KCNE1_HUMAN
ID KCNE1_HUMAN Reviewed; 129 AA.
AC P15382; A5H1P2; Q8N709; Q91Z94;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Potassium voltage-gated channel subfamily E member 1;
DE AltName: Full=Delayed rectifier potassium channel subunit IsK;
DE AltName: Full=IKs producing slow voltage-gated potassium channel subunit beta Mink;
DE AltName: Full=Minimal potassium channel;
GN Name=KCNE1;
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 [GENOMIC DNA].
RX PubMed=2730656; DOI=10.1016/0006-291x(89)91577-5;
RA Murai T., Kakizuka A., Takumi T., Ohkubo H., Nakanishi S.;
RT "Molecular cloning and sequence analysis of human genomic DNA encoding a
RT novel membrane protein which exhibits a slowly activating potassium channel
RT activity.";
RL Biochem. Biophys. Res. Commun. 161:176-181(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-38.
RC TISSUE=Leukocyte;
RX PubMed=7828904; DOI=10.1016/0378-1119(94)90685-8;
RA Lai L.P., Deng C.L., Moss A.J., Kass R.S., Liang C.S.;
RT "Polymorphism of the gene encoding a human minimal potassium ion channel
RT (minK).";
RL Gene 151:339-340(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cornea;
RA Rae J.L.;
RT "Delayed rectifier potassium channel subunit from human cornea
RT epithelium.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-32 AND GLY-38.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=9312006; DOI=10.1093/emboj/16.17.5472;
RA Chouabe C., Neyroud N., Guicheney P., Lazdunski M., Romey G., Barhanin J.;
RT "Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and
RT Lange-Nielsen inherited cardiac arrhythmias.";
RL EMBO J. 16:5472-5479(1997).
RN [7]
RP INTERACTION WITH KCNH2.
RX PubMed=9230439; DOI=10.1038/40882;
RA McDonald T.V., Yu Z., Ming Z., Palma E., Meyers M.B., Wang K.-W.,
RA Goldstein S.A.N., Fishman G.I.;
RT "A minK-HERG complex regulates the cardiac potassium current I(Kr).";
RL Nature 388:289-292(1997).
RN [8]
RP MUTAGENESIS OF LYS-69.
RX PubMed=11874988; DOI=10.1096/fj.01-0520hyp;
RA Abbott G.W., Goldstein S.A.N.;
RT "Disease-associated mutations in KCNE potassium channel subunits (MiRPs)
RT reveal promiscuous disruption of multiple currents and conservation of
RT mechanism.";
RL FASEB J. 16:390-400(2002).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19219384; DOI=10.1007/s00232-009-9154-8;
RA McCrossan Z.A., Roepke T.K., Lewis A., Panaghie G., Abbott G.W.;
RT "Regulation of the Kv2.1 potassium channel by MinK and MiRP1.";
RL J. Membr. Biol. 228:1-14(2009).
RN [10]
RP INTERACTION WITH KCNQ1, AND SUBCELLULAR LOCATION.
RX PubMed=20533308; DOI=10.1002/jcp.22265;
RA Roura-Ferrer M., Sole L., Oliveras A., Dahan R., Bielanska J.,
RA Villarroel A., Comes N., Felipe A.;
RT "Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface
RT targeting.";
RL J. Cell. Physiol. 225:692-700(2010).
RN [11]
RP GLYCOSYLATION AT ASN-5 AND ASN-26, AND CHARACTERIZATION OF VARIANT JLNS2
RP ILE-7.
RX PubMed=21676880; DOI=10.1074/jbc.m111.235168;
RA Bas T., Gao G.Y., Lvov A., Chandrasekhar K.D., Gilmore R., Kobertz W.R.;
RT "Post-translational N-glycosylation of type I transmembrane KCNE1 peptides:
RT implications for membrane protein biogenesis and disease.";
RL J. Biol. Chem. 286:28150-28159(2011).
RN [12]
RP GLYCOSYLATION AT ASN-5 AND THR-7, AND MUTAGENESIS OF ASN-5; THR-6; THR-7
RP AND SER-28.
