Function: Outward rectifying potassium channel. Produces rapidly activating outward rectifier K+ currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation. Ref.1 Ref.2 Ref.8
Subunit structure: Interacts with calcineurin. Interacts with YWHAH, in a phosphorylation-dependent manner. Ref.5 Ref.7
Subcellular location: Cell membrane; Multi-pass membrane protein Ref.9.
Tissue specificity: Detected in brain cortex, cerebellum, dorsal root ganglion, spinal cord and testis. High expression in trigeminal ganglion, also expressed in autonomic nervous system ganglia such as the stellate ganglion and paravertebral sympathetic ganglia. Expressed in all adult spinal cord and brain regions, with slightly higher expression in thalamus, hypothalamus, hippocampus and posterior corte (at protein level). In non-neuronal tissues, substantial expression found in lung and heart and weal expression in liver, testis, kidney, small intestine and spleen. Ref.1 Ref.2 Ref.6 Ref.10
Developmental stage: Expression appears in trigeminal ganglion and dorsal root ganglia from E15.5 and increased through E18 to reach a peak in newborn mouse postnatal day 1. Ref.10
Post-translational modification: Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances channel activity.N-glycosylated. Ref.9
Miscellaneous: Regulated by extracellular protons whereas human ortholog is not. His-132 is responsible for proton-dependent specific activity.
Sequence similarities: Belongs to the two pore domain potassium channel (TC 1.A.1.8) family. [View classification]
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