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 11-NOV-2015, entry version 144. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LQT6 GLU-9; THR-54 AND THR-57, RP VARIANT ALA-8, FUNCTION, CHARACTERIZATION OF VARIANTS LQT6 GLU-9; RP THR-54 AND THR-57, 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., RA Timothy K.W., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., RA 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 ASSOCIATION WITH KCNQ1. 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 RT (MiRPs) reveal promiscuous disruption of multiple currents and RT conservation of mechanism."; RL FASEB J. 16:390-400(2002). RN [9] 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 RT (MiRP1) mutation that alters HERG channel kinetics."; RL J. Mol. Med. 80:524-532(2002). RN [10] 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., RA Lin J., Liu Y., Liu B., Zhou Q., Zhang D., Wang R., Ma N., Su X., RA Niu K., Pei Y., 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 [11] 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 RT cohort of 44 unrelated patients with long QT syndrome."; RL Clin. Genet. 70:214-227(2006). 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. Associated with KCNH2/HERG is proposed to CC form the rapidly activating component of the delayed rectifying CC potassium current in heart (IKr). May associate with KCNQ2 and/or CC KCNQ3 and modulate the native M-type current. May associate with CC KCNQ1/KVLTQ1 and elicit a voltage-independent current. May CC associate with HCN1 and HCN2 and increase potassium current. CC {ECO:0000250|UniProtKB:P63161, ECO:0000269|PubMed:10219239}. CC -!- SUBUNIT: Interacts with KCNB1 (By similarity). Associates with CC KCNH2/ERG1 (PubMed:10219239). May associate with KCNQ1/KVLQT1, CC KCNQ2 and KCNQ3 (PubMed:11034315, PubMed:11101505). Associates CC with HCN1 and probably HCN2. Heteromultimer with KCNC2. Interacts CC with KCNC2 (By similarity). {ECO:0000250|UniProtKB:P63161, CC ECO:0000269|PubMed:10219239, ECO:0000269|PubMed:11034315, CC ECO:0000269|PubMed:11101505}. CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:P63161}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:P63161}. Note=Colocalizes with CC KCNB1 at the plasma membrane. {ECO:0000250|UniProtKB:P63161}. CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, skeletal CC muscle, pancreas, placenta, kidney, colon and thymus. A small but CC significant expression is found in liver, ovary, testis, prostate, CC small intestine and leukocytes. Very low expression, nearly CC undetectable, in lung and 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 CC polymorphic ventricular arrhythmias. They cause syncope and sudden CC death in response to exercise or emotional stress, and can present CC with a sentinel event of sudden cardiac death in infancy. CC {ECO:0000269|PubMed:10219239, ECO:0000269|PubMed:12185453, CC ECO:0000269|PubMed:16922724}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Atrial fibrillation, familial, 4 (ATFB4) [MIM:611493]: A CC familial form of atrial fibrillation, a common sustained cardiac CC rhythm disturbance. Atrial fibrillation is characterized by CC disorganized atrial electrical activity and ineffective atrial CC contraction promoting blood stasis in the atria and reduces CC ventricular filling. It can result in palpitations, syncope, CC thromboembolic stroke, and congestive heart failure. CC {ECO:0000269|PubMed:15368194}. Note=The disease is caused by CC mutations 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 UniGene; Hs.551521; -. DR UniGene; Hs.736062; -. DR PDB; 2M0Q; NMR; -; A=1-123. DR PDBsum; 2M0Q; -. DR ProteinModelPortal; Q9Y6J6; -. DR SMR; Q9Y6J6; 1-123. DR BioGrid; 115313; 2. DR STRING; 9606.ENSP00000290310; -. DR PhosphoSite; Q9Y6J6; -. DR BioMuta; KCNE2; -. DR DMDM; 6685661; -. DR PaxDb; Q9Y6J6; -. DR PRIDE; Q9Y6J6; -. DR DNASU; 9992; -. DR Ensembl; ENST00000290310; ENSP00000290310; ENSG00000159197. DR GeneID; 9992; -. DR KEGG; hsa:9992; -. DR UCSC; uc002ytt.1; human. DR CTD; 9992; -. DR GeneCards; KCNE2; -. DR GeneReviews; KCNE2; -. DR HGNC; HGNC:6242; KCNE2. DR HPA; HPA029706; -. DR HPA; HPA051553; -. DR MIM; 603796; gene. DR MIM; 611493; phenotype. DR MIM; 613693; phenotype. DR neXtProt; NX_Q9Y6J6; -. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 101016; Romano-Ward syndrome. DR PharmGKB; PA392; -. DR eggNOG; ENOG410IX4Y; Eukaryota. DR eggNOG; ENOG411297Y; LUCA. DR GeneTree; ENSGT00510000048894; -. DR HOGENOM; HOG000113208; -. DR HOVERGEN; HBG052227; -. DR InParanoid; Q9Y6J6; -. DR KO; K04896; -. DR OMA; NWRRNTT; -. DR OrthoDB; EOG7WDN4J; -. DR PhylomeDB; Q9Y6J6; -. DR TreeFam; TF336058; -. DR GeneWiki; KCNE2; -. DR GenomeRNAi; 9992; -. DR NextBio; 37747; -. DR PRO; PR:Q9Y6J6; -. DR Proteomes; UP000005640; Chromosome 21. DR Bgee; Q9Y6J6; -. DR CleanEx; HS_KCNE2; -. DR Genevisible; Q9Y6J6; HS. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005764; C:lysosome; IDA: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:0005242; F:inward rectifier potassium channel activity; IEA:Ensembl. DR GO; GO:0044325; F:ion channel binding; IDA:BHF-UCL. DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB. 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:0007568; P:aging; IEA:Ensembl. DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL. DR GO; GO:0035690; P:cellular response to drug; 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: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:1901387; P:positive regulation of voltage-gated calcium channel activity; IEA:Ensembl. DR GO; GO:0071435; P:potassium ion export; IDA:BHF-UCL. DR GO; GO:0010107; P:potassium ion import; IMP:BHF-UCL. DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:1902159; P:regulation of cyclic nucleotide-gated ion channel activity; IEA:Ensembl. 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 Pfam; PF02060; ISK_Channel; 1. DR PRINTS; PR01605; KCNE2CHANNEL. PE 1: Evidence at protein level; KW 3D-structure; Atrial fibrillation; Cell membrane; Complete proteome; KW Disease mutation; Glycoprotein; Ion channel; Ion transport; KW Long QT syndrome; Membrane; Polymorphism; Potassium; KW Potassium channel; Potassium transport; Reference proteome; KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1 123 Potassium voltage-gated channel subfamily FT E member 2. FT /FTId=PRO_0000144285. FT TRANSMEM 49 69 Helical. {ECO:0000255}. FT TOPO_DOM 70 123 Cytoplasmic. {ECO:0000255}. FT CARBOHYD 6 6 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 29 29 N-linked (GlcNAc...). {ECO:0000255}. FT VARIANT 8 8 T -> A (in dbSNP:rs2234916). FT {ECO:0000269|PubMed:10219239, FT ECO:0000269|PubMed:16922724}. FT /FTId=VAR_008375. FT VARIANT 8 8 T -> I (in dbSNP:rs35759083). FT /FTId=VAR_037794. FT VARIANT 9 9 Q -> E (in LQT6; impedes activation and FT increases sensitivity to macrolide FT antibiotics; may lower current in KCNQ1/ FT KCNE2 channel; dbSNP:rs16991652). FT {ECO:0000269|PubMed:10219239}. FT /FTId=VAR_008376. FT VARIANT 27 27 R -> C (in ATFB4; gain-of-function FT mutation associated with the initiation FT and/or maintenance of AF). FT {ECO:0000269|PubMed:15368194}. FT /FTId=VAR_037795. FT VARIANT 54 54 M -> T (in LQT6; forms I(KR) channels FT that deactivate twice as fast as wild FT type). {ECO:0000269|PubMed:10219239}. FT /FTId=VAR_008377. FT VARIANT 57 57 I -> T (in LQT6; may affect KCNQ1/KCNE2 FT channel; dbSNP:rs74315448). FT {ECO:0000269|PubMed:10219239, FT ECO:0000269|PubMed:16922724}. FT /FTId=VAR_008378. FT VARIANT 60 60 F -> L (in LQT6; may be a rare FT polymorphism; dbSNP:rs16991654). FT {ECO:0000269|PubMed:16922724}. FT /FTId=VAR_029334. FT VARIANT 65 65 V -> M (in LQT6). FT {ECO:0000269|PubMed:12185453}. FT /FTId=VAR_015063. FT VARIANT 66 66 A -> V (in dbSNP:rs16991656). FT /FTId=VAR_022052. FT VARIANT 77 77 R -> W (in LQT6). FT {ECO:0000269|PubMed:16922724}. FT /FTId=VAR_035386. FT MUTAGEN 75 75 K->H: Increases tail current in FT KCNH2/KCNE2 channel. FT {ECO:0000269|PubMed:11874988}. FT HELIX 3 38 {ECO:0000244|PDB:2M0Q}. FT HELIX 46 74 {ECO:0000244|PDB:2M0Q}. FT HELIX 88 114 {ECO:0000244|PDB:2M0Q}. SQ SEQUENCE 123 AA; 14472 MW; C3016415E1B44890 CRC64; MSTLSNFTQT LEDVFRRIFI TYMDNWRQNT TAEQEALQAK VDAENFYYVI LYLMVMIGMF SFIIVAILVS TVKSKRREHS NDPYHQYIVE DWQEKYKSQI LNLEESKATI HENIGAAGFK MSP //