KCNK3
entrez
3777
canonical
uniprot
O14649
canonical
ensembl
ENSG00000171303
resolver
ensp
ENSP00000306275
resolver
enst
ENST00000302909
resolver
genesymbol
KCNK3
resolver
genesymbol_syn
TASK
resolver
genesymbol_syn
TASK1
resolver
hgnc
HGNC:6278
resolver
uniprot
Q53SU2
resolver
uniprot_entry
KCNK3_HUMAN
resolver
uniprot_sec
Q53SU2
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by external acidification, diacylglycerol and anandamide. Activated by halothane and isoflurane. {ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:36195757, ECO:0000269|PubMed:9312005}.
uniprot
proteins
amino_acid_sequence
MKRQNVRTLALIVCTFTYLLVGAAVFDALESEPELIERQRLELRQQELRARYNLSQGGYEELERVVLRLKPHKAGVQWRFAGSFYFAITVITTIGYGHAAPSTDGGKVFCMFYALLGIPLTLVMFQSLGERINTLVRYLLHRAKKGLGMRRADVSMANMVLIGFFSCISTLCIGAAAFSHYEHWTFFQAYYYCFITLTTIGFGDYVALQKDQALQTQPQYVAFSFVYILTGLTVIGAFLNLVVLRFMTMNAEDEKRDAEHRALLTRNGQAGGGGGGGSAHTTDTASSTAAAGGGGFRNVYAEVLHFQSMCSCLWYKSREKLQYSIPMIIPRDLSTSDTCVEQSHSSPGGGGRYSDTPSRRCLCSGAPRSAISSVSTGLHSLSTFRGLMKRRSSV
uniprot
proteins
disease_involvement
DISEASE: Pulmonary hypertension, primary, 4 (PPH4) [MIM:615344]: 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. {ECO:0000269|PubMed:23883380}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental delay with sleep apnea (DDSA) [MIM:621402]: An autosomal dominant disorder characterized by global developmental delay, hypotonia, gastrointestinal findings, and central and/or obstructive sleep apnea. {ECO:0000269|PubMed:36195757}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:O35111, ECO:0000250|UniProtKB:O54912, ECO:0000269|PubMed:22948150, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:26919430, ECO:0000269|PubMed:32499642, ECO:0000269|PubMed:36195757, ECO:0000269|PubMed:9312005}.
uniprot
proteins
mass_dalton
43518
uniprot
proteins
mutagenesis
MUTAGEN 4; /note="Q->C: Increases potassium current amplitude."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 5; /note="N->C: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 6; /note="V->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 7; /note="R->C: Increases potassium current amplitude."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 7; /note="R->D: Increases potassium current amplitude associated with a significant decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 7; /note="R->E: Increases potassium current amplitude."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 7; /note="R->K: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 8; /note="T->C,K: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 98; /note="H->N: Greatly reduces pH sensitivity."; /evidence="ECO:0000269|PubMed:11680614"; MUTAGEN 130; /note="E->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 131; /note="R->C,D: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 131; /note="R->E: Markedly increases potassium current amplitude."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 132; /note="I->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 133; /note="N->A,D,F,Q,T,V: Increases potassium current."; /evidence="ECO:0000269|PubMed:36195757"; MUTAGEN 133; /note="N->C: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 134; /note="T->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 199; /note="T->C: Abolishes voltage gating. Conducts currents with linear I-V relationship characteristic of classical leak channels."; /evidence="ECO:0000269|PubMed:26919430"; MUTAGEN 230; /note="T->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 231; /note="G->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 232; /note="L->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 233; /note="T->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 234; /note="V->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 235; /note="I->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 236; /note="G->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 237; /note="A->V: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 238; /note="F->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 239; /note="L->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 240; /note="N->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 241; /note="L->A: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 242; /note="V->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 243; /note="V->A: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 244; /note="L->A: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 245; /note="R->A: Markedly increases potassium current amplitude. Channel hyperactivity is associated with marked decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 246; /note="F->A: Increases potassium current amplitude without changing protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 247; /note="M->A: Increases potassium current amplitude without changing protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 248; /note="T->A: Increases potassium current amplitude without changing protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 249; /note="M->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 250; /note="N->C: Increases channel basal activity associated with a significant decrease of protein surface expression."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 250; /note="N->D: Increases channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 250; /note="N->R: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 251; /note="A->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 252; /note="E->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 253; /note="D->C,R: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 254; /note="E->C,R: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 255; /note="K->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 256; /note="R->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642"; MUTAGEN 257; /note="D->C: No effect on channel basal activity."; /evidence="ECO:0000269|PubMed:32499642
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
10321245
uniprot
proteins
pubmed
10748056
uniprot
proteins
pubmed
11680614
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
22948150
uniprot
proteins
pubmed
23169818
uniprot
proteins
pubmed
23883380
uniprot
proteins
pubmed
26919430
uniprot
proteins
pubmed
32499642
uniprot
proteins
pubmed
36195757
uniprot
proteins
pubmed
9312005
uniprot
proteins
sequence_length
394
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23169818}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 9..29; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 108..128; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 159..179; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 223..243; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins