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Entry version 153 (17 Jun 2020)
Sequence version 1 (13 Sep 2004)
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Protein

Potassium voltage-gated channel subfamily A member 2

Gene

Kcna2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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:12151401, PubMed:21602278, PubMed:24472174). 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:8495559, PubMed:15618540, PubMed:20805574, PubMed:23725331). 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 (PubMed:18003609, PubMed:19713757). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to a 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:1715584, PubMed:16770729, PubMed:17766348, PubMed:18003609, PubMed:18638484, PubMed:19713757, PubMed:20089912). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). 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 (PubMed:23318870). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:12777451). 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 (PubMed:16210348). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (PubMed:16306173). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (PubMed:17869444). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21647367). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (PubMed:24472174). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).By similarityCurated20 Publications

Miscellaneous

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:2555158, PubMed:8495559, PubMed:18638484). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (PubMed:8355670). Inhibited by maurotoxin (PubMed:24472174). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity).By similarity6 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>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 xenopus oocytes, the voltage at half-maximal amplitude is about -34 mV (PubMed:2555158). Unit channel conductance is about 10 pS (PubMed:2555158). For the activation of homotetrameric channels expressed in Chinese hamster ovary (CHO) cells, the voltage at half-maximal amplitude is about -10 mV (PubMed:17324383).2 Publications

      Sites

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei252Important for normal, slow channel gating1 Publication1
      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 toxin1 Publication1

      <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

      GO - Biological processi

      <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

      Enzyme and pathway databases

      Reactome - a knowledgebase of biological pathways and processes

      More...
      Reactomei
      R-RNO-1296072 Voltage gated Potassium channels

      <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

      <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
      Recommended name:
      Potassium voltage-gated channel subfamily A member 2
      Alternative name(s):
      RAK
      RBK21 Publication
      RCK51 Publication
      Voltage-gated potassium channel subunit Kv1.2
      <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
      Name:Kcna2
      <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiRattus norvegicus (Rat)
      <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10116 [NCBI]
      <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
      <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
      • UP000002494 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

      Organism-specific databases

      Rat genome database

      More...
      RGDi
      2950 Kcna2

      <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

      Topology

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 160Cytoplasmic3 PublicationsAdd BLAST160
      <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei161 – 182Helical; Name=Segment S13 PublicationsAdd BLAST22
      Topological domaini183 – 221Extracellular1 Publication3 PublicationsAdd BLAST39
      Transmembranei222 – 243Helical; Name=Segment S23 PublicationsAdd BLAST22
      Topological domaini244 – 254Cytoplasmic3 PublicationsAdd BLAST11
      Transmembranei255 – 275Helical; Name=Segment S32 PublicationsAdd BLAST21
      Topological domaini276 – 289Extracellular3 PublicationsAdd BLAST14
      Transmembranei290 – 310Helical; Voltage-sensor; Name=Segment S42 PublicationsAdd BLAST21
      Topological domaini311 – 325Cytoplasmic3 PublicationsAdd BLAST15
      Transmembranei326 – 347Helical; Name=Segment S53 PublicationsAdd BLAST22
      Topological domaini348 – 361Extracellular3 PublicationsAdd BLAST14
      <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a region that is buried within a membrane, but does not cross it.<p><a href='/help/intramem' target='_top'>More...</a></p>Intramembranei362 – 373Helical; Name=Pore helix3 PublicationsAdd BLAST12
      Intramembranei374 – 3813 Publications8
      Topological domaini382 – 388Extracellular3 Publications7
      Transmembranei389 – 417Helical; Name=Segment S63 PublicationsAdd BLAST29
      Topological domaini418 – 499CytoplasmicCurated1 PublicationAdd BLAST82

