(data stored in ACNUC26070 zone)

SWISSPROT: KCNE3_HUMAN

ID   KCNE3_HUMAN             Reviewed;         103 AA.
AC   Q9Y6H6;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   08-MAY-2019, entry version 154.
DE   RecName: Full=Potassium voltage-gated channel subfamily E member 3;
DE   AltName: Full=MinK-related peptide 2;
DE   AltName: Full=Minimum potassium ion channel-related peptide 2;
DE   AltName: Full=Potassium channel subunit beta MiRP2;
GN   Name=KCNE3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Abbott G.W., Sesti F., Buck M.E., Goldstein S.A.N.;
RL   Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11104781; DOI=10.1074/jbc.M010713200;
RA   Melman Y.F., Domenech A., de La Luna S., McDonald T.V.;
RT   "Structural determinants of KvLQT1 control by the KCNE family of
RT   proteins.";
RL   J. Biol. Chem. 276:6439-6444(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Blood;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=10646604; DOI=10.1038/35003200;
RA   Schroeder B.C., Waldegger S., Fehr S., Bleich M., Warth R., Greger R.,
RA   Jentsch T.J.;
RT   "A constitutively open potassium channel formed by KCNQ1 and KCNE3.";
RL   Nature 403:196-199(2000).
RN   [5]
RP   ASSOCIATION WITH KCNC4, AND VARIANT HIS-83.
RX   PubMed=11207363; DOI=10.1016/S0092-8674(01)00207-0;
RA   Abbott G.W., Butler M.H., Bendahhou S., Dalakas M.C., Ptacek L.J.,
RA   Goldstein S.A.N.;
RT   "MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is
RT   associated with periodic paralysis.";
RL   Cell 104:217-231(2001).
RN   [6]
RP   MUTAGENESIS OF ASP-90.
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
RT   (MiRPs) reveal promiscuous disruption of multiple currents and
RT   conservation of mechanism.";
RL   FASEB J. 16:390-400(2002).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=12954870;
RA   McCrossan Z.A., Lewis A., Panaghie G., Jordan P.N., Christini D.J.,
RA   Lerner D.J., Abbott G.W.;
RT   "MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels
RT   in mammalian brain.";
RL   J. Neurosci. 23:8077-8091(2003).
RN   [8]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH KCNQ1.
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   [9]
RP   VARIANT HIS-83.
RX   PubMed=12414843; DOI=10.1210/jc.2002-020698;
RA   Dias Da Silva M.R., Cerutti J.M., Arnaldi L.A.T., Maciel R.M.B.;
RT   "A mutation in the KCNE3 potassium channel gene is associated with
RT   susceptibility to thyrotoxic hypokalemic periodic paralysis.";
RL   J. Clin. Endocrinol. Metab. 87:4881-4884(2002).
RN   [10]
RP   LACK OF ASSOCIATION OF VARIANT HIS-83 WITH PERIODIC PARALISIS.
RX   PubMed=14504341; DOI=10.1212/01.WNL.0000082392.66713.E3;
RA   Sternberg D., Tabti N., Fournier E., Hainque B., Fontaine B.;
RT   "Lack of association of the potassium channel-associated peptide
RT   MiRP2-R83H variant with periodic paralysis.";
RL   Neurology 61:857-859(2003).
RN   [11]
RP   LACK OF ASSOCIATION OF VARIANT HIS-83 WITH PERIODIC PARALISIS.
RX   PubMed=15037716; DOI=10.1212/01.WNL.0000119392.29624.88;
RA   Jurkat-Rott K., Lehmann-Horn F.;
RT   "Periodic paralysis mutation MiRP2-R83H in controls: Interpretations
RT   and general recommendation.";
RL   Neurology 62:1012-1015(2004).
RN   [12]
RP   VARIANT BRGDA6 HIS-99.
RX   PubMed=19122847; DOI=10.1161/CIRCEP.107.748103;
RA   Delpon E., Cordeiro J.M., Nunez L., Thomsen P.E., Guerchicoff A.,
RA   Pollevick G.D., Wu Y., Kanters J.K., Larsen C.T., Hofman-Bang J.,
RA   Burashnikov E., Christiansen M., Antzelevitch C.;
RT   "Functional effects of KCNE3 mutation and its role in the development
RT   of Brugada syndrome.";
RL   Circ. Arrhythm. Electrophysiol. 1:209-218(2008).
RN   [13]
RP   VARIANTS ALA-4; ARG-39 AND HIS-99.
RX   PubMed=19306396; DOI=10.1002/humu.20834;
RA   Ohno S., Toyoda F., Zankov D.P., Yoshida H., Makiyama T., Tsuji K.,
RA   Honda T., Obayashi K., Ueyama H., Shimizu W., Miyamoto Y.,
RA   Kamakura S., Matsuura H., Kita T., Horie M.;
RT   "Novel KCNE3 mutation reduces repolarizing potassium current and
RT   associated with long QT syndrome.";
RL   Hum. Mutat. 30:557-563(2009).
