KCND3
Domain
Two N-terminal domains regulate binding to and modulation by KCNIP1.
Function
Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). In cardiomyocytes, may generate the transient outward potassium current I(To) (By similarity). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). Channel properties are modulated by interactions with regulatory subunits (PubMed:17187064, PubMed:34997220). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:17187064, PubMed:34997220). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (PubMed:34997220).
Involvement in disease
Spinocerebellar ataxia 19
SCA19
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis.
None
The disease is caused by variants affecting the gene represented in this entry.
Brugada syndrome 9
BRGDA9
A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
None
The gene represented in this entry may be involved in disease pathogenesis.
Post-translational modifications
Regulated through phosphorylation at Ser-569 by CaMK2D.
Sequence Similarities
Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.3/KCND3 sub-subfamily.
Tissue Specificity
Highly expressed in heart and brain, in particular in cortex, cerebellum, amygdala and caudate nucleus (PubMed:10200233, PubMed:10729221, PubMed:9843794). Detected at lower levels in liver, skeletal muscle, kidney and pancreas (PubMed:10200233, PubMed:10729221).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cell membrane
- Sarcolemma
- Multi-pass membrane protein
- Cell projection
- Dendrite
- Interaction with palmitoylated KCNIP2 and KCNIP3 enhances cell surface expression.
Alternative names
A-type voltage-gated potassium channel KCND3, Potassium voltage-gated channel subfamily D member 3, Voltage-gated potassium channel subunit Kv4.3, KCND3