Potassium channel subfamily K member 18

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. 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. Appears to mediate the analgesics effects of hydroxy-alpha-sanshool, a metabolite naturally present in Schezuan pepper and other Xanthoxylum plants (By similarity).

Classification

Family (Pfam)

PF07885 Ion_trans_2

InterPro

2pore_dom_K_chnl, K_chnl_dom

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Gene Ontology · 10

• GO:0005886 plasma membrane
• GO:0015269 calcium-activated potassium channel activity
• GO:0046872 metal ion binding
• GO:0015271 outward rectifier potassium channel activity
• GO:0022841 potassium ion leak channel activity
• GO:0071467 cellular response to pH
• GO:0097623 potassium ion export across plasma membrane
• GO:0071805 potassium ion transmembrane transport
• GO:0006813 potassium ion transport
• GO:0032829 regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation

Disease associations

• migraine, with or without aura, susceptibility to, 13 MONDO:0013344

Drugs targeting this protein · 5

• SEVOFLURANE opener
• DESFLURANE opener
• ISOFLURANE opener
• ENFLURANE opener
• HALOTHANE opener

Related proteins · sequence + function similarity

• Potassium channel subfamily K member 18 0.96
• Potassium channel subfamily K member 18 0.94
• Potassium channel subfamily K member 13 0.79
• Potassium channel subfamily K member 4 0.79
• Potassium channel subfamily K member 4 0.78
• Potassium channel subfamily K member 13 0.77
• Potassium channel subfamily K member 4 0.77
• Potassium channel subfamily K member 13 0.77
• Potassium channel subfamily K member 17 0.72
• Potassium channel, subfamily K, member 16 0.70
• Potassium channel subfamily K member 5 0.70
• Potassium channel subfamily K member 16 0.69

Co-cited proteins · studied together in the literature

• Potassium channel subfamily K member 18 5 shared papers
• Potassium channel subfamily K member 10 2 shared papers
• Potassium channel subfamily K member 10 1 shared papers
• Potassium channel subfamily K member 2 1 shared papers
• Potassium channel subfamily K member 17 1 shared papers
• Potassium channel subfamily K member 5 1 shared papers
• Potassium channel subfamily K member 4 1 shared papers
• Potassium channel subfamily K member 2 1 shared papers
• Potassium channel subfamily K member 9 1 shared papers
• Potassium channel subfamily K member 2 1 shared papers
• Potassium channel subfamily K member 3 1 shared papers
• Potassium channel subfamily K member 16 1 shared papers

Literature · 11 cited papers

• The Special One: Architecture, Physiology and Pharmacology of the TRESK Channel. Cell. Physiol. Biochem. · 2022
• K2P18.1 translates T cell receptor signals into thymic regulatory T cell development. Cell Res. · 2022
• Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK. Neuron · 2019
• A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels. Cell · 2016
• Functional analysis of missense variants in the TRESK (KCNK18) K channel. Sci. Rep. · 2012
• A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nat. Med. · 2010
• N-linked glycosylation determines cell surface expression of two-pore-domain K+ channel TRESK. Biochem. Biophys. Res. Commun. · 2010
• TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones. J. Physiol. (Lond.) · 2007
• Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics. Anesth. Analg. · 2004
• The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
• A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. J. Biol. Chem. · 2003