003091. K_chnl.
      IPR003968. K_chnl_volt-dep_Kv.
      IPR003972. K_chnl_volt-dep_Kv1.
      IPR004049. K_chnl_volt-dep_Kv1.2.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 1 hit.
      PfamiPF02214. BTB_2. 1 hit.
      PF00520. Ion_trans. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01509. KV12CHANNEL.
      PR01491. KVCHANNEL.
      PR01496. SHAKERCHANEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.
      ProtoNetiSearch...

      Publicationsi

      « Hide 'large scale' publications
      1. "A family of three mouse potassium channel genes with intronless coding regions."
        Chandy K.G., Williams C.B., Spencer R.H., Aguilar B.A., Ghanshani S., Tempel B.L., Gutman G.A.
        Science 247:973-975(1990) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      2. "The transcriptional landscape of the mammalian genome."
        Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
        , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
        Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Strain: C57BL/6J.
        Tissue: Retina.
      3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
        Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
        The MGC Project Team
        Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Tissue: BrainImported.
      5. "Expression of voltage-gated K+ channels in insulin-producing cells. Analysis by polymerase chain reaction."
        Betsholtz C., Baumann A., Kenna S., Ashcroft F.M., Ashcroft S.J.H., Berggren P.-O., Grupe A., Pongs O., Rorsman P., Sandblom J., Welsh M.
        FEBS Lett. 263:121-126(1990) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 338-394.
      6. "Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons."
        Wang H., Kunkel D.D., Martin T.M., Schwartzkroin P.A., Tempel B.L.
        Nature 365:75-79(1993) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBUNIT, INTERACTION WITH KCNA1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
      7. "Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain."
        Wang H., Kunkel D.D., Schwartzkroin P.A., Tempel B.L.
        J. Neurosci. 14:4588-4599(1994) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
      8. "The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel."
        Cachero T.G., Morielli A.D., Peralta E.G.
        Cell 93:1077-1085(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH RHOA.
      9. "Heteromultimeric delayed-rectifier K+ channels in Schwann cells: developmental expression and role in cell proliferation."
        Sobko A., Peretz A., Shirihai O., Etkin S., Cherepanova V., Dagan D., Attali B.
        J. Neurosci. 18:10398-10408(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH KCNA5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      10. "Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels."
        Castle N.A., London D.O., Creech C., Fajloun Z., Stocker J.W., Sabatier J.-M.
        Mol. Pharmacol. 63:409-418(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
      11. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
      12. "Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons."
        Brew H.M., Gittelman J.X., Silverstein R.S., Hanks T.D., Demas V.P., Robinson L.C., Robbins C.A., McKee-Johnson J., Chiu S.Y., Messing A., Tempel B.L.
        J. Neurophysiol. 98:1501-1525(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
      13. "Ionic channel function in action potential generation: current perspective."
        Baranauskas G.
        Mol. Neurobiol. 35:129-150(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: REVIEW.
      14. "Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2."
        Ogawa Y., Horresh I., Trimmer J.S., Bredt D.S., Peles E., Rasband M.N.
        J. Neurosci. 28:5731-5739(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION.
      15. "Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
        Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
        J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-429, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
        Tissue: Brain.
      16. "Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes."
        Savvaki M., Panagiotaropoulos T., Stamatakis A., Sargiannidou I., Karatzioula P., Watanabe K., Stylianopoulou F., Karagogeos D., Kleopa K.A.
        Mol. Cell. Neurosci. 39:478-490(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY.
      17. Cited for: FUNCTION, MUTAGENESIS OF ILE-402, SUBCELLULAR LOCATION, MISCELLANEOUS, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
      18. "Contribution of Kv1.2 voltage-gated potassium channel to D2 autoreceptor regulation of axonal dopamine overflow."
        Fulton S., Thibault D., Mendez J.A., Lahaie N., Tirotta E., Borrelli E., Bouvier M., Tempel B.L., Trudeau L.E.
        J. Biol. Chem. 286:9360-9372(2011) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH DRD2.
      19. "Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus."
        Zenker J., Poirot O., de Preux Charles A.S., Arnaud E., Medard J.J., Lacroix C., Kuntzer T., Chrast R.
        J. Neurosci. 32:7493-7498(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY.
      20. "Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine."
        Kourrich S., Hayashi T., Chuang J.Y., Tsai S.Y., Su T.P., Bonci A.
        Cell 152:236-247(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH SIGMAR1, SUBCELLULAR LOCATION.
      21. "Association of the Kv1 family of K+ channels and their functional blueprint in the properties of auditory neurons as revealed by genetic and functional analyses."
        Wang W., Kim H.J., Lv P., Tempel B., Yamoah E.N.
        J. Neurophysiol. 110:1751-1764(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
      22. "Activity-dependent downregulation of D-type K+ channel subunit Kv1.2 in rat hippocampal CA3 pyramidal neurons."
        Hyun J.H., Eom K., Lee K.H., Ho W.K., Lee S.H.
        J. Physiol. (Lond.) 591:5525-5540(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION.

      Entry informationi

      Entry nameiKCNA2_MOUSE
      AccessioniPrimary (citable) accession number: P63141
      Secondary accession number(s): B2RS05
      , P15386, Q02010, Q8C8W4
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: September 13, 2004
      Last sequence update: September 13, 2004
      Last modified: July 22, 2015
      This is version 121 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      Miscellaneous

      Mutagenesis with N-ethyl-N-nitrosourea (ENU) lead to the discovery of the Pingu (Pgu) phenotype. At P21, heterozygous mice are clearly smaller than wild-type and have abnormal gait with a higher stance and splayed hind limbs. Homozygous mice are even smaller, and about half of them die betwen P15 and P35. Mutant mice have difficulty staing on a rotating rod and perform poorly in a beam-walking test, where they display flattened posture, severe tremors, myoclonic jerks and ataxic movement. These symptoms are alleviated by a drug used to treat cerebellar ataxia. Measurements with Purkinje cells from cerebellar brain slices show increased frequency and amplitude of spontaneous inhibitory postsynaptic currents.1 Publication
      The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).1 Publication

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. MGD cross-references
        Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
      2. SIMILARITY comments
        Index of protein domains and families

      External Data

      Dasty 3

      Similar proteinsi

      Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
      100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
      90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
      50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.