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Potassium channel subfamily K member 4 (TWIK-related arachidonic acid-stimulated potassium channel protein) (TRAAK)

 KCNK4_RAT               Reviewed;         397 AA.
G3V8V5; Q924I4;
01-APR-2015, integrated into UniProtKB/Swiss-Prot.
16-NOV-2011, sequence version 1.
08-MAY-2019, entry version 56.
RecName: Full=Potassium channel subfamily K member 4;
AltName: Full=TWIK-related arachidonic acid-stimulated potassium channel protein;
Short=TRAAK;
Name=Kcnk4 {ECO:0000312|RGD:621449};
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116 {ECO:0000312|Proteomes:UP000002494};
[1] {ECO:0000312|EMBL:AAK60504.2}
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
LOCATION, AND TISSUE SPECIFICITY.
STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAK60504.2};
PubMed=11374070; DOI=10.1007/s004240000496;
Kim Y., Bang H., Gnatenco C., Kim D.;
"Synergistic interaction and the role of C-terminus in the activation
of TRAAK K+ channels by pressure, free fatty acids and alkali.";
Pflugers Arch. 442:64-72(2001).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Brown Norway;
PubMed=15057822; DOI=10.1038/nature02426;
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T.,
Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A.,
Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M.,
Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K.,
Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S.,
Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J.,
Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y.,
Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A.,
Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J.,
D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R.,
Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A.,
Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E.,
Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E.,
Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D.,
Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M.,
Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O.,
Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O.,
Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H.,
Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S.,
Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J.,
Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E.,
Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F.,
Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K.,
Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S.,
Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M.,
Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M.,
Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A.,
Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S.,
Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G.,
Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H.,
Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R.,
Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M.,
Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H.,
Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S.,
Collins F.S.;
"Genome sequence of the Brown Norway rat yields insights into
mammalian evolution.";
Nature 428:493-521(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Brown Norway;
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[4]
FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
PubMed=15677687; DOI=10.1113/jphysiol.2004.081059;
Kang D., Choe C., Kim D.;
"Thermosensitivity of the two-pore domain K+ channels TREK-2 and
TRAAK.";
J. Physiol. (Lond.) 564:103-116(2005).
-!- FUNCTION: Voltage-insensitive potassium channel (PubMed:11374070,
PubMed:15677687). Channel opening is triggered by mechanical
forces that deform the membrane, and by raising the intracellular
pH to basic levels (PubMed:11374070, PubMed:15677687). The channel
is inactive at 24 degrees Celsius (in vitro); raising the
temperature to 37 degrees Celsius increases the frequency of
channel opening, with a further increase in channel activity when
the temperature is raised to 42 degrees Celsius (PubMed:15677687).
Plays a role in the perception of pain caused by heat (By
similarity). Plays a role in the sensory perception of pain caused
by pressure (By similarity). {ECO:0000250|UniProtKB:O88454,
ECO:0000269|PubMed:11374070, ECO:0000269|PubMed:15677687}.
-!- ACTIVITY REGULATION: Activated by arachidonic acid.
{ECO:0000269|PubMed:11374070, ECO:0000269|PubMed:15677687}.
-!- SUBUNIT: Homodimer; disulfide-linked.
{ECO:0000250|UniProtKB:Q9NYG8}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11374070};
Multi-pass membrane protein {ECO:0000305}.
-!- TISSUE SPECIFICITY: Detected in brain, and at much lower levels in
liver, skeletal muscle and testis. {ECO:0000269|PubMed:11374070}.
-!- DOMAIN: Channel opening is brought about by a conformation change
that involves buckling of the second transmembrane helix and
affects the position and orientation of the fourth transmembrane
helix. {ECO:0000250|UniProtKB:Q9NYG8}.
