P51787 (KCNQ1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily KQT member 1

Alternative name(s):
IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1
KQT-like 1
Voltage-gated potassium channel subunit Kv7.1

Gene names

Name:	KCNQ1
Synonyms:	KCNA8, KCNA9, KVLQT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	676 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea.
Subunit structure	Heterotetramer with KCNE1 (MinK) or KCNE3 (MiRP2). Interacts with CALM. Ref.11 Ref.12 Ref.13
Subcellular location	Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane; Multi-pass membrane protein Ref.13.
Tissue specificity	Abundantly expressed in heart, pancreas, prostate, kidney, small intestine and peripheral blood leukocytes. Less abundant in placenta, lung, spleen, colon, thymus, testis and ovaries.
Domain	The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Ref.11
Involvement in disease	Long QT syndrome 1 (LQT1) [MIM:192500]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.3 Ref.7 Ref.9 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.40 Ref.41 Ref.42 Jervell and Lange-Nielsen syndrome 1 (JLNS1) [MIM:220400]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24 Ref.28 Ref.36 Familial atrial fibrillation 3 (ATFB3) [MIM:607554]: An autosomal dominant 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.38 Short QT syndrome 2 (SQT2) [MIM:609621]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.39
Miscellaneous	Mutagenesis experiments were carried out by expressing in Xenopus oocytes or COS-7 cells KCNQ1 mutants either individually (homomultimers) or in combination with both wild-type KCNQ1 (mut/wt homomultimers) and minK (heteromultimers).
Sequence similarities	Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily. [View classification]
Sequence caution	The sequence BAA34739.1 differs from that shown. Reason: Frameshift at positions 129 and 159.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Atrial fibrillation Deafness Disease mutation Long QT syndrome Short QT syndrome
Domain	Transmembrane Transmembrane helix
Ligand	Calmodulin-binding Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood circulation Non-traceable author statement Ref.7. Source: ProtInc cardiovascular system development Inferred from electronic annotation. Source: Compara gene silencing Inferred from electronic annotation. Source: Compara muscle contraction Traceable author statement Ref.7. Source: ProtInc negative regulation of insulin secretion Inferred from electronic annotation. Source: Compara potassium ion export Inferred from direct assay PubMed 17289006Ref.6. Source: BHF-UCL regulation of gene expression by genetic imprinting Inferred from electronic annotation. Source: Compara regulation of heart contraction Inferred by curator Ref.6. Source: BHF-UCL regulation of membrane repolarization Inferred from mutant phenotype Ref.7. Source: BHF-UCL response to chemical stimulus Inferred from electronic annotation. Source: Compara sensory perception of sound Traceable author statement PubMed 9020846. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	basolateral plasma membrane Inferred from direct assay PubMed 21957902. Source: BHF-UCL early endosome Inferred from direct assay PubMed 21957902. Source: BHF-UCL late endosome Inferred from direct assay PubMed 21957902. Source: BHF-UCL lysosome Inferred from direct assay PubMed 21957902. Source: BHF-UCL sarcolemma Inferred from electronic annotation. Source: Compara voltage-gated potassium channel complex Inferred from direct assay PubMed 17289006. Source: BHF-UCL zymogen granule membrane Inferred from electronic annotation. Source: Compara
Molecular_function	outward rectifier potassium channel activity Inferred from electronic annotation. Source: Compara voltage-gated potassium channel activity Inferred from direct assay PubMed 17289006Ref.6. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P51787-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P51787-2)

Also known as: TKvLQT1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.
     128-129: AV → MD

Note: Truncated isoform that is non-functional alone but modulatory when coexpressed with the full-length isoform 1.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 676

676

Potassium voltage-gated channel subfamily KQT member 1

PRO_0000054022

Regions

Transmembrane

122 – 142

21

Helical; Name=Segment S1; Potential

Topological domain

143 – 147

5

Extracellular Potential

Transmembrane

148 – 168

21

Helical; Name=Segment S2; Potential

Topological domain

169 – 196

28

Cytoplasmic Potential

Transmembrane

197 – 217

21

Helical; Name=Segment S3; Potential

Topological domain

218 – 225

8

Extracellular Potential

Transmembrane

226 – 248

23

Helical; Voltage-sensor; Name=Segment S4; Potential

Topological domain

249 – 261

13

Cytoplasmic Potential

Transmembrane

262 – 282

21

Helical; Name=Segment S5; Potential

Topological domain

283 – 299

17

Extracellular Potential

Intramembrane

300 – 320

21

Pore-forming; Name=Segment H5; Potential

Topological domain

321 – 327

7

Extracellular Potential

Transmembrane

328 – 348

21

Helical; Name=Segment S6; Potential

Topological domain

349 – 676

328

Cytoplasmic Potential

Region

589 – 620

32

Subunits assembly domain

Motif

312 – 317

6

Selectivity filter By similarity

Amino acid modifications

Glycosylation

289

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 127

127

Missing in isoform 2.

