KCNN4

The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily.

potassium calcium-activated channel subfamily N member 4

Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990).
Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells (PubMed:17157250, PubMed:18796614).
Plays a role in the late stages of EGF-induced macropinocytosis (PubMed:24591580).

Calcium ion transportManual Assertion Based On ExperimentIDA:BHF-UCL
Cell volume homeostasisIEA:Ensembl
Defense responseManual Assertion Based On ExperimentTAS:ProtInc
Immune system processIEA:UniProtKB-KW
Ion transportManual Assertion Based On ExperimentIBA:GO_Central
Phospholipid translocationIEA:Ensembl
Positive regulation of potassium ion transmembrane transportTAS:Reactome
Positive regulation of protein secretionIEA:Ensembl
Positive regulation of T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Potassium ion transmembrane transportManual Assertion Based On ExperimentIBA:GO_Central
Potassium ion transportManual Assertion Based On ExperimentTAS:ProtInc
Saliva secretionIEA:Ensembl
Stabilization of membrane potentialManual Assertion Based On ExperimentIDA:BHF-UCL

Cell membrane

Dehydrated hereditary stomatocytosis 2 (DHS2):
An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. Affected individuals typically manifest mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur.

Phosphorylation at His-358 by NDKB activates the channel, and conversely it's dephosphorylation by PHPT1 inhibits the channel.