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Domain

Each channel subunit contains six transmembrane segments (S1-S6) with S1-S4 forming one voltage sensing domain (VSD) and S5-S6 contributing to form one quarter of an interlocking pore-forming domain (PD).

The segment S6 is involved in the inhibition of voltage-gated potassium channel activity by KCNE4.

The CALM binding domains correspond to the first two membrane-proximal helical regions that interact with a single calmodulin/CALM molecule forming a clamp-like structure (PubMed:16556865, PubMed:25441029). Binding of CALM C-terminus to the first helix is calcium-independent and is essential for assembly of the structure. Binding of CALM N-terminus to the second helix is calcium-dependent and regulates electrophysiological activity of the channel (PubMed:16556865, PubMed:25441029).

Residues Lys-526 and Lys-527 in the second helical region of the proximal C-terminus form a critical site where calcium-bound CALM N-lobe competes with PIP2 for the binding to KCNQ1 in order to stabilize the channel open state.

The C-terminal assembly domain carries the major determinants of tetramerization and subunit assembly specificity. Its coiled-coil region is four-stranded.

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). Promotes also 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).

Isoform 2

Non-functional alone but modulatory when coexpressed with the full-length isoform 1.

Involvement in disease

Long QT syndrome 1

LQT1

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Jervell and Lange-Nielsen syndrome 1

JLNS1

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Atrial fibrillation, familial, 3

ATFB3

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Short QT syndrome 2

SQT2

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Type 2 diabetes mellitus

T2D

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.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Post-translational modifications

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.

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).

Deubiquitinated by USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores the membrane localization.

Sequence similarities

Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily.

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.

Cellular localization

  • Cell membrane
  • Multi-pass membrane protein
  • Cytoplasmic vesicle membrane
  • Early endosome
  • Membrane raft
  • Endoplasmic reticulum
  • Basolateral cell membrane
  • Apical cell membrane
  • Multi-pass membrane protein
  • 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.

Alternative names

KCNA8, KCNA9, KVLQT1, KCNQ1, Potassium voltage-gated channel subfamily KQT member 1, IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1, KQT-like 1, Voltage-gated potassium channel subunit Kv7.1

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

74699Da

We found 3 products in 2 categories

Cell Lines & Lysates

Target

Cell type

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Search our catalogue for 'KCNQ1' (3)

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