KCNK4_MOUSE
ID KCNK4_MOUSE Reviewed; 398 AA.
AC O88454;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Potassium channel subfamily K member 4;
DE AltName: Full=TWIK-related arachidonic acid-stimulated potassium channel protein;
DE Short=TRAAK;
GN Name=Kcnk4; Synonyms=Traak;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9628867; DOI=10.1093/emboj/17.12.3297;
RA Fink M., Lesage F., Duprat F., Heurteaux C., Reyes R., Fosset M.,
RA Lazdunski M.;
RT "A neuronal two P domain K+ channel stimulated by arachidonic acid and
RT polyunsaturated fatty acids.";
RL EMBO J. 17:3297-3308(1998).
RN [2]
RP ACTIVITY REGULATION.
RX PubMed=10321245; DOI=10.1038/8084;
RA Patel A.J., Honore E., Lesage F., Fink M., Romey G., Lazdunski M.;
RT "Inhalational anesthetics activate two-pore-domain background K+
RT channels.";
RL Nat. Neurosci. 2:422-426(1999).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19279663; DOI=10.1038/emboj.2009.57;
RA Noel J., Zimmermann K., Busserolles J., Deval E., Alloui A., Diochot S.,
RA Guy N., Borsotto M., Reeh P., Eschalier A., Lazdunski M.;
RT "The mechano-activated K+ channels TRAAK and TREK-1 control both warm and
RT cold perception.";
RL EMBO J. 28:1308-1318(2009).
CC -!- FUNCTION: Voltage-insensitive potassium channel (PubMed:9628867).
CC Channel opening is triggered by mechanical forces that deform the
CC membrane. Channel opening is triggered by raising the intracellular pH
CC to basic levels (By similarity). The channel is inactive at 24 degrees
CC Celsius (in vitro); raising the temperature to 37 degrees Celsius
CC increases the frequency of channel opening, with a further increase in
CC channel activity when the temperature is raised to 42 degrees Celsius
CC (By similarity). Plays a role in the sensory perception of pain caused
CC by pressure (PubMed:19279663). Plays a role in the perception of pain
CC caused by heat (PubMed:19279663). {ECO:0000250|UniProtKB:G3V8V5,
CC ECO:0000269|PubMed:19279663, ECO:0000269|PubMed:9628867}.
CC -!- ACTIVITY REGULATION: Activated by arachidonic acid and other
CC unsaturated fatty acids (PubMed:9628867). Not affected by volatile
CC general anesthetics such as chloroform, diethyl ether, halothane and
CC isoflurane (PubMed:10321245). {ECO:0000269|PubMed:10321245,
CC ECO:0000269|PubMed:9628867}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:Q9NYG8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9628867};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O88454-1; Sequence=Displayed;
CC Name=2; Synonyms=TRAAKT, Truncated;
CC IsoId=O88454-2; Sequence=VSP_006690, VSP_006691;
CC -!- TISSUE SPECIFICITY: Expressed in brain, spinal cord and eye. Not
CC detected in heart, skeletal muscle, liver, lungs, kidney and testis.
CC {ECO:0000269|PubMed:9628867}.
CC -!- DOMAIN: Channel opening is brought about by a conformation change that
CC involves buckling of the second transmembrane helix and affects the
CC position and orientation of the fourth transmembrane helix.
CC {ECO:0000250|UniProtKB:Q9NYG8}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9NYG8}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show increased sensitivity to pain
CC caused by pressure, but also by heat. {ECO:0000269|PubMed:19279663}.
CC -!- SIMILARITY: Belongs to the two pore domain potassium channel (TC
CC 1.A.1.8) family. {ECO:0000305}.
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DR EMBL; AF056492; AAC40181.1; -; mRNA.
DR CCDS; CCDS29511.1; -. [O88454-1]
DR RefSeq; NP_032457.1; NM_008431.3. [O88454-1]
DR RefSeq; XP_006526783.1; XM_006526720.2. [O88454-1]
DR PDB; 6PIS; X-ray; 2.77 A; A/B=1-275.
DR PDBsum; 6PIS; -.
DR AlphaFoldDB; O88454; -.
DR SMR; O88454; -.
DR STRING; 10090.ENSMUSP00000025908; -.
DR TCDB; 1.A.1.9.3; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; O88454; 2 sites.
DR iPTMnet; O88454; -.
DR PhosphoSitePlus; O88454; -.
DR PaxDb; O88454; -.
DR PRIDE; O88454; -.
DR ProteomicsDB; 269271; -. [O88454-1]
DR ProteomicsDB; 269272; -. [O88454-2]
DR ABCD; O88454; 2 sequenced antibodies.
DR Antibodypedia; 29251; 132 antibodies from 27 providers.
DR DNASU; 16528; -.
DR Ensembl; ENSMUST00000025908; ENSMUSP00000025908; ENSMUSG00000024957. [O88454-1]
DR Ensembl; ENSMUST00000237484; ENSMUSP00000157596; ENSMUSG00000024957. [O88454-2]
DR GeneID; 16528; -.
