Protein Details: Potassium voltage-gated channel subfamily KQT member 1
Protein ID
ICDB_Pro_0588
Protein Name
Potassium voltage-gated channel subfamily KQT member 1
Gene Name
KCNQ1; KCNA8; KCNA9; KVLQT1
Organism
Homo sapiens (Human)
Length
676 amino acids
AlphaFoldDB
AF-P51787-F1-model_v4.pdb
Function
Potassium channel that plays an important role in a number of tissues;including heart;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. 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). 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
Sequence
Ligand Binding
Binding Site
Disease
Long Qt Syndrome 1 and Jervell And Lange-Nielsen Syndrome 1
Location
KvLQT1 has been shown to interact with PRKACA;[11] PPP1CA[11] and AKAP9.[11] KvLQT1 can also associate with any of the five members of the KCNE family of proteins;but interactions with KCNE1;KCNE2;KCNE3 are the only interactions within this protein family that affect the human heart. KCNE2;KCNE4;and KCNE5 have been shown to have an inhibitory effect on the functionality of KvLQT1;while KCNE1 and KCNE3 are activators of KvLQT1.[6] KvLQT1 can associate with KCNE1 and KCNE4 with the activation effects of KCNE1 overriding the inhibitory effects of KCNE4 on the KvLQT1 channel;and KvLQT1 will commonly associate with anywhere from two to four different KCNE proteins in order to be functional.[6] However;KvLQT1 most commonly associates with KCNE1 and forms the KvLQT1/KCNE1 complex since it has only been seen to function in vivo when associated with another protein.[6] KCNQ1 will form a heteromer with KCNE1 in order to slow its activation and enhance the current density at the plasma membrane of the neuron.[6][12] In addition to associating with KCNE proteins;the N-terminal juxtamembranous domain of KvLQT1 can also associate with SGK1;which stimulates the slow delayed potassium rectifier current. Since SGK1 requires structural integrity to stimulate KvLQT1/KCNE1;any mutations present in the KvLQT1 protein can result in reduced stimulation of this channel by SGK1.[13] General mutations in KvLQT1 have been known to cause a decrease in this slow delayed potassium rectifier current;longer cardiac action potentials;and a tendency to have tachyarrhythmias.[12]
DOI ID
RefSeq
NP_000209.2 [P51787-1]; NP_861463.1 [P51787-2]