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Protein

Potassium voltage-gated channel subfamily D member 2

Gene

Kcnd2

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

Functioni

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (PubMed:10818150, PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518). 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 (PubMed:10818150, PubMed:17122039, PubMed:22815518). Contributes to the regulation of the circadian rhytm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (PubMed:22815518). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (PubMed:18045912). 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:9734479, PubMed:10601491, PubMed:11909823, PubMed:23713033). 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:9734479, PubMed:22311982). 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:11909823). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:11909823). 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 (By similarity). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:22311982).By similarity9 Publications

Kineticsi

Homotetrameric channels activate rapidly, i.e within a few msec. After that, they inactivate rapidly, i.e within about 50-100 msec. 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. Homotetrameric channels have a unitary conductance of about 4 pS when expressed in a heterologous system. For the activation of homotetrameric channels expressed in xenopus oocytes, the voltage at half-maximal amplitude is about -10 mV. The time constant for inactivation is about 20 msec. For inactivation, the voltage at half-maximal amplitude is -62 mV. The time constant for recovery after inactivation is about 70 msec.1 Publication

      Sites

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Metal bindingi105 – 1051Zinc; via pros nitrogenBy similarity
      Metal bindingi132 – 1321ZincBy similarity
      Metal bindingi133 – 1331ZincBy similarity

      GO - Molecular functioni

      • A-type (transient outward) potassium channel activity Source: UniProtKB
      • metal ion binding Source: UniProtKB-KW
      • voltage-gated potassium channel activity Source: UniProtKB

      GO - Biological processi

      • action potential Source: MGI
      • cardiac muscle cell action potential Source: UniProtKB
      • cellular response to hypoxia Source: UniProtKB
      • locomotor rhythm Source: UniProtKB
      • neuronal action potential Source: UniProtKB
      • potassium ion transmembrane transport Source: UniProtKB
      • protein homooligomerization Source: InterPro
      • sensory perception of pain Source: UniProtKB
      Complete GO annotation...

      Keywords - Molecular functioni

      Ion channel, Potassium channel, Voltage-gated channel

      Keywords - Biological processi

      Ion transport, Potassium transport, Transport

      Keywords - Ligandi

      Metal-binding, Potassium, Zinc

      Enzyme and pathway databases

      ReactomeiR-MMU-1296072. Voltage gated Potassium channels.
      R-MMU-5576894. Phase 1 - inactivation of fast Na+ channels.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium voltage-gated channel subfamily D member 2
      Alternative name(s):
      Voltage-gated potassium channel subunit Kv4.2
      Gene namesi
      Name:Kcnd2
      Synonyms:Kiaa1044
      ORF Names:MNCb-7013
      OrganismiMus musculus (Mouse)
      Taxonomic identifieri10090 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
      Proteomesi
      • UP000000589 Componenti: Chromosome 6

      Organism-specific databases

      MGIiMGI:102663. Kcnd2.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 182182CytoplasmicBy similarityAdd
      BLAST
      Transmembranei183 – 20422Helical; Name=Segment S1By similarityAdd
      BLAST
      Topological domaini205 – 22824ExtracellularBy similarityAdd
      BLAST
      Transmembranei229 – 25022Helical; Name=Segment S2By similarityAdd
      BLAST
      Topological domaini251 – 26111CytoplasmicBy similarityAdd
      BLAST
      Transmembranei262 – 27918Helical; Name=Segment S3By similarityAdd
      BLAST
      Topological domaini280 – 2867ExtracellularBy similarity
      Transmembranei287 – 30620Helical; Voltage-sensor; Name=Segment S4By similarityAdd
      BLAST
      Topological domaini307 – 32115CytoplasmicBy similarityAdd
      BLAST
      Transmembranei322 – 34322Helical; Name=Segment S5By similarityAdd
      BLAST
      Topological domaini344 – 35714ExtracellularBy similarityAdd
      BLAST
      Intramembranei358 – 36912Helical; Name=Pore helixBy similarityAdd
      BLAST
      Intramembranei370 – 3778By similarity
      Topological domaini378 – 3847ExtracellularBy similarity
      Transmembranei385 – 41329Helical; Name=Segment S6By similarityAdd
      BLAST
      Topological domaini414 – 630217CytoplasmicBy similarityAdd
      BLAST

