KCNC1_MOUSE
ID KCNC1_MOUSE Reviewed; 511 AA.
AC P15388; E9PVV3;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Potassium voltage-gated channel subfamily C member 1;
DE AltName: Full=NGK2 {ECO:0000303|PubMed:2599109};
DE AltName: Full=Voltage-gated potassium channel subunit Kv3.1;
DE AltName: Full=Voltage-gated potassium channel subunit Kv4;
GN Name=Kcnc1 {ECO:0000312|MGI:MGI:96667};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2599109; DOI=10.1016/0014-5793(89)81488-7;
RA Yokoyama S., Imoto K., Kawamura T., Higashida H., Iwabe N., Miyata T.,
RA Numa S.;
RT "Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells.
RT Primary structure and functional expression from cDNAs.";
RL FEBS Lett. 259:37-42(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1400413; DOI=10.1016/s0021-9258(19)36784-5;
RA Grissmer S., Ghanshani S., Dethlefs B., McPherson J.D., Wasmuth J.J.,
RA Gutman G.A., Cahalan M.D., Chandy K.G.;
RT "The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11,
RT encodes the type l K+ channel in T cells.";
RL J. Biol. Chem. 267:20971-20979(1992).
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=9037088; DOI=10.1073/pnas.94.4.1533;
RA Ho C.S., Grange R.W., Joho R.H.;
RT "Pleiotropic effects of a disrupted K+ channel gene: reduced body weight,
RT impaired motor skill and muscle contraction, but no seizures.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:1533-1538(1997).
RN [5]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=11517255; DOI=10.1523/jneurosci.21-17-06657.2001;
RA Espinosa F., McMahon A., Chan E., Wang S., Ho C.S., Heintz N., Joho R.H.;
RT "Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus
RT in mice lacking the potassium channels Kv3.1 and Kv3.3.";
RL J. Neurosci. 21:6657-6665(2001).
RN [6]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=15217387; DOI=10.1111/j.0953-816x.2004.03385.x;
RA McMahon A., Fowler S.C., Perney T.M., Akemann W., Knoepfel T., Joho R.H.;
RT "Allele-dependent changes of olivocerebellar circuit properties in the
RT absence of the voltage-gated potassium channels Kv3.1 and Kv3.3.";
RL Eur. J. Neurosci. 19:3317-3327(2004).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=16923152; DOI=10.1111/j.1601-183x.2005.00184.x;
RA Joho R.H., Street C., Matsushita S., Knoepfel T.;
RT "Behavioral motor dysfunction in Kv3-type potassium channel-deficient
RT mice.";
RL Genes Brain Behav. 5:472-482(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160; SER-474 AND THR-483, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Voltage-gated potassium channel that plays an important role
CC in the rapid repolarization of fast-firing brain neurons. The channel
CC opens in response to the voltage difference across the membrane,
CC forming a potassium-selective channel through which potassium ions pass
CC in accordance with their electrochemical gradient (PubMed:2599109,
CC PubMed:1400413). Can form functional homotetrameric channels and
CC heterotetrameric channels that contain variable proportions of KCNC2,
CC and possibly other family members as well. Contributes to fire
CC sustained trains of very brief action potentials at high frequency in
CC pallidal neurons. {ECO:0000250|UniProtKB:P25122,
CC ECO:0000269|PubMed:1400413, ECO:0000269|PubMed:2599109}.
CC -!- SUBUNIT: Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity).
CC Heteromultimer with KCNC2 (By similarity). Heterotetramer with KCNC3
CC (By similarity). Interacts with the ancillary subunits KCNE1 and KCNE2;
CC the interaction modulates channel activity (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P48547}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1400413,
CC ECO:0000269|PubMed:2599109}; Multi-pass membrane protein {ECO:0000255}.
CC Cell projection, axon {ECO:0000250|UniProtKB:P25122}. Presynaptic cell
CC membrane {ECO:0000250|UniProtKB:P25122}. Note=Localizes in parallel
CC fiber membranes, distributed on the perisynaptic and extrasynaptic
CC membranes away from the active zones. {ECO:0000250|UniProtKB:P25122}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=KV3.1;
CC IsoId=P15388-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15388-3; Sequence=VSP_058604;
CC -!- TISSUE SPECIFICITY: Detected in cerebellum (PubMed:11517255,
CC PubMed:15217387). Detected in brain (at protein level)
CC (PubMed:9037088). Detected in brain (PubMed:9037088).
CC {ECO:0000269|PubMed:11517255, ECO:0000269|PubMed:15217387,
CC ECO:0000269|PubMed:9037088}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. {ECO:0000305}.
CC -!- DOMAIN: The tail may be important in modulation of channel activity
CC and/or targeting of the channel to specific subcellular compartments.
CC {ECO:0000305}.
CC -!- PTM: N-glycosylated; contains sialylated glycans.