      Keywords - Cellular componenti

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

      <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

      Mutagenesis

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi34R → L: No effect on channel opening. 1 Publication1
      Mutagenesisi38N → A: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi40S → A: No effect on channel opening. 1 Publication1
      Mutagenesisi41G → A: Loss of channel activity. 1 Publication1
      Mutagenesisi42L → A: No effect on channel opening. 1 Publication1
      Mutagenesisi43R → L: No effect on channel opening. 1 Publication1
      Mutagenesisi44F → A: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi45E → A: Loss of channel activity. 1 Publication1
      Mutagenesisi46T → D: Impairs protein folding. Loss of tetramerization. 1 Publication1
      Mutagenesisi46T → V or A: No effect on tetramerization. Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi46T → V: Abolishes interaction with KCNAB2 and strongly reduces cell surface expression. No effect phosphorylation in response to increased cAMP levels. 1 Publication1
      Mutagenesisi47Q → A: No effect on channel opening. 1 Publication1
      Mutagenesisi50T → A: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi70D → A: No effect on channel opening. 1 Publication1
      Mutagenesisi73R → A: No effect on channel opening. 1 Publication1
      Mutagenesisi75E → A: No effect on channel opening. 1 Publication1
      Mutagenesisi77F → W: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi79D → N: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi81N → A: No effect on channel opening. 1 Publication1
      Mutagenesisi82R → A: Loss of channel activity. 1 Publication1
      Mutagenesisi86D → A: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi89L → A: No effect on channel opening. 1 Publication1
      Mutagenesisi90Y → A: No effect on channel opening. 1 Publication1
      Mutagenesisi93Q → A: Loss of channel activity. 1 Publication1
      Mutagenesisi97R → A: No effect on channel opening. 1 Publication1
      Mutagenesisi99R → A: No effect on channel opening. 1 Publication1
      Mutagenesisi102V → T: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi103N → A: No effect on channel opening. 1 Publication1
      Mutagenesisi105P → A: No effect on channel opening. 1 Publication1
      Mutagenesisi107D → A: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi108I → A: No effect on channel opening. 1 Publication1
      Mutagenesisi111E → A: Alters voltage-sensitive channel opening. 1 Publication1
      Mutagenesisi207N → Q: Loss of glycosylation site. 1 Publication1
      Mutagenesisi252T → R: Changes channel gating from a predominantly slow mode to a much more rapid mode. 1 Publication1
      Mutagenesisi267 – 302FITLG…LVRVF → YVTIFLTESNKSVLQFQNVR RVVQIFRIM in paddle chimera; changes channel activation to less negative voltage values and renders the channel susceptible to inhibition by the spider toxin VsTx1. 1 PublicationAdd BLAST36
      Mutagenesisi356S → A: Impairs N-glycosylation and abolishes expression at the cell surface. 1 Publication1
      Mutagenesisi360S → A: No effect on N-glycosylation. Abolishes channel activity of the homotetramer, but retains channel activity in the presence of a beta subunit. 1 Publication1
      Mutagenesisi381V → Y: Confers sensitivity to inhibition by tetraethylammonium (TEA). 1 Publication1
      Mutagenesisi383T → A: Impairs N-glycosylation and abolishes expression at the cell surface. 1 Publication1
      Mutagenesisi415Y → F: Nearly abolishes interaction with CTTN; when associated with F-417. 1 Publication1
      Mutagenesisi417Y → F: Nearly abolishes interaction with CTTN; when associated with F-415. Strongly reduces channel activity. 1 Publication1
      Mutagenesisi440S → A: Strongly reduces cell surface expression. Abolishes phosphorylation in response to increased cAMP levels. 1 Publication1
      Mutagenesisi449S → A: Strongly reduces cell surface expression. Abolishes phosphorylation in response to increased cAMP levels. 1 Publication1
      Mutagenesisi458Y → A: Impairs clustering on axon membranes. 1 Publication1

      Chemistry databases

      ChEMBL database of bioactive drug-like small molecules

      More...
      ChEMBLi
      CHEMBL4105982

      DrugCentral

      More...
      DrugCentrali
      P63142

      IUPHAR/BPS Guide to PHARMACOLOGY

      More...
      GuidetoPHARMACOLOGYi
      539

      <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000539751 – 499Potassium voltage-gated channel subfamily A member 2Add BLAST499

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi207N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
      <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi244S-palmitoyl cysteineSequence analysis1
      <p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei429PhosphotyrosineBy similarity1
      Modified residuei434PhosphoserineBy similarity1
      Modified residuei440PhosphoserineCombined sources1 Publication1
      Modified residuei441PhosphoserineCombined sources1
      Modified residuei449Phosphoserine2 Publications1
      Modified residuei458Phosphotyrosine1 Publication1
      Modified residuei468PhosphoserineCombined sources1

      <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

      Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (PubMed:14713306). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (PubMed:7544443). Phosphorylation on tyrosine residues suppresses ion channel activity (PubMed:7544443). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN (PubMed:12151401). This is probably due to endocytosis of the phosphorylated channel subunits. Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (PubMed:18003609).4 Publications
      N-glycosylated, with complex, sialylated N-glycans.2 Publications

