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Entry version 161 (18 Sep 2019)
Sequence version 1 (01 Nov 1996)
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Protein

Potassium voltage-gated channel subfamily D member 2

Gene

Kcnd2

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, but also in rodent heart (PubMed:1840649, PubMed:1722463, PubMed:9093524, PubMed:9058605, PubMed:10676964, PubMed:12592409, PubMed:12754210, PubMed:16207878, PubMed:16123112, PubMed:19279261, PubMed:25352783, PubMed:14980206). Mediates the major part of the dendritic A-type current I(SA) in brain neurons (PubMed:16207878, PubMed:17026528). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member (PubMed:9093524, PubMed:9058605). 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:1840649, PubMed:1722463, PubMed:9093524, PubMed:10676964, PubMed:12451113, PubMed:12592409, PubMed:12754210, PubMed:15452711, PubMed:16207878, PubMed:16820361, PubMed:25352783, PubMed:14980206). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel (PubMed:25352783). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:12451113, PubMed:16123112). Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:12451113, PubMed:15452711, PubMed:16123112, PubMed:16820361, PubMed:20045463, PubMed:14980206). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:15671030, PubMed:16123112, PubMed:19441798, PubMed:19901547, PubMed:19279261).By similarityCurated22 Publications

Miscellaneous

The transient neuronal A-type potassium current called I(SA) is triggered at membrane potentials that are below the threshold for action potentials. It inactivates rapidly and recovers rapidly from inactivation. It regulates the firing of action potentials and plays a role in synaptic integration and plasticity. Potassium channels containing KCND2 account for about 80% of the neuronal A-type potassium current. In contrast, the potassium channel responsible for the cardiac I(to) current differs between species; it is mediated by KCND2 in rodents. In human and other non-rodents KCND3 may play an equivalent role.2 Publications1 Publication
Is specifically and reversibly inhibited by the scorpion toxin Ts8 (AC P69940).1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 5 mM 4-aminopyridine (4-AP) (PubMed:1840649, PubMed:1722463, PubMed:9093524). Not inhibited by dendrotoxins and by tetraethylammonium (TEA) (PubMed:1722463). Inhibited by 10 mM flecainide and 20 mM quinidine (PubMed:9093524). Inhibited by the heteropodatoxins HpTx1, HpTx2, and HpTx3 (PubMed:9058605).4 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 (PubMed:1722463, PubMed:9093524). After that, they inactivate rapidly, i.e within about 50-100 msec (PubMed:1722463, PubMed:9093524). The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system and the presence or absence of ancillary subunits (PubMed:19901547, PubMed:19279261). Homotetrameric channels have a unitary conductance of about 4 pS when expressed in a heterologous system (PubMed:19279261). For the activation of homotetrameric channels expressed in xenopus oocytes, the voltage at half-maximal amplitude is about -10 mV (PubMed:12451113). The time constant for inactivation is about 20 msec (PubMed:12451113). For inactivation, the voltage at half-maximal amplitude is -62 mV (PubMed:12451113). The time constant for recovery after inactivation is about 70 msec (PubMed:12451113).1 Publication5 Publications

      Sites

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi105Zinc; via pros nitrogenCombined sources1
      Metal bindingi132ZincCombined sources1
      Metal bindingi133ZincCombined sources1

      <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
      LigandMetal-binding, Potassium, Zinc

      <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_and_taxonomy_section">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 D member 2
      Alternative name(s):
      RK52 Publications
      Shal11 Publication
      Voltage-gated potassium channel subunit Kv4.21 Publication
      <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:Kcnd2
      <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_manual">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: Unplaced

