Each subunit contributes two pore-forming domains 1 and 2 which assemble to form a single pore with M2 and M4 transmembrane helices lining the central cavity and M1 and M3 facing the lipid bilayer. The transmembrane helices are bridged by the selectivity filters 1 and 2 carrying a signature sequence TxTTxG(Y/F)G(D/H) that coordinate the permeant ions. Up to four ions can simultaneously occupy the selectivity filter and at least two elementary charges must translocate across the filter to convert it into the open conformation.
The X-gate is positioned at the distal ends of M4 transmembrane helices forming a two-turn-helical structure with the methyl group of Thr-248 closing the ion conduction pathway.
K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate (PubMed:23169818, PubMed:26919430, PubMed:32499642, PubMed:36195757, PubMed:9312005). Changes ion selectivity and becomes permeable to Na(+) ions in response to extracellular acidification. Protonation of the pH sensor His-98 stabilizes C-type inactivation conformation likely converting the channel from outward K(+)-conducting, to inward Na(+)-conducting to nonconductive state (PubMed:22948150). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:23169818, PubMed:32499642). Allows K(+) currents with fast-gating kinetics important for the repolarization and hyperpolarization phases of action potentials (By similarity). In cerebellar granule cells, heteromeric KCNK3:KCNK9 channel may hyperpolarize the resting membrane potential to limit intrinsic neuronal excitability, but once the action potential threshold is reached, it may support high-frequency action potential firing and increased neuronal excitability (By similarity). Dispensable for central chemosensory respiration i.e. breathing controlled by brainstem CO2/pH, it rather conducts pH-sensitive currents and controls the firing rate of serotonergic raphe neurons involved in potentiation of the respiratory chemoreflex. Additionally, imparts chemosensitivity to type 1 cells in carotid bodies which respond to a decrease in arterial oxygen pressure or an increase in carbon dioxide pressure or pH to initiate adaptive changes in pulmonary ventilation (By similarity). In adrenal gland, contributes to the maintenance of a hyperpolarized resting membrane potential of aldosterone-producing cells at zona glomerulosa and limits aldosterone release as part of a regulatory mechanism that controls arterial blood pressure and electrolyte homeostasis (By similarity). In brown adipocytes, mediates K(+) efflux that counteracts norepinephrine-induced membrane depolarization, limits Ca(2+) efflux and downstream cAMP and PKA signaling, ultimately attenuating lipid oxidation and adaptive thermogenesis (By similarity).
Pulmonary hypertension, primary, 4
PPH4
A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
None
The disease is caused by variants affecting the gene represented in this entry.
Defects in this gene may cause developmental delay with sleep apnea (DDSA). A disorder characterized by developmental neurologic, skeletal and respiratory anomalies including microcephaly, arthrogryposis, scoliosis, cleft palate, facial dysmorphology, bilateral talipes, feeding difficulties and central and/or obstructive sleep apnea. Malformations are detected as early as 21 weeks post gestation. Severely affected patients require ongoing treatment with nocturnal O2 or pressure-controlled ventilation. The disease is associated with recurrent de novo gain of function variants.
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
Widespread expression in adult. Strongest expression in pancreas and placenta. Lower expression in brain, lung, prostate, heart, kidney, uterus, small intestine and colon.
TASK, TASK1, KCNK3, Potassium channel subfamily K member 3, Acid-sensitive potassium channel protein TASK-1, TWIK-related acid-sensitive K(+) channel 1, Two pore potassium channel KT3.1, Two pore K(+) channel KT3.1
Proteins
Neuroscience
43518Da
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ab238588