      GO - Cellular componenti

      • caveola Source: UniProtKB
      • cell junction Source: UniProtKB-SubCell
      • dendrite Source: UniProtKB
      • dendritic spine Source: MGI
      • integral component of plasma membrane Source: UniProtKB
      • intrinsic component of plasma membrane Source: MGI
      • membrane Source: MGI
      • neuronal cell body Source: UniProtKB
      • neuronal cell body membrane Source: UniProtKB
      • perikaryon Source: UniProtKB-SubCell
      • plasma membrane raft Source: UniProtKB
      • postsynaptic membrane Source: UniProtKB
      • sarcolemma Source: UniProtKB
      • T-tubule Source: UniProtKB
      • voltage-gated potassium channel complex Source: UniProtKB
      Complete GO annotation...

      Keywords - Cellular componenti

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

      Pathology & Biotechi

      Disruption phenotypei

      Mice are viable, fertile and appear to be in good health (PubMed:16293790, PubMed:22738428). The loss of KCND2 has only minor functional consequences, probably due to an increase of the activity of other potassium channels, even though there is no visible change of their expression levels (PubMed:20371829). Mutant mice show no sign of heart dysfunction, but the fast component of the rapidly inactivating and rapidly recovering potassium current I(to) is lost in their ventricular myocytes (PubMed:16293790). Instead, a slowly inactivating current is expressed that is not observed in wild-type (PubMed:16293790). Electrocardiograms of mutant hearts display no significant differences relative to wild-type regarding their QT, PR, QRS and RR intervals (PubMed:16293790). The neuronal A-type current is reduced by about 80% in brain cortex and hippocampus CA1 pyramidal neurons, by about 50% in suprachiasmatic nucleus neurons and by about 60% in dorsal horn neurons (PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518). The dendritic A-type current is abolished in pyramidal neurons from the hippocampus CA1 layer (PubMed:17122039). Concomitantly, the back-propagation of action potential in dendrites is increased (PubMed:17122039). This may lower the treshold for neuronal long-term potentiation (LTP) (PubMed:17122039). Loss of KCND2 does not influence the levels of KCND3 or KCNA4, but leads to reduced KCNIP1, KCNIP2 and KCNIP3 protein levels (PubMed:17122039, PubMed:18187474, PubMed:22612819). Mutant mice show only minor differences in their behavior when compared to wild-type; they display hyperactivity to some, but not all, novel stimuli (PubMed:22738428). Mutant mice show subtle spatial learning deficits (PubMed:20857488). Mutant mice display shorter periods of locomotor activity that wild-type littermates, due to a corresponding change in the circadian rhythm of repetitive firing in suprachiasmatic nucleus neurons (PubMed:22815518). Mutant mice display loss of spontaneous nociceptive behavior that is caused by the activation of GRM5 (PubMed:18045912).9 Publications

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi362 – 3621W → F: Abolishes channel activity. Alters potassium channel kinetics in heart myocytes. Abolishes the fast component of I(to) in heart ventricle. 2 Publications
      Mutagenesisi602 – 6021T → A: No effect on the regulation of neuronal A-type current in response to activation of metabotropic glutamate receptors. 1 Publication
      Mutagenesisi607 – 6071T → A: No effect on the regulation of neuronal A-type current in response to activation of metabotropic glutamate receptors. 1 Publication
      Mutagenesisi616 – 6161S → A: Abolishes regulation of neuronal A-type current in response to activation of metabotropic glutamate receptors. 1 Publication

      Chemistry

      GuidetoPHARMACOLOGYi553.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 630630Potassium voltage-gated channel subfamily D member 2PRO_0000054065Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Modified residuei38 – 381PhosphothreonineBy similarity
      Modified residuei438 – 4381PhosphoserineBy similarity
      Modified residuei548 – 5481PhosphoserineBy similarity
      Modified residuei552 – 5521PhosphoserineCombined sources
      Modified residuei572 – 5721PhosphoserineCombined sources
      Modified residuei575 – 5751PhosphoserineCombined sources
      Modified residuei602 – 6021PhosphothreonineBy similarity
      Modified residuei607 – 6071PhosphothreonineBy similarity
      Modified residuei616 – 6161Phosphoserine1 Publication

      Post-translational modificationi

      Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites. Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3. Phosphorylation at Ser-552 leads to KCND2 internalization (By similarity). Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5 (PubMed:18045912). Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (PubMed:18045912).By similarity1 Publication

      Keywords - PTMi

      Phosphoprotein

      Proteomic databases

      MaxQBiQ9Z0V2.
      PaxDbiQ9Z0V2.
      PRIDEiQ9Z0V2.

