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Protein

Potassium voltage-gated channel subfamily C member 2

Gene

Kcnc2

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. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system (PubMed:10561420, PubMed:10414303, PubMed:11124984, PubMed:10903572, PubMed:11506885, PubMed:15317859, PubMed:15917463, PubMed:17761775, PubMed:21414897). Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly (PubMed:10414303). Forms tetrameric 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 (By similarity). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:10531438, PubMed:12000114). Channel properties may be modulated by either the association with ancillary subunits, such as KCNE1, KCNE2 and KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in thalamocortical and suprachiasmatic nucleus (SCN) neurons, in hippocampal and neocortical interneurons and in retinal ganglion cells (PubMed:10561420, PubMed:10903572, PubMed:11506885, PubMed:17761775). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner (PubMed:10903572). Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release (PubMed:15917463). Required for long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (PubMed:21414897).By similarity2 Publications10 Publications

Enzyme regulationi

Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP). Inhibited by Stichodactyla helianthus peptide ShK.By similarity1 Publication

Kineticsi

Homotetrameric channels expressed in xenopus oocytes or in mammalian non-neuronal cells display delayed-rectifier voltage-dependent potassium currents, that are rapidly activated during membrane depolarization, i.e within a risetime of a few msec. After that, inactivates very slowly, i.e within about >800 msec. Their activation requires a threshold potential at about -10 mV, with a midpoint activation at about 12.1 mV and a steepness parameter of about 8.4 mV. The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, the presence or absence of ancillary subunits and post-translational modifications.By similarity

Manual assertion inferred from sequence similarity toi

1 Publication

      GO - Molecular functioni

      GO - Biological processi

      Complete GO annotation...

      Keywords - Molecular functioni

      Ion channel, Potassium channel, Voltage-gated channel

      Keywords - Biological processi

      Ion transport, Potassium transport, Transport

      Keywords - Ligandi

      Potassium

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium voltage-gated channel subfamily C member 2Imported
      Alternative name(s):
      Shaw-like potassium channelBy similarity
      Voltage-gated potassium channel Kv3.21 Publication
      Gene namesi
      Name:Kcnc2Imported
      OrganismiMus musculus (Mouse)
      Taxonomic identifieri10090 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
      Proteomesi
      • UP000000589 Componenti: Unplaced

      Organism-specific databases

      MGIiMGI:96668. Kcnc2.

      Subcellular locationi

      Topology

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Topological domaini1 – 233CytoplasmicSequence analysisAdd BLAST233
      Transmembranei234 – 254Helical; Name=Segment S1Sequence analysisAdd BLAST21
      Transmembranei287 – 307Helical; Name=Segment S2Sequence analysisAdd BLAST21
      Topological domaini308 – 317CytoplasmicSequence analysis10
      Transmembranei318 – 338Helical; Name=Segment S3Sequence analysisAdd BLAST21
      Transmembranei350 – 372Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST23
      Topological domaini373 – 385CytoplasmicSequence analysisAdd BLAST13
      Transmembranei386 – 406Helical; Name=Segment S5Sequence analysisAdd BLAST21
      Transmembranei457 – 477Helical; Name=Segment S6Sequence analysisAdd BLAST21
      Topological domaini478 – 642CytoplasmicSequence analysisAdd BLAST165

      GO - Cellular componenti

      • apical plasma membrane Source: UniProtKB
      • axon Source: UniProtKB
      • basolateral plasma membrane Source: UniProtKB
      • cell junction Source: UniProtKB-KW
      • dendrite Source: UniProtKB
      • integral component of membrane Source: GO_Central
      • integral component of plasma membrane Source: UniProtKB
      • intracellular Source: GOC
      • membrane Source: UniProtKB
      • neuronal cell body membrane Source: UniProtKB
      • perikaryon Source: UniProtKB
      • postsynaptic membrane Source: UniProtKB
      • presynaptic membrane Source: UniProtKB
      • synapse 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, Synaptosome

      Pathology & Biotechi

      Disruption phenotypei

      Mice are healthy, grow normally, are fertile and show no evidence of severe sensory or motor abnormalities (PubMed:11124984). Show increased seizure susceptibility and reduced long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Thalamocortical neurons show a strong attenuation in maximal peak firing rates, with larger spikes and slower action potential repolarization (PubMed:17761775). Neocortical GABAergic interneurons display broader spikes and sustain lower trains of high-frequency spikes without accommodation or spike doublets in rapid succession (PubMed:11124984, PubMed:22539821). Histamine H2 receptor- and PKA-induced hippocampal inhibitory interneurons display no maximal sustainable firing frequency modulation (PubMed:10903572). Double knockout of KCNC2 and KCNC1 exhibited disrupted daily rhythms in wheel-running behavior (PubMed:21414897). Display smaller outward currents and slower deactivation in starburst amacrine cells compared with KCNC2 knockout mice (PubMed:15317859). Neocortical GABAergic interneuron terminals display also a reduced rate of spike repolarization, broader spike, increased calcium influx and release of GABA neurotransmitter (PubMed:15917463). Suprachiasmatic nucleus (SCN) neurons display a reduction in the magnitude of fast delayed rectifier potassium currents, wider action potentials, reduced spontaneous firing activity during the day and reduced NMDA-evoked increase firing responses during the night (PubMed:21414897).7 Publications