VSP_000981

Alternative sequence

128 – 129

2

AV → MD in isoform 2.

VSP_000982

Natural variant

71 – 73

3

Missing in LQT1.

VAR_009917

Natural variant

73

1

P → T in LQT1. Ref.40

VAR_068287

Natural variant

111

1

Y → C in LQT1.

VAR_009918

Natural variant

115

1

E → G in LQT1. Ref.40

VAR_068288

Natural variant

122

1

C → Y in LQT1. Ref.40

VAR_068289

Natural variant

133

1

V → I in LQT1. Ref.40

VAR_068290

Natural variant

136

1

C → F in LQT1. Ref.40

VAR_068291

Natural variant

140

1

S → G in ATFB3; gain of function. Ref.38

VAR_015742

Natural variant

157

1

F → C in LQT1. Ref.33

VAR_008124

Natural variant

160

1

E → K in LQT1. Ref.40

VAR_009919

Natural variant

167 – 168

2

FG → W in LQT1.

VAR_001515

Natural variant

168

1

G → R in LQT1. Ref.25 Ref.40
Corresponds to variant rs179489 [ dbSNP | Ensembl ].

VAR_001516

Natural variant

174

1

R → C in LQT1. Ref.40

VAR_001517

Natural variant

174

1

R → H in LQT1. Ref.29

VAR_008939

Natural variant

178

1

A → P in LQT1; loss of channel activity. Ref.9

VAR_001518

Natural variant

178

1

A → T in LQT1. Ref.18

VAR_009920

Natural variant

179

1

G → S in LQT1.

VAR_009921

Natural variant

184

1

Y → S in LQT1. Ref.32

VAR_008125

Natural variant

189

1

G → R in LQT1; familial sudden death. Ref.32

VAR_001519

Natural variant

190

1

R → Q in LQT1; loss of channel activity. Ref.36 Ref.40

VAR_001520

Natural variant

194

1

A → P in LQT1.

VAR_009922

Natural variant

204

1

I → F in LQT1. Ref.40

VAR_068292

Natural variant

216

1

G → R in LQT1. Ref.20

VAR_001521

Natural variant

225

1

S → L in LQT1. Ref.30 Ref.40

VAR_009923

Natural variant

235

1

I → N in LQT1. Ref.40

VAR_068293

Natural variant

242

1

D → N in LQT1. Ref.40

VAR_008940

Natural variant

243

1

R → C in LQT1; slower rate of activation and voltage dependence of activation-inactivation shifted to more positive potentials (homomultimers); channels non-functional (heteromultimers). Ref.34 Ref.40

VAR_010933

Natural variant

243

1

R → H in JLNS1; minor changes of wt current (homomultimers); positive voltage shift of the channel activation (heteromultimers). Ref.28 Ref.36

VAR_008941

Natural variant

248

1

W → R in LQT1; slower rate of activation and voltage dependence of activation-inactivation shifted to more positive potentials (homomultimers); channels non-functional (heteromultimers). Ref.34

VAR_008942

Natural variant

250

1

L → H in LQT1.

VAR_008943

Natural variant

254 – 256

3

Missing in LQT1.

VAR_068294

Natural variant

254

1

V → M in LQT1; associated with M-417 in a patient. Ref.17 Ref.40

VAR_001522

Natural variant

259

1

R → C in LQT1. Ref.40

VAR_068295

Natural variant

259

1

R → L in LQT1. Ref.40

VAR_068296

Natural variant

261

1

E → D in JLNS1. Ref.40

VAR_008944

Natural variant

261

1

E → K in LQT1; loss of channel activity and no interaction with wt KVLQT1 or MINK subunits. Ref.34

VAR_001523

Natural variant

266

1

L → P in LQT1. Ref.40

VAR_009924

Natural variant

269

1

G → D in LQT1. Ref.40

VAR_001524

Natural variant

269

1

G → S in LQT1. Ref.40

VAR_009925

Natural variant

273

1

L → F in LQT1; functional channel with reduced macroscopic conductance (homomultimers); alteration of normal KVLQT1 function (mut/wt homomultimers). Ref.9 Ref.40

VAR_001525

Natural variant

273

1

L → R in LQT1. Ref.40

VAR_068297

Natural variant

276

1

Missing in LQT1. Ref.40

VAR_068298

Natural variant

277

1

S → L in LQT1; loss of function mutation acting in a dominant-negative manner. Ref.40 Ref.42

VAR_065777

Natural variant

278

1

Y → H in LQT1. Ref.40

VAR_068299

Natural variant

281

1

Y → C in LQT1. Ref.30

VAR_008945

Natural variant

290

1

E → K in LQT1. Ref.40

VAR_068300

Natural variant

292

1

G → D in LQT1. Ref.40

VAR_068301

Natural variant

293

1

R → C in LQT1. Ref.40

VAR_068302

Natural variant

300

1

A → T in LQT1. Ref.23

VAR_001526

Natural variant

302

1

A → V in LQT1. Ref.40

VAR_068303

Natural variant

304

1

W → R in LQT1. Ref.40

VAR_068304

Natural variant

305

1

W → S in JLNS1. Ref.24 Ref.40

VAR_001527

Natural variant

306

1

G → R in LQT1.

