Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Functional Characteristics
- Activators
- Inhibitors
- Channel Blockers
- Tissue Distribution
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- General Comments
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| 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 |
| 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 |
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| Alphafold | Q9NPC2 (Hs), Q3LS21 (Mm), Q9ES08 (Rn) |
| ChEMBL Target | CHEMBL2321614 (Hs), CHEMBL4295 (Rn) |
| DrugBank Target | Q9NPC2 (Hs) |
| Ensembl Gene | ENSG00000169427 (Hs), ENSMUSG00000036760 (Mm), ENSRNOG00000009265 (Rn) |
| Entrez Gene | 51305 (Hs), 223604 (Mm), 84429 (Rn) |
| Human Protein Atlas | ENSG00000169427 (Hs) |
| KEGG Gene | hsa:51305 (Hs), mmu:223604 (Mm), rno:84429 (Rn) |
| OMIM | 605874 (Hs) |
| Orphanet | ORPHA166255 (Hs) |
| Pharos | Q9NPC2 (Hs) |
| RefSeq Nucleotide | NM_001282534 (Hs), NM_001033876 (Mm), NM_053405 (Rn) |
| RefSeq Protein | NP_001269463 (Hs), NP_001029048 (Mm), NP_445857 (Rn) |
| UniProtKB | Q9NPC2 (Hs), Q3LS21 (Mm), Q9ES08 (Rn) |
| Wikipedia | KCNK9 (Hs) |
| Associated Proteins |
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| 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]. |
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| Functional Characteristics |
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| Background current | |
Download all structure-activity data for this target as a CSV file 
| Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| 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
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]
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