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 KCNB1 modulates the gating
CC       characteristics of the delayed rectifier voltage-dependent
CC       potassium channel KCNB1 (PubMed:12954870). Associated with
CC       KCNC4/Kv3.4 is proposed to form the subthreshold voltage-gated
CC       potassium channel in skeletal muscle and to establish the resting
CC       membrane potential (RMP) in muscle cells. Associated with
CC       KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium
CC       channel involved in chloride secretion that produces a current
CC       with nearly instantaneous activation with a linear current-voltage
CC       relationship. {ECO:0000250|UniProtKB:Q9JJV7,
CC       ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:12954870}.
CC   -!- SUBUNIT: Interacts with KCNB1. Interacts with KCNC2 (By
CC       similarity). Associates with KCNC4/Kv3.4 (PubMed:11207363).
CC       Interacts with KCNQ1; produces a current with nearly instantaneous
CC       activation with a linear current-voltage relationship and alters
CC       membrane raft localization (By similarity) (PubMed:20533308).
CC       {ECO:0000250|UniProtKB:Q9JJV7, ECO:0000269|PubMed:11207363,
CC       ECO:0000269|PubMed:20533308}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12954870};
CC       Single-pass type I membrane protein {ECO:0000305}. Cytoplasm
CC       {ECO:0000269|PubMed:12954870}. Perikaryon
CC       {ECO:0000269|PubMed:12954870}. Cell projection, dendrite
CC       {ECO:0000269|PubMed:12954870}. Membrane raft
CC       {ECO:0000269|PubMed:20533308}. Note=Colocalizes with KCNB1 at
CC       high-density somatodendritic clusters on the surface of
CC       hippocampal neurons. {ECO:0000269|PubMed:12954870}.
CC   -!- TISSUE SPECIFICITY: Expressed in hippocampal neurons (at protein
CC       level) (PubMed:12954870). Widely expressed with highest levels in
CC       kidney and moderate levels in small intestine.
CC       {ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:12954870}.
CC   -!- SIMILARITY: Belongs to the potassium channel KCNE family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Variant His-83 has been associated with periodic
CC       paralysis (PubMed:11207363 and PubMed:12414843). The association
CC       could not be confirmed by further studies leading to the
CC       conclusion that His-83 does not play a causative role in the
CC       disease (PubMed:14504341 and PubMed:15037716). {ECO:0000305}.
DR   EMBL; AF076531; AAD28089.1; -; mRNA.
DR   EMBL; AF302494; AAG16255.1; -; mRNA.
DR   EMBL; BC032235; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS8232.1; -.
DR   RefSeq; NP_005463.1; NM_005472.4.
DR   RefSeq; XP_016872536.1; XM_017017047.1.
DR   RefSeq; XP_016872537.1; XM_017017048.1.
DR   RefSeq; XP_016872538.1; XM_017017049.1.
DR   RefSeq; XP_016872539.1; XM_017017050.1.
DR   RefSeq; XP_016872540.1; XM_017017051.1.
DR   RefSeq; XP_016872541.1; XM_017017052.1.
DR   PDB; 2NDJ; NMR; -; A=1-103.
DR   PDBsum; 2NDJ; -.
DR   SMR; Q9Y6H6; -.
DR   BioGrid; 115326; 10.
DR   CORUM; Q9Y6H6; -.
DR   IntAct; Q9Y6H6; 10.
DR   MINT; Q9Y6H6; -.
DR   STRING; 9606.ENSP00000310557; -.
DR   iPTMnet; Q9Y6H6; -.
DR   PhosphoSitePlus; Q9Y6H6; -.
DR   BioMuta; KCNE3; -.
DR   PaxDb; Q9Y6H6; -.
DR   PeptideAtlas; Q9Y6H6; -.
DR   PRIDE; Q9Y6H6; -.
DR   ProteomicsDB; 86686; -.
DR   DNASU; 10008; -.
DR   Ensembl; ENST00000310128; ENSP00000310557; ENSG00000175538.
DR   Ensembl; ENST00000525550; ENSP00000433633; ENSG00000175538.
DR   GeneID; 10008; -.
DR   KEGG; hsa:10008; -.
DR   UCSC; uc001ovc.4; human.
DR   CTD; 10008; -.
DR   DisGeNET; 10008; -.
DR   GeneCards; KCNE3; -.
DR   GeneReviews; KCNE3; -.
DR   HGNC; HGNC:6243; KCNE3.
DR   HPA; HPA014849; -.
DR   MalaCards; KCNE3; -.
DR   MIM; 604433; gene.
DR   MIM; 613119; phenotype.
DR   neXtProt; NX_Q9Y6H6; -.
DR   OpenTargets; ENSG00000175538; -.
DR   Orphanet; 130; Brugada syndrome.
DR   Orphanet; 681; Hypokalemic periodic paralysis.
DR   PharmGKB; PA393; -.
DR   eggNOG; ENOG410IZ1X; Eukaryota.
DR   eggNOG; ENOG410XU3Y; LUCA.
DR   GeneTree; ENSGT00940000155001; -.
DR   HOGENOM; HOG000113209; -.
DR   InParanoid; Q9Y6H6; -.
