KCNQ3
Domain
Each subunit contains six transmembrane segments (S1-S6) with S1-S4 forming one voltage sensing domain (VSD) and S5-S6 contributing to form one quarter of an interlocking pore-forming domain (PD).
The S4-S5 linker preferentially interacts with PIP2 in the open-state KCNQ2 channel, whereas the S2-S3 loop interacts with PIP2 in the closed state.
The intracellular C-terminal domain is bound constitutively by calmodulin (CaM) (PubMed:27564677). This domain plays key functions in channel tetramerization, trafficking, and gating (PubMed:27564677).
Function
Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:16319223, PubMed:27564677, PubMed:28793216, PubMed:9872318). M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers (PubMed:14534157, PubMed:16319223, PubMed:27564677, PubMed:9872318). The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs (PubMed:14534157, PubMed:16319223, PubMed:28793216). M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) (PubMed:28793216). M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) (PubMed:28793216). Suppressed by activation of M1 muscarinic acetylcholine receptors (PubMed:10713961). KCNQ3 also associates with KCNQ5 to form a functional channel in vitro and may also contribute to the M-current in brain (PubMed:11159685).
Involvement in disease
Seizures, benign familial neonatal 2
BFNS2
A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset.
None
The disease is caused by variants affecting the gene represented in this entry.
Defects in KCNQ3 may be involved in epileptic disorders. These are characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.
Post-translational modifications
KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to protein degradation (Probable). Degradation induced by NEDD4L is inhibited by USP36 (PubMed:27445338).
Sequence Similarities
Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.3/KCNQ3 sub-subfamily.
Tissue Specificity
Predominantly expressed in brain.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
Potassium voltage-gated channel subfamily KQT member 3, KQT-like 3, Potassium channel subunit alpha KvLQT3, Voltage-gated potassium channel subunit Kv7.3, KCNQ3