Channelpedia

Kv12.2

Description: potassium voltage-gated channel, subfamily H (eag-related), member 3
Gene: Kcnh3
Alias: Kv12.2

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Introduction

Kv12.2, encoded by the gene KCNH3, is potassium voltage-gated channel subfamily H member 3 [606], [810]. It is also known as BEC1; ELK2; Kv12.2; KIAA1282.


Experimental data

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Gene

Kv12.2, also known as ether-a-go-go-like 2 (Elk2) or KCNH3, belongs to the ether-a-go-go (EAG) family, which comprises the ether-a-go-go (Eag, Kv10.x), ether-a-go-go-related gene (Erg, Kv11.x), and ether-a-go-go like (Elk, Kv12.x) subfamilies [812], [778].

Species NCBI gene ID Chromosome Position
Human 23416 12 19307
Mouse 16512 15 18303
Rat 27150 7 18266

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Transcript

Species NCBI accession Length (nt)
Human NM_012284.3 4023
Mouse NM_010601.4 3967
Rat NM_017108.1 3715

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Protein Isoforms

Unlike Kv5.x, Kv6.x, Kv8.x, and Kv9.x, which function as modifiers for other Kv channels [606], Kv12.2 can produce a functional channel on its own when heterologously expressed [809], [808], [813]. (From [802])

Species Uniprot ID Length (aa)
Human Q9ULD8 1083
Mouse Q9WVJ0 1095
Rat O89047 1087

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

Glycosylation in CHO Cells

N-glycosylation effects the function of Kv12.2, in as much as that removal of sugar chains causes a depolarizing shift in the steady-state activation without a significant reduction in current amplitude. Unlike the previously reported shift for Shaker-type Kv channels, this shift does not appear to be due to negatively charged sialic acid residues in the sugar chains. Kv12.2 is N-glycosylated in Chinese hamster ovary (CHO) cells and in cultured neurons as well as in the mouse brain. Only glycosylated Kv12.2 channels show proper voltage dependence and are utilized in vivo. [802]

PTM
Position
Type

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Structure

Kv12.2
Visual Representation of Kv12.2 Structure
Methodology for visual representation of structure available here

There is a light oxygen voltage (LOV) and cyclic nucleotide binding (CNB) domain in the N and C terminus, respectively. [606]

Kv12.2 features the longest S5-P loop among all known mammalian Kv channels with the most N-linked glycosylation sites (three sites). [802]

Kv12.2 predicted AlphaFold size

Species Area (Å2) Reference
Human 8831.41 source
Mouse 7533.45 source
Rat 9364.01 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Kinetics

Rat Kv12.2 channels very similar to HERG

RELK2 channels gave rise to slowly activating K+ currents. At more positive potentials, the evoked currents inactivated rapidly. Recovery from inactivation at negative potentials was reminiscent of that seen for HERG channels [809]

Mouse Kv12.2 in CHO cells display Current with EGFP

Kv.11.1 Here we present the evidence that Kv12.2 channels are expressed and N-glycosylated in the mouse brain and that N-glycosylation is essential for proper function of EGFP-Kv12.2 expressed in Chinese hamster ovary (CHO) cells. Furthermore, by a systematic mutational analysis of the three glycosylation sites of Kv12.2, our study provides insight into how glycosylation regulates the trafficking of Kv channels. To improve the reproducibility of our measurements, we fused EGFP to the N terminus of Kv12.2. When cells were transfected with EGFP-Kv12.2, almost all EGFP-positive cells showed voltage-dependent transient outward currents and characteristic tail currents, which were absent in mock-transfected cells. The currents were similar to those of untagged Kv12.2 channels which were previously reported. We, therefore, concluded that EGFP-Kv12.2 could be used for further characterization of the channel [802] For other scenarios in CHO cells EGFP was also used [809]

pH sensitivity of Kv12.1,Kv12.2 and Kv12.3

Kv.12.2 Whole cell patch clamp recordings made on HEK293 cells transfected with Elk channels hKv12.1, hKv12.2, and hKv12.3 demonstrated that external acidification inhibits their activation. High sensitivity to physiological changes in pH may be a general feature of the EAG superfamily of K+ channels as it was also observed for Kv10.1 and Kv11.1.[1832]


