Swiss-Prot entry
ID KCNE1_HUMAN STANDARD; PRT; 129 AA.
AC P15382; Q8N709; Q91Z94;
DT 01-APR-1990 (Rel. 14, Created)
DT 01-APR-1990 (Rel. 14, Last sequence update)
DT 13-SEP-2005 (Rel. 48, Last annotation update)
DE Potassium voltage-gated channel subfamily E member 1 (IKs producing
DE slow voltage-gated potassium channel beta subunit Mink) (Minimal
DE potassium channel) (Delayed rectifier potassium channel subunit IsK).
GN Name=KCNE1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=89273632; PubMed=2730656 [NCBI, ExPASy, EBI, Israel, Japan];
RA Murai T., Kakizuka A., Takumi T., Ohkubo H., Nakanishi S.;
RT "Molecular cloning and sequence analysis of human genomic DNA encoding
RT a novel membrane protein which exhibits a slowly activating potassium
RT channel activity.";
RL Biochem. Biophys. Res. Commun. 161:176-181(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE, AND VARIANT GLY-38.
RC TISSUE=Leukocyte;
RX MEDLINE=95129890; PubMed=7828904 [NCBI, ExPASy, EBI, Israel, Japan]; 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
RT channel (minK).";
RL Gene 151:339-340(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE.
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.
RC TISSUE=Heart;
RA Jiang M., Zhang M., Liu J., Tseng G.-N.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-32 AND
RP GLY-38.
RC TISSUE=Testis;
RX MEDLINE=22388257; PubMed=12477932 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [6]
RP TISSUE SPECIFICITY.
RX MEDLINE=97459933; PubMed=9312006 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1093/emboj/16.17.5472;
RA Chouabe C., Neyroud N., Guicheney P., Lazdunski M., Romey G.,
RA Barhanin J.;
RT "Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell
RT and Lange-Nielsen inherited cardiac arrhythmias.";
RL EMBO J. 16:5472-5479(1997).
RN [7]
RP INTERACTION WITH KCNH2.
RX MEDLINE=97373956; PubMed=9230439 [NCBI, ExPASy, EBI, Israel, Japan]; 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 MEDLINE=21863999; PubMed=11874988 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1096/fj.01-0520hyp;
RA Abbott G.W., Goldstein S.A.N.;
RT "Disease-associated mutations in KCNE potassium channel subunits
RT (MiRPs) reveal promiscuous disruption of multiple currents and
RT conservation of mechanism.";
RL FASEB J. 16:390-400(2002).
RN [9]
RP VARIANT ASN-85.
RX MEDLINE=97055277; PubMed=8899564 [NCBI, ExPASy, EBI, Israel, Japan]; 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-
RT Nielsen syndrome.";
RL J. Mol. Cell. Cardiol. 28:2051-2055(1996).
RN [10]
RP VARIANT JLNS 58-PRO-PRO-59.
RX MEDLINE=97472471; PubMed=9328483 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1093/hmg/6.12.2179;
RA Tyson J., Tranebjaerg L., Bellman S., Wren C., Taylor J.F.N.,
RA Bathen J., Aslaksen B., Soerland S.J., Lund O., Malcolm S.,
RA Pembrey M., 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
RT and Lange-Nielsen syndrome.";
RL Hum. Mol. Genet. 6:2179-2185(1997).
RN [11]
RP VARIANTS JLNS ILE-7 AND ASN-76.
RX MEDLINE=98016403; PubMed=9354783 [NCBI, ExPASy, EBI, Israel, Japan];
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 [12]
RP VARIANTS LQT5 LEU-74 AND ASN-76.
RX MEDLINE=98016422; PubMed=9354802 [NCBI, ExPASy, EBI, Israel, Japan];
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 [13]
RP VARIANT LQT5 ASN-76.
RX MEDLINE=98105943; PubMed=9445165 [NCBI, ExPASy, EBI, Israel, Japan];
RA Duggal P., Vesely M.R., Wattanasirichaigoon D., Villafane J.,
RA Kaushik V., 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 [14]
RP VARIANTS JLNS PHE-47; HIS-51 AND ASN-76, AND VARIANT LQT5 ARG-87.