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      ChainiPRO_00003104171 – 642Potassium voltage-gated channel subfamily C member 2Add BLAST642

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Glycosylationi263N-linked (GlcNAc...)Sequence analysis1
      Glycosylationi270N-linked (GlcNAc...)Sequence analysis1
      Modified residuei604PhosphoserineCombined sources1

      Post-translational modificationi

      Phosphorylated by PKA in cortical synaptosomes. cAMP-dependent phosphorylation inhibits channel activity (By similarity). Histamine H2 receptor- and PKA-induced phosphorylation extends action potential spike duration, reduces action potential spike amplitude, sustains maximum firing frequency in hippocampal interneurons; also reduces the incidence of high-frequency oscillations in hippocampal CA3 pyramidal cell layers (PubMed:10903572).By similarity1 Publication

      Keywords - PTMi

      Glycoprotein, Phosphoprotein

      Proteomic databases

      PaxDbiQ14B80.
      PRIDEiQ14B80.

      PTM databases

      iPTMnetiQ14B80.
      PhosphoSitePlusiQ14B80.

      Expressioni

      Tissue specificityi

      Weakly expressed in the brain at postnatal age day 7 (P7) and increased at P60 (PubMed:21912965). Not detectable in newborn hippocampus. Expressed weakly at P7 in the early developing hippocampus, increasing progressively and reaching a plateau of expression at P14 that is maintained throughout P51. Expressed in paravalbumin- and somatostain-containing inhibitory interneurons of the hippocampus; in the CA1/CA3 stratum oriens-alveus and stratum pyramidale and in cells within the hilus and subgranular layer of the dentate gyrus (DG) (PubMed:12000114, PubMed:10903572). Strongly expressed in parvalbumin (PV)-containing fast-spiking GABAergic inhibitor interneurons in deep cortical layers V and VI (PubMed:10531438). Also expressed in non-fast-spiking calbindin (CB)- and/or somatostatin (SOM)-containing interneurons in deep cortical layers V and VI (PubMed:10531438). Expressed in starburst amacrine cells of the retina in the inner nuclear layer (INL) and ganglion cell layer (GCL) (PubMed:15317859). Expressed in the suprachiasmatic nucleus (SCN) (at protein level) (PubMed:15852012, PubMed:21414897). Expressed in the early developing brain, increasing progressively until P14 (PubMed:21912965).7 Publications

      Developmental stagei

      Weakly expressed in the brain at 14 dpc (at protein level) (PubMed:21912965). Expressed in the brain at 14 dpc (PubMed:21912965).1 Publication

      Interactioni

      Subunit structurei

      Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1 (PubMed:10531438). Interacts with KCNC1 (PubMed:10531438, PubMed:12000114). Homotetramer or heterotetramer channel activity is regulated by association with modulating ancillary subunits such as KCNE1, KCNE2 and KCNE3, creating a functionally diverse range of channel complexes. Interacts with KCNE1, KCNE2 and KCNE3 (By similarity).By similarity2 Publications

      GO - Molecular functioni

      • ion channel binding Source: UniProtKB

      Protein-protein interaction databases

      STRINGi10090.ENSMUSP00000089814.

      Structurei

      3D structure databases

      ProteinModelPortaliQ14B80.
      SMRiQ14B80.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Motif

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Motifi441 – 446Selectivity filterBy similarity6

      Compositional bias

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Compositional biasi56 – 103Gly/Pro-rich (insert)Add BLAST48

      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

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG3713. Eukaryota.
      COG1226. LUCA.
      HOGENOMiHOG000231012.
      HOVERGENiHBG105862.
      InParanoidiQ14B80.
      PhylomeDBiQ14B80.

      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.
      IPR003974. K_chnl_volt-dep_Kv3.
      IPR011333. SKP1/BTB/POZ.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 2 hits.
      PfamiPF02214. BTB_2. 1 hit.
      PF00520. Ion_trans. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01491. KVCHANNEL.
      PR01498. SHAWCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 2 hits.