DR   KO; K04897; -.
DR   OMA; YKSLHAV; -.
DR   OrthoDB; 664798at2759; -.
DR   PhylomeDB; Q9Y6H6; -.
DR   TreeFam; TF335981; -.
DR   Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation.
DR   Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR   ChiTaRS; KCNE3; human.
DR   GeneWiki; KCNE3; -.
DR   GenomeRNAi; 10008; -.
DR   PRO; PR:Q9Y6H6; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000175538; Expressed in 165 organ(s), highest expression level in nasal cavity epithelium.
DR   ExpressionAtlas; Q9Y6H6; baseline and differential.
DR   Genevisible; Q9Y6H6; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR   GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR   GO; GO:0032809; C:neuronal cell body membrane; IDA:UniProtKB.
DR   GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR   GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:Ensembl.
DR   GO; GO:0044325; F:ion channel binding; IBA:GO_Central.
DR   GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
DR   GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:InterPro.
DR   GO; GO:0086011; P:membrane repolarization during action potential; IBA:GO_Central.
DR   GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; IEA:GOC.
DR   GO; GO:1902260; P:negative regulation of delayed rectifier potassium channel activity; IDA:UniProtKB.
DR   GO; GO:1905025; P:negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR   GO; GO:1903765; P:negative regulation of potassium ion export across plasma membrane; IDA:BHF-UCL.
DR   GO; GO:1903817; P:negative regulation of voltage-gated potassium channel activity; IDA:BHF-UCL.
DR   GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IEA:Ensembl.
DR   GO; GO:0097623; P:potassium ion export across plasma membrane; IBA:GO_Central.
DR   GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR   GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IBA:GO_Central.
DR   GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IBA:GO_Central.
DR   InterPro; IPR000369; K_chnl_KCNE.
DR   InterPro; IPR005426; K_chnl_volt-dep_bsu_KCNE3.
DR   PANTHER; PTHR15282; PTHR15282; 1.
DR   PANTHER; PTHR15282:SF6; PTHR15282:SF6; 1.
DR   Pfam; PF02060; ISK_Channel; 1.
DR   PRINTS; PR01606; KCNE3CHANNEL.
DR   PRINTS; PR00168; KCNECHANNEL.
PE   1: Evidence at protein level;
DR   PRODOM; Q9Y6H6.
DR   SWISS-2DPAGE; Q9Y6H6.
KW   3D-structure; Brugada syndrome; Cell membrane; Cell projection;
KW   Complete proteome; Cytoplasm; Disease mutation; Glycoprotein;
KW   Ion channel; Ion transport; Membrane; Polymorphism; Potassium;
KW   Potassium channel; Potassium transport; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN         1    103       Potassium voltage-gated channel subfamily
FT                                E member 3.
FT                                /FTId=PRO_0000144289.
FT   TRANSMEM     58     78       Helical. {ECO:0000255}.
FT   TOPO_DOM     79    103       Cytoplasmic. {ECO:0000255}.
FT   CARBOHYD      5      5       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     22     22       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     41     41       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VARIANT       4      4       T -> A (in dbSNP:rs200856070).
FT                                {ECO:0000269|PubMed:19306396}.
FT                                /FTId=VAR_058635.
FT   VARIANT      39     39       P -> R (in dbSNP:rs34604640).
FT                                {ECO:0000269|PubMed:19306396}.
FT                                /FTId=VAR_058636.
FT   VARIANT      83     83       R -> H (in some patients with periodic
FT                                paralysis; unknown pathological
FT                                significance; alters voltage dependence,
FT                                lowers current and diminishes open
FT                                probability in KCNC4/KCNE3 channel;
FT                                lowers current in KCNQ1/KCNE3 channel;
FT                                dbSNP:rs17215437).
FT                                {ECO:0000269|PubMed:11207363,
FT                                ECO:0000269|PubMed:12414843}.
FT                                /FTId=VAR_015064.
FT   VARIANT      99     99       R -> H (in BRGDA6; also in a patient
FT                                suffering from drug-induced torsades de
FT                                pointes; unknown pathological
FT                                significance; dbSNP:rs121908441).
FT                                {ECO:0000269|PubMed:19122847,
FT                                ECO:0000269|PubMed:19306396}.
FT                                /FTId=VAR_058637.
FT   MUTAGEN      90     90       D->N: Decreases current 4-fold in
FT                                KCNH2/KCNE3 channel.
FT                                {ECO:0000269|PubMed:11874988}.
FT   HELIX         8     29       {ECO:0000244|PDB:2NDJ}.
FT   HELIX        55     80       {ECO:0000244|PDB:2NDJ}.
FT   TURN         91     95       {ECO:0000244|PDB:2NDJ}.
SQ   SEQUENCE   103 AA;  11710 MW;  5235385E8D08BF10 CRC64;
     METTNGTETW YESLHAVLKA LNATLHSNLL CRPGPGLGPD NQTEERRASL PGRDDNSYMY
     ILFVMFLFAV TVGSLILGYT RSRKVDKRSD PYHVYIKNRV SMI
//

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