RX PubMed=21669976; DOI=10.1113/jphysiol.2011.211284;
RA Chandrasekhar K.D., Lvov A., Terrenoire C., Gao G.Y., Kass R.S.,
RA Kobertz W.R.;
RT "O-glycosylation of the cardiac I(Ks) complex.";
RL J. Physiol. (Lond.) 589:3721-3730(2011).
RN [13]
RP MUTAGENESIS OF LYS-15; GLU-19 AND ARG-32, AND SITE GLU-19.
RX PubMed=26307551; DOI=10.1038/srep13399;
RA Sun P., Wu F., Wen M., Yang X., Wang C., Li Y., He S., Zhang L., Zhang Y.,
RA Tian C.;
RT "A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by
RT interacting with the KCNE1 auxiliary subunit.";
RL Sci. Rep. 5:13399-13399(2015).
RN [14]
RP STRUCTURE BY NMR.
RX PubMed=18611041; DOI=10.1021/bi800875q;
RA Kang C., Tian C., Soennichsen F.D., Smith J.A., Meiler J., George A.L. Jr.,
RA Vanoye C.G., Kim H.J., Sanders C.R.;
RT "Structure of KCNE1 and implications for how it modulates the KCNQ1
RT potassium channel.";
RL Biochemistry 47:7999-8006(2008).
RN [15]
RP VARIANT ASN-85.
RX PubMed=8899564; DOI=10.1006/jmcc.1996.0198;
RA Tesson F., Donger C., Denjoy I., Berthet M., Bennaceur M., Petit C.,
RA Coumel P., Schwartz K., Guicheney P.;
RT "Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen
RT syndrome.";
RL J. Mol. Cell. Cardiol. 28:2051-2055(1996).
RN [16]
RP VARIANT JLNS2 58-PRO-PRO-59.
RX PubMed=9328483; DOI=10.1093/hmg/6.12.2179;
RA Tyson J., Tranebjaerg L., Bellman S., Wren C., Taylor J.F.N., Bathen J.,
RA Aslaksen B., Soerland S.J., Lund O., Malcolm S., Pembrey M.,
RA Bhattacharya S., Bitner-Glindzicz M.;
RT "IsK and KvLQT1: mutation in either of the two subunits of the slow
RT component of the delayed rectifier potassium channel can cause Jervell and
RT Lange-Nielsen syndrome.";
RL Hum. Mol. Genet. 6:2179-2185(1997).
RN [17]
RP VARIANTS JLNS2 ILE-7 AND ASN-76.
RX PubMed=9354783; DOI=10.1038/ng1197-267;
RA Schulze-Bahr E., Wang Q., Wedekind H., Haverkamp W., Chen Q., Sun Y.,
RA Rubie C., Hordt M., Towbin J.A., Borggrefe M., Assmann G., Qu X.,
RA Somberg J.C., Breithardt G., Oberti C., Funke H.;
RT "KCNE1 mutations cause Jervell and Lange-Nielsen syndrome.";
RL Nat. Genet. 17:267-268(1997).
RN [18]
RP VARIANTS LQT5 LEU-74 AND ASN-76.
RX PubMed=9354802; DOI=10.1038/ng1197-338;
RA Splawski I., Tristani-Firouzi M., Lehmann M.H., Sanguinetti M.C.,
RA Keating M.T.;
RT "Mutations in the hminK gene cause long QT syndrome and suppress IKs
RT function.";
RL Nat. Genet. 17:338-340(1997).
RN [19]
RP VARIANT LQT5 ASN-76.
RX PubMed=9445165; DOI=10.1161/01.cir.97.2.142;
RA Duggal P., Vesely M.R., Wattanasirichaigoon D., Villafane J., Kaushik V.,
RA Beggs A.H.;
RT "Mutation of the gene for IsK associated with both Jervell and Lange-
RT Nielsen and Romano-Ward forms of Long-QT syndrome.";
RL Circulation 97:142-146(1998).
RN [20]
RP VARIANTS JLNS2 PHE-47; HIS-51 AND ASN-76, AND VARIANT LQT5 ARG-87.
