Potassium channel subfamily K member 9

UniProt Q9NPC2 Organism Homo sapiens Gene KCNK9, TASK3

Also known as: KCNK9, TASK3

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. 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. Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (By similarity). 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).

Classification

Family (Pfam): PF07885 Ion_trans_2
InterPro: 2pore_dom_K_chnl, 2pore_dom_K_chnl_TASK, K_chnl_dom, KCNK9
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 22

3P1N X-ray 1.40A
3P1O X-ray 1.90A
3P1P X-ray 1.95A
3P1Q X-ray 1.70A
3P1R X-ray 1.70A
3P1S X-ray 1.65A
3SMK X-ray 2.10A
3SML X-ray 1.90A
3SMM X-ray 2.00A
3SMN X-ray 2.00A
3SMO X-ray 1.80A
3SP5 X-ray 1.80A
… and 10 more

A predicted model is available from AlphaFold.

Gene Ontology · 18

Disease associations

Birk-Barel syndrome MONDO:0012856

Drugs targeting this protein · 6

SEVOFLURANE opener
DESFLURANE opener
ISOFLURANE opener
ENFLURANE opener
DOXAPRAM HYDROCHLORIDE blocker
HALOTHANE opener

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Potassium channel subfamily K member 9 1 shared papers
Trafficking protein particle complex subunit 9 1 shared papers
Potassium channel subfamily K member 4 2 shared papers
Potassium channel subfamily K member 3 3 shared papers
Potassium channel subfamily K member 1 2 shared papers
Potassium channel subfamily K member 15 1 shared papers
Potassium channel subfamily K member 9 1 shared papers
Potassium channel subfamily K member 1 1 shared papers
Potassium channel subfamily K member 2 1 shared papers
Potassium channel subfamily K member 17 1 shared papers
Potassium channel subfamily K member 5 1 shared papers
Potassium channel subfamily K member 10 1 shared papers

Literature · 12 cited papers

C-type inactivation and proton modulation mechanisms of the TASK3 channel. Proc. Natl. Acad. Sci. U.S.A. · 2024
Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome. Eur. J. Med. Genet. · 2020
KCNK9 imprinting syndrome-further delineation of a possible treatable disorder. Am. J. Med. Genet. A · 2016
A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels. Cell · 2016
SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. Sci. Signal. · 2012
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
Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9. Am. J. Hum. Genet. · 2008
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. Cancer Cell · 2003
KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1. J. Neurophysiol. · 2001
Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel. Brain Res. Mol. Brain Res. · 2000
TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J. Biol. Chem. · 2000

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