KCNK4

Potassium channel, two pore domain subfamily K, member 4

Crystallographic structure of TRAAK. The gray boxes indicate approximate location of the lipid bilayer.^[1]

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
3UM7, 4I9W, 4RUE, 4RUF, 4WFE, 4WFF, 4WFG, 4WFH

Identifiers

Symbols

KCNK4 ; K2p4.1; TRAAK; TRAAK1

External IDs

OMIM: 605720 MGI: 1298234 HomoloGene: 7391 IUPHAR: 516 GeneCards: KCNK4 Gene

Gene ontology
Molecular function	• voltage-gated ion channel activity • potassium channel activity • potassium ion leak channel activity • temperature-gated cation channel activity • mechanically-gated potassium channel activity
Cellular component	• plasma membrane • integral component of plasma membrane • potassium channel complex
Biological process	• potassium ion transport • synaptic transmission • memory • sensory perception of pain • stabilization of membrane potential • regulation of ion transmembrane transport • sensory perception of temperature stimulus • detection of mechanical stimulus involved in sensory perception of touch • cellular response to mechanical stimulus • cellular response to fatty acid • cellular response to alkaline pH • cellular response to temperature stimulus • potassium ion transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 11:
64.29 – 64.3 Mb

Chr 19:
6.93 – 6.93 Mb

PubMed search

Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene.^[2]^[3]^[4]

Function

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 the K_2P4.1 protein, one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. K_2P4.1 homodimerizes and functions as an outwardly rectifying channel. It is expressed primarily in neural tissues and is stimulated by membrane stretch and polyunsaturated fatty acids.^[4]

KCNK4 protein channels are also called TRAAK channels. TRAAK channels are found in mammalian neurons and are part of a protein family of weakly inward rectifying potassium channels. This subfamily of potassium channels is mechanically gated. The C-terminal of TRAAK has a charged cluster that is important in maintaining the mechanosensitive properties of the channel.^[5]

TRAAK is only expressed in neuronal tissue, and can be found in the brain, spinal cord, and retina, which suggests that it has a function beyond mechanotransduction in terms of neuronal excitability.^[6] The highest levels of TRAAK expression are in the olfactory system, cerebral cortex, hippocampal formation, habenula, basal ganglia, and cerebellum.^[6] TRAAK channels are mechanically activated when there is a convex curvature in the membrane that alters the channel’s activity. TRAAK channels are thought to have a role in axonal pathfinding, growth cone motility, and neurite elongation, as well as possibly having a role in touch or pain detection.^[7]^[8]

References

↑ PDB: 3UM7; Brohawn SG, del Mármol J, MacKinnon R (27 January 2012). "Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel". Science 335 (6067): 436–41. doi:10.1126/science.1213808. PMC 3329120. PMID 22282805.
↑ Lesage F, Maingret F, Lazdunski M (May 2000). "Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel". FEBS Lett 471 (2–3): 137–40. doi:10.1016/S0014-5793(00)01388-0. PMID 10767409.
↑ Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (Dec 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacol Rev 57 (4): 527–40. doi:10.1124/pr.57.4.12. PMID 16382106.
1 2 "Entrez Gene: KCNK4 potassium channel, subfamily K, member 4".
↑ Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M (1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience 2 (5): 422–426. doi:10.1038/8084. PMID 10321245.
1 2 Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (1998). "A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids". The EMBO Journal 17 (12): 3297–3308. doi:10.1093/emboj/17.12.3297. PMC 1170668. PMID 9628867.
↑ Vandorpe DH, Morris CE (1992). "Stretch activation of the Aplysia S-channel". The Journal of membrane biology 127 (3): 205–214. PMID 1495087.
↑ Maingret F, Fosset M, Lesage F, Lazdunski M, Honoré E (1999). "TRAAK is a mammalian neuronal mechano-gated K+ channel". The Journal of Biological Chemistry 274 (3): 1381–1387. doi:10.1074/jbc.274.3.1381. PMID 9880510.

External links

KCNK4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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KCNK4

Function

See also

References

Further reading

External links