ID KCNE2_HUMAN Reviewed; 123 AA. AC Q9Y6J6; A5H1P3; D3DSF8; Q52LJ5; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 193. DE RecName: Full=Potassium voltage-gated channel subfamily E member 2; DE AltName: Full=MinK-related peptide 1; DE AltName: Full=Minimum potassium ion channel-related peptide 1; DE AltName: Full=Potassium channel subunit beta MiRP1; GN Name=KCNE2; 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], VARIANTS LQT6 THR-54 AND THR-57, VARIANTS ALA-8 RP AND GLU-9, FUNCTION, CHARACTERIZATION OF VARIANTS LQT6 THR-54 AND THR-57, RP CHARACTERIZATION OF VARIANT GLU-9, AND INTERACTION WITH KCNH2. RC TISSUE=Heart; RX PubMed=10219239; DOI=10.1016/s0092-8674(00)80728-x; RA Abbott G.W., Sesti F., Splawski I., Buck M.E., Lehmann M.H., Timothy K.W., RA Keating M.T., Goldstein S.A.N.; RT "MiRP1 forms IKr potassium channels with HERG and is associated with RT cardiac arrhythmia."; RL Cell 97:175-187(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Domenech A., Estivill X., de la Luna S.; RT "Cloning of human MIRP1 cDNA."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 ASSOCIATION WITH KCNQ2/KCNQ3, AND TISSUE SPECIFICITY. RX PubMed=11034315; DOI=10.1016/s0014-5793(00)01918-9; RA Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M.; RT "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 RT subunit."; RL FEBS Lett. 480:137-141(2000). RN [7] RP INTERACTION WITH KCNQ1, AND FUNCTION. RX PubMed=11101505; DOI=10.1093/emboj/19.23.6326; RA Tinel N., Diochot S., Borsotto M., Lazdunski M., Barhanin J.; RT "KCNE2 confers background current characteristics to the cardiac KCNQ1 RT potassium channel."; RL EMBO J. 19:6326-6330(2000). RN [8] RP MUTAGENESIS OF LYS-75. 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 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 [10] RP VARIANT LQT6 MET-65. RX PubMed=12185453; DOI=10.1007/s00109-002-0364-0; RA Isbrandt D., Friederich P., Solth A., Haverkamp W., Ebneth A., RA Borggrefe M., Funke H., Sauter K., Breithardt G., Pongs O., RA Schulze-Bahr E.; RT "Identification and functional characterization of a novel KCNE2 (MiRP1) RT mutation that alters HERG channel kinetics."; RL J. Mol. Med. 80:524-532(2002). RN [11] RP VARIANT ATFB4 CYS-27, AND CHARACTERIZATION OF VARIANT ATFB4 CYS-27. RX PubMed=15368194; DOI=10.1086/425342; RA Yang Y., Xia M., Jin Q., Bendahhou S., Shi J., Chen Y., Liang B., Lin J., RA Liu Y., Liu B., Zhou Q., Zhang D., Wang R., Ma N., Su X., Niu K., Pei Y., RA Xu W., Chen Z., Wan H., Cui J., Barhanin J., Chen Y.; RT "Identification of a KCNE2 gain-of-function mutation in patients with RT familial atrial fibrillation."; RL Am. J. Hum. Genet. 75:899-905(2004). RN [12] RP VARIANTS LQT6 THR-57; LEU-60 AND TRP-77, AND VARIANT ALA-8. RX PubMed=16922724; DOI=10.1111/j.1399-0004.2006.00671.x; RA Millat G., Chevalier P., Restier-Miron L., Da Costa A., Bouvagnet P., RA Kugener B., Fayol L., Gonzalez Armengod C., Oddou B., Chanavat V., RA Froidefond E., Perraudin R., Rousson R., Rodriguez-Lafrasse C.; RT "Spectrum of pathogenic mutations and associated polymorphisms in a cohort RT of 44 unrelated patients with long QT syndrome."; RL Clin. Genet. 70:214-227(2006). RN [13] RP VARIANTS LQT6 ILE-14; ASN-20; HIS-27; THR-54; THR-57; LEU-65; GLN-77 AND RP GLY-94. 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). 