VAR_001528

Natural variant

307

1

V → L in SQT2; gain of function. Ref.39

VAR_023841

Natural variant

309

1

T → R in LQT1.

VAR_001529

Natural variant

310

1

V → I in LQT1.

VAR_009926

Natural variant

311

1

T → I in LQT1. Ref.26

VAR_009927

Natural variant

312

1

T → I in LQT1; loss of channel activity. Ref.9 Ref.40

VAR_001530

Natural variant

313

1

I → M in LQT1. Ref.18

VAR_001531

Natural variant

314

1

G → D in LQT1. Ref.40

VAR_068305

Natural variant

314

1

G → R in LQT1. Ref.40

VAR_068306

Natural variant

314

1

G → S in LQT1. Ref.15 Ref.25 Ref.32 Ref.40

VAR_001532

Natural variant

315

1

Y → C in LQT1. Ref.25 Ref.30 Ref.40

VAR_008946

Natural variant

315

1

Y → S in LQT1. Ref.32

VAR_001533

Natural variant

316

1

G → R in LQT1. Ref.40

VAR_068307

Natural variant

317

1

D → N in LQT1. Ref.21 Ref.26

VAR_001534

Natural variant

318

1

K → N in LQT1. Ref.25

VAR_008947

Natural variant

320

1

P → A in LQT1; loss of function mutation acting in a dominant-negative manner. Ref.41

VAR_001535

Natural variant

320

1

P → H in LQT1; loss of function mutation acting in a dominant-negative manner. Ref.41

VAR_065778

Natural variant

322

1

T → A in LQT1. Ref.40

VAR_068308

Natural variant

325

1

G → R in LQT1. Ref.18

VAR_001536

Natural variant

339

1

Missing in LQT1. Ref.27 Ref.40

VAR_001537

Natural variant

341

1

A → E in LQT1.
Corresponds to variant rs12720459 [ dbSNP | Ensembl ].

VAR_001538

Natural variant

341

1

A → V in LQT1. Ref.15 Ref.16 Ref.22 Ref.40

VAR_001539

Natural variant

342

1

L → F in LQT1.

VAR_001540

Natural variant

343

1

P → S in LQT1. Ref.40

VAR_068309

Natural variant

344

1

A → E in LQT1. Ref.40

VAR_068310

Natural variant

344

1

A → V in LQT1. Ref.40

VAR_001541

Natural variant

345

1

G → E in LQT1. Ref.40

VAR_001542

Natural variant

345

1

G → R in LQT1; familial sudden death. Ref.32

VAR_008126

Natural variant

349

1

S → W in LQT1. Ref.40

VAR_009928

Natural variant

353

1

L → P in LQT1. Ref.25 Ref.40

VAR_009180

Natural variant

362

1

K → R in LQT1. Ref.40
Corresponds to variant rs12720458 [ dbSNP | Ensembl ].

VAR_048025

Natural variant

366

1

R → P in LQT1. Ref.18

VAR_001543

Natural variant

366

1

R → Q in LQT1.

VAR_009929

Natural variant

366

1

R → W in LQT1. Ref.25 Ref.40

VAR_008948

Natural variant

371

1

A → T in LQT1.

VAR_001544

Natural variant

373

1

S → P in LQT1. Ref.32

VAR_008127

Natural variant

374

1

L → H in LQT1. Ref.40

VAR_068311

Natural variant

380

1

R → S in LQT1. Ref.40

VAR_068312

Natural variant

389

1

S → Y in LQT1. Ref.40

VAR_068313

Natural variant

391

1

T → I in LQT1.

VAR_009930

Natural variant

392

1

W → R in LQT1. Ref.32

VAR_008128

Natural variant

393

1

K → N.
Corresponds to variant rs12720457 [ dbSNP | Ensembl ].

VAR_048026

Natural variant

417

1

V → M in LQT1; associated with M-254 in a patient. Ref.17

VAR_010934

Natural variant

448

1

P → R in LQT1.

