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K2P9.1

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Target not currently curated in GtoImmuPdb

Target id: 520

Nomenclature: K2P9.1

Abbreviated Name: TASK3

Family: Two P domain potassium channels

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 374 8q24.3 KCNK9 potassium two pore domain channel subfamily K member 9 2,5,10
Mouse 4 2 402 15 D3 Kcnk9 potassium channel, subfamily K, member 9
Rat 4 2 396 7q34 Kcnk9 potassium two pore domain channel subfamily K member 9
Previous and Unofficial Names Click here for help
TASK-3 | acid-sensitive potassium channel protein TASK-3 | potassium channel subfamily K member 9 (Task-3) | TWIK-related acid-sensitive K(+) channel 3 | two pore potassium channel KT3.2 | potassium channel, subfamily K, member 9 | potassium channel, two pore domain subfamily K, member 9 | potassium channel
Database Links Click here for help
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
K2P3.1 1,3-4
K2P1.1 9
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
14-3-3 7
COP1 7
Associated Protein Comments
Heteromultimers shown to form in vivo: K2P9 has been shown to form heterodimers with K2P3 in rat cerebellar granule neurons [3], in rat carotid body glomus cells [4] and in motoneurons [1] and with K2P1 in rat cerebellar granule neurons [9].

Protein-protein interactions: K2P9 has been found to associate with 14-3-3 and COP1 to control forward trafficking of the channel from the ER [7]. The activity of K2P9-K2P1 heterodimers is under the control of SUMOylation of the K2P1 subunit [9].
Functional Characteristics Click here for help
Background current

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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 Primary target of this compound Click here for species-specific activity table Hs - - - - - 11
studied at 1-5 mM [11]
Inhibitors
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
anandamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - - - - - 10
studied at 1-10 µM [10]
ruthenium red Click here for species-specific activity table Hs - - - - -
R-(+)-methanandamide Small molecule or natural product Click here for species-specific activity table Hs - - - - - 10
studied at 1-10 µM [10]
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ruthenium red N/A - 6.2 pIC50 - -
pIC50 6.2
Channel Blocker Comments
Expression of TASK-3 in Xenopus oocytes revealed an outwardly rectifying K(+) current that was strongly decreased in the presence of lower extracellular pH (< 6.5). Substitution of the histidine residue His-98 by asparagine or tyrosine abolished pH sensitivity. This histidine, which is located at the outer part of the pore adjacent to the selectivity filter, may be an essential component of the extracellular pH sensor [10].
Tissue Distribution Click here for help
Brain tissues
Species:  Human
Technique:  RT-PCR
References:  2
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
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100509  MGI:3521816  MP:0005402 abnormal action potential PMID: 18094244 
Kcnk9tm1.1Daba Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:3521816  MP:0005402 abnormal action potential PMID: 18094244 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0002909 abnormal adrenal gland physiology PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0003484 abnormal channel response PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0003353 decreased circulating renin level PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0005333 decreased heart rate PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0000231 hypertension PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0004119 hypokalemia PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0002666 increased circulating aldosterone level PMID: 18250325 
Kcnk9tm1Sgb Kcnk9tm1Sgb/Kcnk9tm1Sgb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:3521816  MP:0002169 no abnormal phenotype detected PMID: 17728447 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Birk-Barel mental retardation dysmorphism syndrome
Synonyms: Birk-Barel syndrome [Disease Ontology: DOID:0050675]
Intellectual disability, Birk-Barel type [Orphanet: ORPHA166108]
Disease Ontology: DOID:0050675
OMIM: 612292
Orphanet: ORPHA166108
General Comments
‘Activation’ and ‘deactivation’ with voltage steps appear to be instantaneous. The guinea-pig variant is reported to have the same conductance and distribution as human and have a conductance of 60pS. Northern blot analysis suggests that rat K2P9.1 expression outside the CNS is extremely low, as is noted for the human and guinea pig gene. K2P9 gene is amplified in several human carcinomas and over expression of K2P9 protein in cell lines promotes tumor formation. Like K2P3 surface expression of K2P9 is dependent on its association with 14-3-3 to release it from the endoplasmic reticulum [6,8]. Potential heterodimerisation of K2P9 is discussed under K2P3.

References

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1. Berg AP, Talley EM, Manger JP, Bayliss DA. (2004) Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J Neurosci, 24 (30): 6693-702. [PMID:15282272]

2. Chapman CG, Meadows HJ, Godden RJ, Campbell DA, Duckworth M, Kelsell RE, Murdock PR, Randall AD, Rennie GI, Gloger IS. (2000) Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel. Brain Res Mol Brain Res, 82 (1-2): 74-83. [PMID:11042359]

3. Kang D, Han J, Talley EM, Bayliss DA, Kim D. (2004) Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J Physiol (Lond.), 554 (Pt 1): 64-77. [PMID:14678492]

4. Kim D, Cavanaugh EJ, Kim I, Carroll JL. (2009) Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. J Physiol (Lond.), 587 (Pt 12): 2963-75. [PMID:19403596]

5. Kim Y, Bang H, Kim D. (2000) TASK-3, a new member of the tandem pore K(+) channel family. J Biol Chem, 275 (13): 9340-7. [PMID:10734076]

6. Lauritzen I, Zanzouri M, Honoré E, Duprat F, Ehrengruber MU, Lazdunski M, Patel AJ. (2003) K+-dependent cerebellar granule neuron apoptosis. Role of task leak K+ channels. J Biol Chem, 278 (34): 32068-76. [PMID:12783883]

7. O'Kelly I, Butler MH, Zilberberg N, Goldstein SA. (2002) Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell, 111 (4): 577-88. [PMID:12437930]

8. Pei L, Wiser O, Slavin A, Mu D, Powers S, Jan LY, Hoey T. (2003) Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function. Proc Natl Acad Sci USA, 100 (13): 7803-7. [PMID:12782791]

9. Plant LD, Zuniga L, Araki D, Marks JD, Goldstein SA. (2012) SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. Sci Signal, 5 (251): ra84. [PMID:23169818]

10. Rajan S, Wischmeyer E, Xin Liu G, Preisig-Müller R, Daut J, Karschin A, Derst C. (2000) TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor. J Biol Chem, 275 (22): 16650-7. [PMID:10747866]

11. Talley EM, Bayliss DA. (2002) Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action. J Biol Chem, 277 (20): 17733-42. [PMID:11886861]

Contributors

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