      Organism-specific databases

      Rat genome database

      More...
      RGDi
      68393 Kcnd2

      <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_location_section">'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 – 182CytoplasmicBy similarityAdd BLAST182
      <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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>Transmembranei183 – 204Helical; Name=Segment S1By similarityAdd BLAST22
      Topological domaini205 – 228ExtracellularBy similarityAdd BLAST24
      Transmembranei229 – 250Helical; Name=Segment S2By similarityAdd BLAST22
      Topological domaini251 – 261CytoplasmicBy similarityAdd BLAST11
      Transmembranei262 – 279Helical; Name=Segment S3By similarityAdd BLAST18
      Topological domaini280 – 286ExtracellularBy similarity7
      Transmembranei287 – 306Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST20
      Topological domaini307 – 321CytoplasmicBy similarityAdd BLAST15
      Transmembranei322 – 343Helical; Name=Segment S5By similarityAdd BLAST22
      Topological domaini344 – 357ExtracellularBy similarityAdd BLAST14
      <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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>Intramembranei358 – 369Helical; Name=Pore helixBy similarityAdd BLAST12
      Intramembranei370 – 377By similarity8
      Topological domaini378 – 384ExtracellularBy similarity7
      Transmembranei385 – 413Helical; Name=Segment S6By similarityAdd BLAST29
      Topological domaini414 – 630CytoplasmicBy similarityAdd BLAST217

      Keywords - Cellular componenti

      Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse

      <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_and_biotech_section">'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>Mutagenesisi7 – 11Missing : Greatly reduces interaction with KCNIP1. 1 Publication5
      Mutagenesisi8W → A: Abolishes interaction with KCNP1; when associated with A-11. 1 Publication1
      Mutagenesisi11F → A: Abolishes interaction with KCNP1; when associated with A-8. 1 Publication1
      Mutagenesisi66L → R: Abolishes expression. 1 Publication1
      Mutagenesisi71E → K: Abolishes interaction with KCNIP1. 1 Publication1
      Mutagenesisi73D → M: Abolishes interaction with KCNIP1. 1 Publication1
      Mutagenesisi74F → R: Abolishes interaction with KCNIP1. 1 Publication1
      Mutagenesisi79E → L or R: Abolishes interaction with KCNIP1. 1 Publication1
      Mutagenesisi93R → A: Greatly reduces expression and changes multimerization. 1 Publication1
      Mutagenesisi105H → A: Abolishes tetramerization and assembly of a functional channel. 1 Publication1
      Mutagenesisi111C → A: Abolishes tetramerization and assembly of a functional channel; when associated with A-105; A-132 and A-133. 1 Publication1
      Mutagenesisi132C → A: Abolishes tetramerization and assembly of a functional channel; when associated with A-105; A-111 and A-133. 1 Publication1
      Mutagenesisi133C → A: Abolishes tetramerization and assembly of a functional channel; when associated with A-105; A-111 and A-132. 1 Publication1
      Mutagenesisi481 – 482Missing : Loss of dendritic targeted expression. 1 Publication2
      Mutagenesisi552S → A: Abolishes PKA-mediated modulation of cell surface expression and channel activity. 2 Publications1
      Mutagenesisi627 – 630Missing : Abolishes interaction with DLG4. 2 Publications4

      Chemistry databases

      ChEMBL database of bioactive drug-like small molecules

      More...
      ChEMBLi
      CHEMBL1075227

      IUPHAR/BPS Guide to PHARMACOLOGY

      More...
      GuidetoPHARMACOLOGYi
      553

      <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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000540671 – 630Potassium voltage-gated channel subfamily D member 2Add BLAST630

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      <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 residuei38Phosphothreonine1 Publication1
      Modified residuei438Phosphoserine1 Publication1
      Modified residuei548PhosphoserineCombined sources1 Publication1
      Modified residuei552PhosphoserineCombined sources5 Publications1
      Modified residuei572PhosphoserineCombined sources1 Publication1
      Modified residuei575PhosphoserineCombined sources1 Publication1
      Modified residuei602Phosphothreonine1 Publication1
      Modified residuei607Phosphothreonine1 Publication1
      Modified residuei616Phosphoserine1 Publication1

      <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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

      Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites (PubMed:24404150). Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552 (PubMed:19441798). Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3 (PubMed:12451113). Phosphorylation at Ser-552 leads to KCND2 internalization (PubMed:17582333). Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5 (By similarity). Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (By similarity).By similarity4 Publications

      Keywords - PTMi

      Phosphoprotein

      Proteomic databases

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

      More...
      PaxDbi
      Q63881

      PRoteomics IDEntifications database

      More...
      PRIDEi
      Q63881

      PTM databases

      iPTMnet integrated resource for PTMs in systems biology context

      More...
      iPTMneti
      Q63881

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

      More...
      PhosphoSitePlusi
      Q63881

      <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 brain cortex, hippocampus, dentate gyrus, thalamus and cerebellum (PubMed:16123112). Detected in neurons from the primary visual cortex (PubMed:16207878). Detected in the supraoptic nucleus in hypothalamus, in hippocampus and the habenular nucleus of the thalamus (PubMed:9070739). Detected in the bed nucleus of the stria terminalis (PubMed:24037673). Detected in dendritic fields in the hippocampus CA1 layer, in stratum radiatum, stratum oriens, stratum lacunosum-moleculare and stratum pyramidale (PubMed:10676964, PubMed:22098631). Detected in dendritic fields in the hippocampus CA3 layer and in dentate gyrus (PubMed:10676964). Detected in the cerebellum granule cell layer, where it localizes at synapses (PubMed:11102480, PubMed:10676964, PubMed:15736227). Detected in the main olfactory bulb, especially in the granule cell layer and the external plexiform layer, but also the mitral layer (PubMed:18371079). Detected in heart atrium and ventricle (PubMed:10860776). Detected in heart left ventricle (at protein level) (PubMed:24793047). Highly expressed in heart and throughout the brain, with similar levels in cortex and hypothalamus, and much higher levels in hippocampus, dentate gyrus and the habenular nucleus of the thalamus. Detected in brain, and at lower levels in heart atrium and ventricle (PubMed:1705709). Detected in neurons from the bed nucleus of the stria terminalis (PubMed:24037673). Detected in aorta, cardiac and smooth muscle.11 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

      Down-regulated in response to hypoxia lasting about 15 min, a treatment that leads to spontaneous convulsive seizures in these pups.1 Publication

      <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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

      Homotetramer or heterotetramer with KCND1 or KCND3 (PubMed:12754210, PubMed:15485870, PubMed:20224290, PubMed:25352783). Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (PubMed:10676964, PubMed:12451113, PubMed:11847232, PubMed:11805342, PubMed:15485870, PubMed:15356203, PubMed:15452711, PubMed:16820361, PubMed:20045463, PubMed:24811166, PubMed:14980206).

      Interacts with DPP6, DPP10, DLG4 and DLG1 (PubMed:11923279, PubMed:12575952, PubMed:14559911, PubMed:15671030, PubMed:19213956). In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:16123112, PubMed:19901547). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with KCNIP3 promotes tetramerization and formation of a functional potassium channel (PubMed:15485870). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity).

      Interacts with FLNA and FLNC (PubMed:11102480).

      Interacts with NCS1/FREQ (By similarity).

      Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (PubMed:20224290).

      By similarity2 Publications22 Publications

      GO - Molecular functioni

      Protein-protein interaction databases

      The Biological General Repository for Interaction Datasets (BioGrid)

      More...
      BioGridi
      249292, 2 interactors

      CORUM comprehensive resource of mammalian protein complexes

      More...
      CORUMi
      Q63881

      Protein interaction database and analysis system

      More...
      IntActi
      Q63881, 3 interactors

      Molecular INTeraction database

      More...
      MINTi
      Q63881

      STRING: functional protein association networks

      More...
      STRINGi
      10116.ENSRNOP00000039227

      Chemistry databases

      BindingDB database of measured binding affinities

      More...
      BindingDBi
      Q63881

      <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

      1630
      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
      Q63881

      Database of comparative protein structure models

      More...
      ModBasei
      Search...