      PTM databases

      iPTMnetiQ9Z0V2.
      PhosphoSiteiQ9Z0V2.

      Expressioni

      Tissue specificityi

      Detected in hippocampus, thalamus, medial habenular nucleus, striatum, amygdala, brain cortex and cerebellum (PubMed:11040264, PubMed:17122039, PubMed:18187474, PubMed:20371829, PubMed:22612819). Detected in hippocampus CA1 and CA3 layer, in stratum oriens, stratum radiatum and stratum lacunosum-moleculare and in dentate gyrus (PubMed:16009497, PubMed:22098631). Detected in dorsal horn neurons; colocalizes with GRM5 (PubMed:18045912). C-terminally phosphorylated forms are detected in the stratum radiatum and in basilar dendrites in stratum oriens in hippocampus CA1 and on cell bodies in hippocampus CA3 layers, with lower levels in stratum lacunosum-moleculare (PubMed:11040264). In contrast, N-terminally phosphorylated forms are detected in stratum lacunosum moleculare in the hippocampus CA1 layer (PubMed:11040264). Both C-terminally and N-terminally phosphorylated forms are observed on cell bodies and neuronal processes in the amygdala (PubMed:11040264). C-terminally phosphorylated forms are detected in the dentate gyrus molecular layer, while N-terminally phosphorylated forms are detected in the hilus of the dentate gyrus (PubMed:11040264). Both N-terminally and C-terminally phosphorylated forms are detected in the somatosensory cortex (PubMed:11040264). C-terminally phosphorylated forms are detected in the cerebellum granular layers (PubMed:11040264). Detected in heart ventricle myocytes (at protein level) (PubMed:9734479, PubMed:11909823, PubMed:16293790, PubMed:23713033). Detected in brain and heart (PubMed:16293790).12 Publications

      Gene expression databases

      BgeeiQ9Z0V2.
      GenevisibleiQ9Z0V2. MM.

      Interactioni

      Subunit structurei

      Homotetramer or heterotetramer with KCND3 or KCND1 (PubMed:9734479, PubMed:11909823, PubMed:19713751, PubMed:20943905). Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905). In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Interacts with DLG1 (By similarity). Interacts with DLG4 (By similarity). Interacts with NCS1/FREQ (PubMed:11606724). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity). Interacts with FLNA and FLNC (By similarity). Interacts with DPP6 and DPP10 (PubMed:19713751, PubMed:22311982). Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity).By similarity5 Publications

      Binary interactionsi

      WithEntry#Exp.IntActNotes
      Kif17Q99PW83EBI-959779,EBI-959754

      Protein-protein interaction databases

      BioGridi200890. 4 interactions.
      IntActiQ9Z0V2. 4 interactions.
      MINTiMINT-4099654.
      STRINGi10090.ENSMUSP00000080257.

      Structurei

      3D structure databases

      ProteinModelPortaliQ9Z0V2.
      SMRiQ9Z0V2. Positions 6-415.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni2 – 2019Interaction with KCNIP1, KCNIP2, and other family membersBy similarityAdd
      BLAST
      Regioni71 – 9020Interaction with KCNIP1By similarityAdd
      BLAST
      Regioni308 – 32114S4-S5 linkerBy similarityAdd
      BLAST
      Regioni474 – 630157Important for normal channel activation and inactivation, for interaction with KCNIP2, and probably other family members as wellBy similarityAdd
      BLAST
      Regioni474 – 48916Required for dendritic targetingBy similarityAdd
      BLAST

      Motif

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Motifi370 – 3756Selectivity filterBy similarity
      Motifi627 – 6304PDZ-bindingBy similarity

      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 (By similarity). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By similarity). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation.By similarity1 Publication
      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.By similarity

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG4390. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118846.
      HOGENOMiHOG000231013.
      HOVERGENiHBG106687.
      InParanoidiQ9Z0V2.
      KOiK04892.
      OMAiIPYNGQP.
      OrthoDBiEOG7SR4MG.
      PhylomeDBiQ9Z0V2.
      TreeFamiTF313103.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ_dom.
      IPR027359. Channel_four-helix_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.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 1 hit.
      PfamiPF02214. BTB_2. 1 hit.
      PF11879. DUF3399. 1 hit.
      PF00520. Ion_trans. 1 hit.
      PF11601. Shal-type. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01517. KV42CHANNEL.
      PR01491. KVCHANNEL.
      PR01497. SHALCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.

