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Target not currently curated in GtoImmuPdb

Target id: 571

Nomenclature: Kv10.2

Family: Voltage-gated potassium channels (Kv)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 988 14q23.2 KCNH5 potassium voltage-gated channel subfamily H member 5
Mouse 6 1 988 12 C3 Kcnh5 potassium voltage-gated channel, subfamily H (eag-related), member 5
Rat 6 1 988 6q24 Kcnh5 potassium voltage-gated channel subfamily H member 5
Previous and Unofficial Names Click here for help
eag2 | ether-a-go-go potassium channel 2 | potassium voltage-gated channel, subfamily H (eag-related), member 5 | potassium channel, voltage gated eag related subfamily H, member 5 | potassium voltage-gated channel
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Kv10.1 10
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
α-tubulin 1
Ion Selectivity and Conductance Click here for help
Species:  Rat
Macroscopic current rectification:  Outwardly rectifying, non-inactivating voltage dependent currents
References:  9
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -35.5 202.0 – 14.6 9 Xenopus laevis oocyte Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -11.0 - Xenopus laevis oocyte Human
Inactivation  - -

Download all structure-activity data for this target as a CSV file go icon to follow link

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
LY97241 Small molecule or natural product Click here for species-specific activity table Hs Pore blocker 5.8 pIC50 - - 2,6
pIC50 5.8 [2,6]
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 Hs Pore blocker 3.8 pIC50 - - 2
pIC50 3.8 [2]
Channel Blocker Comments
Intracellular Calcium (Cai2+): At 20ηM Cai2+ current declined ~ 30% after 90 seconds. At 400 ηM Cai2+, only 10% of residual current left after 90 seconds [7]

Terfenadine pIC50 > 5 [5]
Tissue Distribution Click here for help
Skeletal muscle, heart, placenta, lung, liver, kidney, pancreas
Species:  Human
Technique:  Northern Blot, RT-PCR
References:  5
Brain (layer IV of the cerebral cortex, thalamus, inferior colliculus, olfactory bulb, certain brainstem nuclei)
Species:  Rat
Technique:  Northern Blot, in situ hybridization
References:  7,9
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnh5tm1Dgen Kcnh5tm1Dgen/Kcnh5tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:3584508  MP:0001486 abnormal startle reflex
Kcnh5tm1Dgen Kcnh5tm1Dgen/Kcnh5tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:3584508  MP:0002797 increased thigmotaxis
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Epileptic encephalopathy
References:  11-12
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R327H 11-12
Disease:  Medulloblastoma
Disease Ontology: DOID:3858
OMIM: 155255
References:  3
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  Kv10.2 isoform 3
Amino acids:  611
Nucleotide accession: 
Protein accession: 
Type:  Splice variant
Species:  Human
Description:  Kv10.2 isoform 1
Amino acids:  988
Nucleotide accession: 
Protein accession: 
Biologically Significant Variant Comments
The functional significance of isoform-2 and -3 variants is yet to be established.

There are two promoters capable of driving KCNH5 transcription. The upstream promoter appears to be active in placental tissues and some melanomas [8].
General Comments
This channel has the following features:

  • GFG (rather than the common GYG) potassium channel signature sequence,
  • a PAS domain in the distal part of the cytosolic N-terminus
  • a cNBD domain in the proximal portion of the C-terminus
  • a C-terminal assembly domain (CAD)
  • a CaM binding domain
  • a bNLS domain in the C-terminus
  • a C-terminal domain required for assembly [6].

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 [4]. 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.


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1. Bracey K, Ju M, Tian C, Stevens L, Wray D. (2008) Tubulin as a binding partner of the heag2 voltage-gated potassium channel. J Membr Biol, 222 (3): 115-25. [PMID:18458804]

2. 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]

3. Huang X, He Y, Dubuc AM, Hashizume R, Zhang W, Reimand J, Yang H, Wang TA, Stehbens SJ, Younger S et al.. (2015) EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat Neurosci, 18 (9): 1236-46. [PMID:26258683]

4. 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]

5. Ju M, Wray D. (2002) Molecular identification and characterisation of the human eag2 potassium channel. FEBS Lett, 524 (1-3): 204-10. [PMID:12135768]

6. 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]

7. Ludwig J, Weseloh R, Karschin C, Liu Q, Netzer R, Engeland B, Stansfeld C, Pongs O. (2000) Cloning and functional expression of rat eag2, a new member of the ether-à-go-go family of potassium channels and comparison of its distribution with that of eag1. Mol Cell Neurosci, 16 (1): 59-70. [PMID:10882483]

8. Macaulay EC, Roberts HE, Cheng X, Jeffs AR, Baguley BC, Morison IM. (2014) Retrotransposon hypomethylation in melanoma and expression of a placenta-specific gene. PLoS ONE, 9 (4): e95840. [PMID:24759919]

9. Saganich MJ, Vega-Saenz de Miera E, Nadal MS, Baker H, Coetzee WA, Rudy B. (1999) Cloning of components of a novel subthreshold-activating K(+) channel with a unique pattern of expression in the cerebral cortex. J Neurosci, 19 (24): 10789-802. [PMID:10594062]

10. 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]

11. Veeramah KR, Johnstone L, Karafet TM, Wolf D, Sprissler R, Salogiannis J, Barth-Maron A, Greenberg ME, Stuhlmann T, Weinert S et al.. (2013) Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. Epilepsia, 54 (7): 1270-81. [PMID:23647072]

12. Yang Y, Vasylyev DV, Dib-Hajj F, Veeramah KR, Hammer MF, Dib-Hajj SD, Waxman SG. (2013) Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state. J Neurosci, 33 (42): 16586-93. [PMID:24133262]


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