VAR_009931

Natural variant

452

1

R → W in LQT1. Ref.40

VAR_068314

Natural variant

524

1

V → G in LQT1. Ref.40

VAR_068315

Natural variant

525

1

A → T in LQT1. Ref.31

VAR_009181

Natural variant

526

1

K → E in LQT1. Ref.40

VAR_068316

Natural variant

533

1

R → W in LQT1; minor changes of wt current (homomultimers); positive voltage shift of the channel activation (heteromultimers). Ref.36

VAR_008949

Natural variant

539

1

R → W in LQT1; minor changes of wt current (homomultimers); positive voltage shift of the channel activation (heteromultimers). Ref.36 Ref.40

VAR_008950

Natural variant

546

1

S → L in LQT1. Ref.40

VAR_068317

Natural variant

555

1

R → C in LQT1; associated with a fruste phenotype. Ref.40

VAR_001545

Natural variant

555

1

R → H in LQT1. Ref.40

VAR_068318

Natural variant

566

1

S → F in LQT1.

VAR_009932

Natural variant

566

1

S → Y in LQT1. Ref.40

VAR_068319

Natural variant

567

1

I → S in LQT1. Ref.40

VAR_068320

Natural variant

568

1

G → R in LQT1. Ref.40

VAR_068321

Natural variant

583

1

R → C in LQT1.
Corresponds to variant rs17221854 [ dbSNP | Ensembl ].

VAR_009933

Natural variant

587

1

T → M in LQT1. Ref.3 Ref.40

VAR_008951

Natural variant

589

1

G → D in LQT1; reduced cell surface expression and strongly reduced potassium current. Ref.13

VAR_008952

Natural variant

590

1

A → T in LQT1. Ref.40

VAR_068322

Natural variant

591

1

R → H in LQT1. Ref.3 Ref.40

VAR_008953

Natural variant

594

1

R → Q in LQT1. Ref.40

VAR_009934

Natural variant

619

1

L → M in LQT1. Ref.40

VAR_068323

Natural variant

626

1

G → S in LQT1. Ref.40

VAR_068324

Natural variant

643

1

G → S. Ref.2
Corresponds to variant rs1800172 [ dbSNP | Ensembl ].

VAR_008954

Experimental info

Mutagenesis

589

1

G → M: No effect. Ref.13

Mutagenesis

590

1

A → W: Reduced cell surface expression and strongly reduced potassium current. Ref.13

Mutagenesis

593

1

N → G: Reduced cell surface expression and moderately reduced potassium current. Ref.13

Sequence conflict

64 – 65

2

PA → HV in CAB44649. Ref.3

Sequence conflict

96 – 106

11

TRRPVLARTHV → METRGSRLTGG in AAC51781. Ref.6

Sequence conflict

370

1

Missing in AAC05705. Ref.8

Sequence conflict

607 – 608

2

AL → VI in AAM94040. Ref.4

Sequence conflict

619 – 644

26

LHGGS…QPCGS → MQQGGPTCNSRSQVVASNE in AAM94040. Ref.4

Sequence conflict

648 – 649

2

VD → IN in AAM94040. Ref.4

Sequence conflict

658

1

T → S in AAM94040. Ref.4

Sequence conflict

669 – 670

2

RR → QT in AAM94040. Ref.4

Secondary structure

1

.

.

.

676

Helix Strand Turn

Details...

Helix

588 – 609

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 15, 1999. Version 3. Checksum: ADFCA9E2B9763B21	FASTA	676	74,699
	10 20 30 40 50 60 MAAASSPPRA ERKRWGWGRL PGARRGSAGL AKKCPFSLEL AEGGPAGGAL YAPIAPGAPG 70 80 90 100 110 120 PAPPASPAAP AAPPVASDLG PRPPVSLDPR VSIYSTRRPV LARTHVQGRV YNFLERPTGW 130 140 150 160 170 180 KCFVYHFAVF LIVLVCLIFS VLSTIEQYAA LATGTLFWME IVLVVFFGTE YVVRLWSAGC 190 200 210 220 230 240 RSKYVGLWGR LRFARKPISI IDLIVVVASM VVLCVGSKGQ VFATSAIRGI RFLQILRMLH 250 260 270 280 290 300 VDRQGGTWRL LGSVVFIHRQ ELITTLYIGF LGLIFSSYFV YLAEKDAVNE SGRVEFGSYA 310 320 330 340 350 360 DALWWGVVTV TTIGYGDKVP QTWVGKTIAS CFSVFAISFF ALPAGILGSG FALKVQQKQR 370 380 390 400 410 420 QKHFNRQIPA AASLIQTAWR CYAAENPDSS TWKIYIRKAP RSHTLLSPSP KPKKSVVVKK 430 440 450 460 470 480 KKFKLDKDNG VTPGEKMLTV PHITCDPPEE RRLDHFSVDG YDSSVRKSPT LLEVSMPHFM 490 500 510 520 530 540 RTNSFAEDLD LEGETLLTPI THISQLREHH RATIKVIRRM QYFVAKKKFQ QARKPYDVRD 550 560 570 580 590 600 VIEQYSQGHL NLMVRIKELQ RRLDQSIGKP SLFISVSEKS KDRGSNTIGA RLNRVEDKVT 610 620 630 640 650 660 QLDQRLALIT DMLHQLLSLH GGSTPGSGGP PREGGAHITQ PCGSGGSVDP ELFLPSNTLP 670 TYEQLTVPRR GPDEGS
	Isoform 2 (TKvLQT1) [UniParc]. Checksum: 78BF5A267E74AC96	FASTA	549	61,474
	10 20 30 40 50 60 MDFLIVLVCL IFSVLSTIEQ YAALATGTLF WMEIVLVVFF GTEYVVRLWS AGCRSKYVGL 70 80 90 100 110 120 WGRLRFARKP ISIIDLIVVV ASMVVLCVGS KGQVFATSAI RGIRFLQILR MLHVDRQGGT 130 140 150 160 170 180 WRLLGSVVFI HRQELITTLY IGFLGLIFSS YFVYLAEKDA VNESGRVEFG SYADALWWGV 190 200 210 220 230 240 VTVTTIGYGD KVPQTWVGKT IASCFSVFAI SFFALPAGIL GSGFALKVQQ KQRQKHFNRQ 250 260 270 280 290 300 IPAAASLIQT AWRCYAAENP DSSTWKIYIR KAPRSHTLLS PSPKPKKSVV VKKKKFKLDK 310 320 330 340 350 360 DNGVTPGEKM LTVPHITCDP PEERRLDHFS VDGYDSSVRK SPTLLEVSMP HFMRTNSFAE 370 380 390 400 410 420 DLDLEGETLL TPITHISQLR EHHRATIKVI RRMQYFVAKK KFQQARKPYD VRDVIEQYSQ 430 440 450 460 470 480 GHLNLMVRIK ELQRRLDQSI GKPSLFISVS EKSKDRGSNT IGARLNRVED KVTQLDQRLA 490 500 510 520 530 540 LITDMLHQLL SLHGGSTPGS GGPPREGGAH ITQPCGSGGS VDPELFLPSN TLPTYEQLTV PRRGPDEGS

