KCNQ5
Domain
Each channel 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 CALM binding domains correspond to the first two membrane-proximal helical regions that interact with a single calmodulin/CALM molecule forming a clamp-like structure and are essential for channel trafficking and electrophysiological activity (PubMed:29429937). CALM N-terminus binds to the second helix in both calcium-free and calcium-bound forms and regulates channel trafficking. CALM C-terminus binds to the first helice in calcium-free form; this interaction is disrupted by calcium binding which regulates channel electrophysiological activity (PubMed:29429937).
The C-terminal assembly domain carries the major determinants of tetramerization and subunit assembly specificity. Its coiled-coil region is four-stranded.
Function
Pore-forming subunit of the voltage-gated potassium (Kv) channel broadly expressed in brain and involved in the regulation of neuronal excitability (PubMed:10787416, PubMed:10816588, PubMed:11159685, PubMed:28669405). Associates with KCNQ3/Kv7.3 pore-forming subunit to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons (PubMed:10816588, PubMed:11159685). Contributes, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current (PubMed:10816588). Also forms a functional channel with KCNQ1/Kv7.1 subunit that may contribute to vasoconstriction and hypertension (PubMed:24855057). Channel may be selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) = Rb(+) > Cs(+) > Na(+) (PubMed:10816588). Similar to the native M-channel, KCNQ3-KCNQ5 potassium channel is suppressed by activation of the muscarinic acetylcholine receptor CHRM1 (PubMed:10816588).
Involvement in disease
Intellectual developmental disorder, autosomal dominant 46
MRD46
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD46 patients manifest developmental delay and mild to moderate intellectual disability.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.5/KCNQ5 sub-subfamily.
Tissue Specificity
Strongly expressed in brain and skeletal muscle (PubMed:10787416, PubMed:10816588). In brain, expressed in cerebral cortex, occipital pole, frontal lobe and temporal lobe. Lower levels in hippocampus and putamen. Low to undetectable levels in medulla, cerebellum and thalamus (PubMed:10787416, PubMed:10816588).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
Potassium voltage-gated channel subfamily KQT member 5, KQT-like 5, Potassium channel subunit alpha KvLQT5, Voltage-gated potassium channel subunit Kv7.5, KCNQ5