RX PubMed=10400998; DOI=10.1093/hmg/8.8.1499;
RA Bianchi L., Shen Z., Dennis A.T., Priori S.G., Napolitano C., Ronchetti E.,
RA Bryskin R., Schwartz P.J., Brown A.M.;
RT "Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and
RT trafficking in long QT syndrome.";
RL Hum. Mol. Genet. 8:1499-1507(1999).
RN [21]
RP VARIANTS LQT5 HIS-32; TRP-98 AND THR-127.
RX PubMed=10973849; DOI=10.1161/01.cir.102.10.1178;
RA Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S.G.,
RA Robinson J.L., Moss A.J., Schwartz P.J., Towbin J.A., Vincent G.M.,
RA Keating M.T.;
RT "Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A,
RT KCNE1, and KCNE2.";
RL Circulation 102:1178-1185(2000).
RN [22]
RP VARIANT LQT5 ILE-109.
RX PubMed=11692163; DOI=10.1007/s001090100249;
RA Schulze-Bahr E., Schwarz M., Hauenschild S., Wedekind H., Funke H.,
RA Haverkamp W., Breithardt W., Pongs O., Isbrandt D., Breithardt G.;
RT "A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated
RT with a mild phenotype.";
RL J. Mol. Med. 79:504-509(2001).
RN [23]
RP VARIANT ASN-85.
RX PubMed=15051636; DOI=10.1161/01.cir.0000125524.34234.13;
RA Westenskow P., Splawski I., Timothy K.W., Keating M.T., Sanguinetti M.C.;
RT "Compound mutations: a common cause of severe long-QT syndrome.";
RL Circulation 109:1834-1841(2004).
RN [24]
RP VARIANTS LQT5 HIS-36 AND SER-53.
RX PubMed=16414944; DOI=10.1001/jama.294.23.2975;
RA Napolitano C., Priori S.G., Schwartz P.J., Bloise R., Ronchetti E.,
RA Nastoli J., Bottelli G., Cerrone M., Leonardi S.;
RT "Genetic testing in the long QT syndrome: development and validation of an
RT efficient approach to genotyping in clinical practice.";
RL JAMA 294:2975-2980(2005).
RN [25]
RP VARIANTS GLY-38 AND ASN-85, AND CHARACTERIZATION OF VARIANT ASN-85.
RX PubMed=16823764; DOI=10.1002/humu.20360;
RA Van Laer L., Carlsson P.-I., Ottschytsch N., Bondeson M.-L., Konings A.,
RA Vandevelde A., Dieltjens N., Fransen E., Snyders D., Borg E., Raes A.,
RA Van Camp G.;
RT "The contribution of genes involved in potassium-recycling in the inner ear
RT to noise-induced hearing loss.";
RL Hum. Mutat. 27:786-795(2006).
RN [26]
RP VARIANTS LQT5 VAL-8; MET-10; LEU-28; HIS-32; SER-55; PRO-58; PRO-59;
RP CYS-67; HIS-67; MET-70; ASN-76; LYS-83 AND MET-125.
RX PubMed=19716085; DOI=10.1016/j.hrthm.2009.05.021;
RA Kapplinger J.D., Tester D.J., Salisbury B.A., Carr J.L., Harris-Kerr C.,
RA Pollevick G.D., Wilde A.A., Ackerman M.J.;
RT "Spectrum and prevalence of mutations from the first 2,500 consecutive
RT unrelated patients referred for the FAMILION long QT syndrome genetic
RT test.";
RL Heart Rhythm 6:1297-1303(2009).
RN [27]
RP CHARACTERIZATION OF VARIANTS LQT5 ILE-109 AND THR-127, AND MUTAGENESIS OF
RP 109-VAL--PRO-129.
RX PubMed=25037568; DOI=10.1242/jcs.147033;
RA Dvir M., Strulovich R., Sachyani D., Ben-Tal Cohen I., Haitin Y.,
RA Dessauer C., Pongs O., Kass R., Hirsch J.A., Attali B.;
RT "Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt
RT I(KS) regulation by PKA and PIP(2).";
RL J. Cell Sci. 127:3943-3955(2014).