RX MEDLINE=99330558; PubMed=10400998 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1093/hmg/8.8.1499;
RA Bianchi L., Shen Z., Dennis A.T., Priori S.G., Napolitano C.,
RA Ronchetti E., Bryskin R., Schwartz P.J., Brown A.M.;
RT "Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr
RT and trafficking in long QT syndrome.";
RL Hum. Mol. Genet. 8:1499-1507(1999).
RN [15]
RP VARIANTS LQT5 HIS-32; TRP-98 AND THR-127.
RX MEDLINE=20432616; PubMed=10973849 [NCBI, ExPASy, EBI, Israel, Japan];
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 [16]
RP VARIANT LQT5 ILE-109.
RX MEDLINE=21546310; PubMed=11692163 [NCBI, ExPASy, EBI, Israel, Japan]; 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
RT associated with a mild phenotype.";
RL J. Mol. Med. 79:504-509(2001).
CC -!- FUNCTION: Ancillary protein that assembles as a beta subunit with
CC a voltage-gated potassium channel complex of pore-forming alpha
CC subunits. Modulates the gating kinetics and enhances stability of
CC the channel complex. Assembled with KCNQ1/KVLQT1 is proposed to
CC form the slowly activating delayed rectifier cardiac potassium
CC (IKs) channel. The outward current reaches its steady state only
CC after 50 seconds. Assembled with KCNH2/HERG may modulate the
CC rapidly activating component of the delayed rectifying potassium
CC current in heart (IKr).
CC -!- SUBUNIT: Associates with KCNQ1/KVLQT1 and KCNH2/HERG.
CC -!- SUBCELLULAR LOCATION: Type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, kidney, testis,
CC ovaries, small intestine, peripheral blood leukocytes. Not
CC detected in pancreas, spleen, prostate and colon. Restrictively
CC localized in the apical membrane portion of epithelial cells.
CC -!- PTM: Phosphorylation inhibits the potassium current (By
CC similarity).
CC -!- DISEASE: Defects in KCNE1 are a cause of the autosomal recessive
CC Jervell and Lange-Nielsen syndrome (JLNS) [MIM:220400]. JLNS
CC comprises profound congenital sensorineural deafness associated
CC with syncopal episodes. These are caused by ventricular
CC tachyarrhythmia secondary to abnormal repolarization, manifested
CC by a prolonged QT interval on the electrocardiogram.
CC -!- DISEASE: Defects in KCNE1 are the cause of long QT syndrome type 5
CC (LQT5) [MIM:176261]. Long QT syndromes are heart disorders
CC characterized by a prolonged QT interval on the ECG and
CC polymorphic ventricular arrhythmias. They cause syncope and sudden
CC death in response to excercise or emotional stress. KCNE1 mutants
CC form channels that open slowly and close rapidly, thereby
CC diminishing potassium currents.
CC -!- SIMILARITY: Belongs to the potassium channel KCNE family.
CC -!- CAUTION: Ref.4 sequence was originally reported as deriving from
CC C.porcellus.
CC -!- CAUTION: Ref.5 sequence differs from that shown due to a stop
CC codon in position 106.
CC -!- DATABASE: NAME=LQTSdb; NOTE=KCNE1 mutations page;
CC WWW="http://www.ssi.dk/en/forskning/lqtsdb/kcne1.htm".
CC --------------------------------------------------------------------------
CC This Swiss-Prot entry is copyright. It is produced through a collaboration
CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
CC use as long as its content is in no way modified and this statement is not
CC removed.
CC --------------------------------------------------------------------------
DR EMBL; M26685; AAA36129.1; -; Genomic_DNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; L33815; AAA63905.1; -; Genomic_DNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; L28168; AAA58418.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AF135188; AAD25096.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AY050512; AAL13162.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; BC036452; AAH36452.1; ALT_TERM; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PIR; A32447; A32447.
DR Ensembl; ENSG00000180509; Homo_sapiens
DR HGNC; HGNC:6240; KCNE1.
