KCNQ1
entrez
3784
canonical
uniprot
P51787
canonical
ensembl
ENSG00000053918
resolver
ensp
ENSP00000155840
resolver
ensp
ENSP00000334497
resolver
ensp
ENSP00000434560
resolver
ensp
ENSP00000494939
resolver
ensp
ENSP00000669395
resolver
genesymbol
KCNQ1
resolver
genesymbol_syn
KCNA8
resolver
genesymbol_syn
KCNA9
resolver
genesymbol_syn
KVLQT1
resolver
hgnc
HGNC:6294
resolver
uniprot
O00347
resolver
uniprot
O60607
resolver
uniprot
O94787
resolver
uniprot
Q14D14
resolver
uniprot
Q7Z6G9
resolver
uniprot
Q92960
resolver
uniprot
Q96AI9
resolver
uniprot
Q9UMN8
resolver
uniprot
Q9UMN9
resolver
uniprot_entry
KCNQ1_HUMAN
resolver
uniprot_entry
Q96AI9_HUMAN
resolver
uniprot_sec
O00347
resolver
uniprot_sec
O60607
resolver
uniprot_sec
O94787
resolver
uniprot_sec
Q14D14
resolver
uniprot_sec
Q7Z6G9
resolver
uniprot_sec
Q92960
resolver
uniprot_sec
Q9UMN8
resolver
uniprot_sec
Q9UMN9
resolver
activity_regulation
ACTIVITY REGULATION: PIP2 molecule is essential to activate KCNQ channels by inducing the coupling of the voltage-sensing domain (VSD) and the pore-forming domain (PD) (PubMed:28096388, PubMed:31883792). Upon channel activation, PIP2 disrupts the VSD-calmodulin/CALM interactions, causing the release of CALM from the VSD which triggers the opening of the gate (PubMed:28096388, PubMed:31883792). Calcium potentiates KCNQ1 channel current through calcium-bound CALM (PubMed:24595108, PubMed:28096388). Calcium-bound CALM competes with PIP2 to stabilize the channel open state (PubMed:28096388). {ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:28096388, ECO:0000269|PubMed:31883792}.
uniprot
proteins
amino_acid_sequence
MAAASSPPRAERKRWGWGRLPGARRGSAGLAKKCPFSLELAEGGPAGGALYAPIAPGAPGPAPPASPAAPAAPPVASDLGPRPPVSLDPRVSIYSTRRPVLARTHVQGRVYNFLERPTGWKCFVYHFAVFLIVLVCLIFSVLSTIEQYAALATGTLFWMEIVLVVFFGTEYVVRLWSAGCRSKYVGLWGRLRFARKPISIIDLIVVVASMVVLCVGSKGQVFATSAIRGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYIGFLGLIFSSYFVYLAEKDAVNESGRVEFGSYADALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAISFFALPAGILGSGFALKVQQKQRQKHFNRQIPAAASLIQTAWRCYAAENPDSSTWKIYIRKAPRSHTLLSPSPKPKKSVVVKKKKFKLDKDNGVTPGEKMLTVPHITCDPPEERRLDHFSVDGYDSSVRKSPTLLEVSMPHFMRTNSFAEDLDLEGETLLTPITHISQLREHHRATIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLMVRIKELQRRLDQSIGKPSLFISVSEKSKDRGSNTIGARLNRVEDKVTQLDQRLALITDMLHQLLSLHGGSTPGSGGPPREGGAHITQPCGSGGSVDPELFLPSNTLPTYEQLTVPRRGPDEGS
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:10024302, ECO:0000269|PubMed:10220144, ECO:0000269|PubMed:10220146, ECO:0000269|PubMed:10367071, ECO:0000269|PubMed:10409658, ECO:0000269|PubMed:10482963, ECO:0000269|PubMed:10728423, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11799244, ECO:0000269|PubMed:12442276, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:16556865, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:18400097, ECO:0000269|PubMed:19540844, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:19808498, ECO:0000269|PubMed:21241800, ECO:0000269|PubMed:24184248, ECO:0000269|PubMed:24269949, ECO:0000269|PubMed:24713462, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:25139741, ECO:0000269|PubMed:25705178, ECO:0000269|PubMed:28096388, ECO:0000269|PubMed:34398675, ECO:0000269|PubMed:8528244, ECO:0000269|PubMed:8818942, ECO:0000269|PubMed:8872472, ECO:0000269|PubMed:9024139, ECO:0000269|PubMed:9272155, ECO:0000269|PubMed:9302275, ECO:0000269|PubMed:9312006, ECO:0000269|PubMed:9323054, ECO:0000269|PubMed:9386136, ECO:0000269|PubMed:9482580, ECO:0000269|PubMed:9570196, ECO:0000269|PubMed:9641694, ECO:0000269|PubMed:9693036, ECO:0000269|PubMed:9702906, ECO:0000269|PubMed:9799083, ECO:0000269|PubMed:9927399, ECO:0000269|Ref.36}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10090886, ECO:0000269|PubMed:10728423, ECO:0000269|PubMed:18400097, ECO:0000269|PubMed:18441444, ECO:0000269|PubMed:25705178, ECO:0000269|PubMed:9781056}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Atrial