The Primary Information of Tandem Pore Domain Potassium Channel (K2P)
1. Summary
The two-pore-domain or tandem pore domain potassium channels (K2P) are a family of 15 members (K2p1.1, K2p2.1, K2p3.1, K2p4.1, K2p5.1, K2p6.1, K2p7.1, K2p9.1, K2p10.1, K2p12.1, K2p13.1, K2p15.1, K2p16.1, K2p17.1, K2p18.1) that form what is known as leak channels which possess Goldman-Hodgkin-Katz (open) rectification [1].
2. Binding Sites
Ruthenium red binds to the residues (D135 (red sphere) in TREK-2 [2] and E70 (yellow sphere) in TASK-3 [3]) lining the wall of the extracellular ion pathway to inhibit TREK-2 and TASK-3. Mutations of the residues A35, E38 and V42 (black sphere) within the binding site in the extracellular cap of TRAAK significantly increased the TKDC-induced inhibition, indicating that the proposed site was involved in modulating channels. [4] Central cartoon shows the locations of structurally defined K2P small molecule binding sites including the Keystone inhibitor site (white sphere) [5], K2P modulator pocket (grey)[6], Fenestration site (green sphere) [7], Modulatory lipid site (Orange sphere) [8], and Vestibule site (blue) [9].
3. Target List
| ICDB_Pro ID | Protein Name | Organism | Uniport Accession Number | Gene Name |
|---|---|---|---|---|
| ICDB_Pro_1182 | Potassium channel subfamily K member 18 | Homo sapiens (Human) | Q7Z418 | KCNK18; TRESK; TRIK |
| ICDB_Pro_0290 | Potassium channel subfamily K member 2 | Homo sapiens (Human) | O95069 | KCNK2; TREK; TREK1 |
| ICDB_Pro_0717 | Potassium channel subfamily K member 2 | Mus musculus (Mouse) | P97438 | Kcnk2 |
| ICDB_Pro_1366 | Potassium channel subfamily K member 2 | Rattus norvegicus (Rat) | Q920B6 | Kcnk2; Trek |
| ICDB_Pro_0183 | Potassium channel subfamily K member 3 | Homo sapiens (Human) | O14649 | KCNK3; TASK; TASK1 |
| ICDB_Pro_0203 | Potassium channel subfamily K member 3 | Mus musculus (Mouse) | O35111 | Kcnk3; Ctbak; Task; Task1 |
| ICDB_Pro_0227 | Potassium channel subfamily K member 3 | Rattus norvegicus (Rat) | O54912 | Kcnk3; Task; Task1 |
| ICDB_Pro_0133 | Potassium channel subfamily K member 4 | Rattus norvegicus (Rat) | G3V8V5 | Kcnk4 |
| ICDB_Pro_0276 | Potassium channel subfamily K member 4 | Mus musculus (Mouse) | O88454 | Kcnk4; Traak |
| ICDB_Pro_1592 | Potassium channel subfamily K member 4 | Homo sapiens (Human) | Q9NYG8 | KCNK4; TRAAK |