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Potassium voltage-gated channel subfamily A member 2



Mus musculus (Mouse)
Reviewed-Annotation score: -Experimental evidence at protein leveli


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


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 between 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

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


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


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sitei252Important for normal, slow channel gatingBy similarity1
      Sitei381Important for binding with the scorpion mesomartoxin; when the scorpion mesomartoxin-rKv1.2/KCNA2 interaction is modeled, this residue is close to the 'Y-57' residue of the toxinBy similarity1

      GO - Molecular functioni

      GO - Biological processi

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


      Molecular functionIon channel, Potassium channel, Voltage-gated channel
      Biological processIon transport, Potassium transport, Transport

      Enzyme and pathway databases

      ReactomeiR-MMU-1296072 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
      OrganismiMus musculus (Mouse)
      Taxonomic identifieri10090 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
      • UP000000589 Componenti: Chromosome 3

      Organism-specific databases

      MGIiMGI:96659 Kcna2

      Subcellular locationi

      Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Topological domaini1 – 160CytoplasmicBy similarityAdd BLAST160
      Transmembranei161 – 182Helical; Name=Segment S1By similarityAdd BLAST22
      Topological domaini183 – 221ExtracellularBy similarityAdd BLAST39
      Transmembranei222 – 243Helical; Name=Segment S2By similarityAdd BLAST22
      Topological domaini244 – 254CytoplasmicBy similarityAdd BLAST11
      Transmembranei255 – 275Helical; Name=Segment S3By similarityAdd BLAST21
      Topological domaini276 – 289ExtracellularBy similarityAdd BLAST14
      Transmembranei290 – 310Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST21
      Topological domaini311 – 325CytoplasmicBy similarityAdd BLAST15
      Transmembranei326 – 347Helical; Name=Segment S5By similarityAdd BLAST22
      Topological domaini348 – 361ExtracellularBy similarityAdd BLAST14
      Intramembranei362 – 373Helical; Name=Pore helixBy similarityAdd BLAST12
      Intramembranei374 – 381By similarity8
      Topological domaini382 – 388ExtracellularBy similarity7
      Transmembranei389 – 417Helical; Name=Segment S6By similarityAdd BLAST29
      Topological domaini418 – 499CytoplasmicBy similarityAdd BLAST82

      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


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Mutagenesisi402I → T in Pgu; chronic motor incoordination; decreases the number of functional channels at the cell surface. 1 Publication1

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      ChainiPRO_00000539731 – 499Potassium voltage-gated channel subfamily A member 2Add BLAST499

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Glycosylationi207N-linked (GlcNAc...) asparagineSequence analysis1
      Lipidationi244S-palmitoyl cysteineSequence analysis1
      Modified residuei429PhosphotyrosineCombined sources1
      Modified residuei434PhosphoserineCombined sources1
      Modified residuei440PhosphoserineCombined sources1
      Modified residuei441PhosphoserineBy similarity1
      Modified residuei449PhosphoserineBy similarity1
      Modified residuei458PhosphotyrosineBy similarity1
      Modified residuei468PhosphoserineCombined sources1

      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 channel 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


      PTM databases



      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

      GenevisibleiP63141 MM


      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

      Show more details

      GO - Molecular functioni

      Protein-protein interaction databases

      BioGridi200877, 5 interactors
      IntActiP63141, 7 interactors


      3D structure databases


      Family & Domainsi


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Regioni1 – 125Tetramerization domainBy similarityAdd BLAST125
      Regioni312 – 325S4-S5 linkerBy similarityAdd BLAST14


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Motifi374 – 379Selectivity filterBy similarity6
      Motifi497 – 499PDZ-bindingBy similarity3


      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

      eggNOGiKOG1545 Eukaryota
      COG1226 LUCA

      Family and domain databases

      Gene3Di1.20.120.350, 1 hit
      InterProiView protein in InterPro
      IPR000210 BTB/POZ_dom
      IPR005821 Ion_trans_dom
      IPR003968 K_chnl_volt-dep_Kv
      IPR003972 K_chnl_volt-dep_Kv1
      IPR004049 K_chnl_volt-dep_Kv1.2
      IPR011333 SKP1/BTB/POZ_sf
      IPR003131 T1-type_BTB
      IPR028325 VG_K_chnl
      IPR027359 Volt_channel_dom_sf
      PANTHERiPTHR11537 PTHR11537, 1 hit
      PTHR11537:SF23 PTHR11537:SF23, 1 hit
      PfamiView protein in Pfam
      PF02214 BTB_2, 1 hit
      PF00520 Ion_trans, 1 hit
      PR01509 KV12CHANNEL
      PR01491 KVCHANNEL
      SMARTiView protein in SMART
      SM00225 BTB, 1 hit
      SUPFAMiSSF54695 SSF54695, 1 hit


      Sequence statusi: Complete.

      P63141-1 [UniParc]FASTAAdd to basket

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      Mass (Da):56,701
      Last modified:September 13, 2004 - v1

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sequence conflicti33E → G in BAC31877 (PubMed:16141072).Curated1

      Sequence databases

      Select the link destinations:
      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
      PIRiB40090 I84204
      RefSeqiNP_032443.3, NM_008417.5
      XP_006501111.1, XM_006501048.3
      XP_006501112.1, XM_006501049.3
      XP_006501113.1, XM_006501050.3
      XP_006501114.1, XM_006501051.3
      XP_006501115.1, XM_006501052.3
      XP_006501116.1, XM_006501053.3
      XP_006501117.1, XM_006501054.3
      XP_006501118.1, XM_006501055.3

      Genome annotation databases

      EnsembliENSMUST00000038695; ENSMUSP00000041702; ENSMUSG00000040724
      ENSMUST00000196403; ENSMUSP00000142873; ENSMUSG00000040724
      ENSMUST00000197470; ENSMUSP00000143798; ENSMUSG00000040724
      UCSCiuc008qws.2 mouse

      Similar proteinsi

      Entry informationi

      Entry nameiKCNA2_MOUSE
      AccessioniPrimary (citable) accession number: P63141
      Secondary accession number(s): B2RS05
      , P15386, Q02010, Q8C8W4
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2004
      Last sequence update: September 13, 2004
      Last modified: June 20, 2018
      This is version 149 of the entry and version 1 of the sequence. See complete history.
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program


      Keywords - Technical termi

      3D-structure, Complete proteome, Reference proteome


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

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