DR KEGG; mmu:16528; -.
DR UCSC; uc008gjj.1; mouse. [O88454-1]
DR CTD; 50801; -.
DR MGI; MGI:1298234; Kcnk4.
DR VEuPathDB; HostDB:ENSMUSG00000024957; -.
DR eggNOG; KOG1418; Eukaryota.
DR GeneTree; ENSGT00940000160310; -.
DR HOGENOM; CLU_022504_1_1_1; -.
DR InParanoid; O88454; -.
DR OMA; ISNHSAW; -.
DR OrthoDB; 616474at2759; -.
DR PhylomeDB; O88454; -.
DR TreeFam; TF313947; -.
DR Reactome; R-MMU-1299503; TWIK related potassium channel (TREK).
DR Reactome; R-MMU-5576886; Phase 4 - resting membrane potential.
DR BioGRID-ORCS; 16528; 1 hit in 69 CRISPR screens.
DR ChiTaRS; Kcnk4; mouse.
DR PRO; PR:O88454; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O88454; protein.
DR Bgee; ENSMUSG00000024957; Expressed in primary visual cortex and 48 other tissues.
DR ExpressionAtlas; O88454; baseline and differential.
DR Genevisible; O88454; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0034705; C:potassium channel complex; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0098782; F:mechanosensitived potassium channel activity; ISS:UniProtKB.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; ISS:UniProtKB.
DR GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
DR GO; GO:0097604; F:temperature-gated cation channel activity; ISS:UniProtKB.
DR GO; GO:0071469; P:cellular response to alkaline pH; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:MGI.
DR GO; GO:0071502; P:cellular response to temperature stimulus; ISS:UniProtKB.
DR GO; GO:0050976; P:detection of mechanical stimulus involved in sensory perception of touch; IMP:UniProtKB.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0050951; P:sensory perception of temperature stimulus; IMP:UniProtKB.
DR GO; GO:0030322; P:stabilization of membrane potential; IBA:GO_Central.
DR InterPro; IPR003280; 2pore_dom_K_chnl.
DR InterPro; IPR008074; 2pore_dom_K_chnl_TRAAK.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR11003; PTHR11003; 1.
DR Pfam; PF07885; Ion_trans_2; 2.
DR PRINTS; PR01333; 2POREKCHANEL.
DR PRINTS; PR01691; TRAAKCHANNEL.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..398
FT /note="Potassium channel subfamily K member 4"
FT /id="PRO_0000101748"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TOPO_DOM 25..88
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT INTRAMEM 89..103
FT /note="Helical; Name=Pore helix 1"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT INTRAMEM 104..110
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TOPO_DOM 111..118
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TRANSMEM 119..151
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TOPO_DOM 152..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TRANSMEM 174..195
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TOPO_DOM 196..200
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT INTRAMEM 201..214
FT /note="Helical; Name=Pore helix 2"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT INTRAMEM 215..220
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TOPO_DOM 221..234
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TRANSMEM 235..261
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT TOPO_DOM 262..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT REGION 104..109
FT /note="Selectivity filter 1"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT REGION 213..218
FT /note="Selectivity filter 2"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT REGION 282..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..320
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9NYG8"
FT VAR_SEQ 63..67
FT /note="KLLVE -> KAMAI (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006690"
FT VAR_SEQ 68..398
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006691"
FT HELIX 3..28
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 34..49
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 55..71
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 91..102
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 115..151
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 155..160
FT /evidence="ECO:0007829|PDB:6PIS"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 168..184
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 186..195
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 200..211
FT /evidence="ECO:0007829|PDB:6PIS"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:6PIS"
FT HELIX 234..257
FT /evidence="ECO:0007829|PDB:6PIS"
SQ SEQUENCE 398 AA; 43052 MW; 478A834B7B7AEC92 CRC64;
MRSTTLLALL ALVLLYLVSG ALVFQALEQP HEQQAQKKMD HGRDQFLRDH PCVSQKSLED
FIKLLVEALG GGANPETSWT NSSNHSSAWN LGSAFFFSGT IITTIGYGNI VLHTDAGRLF
CIFYALVGIP LFGMLLAGVG DRLGSSLRRG IGHIEAIFLK WHVPPGLVRS LSAVLFLLIG
CLLFVLTPTF VFSYMESWSK LEAIYFVIVT LTTVGFGDYV PGDGTGQNSP AYQPLVWFWI
LFGLAYFASV LTTIGNWLRA VSRRTRAEMG GLTAQAASWT GTVTARVTQR TGPSAPPPEK
EQPLLPSSLP APPAVVEPAG RPGSPAPAEK VETPSPPTAS ALDYPSENLA FIDESSDTQS
ERGCALPRAP RGRRRPNPSK KPSRPRGPGR LRDKAVPV