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 Associated with KCNH2/HERG is proposed to form the rapidly activating CC component of the delayed rectifying potassium current in heart (IKr). CC May associate with KCNQ2 and/or KCNQ3 and modulate the native M-type CC current. May associate with HCN1 and HCN2 and increase potassium CC current. Interacts with KCNQ1; forms a heterooligomer complex leading CC to currents with an apparently instantaneous activation, a rapid CC deactivation process and a linear current-voltage relationship and CC decreases the amplitude of the outward current (PubMed:11101505). CC KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol CC symporter in the apical membrane of choroid plexus epithelium and CC regulates the myo-inositol gradient between blood and cerebrospinal CC fluid with an impact on neuron excitability. CC {ECO:0000250|UniProtKB:P63161, ECO:0000250|UniProtKB:Q9D808, CC ECO:0000269|PubMed:10219239, ECO:0000269|PubMed:11101505}. CC -!- SUBUNIT: Interacts with KCNB1 (By similarity). Associates with CC KCNH2/ERG1 (PubMed:10219239). May associate with KCNQ2 and KCNQ3 CC (PubMed:11034315). Associates with HCN1 and probably HCN2. CC Heteromultimer with KCNC2. Interacts with KCNC2 (By similarity). CC Interacts with KCNQ1; forms a heterooligomer complex that targets to CC the membrane raft and leading to currents with an apparently CC instantaneous activation, a rapid deactivation process and a linear CC current-voltage relationship and decreases the amplitude of the outward CC current (PubMed:11101505, PubMed:20533308). CC {ECO:0000250|UniProtKB:P63161, ECO:0000269|PubMed:10219239, CC ECO:0000269|PubMed:11034315, ECO:0000269|PubMed:11101505, CC ECO:0000269|PubMed:20533308}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20533308}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P63161}. CC Apical cell membrane {ECO:0000250|UniProtKB:Q9D808}; Single-pass CC membrane protein {ECO:0000255}. Note=Colocalizes with KCNB1 at the CC plasma membrane. {ECO:0000250|UniProtKB:P63161}. CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, skeletal muscle, CC pancreas, placenta, kidney, colon and thymus. A small but significant CC expression is found in liver, ovary, testis, prostate, small intestine CC and leukocytes. Very low expression, nearly undetectable, in lung and CC spleen. {ECO:0000269|PubMed:11034315}. CC -!- DISEASE: Long QT syndrome 6 (LQT6) [MIM:613693]: 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:10219239, ECO:0000269|PubMed:12185453, CC ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:19716085}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Atrial fibrillation, familial, 4 (ATFB4) [MIM:611493]: A CC familial form of atrial fibrillation, a common sustained cardiac rhythm CC disturbance. Atrial fibrillation is characterized by disorganized CC atrial electrical activity and ineffective atrial contraction promoting CC blood stasis in the atria and reduces ventricular filling. It can CC result in palpitations, syncope, thromboembolic stroke, and congestive CC heart failure. {ECO:0000269|PubMed:15368194}. Note=The disease is CC caused by variants affecting the gene represented in this entry. 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; AF071002; AAD28086.1; -; mRNA. DR EMBL; AF302095; AAG13416.1; -; mRNA. DR EMBL; DQ784804; ABQ01239.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09791.1; -; Genomic_DNA. DR EMBL; BC093892; AAH93892.1; -; mRNA. DR EMBL; BC112087; AAI12088.1; -; mRNA. DR CCDS; CCDS13635.1; -. DR RefSeq; NP_751951.1; NM_172201.1. DR PDB; 2M0Q; NMR; -; A=1-123. DR PDBsum; 2M0Q; -. DR AlphaFoldDB; Q9Y6J6; -. DR BMRB; Q9Y6J6; -. DR SMR; Q9Y6J6; -. DR BioGRID; 115313; 6. DR ComplexPortal; CPX-3073; Voltage-gated potassium channel complex variant 2. DR CORUM; Q9Y6J6; -. DR STRING; 9606.ENSP00000290310; -. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB01069; Promethazine. DR GlyCosmos; Q9Y6J6; 2 sites, No reported glycans. DR GlyGen; Q9Y6J6; 2 sites. DR iPTMnet; Q9Y6J6; -. DR PhosphoSitePlus; Q9Y6J6; -. DR BioMuta; KCNE2; -. DR DMDM; 6685661; -. DR MassIVE; Q9Y6J6; -. DR PaxDb; 9606-ENSP00000290310; -. DR PeptideAtlas; Q9Y6J6; -. DR Antibodypedia; 22942; 196 antibodies from 28 providers. DR DNASU; 9992; -. DR Ensembl; ENST00000290310.4; ENSP00000290310.2; ENSG00000159197.4. DR GeneID; 9992; -. DR KEGG; hsa:9992; -. DR MANE-Select; ENST00000290310.4; ENSP00000290310.2; NM_172201.2; NP_751951.1. DR UCSC; uc002ytt.2; human. DR AGR; HGNC:6242; -. DR CTD; 9992; -. DR DisGeNET; 9992; -. DR GeneCards; KCNE2; -. DR GeneReviews; KCNE2; -. DR HGNC; HGNC:6242; KCNE2. DR HPA; ENSG00000159197; Tissue enriched (stomach). DR MalaCards; KCNE2; -. DR MIM; 603796; gene. DR MIM; 611493; phenotype. DR MIM; 613693; phenotype. DR neXtProt; NX_Q9Y6J6; -. DR OpenTargets; ENSG00000159197; -. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 101016; Romano-Ward syndrome. DR PharmGKB; PA392; -. DR VEuPathDB; HostDB:ENSG00000159197; -. DR eggNOG; ENOG502S1GJ; Eukaryota. DR GeneTree; ENSGT00940000154497; -. DR HOGENOM; CLU_1991831_0_0_1; -. DR InParanoid; Q9Y6J6; -. DR OMA; RIFVTYM; -. DR OrthoDB; 5361427at2759; -. DR PhylomeDB; Q9Y6J6; -. DR TreeFam; TF336058; -. DR PathwayCommons; Q9Y6J6; -. DR Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation. DR Reactome; R-HSA-5576893; Phase 2 - plateau phase. DR SignaLink; Q9Y6J6; -. DR BioGRID-ORCS; 9992; 31 hits in 1139 CRISPR screens. DR ChiTaRS; KCNE2; human. DR GeneWiki; KCNE2; -. DR GenomeRNAi; 9992; -. DR Pharos; Q9Y6J6; Tbio. DR PRO; PR:Q9Y6J6; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; Q9Y6J6; Protein. DR Bgee; ENSG00000159197; Expressed in body of stomach and 111 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005764; C:lysosome; HDA:UniProtKB. 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:0005251; F:delayed rectifier potassium channel activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0005242; F:inward rectifier potassium channel activity; IEA:Ensembl. DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB. DR GO; GO:0044325; F:transmembrane transporter binding; IDA:BHF-UCL. DR GO; GO:1902282; F:voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; IMP:BHF-UCL. DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:BHF-UCL. DR GO; GO:0086009; P:membrane repolarization; IDA:BHF-UCL. DR GO; GO:0086011; P:membrane repolarization during action potential; IMP: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:1901800; P:positive regulation of proteasomal protein catabolic process; IDA:BHF-UCL. DR GO; GO:0097623; P:potassium ion export across plasma membrane; IDA:BHF-UCL. DR GO; GO:1990573; P:potassium ion import across plasma membrane; IMP: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:1901979; P:regulation of inward rectifier potassium channel activity; IDA:BHF-UCL. DR GO; GO:0060306; P:regulation of membrane repolarization; IDA: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:0043586; P:tongue development; IEA:Ensembl. DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL. DR InterPro; IPR000369; K_chnl_KCNE. DR InterPro; IPR005425; K_chnl_volt-dep_bsu_KCNE2. DR PANTHER; PTHR15282; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY E MEMBER 1, 3; 1. DR PANTHER; PTHR15282:SF8; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY E MEMBER 2; 1. DR Pfam; PF02060; ISK_Channel; 1. DR PRINTS; PR01605; KCNE2CHANNEL. DR Genevisible; Q9Y6J6; HS. PE 1: Evidence at protein