Nomenclature: Kv10.2

Family: Voltage-gated potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 988 14q23.1 KCNH5 potassium voltage-gated channel, subfamily H (eag-related), 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 (eag-related), member 5
Previous and Unofficial Names
eag2
KCNH5
Kv10.2
H-EAG2
ether-a-go-go potassium channel 2
potassium voltage-gated channel subfamily H member 5
rEAG2
voltage-gated potassium channel subunit Kv10.2
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Ion Selectivity and Conductance
Species:  Rat
Macroscopic current rectification:  Outwardly rectifying, non-inactivating voltage dependent currents
References:  6
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -100.0 - 6 Xenopus laevis oocyte Rat
Inactivation  - -
Associated subunits (Human)
minK
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
LY97241 Rn - 5.8 pIC50 - - 1,4
pIC50 5.8 [1,4]
quinidine Rn - 3.8 pIC50 - - 1
pIC50 3.8 [1]
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 [5]

Terfenadine pIC50 > 5 [3]
Tissue Distribution
Skeletal muscle, heart, placenta, lung, liver, kidney, pancreas
Species:  Human
Technique:  Northern Blot, RT-PCR
References:  3
Brain (layer IV of the cerebral cortex, thalamus, inferior colliculus, olfactory bulb, certain brainstem nuclei)
Species:  Rat
Technique:  Northern Blot, in situ hybridization
References:  5-6
Phenotypes, Alleles and Disease Models 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
Biologically Significant Variants
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: 
Type:  Splice variant
Species:  Human
Description:  Kv10.2 isoform 2
Amino acids:  624
Nucleotide accession: 
Protein accession: 
Biologically Significant Variant Comments
The funtional significance of isoform-2 and -3 variants is yet to be established
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 [4].

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 [2]. 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.

REFERENCES

1. 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]

2. 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]

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

4. 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]

5. 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]

6. 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]

To cite this database page, please use the following:

K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Michael C. Sanguinetti, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv10.2. Last modified on 31/01/2014. Accessed on 23/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=571.

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