CC -!- FUNCTION: Ancillary protein that assembles as a beta subunit with a
CC voltage-gated potassium channel complex of pore-forming alpha subunits.
CC Modulates the gating kinetics and enhances stability of the channel
CC complex. Assembled with KCNB1 modulates the gating characteristics of
CC the delayed rectifier voltage-dependent potassium channel KCNB1
CC (PubMed:19219384). Assembled with KCNQ1/KVLQT1 is proposed to form the
CC slowly activating delayed rectifier cardiac potassium (IKs) channel.
CC The outward current reaches its steady state only after 50 seconds.
CC Assembled with KCNH2/HERG may modulate the rapidly activating component
CC of the delayed rectifying potassium current in heart (IKr).
CC {ECO:0000269|PubMed:19219384}.
CC -!- SUBUNIT: Interacts with KCNB1. Interacts with KCNC2 (By similarity).
CC Associates with KCNH2/HERG (PubMed:9230439). Interacts with KNCQ1;
CC targets the complex KNCQ1-KCNE1 to the membrane raft (PubMed:20533308).
CC The complex KNCQ1-KNCE1 interacts with the scolopendra toxin SSD609
CC (PubMed:26307551). {ECO:0000250|UniProtKB:P15383,
CC ECO:0000269|PubMed:20533308, ECO:0000269|PubMed:9230439}.
CC -!- INTERACTION:
CC P15382; P51787: KCNQ1; NbExp=4; IntAct=EBI-7043557, EBI-359667;
CC P15382; A6HIS0: Tcap; Xeno; NbExp=3; IntAct=EBI-7043557, EBI-8784724;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19219384};
CC Single-pass type I membrane protein {ECO:0000305}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P15383}. Membrane raft
CC {ECO:0000269|PubMed:20533308}. Note=Colocalizes with KCNB1 at the
CC plasma membrane (By similarity). Targets to the membrane raft when
CC associated with KCNQ1 (PubMed:20533308). {ECO:0000250|UniProtKB:P15383,
CC ECO:0000269|PubMed:20533308}.
CC -!- TISSUE SPECIFICITY: Expressed in lung, kidney, testis, ovaries, small
CC intestine, peripheral blood leukocytes. Expressed in the heart
CC (PubMed:19219384). Not detected in pancreas, spleen, prostate and
CC colon. Restrictively localized in the apical membrane portion of
CC epithelial cells. {ECO:0000269|PubMed:19219384,
CC ECO:0000269|PubMed:9312006}.
CC -!- PTM: Phosphorylation inhibits the potassium current. {ECO:0000250}.
CC -!- PTM: N-glycosylation at Asn-26 occurs post-translationally, and
CC requires prior cotranslational glycosylation at Asn-5.
CC {ECO:0000269|PubMed:21669976, ECO:0000269|PubMed:21676880}.
CC -!- DISEASE: Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347]: An
CC autosomal recessive disorder characterized by congenital deafness,
CC prolongation of the QT interval, syncopal attacks due to ventricular
CC arrhythmias, and a high risk of sudden death.
CC {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:21676880,
CC ECO:0000269|PubMed:9328483, ECO:0000269|PubMed:9354783}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Long QT syndrome 5 (LQT5) [MIM:613695]: A heart disorder
CC characterized by a prolonged QT interval on the ECG and polymorphic
CC ventricular arrhythmias. They cause syncope and sudden death in
CC response to exercise or emotional stress, and can present with a
CC sentinel event of sudden cardiac death in infancy.
CC {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:10973849,
CC ECO:0000269|PubMed:11692163, ECO:0000269|PubMed:16414944,
CC ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:25037568,
CC ECO:0000269|PubMed:9354802, ECO:0000269|PubMed:9445165}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the potassium channel KCNE family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH36452.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; M26685; AAA36129.1; -; Genomic_DNA.
DR EMBL; L33815; AAA63905.1; -; Genomic_DNA.
