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Potassium voltage-gated channel subfamily E member 2 (MinK-related peptide 1) (Minimum potassium ion channel-related peptide 1) (Potassium channel subunit beta MiRP1)

 KCNE2_HUMAN             Reviewed;         123 AA.
Q9Y6J6; A5H1P3; D3DSF8; Q52LJ5;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
01-NOV-1999, sequence version 1.
22-NOV-2017, entry version 160.
RecName: Full=Potassium voltage-gated channel subfamily E member 2;
AltName: Full=MinK-related peptide 1;
AltName: Full=Minimum potassium ion channel-related peptide 1;
AltName: Full=Potassium channel subunit beta MiRP1;
Name=KCNE2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LQT6 THR-54 AND THR-57, VARIANTS
ALA-8 AND GLU-9, FUNCTION, CHARACTERIZATION OF VARIANTS LQT6 THR-54
AND THR-57, CHARACTERIZATION OF VARIANT GLU-9, AND INTERACTION WITH
KCNH2.
TISSUE=Heart;
PubMed=10219239; DOI=10.1016/S0092-8674(00)80728-X;
Abbott G.W., Sesti F., Splawski I., Buck M.E., Lehmann M.H.,
Timothy K.W., Keating M.T., Goldstein S.A.N.;
"MiRP1 forms IKr potassium channels with HERG and is associated with
cardiac arrhythmia.";
Cell 97:175-187(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Domenech A., Estivill X., de la Luna S.;
"Cloning of human MIRP1 cDNA.";
Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NHLBI resequencing and genotyping service (RS&G);
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
ASSOCIATION WITH KCNQ2/KCNQ3, AND TISSUE SPECIFICITY.
PubMed=11034315; DOI=10.1016/S0014-5793(00)01918-9;
Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M.,
Borsotto M.;
"M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2
subunit.";
FEBS Lett. 480:137-141(2000).
[7]
INTERACTION WITH KCNQ1, AND FUNCTION.
PubMed=11101505; DOI=10.1093/emboj/19.23.6326;
Tinel N., Diochot S., Borsotto M., Lazdunski M., Barhanin J.;
"KCNE2 confers background current characteristics to the cardiac KCNQ1
potassium channel.";
EMBO J. 19:6326-6330(2000).
[8]
MUTAGENESIS OF LYS-75.
PubMed=11874988; DOI=10.1096/fj.01-0520hyp;
Abbott G.W., Goldstein S.A.N.;
"Disease-associated mutations in KCNE potassium channel subunits
(MiRPs) reveal promiscuous disruption of multiple currents and
conservation of mechanism.";
FASEB J. 16:390-400(2002).
[9]
SUBCELLULAR LOCATION, AND INTERACTION WITH KCNQ1.
PubMed=20533308; DOI=10.1002/jcp.22265;
Roura-Ferrer M., Sole L., Oliveras A., Dahan R., Bielanska J.,
Villarroel A., Comes N., Felipe A.;
"Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface
targeting.";
J. Cell. Physiol. 225:692-700(2010).
[10]
VARIANT LQT6 MET-65.
PubMed=12185453; DOI=10.1007/s00109-002-0364-0;
Isbrandt D., Friederich P., Solth A., Haverkamp W., Ebneth A.,
Borggrefe M., Funke H., Sauter K., Breithardt G., Pongs O.,
Schulze-Bahr E.;
"Identification and functional characterization of a novel KCNE2
(MiRP1) mutation that alters HERG channel kinetics.";
J. Mol. Med. 80:524-532(2002).
[11]
VARIANT ATFB4 CYS-27, AND CHARACTERIZATION OF VARIANT ATFB4 CYS-27.
PubMed=15368194; DOI=10.1086/425342;
Yang Y., Xia M., Jin Q., Bendahhou S., Shi J., Chen Y., Liang B.,
Lin J., Liu Y., Liu B., Zhou Q., Zhang D., Wang R., Ma N., Su X.,
Niu K., Pei Y., Xu W., Chen Z., Wan H., Cui J., Barhanin J., Chen Y.;
"Identification of a KCNE2 gain-of-function mutation in patients with
familial atrial fibrillation.";
Am. J. Hum. Genet. 75:899-905(2004).
[12]
VARIANTS LQT6 THR-57; LEU-60 AND TRP-77, AND VARIANT ALA-8.
PubMed=16922724; DOI=10.1111/j.1399-0004.2006.00671.x;
Millat G., Chevalier P., Restier-Miron L., Da Costa A., Bouvagnet P.,
Kugener B., Fayol L., Gonzalez Armengod C., Oddou B., Chanavat V.,
Froidefond E., Perraudin R., Rousson R., Rodriguez-Lafrasse C.;
"Spectrum of pathogenic mutations and associated polymorphisms in a
cohort of 44 unrelated patients with long QT syndrome.";
Clin. Genet. 70:214-227(2006).
