Recombinant Human Potassium channel subfamily K member 9 (KCNK9) Protein

Function

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:11042359, PubMed:11431495, PubMed:26919430, PubMed:38630723). 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, PubMed:38630723). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (By similarity) (PubMed:23169818, PubMed:38630723). Allows K(+) currents with fast-gating kinetics important for the repolarization and hyperpolarization phases of action potentials (By similarity). In granule neurons, hyperpolarizes the resting membrane potential to limit intrinsic neuronal excitability, but once the action potential threshold is reached, supports high-frequency action potential firing and increased neuronal excitability. Homomeric and/or heteromeric KCNK3:KCNK9 channels operate in cerebellar granule cells, whereas heteromeric KCNK1:KCNK9 enables currents in hippocampal dentate gyrus granule neurons (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 (By similarity). In retinal ganglion cells, mediates outward currents that regulate action potentials in response to acidification of the synaptic cleft. Involved in transmission of image-forming and nonimage-forming visual information in the retina (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)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Mitochondrion inner membrane (Multi-pass membrane protein); Cell projection, dendrite

Disease Association

Birk-Barel syndrome (BIBARS) : A syndrome characterized by intellectual disability, hypotonia, hyperactivity, and facial dysmorphism. BIBARS transmission pattern is consistent with autosomal dominant inheritance with paternal imprinting. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Mainly found in the cerebellum. Also found in adrenal gland, kidney and lung

Subunit

Homodimer (PubMed:38630723). Heterodimer with KCNK1 (PubMed:23169818). Heterodimer with KCNK3 (By similarity)

• Rajan S. et al. TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. — J. Biol. Chem. (2000)
• Chapman C.G. et al. Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel. — Brain Res. Mol. Brain Res. (2000)
• Vega-Saenz de Miera E. et al. KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1. — J. Neurophysiol. (2001)
• Mu D. et al. Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. — Cancer Cell (2003)
• Girard C. et al. Human Task-3, a novel 2P domain potassium channel related to Task. (JUN-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Ma L. et al. Acid-sensitive TWIK and TASK two-pore domain potassium channels change ion selectivity and become permeable to sodium in extracellular acidification. — J. Biol. Chem. (2012)
• Plant L.D. et al. SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. — Sci. Signal. (2012)