DR EMBL; L28168; AAA58418.1; -; mRNA.
DR EMBL; AF135188; AAD25096.1; -; mRNA.
DR EMBL; DQ784803; ABQ01238.1; -; Genomic_DNA.
DR EMBL; BC036452; AAH36452.1; ALT_SEQ; mRNA.
DR CCDS; CCDS13636.1; -.
DR PIR; A32447; A32447.
DR RefSeq; NP_000210.2; NM_000219.5.
DR RefSeq; NP_001121140.1; NM_001127668.3.
DR RefSeq; NP_001121141.1; NM_001127669.3.
DR RefSeq; NP_001121142.1; NM_001127670.3.
DR RefSeq; NP_001257331.1; NM_001270402.2.
DR RefSeq; NP_001257332.1; NM_001270403.2.
DR RefSeq; NP_001257333.1; NM_001270404.2.
DR RefSeq; NP_001257334.1; NM_001270405.2.
DR PDB; 2K21; NMR; -; A=1-129.
DR PDBsum; 2K21; -.
DR AlphaFoldDB; P15382; -.
DR BMRB; P15382; -.
DR SMR; P15382; -.
DR BioGRID; 109955; 21.
DR ComplexPortal; CPX-3072; Voltage-gated potassium channel complex variant 1.
DR ComplexPortal; CPX-3271; KCNQ1-KCNE1 I(Ks) channel complex.
DR CORUM; P15382; -.
DR IntAct; P15382; 4.
DR MINT; P15382; -.
DR STRING; 9606.ENSP00000337255; -.
DR BindingDB; P15382; -.
DR ChEMBL; CHEMBL4872; -.
DR DrugBank; DB04957; Azimilide.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR GlyGen; P15382; 3 sites.
DR iPTMnet; P15382; -.
DR PhosphoSitePlus; P15382; -.
DR BioMuta; KCNE1; -.
DR DMDM; 116416; -.
DR PaxDb; P15382; -.
DR PeptideAtlas; P15382; -.
DR PRIDE; P15382; -.
DR Antibodypedia; 22953; 273 antibodies from 29 providers.
DR DNASU; 3753; -.
DR Ensembl; ENST00000337385.7; ENSP00000337255.3; ENSG00000180509.13.
DR Ensembl; ENST00000399284.1; ENSP00000382225.1; ENSG00000180509.13.
DR Ensembl; ENST00000399286.3; ENSP00000382226.2; ENSG00000180509.13.
DR Ensembl; ENST00000399289.7; ENSP00000382228.3; ENSG00000180509.13.
DR Ensembl; ENST00000416357.6; ENSP00000416258.2; ENSG00000180509.13.
DR Ensembl; ENST00000432085.5; ENSP00000412498.1; ENSG00000180509.13.
DR Ensembl; ENST00000611936.1; ENSP00000478215.1; ENSG00000180509.13.
DR Ensembl; ENST00000621601.4; ENSP00000483895.1; ENSG00000180509.13.
DR GeneID; 3753; -.
DR KEGG; hsa:3753; -.
DR MANE-Select; ENST00000399286.3; ENSP00000382226.2; NM_000219.6; NP_000210.2.
DR UCSC; uc002ytz.5; human.
DR CTD; 3753; -.
DR DisGeNET; 3753; -.
DR GeneCards; KCNE1; -.
DR GeneReviews; KCNE1; -.
DR HGNC; HGNC:6240; KCNE1.
DR HPA; ENSG00000180509; Group enriched (choroid plexus, fallopian tube, heart muscle).
DR MalaCards; KCNE1; -.
DR MIM; 176261; gene.
DR MIM; 612347; phenotype.
DR MIM; 613695; phenotype.
DR neXtProt; NX_P15382; -.
DR OpenTargets; ENSG00000180509; -.
DR Orphanet; 334; Familial atrial fibrillation.
DR Orphanet; 90647; Jervell and Lange-Nielsen syndrome.
DR Orphanet; 101016; Romano-Ward syndrome.
DR PharmGKB; PA211; -.
