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 03-AUG-2022, entry version 171.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 project:
RT 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 (MiRPs)
RT reveal promiscuous disruption of multiple currents and conservation of
RT mechanism.";
RL FASEB J. 16:390-400(2002).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12954870; DOI=10.1523/jneurosci.23-22-08077.2003;
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 in
RT 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 MiRP2-R83H
RT 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 and
RT 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 of
RT 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., Kamakura S.,
RA Matsuura H., Kita T., Horie M.;
RT "Novel KCNE3 mutation reduces repolarizing potassium current and associated
RT with long QT syndrome.";
RL Hum. Mutat. 30:557-563(2009).
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:12954870). Associated with KCNC4/Kv3.4 is proposed to form the
CC subthreshold voltage-gated potassium channel in skeletal muscle and to
CC establish the resting membrane potential (RMP) in muscle cells.
CC Associated with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated
CC potassium channel involved in chloride secretion that produces a
CC current with nearly instantaneous activation with a linear current-
CC voltage relationship. {ECO:0000250|UniProtKB:Q9JJV7,
CC ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:12954870}.
CC -!- SUBUNIT: Interacts with KCNB1. Interacts with KCNC2 (By similarity).
CC Associates with KCNC4/Kv3.4 (PubMed:11207363). Interacts with KCNQ1;
CC produces a current with nearly instantaneous activation with a linear
CC current-voltage relationship and alters membrane raft localization (By
CC similarity) (PubMed:20533308). {ECO:0000250|UniProtKB:Q9JJV7,
CC ECO:0000269|PubMed:11207363, 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 high-
CC density somatodendritic clusters on the surface of hippocampal neurons.
CC {ECO:0000269|PubMed:12954870}.
CC -!- TISSUE SPECIFICITY: Expressed in hippocampal neurons (at protein level)
CC (PubMed:12954870). Widely expressed with highest levels in kidney and
CC moderate levels in small intestine. {ECO:0000269|PubMed:10646604,
CC 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 paralysis
CC (PubMed:11207363 and PubMed:12414843). The association could not be
CC confirmed by further studies leading to the conclusion that His-83 does
CC not play a causative role in the disease (PubMed:14504341 and
CC PubMed:15037716). {ECO:0000305}.
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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 PDB; 6V00; EM; 3.10 A; C/F/I/L=1-103.
DR PDB; 6V01; EM; 3.90 A; C/F/I/L=1-103.
DR PDBsum; 2NDJ; -.
DR PDBsum; 6V00; -.
DR PDBsum; 6V01; -.
DR AlphaFoldDB; Q9Y6H6; -.
DR BMRB; Q9Y6H6; -.
DR SMR; Q9Y6H6; -.
DR BioGRID; 115326; 305.
DR CORUM; Q9Y6H6; -.
DR IntAct; Q9Y6H6; 10.
DR MINT; Q9Y6H6; -.
DR STRING; 9606.ENSP00000310557; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR GlyGen; Q9Y6H6; 3 sites.
DR iPTMnet; Q9Y6H6; -.
DR PhosphoSitePlus; Q9Y6H6; -.
DR BioMuta; KCNE3; -.
DR PaxDb; Q9Y6H6; -.
DR PeptideAtlas; Q9Y6H6; -.
DR PRIDE; Q9Y6H6; -.
DR ProteomicsDB; 86686; -.
DR Antibodypedia; 2753; 155 antibodies from 28 providers.
DR DNASU; 10008; -.
DR Ensembl; ENST00000310128.9; ENSP00000310557.4; ENSG00000175538.11.
DR Ensembl; ENST00000525550.1; ENSP00000433633.1; ENSG00000175538.11.
DR GeneID; 10008; -.
DR KEGG; hsa:10008; -.
DR MANE-Select; ENST00000310128.9; ENSP00000310557.4; NM_005472.5; NP_005463.1.
DR UCSC; uc001ovc.4; human.
DR CTD; 10008; -.
DR DisGeNET; 10008; -.
