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1.A.1.15.6
K+ voltage-gated channel, LQT-like subfamily; Kv7.1; KvLQT1; KCNQ1 (regulated by KCNE peptides which affect voltage sensor equilibrium; Rocheleau and Kobertz, 2007). Almost 300 mutations of KCNQ1 have been identified in patients, and most are linked to the long QT syndrome (LQT1), some in the voltage sensor (Peroz et al., 2008; Eldstrom et al. 2010; Qureshi et al. 2013; Ikrar et al. 2008). KCNQ1-KCNE1 complexes may interact intermittently with the actin cytoskeleton via the C-terminal region (Mashanov et al., 2010). The stoichiometry of the KCNQ1 - KCNE1 complex is flexible, with up to four KCNE1 subunits associating with the four KCNQ1 subunits of the channel (Nakajo et al., 2010). A familial mutation in the voltage-sensor of the KCNQ1 channel results in a cardiac phenotype (Henrion et al., 2012). KCNQ1 regulates insulin secretion in the MIN6 beta-cell line (Yamagata et al., 2011; Gofman et al., 2012).  Electrostatic interactions of S4 arginines with E1 and S2 contribute to gating movements of S4, but coupling requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2) as voltage-sensing domain activation failed to open the pore in the absence of PIP2 (Zaydman et al. 2013). The D242N mutation causes impaired action potential adaptation to exercise and an increase in heart rate. Moreover, the D242 amino acylposition is involved in the KCNE1-mediated regulation of the voltage dependence of activation of the KV7.1 channel (Eldstrom et al. 2010; Qureshi et al. 2013; Ikrar et al. 2008). KCNQ1-KCNE1 complexes may interact intermittently with the actin cytoskeleton via the C-terminal region (Mashanov et al., 2010). The stoichiometry of the KCNQ1 - KCNE1 complex is flexible, with up to four KCNE1 subunits associating with the four KCNQ1 subunits of the channel (Nakajo et al., 2010). A familial mutation in the voltage-sensor of the KCNQ1 channel results in a cardiac phenotype (Henrion et al., 2012). KCNQ1 regulates insulin secretion in the MIN6 beta-cell line (Yamagata et al., 2011; Gofman et al., 2012).  Electrostatic interactions of S4 arginines with E1 and S2 contribute to gating movements of S4, but coupling requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2) as voltage-sensing domain activation failed to open the pore in the absence of PIP2 (Zaydman et al. 2013). The D242N mutation causes impaired action potential adaptation to exercise and an increase in heart rate. Moreover, the D242 amino acylposition is involved in the KCNE1-mediated regulation of the voltage dependence of activation of the KV7.1 channel (Moreno et al. 2017). .

Accession Number:P51787
Protein Name:KCNQ1
Length:676
Molecular Weight:74699.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: P51787
DIP: DIP-27591N
RefSeq: NP_000209.2    NP_861463.1   
Entrez Gene ID: 3784   
Pfam: PF00520    PF03520   
Drugbank: Drugbank Link   
OMIM: 192500  phenotype
220400  phenotype
607542  gene
607554  phenotype
609621  phenotype
KEGG: hsa:3784   

Gene Ontology

GO:0030659 C:cytoplasmic vesicle membrane
GO:0008076 C:voltage-gated potassium channel complex
GO:0005251 F:delayed rectifier potassium channel activity
GO:0005515 F:protein binding
GO:0008015 P:blood circulation
GO:0051899 P:membrane depolarization
GO:0006936 P:muscle contraction
GO:0006813 P:potassium ion transport
GO:0008016 P:regulation of heart contraction
GO:0007605 P:sensory perception of sound
GO:0055085 P:transmembrane transport

References (36)