      Sequencei

      Sequence statusi: Complete.

      Q14B80-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MGKIESNERV ILNVGGTRHE TYRSTLKTLP GTRLALLASS EPQGDCLTAA
      60 70 80 90 100
      GDKLQPLPPP LSPPPRPPPL SPVPSGCFEG GAGNCSSHGG NGGNGGSDHP
      110 120 130 140 150
      GGGREFFFDR HPGVFAYVLN YYRTGKLHCP ADVCGPLFEE ELAFWGIDET
      160 170 180 190 200
      DVEPCCWMTY RQHRDAEEAL DIFETPDLIG GDPGDDEDLA AKRLGIEDAA
      210 220 230 240 250
      GLGGPDGKSG RWRKLQPRMW ALFEDPYSSR AARFIAFASL FFILVSITTF
      260 270 280 290 300
      CLETHEAFNI VKNKTEPVIN GTSPVLQYEI ETDPALTYVE GVCVVWFTFE
      310 320 330 340 350
      FLVRIVFSPN KLEFIKNLLN IIDFVAILPF YLEVGLSGLS SKAAKDVLGF
      360 370 380 390 400
      LRVVRFVRIL RIFKLTRHFV GLRVLGHTLR ASTNEFLLLI IFLALGVLIF
      410 420 430 440 450
      ATMIYYAERV GAQPNDPSAS EHTQFKNIPI GFWWAVVTMT TLGYGDMYPQ
      460 470 480 490 500
      TWSGMLVGAL CALAGVLTIA MPVPVIVNNF GMYYSLAMAK QKLPRKRKKH
      510 520 530 540 550
      IPPAPLASSP TFCKTELNMA CNSTQSDTCL GKENRLLEHN RSVLSGDDST
      560 570 580 590 600
      GSEPPLSPPE RLPIRRSSTR DKNRRGETCF LLTTGDYTCA SDGGIRKGYE
      610 620 630 640
      KSRSLNNIAG LAGNALRLSP VTSPYNSPCP LRRSRSPIPS IL
      Length:642
      Mass (Da):70,503
      Last modified:August 22, 2006 - v1
      Checksum:i2B9B6D29A40A80E3
      GO

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      BC116289 mRNA. Translation: AAI16290.1.
      BC116290 mRNA. Translation: AAI16291.1.
      RefSeqiXP_006513748.1. XM_006513685.3.
      XP_006513750.1. XM_006513687.3.
      XP_006513751.1. XM_006513688.1.
      XP_006513752.1. XM_006513689.3.
      XP_006513753.1. XM_006513690.2.
      UniGeneiMm.336242.

      Genome annotation databases

      GeneIDi268345.
      UCSCiuc007hao.1. mouse.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      BC116289 mRNA. Translation: AAI16290.1.
      BC116290 mRNA. Translation: AAI16291.1.
      RefSeqiXP_006513748.1. XM_006513685.3.
      XP_006513750.1. XM_006513687.3.
      XP_006513751.1. XM_006513688.1.
      XP_006513752.1. XM_006513689.3.
      XP_006513753.1. XM_006513690.2.
      UniGeneiMm.336242.

      3D structure databases

      ProteinModelPortaliQ14B80.
      SMRiQ14B80.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      STRINGi10090.ENSMUSP00000089814.

      PTM databases

      iPTMnetiQ14B80.
      PhosphoSitePlusiQ14B80.

      Proteomic databases

      PaxDbiQ14B80.
      PRIDEiQ14B80.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      GeneIDi268345.
      UCSCiuc007hao.1. mouse.

      Organism-specific databases

      CTDi3747.
      MGIiMGI:96668. Kcnc2.

      Phylogenomic databases

      eggNOGiKOG3713. Eukaryota.
      COG1226. LUCA.
      HOGENOMiHOG000231012.
      HOVERGENiHBG105862.
      InParanoidiQ14B80.
      PhylomeDBiQ14B80.

      Miscellaneous databases

      ChiTaRSiKcnc2. mouse.
      PROiQ14B80.
      SOURCEiSearch...

      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.
      IPR003974. K_chnl_volt-dep_Kv3.
      IPR011333. SKP1/BTB/POZ.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 2 hits.
      PfamiPF02214. BTB_2. 1 hit.
      PF00520. Ion_trans. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01491. KVCHANNEL.
      PR01498. SHAWCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 2 hits.
      ProtoNetiSearch...

      Entry informationi

      Entry nameiKCNC2_MOUSE
      AccessioniPrimary (citable) accession number: Q14B80
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: November 13, 2007
      Last sequence update: August 22, 2006
      Last modified: November 30, 2016
      This is version 83 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      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.