Kcnk18
entrez
332396
canonical
uniprot
Q6VV64
canonical
ensembl
ENSMUSG00000040901
resolver
ensp
ENSMUSP00000065713
resolver
enst
ENSMUST00000065204
resolver
genesymbol
Kcnk18
resolver
genesymbol_syn
Tresk-2
resolver
genesymbol_syn
Tresk2
resolver
uniprot
Q1LZJ5
resolver
uniprot
Q1LZM8
resolver
uniprot
Q3MI50
resolver
uniprot
Q3MI51
resolver
uniprot_entry
KCNKI_MOUSE
resolver
uniprot_sec
Q1LZJ5
resolver
uniprot_sec
Q1LZM8
resolver
uniprot_sec
Q3MI50
resolver
uniprot_sec
Q3MI51
resolver
activity_regulation
ACTIVITY REGULATION: Activated upon cell stimulation via Ca(2+)-mobilizing receptors, such as CHRM1/M1 muscarinic receptor and AGTR1/AT1a angiotensin receptor (PubMed:14981085). Activated by volatile anesthetics, such as isoflurane and inhibited by local anesthetics such as bupivacaine and lidocaine. Inhibited by extracellular acidic pH (PubMed:16192517, PubMed:18568022). Inhibited by Zn(2+) ions (PubMed:16192517). Inhibited by hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. Inhibited by Ba(2+) ions (PubMed:18568022). {ECO:0000269|PubMed:14981085, ECO:0000269|PubMed:16192517, ECO:0000269|PubMed:18568022}.
uniprot
proteins
amino_acid_sequence
MEAEEPPEARRCCPEALGKARGCCPEALGKLLPGLCFLCCLVTYALVGAALFSAVEGRPDPEAEENPELKKFLDDLCNILKCNLTVVEGSRKNLCEHLQHLKPQWLKAPQDWSFLSALFFCCTVFSTVGYGHMYPVTRLGKFLCMLYALFGIPLMFLVLTDIGDILATILSRAYSRFQALLCLPHDIFKWRSLPLCRKQPDSKPVEEAIPQIVIDAGVDELLNPQPSKDPPSPSCNVELFERLVAREKKNKLQPPTRPVERSNSCPELVLGRLSCSILSNLDEVGQQVERLDIPLPVIALVVFAYISCAAAILPFWETELGFEDAFYFCFVTLTTIGFGDIVLVHPHFFLFFSIYIIVGMEILFIAFKLMQNRLLHTYKTLMLFVCQREVSLPW
uniprot
proteins
disease_involvement
DISEASE: Note=Frameshift variants combined with alternative initiation of translation result in the production of aberrant truncated KCNK18/TRESK proteins with dominant negative effects on KCNK2/TREK-1 and KCNK10/TREK-2 channel subunits, causing trigeminal neuron hyperexcitability and migraine-like phenotype, similarly to TREK-1 and TREK-2 double knockout mice. {ECO:0000269|PubMed:30573346}.
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:14981085, PubMed:16192517, PubMed:16569637, PubMed:17962323). 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 (PubMed:17962323, PubMed:30573346, PubMed:32641496, PubMed:34458705). 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 (PubMed:18568022). {ECO:0000269|PubMed:14981085, ECO:0000269|PubMed:16192517, ECO:0000269|PubMed:16569637, ECO:0000269|PubMed:17962323, ECO:0000269|PubMed:18568022, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:32641496, ECO:0000269|PubMed:34458705, ECO:0000269|PubMed:34702947}.
uniprot
proteins
mass_dalton
44403
uniprot
proteins
mutagenesis
MUTAGEN 83; /note="N->Q: Strongly reduced current amplitude and localization to cell membrane."; /evidence="ECO:0000269|PubMed:20006580"; MUTAGEN 131; /note="G->E: Acts as a dominant negative on wild-type KCNK18 or KCNK10 subunits."; /evidence="ECO:0000269|PubMed:32641496"; MUTAGEN 132; /note="H->N: Insensitive to extracellular protons."; /evidence="ECO:0000269|PubMed:17962323"; MUTAGEN 212; /note="I->A: Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-214."; /evidence="ECO:0000269|PubMed:16569637"; MUTAGEN 214; /note="I->A: Strongly reduced activation by elevated intracellular Ca(2+). Loss of interaction with calcineurin and activation by elevated intracellular Ca(2+); when associated with A-212."; /evidence="ECO:0000269|PubMed:16569637"; MUTAGEN 264; /note="S->A: Loss of interaction with YWHAH. No effect on channel conductance."; /evidence="ECO:0000269|PubMed:18397886, ECO:0000269|PubMed:32641496"; MUTAGEN 264; /note="S->E: Further decreases the open probability of the channel, without affecting the single channel conductance; when associated with E-276."; /evidence="ECO:0000269|PubMed:32641496"; MUTAGEN 276; /note="S->A: Increases the open probability of the channel, without affecting the single channel conductance. Confers resistance to stimulation by calcineurin. Mice carrying the mutant allele display increased Treg numbers in thymus and spleen."; /evidence="ECO:0000269|PubMed:14981085, ECO:0000269|PubMed:32641496, ECO:0000269|PubMed:34702947"; MUTAGEN 276; /note="S->E: Decreases the open probability of the channel, without affecting the single channel conductance."; /evidence="ECO:0000269|PubMed:32641496"; MUTAGEN 339; /note="G->R: Loss of channel conductance. In DRG sensory neurons, results in decreased rheobase current, decreased action potential duration and amplitude upon hyperpolarization and increased sensitivity to depolarizing stimuli, but has no effect on resting membrane potential. Mice carrying the mutant allele display impaired thymic Treg development and increased susceptibility to autoimmune encephalomyelitis."; /evidence="ECO:0000269|PubMed:17962323, ECO:0000269|PubMed:34702947
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances channel activity. {ECO:0000269|PubMed:14981085, ECO:0000269|PubMed:18397886}.; PTM: N-glycosylated. {ECO:0000269|PubMed:20006580}.
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
14981085
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16192517
uniprot
proteins
pubmed
16569637
uniprot
proteins
pubmed
17962323
uniprot
proteins
pubmed
18397886
uniprot
proteins
pubmed
18568022
uniprot
proteins
pubmed
20006580
uniprot
proteins
pubmed
20871611
uniprot
proteins
pubmed
30573346
uniprot
proteins
pubmed
32641496
uniprot
proteins
pubmed
34458705
uniprot
proteins
pubmed
34702947
uniprot
proteins
sequence_length
394
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 32..52; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 142..162; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 293..313; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 347..367; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins