Potassium voltage-gated channel subfamily C member 1 (NGK2) (Voltage-gated potassium channel subunit Kv3.1) (Voltage-gated potassium channel subunit Kv4)

 KCNC1_MOUSE             Reviewed;         511 AA.
 P15388; E9PVV3;
 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
 01-APR-1990, sequence version 1.
 23-FEB-2022, entry version 185.
 RecName: Full=Potassium voltage-gated channel subfamily C member 1;
 AltName: Full=NGK2 {ECO:0000303|PubMed:2599109};
 AltName: Full=Voltage-gated potassium channel subunit Kv3.1;
 AltName: Full=Voltage-gated potassium channel subunit Kv4;
 Name=Kcnc1 {ECO:0000312|MGI:MGI:96667};
 Mus musculus (Mouse).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
 Murinae; Mus; Mus.
 NCBI_TaxID=10090;
 [1]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
 PubMed=2599109; DOI=10.1016/0014-5793(89)81488-7;
 Yokoyama S., Imoto K., Kawamura T., Higashida H., Iwabe N., Miyata T.,
 Numa S.;
 "Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells.
 Primary structure and functional expression from cDNAs.";
 FEBS Lett. 259:37-42(1989).
 [2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 STRAIN=C57BL/6J;
 PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
 Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
 Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
 Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
 Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
 Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
 Eichler E.E., Ponting C.P.;
 "Lineage-specific biology revealed by a finished genome assembly of the
 mouse.";
 PLoS Biol. 7:E1000112-E1000112(2009).
 [3]
 FUNCTION, AND SUBCELLULAR LOCATION.
 PubMed=1400413;
 Grissmer S., Ghanshani S., Dethlefs B., McPherson J.D., Wasmuth J.J.,
 Gutman G.A., Cahalan M.D., Chandy K.G.;
 "The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11,
 encodes the type l K+ channel in T cells.";
 J. Biol. Chem. 267:20971-20979(1992).
 [4]
 DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
 PubMed=9037088; DOI=10.1073/pnas.94.4.1533;
 Ho C.S., Grange R.W., Joho R.H.;
 "Pleiotropic effects of a disrupted K+ channel gene: reduced body weight,
 impaired motor skill and muscle contraction, but no seizures.";
 Proc. Natl. Acad. Sci. U.S.A. 94:1533-1538(1997).
 [5]
 DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
 PubMed=11517255; DOI=10.1523/jneurosci.21-17-06657.2001;
 Espinosa F., McMahon A., Chan E., Wang S., Ho C.S., Heintz N., Joho R.H.;
 "Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus
 in mice lacking the potassium channels Kv3.1 and Kv3.3.";
 J. Neurosci. 21:6657-6665(2001).
 [6]
 DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
 PubMed=15217387; DOI=10.1111/j.0953-816x.2004.03385.x;
 McMahon A., Fowler S.C., Perney T.M., Akemann W., Knoepfel T., Joho R.H.;
 "Allele-dependent changes of olivocerebellar circuit properties in the
 absence of the voltage-gated potassium channels Kv3.1 and Kv3.3.";
 Eur. J. Neurosci. 19:3317-3327(2004).
 [7]
 DISRUPTION PHENOTYPE.
 PubMed=16923152; DOI=10.1111/j.1601-183x.2005.00184.x;
 Joho R.H., Street C., Matsushita S., Knoepfel T.;
 "Behavioral motor dysfunction in Kv3-type potassium channel-deficient
 mice.";
 Genes Brain Behav. 5:472-482(2006).
 [8]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160; SER-474 AND THR-483, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Brain;
 PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
 Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
 Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
 "A tissue-specific atlas of mouse protein phosphorylation and expression.";
 Cell 143:1174-1189(2010).
 -!- FUNCTION: Voltage-gated potassium channel that plays an important role
     in the rapid repolarization of fast-firing brain neurons. The channel
     opens in response to the voltage difference across the membrane,
     forming a potassium-selective channel through which potassium ions pass
     in accordance with their electrochemical gradient (PubMed:2599109,
     PubMed:1400413). Can form functional homotetrameric channels and
     heterotetrameric channels that contain variable proportions of KCNC2,
     and possibly other family members as well. Contributes to fire
     sustained trains of very brief action potentials at high frequency in
     pallidal neurons. {ECO:0000250|UniProtKB:P25122,
     ECO:0000269|PubMed:1400413, ECO:0000269|PubMed:2599109}.
