Swiss-Prot entry
ID KCNE2_HUMAN STANDARD; PRT; 123 AA.
AC Q9Y6J6;
DT 30-MAY-2000 (Rel. 39, Created)
DT 30-MAY-2000 (Rel. 39, Last sequence update)
DT 13-SEP-2005 (Rel. 48, Last annotation update)
DE Potassium voltage-gated channel subfamily E member 2 (Minimum
DE potassium ion channel-related peptide 1) (Potassium channel beta
DE subunit MiRP1) (MinK-related peptide 1).
GN Name=KCNE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE, VARIANTS LQT6 GLU-9; THR-54 AND THR-57, VARIANT
RP ALA-8, AND INTERACTION WITH KCNH2.
RC TISSUE=Heart;
RX MEDLINE=99235979; PubMed=10219239 [NCBI, ExPASy, EBI, Israel, Japan]; 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.
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 ASSOCIATION WITH KCNQ2/KCNQ3, AND TISSUE SPECIFICITY.
RX MEDLINE=20487128; PubMed=11034315 [NCBI, ExPASy, EBI, Israel, Japan]; 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 [4]
RP ASSOCIATION WITH KCNQ1.
RX MEDLINE=20553212; PubMed=11101505 [NCBI, ExPASy, EBI, Israel, Japan]; 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 [5]
RP MUTAGENESIS OF LYS-75.
RX MEDLINE=21863999; PubMed=11874988 [NCBI, ExPASy, EBI, Israel, Japan]; 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 [6]
RP VARIANT LQT6 MET-65.
RX MEDLINE=22173005; PubMed=12185453 [NCBI, ExPASy, EBI, Israel, Japan]; 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).
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. 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 -!- SUBUNIT: Associates with KCNH2/ERG1. May associate with
CC KCNQ1/KVLQT1, KCNQ2 and KCNQ3. Associates with HCN1 and probably
CC HCN2 (By similarity).
CC -!- SUBCELLULAR LOCATION: Type I membrane protein.
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.
CC -!- DISEASE: Defects in KCNE2 are the cause of long QT syndrome type 6
CC (LQT6) [MIM:603796]. Long QT syndromes are heart disorders
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 excercise or emotional stress. KCNE2 mutants
CC form channels that open slowly and close rapidly, thereby
CC diminishing potassium currents.
CC -!- SIMILARITY: Belongs to the potassium channel KCNE family.
CC -!- DATABASE: NAME=LQTSdb; NOTE=KCNE2 mutations page;
CC WWW="http://Www.ssi.dk/en/forskning/lqtsdb/kcne2.htm".
CC --------------------------------------------------------------------------
CC This Swiss-Prot entry is copyright. It is produced through a collaboration
CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
CC use as long as its content is in no way modified and this statement is not
CC removed.
CC --------------------------------------------------------------------------
DR EMBL; AF071002; AAD28086.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AF302095; AAG13416.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR Ensembl; ENSG00000159197; Homo_sapiens
DR HGNC; HGNC:6242; KCNE2.
DR CleanEx; HGNC:6242; KCNE2.
DR MIM; 603796; -. [NCBI / EBI]
DR GeneCards; KCNE2.
DR GeneLynx; KCNE2.
DR GenAtlas; KCNE2.
DR SOURCE; KCNE2.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; TAS.
DR GO; GO:0006936; P:muscle contraction; TAS.
DR GO; GO:0006813; P:potassium ion transport; TAS.
DR GO; GO:0008016; P:regulation of heart contraction rate; TAS.
DR InterPro; IPR000369; ISK_Channel.
DR InterPro; IPR005425; KCNE_beta2.
DR InterPro; Graphical view of domain structure.
DR Pfam; PF02060; ISK_Channel; 1.
DR Pfam; Graphical view of domain structure.
DR PRINTS; PR01605; KCNE2CHANNEL.
DR PRINTS; PR00168; KCNECHANNEL.
DR CMR; Q9Y6J6.
DR ProDom [Domain structure / List of seq. sharing at least 1 domain]
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; Q9Y6J6.
DR ProtoNet; Q9Y6J6.
DR ProtoMap; Q9Y6J6.
DR PRESAGE; Q9Y6J6.
DR DIP; Q9Y6J6.
DR ModBase; Q9Y6J6.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW Disease mutation; Glycoprotein; Ion transport; Ionic channel;
KW Long QT syndrome; Polymorphism; Potassium; Potassium channel;
KW Potassium transport; Transmembrane; Transport; Voltage-gated channel.
FT TRANSMEM 49 69 Potential.
FT TOPO_DOM 70 123 Cytoplasmic (Potential).
FT CARBOHYD 6 6 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 29 29 N-linked (GlcNAc...) (Potential).
FT VARIANT 8 8 T -> A (in dbSNP:2234916).
FT /FTId=VAR_008375.
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:16991652).
FT /FTId=VAR_008376.
FT VARIANT 54 54 M -> T (in LQT6; forms I(KR) channels
FT that deactivate twice as fast as wild
FT type).
FT /FTId=VAR_008377.
FT VARIANT 57 57 I -> T (in LQT6; may affect KCNQ1/KCNE2
FT channel).
FT /FTId=VAR_008378.
FT VARIANT 65 65 V -> M (in LQT6).
FT /FTId=VAR_015063.
FT VARIANT 66 66 A -> V (in dbSNP:16991656).
FT /FTId=VAR_022052.
FT MUTAGEN 75 75 K->H: Increases tail current in
FT KCNH2/KCNE2 channel.
SQ SEQUENCE 123 AA; 14472 MW; C3016415E1B44890 CRC64;
MSTLSNFTQT LEDVFRRIFI TYMDNWRQNT TAEQEALQAK VDAENFYYVI LYLMVMIGMF
SFIIVAILVS TVKSKRREHS NDPYHQYIVE DWQEKYKSQI LNLEESKATI HENIGAAGFK
MSP
//