Description: potassium voltage-gated channel, subfamily G, member 3
Gene: Kcng3     Synonyms: Kv6.3, kcng3, kv10.1

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KV6.3 is a member of the potassium channel, voltage-gated, subfamily G, encoded by and also known as KCNG3. This member is a gamma subunit of the voltage-gated potassium channel. The delayed-rectifier type channels containing this subunit may contribute to cardiac action potential repolarization.

Experimental data



RGD ID Chromosome Position Species
628832 6 6947526-6995735 Rat
735864 17 83985297-84031235 Mouse
735863 2 42669157-42721237 Human

Kcng3 : potassium voltage-gated channel, subfamily G, member 3



Acc No Sequence Length Source
NM_001033957 n/A n/A NCBI
NM_133426 n/A n/A NCBI
NM_153512 n/A n/A NCBI
NM_133329 n/A n/A NCBI
NM_172344 n/A n/A NCBI






The voltage-activated K(+) channel subunit Kv2.1 can form heterotetramers with members of the Kv6 subfamily, generating channels with biophysical properties different from homomeric Kv2.1 channels. The N-terminal tetramerization domain (T1) has been shown previously to play a role in Kv channel assembly [644]





The following is paraphrased from [664]: Kv channels are composed of four subunits that surround the central ion permeation pathway. Each subunit has six transmembrane domains (S1–S6) and a pore region containing the signature sequence GYG character- istic for potassium channels [667], [619]. Post-translational assembly of tetrameric Kv channels takes place in the ER2 membrane; sub- sequently the channels traffic to the plasma membrane [619], [668]. A highly conserved sequence in the cytoplasmic N terminus of Kv channels, the tetramerization domain or T1 domain, has been shown to play an important role in channel assembly [619], [669]. The T1 domain contains some of the molecular determinants for subfamily-specific homo- or heterotetrameric assembly of Kv alpha-subunits [669], [660],[598], [670]. The most striking difference between the T1 domains of Kv1 (Shaker) and Kv2–4 (non-Shaker) channels is the presence of intersubunit-coordinated Zn2+ ions at the assembly interface in non-Shaker channels. The Zn2+ ions are coordinated by a C3H1 motif embedded in a conserved sequence motif (HX5CX20CC) of the T1 domain, which is located near the distal end of the N terminus [671], [672], [673]. These four amino acids are exposed on the subunit interface, with one histidine and two cysteine residues belonging to one subunit and one cysteine residue belonging to the neighboring subunit [671]. The T1 domain facilitates tetrameric assembly of Kv channels. Kv subunits in which the T1 has been deleted have been reported to assemble in a promiscuous way via their transmembrane domains and to form stable, functional channels, but both the rates and the efficiency of channel assembly are significantly lower in the mutant channels as compared with their wild-type counterparts [668], [674]. Heteromeric assembly of channel subunits is a potential source of diversity of K+ channel properties.





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Kv6.3 regulates Kv current amplitude and kinetics observed in vascular smooth muscle cells, suggesting that the remodelling of Kv2 current could be an important determinant of the hypertensive phenotype in resistance arteries. [662], [663]

The voltage-activated potassium channel subunits Kv2.1 and Kv2.2 are capable of heteromeric assembly with members of the Kv6 subfamily, which generates channels with different biophysical properties compared with homomeric Kv2.1 channels [661], [675], [676], [648], [398]. For the influence of Kv6.3 on Kv2.1, see [664].

In Kv6.x channels the histidine residue of the zinc ion-coordinating C3H1 motif of Kv2.1 is replaced by arginine or valine. Using a yeast two-hybrid assay, we found that substitution of the corresponding histidine 105 in Kv2.1 by valine (H105V) or arginine (H105R) disrupted the interaction of the T1 domain of Kv2.1 with the T1 domains of both Kv6.3 and Kv6.4, whereas interaction of the T1 domain of Kv2.1 with itself was unaffected by this mutation [664]

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Interaction of all Kv6.3 subunit on Kv2.1

Kv1.1 structure [664]

Whole-cell current recordings and subcellular localization of Kv2.1GFP, Kv6.3GFP and the coexpression Currents were evoked by stepping from −80 mV to +70 mV, 500 ms in duration, followed by a repolarizing pulse at −30 mV, 1 s in duration. Co-expression of Kv2.1 with Kv6.3GFP resulted in outward currents and green plasma membrane staining. This demonstrates that Kv2.1 was able to rescue the Kv6.3GFP subunits out of the ER [1708]

The profound effects of Kv6.3 on Kv2.1 gating properties suggest an important role for these heterotetramers: the latter would be inactivated at potentials close to resting potential (V½ for inactivation is −56 mV) in contrast to the homotetrameric Kv2.1 channels (V½ = −16 mV). Because both subunits are expressed in the brain functional heterotetramers could exist. Previous studies on the sustained delayed rectifier component of hippocampal neurons showed properties that are comparable with those of Kv2.1 and Kv6.3 heteromultimers. At −5 mV the two time constants for activation for the current in those neurons were 53 ms and 190 ms, which is comparable with heterotetrameric channels of Kv2.1 and Kv6.3 (Table 1). In addition, the midpoint of inactivation was more negative (−96 mV), which is at least closer to −56 mV for Kv2.1 and Kv6.3 compared with −16 mV for Kv2.1 alone [648]





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Nat. Struct. Biol., 1999 Jan , 6 (38-43).


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Strang C et al. The role of Zn2+ in Shal voltage-gated potassium channel formation.
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Tu L et al. Voltage-gated K+ channels contain multiple intersubunit association sites.
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Vega-Saenz de Miera EC Modification of Kv2.1 K+ currents by the silent Kv10 subunits.
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Ottschytsch N et al. Domain analysis of Kv6.3, an electrically silent channel.
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Contributors: Rajnish Ranjan, Michael Schartner

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