DR VEuPathDB; HostDB:ENSG00000180509; -.
DR eggNOG; ENOG502SG7D; Eukaryota.
DR GeneTree; ENSGT00940000154497; -.
DR HOGENOM; CLU_159026_0_0_1; -.
DR InParanoid; P15382; -.
DR OMA; ESCRACY; -.
DR OrthoDB; 1452030at2759; -.
DR PhylomeDB; P15382; -.
DR TreeFam; TF335976; -.
DR PathwayCommons; P15382; -.
DR Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation.
DR Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR SignaLink; P15382; -.
DR SIGNOR; P15382; -.
DR BioGRID-ORCS; 3753; 12 hits in 1067 CRISPR screens.
DR ChiTaRS; KCNE1; human.
DR EvolutionaryTrace; P15382; -.
DR GeneWiki; KCNE1; -.
DR GenomeRNAi; 3753; -.
DR Pharos; P15382; Tchem.
DR PRO; PR:P15382; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P15382; protein.
DR Bgee; ENSG00000180509; Expressed in blood and 93 other tissues.
DR ExpressionAtlas; P15382; baseline and differential.
DR Genevisible; P15382; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0031433; F:telethonin binding; IPI:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IBA:GO_Central.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
DR GO; GO:0071468; P:cellular response to acidic pH; IEA:Ensembl.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:BHF-UCL.
DR GO; GO:0071482; P:cellular response to light stimulus; IEA:Ensembl.
DR GO; GO:0002070; P:epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0086009; P:membrane repolarization; IDA:BHF-UCL.
DR GO; GO:0086011; P:membrane repolarization during action potential; IDA:BHF-UCL.
DR GO; GO:0086013; P:membrane repolarization during cardiac muscle cell action potential; IDA:BHF-UCL.
DR GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:1902260; P:negative regulation of delayed rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0090315; P:negative regulation of protein targeting to membrane; ISS:BHF-UCL.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IEA:Ensembl.
DR GO; GO:1903818; P:positive regulation of voltage-gated potassium channel activity; IEA:Ensembl.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:1902259; P:regulation of delayed rectifier potassium channel activity; IDA:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
DR GO; GO:0033363; P:secretory granule organization; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0021750; P:vestibular nucleus development; IEA:Ensembl.
DR DisProt; DP00796; -.
DR InterPro; IPR000369; K_chnl_KCNE.
DR InterPro; IPR005424; KCNE1.
DR PANTHER; PTHR15282; PTHR15282; 1.
DR Pfam; PF02060; ISK_Channel; 1.
DR PRINTS; PR01604; KCNE1CHANNEL.
DR PRINTS; PR00168; KCNECHANNEL.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Deafness; Disease variant; Glycoprotein;
KW Ion channel; Ion transport; Long QT syndrome; Membrane; Phosphoprotein;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..129
FT /note="Potassium voltage-gated channel subfamily E member
FT 1"
FT /id="PRO_0000144278"
FT TRANSMEM 44..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..129
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 109..129
FT /note="interaction with KCNQ1 C-terminus"
FT /evidence="ECO:0000269|PubMed:25037568"
FT SITE 19
FT /note="Interacts with the scolopendra toxin SSD609"
FT /evidence="ECO:0000269|PubMed:26307551"
FT MOD_RES 102
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21669976,
FT ECO:0000269|PubMed:21676880"
FT CARBOHYD 7
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:21669976"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21676880"
FT VARIANT 7
FT /note="T -> I (in JLNS2; impairs glycosylation at N-5;
FT dbSNP:rs28933384)"
FT /evidence="ECO:0000269|PubMed:21676880,
FT ECO:0000269|PubMed:9354783"
FT /id="VAR_008897"
FT VARIANT 8
FT /note="A -> V (in LQT5; unknown pathological significance;
FT dbSNP:rs199473348)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074908"
FT VARIANT 10
FT /note="T -> M (in LQT5; unknown pathological significance;
FT dbSNP:rs144917638)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074909"
FT VARIANT 28
FT /note="S -> L (in LQT5; unknown pathological significance;
FT dbSNP:rs199473350)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074910"
FT VARIANT 32
FT /note="R -> H (in LQT5; unknown pathological significance;
FT dbSNP:rs17857111)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:19716085"
