Potassium voltage-gated channel subfamily KQT member 1
Also known as: KCNA8, KCNA9, KCNQ1, KVLQT1
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. Associates with KCNE beta subunits that modulates current kinetics. Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current. 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). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current. When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions. 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. When associated with KCNE4, inhibits voltage-gated potassium channel activity. When associated with KCNE5, this complex only conducts current upon strong and continued depolarization. Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity. Binds with phosphatidylinositol 4,5-bisphosphate. 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).
Classification
- Family (Pfam)
- PF00520 Ion_trans, PF03520 KCNQ_channel
- InterPro
- Ion_trans_dom, K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ_C, K_chnl_volt-dep_KCQN1, Volt_channel_dom_sf
- Functional cluster
- Ribosome-Biogenesis GTPases (Obg/Era/Der)
Experimental structures · PDB · 26
- 3BJ4 X-ray 2.00A
- 3HFC X-ray 2.45A
- 3HFE X-ray 1.70A
- 4UMO X-ray 3.00A
- 4V0C X-ray 2.86A
- 6MIE NMR
- 6UZZ EM 3.10A
- 6V00 EM 3.10A
- 6V01 EM 3.90A
- 7VUO X-ray 2.68A
- 7VVD X-ray 3.13A
- 7VVH X-ray 2.30A
- … and 14 more
A predicted model is available from AlphaFold.
Gene Ontology · 84
- GO:0016324 apical plasma membrane
- GO:1990794 basolateral part of cell
- GO:0016323 basolateral plasma membrane
- GO:0097546 ciliary base
- GO:0005737 cytoplasm
- GO:0030659 cytoplasmic vesicle membrane
- GO:0005769 early endosome
- GO:0005783 endoplasmic reticulum
- GO:0005770 late endosome
- GO:0098576 lumenal side of membrane
- GO:0005764 lysosome
- GO:0016020 membrane
- GO:0045121 membrane raft
- GO:0034702 monoatomic ion channel complex
- GO:0043005 neuron projection
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0030133 transport vesicle
- GO:0008076 voltage-gated potassium channel complex
- GO:0005516 calmodulin binding
- GO:0005251 delayed rectifier potassium channel activity
- GO:0015271 outward rectifier potassium channel activity
- GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
- GO:0034236 protein kinase A catalytic subunit binding
- GO:0034237 protein kinase A regulatory subunit binding
- GO:0008157 protein phosphatase 1 binding
- GO:0097110 scaffold protein binding
- GO:0044325 transmembrane transporter binding
- GO:0031625 ubiquitin protein ligase binding
- GO:0005249 voltage-gated potassium channel activity
- GO:0086089 voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization
- GO:0086008 voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization
- GO:1902282 voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- GO:0001508 action potential
- GO:0071875 adrenergic receptor signaling pathway
- GO:0086014 atrial cardiac muscle cell action potential
- GO:0060117 auditory receptor cell development
- GO:0086003 cardiac muscle cell contraction
- GO:0060048 cardiac muscle contraction
- GO:0071320 cellular response to cAMP
- GO:0071872 cellular response to epinephrine stimulus
- GO:0071466 cellular response to xenobiotic stimulus
- GO:0090102 cochlea development
- GO:0035934 corticosterone secretion
- GO:0050910 detection of mechanical stimulus involved in sensory perception of sound
- GO:0030218 erythrocyte differentiation
- GO:0001698 gastrin-induced gastric acid secretion
- GO:0006006 glucose metabolic process
- GO:0007507 heart development
- GO:0048839 inner ear development
- GO:0042472 inner ear morphogenesis
- GO:0050892 intestinal absorption
- GO:0030644 intracellular chloride ion homeostasis
- GO:0015705 iodide transport
- GO:0086011 membrane repolarization during action potential
- GO:0098914 membrane repolarization during atrial cardiac muscle cell action potential
- GO:0086013 membrane repolarization during cardiac muscle cell action potential
- GO:0098915 membrane repolarization during ventricular cardiac muscle cell action potential
- GO:1902260 negative regulation of delayed rectifier potassium channel activity
- GO:1903817 negative regulation of voltage-gated potassium channel activity
- GO:1905515 non-motile cilium assembly
- GO:0060452 positive regulation of cardiac muscle contraction
- GO:0010460 positive regulation of heart rate