 -!- SUBUNIT: Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity).
     Heteromultimer with KCNC2 (By similarity). Heterotetramer with KCNC3
     (By similarity). Interacts with the ancillary subunits KCNE1 and KCNE2;
     the interaction modulates channel activity (By similarity).
     {ECO:0000250, ECO:0000250|UniProtKB:P48547}.
 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1400413,
     ECO:0000269|PubMed:2599109}; Multi-pass membrane protein {ECO:0000255}.
     Cell projection, axon {ECO:0000250|UniProtKB:P25122}. Cell junction,
     synapse, presynaptic cell membrane {ECO:0000250|UniProtKB:P25122}.
     Note=Localizes in parallel fiber membranes, distributed on the
     perisynaptic and extrasynaptic membranes away from the active zones.
     {ECO:0000250|UniProtKB:P25122}.
 -!- ALTERNATIVE PRODUCTS:
     Event=Alternative splicing; Named isoforms=2;
     Name=1; Synonyms=KV3.1;
       IsoId=P15388-1; Sequence=Displayed;
     Name=2;
       IsoId=P15388-3; Sequence=VSP_058604;
 -!- TISSUE SPECIFICITY: Detected in cerebellum (PubMed:11517255,
     PubMed:15217387). Detected in brain (at protein level)
     (PubMed:9037088). Detected in brain (PubMed:9037088).
     {ECO:0000269|PubMed:11517255, ECO:0000269|PubMed:15217387,
     ECO:0000269|PubMed:9037088}.
 -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
     characterized by a series of positively charged amino acids at every
     third position. {ECO:0000305}.
 -!- DOMAIN: The tail may be important in modulation of channel activity
     and/or targeting of the channel to specific subcellular compartments.
     {ECO:0000305}.
 -!- PTM: N-glycosylated; contains sialylated glycans.
     {ECO:0000250|UniProtKB:P25122}.
 -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
     rate. They are viable and fertile, but have lower body weight than
     wild-type. They have normal spontaneous locomotor activity, but
     impaired motor skills (PubMed:9037088). Mice lacking both Kcnc3 and
     Kcnc1 are born at the expected Mendelian rate, but the pups do not
     thrive and all die about 26 days after birth when kept together with
     other littermates. Their failure to thrive may be due to motor
     problems; mutant pups survive when fed separately, but 45 days after
     birth their body weight is only 50 to 60 % of that of wild-type
     (PubMed:11517255). They appear uncoordinated and display severe ataxia,
     myoclonus and spontaneous whole-body muscle jerks, but display no
     obvious alterations in brain morphology (PubMed:11517255,
     PubMed:15217387, PubMed:16923152). Mutant mice are also much more
     sensitive to ethanol and fall sideways at ethanol concentrations that
     have no effect on wild-type mice (PubMed:11517255). They display
     increased locomotor and exploratory activity (PubMed:11517255,
     PubMed:15217387). Mice lacking Kcnc1 show reduced response to
     tremorogenic agent harmaline; mice lacking both Kcnc3 and Kcnc1 are
     resistant to the tremorogenic agent harmaline (PubMed:15217387).
     {ECO:0000269|PubMed:11517255, ECO:0000269|PubMed:15217387,
     ECO:0000269|PubMed:16923152}.
 -!- SIMILARITY: Belongs to the potassium channel family. C (Shaw) (TC
     1.A.1.2) subfamily. Kv3.1/KCNC1 sub-subfamily. {ECO:0000305}.
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 EMBL; Y07521; CAA68814.1; -; mRNA.
 EMBL; AC020786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
 EMBL; AC090652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
 CCDS; CCDS21278.1; -. [P15388-1]
 CCDS; CCDS52252.1; -. [P15388-3]
 PIR; S07095; S07095.
 RefSeq; NP_032447.1; NM_008421.3. [P15388-1]
 SMR; P15388; -.
 BioGRID; 200887; 3.
 STRING; 10090.ENSMUSP00000124938; -.
 ChEMBL; CHEMBL4105978; -.
 DrugCentral; P15388; -.
 GuidetoPHARMACOLOGY; 548; -.
 GlyGen; P15388; 2 sites.
 iPTMnet; P15388; -.
 PhosphoSitePlus; P15388; -.
 SwissPalm; P15388; -.
 PaxDb; P15388; -.
 PeptideAtlas; P15388; -.
 PRIDE; P15388; -.
