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K2P10.1

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Target not currently curated in GtoImmuPdb

Target id: 521

Nomenclature: K2P10.1

Abbreviated Name: TREK2

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 2 538 14q31.3 KCNK10 potassium two pore domain channel subfamily K member 10 1
Mouse 4 2 535 12 E Kcnk10 potassium channel, subfamily K, member 10
Rat 4 2 538 6q32 Kcnk10 potassium two pore domain channel subfamily K member 10
Previous and Unofficial Names Click here for help
TREK-2 | potassium channel, two pore domain subfamily K, member 10 | potassium channel
Database Links Click here for help
Alphafold P57789 (Hs), Q9JIS4 (Rn)
ChEMBL Target CHEMBL2331041 (Hs), CHEMBL3308951 (Rn)
Ensembl Gene ENSG00000100433 (Hs), ENSMUSG00000033854 (Mm), ENSRNOG00000003813 (Rn)
Entrez Gene 54207 (Hs), 72258 (Mm), 65272 (Rn)
Human Protein Atlas ENSG00000100433 (Hs)
KEGG Gene hsa:54207 (Hs), mmu:72258 (Mm), rno:65272 (Rn)
OMIM 605873 (Hs)
Pharos P57789 (Hs)
RefSeq Nucleotide NM_021161 (Hs), NM_029911 (Mm), NM_023096 (Rn)
RefSeq Protein NP_066984 (Hs), NP_084187 (Mm), NP_075584 (Rn)
UniProtKB P57789 (Hs), Q9JIS4 (Rn)
Wikipedia KCNK10 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1) in complex with norfluoxetine
PDB Id:  4XDK
Ligand:  norfluoxetine
Resolution:  3.6Å
Species:  Human
References:  3
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PLD2 2
AKAP150 13
Mtap2 12
Associated Protein Comments
Heteromultimers shown to form in vivo: K2P10 has been reported to form a heterodimer with K2P1 in heterologous expression systems, however the in vivo formation of this heterodimer and its function remain unknown [6].

Protein-protein interactions: K2P10 has been reported to respond to numerous proteins, including:

AKAP150: The A-kinase-anchoring protein AKAP150 binds to the C-terminus of K2P10, increasing the kinetic of channel inactivation by Gs coupled receptors and decreasing inhibition by Gq coupled receptors [13].
Mtap2: The microtubule associated protein 2 Mtap2 binds to the C-terminus of K2P10 to increase channel density at the plasma membrane [12].
PLD2: PLD2, a phosphatidic acid (PA) producing enzyme, binds to the C-terminus of K2P10 to potentiate channel activity in a PA-dependent manner [2].
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
BL-1249 Small molecule or natural product Click here for species-specific activity table Hs - 5.1 pEC50 - - 11
⤷ pEC50 5.1 (EC50 8x10-6 M) [11]
docosahexaenoic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - - - - - 9
⤷ [9]
linoleic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - - - - - 9
⤷ [9]
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 - - - - - 9
⤷ studied at 1-10 µM [9]
halothane Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs - - - - - 9
⤷ studied at 1-5 mM [9]
lysophosphatidylcholine Small molecule or natural product Click here for species-specific activity table Hs - - - - - 9
⤷ [9]
GI‐530159 Small molecule or natural product Click here for species-specific activity table Hs - - - - - 10
⤷ [10]
Description: Whole‐cell recording from tsA‐201 cells shows a 42% enhancement in hTREK2 channel current upon activation by 1 μM GI‐530139.
Activator Comments
A concentration of 0.5 mM halothane maximally activates the channel by 2.6-fold [9]. The channel is also activated by the neuroprotective drug riluzole. Channel activity is stimulated by 8.4 times by arachidonic acid, and 5.1 times by lysophosphatidylinositol [9].
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
quinidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Rn - - - - - 5
⤷ [5]
Tissue Distribution Click here for help
Kidney, pancreas, thymus, liver, heart.
Species:  Human
Technique:  RT-PCR
References:  4
Biologically Significant Variant Comments
Three alternate splice forms of K2P10 have been identified [4,9]. To date, the pharmacological and physiological significance of the variant isoforms remains unknown.
General Comments
‘Activation’ and ‘deactivation’ with voltage steps appear to be instantaneous. Splice variants have been identified in human and rat. The rat variant is reported to have a conductance of 68pS and to be expressed in brain. K2P10 like currents are observed in cerebellar granular neurons, magnocellular neurosecretory cells of rat supraoptic nucleus [5,8] and rat cortical astrocytes [7].

References

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1. Bang H, Kim Y, Kim D. (2000) TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J Biol Chem, 275 (23): 17412-9. [PMID:10747911]

2. Comoglio Y, Levitz J, Kienzler MA, Lesage F, Isacoff EY, Sandoz G. (2014) Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid. Proc Natl Acad Sci USA, 111 (37): 13547-52. [PMID:25197053]

3. Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S et al.. (2015) K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science, 347 (6227): 1256-9. [PMID:25766236]

4. Gu W, Schlichthörl G, Hirsch JR, Engels H, Karschin C, Karschin A, Derst C, Steinlein OK, Daut J. (2002) Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. J Physiol (Lond.), 539 (Pt 3): 657-68. [PMID:11897838]

5. Han J, Truell J, Gnatenco C, Kim D. (2002) Characterization of four types of background potassium channels in rat cerebellar granule neurons. J Physiol (Lond.), 542 (Pt 2): 431-44. [PMID:12122143]

6. Hwang EM, Kim E, Yarishkin O, Woo DH, Han KS, Park N, Bae Y, Woo J, Kim D, Park M et al.. (2014) A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat Commun, 5: 3227. [PMID:24496152]

7. Kang D, Choe C, Kim D. (2004) Functional expression of TREK-2 in insulin-secreting MIN6 cells. Biochem Biophys Res Commun, 323 (1): 323-31. [PMID:15351740]

8. 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]

9. Lesage F, Terrenoire C, Romey G, Lazdunski M. (2000) Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J Biol Chem, 275 (37): 28398-405. [PMID:10880510]

10. Loucif AJC, Saintot PP, Liu J, Antonio BM, Zellmer SG, Yoger K, Veale EL, Wilbrey A, Omoto K, Cao L et al.. (2018) GI-530159, a novel, selective, mechanosensitive two-pore-domain potassium (K2P ) channel opener, reduces rat dorsal root ganglion neuron excitability. Br J Pharmacol, 175 (12): 2272-2283. [PMID:29150838]

11. Pope L, Arrigoni C, Lou H, Bryant C, Gallardo-Godoy A, Renslo AR, Minor Jr DL. (2018) Protein and Chemical Determinants of BL-1249 Action and Selectivity for K2P Channels. ACS Chem Neurosci, 9 (12): 3153-3165. [PMID:30089357]

12. Sandoz G, Tardy MP, Thümmler S, Feliciangeli S, Lazdunski M, Lesage F. (2008) Mtap2 is a constituent of the protein network that regulates twik-related K+ channel expression and trafficking. J Neurosci, 28 (34): 8545-52. [PMID:18716213]

13. Sandoz G, Thümmler S, Duprat F, Feliciangeli S, Vinh J, Escoubas P, Guy N, Lazdunski M, Lesage F. (2006) AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K(+) channels into open leak channels. EMBO J, 25 (24): 5864-72. [PMID:17110924]

Contributors

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