Potassium voltage-gated channel subfamily C member 3
Domain
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
The cytoplasmic N-terminus mediates N-type inactivation.
The C-terminal cytoplasmic tail contributes to the regulation of channel inactivation and to the interaction with HAX1 and the Arp2/3 complex.
Function
Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:10712820, PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:22289912, PubMed:23734863, PubMed:25756792, PubMed:26997484). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (By similarity). Required for normal motor function (PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:23734863, PubMed:25756792). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).
Involvement in disease
Spinocerebellar ataxia 13
SCA13
Spinocerebellar ataxia is 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. SCA13 is an autosomal dominant cerebellar ataxia (ADCA) characterized by slow progression and variable age at onset, ranging from childhood to late adulthood. Intellectual disability can be present in some patients.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.3/KCNC3 sub-subfamily.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Presynaptic cell membrane
- Multi-pass membrane protein
- Perikaryon
- Cell projection
- Axon
- Cell projection
- Dendrite
- Cell projection
- Dendritic spine membrane
- Multi-pass membrane protein
- Cytoplasm
- Cell cortex
- Cytoplasm
- Cytoskeleton
- Detected on Purkinje cell dendritic spines, positioned perisynaptically but also in extrasynaptic positions along the spine membranes (By similarity). Detected at presynaptic calices of Held (By similarity). Colocalizes with the cortical actin cytoskeleton and the Arp2/3 complex (PubMed:26997484).
Alternative names
Voltage-gated potassium channel KCNC3, KSHIIID, Potassium voltage-gated channel subfamily C member 3, Voltage-gated potassium channel subunit Kv3.3, KCNC3