References

[1]	"Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias." Chouabe C., Neyroud N., Guicheney P., Lazdunski M., Romey G., Barhanin J. EMBO J. 16:5472-5479(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[2]	"Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome." Itoh T., Tanaka T., Nagai R., Kikuchi K., Ogawa S., Okada S., Yamagata S., Yano K., Yazaki Y., Nakamura Y. Hum. Genet. 103:290-294(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANTS LQT1, VARIANT SER-643.
[3]	"Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome." Neyroud N., Richard P., Vignier N., Donger C., Denjoy I., Demay L., Shkolnikova M., Pesce R., Chevalier P., Hainque B., Coumel P., Schwartz K., Guicheney P. Circ. Res. 84:290-297(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANTS LQT1 MET-587 AND HIS-591.
[4]	Seebohm G. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[5]	"KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias." Yang W.-P., Levesque P.C., Little W.A., Conder M.L., Shalaby F.Y., Blanar M.A. Proc. Natl. Acad. Sci. U.S.A. 94:4017-4021(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-129.
[6]	"Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel." Sanguinetti M.C., Curran M.E., Zou A., Shen J., Spector P.S., Atkinson D.L., Keating M.T. Nature 384:80-83(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 96-156. Tissue: Pancreas.
[7]	"Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias." Wang Q., Curran M.E., Splawski I., Burn T.C., Millholland J.M., Vanraay T.J., Shen J., Timothy K.W., Vincent G.M., de Jager T., Schwartz P.J., Towbin J.A., Moss A.J., Atkinson D.L., Landes G.M., Connors T.D., Keating M.T. Nat. Genet. 12:17-23(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 130-676, VARIANTS LQT1.
[8]	"Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart." Jiang M., Tseng-Crank J., Tseng G.-N. J. Biol. Chem. 272:24109-24112(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Heart.
[9]	"Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome." Shalaby F.Y., Levesque P.C., Yang W.-P., Little W.A., Conder M.L., Jenkins-West T., Blanar M.A. Circulation 96:1733-1736(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS LQT1 PRO-178; PHE-273 AND ILE-312.
[10]	"Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors." Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Jentsch T.J., Brown D.A. J. Physiol. (Lond.) 522:349-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[11]	"A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly." Schmitt N., Schwarz M., Peretz A., Abitbol I., Attali B., Pongs O. EMBO J. 19:332-340(2000) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF A SUBUNITS ASSEMBLY DOMAIN.
[12]	"A constitutively open potassium channel formed by KCNQ1 and KCNE3." Schroeder B.C., Waldegger S., Fehr S., Bleich M., Warth R., Greger R., Jentsch T.J. Nature 403:196-199(2000) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INTERACTION WITH KCNE3.
[13]	"The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction." Wiener R., Haitin Y., Shamgar L., Fernandez-Alonso M.C., Martos A., Chomsky-Hecht O., Rivas G., Attali B., Hirsch J.A. J. Biol. Chem. 283:5815-5830(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 574-622, INTERACTION WITH CALM, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-589; ALA-590 AND ASN-593, CHARACTERIZATION OF VARIANT LQT1 ASP-589, SUBUNIT.
[14]	"Jervell and Lange-Nielsen syndrome: a Norwegian perspective." Tranebjaerg L., Bathen J., Tyson J., Bitner-Glindzicz M. Am. J. Med. Genet. 89:137-146(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[15]	"KVLQT1 mutations in three families with familial or sporadic long QT syndrome." Russell M.W., Dick M. II, Collins F.S., Brody L.C. Hum. Mol. Genet. 5:1319-1324(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 SER-314 AND VAL-341.
[16]	"Evidence of a long QT founder gene with varying phenotypic expression in South African families." de Jager T., Corbett C.H., Badenhorst J.C., Brink P.A., Corfield V.A. J. Med. Genet. 33:567-573(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 VAL-341.
[17]	"A severe form of long-QT syndrome caused by KVLQT1 mutations located in cis (Abstract #2051)." Wedekind H., Schulze-Bahr E., Lange S., Rubie C., Haverkamp W., Hoerdt M., Borggrefe M., Assmann G., Breithardt G., Funke H. Am. J. Hum. Genet. Suppl. 61:A350-A350(1997) Cited for: VARIANTS LQT1 MET-254 AND MET-417.
[18]	"Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome." Tanaka T., Nagai R., Tomoike H., Takata S., Yano K., Yabuta K., Haneda N., Nakano O., Shibata A., Sawayama T., Kasai H., Yazaki Y., Nakamura Y. Circulation 95:565-567(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 THR-178; MET-313; ARG-325 AND PRO-366.
[19]	"KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome." Donger C., Denjoy I., Berthet M., Neyroud N., Cruaud C., Bennaceur M., Chivoret G., Schwartz K., Coumel P., Guicheney P. Circulation 96:2778-2781(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1.
[20]	"The long QT syndrome: a novel missense mutation in the S6 region of the KVLQT1 gene." van den Berg M.H., Wilde A.A.M., Robles de Medina E.O., Meyer H., Geelen J.L.M.C., Jongbloed R.J.E., Wellens H.J., Geraedts J.P.M. Hum. Genet. 100:356-361(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 ARG-216.
[21]	"Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias." Wollnik B., Schroeder B.C., Kubisch C., Esperer H.D., Wieacker P., Jentsch T.J. Hum. Mol. Genet. 6:1943-1949(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 ASN-317.
[22]	"New mutations in the KVLQT1 potassium channel that cause long-QT syndrome." Li H., Chen Q., Moss A.J., Robinson J.L., Goytia V., Perry J.C., Vincent G.M., Priori S.G., Lehmann M.H., Denfield S.W., Duff D., Kaine S., Shimizu W., Schwartz P.J., Wang Q., Towbin J.A. Circulation 97:1264-1269(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 VAL-341.
[23]	"A recessive variant of the Romano-Ward Long-QT syndrome?" Priori S.G., Schwartz P.J., Napolitano C., Bianchi L., Dennis A.T., de Fusco M., Brown A.M., Casari G. Circulation 97:2420-2425(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 THR-300.