      Keywords - PTMi

      Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

      Proteomic databases

      PaxDb, a database of protein abundance averages across all three domains of life

      More...
      PaxDbi
      P63142

      PRoteomics IDEntifications database

      More...
      PRIDEi
      P63142

      PTM databases

      iPTMnet integrated resource for PTMs in systems biology context

      More...
      iPTMneti
      P63142

      Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

      More...
      PhosphoSitePlusi
      P63142

      <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

      <p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

      Detected in neurons in dorsal root ganglion (PubMed:24472174). Detected in hippocampus neurons (PubMed:21602278). Detected on neurons of the anteroventral cochlear nucleus (PubMed:12777451). Detected in renal arteries (PubMed:12632190). Detected in neurons of the medial nucleus of the trapezoid body (PubMed:12177193). Detected in neurons in the brain cortex (PubMed:14713306). Detected in axon tracts of the corpus callosum, specific terminal fields of the brain cortex neuropil, neurons in the medial entorhinal cortex, and in puncta representing mossy fiber terminals in the hippocampus mossy fiber tract; these puncta correspond to synapses made by dentate granule cells (PubMed:8361540). Detected in paranodal and juxtanodal zones in the central nervous system, including myelinated spinal cord (PubMed:11086297, PubMed:20089912). Detected in the juxtaparanodal region in optic nerve (PubMed:10624965). Detected at nerve terminal plexuses of basket cells in the cerebellum (at protein level) (PubMed:7477295, PubMed:20089912). Detected in brain (PubMed:2722779). Detected in heart atrium and ventricle (PubMed:1715584). Detected in renal arteries (PubMed:12632190).12 Publications

      <p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

      Up-regulated in brain cortex in response to ischemia (at protein level) (PubMed:14713306). Down-regulated in dorsal root ganglion neurons after peripheral nerve injury (at protein level) (PubMed:24472174). Down-regulated in pulmonary artery myocytes in response to chronic moderate hypoxia.3 Publications

      Gene expression databases

      Bgee dataBase for Gene Expression Evolution

      More...
      Bgeei
      ENSRNOG00000018285 Expressed in brain and 8 other tissues

      ExpressionAtlas, Differential and Baseline Expression

      More...
      ExpressionAtlasi
      P63142 baseline and differential

      Genevisible search portal to normalized and curated expression data from Genevestigator

      More...
      Genevisiblei
      P63142 RN

      <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

      <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

      Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8495559, PubMed:8361540, PubMed:10896669, PubMed:12777451, PubMed:12632190, PubMed:15618540, PubMed:11007484, PubMed:16002581, PubMed:18004376, PubMed:20534430). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (PubMed:18003609, PubMed:19713757, PubMed:16002581, PubMed:18004376, PubMed:20534430, PubMed:20360102, PubMed:23705070).

      Identified in a complex with KCNA1 and KCNAB2 (PubMed:11086297, PubMed:23318870).

      Identified in a complex with KCNA5 and KCNAB1 (By similarity).

      Identified in a complex with KCNA4 and FYN (By similarity).

      Interacts (via C-terminus) with the PDZ domains of DLG1 and DLG2 (PubMed:7477295).

      Interacts with DLG4 (via PDZ domain) (PubMed:7477295, PubMed:20089912).

      Interacts with PTK2B (PubMed:11739373).

      Interacts (via C-terminus) with CTTN (PubMed:12151401).

      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 (By similarity).

      Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity).

      Interacts with CNTNAP2 (PubMed:10624965).

      Interacts with ADAM22 (PubMed:20089912).

      By similarityCurated20 Publications

      <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

      GO - Molecular functioni

      Protein-protein interaction databases

      The Biological General Repository for Interaction Datasets (BioGRID)

      More...
      BioGRIDi
      247501, 5 interactors

      CORUM comprehensive resource of mammalian protein complexes

      More...
      CORUMi
      P63142

      Protein interaction database and analysis system

      More...
      IntActi
      P63142, 4 interactors

      STRING: functional protein association networks

      More...
      STRINGi
      10116.ENSRNOP00000042653

      Chemistry databases

      BindingDB database of measured binding affinities

      More...
      BindingDBi
      P63142

      <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

      Secondary structure

      1499
      Legend: HelixTurnBeta strandPDB Structure known for this area
      Show more details

      3D structure databases

      SWISS-MODEL Repository - a database of annotated 3D protein structure models

      More...
      SMRi
      P63142

      Database of comparative protein structure models

      More...
      ModBasei
      Search...

      Protein Data Bank in Europe - Knowledge Base

      More...
      PDBe-KBi
      Search...

