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K2P5.1

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Target not currently curated in GtoImmuPdb

Target id: 517

Nomenclature: K2P5.1

Abbreviated Name: TASK2

Family: Two-pore domain potassium channels (K2P)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 499 6p21.2 KCNK5 potassium two pore domain channel subfamily K member 5 8
Mouse 4 2 502 14 Kcnk5 potassium channel, subfamily K, member 5
Rat 4 2 503 15p16 Kcnk5 potassium two pore domain channel subfamily K member 5
Previous and Unofficial Names Click here for help
TASK-2 | potassium channel subfamily K member 5 | potassium channel, two pore domain subfamily K, member 5 | potassium channel
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
Interaction with G protein β subunits 1 and 2 reported in vitro [1].
Functional Characteristics Click here for help
Background current

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
halothane Small molecule or natural product Approved drug Click here for species-specific activity table Hs - 3.7 pIC50 1x10-4 - 1x10-3 - 4
pIC50 3.7 Conc range: 1x10-4 - 1x10-3 M [4]
Activator Comments
Volatile anesthetics appear to activate the human tandem pore domain baseline K+ channel K2P5.1 [4].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
clofilium Small molecule or natural product Mm - 4.6 pIC50 - - 7
pIC50 4.6 [7]
quinidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - - 5
[5]
View species-specific channel blocker tables
Channel Blocker Comments
K2P5.1 is sensitive to (blocked by) external pH is seen over a wide pHo range of 6-10. The effect of pH changes is mainly on the opening frequency [5].
Tissue Distribution Click here for help
Brain
Expression level:  High
Species:  Rat
Technique:  Immunohistochemistry
References:  3
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnk5+|Kcnk5Gt(KST024)Byg|Phox2b+|Phox2btm2Jbr Kcnk5Gt(KST024)Byg/Kcnk5+,Phox2btm2Jbr/Phox2b+
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
MGI:1100882  MGI:1336175  MP:0005277 abnormal brainstem morphology PMID: 20133877 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0005556 abnormal kidney clearance PMID: 15141089 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0005555 abnormal kidney excretion PMID: 15141089 
Kcnk5Gt(KST024)Byg Kcnk5Gt(KST024)Byg/Kcnk5Gt(KST024)Byg
B6.129P2-Kcnk5
MGI:1336175  MP:0003633 abnormal nervous system physiology PMID: 20133877 
Kcnk5Gt(KST024)Byg Kcnk5Gt(KST024)Byg/Kcnk5Gt(KST024)Byg
B6.129P2-Kcnk5
MGI:1336175  MP:0001943 abnormal respiration PMID: 20133877 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0001262 decreased body weight PMID: 15141089 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0006275 natriuresis PMID: 15141089 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
involves: 129P2/OlaHsd * C57BL/6J
MGI:1336175  MP:0002080 prenatal lethality PMID: 12707131 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0002080 prenatal lethality PMID: 15141089 
General Comments
A role in cell volume regulation [2,7] and sensing external basolateral pH changes associated HCO3- transport primary cultured proximal tubular cells [9]. ‘Activation’ and ‘deactivation’ with voltage steps appear instantaneous. The conductance of K2P5 is dependent on the ionic conditions. The slope conductance was reported as 15 pS with 5 mM external potassium and as high as 60 pS when external potassium is high (155 mM) 1. This may reflect a Na+ dependent inward rectification which becomes progressively less pronounced with time [6]. Like K2P16 and 17 current through K2P5 channels is diminished at physiological pH. Channel open probability increases with external pH. Formation of an inter-subunit disulfide bridge in K2P5 does not affect channel activity. Exposure to hypotonicity (change from 300 to 200 mOsm in external solution) enhanced mK2P5 currents when this channel was heterologously expressed in HEK293 cells and osmotic cell shrinkage led to inhibition (change from 300 to 400 mOsm in external solution).

References

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1. Añazco C, Peña-Münzenmayer G, Araya C, Cid LP, Sepúlveda FV, Niemeyer MI. (2013) G protein modulation of K2P potassium channel TASK-2 : a role of basic residues in the C terminus domain. Pflugers Arch, 465 (12): 1715-26. [PMID:23812165]

2. Barriere H, Belfodil R, Rubera I, Tauc M, Lesage F, Poujeol C, Guy N, Barhanin J, Poujeol P. (2003) Role of TASK2 potassium channels regarding volume regulation in primary cultures of mouse proximal tubules. J Gen Physiol, 122 (2): 177-90. [PMID:12860925]

3. Gabriel A, Abdallah M, Yost CS, Winegar BD, Kindler CH. (2002) Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system. Brain Res Mol Brain Res, 98 (1-2): 153-63. [PMID:11834308]

4. Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, Yost CS. (2000) Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5. Anesthesiology, 92 (6): 1722-30. [PMID:10839924]

5. Kang D, Kim D. (2004) Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochem Biophys Res Commun, 315 (4): 836-44. [PMID:14985088]

6. Morton MJ, Chipperfield S, Abohamed A, Sivaprasadarao A, Hunter M. (2005) Na(+)-induced inward rectification in the two-pore domain K(+) channel, TASK-2. Am J Physiol Renal Physiol, 288 (1): F162-9. [PMID:15328068]

7. Niemeyer MI, Cid LP, Barros LF, Sepúlveda FV. (2001) Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J Biol Chem, 276 (46): 43166-74. [PMID:11560934]

8. Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M. (1998) Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem, 273 (47): 30863-9. [PMID:9812978]

9. Warth R, Barrière H, Meneton P, Bloch M, Thomas J, Tauc M, Heitzmann D, Romeo E, Verrey F, Mengual R et al.. (2004) Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Proc Natl Acad Sci USA, 101 (21): 8215-20. [PMID:15141089]

Contributors

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