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K2P4.1

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Target id: 516

Nomenclature: K2P4.1

Abbreviated Name: TRAAK1

Family: Two-pore domain potassium channels (K2P)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 393 11q13.1 KCNK4 potassium two pore domain channel subfamily K member 4 5
Mouse 4 2 398 19 5.08 cM Kcnk4 potassium channel, subfamily K, member 4
Rat 4 2 397 1q43 Kcnk4 potassium two pore domain channel subfamily K member 4
Previous and Unofficial Names Click here for help
TRAAK | KT4.1 | potassium channel, subfamily K, member 4 | potassium channel, two pore domain subfamily K, member 4 | potassium channel
Database Links Click here for help
Alphafold Q9NYG8 (Hs), O88454 (Mm)
ChEMBL Target CHEMBL3714486 (Hs)
Ensembl Gene ENSG00000182450 (Hs), ENSMUSG00000024957 (Mm), ENSRNOG00000021140 (Rn)
Entrez Gene 50801 (Hs), 16528 (Mm), 116489 (Rn)
Human Protein Atlas ENSG00000182450 (Hs)
KEGG Gene hsa:50801 (Hs), mmu:16528 (Mm), rno:116489 (Rn)
OMIM 605720 (Hs)
Pharos Q9NYG8 (Hs)
RefSeq Nucleotide NM_033310 (Hs), NM_008431 (Mm), NM_053804 (Rn)
RefSeq Protein NP_201567 (Hs), NP_032457 (Mm), NP_446256 (Rn)
UniProtKB Q9NYG8 (Hs), O88454 (Mm)
Wikipedia KCNK4 (Hs)
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
No heteromultimers have been shown to form in vivo. Protein-protein interactions: No in vivo or in vitro partners reported to date.
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
riluzole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Positive - - 3x10-6 - 1x10-4 - 1
⤷ Conc range: 3x10-6 - 1x10-4 M [1]
arachidonic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Positive - - 5x10-6 - 5x10-5 - 4
⤷ Conc range: 5x10-6 - 5x10-5 M [4]
riluzole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - - 1
⤷ studied at 1-100 µM [1]
arachidonic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs - - - - - 2
⤷ studied at 1-10 µM [2]
View species-specific activator tables
Activator Comments
Mechanical stress [6], heat [3], some unsaturated fatty acids [2] and lysophospholipids [7] have been reported to activate K2P4.1 voltage gated ion channels.
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Ba2+ Click here for species-specific activity table Rn - - - 2x10-3 - 4
⤷ Conc range: 2x10-3 M [4]
Tissue Distribution Click here for help
Brain, spinal cord, retina
Expression level:  High
Species:  Mouse
Technique:  Northern Blot, RT-PCR
References:  2
Brain
Expression level:  High
Species:  Mouse
Technique:  Immunohistochemistry
References:  9
Tissue Distribution Comments
Unlike TWIK-1, TREK-1 and TASK which are widely distributed in many different mouse tissues, TRAAK is present exclusively in brain, spinal cord and retina in mice [2].
Biologically Significant Variant Comments
Two splice variants have been identified from the human gene [8]. Six splice variants are predicted from the mouse gene by automated sequencing and computational analysis (XP_00652779 to XP_00652784), as well as a truncated variant produced by exon skipping [2]. The pharmacological and physiological significance of these variants is unknown.
General Comments
'Activation' and 'deactivation' with voltage steps appear to be instantaneous. Knockout mice have no obvious phenotype. The open probability of K2P4.1 increases with temperature with an activation threshold of 31oC in COS-7 cells.

References

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1. Duprat F, Lesage F, Patel AJ, Fink M, Romey G, Lazdunski M. (2000) The neuroprotective agent riluzole activates the two P domain K(+) channels TREK-1 and TRAAK. Mol Pharmacol, 57 (5): 906-12. [PMID:10779373]

2. Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M. (1998) A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J, 17 (12): 3297-308. [PMID:9628867]

3. Kang D, Choe C, Kim D. (2005) Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. J Physiol (Lond.), 564 (Pt 1): 103-16. [PMID:15677687]

4. Kim D, Sladek CD, Aguado-Velasco C, Mathiasen JR. (1995) Arachidonic acid activation of a new family of K+ channels in cultured rat neuronal cells. J Physiol (Lond.), 484 ( Pt 3): 643-60. [PMID:7623282]

5. Lesage F, Maingret F, Lazdunski M. (2000) Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel. FEBS Lett, 471 (2-3): 137-40. [PMID:10767409]

6. Maingret F, Fosset M, Lesage F, Lazdunski M, Honoré E. (1999) TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem, 274 (3): 1381-7. [PMID:9880510]

7. Maingret F, Patel AJ, Lesage F, Lazdunski M, Honoré E. (2000) Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. J Biol Chem, 275 (14): 10128-33. [PMID:10744694]

8. Ozaita A, Vega-Saenz de Miera E. (2002) Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression. Brain Res Mol Brain Res, 102 (1-2): 18-27. [PMID:12191490]

9. Reyes R, Lauritzen I, Lesage F, Ettaiche M, Fosset M, Lazdunski M. (2000) Immunolocalization of the arachidonic acid and mechanosensitive baseline traak potassium channel in the nervous system. Neuroscience, 95 (3): 893-901. [PMID:10670456]

Contributors

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