[1] “Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias.”  Chouabe C.et.al.   9312006
[2] “Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome.”  Itoh T.et.al.   9799083
[3] “Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.”  Neyroud N.et.al.   10024302
[4] “KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias.”  Yang W.-P.et.al.   9108097
[5] “Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.”  Sanguinetti M.C.et.al.   8900283
[6] “Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.”  Wang Q.et.al.   8528244
[7] “Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart.”  Jiang M.et.al.   9305853
[8] “Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.”  Shalaby F.Y.et.al.   9323054
[9] “Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors.”  Selyanko A.A.et.al.   10713961
[10] “A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly.”  Schmitt N.et.al.   10654932
[11] “A constitutively open potassium channel formed by KCNQ1 and KCNE3.”  Schroeder B.C.et.al.   10646604
[12] “The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction.”  Wiener R.et.al.   18165683
[13] “Jervell and Lange-Nielsen syndrome: a Norwegian perspective.”  Tranebjaerg L.et.al.   10704188
[14] “KVLQT1 mutations in three families with familial or sporadic long QT syndrome.”  Russell M.W.et.al.   8872472
[15] “Evidence of a long QT founder gene with varying phenotypic expression in South African families.”  de Jager T.et.al.   8818942
[16] “Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.”  Tanaka T.et.al.   9024139
[17] “KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome.”  Donger C.et.al.   9386136
[18] “The long QT syndrome: a novel missense mutation in the S6 region of the KVLQT1 gene.”  van den Berg M.H.et.al.   9272155
[19] “Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias.”  Wollnik B.et.al.   9302275
[20] “New mutations in the KVLQT1 potassium channel that cause long-QT syndrome.”  Li H.et.al.   9570196
[21] “A recessive variant of the Romano-Ward Long-QT syndrome?”  Priori S.G.et.al.   9641694
[22] “Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an apparently normal phenotype in long QT syndrome.”  Neyroud N.et.al.   9781056
[23] “Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1.”  Splawski I.et.al.   9693036
[24] “Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred.”  Saarinen K.et.al.   9482580
[25] “A novel mutation in KVLQT1 is the molecular basis of inherited long QT syndrome in a near-drowning patient's family.”  Ackerman M.J.et.al.   9702906
[26] “Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias.”  Mohammad-Panah R.et.al.   10090886
[27] “Congenital long QT syndrome. The value of genetics in prognostic evaluation.”  Denjoy I.et.al.   10367071
[28] “Low penetrance in the long-QT syndrome: clinical impact.”  Priori S.G.et.al.   9927399
[29] “Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene.”  Larsen L.A.et.al.   10482963
[30] “Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.”  Jongbloed R.J.E.et.al.   10220144
[31] “High-throughput single-strand conformation polymorphism analysis by automated capillary electrophoresis: robust multiplex analysis and pattern-based identification of allelic variants.”  Larsen L.A.et.al.   10220146
[32] “Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits.”  Franqueza L.et.al.   10409658
[33] “Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk.”  Chouabe C.et.al.   10728423
[34] “Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.”  Splawski I.et.al.   10973849
[35] “KCNQ1 gain-of-function mutation in familial atrial fibrillation.”  Chen Y.-H.et.al.   12522251
[36] “Mutation in the KCNQ1 gene leading to the short QT-interval syndrome.”  Bellocq C.et.al.   15159330
Structure:
3BJ4   3HFC   3HFE   4UMO   4V0C     

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FASTA formatted sequence
1:	MAAASSPPRA ERKRWGWGRL PGARRGSAGL AKKCPFSLEL AEGGPAGGAL YAPIAPGAPG 
61:	PAPPASPAAP AAPPVASDLG PRPPVSLDPR VSIYSTRRPV LARTHVQGRV YNFLERPTGW 
121:	KCFVYHFAVF LIVLVCLIFS VLSTIEQYAA LATGTLFWME IVLVVFFGTE YVVRLWSAGC 
181:	RSKYVGLWGR LRFARKPISI IDLIVVVASM VVLCVGSKGQ VFATSAIRGI RFLQILRMLH 
241:	VDRQGGTWRL LGSVVFIHRQ ELITTLYIGF LGLIFSSYFV YLAEKDAVNE SGRVEFGSYA 
301:	DALWWGVVTV TTIGYGDKVP QTWVGKTIAS CFSVFAISFF ALPAGILGSG FALKVQQKQR 
361:	QKHFNRQIPA AASLIQTAWR CYAAENPDSS TWKIYIRKAP RSHTLLSPSP KPKKSVVVKK 
421:	KKFKLDKDNG VTPGEKMLTV PHITCDPPEE RRLDHFSVDG YDSSVRKSPT LLEVSMPHFM 
481:	RTNSFAEDLD LEGETLLTPI THISQLREHH RATIKVIRRM QYFVAKKKFQ QARKPYDVRD 
541:	VIEQYSQGHL NLMVRIKELQ RRLDQSIGKP SLFISVSEKS KDRGSNTIGA RLNRVEDKVT 
601:	QLDQRLALIT DMLHQLLSLH GGSTPGSGGP PREGGAHITQ PCGSGGSVDP ELFLPSNTLP 
661:	TYEQLTVPRR GPDEGS