- GO:1901381 positive regulation of potassium ion transmembrane transport
- GO:0097623 potassium ion export across plasma membrane
- GO:0055075 potassium ion homeostasis
- GO:1990573 potassium ion import across plasma membrane
- GO:0071805 potassium ion transmembrane transport
- GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization
- GO:0008217 regulation of blood pressure
- GO:0060453 regulation of gastric acid secretion
- GO:0008016 regulation of heart contraction
- GO:0086091 regulation of heart rate by cardiac conduction
- GO:0042391 regulation of membrane potential
- GO:0060306 regulation of membrane repolarization
- GO:0060307 regulation of ventricular cardiac muscle cell membrane repolarization
- GO:0070293 renal absorption
- GO:0070294 renal sodium ion absorption
- GO:0032868 response to insulin
- GO:0007622 rhythmic behavior
- GO:0007605 sensory perception of sound
- GO:0035176 social behavior
- GO:0062094 stomach development
- GO:0086005 ventricular cardiac muscle cell action potential
Disease associations
- type 2 diabetes mellitus MONDO:0005148
- long QT syndrome 1 MONDO:0100316
- Jervell and Lange-Nielsen syndrome 1 MONDO:0024540
- atrial fibrillation, familial, 3 MONDO:0011857
- short QT syndrome type 2 MONDO:0012313
Drugs targeting this protein · 7
- TEDISAMIL blocker
- GUANIDINE HYDROCHLORIDE blocker
- NERISPIRDINE blocker
- DALFAMPRIDINE blocker
- AMIFAMPRIDINE PHOSPHATE blocker
- AMIFAMPRIDINE blocker
- EZOGABINE opener
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Potassium voltage-gated channel subfamily KQT member 1 0.98
- Potassium voltage-gated channel subfamily KQT member 1 0.97
- Potassium voltage-gated channel subfamily KQT member 1 0.96
- Potassium voltage-gated channel subfamily KQT member 1 0.92
- Potassium voltage-gated channel subfamily KQT member 4 0.92
- Potassium voltage-gated channel subfamily KQT member 4 0.91
- Potassium voltage-gated channel subfamily KQT member 4 0.90
- Potassium voltage-gated channel subfamily KQT member 1 0.88
- Potassium voltage-gated channel subfamily KQT member 1 0.87
- Potassium voltage-gated channel subfamily KQT member 2 0.84
- Potassium voltage-gated channel subfamily KQT member 2 0.83
- Potassium voltage-gated channel subfamily KQT member 2 0.82
Co-cited proteins · studied together in the literature
- Voltage-gated inwardly rectifying potassium channel KCNH2 10 shared papers
- Potassium voltage-gated channel subfamily KQT member 1 1 shared papers
- Potassium voltage-gated channel subfamily E member 3 3 shared papers
- Potassium voltage-gated channel subfamily E member 1 6 shared papers
- Potassium voltage-gated channel subfamily E member 4 2 shared papers
- Potassium voltage-gated channel subfamily E regulatory beta subunit 5 2 shared papers
- Potassium voltage-gated channel subfamily E member 2 4 shared papers
- Potassium voltage-gated channel subfamily KQT member 5 1 shared papers
- Sodium channel protein type 5 subunit alpha 5 shared papers
- A-kinase anchor protein 9 1 shared papers
- Calmodulin-1 2 shared papers
- Sodium/myo-inositol cotransporter 1 shared papers
Literature · 74 cited papers
- Recurrent pregnancy loss and concealed Long-QT syndrome. J. Am. Heart Assoc. · 2021
- Structural Basis of Human KCNQ1 Modulation and Gating. Cell · 2020
- Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel. Proc. Natl. Acad. Sci. U.S.A. · 2017
- Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome. Front. Cell. Neurosci. · 2015
- Structural basis of a Kv7.1 potassium channel gating module: studies of the intracellular c-terminal domain in complex with calmodulin. Structure · 2014
- Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but preserved cAMP-dependent up-regulation. Cardiovasc. Res. · 2014
- Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP(2). J. Cell Sci. · 2014
- Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology. Arterioscler. Thromb. Vasc. Biol. · 2014
- A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction. J. Mol. Cell. Cardiol. · 2014
- KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability. Sci. Signal. · 2014
- Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature · 2014
- A KCNQ1 mutation contributes to the concealed type 1 long QT phenotype by limiting the Kv7.1 channel conformational changes associated with protein kinase A phosphorylation. Heart Rhythm · 2014
- … and 62 more in the literature graph