      Miscellaneous databases

      Relative evolutionary importance of amino acids within a protein sequence

      More...
      EvolutionaryTracei
      P63142

      <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

      Region

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 125Tetramerization domain1 PublicationAdd BLAST125
      Regioni312 – 325S4-S5 linker1 PublicationAdd BLAST14

      Motif

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi374 – 379Selectivity filterCurated6
      Motifi497 – 499PDZ-binding1 Publication3

      <p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

      The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (PubMed:11007484). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (PubMed:9635436).3 Publications
      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.2 Publications

      <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      evolutionary genealogy of genes: Non-supervised Orthologous Groups

      More...
      eggNOGi
      KOG1545 Eukaryota
      COG1226 LUCA

      Ensembl GeneTree

      More...
      GeneTreei
      ENSGT00940000158688

      The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

      More...
      HOGENOMi
      CLU_011722_4_0_1

      InParanoid: Eukaryotic Ortholog Groups

      More...
      InParanoidi
      P63142

      KEGG Orthology (KO)

      More...
      KOi
      K04875

      Identification of Orthologs from Complete Genome Data

      More...
      OMAi
      QPHDQYD

      Database of Orthologous Groups

      More...
      OrthoDBi
      695337at2759

      Database for complete collections of gene phylogenies

      More...
      PhylomeDBi
      P63142

      TreeFam database of animal gene trees

      More...
      TreeFami
      TF313103

      Family and domain databases

      Gene3D Structural and Functional Annotation of Protein Families

      More...
      Gene3Di
      1.20.120.350, 1 hit

      Integrated resource of protein families, domains and functional sites

      More...
      InterProi
      View 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

      The PANTHER Classification System

      More...
      PANTHERi
      PTHR11537 PTHR11537, 1 hit
      PTHR11537:SF23 PTHR11537:SF23, 1 hit

      Pfam protein domain database

      More...
      Pfami
      View protein in Pfam
      PF02214 BTB_2, 1 hit
      PF00520 Ion_trans, 1 hit

      Protein Motif fingerprint database; a protein domain database

      More...
      PRINTSi
      PR01509 KV12CHANNEL
      PR01491 KVCHANNEL
      PR01496 SHAKERCHANEL

      Simple Modular Architecture Research Tool; a protein domain database

      More...
      SMARTi
      View protein in SMART
      SM00225 BTB, 1 hit

      Superfamily database of structural and functional annotation

      More...
      SUPFAMi
      SSF54695 SSF54695, 1 hit

      <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

      <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

      This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

      P63142-1 [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
      <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iA8FEA6F3F59AF42A
      GO

      <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

      There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
      EntryEntry nameProtein names
      Gene namesLengthAnnotation
      A0A0G2K942A0A0G2K942_RAT
      Potassium voltage-gated channel sub...
      Kcna2
      77Annotation score:

      Annotation score:1 out of 5

      <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti411S → F in AAA19867 (PubMed:1715584).Curated1

      Sequence databases

      Select the link destinations:

      EMBL nucleotide sequence database

      More...
      EMBLi

      GenBank nucleotide sequence database

      More...
      GenBanki

      DNA Data Bank of Japan; a nucleotide sequence database

      More...
      DDBJi
      Links Updated
      J04731 mRNA Translation: AAA40819.1
      X16003 mRNA Translation: CAA34134.1
      M74449 mRNA Translation: AAA19867.1

      Protein sequence database of the Protein Information Resource

      More...
      PIRi
      A33814

      NCBI Reference Sequences

      More...
      RefSeqi
      NP_037102.1, NM_012970.3
      XP_006233194.1, XM_006233132.3
      XP_006233195.1, XM_006233133.3
      XP_006233196.1, XM_006233134.3
      XP_006233197.1, XM_006233135.3
      XP_008759593.1, XM_008761371.2

      Genome annotation databases

      Ensembl eukaryotic genome annotation project

      More...
      Ensembli
      ENSRNOT00000050149; ENSRNOP00000042653; ENSRNOG00000018285
      ENSRNOT00000092365; ENSRNOP00000075841; ENSRNOG00000018285
      ENSRNOT00000092450; ENSRNOP00000075852; ENSRNOG00000018285

      Database of genes from NCBI RefSeq genomes

      More...
      GeneIDi
      25468

      KEGG: Kyoto Encyclopedia of Genes and Genomes

      More...
      KEGGi
      rno:25468

      <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

      <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      J04731 mRNA Translation: AAA40819.1
      X16003 mRNA Translation: CAA34134.1
      M74449 mRNA Translation: AAA19867.1
      PIRiA33814
      RefSeqiNP_037102.1, NM_012970.3
      XP_006233194.1, XM_006233132.3
      XP_006233195.1, XM_006233133.3
      XP_006233196.1, XM_006233134.3
      XP_006233197.1, XM_006233135.3
      XP_008759593.1, XM_008761371.2

