MKRQNVRTLALIVCTFTYLLVGAAVFDALESEPELIERQRLELRQQELRARYNLSQGGYEELERVVLRLKPHKAGVQWRFAGSFYFAITVITTIGYGHAAPSTDGGKVFCMFYALLGIPLTLVMFQSLGERINTLVRYLLHRAKKGLGMRRADVSMANMVLIGFFSCISTLCIGAAAFSHYEHWTFFQAYYYCFITLTTIGFGDYVALQKDQALQTQPQYVAFSFVYILTGLTVIGAFLNLVVLRFMTMNAEDEKRDAEHRALLTRNGQAGGGGGGGSAHTTDTASSTAAAGGGGFRNVYAEVLHFQSMCSCLWYKSREKLQYSIPMIIPRDLSTSDTCVEQSHSSPGGGGRYSDTPSRRCLCSGAPRSAISSVSTGLHSLSTFRGLMKRRSSV
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pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward.
Gene References into Functions
The results of the present study suggested that miR138 promoted proliferation and suppressed mitochondrial depolarization of human pulmonary artery smooth muscle cells by targeting TASK1.PMID:29257242
Screening for mutations in the human TASK-1 gene in 155 cases of sudden infant death syndrome (SIDS) was inconclusive. Results are suggestive for an increased hypoxia-sensitivity of neonatal TASK-1(-/-) mice, however, without causing an increase in neonatal lethality. In adult female TASK-1(-/-) mice respiration was unaffected, whereas adult male TASK-1(-/-) mice showed a modified breathing pattern.PMID:27838333
Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. Furthermore, mutations in KCNK3 have been identified as a rare cause of both familial and idiopathic pulmonary arterial hypertension. [review]PMID:29122916
Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes in infants with pulmonary hypoplasia and pulmonary hypertension.PMID:28162765
Heterozygous KCNK3 mutations in pulmonary arterial hypertension lead to variable loss of channel function via distinct mechanisms.PMID:28889099
Familial cases of Pulmonary Arterial Hypertension related to heterozygous missense variants in the KCNK3 gene (encoding the two-pore-domain potassium channel TASK-1) has been described with a prevalence of 1.3 and 3.2% in idiopathic Pulmonary Arterial Hypertension and heritable Pulmonary Arterial Hypertension, respectively.PMID:28582316
our study indicates that TASK-1 is functionally regulated by caveolin-3, possibly via association with each other on the cell surface. These results point out a novel mechanism in the regulation of TASK-1.PMID:28648645
A burden of rare variants in BMPR2 significantly contributed to the risk of pulmonary arterial hypertension. In the remaining one family, the patient carried a pathogenic variant in a member of potassium channels, KCNK3, which was the first replicative finding of channelopathy in an Asian population.PMID:28388887
The results suggested that heterodimerization of TASK1 and TALK2 provides cells with the ability to make multiple responses to a variety of physiological and pharmacological stimuli.PMID:29016681
Genetic variation in the KCNK3 gene may contribute to Blood pressure variation and less severe Hypertensive disorders in which aldosterone may be one of several causative factorsPMID:27296998
Knockdown of TASK-1 by siRNA significantly enhanced apoptosis and reduced proliferation in Non-Small Cell Lung Cancer A549 cells, but not in weakly TASK-1 expressing NCI-H358 cells.PMID:27294516
The present report supports the contribution of KCNK3 mutations to the genetic etiology of Pulmonary arterial hypertension and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients.PMID:27649371
In a cohort with idiopathic or hereditary pulmonary arterial hypertension, a possibly associated mutation was found in 11.10% of the idiopathic cases (n = 16) and in 68.18% of the hereditary cases. There were 3 mutations found in KCNK3.PMID:27453251
Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap.PMID:26794006
control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic.PMID:26743085
KCNK3 expression and function were reduced in pulmonary artery smooth muscle cells and endothelial cells in human pulmonary arterial hypertension.PMID:26912814
TASK-1 and TASK-3 may form heterodimers in human atrial cardiomyocytes.PMID:25655935
Diacylglycerol mediates regulation of TASK1 and TASK3 potassium channels by GNAQ.PMID:25420509
Enhancement of atrium-selective K(2P)3.1 currents contributes to action potential shortening in atrial fibrillation patients.PMID:25951834
K2P3.1 and K2P9.1 undergo rapid dynamin-dependent endocytosisPMID:23807092
Syntaxin-8 regulates the endocytosis of TASK-1.PMID:24743596
A glucose-dependent role for beta-cell TASK-1 channels of limiting glucose-stimulated Deltapsip depolarization and insulin secretion, which modulates glucose homeostasis.PMID:24932805