DR CleanEx; HGNC:6240; KCNE1.
DR MIM; 176261; -. [NCBI / EBI]
DR GeneCards; KCNE1.
DR GeneLynx; KCNE1.
DR GenAtlas; KCNE1.
DR SOURCE; KCNE1.
DR MIM; 220400; -. [NCBI / EBI]
DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; TAS.
DR GO; GO:0015459; F:potassium channel regulator activity; TAS.
DR GO; GO:0006936; P:muscle contraction; TAS.
DR GO; GO:0007605; P:perception of sound; TAS.
DR GO; GO:0006813; P:potassium ion transport; TAS.
DR GO; GO:0008016; P:regulation of heart contraction rate; TAS.
DR InterPro; IPR000369; ISK_Channel.
DR InterPro; IPR005424; KCNE_beta1.
DR InterPro; Graphical view of domain structure.
DR Pfam; PF02060; ISK_Channel; 1.
DR Pfam; Graphical view of domain structure.
DR PRINTS; PR01604; KCNE1CHANNEL.
DR PRINTS; PR00168; KCNECHANNEL.
DR CMR; P15382.
DR ProDom [Domain structure / List of seq. sharing at least 1 domain]
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; P15382.
DR ProtoNet; P15382.
DR ProtoMap; P15382.
DR PRESAGE; P15382.
DR DIP; P15382.
DR ModBase; P15382.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW Deafness; Disease mutation; Glycoprotein; Ion transport;
KW Ionic channel; Long QT syndrome; Phosphorylation; Polymorphism;
KW Potassium; Potassium channel; Potassium transport; Transmembrane;
KW Transport; Voltage-gated channel.
FT TRANSMEM 44 66 Potential.
FT TOPO_DOM 67 129 Cytoplasmic (Potential).
FT MOD_RES 102 102 Phosphoserine (by PKC) (By similarity).
FT CARBOHYD 5 5 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 26 26 N-linked (GlcNAc...) (Potential).
FT VARIANT 7 7 T -> I (in JLNS).
FT /FTId=VAR_008897.
FT VARIANT 32 32 R -> H (in LQT5; could be a
FT polymorphism).
FT /FTId=VAR_009906.
FT VARIANT 38 38 S -> G (in dbSNP:1805127).
FT /FTId=VAR_001558.
FT VARIANT 47 47 V -> F (in JLNS).
FT /FTId=VAR_008898.
FT VARIANT 51 51 L -> H (in JLNS).
FT /FTId=VAR_008899.
FT VARIANT 58 59 TL -> PP (in JLNS).
FT /FTId=VAR_001559.
FT VARIANT 74 74 S -> L (in LQT5).
FT /FTId=VAR_008900.
FT VARIANT 76 76 D -> N (in LQT5 and JLNS; suppresses
FT KCNQ1 currents markedly).
FT /FTId=VAR_008901.
FT VARIANT 85 85 D -> N (in dbSNP:1805128).
FT /FTId=VAR_008902.
FT VARIANT 87 87 W -> R (in LQT5).
FT /FTId=VAR_008903.
FT VARIANT 98 98 R -> W (in LQT5).
FT /FTId=VAR_009907.
FT VARIANT 109 109 V -> I (in LQT5; mild phenotype;
FT significantly reduced the wild-type I(KS)
FT current amplitude).
FT /FTId=VAR_012802.
FT VARIANT 127 127 P -> T (in LQT5).
FT /FTId=VAR_009908.
FT MUTAGEN 69 69 K->H: Lowers current 2-fold and leads to
FT faster deactivation of KCNQ1/KCNE1
FT channel.
SQ SEQUENCE 129 AA; 14675 MW; 5442D70929D4E87E CRC64;
MILSNTTAVT PFLTKLWQET VQQGGNMSGL ARRSPRSSDG KLEALYVLMV LGFFGFFTLG
IMLSYIRSKK LEHSNDPFNV YIESDAWQEK DKAYVQARVL ESYRSCYVVE NHLAIEQPNT
HLPETKPSP
//