[13]
VARIANTS LQT6 ILE-14; ASN-20; HIS-27; THR-54; THR-57; LEU-65; GLN-77
AND GLY-94.
PubMed=19716085; DOI=10.1016/j.hrthm.2009.05.021;
Kapplinger J.D., Tester D.J., Salisbury B.A., Carr J.L.,
Harris-Kerr C., Pollevick G.D., Wilde A.A., Ackerman M.J.;
"Spectrum and prevalence of mutations from the first 2,500 consecutive
unrelated patients referred for the FAMILION long QT syndrome genetic
test.";
Heart Rhythm 6:1297-1303(2009).
-!- FUNCTION: Ancillary protein that assembles as a beta subunit with
a voltage-gated potassium channel complex of pore-forming alpha
subunits. Modulates the gating kinetics and enhances stability of
the channel complex. Assembled with KCNB1 modulates the gating
characteristics of the delayed rectifier voltage-dependent
potassium channel KCNB1. Associated with KCNH2/HERG is proposed to
form the rapidly activating component of the delayed rectifying
potassium current in heart (IKr). May associate with KCNQ2 and/or
KCNQ3 and modulate the native M-type current. May associate with
HCN1 and HCN2 and increase potassium current. Interacts with
KCNQ1; forms a heterooligomer complex leading to currents with an
apparently instantaneous activation, a rapid deactivation process
and a linear current-voltage relationship and decreases the
amplitude of the outward current (PubMed:11101505).
{ECO:0000250|UniProtKB:P63161, ECO:0000269|PubMed:10219239,
ECO:0000269|PubMed:11101505}.
-!- SUBUNIT: Interacts with KCNB1 (By similarity). Associates with
KCNH2/ERG1 (PubMed:10219239). May associate with KCNQ2 and KCNQ3
(PubMed:11034315,). Associates with HCN1 and probably HCN2.
Heteromultimer with KCNC2. Interacts with KCNC2 (By similarity).
Interacts with KCNQ1; forms a heterooligomer complex that targets
to the membrane raft and leading to currents with an apparently
instantaneous activation, a rapid deactivation process and a
linear current-voltage relationship and decreases the amplitude of
the outward current (PubMed:11101505, PubMed:20533308).
{ECO:0000250|UniProtKB:P63161, ECO:0000269|PubMed:10219239,
ECO:0000269|PubMed:11034315, ECO:0000269|PubMed:11101505,
ECO:0000269|PubMed:20533308}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20533308};
Single-pass type I membrane protein
{ECO:0000250|UniProtKB:P63161}. Note=Colocalizes with KCNB1 at the
plasma membrane. {ECO:0000250|UniProtKB:P63161}.
-!- TISSUE SPECIFICITY: Highly expressed in brain, heart, skeletal
muscle, pancreas, placenta, kidney, colon and thymus. A small but
significant expression is found in liver, ovary, testis, prostate,
small intestine and leukocytes. Very low expression, nearly
undetectable, in lung and spleen. {ECO:0000269|PubMed:11034315}.
-!- DISEASE: Long QT syndrome 6 (LQT6) [MIM:613693]: A heart disorder
characterized by a prolonged QT interval on the ECG and
polymorphic ventricular arrhythmias. They cause syncope and sudden
death in response to exercise or emotional stress, and can present
with a sentinel event of sudden cardiac death in infancy.
{ECO:0000269|PubMed:10219239, ECO:0000269|PubMed:12185453,
ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:19716085}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- DISEASE: Atrial fibrillation, familial, 4 (ATFB4) [MIM:611493]: A
familial form of atrial fibrillation, a common sustained cardiac
rhythm disturbance. Atrial fibrillation is characterized by
disorganized atrial electrical activity and ineffective atrial
contraction promoting blood stasis in the atria and reduces
ventricular filling. It can result in palpitations, syncope,
thromboembolic stroke, and congestive heart failure.
{ECO:0000269|PubMed:15368194}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the potassium channel KCNE family.
{ECO:0000305}.
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EMBL; AF071002; AAD28086.1; -; mRNA.
EMBL; AF302095; AAG13416.1; -; mRNA.
EMBL; DQ784804; ABQ01239.1; -; Genomic_DNA.
EMBL; CH471079; EAX09791.1; -; Genomic_DNA.
EMBL; BC093892; AAH93892.1; -; mRNA.
EMBL; BC112087; AAI12088.1; -; mRNA.