demonstrate the functional importance of ITASK in the atrium and suggest that inactivation of TASK-1 may have diverse effects on atrial size and electrophysiological properties that can contribute to an arrhythmogenic substratePMID:24374141
Sec61 complex reorientation of the first signal-anchor sequence of TASK-1 determines membrane topology of the other membrane spanning regions.PMID:24015703
Our study identified the association of a novel gene, KCNK3, with familial and idiopathic pulmonary arterial hypertension.PMID:23883380
Ability to induce atrial fibrillation in the peri-operative period is associated with phosphorylation-dependent inhibition of TWIK protein-related acid-sensitive potassium channel 1PMID:23229553
There were no associations between KCNK3 single nucleotide polymorphisms and blood pressure or aldosterone production.PMID:22893713
ET-1 inhibited TASK1-mediated I(KN) currents in hPASMC.PMID:21838752
I(TASK-1) contributes to the sustained outward current I(Ksus) and that I(TASK-1) is a major component of the background conductance in human atrial cardiomyocytes.PMID:22178873
TASK-1- and TASK-3-mediated currents are not affected by depletion of plasma membrane PI4,5P2 either via the voltage-activated phosphatase Ci-VSP or via chemically triggered recruitment of a PI4,5P2-5'-phosphatase.PMID:21540350
TASK-1 immunoreactivity was observed in astrocytes of temporal lobe epilepsy patients.PMID:21710317
analysis of how the specific two-pore domain potassium channel blocker A1899 defines the structure of the TASK-1 open porePMID:21362619
cAMP-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both K(2P)3.1 and K(2P)9.1PMID:21357689
Western analysis confirms expression of TASK1 and TASK3 in medulloblastoma cells.PMID:20931182
TASK-1 and 3 are determinant of aldosterone secretion and adrenocortical zonation.PMID:20049674
TASK-1 and TASK-3 differed insofar as a large portion of the C terminus was necessary for the full effects of halothane and TRH on TASK-3 but not on TASK-1PMID:11886861
Renal Oat1 expression gradually increased throughout development, approaching adult levels at 30 days of age, where at days 40 and 45 Oat1 levels were greater in males than femalesPMID:11907168
C-PAF blocks TASK-1 or a closely related channel, the effect is PKC dependent, and the inhibition alters the electrical activity of myocytes in ways that would be arrhythmogenic in the intact heart.PMID:12003807
Association with p11 is essential for trafficking of TASK-1 to the plasma membrane. This association masks an ER retention signal identified as Lys-Arg-Arg that precedes the Ser-Ser-Val sequence.PMID:12198146
KCNK3 potassium channels are shown to bear two cytoplasmic trafficking motifs: an N-terminal dibasic site that binds beta-COP to hold channels in ER and a C-terminal "release" site that binds the ubiquitous intracellular regulator 14-3-3betaPMID:12437930
hOAT1-expressing cell line showed extensive para-aminohippuric acid transport. hOAT1 also demonstrated 1:1 coupling between organic anion and dicarboxylate.PMID:12837685
Host TASK-1 protein and HIV-1 Vpu undergo mutual functional destruction.PMID:15099524
TASK1 is expressed in pia mater, astrocytes, Purkinje and granule cellsPMID:15197476
Human cytotrophoblast cells from term placenta are a site of expression for various K2P genes, two of which, namely, TASK1 and TREK1, are transcribed into protein.PMID:15695101
TASK-1 is hypoxia-sensitive and controls the resting membrane potential, thus implicating an important role for TASK-1 K+ channels in the regulation of pulmonary vascular tone.PMID:16574908
the role of TASK channels in sensing physiological stimuli.PMID:17945357
K(2)P channels as novel potassium conductance on T lymphocytes critically influencing T cell effector function and identify a possible molecular target for immunomodulation in T cell-mediated autoimmune disordersPMID:18375952
Thus, regulated expression of TASK channels might contribute to a molecular switch between death and survival of neurons in autoimmune CNS inflammation.PMID:18824070
ET-1 depolarized human primary pulmonary artery smooth muscle cells by phosphorylating TASK-1. This effect was abrogated by TASK-1 siRNA. This might represent a novel pathologic mechanism related to pulmonary arterial hypertension.PMID:19188660
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Subcellular Location
Cell membrane; Multi-pass membrane protein.
Protein Families
Two pore domain potassium channel (TC 1.A.1.8) family
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.