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Expression and Distribution

Kv12.2 was found in infant brain, lung (small cell carcinoma), eye (retinoblastoma), sciatic nerve, cortex, amygdala, hippocampus (mainly in CA1 and CA3 pyramidal cell body layers and in the granule cell layers of the dentate gyrus); in the striatal regions, including the putamen and caudate nucleus, lymphocytes, leukemias, and NG108-15 cell line. [327], [793], [810], [809], [811]. (Summary from [606])


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Function

Astrocytoma

ELK2 channels are very effective at dampening the neuronal excitability, but less so at producing adaptation of action potential firing frequency. In addition, we suggest experimental ways to recognize HELK2 currents in vivo and raise the issue of the possible function of these channels in astrocytoma [813]

Hyppocampal Hyperexcitability and Epilepsy

Human Kv12.2 may be implicated in epilepsy [814]. We show here that the voltage-gated K+ channel Kv12.2 is a potent regulator of excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic block of Kv12.2 significantly reduced firing threshold in these neurons. Kv12.2−/− mice displayed signs of persistent neuronal hyperexcitability including frequent interictal spiking, spontaneous seizures and increased sensitivity to the chemoconvulsant pentylenetetrazol [803]

Cognitive Function

Disruption of the Ether-à-go-go K+ Channel Gene Kv12.2/KCNH3 Enhances Cognitive Function [1786]

Transcription of KCNH3

The transcription of KCNH3 the gene coding for Kv12.2 may be activated by the transcription factor FOXG1 in mature neurons of the CNS suggesting a possible link to the FOXG1 syndrome pathology [2086]


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Interaction

KCNE1 and KCNE3

KCNE1 and KCNE3 beta-subunits regulate membrane surface expression of kv12.2 channels in vitro and form tripartite complex in vivo [801]

E4031

RELK1 and RELK2 currents were not blocked by 10 μm E4031 (n = 5), which blocks HERG channels, nor by 10 μm linopirdine (n = 5), which blocks M-channels [809]


References

327

778

Bauer CK et al. Physiology of EAG K+ channels.
J. Membr. Biol., 2001 Jul 1 , 182 (1-15).

793

Meves H et al. Separation of M-like current and ERG current in NG108-15 cells.
Br. J. Pharmacol., 1999 Jul , 127 (1213-23).

803

808

Zou A et al. Distribution and functional properties of human KCNH8 (Elk1) potassium channels.
Am. J. Physiol., Cell Physiol., 2003 Dec , 285 (C1356-66).

809

Engeland B et al. Cloning and functional expression of rat ether-à-go-go-like K+ channel genes.
J. Physiol. (Lond.), 1998 Dec 15 , 513 ( Pt 3) (647-54).

810

Miyake A et al. New ether-à-go-go K(+) channel family members localized in human telencephalon.
J. Biol. Chem., 1999 Aug 27 , 274 (25018-25).

811

Smith GA et al. Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells.
J. Biol. Chem., 2002 May 24 , 277 (18528-34).

812

Ganetzky B et al. The eag family of K+ channels in Drosophila and mammals.
Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (356-69).

813

Becchetti A et al. The functional properties of the human ether-à-go-go-like (HELK2) K+ channel.
Eur. J. Neurosci., 2002 Aug , 16 (415-28).

814

Grosso S et al. Epilepsy and electroencephalographic findings in pericentric inversion of chromosome 12.
J. Child Neurol., 2004 Aug , 19 (604-8).

Miyake A et al. Disruption of the ether-a-go-go K+ channel gene BEC1/KCNH3 enhances cognitive function.
J. Neurosci., 2009 Nov 18 , 29 (14637-45).


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Credits

Contributors: Rajnish Ranjan, Katherine Johnston

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/39/ , accessed on 2024 Dec 02



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