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 24-JAN-2024, entry version 179. 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 -!- DISEASE: Brugada syndrome 6 (BRGDA6) [MIM:613119]: A tachyarrhythmia CC characterized by right bundle branch block and ST segment elevation on CC an electrocardiogram (ECG). It can cause the ventricles to beat so fast CC that the blood is prevented from circulating efficiently in the body. CC When this situation occurs, the individual will faint and may die in a CC few minutes if the heart is not reset. {ECO:0000269|PubMed:19122847}. CC Note=The gene represented in this entry may be involved in disease CC pathogenesis. CC -!- SIMILARITY: Belongs to the potassium channel KCNE family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-20967; -. 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 TCDB; 8.A.10.3.3; the slow voltage-gated k+ channel accessory protein (mink) family. DR GlyCosmos; Q9Y6H6; 3 sites, No reported glycans. DR GlyGen; Q9Y6H6; 3 sites. DR iPTMnet; Q9Y6H6; -. DR PhosphoSitePlus; Q9Y6H6; -. DR BioMuta; KCNE3; -. DR MassIVE; Q9Y6H6; -. DR PaxDb; 9606-ENSP00000310557; -. DR PeptideAtlas; Q9Y6H6; -. DR Antibodypedia; 2753; 168 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 AGR; HGNC:6243; -. 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; ANAYMYI; -. DR OrthoDB; 5320971at2759; -. 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; 14 hits in 1157 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 159 other cell types or tissues. DR ExpressionAtlas; Q9Y6H6; baseline and differential. 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:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW. 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:intracellular 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; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY E MEMBER 1, 3; 1. DR PANTHER; PTHR15282:SF6; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY E MEMBER 3; 1. DR Pfam; PF02060; ISK_Channel; 1. DR PRINTS; PR01606; KCNE3CHANNEL. DR PRINTS; PR00168; KCNECHANNEL. DR Genevisible; Q9Y6H6; HS. 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 (found in some patients with periodic FT paralysis; uncertain 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, ECO:0000269|PubMed:14504341, FT ECO:0000269|PubMed:15037716" FT /id="VAR_015064" FT VARIANT 99 FT /note="R -> H (in BRGDA6; uncertain significance; also in a FT patient suffering from drug-induced torsades de pointes; FT uncertain 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 //