      Sequencei

      Sequence statusi: Complete.

      Q9Z0V2-1 [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 EDEPAFISKS GSSFETQHHH LLHCLEKTTN HEFVDEQVFE
      510 520 530 540 550
      ESCMEVATVN RPSSHSPSLS SQQGVTSTCC SRRHKKTFRI PNANVSGSHR
      560 570 580 590 600
      GSVQELSTIQ IRCVERTPLS NSRSSLNAKM EECVKLNCEQ PYVTTAIISI
      610 620 630
      PTPPVTTPEG DDRPESPEYS GGNIVRVSAL
      Length:630
      Mass (Da):70,577
      Last modified:May 1, 1999 - v1
      Checksum:i7FB94277429E7683
      GO

      Sequence cautioni

      The sequence BAA97986.1 differs from that shown. Reason: Frameshift at position 520. Curated
      The sequence BAC41464.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

      Experimental Info

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Sequence conflicti22 – 221V → A in BAA97986 (Ref. 2) Curated
      Sequence conflicti516 – 5161S → R in BAC41464 (PubMed:12465718).Curated

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF107780 mRNA. Translation: AAD16972.1.
      AB045326 mRNA. Translation: BAA97986.1. Frameshift.
      AB093280 mRNA. Translation: BAC41464.1. Different initiation.
      AK032268 mRNA. Translation: BAC27787.1.
      AK032772 mRNA. Translation: BAC28015.1.
      BC079667 mRNA. Translation: AAH79667.1.
      CCDSiCCDS19934.1.
      RefSeqiNP_062671.1. NM_019697.3.
      UniGeneiMm.425316.

      Genome annotation databases

      EnsembliENSMUST00000081542; ENSMUSP00000080257; ENSMUSG00000060882.
      GeneIDi16508.
      KEGGimmu:16508.
      UCSCiuc009baq.1. mouse.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF107780 mRNA. Translation: AAD16972.1.
      AB045326 mRNA. Translation: BAA97986.1. Frameshift.
      AB093280 mRNA. Translation: BAC41464.1. Different initiation.
      AK032268 mRNA. Translation: BAC27787.1.
      AK032772 mRNA. Translation: BAC28015.1.
      BC079667 mRNA. Translation: AAH79667.1.
      CCDSiCCDS19934.1.
      RefSeqiNP_062671.1. NM_019697.3.
      UniGeneiMm.425316.

      3D structure databases

      ProteinModelPortaliQ9Z0V2.
      SMRiQ9Z0V2. Positions 6-415.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi200890. 4 interactions.
      IntActiQ9Z0V2. 4 interactions.
      MINTiMINT-4099654.
      STRINGi10090.ENSMUSP00000080257.

      Chemistry

      GuidetoPHARMACOLOGYi553.

      PTM databases

      iPTMnetiQ9Z0V2.
      PhosphoSiteiQ9Z0V2.

      Proteomic databases

      MaxQBiQ9Z0V2.
      PaxDbiQ9Z0V2.
      PRIDEiQ9Z0V2.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENSMUST00000081542; ENSMUSP00000080257; ENSMUSG00000060882.
      GeneIDi16508.
      KEGGimmu:16508.
      UCSCiuc009baq.1. mouse.

      Organism-specific databases

      CTDi3751.
      MGIiMGI:102663. Kcnd2.
      RougeiSearch...

      Phylogenomic databases

      eggNOGiKOG4390. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118846.
      HOGENOMiHOG000231013.
      HOVERGENiHBG106687.
      InParanoidiQ9Z0V2.
      KOiK04892.
      OMAiIPYNGQP.
      OrthoDBiEOG7SR4MG.
      PhylomeDBiQ9Z0V2.
      TreeFamiTF313103.

      Enzyme and pathway databases

      ReactomeiR-MMU-1296072. Voltage gated Potassium channels.
      R-MMU-5576894. Phase 1 - inactivation of fast Na+ channels.