[24]	"Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an apparently normal phenotype in long QT syndrome." Neyroud N., Denjoy I., Donger C., Gary F., Villain E., Leenhardt A., Benali K., Schwartz K., Coumel P., Guicheney P. Eur. J. Hum. Genet. 6:129-133(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT JLNS1 SER-305.
[25]	"Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1." Splawski I., Shen J., Timothy K.W., Vincent G.M., Lehmann M.H., Keating M.T. Genomics 51:86-97(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 ARG-168; SER-314; CYS-315; ASN-318; PRO-353 AND TRP-366.
[26]	"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., Swan H., Kainulainen K., Toivonen L., Viitasalo M., Kontula K. Hum. Mutat. 11:158-165(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 ILE-311 AND ASN-317.
[27]	"A novel mutation in KVLQT1 is the molecular basis of inherited long QT syndrome in a near-drowning patient's family." Ackerman M.J., Schroeder J.J., Berry R., Schaid D.J., Porter C.-B.J., Michels V.V., Thibodeau S.N. Pediatr. Res. 44:148-153(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 PHE-339 DEL.
[28]	"Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias." Mohammad-Panah R., Demolombe S., Neyroud N., Guicheney P., Kyndt F., van den Hoff M., Baro I., Escande D. Am. J. Hum. Genet. 64:1015-1023(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT JLNS1 HIS-243.
[29]	"Congenital long QT syndrome. The value of genetics in prognostic evaluation." Denjoy I., Lupoglazoff J.M., Donger C., Berthet M., Richard P., Neyroud N., Villain E., Lucet V., Coumel P., Guicheney P. Arch. Mal. Coeur Vaiss. 92:557-563(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 HIS-174.
[30]	"Low penetrance in the long-QT syndrome: clinical impact." Priori S.G., Napolitano C., Schwartz P.J. Circulation 99:529-533(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 LEU-225; CYS-281 AND CYS-315.
[31]	"Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene." Larsen L.A., Fosdal I., Andersen P.S., Kanters J.K., Vuust J., Wettrell G., Christiansen M. Eur. J. Hum. Genet. 7:724-728(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 THR-525.
[32]	"Novel KCNQ1 and HERG missense mutations in Dutch long-QT families." Jongbloed R.J.E., Wilde A.A.M., Geelen J.L.M.C., Doevendans P., Schaap C., van Langen I., van Tintelen J.P., Cobben J.M., Beaufort-Krol G.C.M., Geraedts J.P.M., Smeets H.J.M. Hum. Mutat. 13:301-310(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 SER-184; ARG-189; SER-314; SER-315; ARG-345; PRO-373 AND ARG-392.
[33]	"High-throughput single-strand conformation polymorphism analysis by automated capillary electrophoresis: robust multiplex analysis and pattern-based identification of allelic variants." Larsen L.A., Christiansen M., Vuust J., Andersen P.S. Hum. Mutat. 13:318-327(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 CYS-157.
[34]	"Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits." Franqueza L., Lin M., Shen J., Keating M.T., Sanguinetti M.C. J. Biol. Chem. 274:21063-21070(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS LQT1 CYS-243; ARG-248 AND LYS-261.
[35]	Erratum Franqueza L., Lin M., Shen J., Keating M.T., Sanguinetti M.C. J. Biol. Chem. 274:25188-25188(1999)
[36]	"Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk." Chouabe C., Neyroud N., Richard P., Denjoy I., Hainque B., Romey G., Drici M.-D., Guicheney P., Barhanin J. Cardiovasc. Res. 45:971-980(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 GLN-190; TRP-533 AND TRP-539, VARIANT JLNS1 HIS-243, CHARACTERIZATION OF VARIANTS LQT1 GLN-190; TRP-533 AND TRP-539, CHARACTERIZATION OF VARIANT JLNS1 HIS-243.
[37]	"Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2." Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S.G., Robinson J.L., Moss A.J., Schwartz P.J., Towbin J.A., Vincent G.M., Keating M.T. Circulation 102:1178-1185(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1.
[38]	"KCNQ1 gain-of-function mutation in familial atrial fibrillation." Chen Y.-H., Xu S.-J., Bendahhou S., Wang X.-L., Wang Y., Xu W.-Y., Jin H.-W., Sun H., Su X.-Y., Zhuang Q.-N., Yang Y.-Q., Li Y.-B., Liu Y., Xu H.-J., Li X.-F., Ma N., Mou C.-P., Chen Z., Barhanin J., Huang W. Science 299:251-254(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ATFB3 GLY-140.
[39]	"Mutation in the KCNQ1 gene leading to the short QT-interval syndrome." Bellocq C., van Ginneken A.C.G., Bezzina C.R., Alders M., Escande D., Mannens M.M.A.M., Baro I., Wilde A.A.M. Circulation 109:2394-2397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SQT2 LEU-307, CHARACTERIZATION OF VARIANT SQT2 LEU-307.
[40]	"Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing." Tester D.J., Will M.L., Haglund C.M., Ackerman M.J. Heart Rhythm 2:507-517(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT1 71-ALA--PRO-73 DEL; THR-73; GLY-115; TYR-122; ILE-133; PHE-136; LYS-160; ARG-168; CYS-174; GLN-190; PHE-204; LEU-225; ASN-235; ASN-242; CYS-243; MET-254; 254-VAL--PHE-256 DEL; CYS-259; LEU-259; ASP-261; PRO-266; SER-269; ASP-269; PHE-273; ARG-273; SER-276 DEL; LEU-277; HIS-278; LYS-290; ASP-292; CYS-293; VAL-302; ARG-304; SER-305; ILE-312; SER-314; ARG-314; ASP-314; CYS-315; ARG-316; ALA-322; PHE-339 DEL; VAL-341; SER-343; GLU-344; VAL-344; GLU-345; TRP-349; PRO-353; ARG-362; TRP-366; HIS-374; SER-380; TYR-389; TRP-452; GLY-524; GLU-526; TRP-539; LEU-546; CYS-555; HIS-555; TYR-566; SER-567; ARG-568; MET-587; THR-590; HIS-591; GLN-594; MET-619 AND SER-626.
[41]	"Biophysical characterization of KCNQ1 P320 mutations linked to long QT syndrome 1." Thomas D., Khalil M., Alter M., Schweizer P.A., Karle C.A., Wimmer A.B., Licka M., Katus H.A., Koenen M., Ulmer H.E., Zehelein J. J. Mol. Cell. Cardiol. 48:230-237(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 HIS-320, CHARACTERIZATION OF VARIANTS LQT1 ALA-320 AND HIS-320.
[42]	"Biophysical properties of mutant KCNQ1 S277L channels linked to hereditary long QT syndrome with phenotypic variability." Aidery P., Kisselbach J., Schweizer P.A., Becker R., Katus H.A., Thomas D. Biochim. Biophys. Acta 1812:488-494(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT1 LEU-277, CHARACTERIZATION OF VARIANT LQT1 LEU-277.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