DR GeneCards; KCNE3; -.
DR GeneReviews; KCNE3; -.
DR HGNC; HGNC:6243; KCNE3.
DR HPA; ENSG00000175538; Tissue enhanced (intestine, stomach).
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 VEuPathDB; HostDB:ENSG00000175538; -.
DR eggNOG; ENOG502S4UF; Eukaryota.
DR GeneTree; ENSGT00940000155001; -.
DR HOGENOM; CLU_180169_0_0_1; -.
DR InParanoid; Q9Y6H6; -.
DR OMA; AYMYILF; -.
DR OrthoDB; 1608208at2759; -.
DR PhylomeDB; Q9Y6H6; -.
DR TreeFam; TF335981; -.
DR PathwayCommons; Q9Y6H6; -.
DR Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation.
DR Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR SignaLink; Q9Y6H6; -.
DR SIGNOR; Q9Y6H6; -.
DR BioGRID-ORCS; 10008; 13 hits in 1075 CRISPR screens.
DR ChiTaRS; KCNE3; human.
DR GeneWiki; KCNE3; -.
DR GenomeRNAi; 10008; -.
DR Pharos; Q9Y6H6; Tbio.
DR PRO; PR:Q9Y6H6; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y6H6; protein.
DR Bgee; ENSG00000175538; Expressed in nasal cavity epithelium and 157 other tissues.
DR ExpressionAtlas; Q9Y6H6; baseline and differential.
DR Genevisible; Q9Y6H6; HS.
DR GO; GO:1990794; C:basolateral part of cell; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IBA:GO_Central.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:InterPro.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IEA:Ensembl.
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: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:0006814; P:sodium ion transport; IEA:Ensembl.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IBA:GO_Central.
DR DisProt; DP01608; -.
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;
KW 3D-structure; Brugada syndrome; Cell membrane; Cell projection; Cytoplasm;
KW Disease variant; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..103
FT /note="Potassium voltage-gated channel subfamily E member
FT 3"
FT /id="PRO_0000144289"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 32..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 22
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 4
FT /note="T -> A (in dbSNP:rs200856070)"
FT /evidence="ECO:0000269|PubMed:19306396"
FT /id="VAR_058635"
FT VARIANT 39
FT /note="P -> R (in dbSNP:rs34604640)"
FT /evidence="ECO:0000269|PubMed:19306396"
FT /id="VAR_058636"
FT VARIANT 83
FT /note="R -> H (in some patients with periodic paralysis;
FT unknown pathological significance; alters voltage
FT dependence, lowers current and diminishes open probability
FT in KCNC4/KCNE3 channel; lowers current in KCNQ1/KCNE3
FT channel; dbSNP:rs17215437)"
FT /evidence="ECO:0000269|PubMed:11207363,
FT ECO:0000269|PubMed:12414843"
FT /id="VAR_015064"
FT VARIANT 99
FT /note="R -> H (in BRGDA6; also in a patient suffering from
FT drug-induced torsades de pointes; unknown pathological
FT significance; dbSNP:rs121908441)"
FT /evidence="ECO:0000269|PubMed:19122847,
FT ECO:0000269|PubMed:19306396"
FT /id="VAR_058637"
FT MUTAGEN 90
FT /note="D->N: Decreases current 4-fold in KCNH2/KCNE3
FT channel."
FT /evidence="ECO:0000269|PubMed:11874988"
FT HELIX 8..29
FT /evidence="ECO:0007829|PDB:2NDJ"
FT HELIX 57..80
FT /evidence="ECO:0007829|PDB:6V00"
FT HELIX 91..98
FT /evidence="ECO:0007829|PDB:6V00"
SQ SEQUENCE 103 AA; 11710 MW; 5235385E8D08BF10 CRC64;
METTNGTETW YESLHAVLKA LNATLHSNLL CRPGPGLGPD NQTEERRASL PGRDDNSYMY
ILFVMFLFAV TVGSLILGYT RSRKVDKRSD PYHVYIKNRV SMI