 ProteomicsDB; 269257; -. [P15388-1]
 ProteomicsDB; 269258; -. [P15388-3]
 ABCD; P15388; 1 sequenced antibody.
 Antibodypedia; 24953; 419 antibodies from 32 providers.
 DNASU; 16502; -.
 Ensembl; ENSMUST00000025202; ENSMUSP00000025202; ENSMUSG00000058975. [P15388-1]
 Ensembl; ENSMUST00000160433; ENSMUSP00000124938; ENSMUSG00000058975. [P15388-3]
 GeneID; 16502; -.
 KEGG; mmu:16502; -.
 UCSC; uc009gyo.2; mouse. [P15388-1]
 CTD; 3746; -.
 MGI; MGI:96667; Kcnc1.
 VEuPathDB; HostDB:ENSMUSG00000058975; -.
 eggNOG; KOG3713; Eukaryota.
 GeneTree; ENSGT00940000156912; -.
 HOGENOM; CLU_011722_4_3_1; -.
 InParanoid; P15388; -.
 OMA; PNFCKSG; -.
 OrthoDB; 818306at2759; -.
 PhylomeDB; P15388; -.
 TreeFam; TF352511; -.
 Reactome; R-MMU-1296072; Voltage gated Potassium channels.
 BioGRID-ORCS; 16502; 0 hits in 66 CRISPR screens.
 ChiTaRS; Kcnc1; mouse.
 PRO; PR:P15388; -.
 Proteomes; UP000000589; Chromosome 7.
 RNAct; P15388; protein.
 Bgee; ENSMUSG00000058975; Expressed in cerebellum and 160 other tissues.
 Genevisible; P15388; MM.
 GO; GO:0030673; C:axolemma; IDA:MGI.
 GO; GO:0030424; C:axon; IBA:GO_Central.
 GO; GO:0044305; C:calyx of Held; ISO:MGI.
 GO; GO:0009986; C:cell surface; ISO:MGI.
 GO; GO:0030425; C:dendrite; ISO:MGI.
 GO; GO:0032590; C:dendrite membrane; IDA:MGI.
 GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
 GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
 GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
 GO; GO:0016020; C:membrane; ISO:MGI.
 GO; GO:0032589; C:neuron projection membrane; ISO:MGI.
 GO; GO:0043025; C:neuronal cell body; ISO:MGI.
 GO; GO:0032809; C:neuronal cell body membrane; IDA:MGI.
 GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
 GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
 GO; GO:0019894; F:kinesin binding; IDA:MGI.
 GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
 GO; GO:0099508; F:voltage-gated ion channel activity involved in regulation of presynaptic membrane potential; ISO:MGI.
 GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
 GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
 GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
 GO; GO:0021759; P:globus pallidus development; IEA:Ensembl.
 GO; GO:0034767; P:positive regulation of ion transmembrane transport; ISO:MGI.
 GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; ISO:MGI.
 GO; GO:1903818; P:positive regulation of voltage-gated potassium channel activity; ISO:MGI.
 GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
 GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
 GO; GO:0051262; P:protein tetramerization; ISS:UniProtKB.
 GO; GO:0034765; P:regulation of ion transmembrane transport; ISO:MGI.
 GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO:MGI.
 GO; GO:0014075; P:response to amine; IEA:Ensembl.
 GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
 GO; GO:0071774; P:response to fibroblast growth factor; IEA:Ensembl.
 GO; GO:0009642; P:response to light intensity; IEA:Ensembl.
 GO; GO:1990089; P:response to nerve growth factor; IEA:Ensembl.
 GO; GO:0035864; P:response to potassium ion; IEA:Ensembl.
 GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
 Gene3D; 1.20.120.350; -; 1.
 Gene3D; 3.30.710.10; -; 1.
 InterPro; IPR000210; BTB/POZ_dom.
 InterPro; IPR005821; Ion_trans_dom.
 InterPro; IPR003968; K_chnl_volt-dep_Kv.
 InterPro; IPR003974; K_chnl_volt-dep_Kv3.
 InterPro; IPR005403; K_chnl_volt-dep_Kv3.1.
 InterPro; IPR011333; SKP1/BTB/POZ_sf.
 InterPro; IPR003131; T1-type_BTB.
 InterPro; IPR028325; VG_K_chnl.
 InterPro; IPR027359; Volt_channel_dom_sf.
 PANTHER; PTHR11537; PTHR11537; 1.
 Pfam; PF02214; BTB_2; 1.
 Pfam; PF00520; Ion_trans; 1.