KvLQT1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF000571 mRNA. Translation: AAC51776.1.
AB015163 Genomic DNA. Translation: BAA34738.1.
AB015163 Genomic DNA. Translation: BAA34739.1. Frameshift.
AJ006345 Genomic DNA. Translation: CAB44649.1.
AJ006345 Genomic DNA. Translation: CAB44650.1.
AY114213 mRNA. Translation: AAM94040.1.
U86146 mRNA. Translation: AAB53974.1.
U89364 mRNA. Translation: AAC51781.1.
AF051426 mRNA. Translation: AAC05705.1.

IPI

IPI00020502.
IPI00790656.

RefSeq

NP_000209.2. NM_000218.2.

UniGene

Hs.95162.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BJ4	X-ray	2.00	A/B	574-622	[»]
3HFC	X-ray	2.45	A/B/C	583-611	[»]
3HFE	X-ray	1.70	A/B/C	583-611	[»]

ProteinModelPortal

P51787.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27591N.

IntAct

P51787. 1 interaction.

MINT

MINT-1145466.

STRING

9606.ENSP00000155840.

Protein family/group databases

TCDB

1.A.1.15.6. voltage-gated ion channel (VIC) superfamily.

PTM databases

PhosphoSite

P51787.

Polymorphism databases

DMDM

6166005.

Proteomic databases

PaxDb

P51787.

PRIDE

P51787.

Protocols and materials databases

DNASU

3784.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000155840; ENSP00000155840; ENSG00000053918.
ENST00000335475; ENSP00000334497; ENSG00000053918.

GeneID

3784.

KEGG

hsa:3784.

UCSC

uc001lwn.3. human.

Organism-specific databases

CTD

3784.

GeneCards

GC11P002466.

HGNC

HGNC:6294. KCNQ1.

HPA

CAB018656.

MIM

192500. phenotype.
220400. phenotype.
607542. gene.
607554. phenotype.
609621. phenotype.

neXtProt

NX_P51787.

Orphanet

334. Familial atrial fibrillation.
51083. Familial short QT syndrome.
90647. Jervell and Lange-Nielsen syndrome.
101016. Romano-Ward syndrome.

PharmGKB

PA223.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1226.

HOVERGEN

HBG059014.

InParanoid

P51787.

KO

K04926.

OMA

GWGRLPG.

OrthoDB

EOG4Q58PW.

PhylomeDB

P51787.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

P51787.

Bgee

P51787.

CleanEx

HS_KCNQ1.

Genevestigator

P51787.

GermOnline

ENSG00000053918. Homo sapiens.

Family and domain databases

InterPro

IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
IPR003937. K_chnl_volt-dep_KCNQ.
IPR013821. K_chnl_volt-dep_KCNQ_C.
IPR005827. K_chnl_volt-dep_KCQN1.
[Graphical view]

PANTHER

PTHR11537. PTHR11537. 1 hit.
PTHR11537:SF9. PTHR11537:SF9. 1 hit.

Pfam

PF00520. Ion_trans. 1 hit.
PF03520. KCNQ_channel. 1 hit.
[Graphical view]

PRINTS

PR00169. KCHANNEL.
PR01460. KCNQ1CHANNEL.
PR01459. KCNQCHANNEL.

ProtoNet

Search...

Other

BindingDB

P51787.

ChEMBL

CHEMBL1866.

ChiTaRS

KCNQ1. human.

DrugBank

DB01244. Bepridil.
DB00808. Indapamide.

EvolutionaryTrace

P51787.

GenomeRNAi

3784.

NextBio

14853.

SOURCE

Search...

Entry information

Entry name

KCNQ1_HUMAN

Accession

Primary (citable) accession number: P51787
Secondary accession number(s): O00347 , O60607, O94787, Q7Z6G9, Q92960, Q9UMN8, Q9UMN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 148 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.