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Kv12.1

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Target not currently curated in GtoImmuPdb

Target id: 575

Nomenclature: Kv12.1

Family: Voltage-gated potassium channels (Kv)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1107 3p24.3 KCNH8 potassium voltage-gated channel subfamily H member 8
Mouse 6 1 1102 17 C Kcnh8 potassium voltage-gated channel, subfamily H (eag-related), member 8
Rat 6 1 1102 9q11 Kcnh8 potassium voltage-gated channel subfamily H member 8
Previous and Unofficial Names Click here for help
elk1 | elk3 | ELK channel 3 | ether-a-go-go-like potassium channel 1 | ether-a-go-go-like potassium channel 3 | Ets-1 | potassium voltage-gated channel, subfamily H (eag-related), member 8 | potassium channel, voltage gated eag related subfamily H, member 8 | potassium voltage-gated channel
Database Links Click here for help
Alphafold Q96L42 (Hs), P59111 (Mm), Q9QWS8 (Rn)
CATH/Gene3D 2.60.120.10
Ensembl Gene ENSG00000183960 (Hs), ENSMUSG00000035580 (Mm), ENSRNOG00000058626 (Rn)
Entrez Gene 131096 (Hs), 211468 (Mm), 246325 (Rn)
Human Protein Atlas ENSG00000183960 (Hs)
KEGG Gene hsa:131096 (Hs), mmu:211468 (Mm), rno:246325 (Rn)
OMIM 608260 (Hs)
Pharos Q96L42 (Hs)
RefSeq Nucleotide NM_144633 (Hs), NM_001031811 (Mm), NM_145095 (Rn)
RefSeq Protein NP_653234 (Hs), NP_001026981 (Mm), NP_659563 (Rn)
UniProtKB Q96L42 (Hs), P59111 (Mm), Q9QWS8 (Rn)
Wikipedia KCNH8 (Hs)
Ion Selectivity and Conductance Click here for help
Species:  Human
Macroscopic current rectification:  Ik
References:  5
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -62.0 259.0 – 45.0 5 Xenopus laevis Oocytes Human
Inactivation  - -
Deactivation  - 331.0 – 66.0 5
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  9.0 - 2 Xenopus laevis Oocytes Rat
Inactivation  - -
Comments  Voltage sensitivity is sensitive to internal pH:
V0.5=10mV at pH 7.7

V0.5=28mV at pH 6.6
[2]
Associated subunits (Human)
minK (KCNE1)

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Gating inhibitors Click here for help
Key to terms and symbols Click column headers to sort
Ligand
Sp.
Reference
Zn2+ Click here for species-specific activity table Mm - - - - - 4
⤷ [4]
Description: 1 mM Zn2+ slows activation 10-fold and shifts V0.5 for activation by ~+47 mV
Conditions: Heterologous expression in Xenopus oocytes
Cd2+ Click here for species-specific activity table Mm - - - - - 4
⤷ [4]
Description: 1 mM Cd2+ slows activation 5-fold and shifts V0.5 for activation by +35 mV
Conditions: Heterologous expression in Xenopus oocytes
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand
Sp.
Value
Parameter
Reference
Ba2+ Click here for species-specific activity table Hs - 3.7 pIC50 - - 5
⤷ pIC50 3.7 [5]
Tissue Distribution Click here for help
Primarily expressed in nervous system, especially prominent in the forebrain, cerebral cortex, hippocampus, amygdala, caudate, and nucleus accumbens. KCNH8 and KCNH3 genes also expressed together in the thalamus, substantia nigra, pons, and cerebellum; however the balance of expression level is shifted toward KCNH8. Expression very low in nonneuronal tissues.
Species:  Human
Technique:  RT-PCR
References:  5
Caudate / putamen, accumbens nuclei > cerebral cortex
Species:  Rat
Technique:  In situ hybridisation
References:  1
Functional Assays Click here for help
Voltage clamp of heterologously expressed Kv12.1 currents
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  K+-selective channel, co-assembly with Kv12.2 and Kv12.3
References:  5
Voltage clamp of heterologously expressed Kv12.1 currents
Species:  Rat
Tissue:  Xenopus laevis oocytes
Response measured:  Slowly activating outward rectifier
References:  2
Physiological Consequences of Altering Gene Expression Click here for help
β-catenin regulates gene expression
Species:  Rat
Tissue:  Thalamic neurons
Technique: 
References:  3
General Comments
This channel has:
  • 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

References

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1. 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]

2. Shi W, Wang HS, Pan Z, Wymore RS, Cohen IS, McKinnon D, Dixon JE. (1998) Cloning of a mammalian elk potassium channel gene and EAG mRNA distribution in rat sympathetic ganglia. J Physiol (Lond.), 511 ( Pt 3): 675-82. [PMID:9714851]

3. Wisniewska MB, Nagalski A, Dabrowski M, Misztal K, Kuznicki J. (2012) Novel β-catenin target genes identified in thalamic neurons encode modulators of neuronal excitability. BMC Genomics, 13: 635. [PMID:23157480]

4. Zhang X, Bursulaya B, Lee CC, Chen B, Pivaroff K, Jegla T. (2009) Divalent cations slow activation of EAG family K+ channels through direct binding to S4. Biophys J, 97 (1): 110-20. [PMID:19580749]

5. Zou A, Lin Z, Humble M, Creech CD, Wagoner PK, Krafte D, Jegla TJ, Wickenden AD. (2003) Distribution and functional properties of human KCNH8 (Elk1) potassium channels. Am J Physiol, Cell Physiol, 285 (6): C1356-66. [PMID:12890647]

Contributors

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How to cite this page

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.