Recombinant Human Potassium channel subfamily K member 3 (KCNK3) 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: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)

Subcellular Location

Cell membrane (Multi-pass membrane protein)

Disease Association

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. [The disease is caused by variants affecting the gene represented in this entry] | Developmental delay with sleep apnea (DDSA) : An autosomal dominant disorder characterized by global developmental delay, hypotonia, gastrointestinal findings, and central and/or obstructive sleep apnea. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widespread expression in adult. Strongest expression in pancreas and placenta. Lower expression in brain, lung, prostate, heart, kidney, uterus, small intestine and colon

Subunit

Homodimer (PubMed:32499642). Heterodimer with KCNK1 (PubMed:23169818). Heterodimer with KCNK9 (By similarity). Interacts with SERTM2; the interaction may affect the resting potential of neurons (By similarity)

• Duprat F. et al. TASK, a human background K+ channel to sense external pH variations near physiological pH. — EMBO J. (1997)
• Lopes C.M.B. et al. Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. — J. Biol. Chem. (2000)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• Patel A.J. et al. Inhalational anesthetics activate two-pore-domain background K+ channels. — Nat. Neurosci. (1999)
• Ashmole I. et al. TASK-5, a novel member of the tandem pore K+ channel family. — Pflugers Arch. (2001)
• Plant L.D. et al. SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. — Sci. Signal. (2012)
• 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)