level; KW 3D-structure; Atrial fibrillation; Cell membrane; Disease variant; KW Glycoprotein; Ion channel; Ion transport; Long QT syndrome; Membrane; KW Potassium; Potassium channel; Potassium transport; Reference proteome; KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1..123 FT /note="Potassium voltage-gated channel subfamily E member FT 2" FT /id="PRO_0000144285" FT TRANSMEM 49..69 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 70..123 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT CARBOHYD 6 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 29 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 8 FT /note="T -> A (in dbSNP:rs2234916)" FT /evidence="ECO:0000269|PubMed:10219239, FT ECO:0000269|PubMed:16922724" FT /id="VAR_008375" FT VARIANT 8 FT /note="T -> I (in dbSNP:rs35759083)" FT /id="VAR_037794" FT VARIANT 9 FT /note="Q -> E (risk factor for drug-induced arrhythmia; FT impedes activation and increases sensitivity to macrolide FT antibiotics; may lower current in KCNQ1/KCNE2 channel; FT dbSNP:rs16991652)" FT /evidence="ECO:0000269|PubMed:10219239" FT /id="VAR_008376" FT VARIANT 14 FT /note="V -> I (in LQT6; uncertain significance; FT dbSNP:rs142153692)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074921" FT VARIANT 20 FT /note="I -> N (in LQT6; uncertain significance; FT dbSNP:rs199473363)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074922" FT VARIANT 27 FT /note="R -> C (in ATFB4; gain-of-function mutation FT associated with the initiation and/or maintenance of AF; FT dbSNP:rs74315449)" FT /evidence="ECO:0000269|PubMed:15368194" FT /id="VAR_037795" FT VARIANT 27 FT /note="R -> H (in LQT6; uncertain significance; FT dbSNP:rs148968498)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074923" FT VARIANT 54 FT /note="M -> T (in LQT6; forms I(KR) channels that FT deactivate twice as fast as wild type; dbSNP:rs74315447)" FT /evidence="ECO:0000269|PubMed:10219239, FT ECO:0000269|PubMed:19716085" FT /id="VAR_008377" FT VARIANT 57 FT /note="I -> T (in LQT6; may affect KCNQ1/KCNE2 channel; FT dbSNP:rs74315448)" FT /evidence="ECO:0000269|PubMed:10219239, FT ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:19716085" FT /id="VAR_008378" FT VARIANT 60 FT /note="F -> L (in LQT6; uncertain significance; FT dbSNP:rs16991654)" FT /evidence="ECO:0000269|PubMed:16922724" FT /id="VAR_029334" FT VARIANT 65 FT /note="V -> L (in LQT6; uncertain significance; FT dbSNP:rs199473364)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074924" FT VARIANT 65 FT /note="V -> M (in LQT6; dbSNP:rs199473364)" FT /evidence="ECO:0000269|PubMed:12185453" FT /id="VAR_015063" FT VARIANT 66 FT /note="A -> V (in dbSNP:rs16991656)" FT /id="VAR_022052" FT VARIANT 77 FT /note="R -> Q (in LQT6; uncertain significance; FT dbSNP:rs199473365)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074925" FT VARIANT 77 FT /note="R -> W (in LQT6; dbSNP:rs141423405)" FT /evidence="ECO:0000269|PubMed:16922724" FT /id="VAR_035386" FT VARIANT 94 FT /note="E -> G (in LQT6; uncertain significance; FT dbSNP:rs74424227)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074926" FT MUTAGEN 75 FT /note="K->H: Increases tail current in KCNH2/KCNE2 FT channel." FT /evidence="ECO:0000269|PubMed:11874988" FT HELIX 3..38 FT /evidence="ECO:0007829|PDB:2M0Q" FT HELIX 46..74 FT /evidence="ECO:0007829|PDB:2M0Q" FT HELIX 88..114 FT /evidence="ECO:0007829|PDB:2M0Q" SQ SEQUENCE 123 AA; 14472 MW; C3016415E1B44890 CRC64; MSTLSNFTQT LEDVFRRIFI TYMDNWRQNT TAEQEALQAK VDAENFYYVI LYLMVMIGMF SFIIVAILVS TVKSKRREHS NDPYHQYIVE DWQEKYKSQI LNLEESKATI HENIGAAGFK MSP //