      3D structure databases

      Select the link destinations:

      Protein Data Bank Europe

      More...
      PDBei

      Protein Data Bank RCSB

      More...
      RCSB PDBi

      Protein Data Bank Japan

      More...
      PDBji
      Links Updated
      PDB entryMethodResolution (Å)ChainPositionsPDBsum
      1DSXX-ray1.60A/B/C/D/E/F/G/H33-119[»]
      1QDVX-ray1.60A/B/C/D33-131[»]
      1QDWX-ray2.10A/B/C/D/E/F/G/H33-119[»]
      2A79X-ray2.90B1-499[»]
      2R9RX-ray2.40B/H1-499[»]
      3LNMX-ray2.90B/D1-266[»]
      B/D303-499[»]
      3LUTX-ray2.90B1-499[»]
      4JTAX-ray2.50B/Q1-266[»]
      B/Q304-499[»]
      4JTCX-ray2.56B/H1-266[»]
      B/H304-499[»]
      4JTDX-ray2.54B/H1-266[»]
      B/H304-499[»]
      5WIEX-ray3.30B/H1-42[»]
      6EBKelectron microscopy3.30B/D/F/H1-266[»]
      B/D/F/H305-499[»]
      6EBLelectron microscopy3.00B/D/F/H1-266[»]
      B/D/F/H305-499[»]
      6EBMelectron microscopy4.00B/D/F/H1-266[»]
      B/D/F/H305-499[»]
      SMRiP63142
      ModBaseiSearch...
      PDBe-KBiSearch...

      Protein-protein interaction databases

      BioGRIDi247501, 5 interactors
      CORUMiP63142
      IntActiP63142, 4 interactors
      STRINGi10116.ENSRNOP00000042653

      Chemistry databases

      BindingDBiP63142
      ChEMBLiCHEMBL4105982
      DrugCentraliP63142
      GuidetoPHARMACOLOGYi539

      PTM databases

      iPTMnetiP63142
      PhosphoSitePlusiP63142

      Proteomic databases

      PaxDbiP63142
      PRIDEiP63142

      Genome annotation databases

      EnsembliENSRNOT00000050149; ENSRNOP00000042653; ENSRNOG00000018285
      ENSRNOT00000092365; ENSRNOP00000075841; ENSRNOG00000018285
      ENSRNOT00000092450; ENSRNOP00000075852; ENSRNOG00000018285
      GeneIDi25468
      KEGGirno:25468

      Organism-specific databases

      Comparative Toxicogenomics Database

      More...
      CTDi
      3737
      RGDi2950 Kcna2

      Phylogenomic databases

      eggNOGiKOG1545 Eukaryota
      COG1226 LUCA
      GeneTreeiENSGT00940000158688
      HOGENOMiCLU_011722_4_0_1
      InParanoidiP63142
      KOiK04875
      OMAiQPHDQYD
      OrthoDBi695337at2759
      PhylomeDBiP63142
      TreeFamiTF313103

      Enzyme and pathway databases

      ReactomeiR-RNO-1296072 Voltage gated Potassium channels

      Miscellaneous databases

      EvolutionaryTraceiP63142

      Protein Ontology

      More...
      PROi
      PR:P63142

      Gene expression databases

      BgeeiENSRNOG00000018285 Expressed in brain and 8 other tissues
      ExpressionAtlasiP63142 baseline and differential
      GenevisibleiP63142 RN

      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
      PRINTSiPR01509 KV12CHANNEL
      PR01491 KVCHANNEL
      PR01496 SHAKERCHANEL
      SMARTiView protein in SMART
      SM00225 BTB, 1 hit
      SUPFAMiSSF54695 SSF54695, 1 hit

      ProtoNet; Automatic hierarchical classification of proteins

      More...
      ProtoNeti
      Search...

      MobiDB: a database of protein disorder and mobility annotations

      More...
      MobiDBi
      Search...

      <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

      <p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiKCNA2_RAT
      <p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P63142
      Secondary accession number(s): P15386, Q02010
      <p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2004
      Last sequence update: September 13, 2004
      Last modified: June 17, 2020
      This is version 153 of the entry and version 1 of the sequence. See complete history.
      <p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      <p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

      Keywords - Technical termi

      3D-structure, Reference proteome

      Documents

      1. PDB cross-references
        Index of Protein Data Bank (PDB) cross-references
      2. SIMILARITY comments
        Index of protein domains and families
      3. UniProtKB entry view manual
        User manual for the UniProtKB entry view
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