KCNK2
entrez
3776
canonical
uniprot
O95069
canonical
ensembl
ENSG00000082482
resolver
ensp
ENSP00000375764
resolver
ensp
ENSP00000375765
resolver
ensp
ENSP00000394033
resolver
ensp
ENSP00000418706
resolver
enst
ENST00000486921
resolver
genesymbol
KCNK2
resolver
genesymbol_syn
TREK
resolver
genesymbol_syn
TREK1
resolver
hgnc
HGNC:6277
resolver
uniprot
A1Z1V3
resolver
uniprot
A8K618
resolver
uniprot
B2RCS4
resolver
uniprot
B7ZL56
resolver
uniprot
D3DTA5
resolver
uniprot
F6VUL8
resolver
uniprot
Q5DP47
resolver
uniprot
Q5DP48
resolver
uniprot
Q6ZW95
resolver
uniprot
Q9NRT2
resolver
uniprot
Q9UNE3
resolver
uniprot
U3N6F0
resolver
uniprot
U3N834
resolver
uniprot_entry
F6VUL8_HUMAN
resolver
uniprot_entry
KCNK2_HUMAN
resolver
uniprot_entry
Q6ZW95_HUMAN
resolver
uniprot_entry
U3N6F0_HUMAN
resolver
uniprot_entry
U3N834_HUMAN
resolver
uniprot_sec
A1Z1V3
resolver
uniprot_sec
A8K618
resolver
uniprot_sec
B2RCS4
resolver
uniprot_sec
B7ZL56
resolver
uniprot_sec
D3DTA5
resolver
uniprot_sec
Q5DP47
resolver
uniprot_sec
Q5DP48
resolver
uniprot_sec
Q9NRT2
resolver
uniprot_sec
Q9UNE3
resolver
activity_regulation
ACTIVITY REGULATION: Activated by various stimuli including intracellular acidic pH, mechanical stretch and polyunsaturated fatty acids such as arachidonic acid. Activated by volatile anesthetics such as chloroform, halothane, and isoflurane. {ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:10784345, ECO:0000269|PubMed:11319556, ECO:0000269|PubMed:38605031}.
uniprot
proteins
amino_acid_sequence
MLPSASRERPGYRAGVAAPDLLDPKSAAQNSKPRLSFSTKPTVLASRVESDTTINVMKWKTVSTIFLVVVLYLIIGATVFKALEQPHEISQRTTIVIQKQTFISQHSCVNSTELDELIQQIVAAINAGIIPLGNTSNQISHWDLGSSFFFAGTVITTIGFGNISPRTEGGKIFCIIYALLGIPLFGFLLAGVGDQLGTIFGKGIAKVEDTFIKWNVSQTKIRIISTIIFILFGCVLFVALPAIIFKHIEGWSALDAIYFVVITLTTIGFGDYVAGGSDIEYLDFYKPVVWFWILVGLAYFAAVLSMIGDWLRVISKKTKEEVGEFRAHAAEWTANVTAEFKETRRRLSVEIYDKFQRATSIKRKLSAELAGNHNQELTPCRRTLSVNHLTSERDVLPPLLKTESIYLNGLTPHCAGEEIAVIENIK
uniprot
proteins
function
FUNCTION: K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate. Converts to voltage-independent 'leak' conductance mode upon stimulation by various stimuli including mechanical membrane stretch, acidic pH, heat and lipids. Reversibly converts between a voltage-insensitive K(+) 'leak' channel and a voltage-dependent outward rectifying K(+) channel in a phosphorylation-dependent manner (PubMed:10321245, PubMed:10784345, PubMed:11319556, PubMed:23169818, PubMed:30573346, PubMed:38605031). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (By similarity). In trigeminal ganglia sensory neurons, the heterodimer of KCNK2/TREK-1 and KCNK18/TRESK inhibits 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). At trigeminal A-beta afferent nerves, the heterodimer of KCNK2/TREK-1 and KCNK4/TRAAK is mostly coexpressed at nodes of Ranvier where it conducts voltage-independent mechanosensitive and thermosensitive currents, allowing rapid action potential repolarization, high speed and high frequence saltatory conduction on myelinated nerves to ensure prompt sensory responses (By similarity). In hippocampal astrocytes, the heterodimer of KCNK2/TREK-1 and KCNK1/TWIK-1 allows passive K(+) conductance under basal conditions, but changes ion selectivity and becomes permeable to L-glutamate and Cl(-) ions upon binding to G protein subunit GNG4 in stimulated astrocytes. Mediates rapid L-glutamate release in response to activation of G protein-coupled receptors, such as F2R and CNR1 (By similarity). In hippocampal pyramidal neurons, the homodimer of KCNK2/TREK-1 contributes to gamma-aminobutyric acid (GABA) B-induced slow inhibitory postsynaptic potential. Associates with AKAP5 and Gs-protein-coupled receptor B2AR at postsynaptic dense bodies and converts to a leak channel no longer sensitive to stimulation by arachidonic acid, acidic pH or mechanical stress, nor inhibited by Gq-coupled receptors but still under the negative control of Gs-coupled receptors (By similarity). Permeable to other monovalent cations such as Rb(+) and Cs(+) (By similarity). {ECO:0000250|UniProtKB:P97438, ECO:0000250|UniProtKB:Q920B6, ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:10784345, ECO:0000269|PubMed:11319556, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:38605031}.; FUNCTION: [Isoform 4]: Does not display channel activity but reduces the channel activity of isoform 1 and isoform 2 and reduces cell surface expression of isoform 2. {ECO:0000250|UniProtKB:Q920B6}.
uniprot
proteins
mass_dalton
47093
uniprot
proteins
mutagenesis
MUTAGEN 348; /note="S->A: Mimics non-phosphorylated state and has no effect on leak channel activity."; /evidence="ECO:0000269|PubMed:11319556"; MUTAGEN 348; /note="S->D: Phosphomimetic mutant which causes switch to voltage-dependent outward rectifier channel activity."; /evidence="ECO:0000269|PubMed:11319556
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-348 controls the reversible conversion from a leak channel to a voltage-dependent channel. {ECO:0000269|PubMed:11319556}.
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
10321245
uniprot
proteins
pubmed
10784345
uniprot
proteins
pubmed
11319556
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
23169818
uniprot
proteins
pubmed
24196565
uniprot
proteins
pubmed
26642364
uniprot
proteins
pubmed
30573346
uniprot
proteins
pubmed
38605031
uniprot
proteins
sequence_length
426
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:10784345}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000269|PubMed:23169818}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 4]: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q920B6}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: Cell projection, axon {ECO:0000250|UniProtKB:Q920B6}. Cell projection, dendrite {ECO:0000250|UniProtKB:P97438}. Postsynaptic density membrane {ECO:0000250|UniProtKB:P97438}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:Q920B6}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes at the Ranvier nodes of myelinated afferent nerves. {ECO:0000250|UniProtKB:Q920B6}.
uniprot
proteins
transmembrane_region
TRANSMEM 58..80; /note="Helical; Name=M1"; /evidence="ECO:0000269|Ref.15, ECO:0007744|PDB:4TWK"; TRANSMEM 171..197; /note="Helical; Name=M2"; /evidence="ECO:0000269|Ref.15, ECO:0007744|PDB:4TWK"; TRANSMEM 225..244; /note="Helical; Name=M3"; /evidence="ECO:0000269|Ref.15, ECO:0007744|PDB:4TWK"; TRANSMEM 286..307; /note="Helical; Name=M4"; /evidence="ECO:0000269|Ref.15, ECO:0007744|PDB:4TWK
uniprot
proteins