background:
Potassium channels play a role in many cellular processes including maintenance of the action potential, muscle contraction, hormone secretion, osmotic regulation, and ion flow. This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains and the encoded protein functions as an outward rectifying potassium channel. A mutation in this gene has been found to be associated with migraine with aura.[provided by RefSeq, Jan 2011]
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.
Subcellular Location:
Cell membrane.
Tissue Specificity:
Expressed specifically in dorsal root ganglion and trigeminal ganglion neurons. Detected at low levels in spinal cord.
Post-translational modifications:
Phosphorylation of Ser-252 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-264 enhances channel activity.
N-glycosylated.
DISEASE:
Defects in KCNK18 are a cause of migraine with or without aura type 13 (MGR13) [MIM:613656]. A form of migraine trasmitted in an autosomal dominant pattern. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. Note=Susceptibility to migraine has been shown to be conferred by a frameshift mutation that segregates with the disorder in a large multigenerational family. Migraine was associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting. Triggers included fatigue, alcohol and bright lights. Mutations in KCNK18 are a rare cause of migraine.
Similarity:
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
Database links:
Entrez Gene: 338567 Human
Entrez Gene: 332396 Mouse
Entrez Gene: 445371 Rat
Omim: 613655 Human
SwissProt: Q7Z418 Human
SwissProt: Q6VV64 Mouse
SwissProt: Q6Q1P3 Rat
Unigene: 449650 Human
Unigene: 329947 Mouse
Unigene: 124394 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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