KCNC1_HUMAN
ID KCNC1_HUMAN Reviewed; 511 AA.
AC P48547; K4DI87;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Potassium voltage-gated channel subfamily C member 1;
DE AltName: Full=NGK2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv3.1;
DE AltName: Full=Voltage-gated potassium channel subunit Kv4;
GN Name=KCNC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8449507; DOI=10.1006/geno.1993.1075;
RA Ried T., Rudy B., de Miera E., Lau D., Ward D.C., Sen K.;
RT "Localization of a highly conserved human potassium channel gene (NGK2-KV4;
RT KCNC1) to chromosome 11p15.";
RL Genomics 15:405-411(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 244-475 (ISOFORM 1).
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 [5]
RP INTERACTION WITH KCNC3.
RX PubMed=23734863; DOI=10.1042/bj20130034;
RA Zhao J., Zhu J., Thornhill W.B.;
RT "Spinocerebellar ataxia-13 Kv3.3 potassium channels: arginine-to-histidine
RT mutations affect both functional and protein expression on the cell
RT surface.";
RL Biochem. J. 454:259-265(2013).
RN [6]
RP INVOLVEMENT IN EPM7, VARIANT EPM7 HIS-320, CHARACTERIZATION OF VARIANT EPM7
RP HIS-320, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25401298; DOI=10.1038/ng.3144;
RA Muona M., Berkovic S.F., Dibbens L.M., Oliver K.L., Maljevic S.,
RA Bayly M.A., Joensuu T., Canafoglia L., Franceschetti S., Michelucci R.,
RA Markkinen S., Heron S.E., Hildebrand M.S., Andermann E., Andermann F.,
RA Gambardella A., Tinuper P., Licchetta L., Scheffer I.E., Criscuolo C.,
RA Filla A., Ferlazzo E., Ahmad J., Ahmad A., Baykan B., Said E., Topcu M.,
RA Riguzzi P., King M.D., Ozkara C., Andrade D.M., Engelsen B.A., Crespel A.,
RA Lindenau M., Lohmann E., Saletti V., Massano J., Privitera M., Espay A.J.,
RA Kauffmann B., Duchowny M., Moeller R.S., Straussberg R., Afawi Z.,
RA Ben-Zeev B., Samocha K.E., Daly M.J., Petrou S., Lerche H., Palotie A.,
RA Lehesjoki A.E.;
RT "A recurrent de novo mutation in KCNC1 causes progressive myoclonus
RT epilepsy.";
RL Nat. Genet. 47:39-46(2015).
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:25401298).
CC Can form functional homotetrameric channels and heterotetrameric
CC channels that contain variable proportions of KCNC2, and possibly other
CC family members as well. Contributes to fire sustained trains of very
CC brief action potentials at high frequency in pallidal neurons.
CC {ECO:0000250|UniProtKB:P25122, ECO:0000269|PubMed:25401298}.
CC -!- SUBUNIT: Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity).
CC Heteromultimer with KCNC2 (By similarity). Heterotetramer with KCNC3
CC (PubMed:23734863). Interacts with the ancillary subunits KCNE1 and
CC KCNE2; the interaction modulates channel activity (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P25122,
CC ECO:0000269|PubMed:23734863}.
CC -!- INTERACTION:
CC P48547; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-12830942, EBI-12033434;
CC P48547; P55061: TMBIM6; NbExp=3; IntAct=EBI-12830942, EBI-1045825;
CC P48547; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-12830942, EBI-11988865;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25401298};
CC Multi-pass membrane protein {ECO:0000255}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P25122}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:P25122}. Note=Localizes in parallel fiber
CC membranes, distributed on the perisynaptic and extrasynaptic membranes
CC away from the active zones. {ECO:0000250|UniProtKB:P25122}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48547-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48547-2; Sequence=VSP_055129;
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 -!- DISEASE: Epilepsy, progressive myoclonic 7 (EPM7) [MIM:616187]: A form
CC of progressive myoclonic epilepsy, a clinically and genetically
CC heterogeneous group of disorders defined by the combination of action
CC and reflex myoclonus, other types of epileptic seizures, and
CC progressive neurodegeneration and neurocognitive impairment. EPM7 is an
CC autosomal dominant form characterized by myoclonic epilepsy apparent in
CC the first or second decades of life. Cognitive function may decline in
CC some patients. {ECO:0000269|PubMed:25401298}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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; S56770; AAB25764.1; -; mRNA.