CC {ECO:0000250|UniProtKB:P25122}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate. They are viable and fertile, but have lower body weight than
CC wild-type. They have normal spontaneous locomotor activity, but
CC impaired motor skills (PubMed:9037088). Mice lacking both Kcnc3 and
CC Kcnc1 are born at the expected Mendelian rate, but the pups do not
CC thrive and all die about 26 days after birth when kept together with
CC other littermates. Their failure to thrive may be due to motor
CC problems; mutant pups survive when fed separately, but 45 days after
CC birth their body weight is only 50 to 60 % of that of wild-type
CC (PubMed:11517255). They appear uncoordinated and display severe ataxia,
CC myoclonus and spontaneous whole-body muscle jerks, but display no
CC obvious alterations in brain morphology (PubMed:11517255,
CC PubMed:15217387, PubMed:16923152). Mutant mice are also much more
CC sensitive to ethanol and fall sideways at ethanol concentrations that
CC have no effect on wild-type mice (PubMed:11517255). They display
CC increased locomotor and exploratory activity (PubMed:11517255,
CC PubMed:15217387). Mice lacking Kcnc1 show reduced response to
CC tremorogenic agent harmaline; mice lacking both Kcnc3 and Kcnc1 are
CC resistant to the tremorogenic agent harmaline (PubMed:15217387).
CC {ECO:0000269|PubMed:11517255, ECO:0000269|PubMed:15217387,
CC ECO:0000269|PubMed:16923152}.
CC -!- SIMILARITY: Belongs to the potassium channel family. C (Shaw) (TC
CC 1.A.1.2) subfamily. Kv3.1/KCNC1 sub-subfamily. {ECO:0000305}.
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DR EMBL; Y07521; CAA68814.1; -; mRNA.
DR EMBL; AC020786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS21278.1; -. [P15388-1]
DR CCDS; CCDS52252.1; -. [P15388-3]
DR PIR; S07095; S07095.
DR RefSeq; NP_032447.1; NM_008421.3. [P15388-1]
DR AlphaFoldDB; P15388; -.
DR SMR; P15388; -.
DR BioGRID; 200887; 3.
DR STRING; 10090.ENSMUSP00000124938; -.
DR ChEMBL; CHEMBL4105978; -.
DR DrugCentral; P15388; -.
DR GuidetoPHARMACOLOGY; 548; -.
DR GlyGen; P15388; 2 sites.
DR iPTMnet; P15388; -.
DR PhosphoSitePlus; P15388; -.
DR SwissPalm; P15388; -.
DR PaxDb; P15388; -.
DR PeptideAtlas; P15388; -.
DR PRIDE; P15388; -.
DR ProteomicsDB; 269257; -. [P15388-1]
DR ProteomicsDB; 269258; -. [P15388-3]
DR ABCD; P15388; 1 sequenced antibody.
DR Antibodypedia; 24953; 421 antibodies from 32 providers.
DR DNASU; 16502; -.
DR Ensembl; ENSMUST00000025202; ENSMUSP00000025202; ENSMUSG00000058975. [P15388-1]
DR Ensembl; ENSMUST00000160433; ENSMUSP00000124938; ENSMUSG00000058975. [P15388-3]
DR GeneID; 16502; -.
DR KEGG; mmu:16502; -.
DR UCSC; uc009gyo.2; mouse. [P15388-1]
DR CTD; 3746; -.
DR MGI; MGI:96667; Kcnc1.
DR VEuPathDB; HostDB:ENSMUSG00000058975; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000156912; -.
DR HOGENOM; CLU_011722_4_3_1; -.
DR InParanoid; P15388; -.
DR OMA; MGQGDDS; -.
DR OrthoDB; 818306at2759; -.
DR PhylomeDB; P15388; -.
DR TreeFam; TF352511; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR BioGRID-ORCS; 16502; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Kcnc1; mouse.
DR PRO; PR:P15388; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P15388; protein.
DR Bgee; ENSMUSG00000058975; Expressed in cerebellar cortex and 103 other tissues.
DR ExpressionAtlas; P15388; baseline and differential.
DR Genevisible; P15388; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030673; C:axolemma; IDA:MGI.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0044305; C:calyx of Held; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0032590; C:dendrite membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0032589; C:neuron projection membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:MGI.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; IDA:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0099508; F:voltage-gated ion channel activity involved in regulation of presynaptic membrane potential; ISO:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0021759; P:globus pallidus development; IEA:Ensembl.
DR GO; GO:0034767; P:positive regulation of ion transmembrane transport; ISO:MGI.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:1903818; P:positive regulation of voltage-gated potassium channel activity; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0051262; P:protein tetramerization; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; ISO:MGI.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:0014075; P:response to amine; IEA:Ensembl.
DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
DR GO; GO:0071774; P:response to fibroblast growth factor; IEA:Ensembl.
DR GO; GO:0009642; P:response to light intensity; IEA:Ensembl.
DR GO; GO:1990089; P:response to nerve growth factor; IEA:Ensembl.
DR GO; GO:0035864; P:response to potassium ion; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003974; K_chnl_volt-dep_Kv3.
DR InterPro; IPR005403; K_chnl_volt-dep_Kv3.1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01581; KV31CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01498; SHAWCHANNEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Synapse;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..511
FT /note="Potassium voltage-gated channel subfamily C member
FT 1"
FT /id="PRO_0000054052"
FT TOPO_DOM 1..190
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..209
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..267
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 268..276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..295
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..331
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..344
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..366
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..436
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..511
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 121..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 400..405
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25122"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25122"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25122"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25122"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 483
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 502..511
FT /note="GRKPLRGMSI -> DSKLNGEVAKAALANEDCPHIDQALTPDEGLPFTRSGT
FT RERYGPCFLLSTGEYACPPGGGMRKDLCKESPVIAKYMPTEAVRVT (in isoform
FT 2)"
FT /id="VSP_058604"
SQ 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
