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Details on Person UniProt:O15554 KCNN4
| Class:Id | ReferenceGeneProduct:57943 |
|---|---|
| _chainChangeLog | chain:1-427 added on Fri February 6 2015 |
| _displayName | UniProt:O15554 KCNN4 |
| _timestamp | 2026-02-20 22:22:55 |
| chain | chain:1-427 |
| checksum | 23F9AF66609B410F |
| comment | FUNCTION Intermediate 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:10026195, PubMed:10961988, PubMed:11425865, PubMed:15831468, PubMed:17157250, PubMed:18796614, PubMed:26148990, PubMed:9326665, PubMed:9380751, PubMed:9407042). The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of about 25 picosiemens (PubMed:9326665, PubMed:9380751, PubMed:9407042). 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:9326665, PubMed:9380751, PubMed:9407042). Controls calcium influx during vascular contractility by being responsible of membrane hyperpolarization induced by vasoactive factors in proliferative vascular smooth muscle cell types (By similarity). Following calcium influx, the consecutive activation of KCNN4 channel leads to a hyperpolarization of the cell membrane potential and hence an increase of the electrical driving force for further calcium influx promoting sustained calcium entry in response to stimulation with chemotactic peptides (PubMed:26418693). 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 through activation by PI(3)P (PubMed:24591580).CATALYTIC ACTIVITY K(+)(in) = K(+)(out)ACTIVITY REGULATION The channel is inhibited by clotrimazole and charybdotoxin but is insensitive to apamin.SUBUNIT Homodimer (PubMed:29953543). Homotetramer (PubMed:29724949). Heterotetramer of potassium channel proteins (Probable). Interacts with MTMR6; this interaction leads to selective dephosphorylation of PI(3)P in a lipid microdomain adjacent to KCNN4, resulting in a decrease of intermediate conductance calcium-activated potassium channel activity (PubMed:15831468). Interacts (via the C-tail domain) with CALM1; the calmodulin binding is constitutive, does not require calcium and mediates calcium-dependent gating and four calmodulin molecules bind to one channel tetramer (PubMed:10026195).INTERACTION Targeted to membrane ruffles after EGF stimulation.TISSUE SPECIFICITY Widely expressed in non-excitable tissues.INDUCTION Up-regulated by phorbol myristate acetate (PMA) and phytohemagglutinin (PHA) in T-cells.DOMAIN Transmembrane helices S5 and S6 form the ion channel pore, which is surrounded bymembrane embedded helices S1 to S4 (PubMed:29724949). The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon calmodulin binding to open the channel pore (PubMed:29724949).PTM Phosphorylation at His-358 by NDKB activates the intermediate conductance calcium-activated potassium channel activity, and conversely its dephosphorylation by PHPT1 inhibits this activity.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the potassium channel KCNN family. KCa3.1/KCNN4 subfamily. |
| description | recommendedName: fullName evidence="24"Intermediate conductance calcium-activated potassium channel protein 4 shortName: SKCa 4 shortName: SKCa4 shortName evidence="22"hSK4 alternativeName: fullName evidence="19"Gardos channel alternativeName: IKCa1 shortName evidence="21"hIK1 alternativeName: fullName evidence="20"KCa3.1 alternativeName: Putative Gardos channel alternativeName: fullName evidence="23"hKCa4 |
| geneName | KCNN4 IK1 IKCA1 KCA4 SK4 |
| identifier | O15554 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Calmodulin-binding Cell membrane Cell projection Disease variant Hereditary hemolytic anemia Immunity Ion channel Ion transport Membrane Phosphoprotein Proteomics identification Reference proteome Transmembrane Transmembrane helix Transport |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | KCNN4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989020] ENSEMBL:ENSG00000104783 KCNN4 [Homo sapiens] |
| secondaryIdentifier | KCNN4_HUMAN Q53XR4 |
| sequenceLength | 427 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:977543] KCNN4 [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:O15554 KCNN4 (57943)