fibrillation, familial, 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. {ECO:0000269|PubMed:12522251}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Short QT syndrome 2 (SQT2) [MIM:609621]: An autosomal dominant form of short QT syndrome, 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 can cause syncope and sudden death. {ECO:0000269|PubMed:15159330}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:18711366, ECO:0000269|PubMed:18711367, ECO:0000269|PubMed:24390345}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Also promotes a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation, participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, 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). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.; FUNCTION: [Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269|PubMed:9305853}.
uniprot
proteins
mass_dalton
74699
uniprot
proteins
mutagenesis
MUTAGEN 27; /note="S->A: No phosphorylation by PKA. Decreases delayed rectifier potassium channel activity."; /evidence="ECO:0000269|PubMed:11799244"; MUTAGEN 231; /note="R->A: Strongly inhibits SLC5A3 transporter activity."; /evidence="ECO:0000269|PubMed:24595108"; MUTAGEN 324; /note="V->L: Has a voltage-gated potassium channel activity. Inhibition of voltage-gated potassium channel activity by KCNE4."; /evidence="ECO:0000269|PubMed:19687231"; MUTAGEN 326; /note="K->R: Has a voltage-gated potassium channel activity. Disrupts KCNE4-mediated voltage-gated potassium channel activity inhibition."; /evidence="ECO:0000269|PubMed:19687231"; MUTAGEN 327; /note="T->V: Has a voltage-gated potassium channel activity. Disrupts KCNE4-mediated voltage-gated potassium channel activity inhibition."; /evidence="ECO:0000269|PubMed:19687231"; MUTAGEN 328; /note="I->L: Has a voltage-gated potassium channel activity. Inhibition of voltage-gated potassium channel activity by KCNE4."; /evidence="ECO:0000269|PubMed:19687231"; MUTAGEN 338; /note="S->C: Inhibits voltage-gated potassium channel activity."; /evidence="ECO:0000269|PubMed:19687231"; MUTAGEN 340; /note="F->C: Inhibits voltage-gated potassium channel activity."; /evidence="ECO:0000269|PubMed:19687231"; MUTAGEN 375; /note="I->D: Reduced protein expression, probably due to misfolding and proteasomal degradation. No detectable electrophysiological activity. Reduced electrophysiological activity in the presence of KCNE1."; /evidence="ECO:0000269|PubMed:25441029"; MUTAGEN 516; /note="V->D: Reduced protein expression, probably due to misfolding and proteasomal degradation. Significantly reduced electrophysiological activity. Reduced electrophysiological activity in the presence of KCNE1."; /evidence="ECO:0000269|PubMed:25441029"; MUTAGEN 526; /note="K->N: Decreased interaction with PIP2 and calmodulin/CALM in the presence of calcium. Insensitive to gating modulation by calcified CALM. Impaired IKS current. Decreased interaction with PIP2 and CALM in the presence of