      Miscellaneous databases

      NextBioi289839.
      PROiQ9Z0V2.
      SOURCEiSearch...

      Gene expression databases

      BgeeiQ9Z0V2.
      GenevisibleiQ9Z0V2. MM.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ_dom.
      IPR027359. Channel_four-helix_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.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 1 hit.
      PfamiPF02214. BTB_2. 1 hit.
      PF11879. DUF3399. 1 hit.
      PF00520. Ion_trans. 1 hit.
      PF11601. Shal-type. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01517. KV42CHANNEL.
      PR01491. KVCHANNEL.
      PR01497. SHALCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.
      ProtoNetiSearch...

      Publicationsi

      « Hide 'large scale' publications
      1. "Cloning and functional characterization of mouse heart K+ channel alpha subunits, Kv1.5, Kv4.2 and Kv4.3."
        Tanaka H., Janzen K., Winkfein R.J., Fiset C., Clark R.B., Giles W.R.
        Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
        Cited for: NUCLEOTIDE SEQUENCE [MRNA].
        Strain: Swiss Webster.
        Tissue: Heart ventricle.
      2. "Isolation of full-length cDNA clones from mouse brain cDNA library made by oligo-capping method."
        Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.
        Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Strain: C57BL/6J.
        Tissue: Brain.
      3. "Prediction of the coding sequences of mouse homologues of KIAA gene: I. The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
        Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O., Koga H.
        DNA Res. 9:179-188(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Tissue: Brain.
      4. "The transcriptional landscape of the mammalian genome."
        Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
        , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
        Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Strain: C57BL/6J.
        Tissue: Mesonephros and Olfactory bulb.
      5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
        The MGC Project Team
        Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Strain: C57BL/6J.
        Tissue: Brain.
      6. "Functional knockout of the transient outward current, long-QT syndrome, and cardiac remodeling in mice expressing a dominant-negative Kv4 alpha subunit."
        Barry D.M., Xu H., Schuessler R.B., Nerbonne J.M.
        Circ. Res. 83:560-567(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH KCND3, SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-362, TISSUE SPECIFICITY.
      7. "Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes."
        Guo W., Xu H., London B., Nerbonne J.M.
        J. Physiol. (Lond.) 521:587-599(1999) [PubMed] [Europe PMC] [Abstract]
        Cited for: MUTAGENESIS OF TRP-362, FUNCTION.
      8. "A-type K+ current mediated by the Kv4 channel regulates the generation of action potential in developing cerebellar granule cells."
        Shibata R., Nakahira K., Shibasaki K., Wakazono Y., Imoto K., Ikenaka K.
        J. Neurosci. 20:4145-4155(2000) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION.
      9. "Input-specific immunolocalization of differentially phosphorylated Kv4.2 in the mouse brain."
        Varga A.W., Anderson A.E., Adams J.P., Vogel H., Sweatt J.D.
        Learn. Memory 7:321-332(2000) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      10. "A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-currents."
        Nakamura T.Y., Pountney D.J., Ozaita A., Nandi S., Ueda S., Rudy B., Coetzee W.A.
        Proc. Natl. Acad. Sci. U.S.A. 98:12808-12813(2001) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH KCNIP1 AND NCS1, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      11. "Role of heteromultimers in the generation of myocardial transient outward K+ currents."
        Guo W., Li H., Aimond F., Johns D.C., Rhodes K.J., Trimmer J.S., Nerbonne J.M.
        Circ. Res. 90:586-593(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH KCND3 AND KCNIP2, SUBUNIT, TISSUE SPECIFICITY.
      12. "Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical and molecular remodeling, with no evidence of ventricular hypertrophy or myocardial dysfunction."
        Guo W., Jung W.E., Marionneau C., Aimond F., Xu H., Yamada K.A., Schwarz T.L., Demolombe S., Nerbonne J.M.
        Circ. Res. 97:1342-1350(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
      13. "Postsynaptic and extrasynaptic localization of Kv4.2 channels in the mouse hippocampal region, with special reference to targeted clustering at gabaergic synapses."
        Jinno S., Jeromin A., Kosaka T.
        Neuroscience 134:483-494(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      14. "Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons."
        Chen X., Yuan L.L., Zhao C., Birnbaum S.G., Frick A., Jung W.E., Schwarz T.L., Sweatt J.D., Johnston D.
