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1.A.1.9.2
KCNK3 K+ channel (TASK1, OAT1, TBAK1) (the K+ leak conductance). TASK1 and 3 may play roles in nontumorigenic primary hyperaldosteronism (Davies et al., 2008).  KCNK3/9/15 expression limits membrane depolarization and depolarization-induced secretion at least in part by maintaining intracellular K+ (Huang et al. 2011). TWIK-related acid-sensitive potassium (TASK) channels, members of the two pore domain potassium (K2P) channel family, are found in neurons, cardiomyocytes and vascular smooth muscle cells, where they are involved in the regulation of heart rate, pulmonary artery tone, sleep/wake cycles and responses to volatile anaesthetics (Rödström et al. 2020). K2P channels regulate the resting membrane potential, providing background K+ currents controlled by numerous physiological stimuli. Unlike other K2P channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below, but the K2P channels studied so far all lack a lower gate. Rödström et al. 2020 presented the X-ray crystal structure of TASK-1, and showed that it contains a lower gate designated 'X-gate', created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues ((243)VLRFMT(248)) that are essential for responses to volatile anaesthetics, neurotransmitters and G-protein-coupled receptors. Mutations within the X-gate and the surrounding regions affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors showed that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates (Rödström et al. 2020).

Accession Number:O14649
Protein Name:KcnK3
Length:394
Molecular Weight:43518.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

RefSeq: NP_002237.1   
Entrez Gene ID: 3777   
Pfam: PF07885   
OMIM: 603220  gene
KEGG: hsa:3777   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005267 F:potassium channel activity
GO:0005244 F:voltage-gated ion channel activity
GO:0006813 P:potassium ion transport
GO:0007268 P:synaptic transmission

References (4)

[1] “TASK, a human background K+ channel to sense external pH variations near physiological pH.”  Duprat F.et.al.   9312005
[2] “Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3.”  Lopes C.M.B.et.al.   10748056
[3] “Inhalational anesthetics activate two-pore-domain background K+ channels.”  Patel A.J.et.al.   10321245
[4] “TASK-5, a novel member of the tandem pore K+ channel family.”  Ashmole I.et.al.   11680614
Structure:
6RV2   6RV3   6RV4     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA RYNLSQGGYE 
61:	ELERVVLRLK PHKAGVQWRF AGSFYFAITV ITTIGYGHAA PSTDGGKVFC MFYALLGIPL 
121:	TLVMFQSLGE RINTLVRYLL HRAKKGLGMR RADVSMANMV LIGFFSCIST LCIGAAAFSH 
181:	YEHWTFFQAY YYCFITLTTI GFGDYVALQK DQALQTQPQY VAFSFVYILT GLTVIGAFLN 
241:	LVVLRFMTMN AEDEKRDAEH RALLTRNGQA GGGGGGGSAH TTDTASSTAA AGGGGFRNVY 
301:	AEVLHFQSMC SCLWYKSREK LQYSIPMIIP RDLSTSDTCV EQSHSSPGGG GRYSDTPSRR 
361:	CLCSGAPRSA ISSVSTGLHS LSTFRGLMKR RSSV