calcium; when associated with N-527. Increased binding to PIP2 and CALM in the absence of calcium. Increased binding to CALM and no change in PIP2 binding in the absence of calcium; when associated with N-527."; /evidence="ECO:0000269|PubMed:28096388"; MUTAGEN 527; /note="K->N: Decreased interaction with PIP2 and calmodulin/CALM in the presence of calcium. Decreased interaction with PIP2 and CALM in the presence of calcium; when associated with N-526. Increased binding to PIP2 and CALM in the absence of calcium. Increased binding to CALM and no change in PIP2 binding in the absence of calcium; when associated with N-526."; /evidence="ECO:0000269|PubMed:28096388"; MUTAGEN 589; /note="G->M: No effect."; /evidence="ECO:0000269|PubMed:18165683"; MUTAGEN 590; /note="A->W: Reduced cell surface expression and strongly reduced potassium current."; /evidence="ECO:0000269|PubMed:18165683"; MUTAGEN 593; /note="N->G: Reduced cell surface expression and moderately reduced potassium current."; /evidence="ECO:0000269|PubMed:18165683"; MUTAGEN 602; /note="L->A: Does not interact with AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with I-609."; /evidence="ECO:0000269|PubMed:11799244"; MUTAGEN 609; /note="I->A: Does not interact with AKAP9 and the kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with L-602."; /evidence="ECO:0000269|PubMed:11799244
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-27 by PKA; increases delayed rectifier potassium channel activity of the KCNQ1-KCNE1 complex through a macromolecular complex that includes PKA, PP1, and the targeting protein AKAP9. {ECO:0000269|PubMed:11799244, ECO:0000269|PubMed:25037568}.; PTM: Ubiquitinated by NEDD4L; promotes internalization (PubMed:22024150). The ubiquitinylated form is internalized through a clathrin-mediated endocytosis by interacting with AP2M1 and is recycled back to the cell membrane via RAB4A and RAB11A (PubMed:23529131). {ECO:0000269|PubMed:22024150, ECO:0000269|PubMed:23529131}.; PTM: Deubiquitinated by USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores the membrane localization. {ECO:0000269|PubMed:22024150}.
uniprot
proteins
protein_family
KQT (TC 1.A.1.15) subfamily
uniprot
proteins
protein_family
Kv7.1/KCNQ1 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10024302
uniprot
proteins
pubmed
10090886
uniprot
proteins
pubmed
10220144
uniprot
proteins
pubmed
10220146
uniprot
proteins
pubmed
10367071
uniprot
proteins
pubmed
10409658
uniprot
proteins
pubmed
10482963
uniprot
proteins
pubmed
10646604
uniprot
proteins
pubmed
10654932
uniprot
proteins
pubmed
10704188
uniprot
proteins
pubmed
10713961
uniprot
proteins
pubmed
10728423
uniprot
proteins
pubmed
10973849
uniprot
proteins
pubmed
11101505
uniprot
proteins
pubmed
11799244
uniprot
proteins
pubmed
12324418
uniprot
proteins
pubmed
12442276
uniprot
proteins
pubmed
12522251
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15159330
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15840476
uniprot
proteins
pubmed
16414944
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16556865
uniprot
proteins
pubmed
16922724
uniprot
proteins
pubmed
18165683
uniprot
proteins
pubmed
18400097
uniprot
proteins
pubmed
18441444
uniprot
proteins
pubmed
18711366
uniprot
proteins
pubmed
18711367
uniprot
proteins
pubmed
19540844
uniprot
proteins
pubmed
19687231
uniprot
proteins
pubmed
19693805
uniprot
proteins
pubmed
19716085
uniprot
proteins
pubmed
19808498
uniprot
proteins
pubmed
20533308
uniprot
proteins
pubmed
21228319
uniprot
proteins
pubmed
21241800
uniprot
proteins
pubmed
22024150
uniprot
proteins
pubmed
23529131
uniprot
proteins
pubmed
24184248
uniprot
proteins
pubmed
24269949
uniprot
proteins
pubmed
24390345
uniprot
proteins
pubmed
24595108
uniprot
proteins
pubmed
24713462
uniprot
proteins
pubmed
24855057
uniprot
proteins
pubmed
25037568
uniprot
proteins
pubmed
25139741
uniprot
proteins
pubmed
25441029
uniprot
proteins
pubmed
25705178
uniprot
proteins
pubmed
28096388
uniprot
proteins
pubmed
31883792
uniprot
proteins
pubmed
34398675
uniprot
proteins
pubmed
8528244
uniprot
proteins
pubmed
8818942
uniprot
proteins
pubmed
8872472
uniprot
proteins
pubmed
8900283
uniprot
proteins
pubmed
9024139
uniprot
proteins
pubmed
9108097
uniprot
proteins
pubmed
9272155
uniprot
proteins
pubmed
9302275
uniprot
proteins
pubmed
9305853
uniprot
proteins
pubmed
9312006
uniprot
proteins
pubmed
9323054
uniprot
proteins
pubmed
9386136
uniprot
proteins
pubmed
9482580
uniprot
proteins
pubmed
9570196
uniprot
proteins
pubmed
9641694
uniprot
proteins
pubmed
9693036
uniprot
proteins
pubmed
9702906
uniprot
proteins
pubmed
9781056
uniprot
proteins
pubmed
9799083
uniprot
proteins
pubmed
9927399
uniprot
proteins
sequence_length
676
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:21228319, ECO:0000269|PubMed:22024150, ECO:0000269|PubMed:25037568}; Multi-pass membrane protein {ECO:0000269|PubMed:18165683}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:23529131}. Early endosome {ECO:0000269|PubMed:23529131}. Membrane raft {ECO:0000269|PubMed:20533308, ECO:0000269|PubMed:24855057}. Endoplasmic reticulum {ECO:0000269|PubMed:21228319, ECO:0000269|PubMed:24855057}. Basolateral cell membrane {ECO:0000269|PubMed:21228319}. Apical cell membrane {ECO:0000250|UniProtKB:P97414}; Multi-pass membrane protein {ECO:0000255}. Note=Colocalized with KCNE3 at the plasma membrane (PubMed:10646604). Upon 17beta-oestradiol treatment, colocalizes with RAB5A at early endosome (PubMed:23529131). Heterotetramer with KCNQ5 is highly retained at the endoplasmic reticulum and is localized outside of lipid raft microdomains (PubMed:24855057). During the early stages of epithelial cell polarization induced by the calcium switch, it is removed from the plasma membrane to the endoplasmic reticulum, where it is retained, and redistributed to the basolateral cell surface in a PI3K-dependent manner at a later stage (PubMed:21228319). Colocalizes with SLC5A3 at the apical membrane of choroid plexus epithelium. {ECO:0000250|UniProtKB:P97414, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:21228319, ECO:0000269|PubMed:23529131, ECO:0000269|PubMed:24855057}.
uniprot
proteins
transmembrane_region
TRANSMEM 121..142; /note="Helical; Name=Segment S1"; /evidence="ECO:0000269|PubMed:31883792, ECO:0007744|PDB:6V01"; TRANSMEM 154..176; /note="Helical; Name=Segment S2"; /evidence="ECO:0000269|PubMed:31883792, ECO:0007744|PDB:6V01"; TRANSMEM 193..218; /note="Helical; Name=Segment S3"; /evidence="ECO:0000269|PubMed:31883792, ECO:0007744|PDB:6V01"; TRANSMEM 227..242; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000269|PubMed:31883792, ECO:0007744|PDB:6V01"; TRANSMEM 261..283; /note="Helical; Name=Segment S5"; /evidence="ECO:0000269|PubMed:31883792, ECO:0007744|PDB:6V01"; TRANSMEM 323..348; /note="Helical; Name=Segment S6"; /evidence="ECO:0000269|PubMed:31883792, ECO:0007744|PDB:6V01
uniprot
proteins