FT /id="VAR_009906"
FT VARIANT 36
FT /note="R -> H (in LQT5; unknown pathological significance;
FT dbSNP:rs199473351)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074911"
FT VARIANT 38
FT /note="S -> G (in dbSNP:rs1805127)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16823764, ECO:0000269|PubMed:7828904"
FT /id="VAR_001558"
FT VARIANT 47
FT /note="V -> F (in JLNS2; dbSNP:rs199473353)"
FT /evidence="ECO:0000269|PubMed:10400998"
FT /id="VAR_008898"
FT VARIANT 51
FT /note="L -> H (in JLNS2)"
FT /evidence="ECO:0000269|PubMed:10400998"
FT /id="VAR_008899"
FT VARIANT 52
FT /note="G -> A (in dbSNP:rs17173509)"
FT /id="VAR_048024"
FT VARIANT 53
FT /note="F -> S (in LQT5; unknown pathological significance;
FT dbSNP:rs199473355)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074912"
FT VARIANT 55
FT /note="G -> S (in LQT5; unknown pathological significance;
FT dbSNP:rs199473644)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074913"
FT VARIANT 58..59
FT /note="TL -> PP (in JLNS2; dbSNP:rs281865421)"
FT /id="VAR_001559"
FT VARIANT 58
FT /note="T -> P (in LQT5; unknown pathological significance;
FT dbSNP:rs147187721)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074914"
FT VARIANT 59
FT /note="L -> P (in LQT5; unknown pathological significance;
FT dbSNP:rs141813529)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074915"
FT VARIANT 67
FT /note="R -> C (in LQT5; unknown pathological significance;
FT dbSNP:rs199473645)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074916"
FT VARIANT 67
FT /note="R -> H (in LQT5; unknown pathological significance;
FT dbSNP:rs79654911)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074917"
FT VARIANT 70
FT /note="K -> M (in LQT5; unknown pathological significance;
FT dbSNP:rs199473646)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074918"
FT VARIANT 74
FT /note="S -> L (in LQT5; dbSNP:rs74315446)"
FT /evidence="ECO:0000269|PubMed:9354802"
FT /id="VAR_008900"
FT VARIANT 76
FT /note="D -> N (in LQT5 and JLNS2; suppresses KCNQ1 currents
FT markedly; dbSNP:rs74315445)"
FT /evidence="ECO:0000269|PubMed:10400998,
FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:9354783,
FT ECO:0000269|PubMed:9354802, ECO:0000269|PubMed:9445165"
FT /id="VAR_008901"
FT VARIANT 83
FT /note="E -> K (in LQT5; unknown pathological significance;
FT dbSNP:rs199473360)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074919"
FT VARIANT 85
FT /note="D -> N (predisposes to acquired LQT5 susceptibility;
FT shows a significant difference in current density and
FT midpoint potential compared to the wild-type channel;
FT dbSNP:rs1805128)"
FT /evidence="ECO:0000269|PubMed:15051636,
FT ECO:0000269|PubMed:16823764, ECO:0000269|PubMed:8899564"
FT /id="VAR_008902"
FT VARIANT 87
FT /note="W -> R (in LQT5; dbSNP:rs199473361)"
FT /evidence="ECO:0000269|PubMed:10400998"
FT /id="VAR_008903"
FT VARIANT 98
FT /note="R -> W (in LQT5; dbSNP:rs199473362)"
FT /evidence="ECO:0000269|PubMed:10973849"
FT /id="VAR_009907"
FT VARIANT 109
FT /note="V -> I (in LQT5; mild phenotype; unknown
FT pathological significance; no effect on KCNQ1 C-terminus
FT interaction; increases cAMP-mediated up-regulation of the
FT I(KS) current; no effect on phosphorylation at S27;
FT dbSNP:rs77442996)"
FT /evidence="ECO:0000269|PubMed:11692163,
FT ECO:0000269|PubMed:25037568"
FT /id="VAR_012802"
FT VARIANT 125
FT /note="T -> M (in LQT5; unknown pathological significance;
FT dbSNP:rs142511345)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074920"
FT VARIANT 127
FT /note="P -> T (in LQT5; moderately reduces I(KS) current
FT density; no change of the voltage dependence of channel
FT activation; markedly reduces interaction with KCNQ1 C-
FT terminus; no effect on plasma membrane localization; loss
FT of cAMP-mediated up-regulation of the I(KS) current; no
FT effect on interaction with AKAP9; impairs phosphorylation
FT at S-27 during cAMP-dependent stimulation;
FT dbSNP:rs199473647)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:25037568"
FT /id="VAR_009908"
FT MUTAGEN 5
FT /note="N->Q: No measurable effect on assembly with KCNQ1 or
FT cell surface expression of the KCNE1/KCNQ1 channel complex,
FT and loss of glycosylation at N-5; when associated with T-
FT 28."