      Miscellaneous databases

      Relative evolutionary importance of amino acids within a protein sequence

      More...
      EvolutionaryTracei
      Q63881

      <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>Regioni2 – 20Interaction with KCNIP1, KCNIP2, and other family members2 PublicationsAdd BLAST19
      Regioni71 – 90Interaction with KCNIP11 PublicationAdd BLAST20
      Regioni308 – 321S4-S5 linkerBy similarityAdd BLAST14
      Regioni474 – 630Important for normal channel activation and inactivation, for interaction with KCNIP2, and probably other family members as well1 PublicationAdd BLAST157
      Regioni474 – 489Required for dendritic targeting1 PublicationAdd BLAST16

      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>Motifi370 – 375Selectivity filterBy similarity6
      Motifi627 – 630PDZ-binding2 Publications4

      <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 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
      The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (PubMed:15452711). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (PubMed:16820361, PubMed:18357523, PubMed:14980206). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (PubMed:12754210). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation.By similarity3 Publications2 Publications
      The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation. It is required for interaction with KCNIP2, and probably other family members as well.1 Publication

      <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
      KOG4390 Eukaryota
      COG1226 LUCA

      The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

      More...
      HOGENOMi
      HOG000231013

      InParanoid: Eukaryotic Ortholog Groups

      More...
      InParanoidi
      Q63881

      KEGG Orthology (KO)

      More...
      KOi
      K04892

      Database of Orthologous Groups

      More...
      OrthoDBi
      469107at2759

      Database for complete collections of gene phylogenies

      More...
      PhylomeDBi
      Q63881

      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
      IPR003975 K_chnl_volt-dep_Kv4
      IPR004055 K_chnl_volt-dep_Kv4.2
      IPR024587 K_chnl_volt-dep_Kv4_C
      IPR021645 Shal-type_N
      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

      Pfam protein domain database

      More...
      Pfami
      View protein in Pfam
      PF02214 BTB_2, 1 hit
      PF11879 DUF3399, 1 hit
      PF00520 Ion_trans, 1 hit
      PF11601 Shal-type, 1 hit

      Protein Motif fingerprint database; a protein domain database

      More...
      PRINTSi
      PR01517 KV42CHANNEL
      PR01491 KVCHANNEL
      PR01497 SHALCHANNEL

      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_length">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>Sequencei

      <p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

      Q63881-1 [UniParc]FASTAAdd to basket
      « Hide
              10         20         30         40         50
      MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT
      60 70 80 90 100
      RFQTWQDTLE RYPDTLLGSS ERDFFYHPET QQYFFDRDPD IFRHILNFYR
      110 120 130 140 150
      TGKLHYPRHE CISAYDEELA FFGLIPEIIG DCCYEEYKDR RRENAERLQD
      160 170 180 190 200
      DADTDNTGES ALPTMTARQR VWRAFENPHT STMALVFYYV TGFFIAVSVI
      210 220 230 240 250
      ANVVETVPCG SSPGHIKELP CGERYAVAFF CLDTACVMIF TVEYLLRLAA
      260 270 280 290 300
      APSRYRFVRS VMSIIDVVAI LPYYIGLVMT DNEDVSGAFV TLRVFRVFRI
      310 320 330 340 350
      FKFSRHSQGL RILGYTLKSC ASELGFLLFS LTMAIIIFAT VMFYAEKGSS
      360 370 380 390 400
      ASKFTSIPAA FWYTIVTMTT LGYGDMVPKT IAGKIFGSIC SLSGVLVIAL
      410 420 430 440 450
      PVPVIVSNFS RIYHQNQRAD KRRAQKKARL ARIRAAKSGS ANAYMQSKRN
      460 470 480 490 500
      GLLSNQLQSS EDEPAFVSKS GSSFETQHHH LLHCLEKTTN HEFVDEQVFE
      510 520 530 540 550
      ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKSFRI PNANVSGSHR
      560 570 580 590 600
      GSVQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI
      610 620 630
      PTPPVTTPEG DDRPESPEYS GGNIVRVSAL
      Length:630
      Mass (Da):70,549
      Last modified:November 1, 1996 - 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:iFDE57E8A5113BABF
      GO

      <p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

      The sequence AAA40929 differs from that shown. Reason: Frameshift at position 477.Curated

      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
      S64320 mRNA Translation: AAB19939.1
      M59980 mRNA Translation: AAA40929.1 Frameshift.

      Protein sequence database of the Protein Information Resource

      More...
      PIRi
      I57681
      JU0271

      NCBI Reference Sequences

      More...
      RefSeqi
      NP_113918.2, NM_031730.2

      Genome annotation databases

      Database of genes from NCBI RefSeq genomes

      More...
      GeneIDi
      65180

      KEGG: Kyoto Encyclopedia of Genes and Genomes

      More...
      KEGGi
      rno:65180

      UCSC genome browser

      More...
      UCSCi
      RGD:68393 rat

      <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
      S64320 mRNA Translation: AAB19939.1
      M59980 mRNA Translation: AAA40929.1 Frameshift.
      PIRiI57681
      JU0271
      RefSeqiNP_113918.2, NM_031730.2

      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
      1NN7X-ray2.10A42-146[»]
      1S6CX-ray2.00B1-30[»]
      SMRiQ63881
      ModBaseiSearch...

      Protein-protein interaction databases

      BioGridi249292, 2 interactors
      CORUMiQ63881
      IntActiQ63881, 3 interactors
      MINTiQ63881
      STRINGi10116.ENSRNOP00000039227

      Chemistry databases

      BindingDBiQ63881
      ChEMBLiCHEMBL1075227

      DrugCentral

      More...
      DrugCentrali
      Q63881
      GuidetoPHARMACOLOGYi553

      PTM databases

      iPTMnetiQ63881
      PhosphoSitePlusiQ63881

      Proteomic databases

      PaxDbiQ63881
      PRIDEiQ63881

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      GeneIDi65180
      KEGGirno:65180
      UCSCiRGD:68393 rat

      Organism-specific databases

      Comparative Toxicogenomics Database

      More...
      CTDi
      3751
      RGDi68393 Kcnd2

      Phylogenomic databases

      eggNOGiKOG4390 Eukaryota
      COG1226 LUCA
      HOGENOMiHOG000231013
      InParanoidiQ63881
      KOiK04892
      OrthoDBi469107at2759
      PhylomeDBiQ63881

      Miscellaneous databases

      EvolutionaryTraceiQ63881

      Protein Ontology

      More...
      PROi
      PR:Q63881

      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
      IPR003975 K_chnl_volt-dep_Kv4
      IPR004055 K_chnl_volt-dep_Kv4.2
      IPR024587 K_chnl_volt-dep_Kv4_C
      IPR021645 Shal-type_N
      IPR011333 SKP1/BTB/POZ_sf
      IPR003131 T1-type_BTB
      IPR028325 VG_K_chnl
      IPR027359 Volt_channel_dom_sf
      PANTHERiPTHR11537 PTHR11537, 1 hit
      PfamiView protein in Pfam
      PF02214 BTB_2, 1 hit
      PF11879 DUF3399, 1 hit
      PF00520 Ion_trans, 1 hit
      PF11601 Shal-type, 1 hit
      PRINTSiPR01517 KV42CHANNEL
      PR01491 KVCHANNEL
      PR01497 SHALCHANNEL
      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 nameiKCND2_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: Q63881
      Secondary accession number(s): Q00090, Q99249
      <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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
      Last sequence update: November 1, 1996
      Last modified: September 18, 2019
      This is version 161 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, Complete proteome, Reference proteome

      Documents

      1. PDB cross-references
        Index of Protein Data Bank (PDB) cross-references
      2. SIMILARITY comments
        Index of protein domains and families
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