 PRINTS; PR01581; KV31CHANNEL.
 PRINTS; PR01491; KVCHANNEL.
 PRINTS; PR01498; SHAWCHANNEL.
 SMART; SM00225; BTB; 1.
 SUPFAM; SSF54695; SSF54695; 1.
 1: Evidence at protein level;
 Alternative splicing; Cell junction; Cell membrane; Cell projection;
 Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
 Potassium; Potassium channel; Potassium transport; Reference proteome;
 Synapse; Transmembrane; Transmembrane helix; Transport;
 Voltage-gated channel.
 CHAIN           1..511
                 /note="Potassium voltage-gated channel subfamily C member
                 1"
                 /id="PRO_0000054052"
 TOPO_DOM        1..190
                 /note="Cytoplasmic"
                 /evidence="ECO:0000255"
 TRANSMEM        191..209
                 /note="Helical; Name=Segment S1"
                 /evidence="ECO:0000255"
 TRANSMEM        248..267
                 /note="Helical; Name=Segment S2"
                 /evidence="ECO:0000255"
 TOPO_DOM        268..276
                 /note="Cytoplasmic"
                 /evidence="ECO:0000255"
 TRANSMEM        277..295
                 /note="Helical; Name=Segment S3"
                 /evidence="ECO:0000255"
 TRANSMEM        309..331
                 /note="Helical; Voltage-sensor; Name=Segment S4"
                 /evidence="ECO:0000255"
 TOPO_DOM        332..344
                 /note="Cytoplasmic"
                 /evidence="ECO:0000255"
 TRANSMEM        345..366
                 /note="Helical; Name=Segment S5"
                 /evidence="ECO:0000255"
 TRANSMEM        415..436
                 /note="Helical; Name=Segment S6"
                 /evidence="ECO:0000255"
 TOPO_DOM        437..511
                 /note="Cytoplasmic"
                 /evidence="ECO:0000255"
 REGION          121..147
                 /note="Disordered"
                 /evidence="ECO:0000256|SAM:MobiDB-lite"
 MOTIF           400..405
                 /note="Selectivity filter"
                 /evidence="ECO:0000250"
 MOD_RES         44
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P25122"
 MOD_RES         130
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P25122"
 MOD_RES         142
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P25122"
 MOD_RES         158
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P25122"
 MOD_RES         160
                 /note="Phosphoserine"
                 /evidence="ECO:0007744|PubMed:21183079"
 MOD_RES         474
                 /note="Phosphoserine"
                 /evidence="ECO:0007744|PubMed:21183079"
 MOD_RES         483
                 /note="Phosphothreonine"
                 /evidence="ECO:0007744|PubMed:21183079"
 CARBOHYD        220
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        229
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 VAR_SEQ         502..511
                 /note="GRKPLRGMSI -> DSKLNGEVAKAALANEDCPHIDQALTPDEGLPFTRSGT
                 RERYGPCFLLSTGEYACPPGGGMRKDLCKESPVIAKYMPTEAVRVT (in isoform
                 2)"
                 /id="VSP_058604"
 SEQUENCE   511 AA;  57928 MW;  50A939E8F7120F37 CRC64;
 MGQGDESERI VINVGGTRHQ TYRSTLRTLP GTRLAWLAEP DAHSHFDYDP RADEFFFDRH
 PGVFAHILNY YRTGKLHCPA DVCGPLYEEE LAFWGIDETD VEPCCWMTYR QHRDAEEALD
 SFGGAPLDNS ADDADADGPG DSGDGEDELE MTKRLALSDS PDGRPGGFWR RWQPRIWALF
 EDPYSSRYAR YVAFASLFFI LVSITTFCLE THERFNPIVN KTEIENVRNG TQVRYYREAE
 TEAFLTYIEG VCVVWFTFEF LMRVVFCPNK VEFIKNSLNI IDFVAILPFY LEVGLSGLSS
 KAAKDVLGFL RVVRFVRILR IFKLTRHFVG LRVLGHTLRA STNEFLLLII FLALGVLIFA
 TMIYYAERIG AQPNDPSASE HTHFKNIPIG FWWAVVTMTT LGYGDMYPQT WSGMLVGALC
 ALAGVLTIAM PVPVIVNNFG MYYSLAMAKQ KLPKKKKKHI PRPPQLGSPN YCKSVVNSPH
 HSTQSDTCPL AQEEILEINR AGRKPLRGMS I

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