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KCNN2

Domain

The coiled-coil domaim mediates heteromeic assembly.

The calmodulin-binding domain (CaMBD) forms an elongated dimer with a calmodulin molecule bound at each end; each calmodulin wraps around three alpha-helices, two from one CaMBD subunit and one from the other.

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:10991935, PubMed:33242881, PubMed:9287325). The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of about 3 picosiemens (PubMed:10991935). 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:10991935). The inward rectification could be due to a blockade of the outward current by intracellular divalent cations such as calcium and magnesium and could also be due to an intrinsic property of the channel pore, independent of intracellular divalent ions. There are three positively charged amino acids in the S6 transmembrane domain, close to the pore, that collectively control the conductance and rectification through an electrostatic mechanism. Additionally, electrostatic contributions from these residues also play an important role in determining the intrinsic open probability of the channel in the absence of calcium, affecting the apparent calcium affinity for activation. Forms an heteromeric complex with calmodulin, which is constitutively associated in a calcium-independent manner. Channel opening is triggered when calcium binds the calmodulin resulting in a rotary movement leading to the formation of the dimeric complex to open the gate (By similarity). Plays a role in the repolarization phase of cardiac action potential (PubMed:13679367).

Involvement in disease

Dystonia 34, myoclonic

DYT34

A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT34 is an autosomal dominant form characterized by childhood-onset dystonia predominantly affecting hands and neck, with a fast tremor with superimposed myoclonus and, in some individuals, subtle cerebellar signs.

None

The disease may be caused by variants affecting the gene represented in this entry.

Neurodevelopmental disorder with or without variable movement or behavioral abnormalities

NEDMAB

An autosomal dominant disorder characterized by motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Other variable features include autism spectrum disorder or autistic features and epilepsy.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence Similarities

Belongs to the potassium channel KCNN family. KCa2.2/KCNN2 subfamily.

Tissue Specificity

Expressed in atrial myocytes (at protein level) (PubMed:13679367). Widely expressed.

Cellular localization

Alternative names

Small conductance calcium-activated potassium channel protein 2, SK2, SKCa 2, SKCa2, KCa2.2, KCNN2

swissprot:Q9H2S1 omim:605879 swissprot:Q6PJI0 entrezGene:3781