KCNK18
entrez
338567
canonical
uniprot
Q7Z418
canonical
ensembl
ENSG00000186795
resolver
ensp
ENSP00000334650
resolver
ensp
ENSP00000521071
resolver
enst
ENST00000334549
resolver
enst
ENST00000850990
resolver
genesymbol
KCNK18
resolver
genesymbol_syn
TRESK
resolver
genesymbol_syn
TRIK
resolver
hgnc
HGNC:19439
resolver
uniprot
Q5SQQ8
resolver
uniprot_entry
KCNKI_HUMAN
resolver
uniprot_sec
Q5SQQ8
resolver
activity_regulation
ACTIVITY REGULATION: Activated by volatile anesthetics but inhibited by amide local anesthetics. Inhibited by Ba(2+) ions. Inhibited by free polyunsaturated fatty acids. Channel conductance is sensitive to intracellular pH, it decreases at acidic pH and increases at basic pH. In contrast to its mouse ortholog, it is not regulated by extracellular protons. Insensitive to changes in temperature. {ECO:0000269|PubMed:12754259, ECO:0000269|PubMed:15562060}.
uniprot
proteins
amino_acid_sequence
MEVSGHPQARRCCPEALGKLFPGLCFLCFLVTYALVGAVVFSAIEDGQVLVAADDGEFEKFLEELCRILNCSETVVEDRKQDLQGHLQKVKPQWFNRTTHWSFLSSLFFCCTVFSTVGYGYIYPVTRLGKYLCMLYALFGIPLMFLVLTDTGDILATILSTSYNRFRKFPFFTRPLLSKWCPKSLFKKKPDPKPADEAVPQIIISAEELPGPKLGTCPSRPSCSMELFERSHALEKQNTLQLPPQAMERSNSCPELVLGRLSYSIISNLDEVGQQVERLDIPLPIIALIVFAYISCAAAILPFWETQLDFENAFYFCFVTLTTIGFGDTVLEHPNFFLFFSIYIIVGMEIVFIAFKLVQNRLIDIYKNVMLFFAKGKFYHLVKK
uniprot
proteins
disease_involvement
DISEASE: Migraine with or without aura 13 (MGR13) [MIM:613656]: A form of migraine transmitted 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 photophobia, 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. {ECO:0000269|PubMed:20871611}. Note=The disease is caused by variants affecting the gene represented in this entry. 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.
uniprot
proteins
function
FUNCTION: K(+) channel that conducts outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively. The outward rectifying currents are voltage-dependent, coupled to K(+) electrochemical gradient across the membrane, whereas the inward currents can be induced in response to activation of Ca(2+)-mobilizing receptors (PubMed:12754259, PubMed:15562060, PubMed:20871611, PubMed:22355750, PubMed:26919430, PubMed:30573346). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. In trigeminal ganglia sensory neurons, the heterodimers of KCNK18/TRESK and KCNK2/TREK-1 or KCNK10/TREK-2 inhibit neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). In thymocytes, conducts K(+) currents upon T cell receptor (TCR) signaling leading to sustained Ca(2+) influx and NF-kappa-B activation, FOXP3 transcription and positive selection of regulatory T cell (Treg) progenitor subsets (PubMed:34702947). Appears to mediate the analgesics effects of hydroxy-alpha-sanshool, a metabolite naturally present in Schezuan pepper and other Xanthoxylum plants (By similarity). {ECO:0000250|UniProtKB:Q6VV64, ECO:0000269|PubMed:12754259, ECO:0000269|PubMed:15562060, ECO:0000269|PubMed:20871611, ECO:0000269|PubMed:22355750, ECO:0000269|PubMed:26919430, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:34702947}.
uniprot
proteins
mass_dalton
43671
uniprot
proteins
mutagenesis
MUTAGEN 70; /note="N->Q: Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-96."; /evidence="ECO:0000269|PubMed:20006580"; MUTAGEN 96; /note="N->Q: Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-70."; /evidence="ECO:0000269|PubMed:20006580"; MUTAGEN 121; /note="Y->H: Restores sensitivity to extracellular protons."; /evidence="ECO:0000269|PubMed:17962323
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:20006580}.; PTM: Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation enhances channel activity. {ECO:0000250|UniProtKB:Q6VV64}.
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
12754259
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15562060
uniprot
proteins
pubmed
17962323
uniprot
proteins
pubmed
20006580
uniprot
proteins
pubmed
20871611
uniprot
proteins
pubmed
22355750
uniprot
proteins
pubmed
26919430
uniprot
proteins
pubmed
30573346
uniprot
proteins
pubmed
34702947
uniprot
proteins
pubmed
36426390
uniprot
proteins
sequence_length
384
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20006580}; Multi-pass membrane protein {ECO:0000269|PubMed:20006580}.
uniprot
proteins
transmembrane_region
TRANSMEM 24..44; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 130..148; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 281..301; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 335..355; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins