KCNN3
Domain
The coiled-coil domaim mediates heteromeic assembly.
Function
Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calcium allowing its opening (PubMed:12808432, PubMed:20562108, PubMed:31155282, PubMed:36502918). The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of 10 picosiemens (PubMed:12808432, PubMed:20562108, PubMed:31155282, PubMed:36502918). Also presents an inwardly rectifying current, thus reducing its already small outward conductance of potassium ions, which is particularly the case when the membrane potential displays positive values, above + 20 mV (PubMed:12808432). Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization (By similarity).
Isoform 3
Does not function as a small conductance calcium-activated potassium channel (Probable). Selectively suppresses endogenous KCNN3 currents, in a dominant-negative fashion by decreasing the abundance of functional channels in the plasma membrane, possibly by selectively coassembling with and sequestering native KCNN3 protein in intracellular compartments (PubMed:12808432). This dominant inhibitory effect extends to other members of the SK subfamily (PubMed:12808432).
Involvement in disease
Zimmermann-Laband syndrome 3
ZLS3
A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some patients manifest intellectual disability with or without epilepsy. ZLS3 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the potassium channel KCNN family. KCa2.3/KCNN3 subfamily.
Tissue Specificity
Isoform 3
Widely distributed in human tissues and is present at 20-60% of KCNN3 in the brain.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cytoplasm
- Myofibril
- Sarcomere
- Z line
Alternative names
K3, KCNN3, Small conductance calcium-activated potassium channel protein 3, SK3, SKCa 3, SKCa3, KCa2.3