FT /evidence="ECO:0000269|PubMed:21669976"
FT MUTAGEN 6
FT /note="T->F: No measurable effect on assembly with KCNQ1 or
FT cell surface expression of the KCNE1/KCNQ1 channel complex.
FT Loss of glycosylation at T-7."
FT /evidence="ECO:0000269|PubMed:21669976"
FT MUTAGEN 7
FT /note="T->A: 50% reduction of cell surface expression of
FT the KCNE1/KCNQ1 channel complex, and loss of glycosylation
FT at N-5 and T-7; when associated with T-28."
FT /evidence="ECO:0000269|PubMed:21669976"
FT MUTAGEN 15
FT /note="K->D: No change in inhibition of the complex KCNQ1-
FT KCNE1 by the scolopendra toxin SSD609."
FT /evidence="ECO:0000269|PubMed:26307551"
FT MUTAGEN 19
FT /note="E->K: Loss inhibition of the complex KCNQ1-KCNE1 by
FT the scolopendra toxin SSD609."
FT /evidence="ECO:0000269|PubMed:26307551"
FT MUTAGEN 28
FT /note="S->T: No measurable effect on assembly with KCNQ1 or
FT cell surface expression of the KCNE1/KCNQ1 channel complex,
FT and loss of glycosylation at N-5; when associated with Q-5.
FT 50% reduction of cell surface expression of the KCNE1/KCNQ1
FT channel complex, and loss of glycosylation at N-5 and T-7;
FT when associated with A-7."
FT /evidence="ECO:0000269|PubMed:21669976"
FT MUTAGEN 32
FT /note="R->D: Increase in inhibition of the complex KCNQ1-
FT KCNE1 by the scolopendra toxin SSD609."
FT /evidence="ECO:0000269|PubMed:26307551"
FT MUTAGEN 69
FT /note="K->H: Lowers current 2-fold and leads to faster
FT deactivation of KCNQ1/KCNE1 channel."
FT /evidence="ECO:0000269|PubMed:11874988"
FT MUTAGEN 109..129
FT /note="Missing: Totally suppressed interaction with KCNQ1
FT C-terminus."
FT /evidence="ECO:0000269|PubMed:25037568"
FT HELIX 4..9
FT /evidence="ECO:0007829|PDB:2K21"
FT HELIX 13..22
FT /evidence="ECO:0007829|PDB:2K21"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:2K21"
FT HELIX 46..71
FT /evidence="ECO:0007829|PDB:2K21"
FT TURN 77..81
FT /evidence="ECO:0007829|PDB:2K21"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:2K21"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:2K21"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:2K21"
SQ SEQUENCE 129 AA; 14675 MW; 5442D70929D4E87E CRC64;
MILSNTTAVT PFLTKLWQET VQQGGNMSGL ARRSPRSSDG KLEALYVLMV LGFFGFFTLG
IMLSYIRSKK LEHSNDPFNV YIESDAWQEK DKAYVQARVL ESYRSCYVVE NHLAIEQPNT
HLPETKPSP
