KCNA4
Domain
The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.
The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368).
Involvement in disease
Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum
MCIDDS
An autosomal recessive syndrome characterized by cognitive impairment, attention deficit-hyperactivity disorder, microcephaly, growth retardation, congenital cataract, and dystonia. Brain MRI shows unusual thinning of the lentiform nucleus, predominantly involving the putamen, and swelling in the caudate heads.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily.
Tissue Specificity
Expressed in brain, and at lower levels in the testis, lung, kidney, colon and heart (PubMed:27582084). Detected in heart ventricle.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cell projection
- Axon
Alternative names
KCNA4L, KCNA4, Potassium voltage-gated channel subfamily A member 4, HPCN2, Voltage-gated K(+) channel HuKII, Voltage-gated potassium channel HBK4, Voltage-gated potassium channel HK1, Voltage-gated potassium channel subunit Kv1.4