Kcnk2
entrez
16526
canonical
uniprot
P97438
canonical
ensembl
ENSMUSG00000037624
resolver
ensp
ENSMUSP00000078416
resolver
ensp
ENSMUSP00000141849
resolver
ensp
ENSMUSP00000141891
resolver
ensp
ENSMUSP00000142026
resolver
enst
ENSMUST00000079451
resolver
enst
ENSMUST00000194402
resolver
genesymbol
Kcnk2
resolver
uniprot
A0A0A6YXK1
resolver
uniprot
A0A0R4J0Z6
resolver
uniprot
Q4VQI2
resolver
uniprot
Q6P6P9
resolver
uniprot_entry
A0A0A6YXK1_MOUSE
resolver
uniprot_entry
A0A0R4J0Z6_MOUSE
resolver
uniprot_entry
KCNK2_MOUSE
resolver
uniprot_entry
Q6P6P9_MOUSE
resolver
uniprot_sec
Q4VQI2
resolver
activity_regulation
ACTIVITY REGULATION: Activated by various stimuli including intracellular acidic pH, mechanical stretch and polyunsaturated fatty acids such as arachidonic acid (PubMed:17110924, PubMed:19667202, PubMed:27035963). Activated by volatile general anesthetics such as chloroform, diethyl ether, halothane and isoflurane (PubMed:10321245). Activated by arylsulfonamide ML335 and thiophene-carboxamide ML402 compounds (PubMed:28693035). Inhibited by extracellular acidification (PubMed:19667202). Inhibited by antidepressant metabolite fluoxetine (Prozac) (PubMed:27035965). Inhibited by barium (PubMed:9003761). Not sensitive to polycationic dye ruthenium red (PubMed:27035965). {ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:17110924, ECO:0000269|PubMed:19667202, ECO:0000269|PubMed:27035963, ECO:0000269|PubMed:27035965, ECO:0000269|PubMed:28693035, ECO:0000269|PubMed:9003761}.
uniprot
proteins
amino_acid_sequence
MLASASRERPGYTAGVAAPDLLDPKSAAQNSKPRLSFSSKPTVLASRVESDSAINVMKWKTVSTIFLVVVLYLIIGATVFKALEQPQEISQRTTIVIQKQTFIAQHACVNSTELDELIQQIVAAINAGIIPLGNSSNQVSHWDLGSSFFFAGTVITTIGFGNISPRTEGGKIFCIIYALLGIPLFGFLLAGVGDQLGTIFGKGIAKVEDTFIKWNVSQTKIRIISTIIFILFGCVLFVALPAVIFKHIEGWSALDAIYFVVITLTTIGFGDYVAGGSDIEYLDFYKPVVWFWILVGLAYFAAVLSMIGDWLRVISKKTKEEVGEFRAHAAEWTANVTAEFKETRRRLSVEIYDKFQRATSVKRKLSAELAGNHNQELTPCRRTLSVNHLTSEREVLPPLLKAESIYLNGLTPHCAGEDIAVIENMK
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:16636285, PubMed:17110924, PubMed:19667202, PubMed:28693035, PubMed:9003761). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:24496152, PubMed:27035963, PubMed:27035965). 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 (PubMed:30573346, PubMed:34458705). 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 (PubMed:23021213, PubMed:24496152). 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 (PubMed:17110924, PubMed:22726831). Permeable to other monovalent cations such as Rb(+) and Cs(+) (By similarity). {ECO:0000250|UniProtKB:O95069, ECO:0000250|UniProtKB:Q920B6, ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:16636285, ECO:0000269|PubMed:17110924, ECO:0000269|PubMed:19667202, ECO:0000269|PubMed:22726831, ECO:0000269|PubMed:23021213, ECO:0000269|PubMed:24496152, ECO:0000269|PubMed:27035963, ECO:0000269|PubMed:27035965, ECO:0000269|PubMed:28693035, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:34458705, ECO:0000269|PubMed:9003761}.