DR EMBL; AC124056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC124078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC124301; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68425.1; -; Genomic_DNA.
DR EMBL; M96747; AAA59458.1; -; mRNA.
DR CCDS; CCDS44547.1; -. [P48547-2]
DR CCDS; CCDS7827.1; -. [P48547-1]
DR PIR; A46020; A46020.
DR RefSeq; NP_001106212.1; NM_001112741.1. [P48547-2]
DR RefSeq; NP_004967.1; NM_004976.4. [P48547-1]
DR AlphaFoldDB; P48547; -.
DR SMR; P48547; -.
DR BioGRID; 109948; 12.
DR IntAct; P48547; 4.
DR STRING; 9606.ENSP00000265969; -.
DR BindingDB; P48547; -.
DR ChEMBL; CHEMBL5529; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; P48547; -.
DR TCDB; 1.A.1.2.24; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; P48547; 2 sites.
DR iPTMnet; P48547; -.
DR PhosphoSitePlus; P48547; -.
DR BioMuta; KCNC1; -.
DR DMDM; 1352085; -.
DR MassIVE; P48547; -.
DR PaxDb; P48547; -.
DR PeptideAtlas; P48547; -.
DR PRIDE; P48547; -.
DR ProteomicsDB; 55903; -. [P48547-1]
DR Antibodypedia; 24953; 421 antibodies from 32 providers.
DR DNASU; 3746; -.
DR Ensembl; ENST00000265969.8; ENSP00000265969.7; ENSG00000129159.9. [P48547-2]
DR Ensembl; ENST00000379472.4; ENSP00000368785.3; ENSG00000129159.9. [P48547-1]
DR Ensembl; ENST00000640909.2; ENSP00000491644.2; ENSG00000129159.9. [P48547-2]
DR GeneID; 3746; -.
DR KEGG; hsa:3746; -.
DR MANE-Select; ENST00000265969.8; ENSP00000265969.7; NM_001112741.2; NP_001106212.1. [P48547-2]
DR UCSC; uc001mnk.5; human. [P48547-1]
DR CTD; 3746; -.
DR DisGeNET; 3746; -.
DR GeneCards; KCNC1; -.
DR HGNC; HGNC:6233; KCNC1.
DR HPA; ENSG00000129159; Tissue enriched (brain).
DR MalaCards; KCNC1; -.
DR MIM; 176258; gene.
DR MIM; 616187; phenotype.
DR neXtProt; NX_P48547; -.
DR OpenTargets; ENSG00000129159; -.
DR Orphanet; 435438; Progressive myoclonic epilepsy type 7.
DR PharmGKB; PA30026; -.
DR VEuPathDB; HostDB:ENSG00000129159; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000156912; -.
DR HOGENOM; CLU_011722_4_3_1; -.
DR InParanoid; P48547; -.
DR OMA; MGQGDDS; -.
DR OrthoDB; 818306at2759; -.
DR PhylomeDB; P48547; -.
DR TreeFam; TF352511; -.
DR PathwayCommons; P48547; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; P48547; -.
DR SIGNOR; P48547; -.
DR BioGRID-ORCS; 3746; 22 hits in 1063 CRISPR screens.
DR GenomeRNAi; 3746; -.
DR Pharos; P48547; Tclin.
DR PRO; PR:P48547; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P48547; protein.
DR Bgee; ENSG00000129159; Expressed in right hemisphere of cerebellum and 139 other tissues.
DR ExpressionAtlas; P48547; baseline and differential.
DR Genevisible; P48547; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030673; C:axolemma; IEA:Ensembl.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0044305; C:calyx of Held; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; IEA:Ensembl.
DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR GO; GO:0099508; F:voltage-gated ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl.
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:1903818; P:positive regulation of voltage-gated potassium channel activity; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
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; Disease variant;
KW Epilepsy; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Neurodegeneration; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..511
FT /note="Potassium voltage-gated channel subfamily C member
FT 1"
FT /id="PRO_0000054051"
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:0000250|UniProtKB:P15388"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15388"
FT MOD_RES 483
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15388"
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 /evidence="ECO:0000305"
FT /id="VSP_055129"
FT VARIANT 320
FT /note="R -> H (in EPM7; causes a dominant-negative loss of
FT current upon membrane depolarization; dbSNP:rs727502818)"
FT /evidence="ECO:0000269|PubMed:25401298"
FT /id="VAR_072705"
SQ SEQUENCE 511 AA; 57942 MW; 10A93478F7120ABB 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 LMRVIFCPNK 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