        J. Neurosci. 26:12143-12151(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
      15. "Differential expression of I(A) channel subunits Kv4.2 and Kv4.3 in mouse visual cortical neurons and synapses."
        Burkhalter A., Gonchar Y., Mellor R.L., Nerbonne J.M.
        J. Neurosci. 26:12274-12282(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      16. "Metabotropic glutamate receptor 5 modulates nociceptive plasticity via extracellular signal-regulated kinase-Kv4.2 signaling in spinal cord dorsal horn neurons."
        Hu H.J., Alter B.J., Carrasquillo Y., Qiu C.S., Gereau R.W.
        J. Neurosci. 27:13181-13191(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-616, MUTAGENESIS OF THR-602; THR-607 AND SER-616, TISSUE SPECIFICITY.
      17. "Ionic channel function in action potential generation: current perspective."
        Baranauskas G.
        Mol. Neurobiol. 35:129-150(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: REVIEW.
      18. "Electrical remodelling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents."
        Nerbonne J.M., Gerber B.R., Norris A., Burkhalter A.
        J. Physiol. (Lond.) 586:1565-1579(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
      19. Cited for: REVIEW.
      20. "Proteomic analyses of native brain K(V)4.2 channel complexes."
        Marionneau C., LeDuc R.D., Rohrs H.W., Link A.J., Townsend R.R., Nerbonne J.M.
        Channels 3:284-294(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBUNIT.
      21. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-552; SER-572 AND SER-575, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
        Tissue: Brain and Heart.
      22. "Molecular dissection of I(A) in cortical pyramidal neurons reveals three distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits."
        Norris A.J., Nerbonne J.M.
        J. Neurosci. 30:5092-5101(2010) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
      23. "Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in the generation of Kv4-encoded IA channels in cortical pyramidal neurons."
        Norris A.J., Foeger N.C., Nerbonne J.M.
        J. Neurosci. 30:13644-13655(2010) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH KCND3; KCNIP2; KCNIP3 AND KCNIP4.
      24. "Spatial learning deficits in mice lacking A-type K(+) channel subunits."
        Lockridge A., Yuan L.L.
        Hippocampus 21:1152-1156(2011) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE.
      25. "Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors."
        Kiselycznyk C., Hoffman D.A., Holmes A.
        Biol. Mood Anxiety Disord. 2:5-5(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE.
      26. "The importance of immunohistochemical analyses in evaluating the phenotype of Kv channel knockout mice."
        Menegola M., Clark E., Trimmer J.S.
        Epilepsia 53:142-149(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
      27. "Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells."
        Kerti K., Lorincz A., Nusser Z.
        Eur. J. Neurosci. 35:66-75(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      28. "Augmentation of Kv4.2-encoded currents by accessory dipeptidyl peptidase 6 and 10 subunits reflects selective cell surface Kv4.2 protein stabilization."
        Foeger N.C., Norris A.J., Wren L.M., Nerbonne J.M.
        J. Biol. Chem. 287:9640-9650(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH DPP6 AND DPP10.
      29. "I(A) channels encoded by Kv1.4 and Kv4.2 regulate neuronal firing in the suprachiasmatic nucleus and circadian rhythms in locomotor activity."
        Granados-Fuentes D., Norris A.J., Carrasquillo Y., Nerbonne J.M., Herzog E.D.
        J. Neurosci. 32:10045-10052(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: DISRUPTION PHENOTYPE, FUNCTION.
      30. "Stabilization of Kv4 protein by the accessory K(+) channel interacting protein 2 (KChIP2) subunit is required for the generation of native myocardial fast transient outward K(+) currents."
        Foeger N.C., Wang W., Mellor R.L., Nerbonne J.M.
        J. Physiol. (Lond.) 591:4149-4166(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, TISSUE SPECIFICITY.

      Entry informationi

      Entry nameiKCND2_MOUSE
      AccessioniPrimary (citable) accession number: Q9Z0V2
      Secondary accession number(s): Q8BSK3, Q8CHB7, Q9JJ60
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: November 7, 2003
      Last sequence update: May 1, 1999
      Last modified: May 11, 2016
      This is version 150 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      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 Publications4 Publications

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

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

      Similar proteinsi

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