CCDS; CCDS13635.1; -.
RefSeq; NP_751951.1; NM_172201.1.
UniGene; Hs.551521; -.
UniGene; Hs.736062; -.
PDB; 2M0Q; NMR; -; A=1-123.
PDBsum; 2M0Q; -.
ProteinModelPortal; Q9Y6J6; -.
SMR; Q9Y6J6; -.
BioGrid; 115313; 2.
CORUM; Q9Y6J6; -.
STRING; 9606.ENSP00000290310; -.
iPTMnet; Q9Y6J6; -.
PhosphoSitePlus; Q9Y6J6; -.
BioMuta; KCNE2; -.
DMDM; 6685661; -.
PaxDb; Q9Y6J6; -.
PeptideAtlas; Q9Y6J6; -.
PRIDE; Q9Y6J6; -.
DNASU; 9992; -.
Ensembl; ENST00000290310; ENSP00000290310; ENSG00000159197.
GeneID; 9992; -.
KEGG; hsa:9992; -.
UCSC; uc002ytt.2; human.
CTD; 9992; -.
DisGeNET; 9992; -.
EuPathDB; HostDB:ENSG00000159197.3; -.
GeneCards; KCNE2; -.
GeneReviews; KCNE2; -.
HGNC; HGNC:6242; KCNE2.
HPA; HPA029706; -.
HPA; HPA051553; -.
MalaCards; KCNE2; -.
MIM; 603796; gene.
MIM; 611493; phenotype.
MIM; 613693; phenotype.
neXtProt; NX_Q9Y6J6; -.
OpenTargets; ENSG00000159197; -.
Orphanet; 334; Familial atrial fibrillation.
Orphanet; 101016; Romano-Ward syndrome.
PharmGKB; PA392; -.
eggNOG; ENOG410IX4Y; Eukaryota.
eggNOG; ENOG411297Y; LUCA.
GeneTree; ENSGT00510000048894; -.
HOGENOM; HOG000113208; -.
HOVERGEN; HBG052227; -.
InParanoid; Q9Y6J6; -.
KO; K04896; -.
OMA; NWRRNTT; -.
OrthoDB; EOG091G0UDJ; -.
PhylomeDB; Q9Y6J6; -.
TreeFam; TF336058; -.
Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation.
Reactome; R-HSA-5576893; Phase 2 - plateau phase.
GeneWiki; KCNE2; -.
GenomeRNAi; 9992; -.
PRO; PR:Q9Y6J6; -.
Proteomes; UP000005640; Chromosome 21.
Bgee; ENSG00000159197; -.
CleanEx; HS_KCNE2; -.
Genevisible; Q9Y6J6; HS.
GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
GO; GO:0005764; C:lysosome; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL.
GO; GO:0005251; F:delayed rectifier potassium channel activity; IEA:Ensembl.
GO; GO:0005242; F:inward rectifier potassium channel activity; IEA:Ensembl.
GO; GO:0044325; F:ion channel binding; IDA:BHF-UCL.
GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:1902282; F:voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; IMP:BHF-UCL.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0061337; P:cardiac conduction; TAS:Reactome.
GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
GO; GO:0035690; P:cellular response to drug; IDA:BHF-UCL.
GO; GO:0086009; P:membrane repolarization; IDA:BHF-UCL.
GO; GO:0086011; P:membrane repolarization during action potential; IMP:BHF-UCL.
GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
GO; GO:1902260; P:negative regulation of delayed rectifier potassium channel activity; IDA:UniProtKB.
GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IDA:BHF-UCL.
GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IEA:Ensembl.
GO; GO:0071435; P:potassium ion export; IDA:BHF-UCL.
GO; GO:0010107; P:potassium ion import; IMP:BHF-UCL.
GO; GO:0071805; P:potassium ion transmembrane transport; IDA:BHF-UCL.
GO; GO:1902159; P:regulation of cyclic nucleotide-gated ion channel activity; IEA:Ensembl.
GO; GO:1902259; P:regulation of delayed rectifier potassium channel activity; IDA:BHF-UCL.
GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
GO; GO:1901979; P:regulation of inward rectifier potassium channel activity; IDA:BHF-UCL.
GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL.
GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
GO; GO:0043586; P:tongue development; IEA:Ensembl.
GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
InterPro; IPR000369; K_chnl_KCNE.
InterPro; IPR005425; K_chnl_volt-dep_bsu_KCNE2.
PANTHER; PTHR15282; PTHR15282; 1.
Pfam; PF02060; ISK_Channel; 1.
PRINTS; PR01605; KCNE2CHANNEL.