uniprot
proteins
mass_dalton
46844
uniprot
proteins
mutagenesis
MUTAGEN 108; /note="C->S: Abolishes formation of a disulfide-linked heterodimer with KCNK1."; /evidence="ECO:0000269|PubMed:24496152"; MUTAGEN P97438-2:91; /note="H->A,K: No effect on pH-dependence."; /evidence="ECO:0000269|PubMed:19667202"; MUTAGEN P97438-2:93; /note="C->A,D: No effect on pH-dependence."; /evidence="ECO:0000269|PubMed:19667202"; MUTAGEN P97438-2:110; /note="I->D: Confers sensitivity to ruthenium red."; /evidence="ECO:0000269|PubMed:27035965"; MUTAGEN P97438-2:126; /note="H->A: In homodimer, displays increased basal current. In heterodimer with KCNK10, displays increased basal current and KCNK10-like pH-dependence."; /evidence="ECO:0000269|PubMed:19667202, ECO:0000269|PubMed:27035963"; MUTAGEN P97438-2:126; /note="H->K: In homodimer, displays decreased basal current. In heterodimer with KCNK10, displays decreased basal current and KCNK10-like pH-dependence."; /evidence="ECO:0000269|PubMed:19667202, ECO:0000269|PubMed:27035963"; MUTAGEN P97438-2:137; /note="G->I: Results in voltage-independent channel gating."; /evidence="ECO:0000269|PubMed:28693035"; MUTAGEN P97438-2:232; /note="H->A,K: No effect on pH-dependence."; /evidence="ECO:0000269|PubMed:19667202"; MUTAGEN P97438-2:271; /note="K->Q: Loss of a cryptic cation-pi interaction that activates channel gating."; /evidence="ECO:0000269|PubMed:28693035"; MUTAGEN P97438-2:297; /note="R->A: Disrupts colocalization with AKAP5 at the plasma membrane; when associated with A-301; A302; A-304 and A-311."; /evidence="ECO:0000269|PubMed:17110924"; MUTAGEN P97438-2:301; /note="K->A: Disrupts colocalization with AKAP5 at the plasma membrane; when associated with A-297; A302; A-304 and A-311."; /evidence="ECO:0000269|PubMed:17110924"; MUTAGEN P97438-2:302; /note="K->A: Disrupts colocalization with AKAP5 at the plasma membrane; when associated with A-297; A-301; A-304 and A-311."; /evidence="ECO:0000269|PubMed:17110924"; MUTAGEN P97438-2:304; /note="K->A: Disrupts colocalization with AKAP5 at the plasma membrane; when associated with A-297; A-301; A302 and A-311."; /evidence="ECO:0000269|PubMed:17110924"; MUTAGEN P97438-2:306; /note="E->A: No effect on pH-dependence."; /evidence="ECO:0000269|PubMed:19667202"; MUTAGEN P97438-2:311; /note="R->A: Disrupts colocalization with AKAP5 at the plasma membrane; when associated with A-297; A-301; A302 and A-304."; /evidence="ECO:0000269|PubMed:17110924"; MUTAGEN P97438-2:333; /note="S->D: Mimics the phosphorylated state and reduces the enhancement of current by activation via Gi-coupled GPCRs."; /evidence="ECO:0000269|PubMed:22726831
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-348 controls the reversible conversion from a leak channel to a voltage-dependent channel. {ECO:0000250}.
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
10321245
uniprot
proteins
pubmed
16636285
uniprot
proteins
pubmed
17110924
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19667202
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22354168
uniprot
proteins
pubmed
22726831
uniprot
proteins
pubmed
23021213
uniprot
proteins
pubmed
24496152
uniprot
proteins
pubmed
26642364
uniprot
proteins
pubmed
27035963
uniprot
proteins
pubmed
27035965
uniprot
proteins
pubmed
28693035
uniprot
proteins
pubmed
30573346
uniprot
proteins
pubmed
33127683
uniprot
proteins
pubmed
34458705
uniprot
proteins
pubmed
9003761
uniprot
proteins
sequence_length
426
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:16636285, ECO:0000269|PubMed:22354168}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:17110924, ECO:0000269|PubMed:24496152, ECO:0000269|PubMed:27035965, ECO:0000269|PubMed:9003761}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendrite {ECO:0000269|PubMed:17110924}. Postsynaptic density membrane {ECO:0000305|PubMed:17110924}; Multi-pass membrane protein {ECO:0000255}. Note=Location at the cell membrane requires interaction with KCNK1. Is not detected at the cell membrane when KCNK1 is absent. {ECO:0000269|PubMed:24496152}.; SUBCELLULAR LOCATION: Cell projection, axon {ECO:0000250|UniProtKB:Q920B6}. 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:0000250|UniProtKB:O95069"; TRANSMEM 171..197; /note="Helical; Name=M2"; /evidence="ECO:0000250|UniProtKB:O95069"; TRANSMEM 225..244; /note="Helical; Name=M3"; /evidence="ECO:0000250|UniProtKB:O95069"; TRANSMEM 286..307; /note="Helical; Name=M4"; /evidence="ECO:0000250|UniProtKB:O95069
uniprot
proteins