Top ▲
GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.
Gene and Protein Information ![]() |
|||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 6 | 1 | 989 | 1q32.2 | KCNH1 | potassium voltage-gated channel subfamily H member 1 | 32 |
Mouse | 6 | 1 | 989 | 1 H6 | Kcnh1 | potassium voltage-gated channel, subfamily H (eag-related), member 1 | |
Rat | 6 | 1 | 962 | 13q27 | Kcnh1 | potassium voltage-gated channel subfamily H member 1 |
Database Links ![]() |
|
Alphafold | O95259 (Hs), Q60603 (Mm), Q63472 (Rn) |
CATH/Gene3D | 2.60.120.10 |
ChEMBL Target | CHEMBL3841 (Hs), CHEMBL4295858 (Rn) |
Ensembl Gene | ENSG00000143473 (Hs), ENSMUSG00000058248 (Mm), ENSRNOG00000003841 (Rn) |
Entrez Gene | 3756 (Hs), 16510 (Mm), 65198 (Rn) |
Human Protein Atlas | ENSG00000143473 (Hs) |
KEGG Gene | hsa:3756 (Hs), mmu:16510 (Mm), rno:65198 (Rn) |
OMIM | 603305 (Hs) |
Pharos | O95259 (Hs) |
RefSeq Nucleotide | NM_002238 (Hs), NM_172362 (Hs), NM_010600 (Mm), NM_031742 (Rn) |
RefSeq Protein | NP_758872 (Hs), NP_002229 (Hs), NP_034730 (Mm), NP_113930 (Rn) |
UniProtKB | O95259 (Hs), Q60603 (Mm), Q63472 (Rn) |
Wikipedia | KCNH1 (Hs) |
Associated Proteins ![]() |
||||||||||||||||||||||||||||||||||
|
|
|
Ion Selectivity and Conductance ![]() |
||||||
|
||||||
|
||||||
Ion Selectivity and Conductance Comments | ||||||
Download all structure-activity data for this target as a CSV file
Gating inhibitors ![]() |
||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||
|
Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
View species-specific channel blocker tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
mAb56 monoclonal antibody pIC50 7.1 [13] |
Tissue Distribution ![]() |
||||||||
|
||||||||
|
||||||||
|
||||||||
|
Physiological Functions ![]() |
||||||||
|
||||||||
|
Clinically-Relevant Mutations and Pathophysiology ![]() |
||||||||||||||||
|
Gene Expression and Pathophysiology ![]() |
||||||||||||
|
||||||||||||
|
General Comments |
Extracellular Mg2+ and other divalent cations slow activation in a dose- and voltage-dependent manner, based on their enthalpy of hydration [42]. Low external pH also slows activation. Hyperpolarisation slows down the kinetics of activation, depolarisation accelerates the kinetics of activation [22]. This channel has the following features:
The tetramerizing coiled-coil (TCC) domain at the C-terminal end of Kv10 and Kv11 confers specificity for multimer formation, allowing Kv10.1 / Kv10.2 heteromerization, and Kv11.1 homomerization, but not Kv10.x / Kv11.1 heteromerization [18]. This C-terminal TCC domain has been identified in many other channels, and mutations of the TCC have been found to be linked to genetic channelopathies. |
1. Brüggemann A, Pardo LA, Stühmer W, Pongs O. (1993) Ether-à-go-go encodes a voltage-gated channel permeable to K+ and Ca2+ and modulated by cAMP. Nature, 365 (6445): 445-8. [PMID:7692301]
2. Brüggemann A, Stühmer W, Pardo LA. (1997) Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier potassium channel expressed in Xenopus oocytes. Proc Natl Acad Sci USA, 94 (2): 537-42. [PMID:9012819]
3. Camacho J, Sánchez A, Stühmer W, Pardo LA. (2000) Cytoskeletal interactions determine the electrophysiological properties of human EAG potassium channels. Pflugers Arch, 441 (2-3): 167-74. [PMID:11211100]
4. Ding XW, Yan JJ, An P, Lü P, Luo HS. (2007) Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines. World J Gastroenterol, 13 (8): 1257-61. [PMID:17451210]
5. Downie BR, Sánchez A, Knötgen H, Contreras-Jurado C, Gymnopoulos M, Weber C, Stühmer W, Pardo LA. (2008) Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors. J Biol Chem, 283 (52): 36234-40. [PMID:18927085]
6. Farias LM, Ocaña DB, Díaz L, Larrea F, Avila-Chávez E, Cadena A, Hinojosa LM, Lara G, Villanueva LA, Vargas C, Hernández-Gallegos E, Camacho-Arroyo I, Dueñas-González A, Pérez-Cárdenas E, Pardo LA, Morales A, Taja-Chayeb L, Escamilla J, Sánchez-Peña C, Camacho J. (2004) Ether a go-go potassium channels as human cervical cancer markers. Cancer Res, 64 (19): 6996-7001. [PMID:15466192]
7. Frings S, Brüll N, Dzeja C, Angele A, Hagen V, Kaupp UB, Baumann A. (1998) Characterization of ether-à-go-go channels present in photoreceptors reveals similarity to IKx, a K+ current in rod inner segments. J Gen Physiol, 111 (4): 583-99. [PMID:9524140]
8. García-Ferreiro RE, Kerschensteiner D, Major F, Monje F, Stühmer W, Pardo LA. (2004) Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J Gen Physiol, 124 (4): 301-17. [PMID:15365094]
9. Garg V, Stary-Weinzinger A, Sanguinetti MC. (2013) ICA-105574 interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels. Mol Pharmacol, 83 (4): 805-13. [PMID:23319419]
10. Gessner G, Heinemann SH. (2003) Inhibition of hEAG1 and hERG1 potassium channels by clofilium and its tertiary analogue LY97241. Br J Pharmacol, 138 (1): 161-71. [PMID:12522086]
11. Gessner G, Zacharias M, Bechstedt S, Schönherr R, Heinemann SH. (2004) Molecular determinants for high-affinity block of human EAG potassium channels by antiarrhythmic agents. Mol Pharmacol, 65 (5): 1120-9. [PMID:15102940]
12. Gómez-Varela D, Contreras-Jurado C, Furini S, García-Ferreiro R, Stühmer W, Pardo LA. (2006) Different relevance of inactivation and F468 residue in the mechanisms of hEag1 channel blockage by astemizole, imipramine and dofetilide. FEBS Lett, 580 (21): 5059-66. [PMID:16949586]
13. Gómez-Varela D, Zwick-Wallasch E, Knötgen H, Sánchez A, Hettmann T, Ossipov D, Weseloh R, Contreras-Jurado C, Rothe M, Stühmer W et al.. (2007) Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity. Cancer Res, 67 (15): 7343-9. [PMID:17671204]
14. Hemmerlein B, Weseloh RM, Mello de Queiroz F, Knötgen H, Sánchez A, Rubio ME, Martin S, Schliephacke T, Jenke M, Heinz-Joachim-Radzun W, Pardo LA. (2006) Overexpression of Eag1 potassium channels in clinical tumours. Mol Cancer, 5: 41. [PMID:17022810]
15. Herrmann S, Ninkovic M, Kohl T, Lörinczi É, Pardo LA. (2012) Cortactin controls surface expression of the voltage-gated potassium channel K(V)10.1. J Biol Chem, 287 (53): 44151-63. [PMID:23144454]
16. Herrmann S, Ninkovic M, Kohl T, Pardo LA. (2013) PIST (GOPC) modulates the oncogenic voltage-gated potassium channel KV10.1. Front Physiol, 4: 201. [PMID:23966943]
17. Hoshi N, Takahashi H, Shahidullah M, Yokoyama S, Higashida H. (1998) KCR1, a membrane protein that facilitates functional expression of non-inactivating K+ currents associates with rat EAG voltage-dependent K+ channels. J Biol Chem, 273 (36): 23080-5. [PMID:9722534]
18. Jenke M, Sánchez A, Monje F, Stühmer W, Weseloh RM, Pardo LA. (2003) C-terminal domains implicated in the functional surface expression of potassium channels. EMBO J, 22 (3): 395-403. [PMID:12554641]
19. Ju M, Wray D. (2002) Molecular identification and characterisation of the human eag2 potassium channel. FEBS Lett, 524 (1-3): 204-10. [PMID:12135768]
20. Lecain E, Sauvaget E, Crisanti P, Van Den Abbeele T, Huy PT. (1999) Potassium channel ether à go-go mRNA expression in the spiral ligament of the rat. Hear Res, 133 (1-2): 133-8. [PMID:10416871]
21. Ludwig J, Owen D, Pongs O. (1997) Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-à-go-go potassium channel. EMBO J, 16 (21): 6337-45. [PMID:9400421]
22. Ludwig J, Terlau H, Wunder F, Brüggemann A, Pardo LA, Marquardt A, Stühmer W, Pongs O. (1994) Functional expression of a rat homologue of the voltage gated either á go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart. EMBO J, 13 (19): 4451-8. [PMID:7925287]
23. Mareschi K, Novara M, Rustichelli D, Ferrero I, Guido D, Carbone E, Medico E, Madon E, Vercelli A, Fagioli F. (2006) Neural differentiation of human mesenchymal stem cells: Evidence for expression of neural markers and eag K+ channel types. Exp Hematol, 34 (11): 1563-72. [PMID:17046576]
24. Mello de Queiroz F, Suarez-Kurtz G, Stühmer W, Pardo LA. (2006) Ether à go-go potassium channel expression in soft tissue sarcoma patients. Mol Cancer, 5: 42. [PMID:17022811]
25. Meyer R, Heinemann SH. (1998) Characterization of an eag-like potassium channel in human neuroblastoma cells. J Physiol (Lond.), 508 ( Pt 1): 49-56. [PMID:9490815]
26. Meyer R, Schönherr R, Gavrilova-Ruch O, Wohlrab W, Heinemann SH. (1999) Identification of ether à go-go and calcium-activated potassium channels in human melanoma cells. J Membr Biol, 171 (2): 107-15. [PMID:10489423]
27. Ninkovic M, Mitkovski M, Kohl T, Stühmer W, Pardo LA. (2012) Physical and functional interaction of KV10.1 with Rabaptin-5 impacts ion channel trafficking. FEBS Lett, 586 (19): 3077-84. [PMID:22841712]
28. Occhiodoro T, Bernheim L, Liu JH, Bijlenga P, Sinnreich M, Bader CR, Fischer-Lougheed J. (1998) Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion. FEBS Lett, 434 (1-2): 177-82. [PMID:9738473]
29. Ouadid-Ahidouch H, Le Bourhis X, Roudbaraki M, Toillon RA, Delcourt P, Prevarskaya N. (2001) Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel. Recept Channels, 7 (5): 345-56. [PMID:11697078]
30. Ousingsawat J, Spitzner M, Puntheeranurak S, Terracciano L, Tornillo L, Bubendorf L, Kunzelmann K, Schreiber R. (2007) Expression of voltage-gated potassium channels in human and mouse colonic carcinoma. Clin Cancer Res, 13 (3): 824-31. [PMID:17289873]
31. Pardo LA, Brüggemann A, Camacho J, Stühmer W. (1998) Cell cycle-related changes in the conducting properties of r-eag K+ channels. J Cell Biol, 143 (3): 767-75. [PMID:9813096]
32. Pardo LA, del Camino D, Sánchez A, Alves F, Brüggemann A, Beckh S, Stühmer W. (1999) Oncogenic potential of EAG K(+) channels. EMBO J, 18 (20): 5540-7. [PMID:10523298]
33. Piros ET, Shen L, Huang XY. (1999) Purification of an EH domain-binding protein from rat brain that modulates the gating of the rat ether-à-go-go channel. J Biol Chem, 274 (47): 33677-83. [PMID:10559257]
34. Saganich MJ, Machado E, Rudy B. (2001) Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain. J Neurosci, 21 (13): 4609-24. [PMID:11425889]
35. Sahoo N, Tröger J, Heinemann SH, Schönherr R. (2010) Current inhibition of human EAG1 potassium channels by the Ca2+ binding protein S100B. FEBS Lett, 584 (18): 3896-900. [PMID:20708613]
36. Schopperle WM, Holmqvist MH, Zhou Y, Wang J, Wang Z, Griffith LC, Keselman I, Kusinitz F, Dagan D, Levitan IB. (1998) Slob, a novel protein that interacts with the Slowpoke calcium-dependent potassium channel. Neuron, 20 (3): 565-73. [PMID:9539129]
37. Schönherr R, Gessner G, Löber K, Heinemann SH. (2002) Functional distinction of human EAG1 and EAG2 potassium channels. FEBS Lett, 514 (2-3): 204-8. [PMID:11943152]
38. Schönherr R, Löber K, Heinemann SH. (2000) Inhibition of human ether à go-go potassium channels by Ca(2+)/calmodulin. EMBO J, 19 (13): 3263-71. [PMID:10880439]
39. Silverman WR, Tang CY, Mock AF, Huh KB, Papazian DM. (2000) Mg(2+) modulates voltage-dependent activation in ether-à-go-go potassium channels by binding between transmembrane segments S2 and S3. J Gen Physiol, 116 (5): 663-78. [PMID:11055995]
40. Spitzner M, Ousingsawat J, Scheidt K, Kunzelmann K, Schreiber R. (2007) Voltage-gated K+ channels support proliferation of colonic carcinoma cells. FASEB J, 21 (1): 35-44. [PMID:17135369]
41. Stansfeld CE, Röper J, Ludwig J, Weseloh RM, Marsh SJ, Brown DA, Pongs O. (1996) Elevation of intracellular calcium by muscarinic receptor activation induces a block of voltage-activated rat ether-à-go-go channels in a stably transfected cell line. Proc Natl Acad Sci USA, 93 (18): 9910-4. [PMID:8790430]
42. Terlau H, Ludwig J, Steffan R, Pongs O, Stühmer W, Heinemann SH. (1996) Extracellular Mg2+ regulates activation of rat eag potassium channel. Pflugers Arch, 432 (2): 301-12. [PMID:8662307]
43. Weber C, Mello de Queiroz F, Downie BR, Suckow A, Stühmer W, Pardo LA. (2006) Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference. J Biol Chem, 281 (19): 13030-7. [PMID:16537547]
44. Ziechner U, Schönherr R, Born AK, Gavrilova-Ruch O, Glaser RW, Malesevic M, Küllertz G, Heinemann SH. (2006) Inhibition of human ether à go-go potassium channels by Ca2+/calmodulin binding to the cytosolic N- and C-termini. FEBS J, 273 (5): 1074-86. [PMID:16478480]
Attali B, Chandy KG, Giese MH, Grissmer S, Gutman GA, Jan LY, Lazdunski M, Mckinnon D, Nerbonne J, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Trimmer JS, Wang X. Voltage-gated potassium channels (Kv) in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE. 2023; 2023(1). Available from: https://doi.org/10.2218/gtopdb/F81/2023.1.