1: Evidence at protein level;
3D-structure; Atrial fibrillation; Cell membrane; Complete proteome;
Disease mutation; Glycoprotein; Ion channel; Ion transport;
Long QT syndrome; Membrane; Polymorphism; Potassium;
Potassium channel; Potassium transport; Reference proteome;
Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
CHAIN 1 123 Potassium voltage-gated channel subfamily
E member 2.
/FTId=PRO_0000144285.
TRANSMEM 49 69 Helical. {ECO:0000255}.
TOPO_DOM 70 123 Cytoplasmic. {ECO:0000255}.
CARBOHYD 6 6 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 29 29 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VARIANT 8 8 T -> A (in dbSNP:rs2234916).
{ECO:0000269|PubMed:10219239,
ECO:0000269|PubMed:16922724}.
/FTId=VAR_008375.
VARIANT 8 8 T -> I (in dbSNP:rs35759083).
/FTId=VAR_037794.
VARIANT 9 9 Q -> E (polymorphism; risk factor for
drug-induced arrhythmia; impedes
activation and increases sensitivity to
macrolide antibiotics; may lower current
in KCNQ1/KCNE2 channel;
dbSNP:rs16991652).
{ECO:0000269|PubMed:10219239}.
/FTId=VAR_008376.
VARIANT 14 14 V -> I (in LQT6; unknown pathological
significance; dbSNP:rs142153692).
{ECO:0000269|PubMed:19716085}.
/FTId=VAR_074921.
VARIANT 20 20 I -> N (in LQT6; unknown pathological
significance; dbSNP:rs199473363).
{ECO:0000269|PubMed:19716085}.
/FTId=VAR_074922.
VARIANT 27 27 R -> C (in ATFB4; gain-of-function
mutation associated with the initiation
and/or maintenance of AF;
dbSNP:rs74315449).
{ECO:0000269|PubMed:15368194}.
/FTId=VAR_037795.
VARIANT 27 27 R -> H (in LQT6; unknown pathological
significance; dbSNP:rs148968498).
{ECO:0000269|PubMed:19716085}.
/FTId=VAR_074923.
VARIANT 54 54 M -> T (in LQT6; forms I(KR) channels
that deactivate twice as fast as wild
type; dbSNP:rs74315447).
{ECO:0000269|PubMed:10219239,
ECO:0000269|PubMed:19716085}.
/FTId=VAR_008377.
VARIANT 57 57 I -> T (in LQT6; may affect KCNQ1/KCNE2
channel; dbSNP:rs74315448).
{ECO:0000269|PubMed:10219239,
ECO:0000269|PubMed:16922724,
ECO:0000269|PubMed:19716085}.
/FTId=VAR_008378.
VARIANT 60 60 F -> L (in LQT6; may be a rare
polymorphism; dbSNP:rs16991654).
{ECO:0000269|PubMed:16922724}.
/FTId=VAR_029334.
VARIANT 65 65 V -> L (in LQT6; unknown pathological
significance; dbSNP:rs199473364).
{ECO:0000269|PubMed:19716085}.
/FTId=VAR_074924.
VARIANT 65 65 V -> M (in LQT6; dbSNP:rs199473364).
{ECO:0000269|PubMed:12185453}.
/FTId=VAR_015063.
VARIANT 66 66 A -> V (in dbSNP:rs16991656).
/FTId=VAR_022052.
VARIANT 77 77 R -> Q (in LQT6; unknown pathological
significance; dbSNP:rs199473365).
{ECO:0000269|PubMed:19716085}.
/FTId=VAR_074925.
VARIANT 77 77 R -> W (in LQT6; dbSNP:rs141423405).
{ECO:0000269|PubMed:16922724}.
/FTId=VAR_035386.
VARIANT 94 94 E -> G (in LQT6; unknown pathological
significance; dbSNP:rs74424227).
{ECO:0000269|PubMed:19716085}.
/FTId=VAR_074926.
MUTAGEN 75 75 K->H: Increases tail current in
KCNH2/KCNE2 channel.
{ECO:0000269|PubMed:11874988}.
HELIX 3 38 {ECO:0000244|PDB:2M0Q}.
HELIX 46 74 {ECO:0000244|PDB:2M0Q}.
HELIX 88 114 {ECO:0000244|PDB:2M0Q}.
SEQUENCE 123 AA; 14472 MW; C3016415E1B44890 CRC64;
MSTLSNFTQT LEDVFRRIFI TYMDNWRQNT TAEQEALQAK VDAENFYYVI LYLMVMIGMF
SFIIVAILVS TVKSKRREHS NDPYHQYIVE DWQEKYKSQI LNLEESKATI HENIGAAGFK
MSP


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