-!- SIMILARITY: Belongs to the two pore domain potassium channel (TC
1.A.1.8) family. {ECO:0000255|RuleBase:RU003857}.
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EMBL; AF302842; AAK60504.2; -; mRNA.
EMBL; AABR06009566; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH473953; EDM12628.1; -; Genomic_DNA.
RefSeq; NP_446256.2; NM_053804.2.
RefSeq; XP_008758276.1; XM_008760054.2.
RefSeq; XP_008758277.1; XM_008760055.2.
RefSeq; XP_008758278.1; XM_008760056.2.
SMR; G3V8V5; -.
STRING; 10116.ENSRNOP00000028704; -.
PaxDb; G3V8V5; -.
PRIDE; G3V8V5; -.
Ensembl; ENSRNOT00000028704; ENSRNOP00000028704; ENSRNOG00000021140.
GeneID; 116489; -.
KEGG; rno:116489; -.
CTD; 50801; -.
RGD; 621449; Kcnk4.
eggNOG; KOG1418; Eukaryota.
eggNOG; COG1226; LUCA.
GeneTree; ENSGT00940000160310; -.
HOGENOM; HOG000013106; -.
InParanoid; G3V8V5; -.
KO; K04915; -.
OMA; GWSKLEA; -.
OrthoDB; 616474at2759; -.
PhylomeDB; G3V8V5; -.
TreeFam; TF313947; -.
Reactome; R-RNO-1299503; TWIK related potassium channel (TREK).
Reactome; R-RNO-5576886; Phase 4 - resting membrane potential.
PRO; PR:G3V8V5; -.
Proteomes; UP000002494; Chromosome 1.
Bgee; ENSRNOG00000021140; Expressed in 8 organ(s), highest expression level in brain.
Genevisible; G3V8V5; RN.
GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
GO; GO:0034705; C:potassium channel complex; IEA:Ensembl.
GO; GO:0098782; F:mechanosensitived potassium channel activity; IDA:UniProtKB.
GO; GO:0005267; F:potassium channel activity; IDA:UniProtKB.
GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
GO; GO:0097604; F:temperature-gated cation channel activity; IDA:UniProtKB.
GO; GO:0071469; P:cellular response to alkaline pH; IDA:UniProtKB.
GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
GO; GO:0071502; P:cellular response to temperature stimulus; IDA:UniProtKB.
GO; GO:0050976; P:detection of mechanical stimulus involved in sensory perception of touch; ISS:UniProtKB.
GO; GO:0007613; P:memory; IEP:RGD.
GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
GO; GO:0050951; P:sensory perception of temperature stimulus; ISS:UniProtKB.
GO; GO:0030322; P:stabilization of membrane potential; IBA:GO_Central.
InterPro; IPR003280; 2pore_dom_K_chnl.
InterPro; IPR008074; 2pore_dom_K_chnl_TRAAK.
InterPro; IPR013099; K_chnl_dom.
Pfam; PF07885; Ion_trans_2; 2.
PRINTS; PR01333; 2POREKCHANEL.
PRINTS; PR01691; TRAAKCHANNEL.
2: Evidence at transcript level;
Cell membrane; Complete proteome; Disulfide bond; Glycoprotein;
Ion channel; Ion transport; Membrane; Potassium; Potassium channel;
Potassium transport; Reference proteome; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 397 Potassium channel subfamily K member 4.
/FTId=PRO_0000432591.
TOPO_DOM 1 3 Cytoplasmic.
{ECO:0000250|UniProtKB:Q9NYG8}.
TRANSMEM 4 24 Helical. {ECO:0000250|UniProtKB:Q9NYG8}.
TOPO_DOM 25 88 Extracellular.
{ECO:0000250|UniProtKB:Q9NYG8}.
INTRAMEM 89 103 Helical; Name=Pore helix 1.
{ECO:0000250|UniProtKB:Q9NYG8}.
INTRAMEM 104 110 {ECO:0000250|UniProtKB:Q9NYG8}.
TOPO_DOM 111 118 Extracellular.
{ECO:0000250|UniProtKB:Q9NYG8}.
TRANSMEM 119 151 Helical. {ECO:0000250|UniProtKB:Q9NYG8}.
TOPO_DOM 152 173 Cytoplasmic.
{ECO:0000250|UniProtKB:Q9NYG8}.
TRANSMEM 174 195 Helical. {ECO:0000250|UniProtKB:Q9NYG8}.
TOPO_DOM 196 200 Extracellular.
{ECO:0000250|UniProtKB:Q9NYG8}.
INTRAMEM 201 214 Helical; Name=Pore helix 2.
{ECO:0000250|UniProtKB:Q9NYG8}.
INTRAMEM 215 220 {ECO:0000250|UniProtKB:Q9NYG8}.
TOPO_DOM 221 234 Extracellular.
{ECO:0000250|UniProtKB:Q9NYG8}.
TRANSMEM 235 261 Helical. {ECO:0000250|UniProtKB:Q9NYG8}.
TOPO_DOM 262 397 Cytoplasmic.
{ECO:0000250|UniProtKB:Q9NYG8}.
REGION 104 109 Selectivity filter 1.
{ECO:0000250|UniProtKB:Q9NYG8}.
REGION 213 218 Selectivity filter 2.
{ECO:0000250|UniProtKB:Q9NYG8}.
COMPBIAS 293 336 Pro-rich. {ECO:0000255|PROSITE-
ProRule:PRU00015}.
CARBOHYD 81 81 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 52 52 Interchain.
{ECO:0000250|UniProtKB:Q9NYG8}.
CONFLICT 25 25 Q -> Y (in Ref. 1; AAK60504).
{ECO:0000305}.
CONFLICT 196 196 E -> K (in Ref. 1; AAK60504).
{ECO:0000305}.
CONFLICT 202 202 E -> K (in Ref. 1; AAK60504).
{ECO:0000305}.
CONFLICT 251 251 L -> F (in Ref. 1; AAK60504).
{ECO:0000305}.
SEQUENCE 397 AA; 42920 MW; 5369F0841EE72831 CRC64;
MRSTTLLALL ALVLLYLVSG ALVFQALEQP HEQQVQKDLE DGRDQFLKDH PCVSQKNLEG
FIKLVAEALG GGANPETSWT NSSNHSSAWN LGSAFFFSGT IITTIGYGNI ALHTDAGRLF
CIFYALVGIP LFGMLLAGVG DRLGSSLRRG IGHIEAVFLK WHVPPGLVRM LSAVLFLLIG
CLLFVLTPTF VFSYMESWSK LEAIYFVIVT LTTVGFGDYV PGDGTGQNSP AYQPLVWFWI
LFGLAYFASV LTTIGNWLRA VSRRTRAEMG GLTAQAASWT GTVTARVTQR TGPSAPPPEK
EQPLLPSSLP APPAVAEPAH RPGSPAPAEK VETPPPTASA LDYPSENLAF IDESSDTQSE
RGCALPRAPR GRRRPNPTKK PSRPRGPGRL RDKAVPV


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WP1893: Pyruvate metabolism and Citric Acid (TCA) cycle
WP368: Mitochondrial LC-Fatty Acid Beta-Oxidation
WP891: amino acid conjugation of benzoic acid
WP1075: Folic Acid Network

Related Genes :
[KCNK18 TRESK TRIK] Potassium channel subfamily K member 18 (TWIK-related individual potassium channel) (TWIK-related spinal cord potassium channel)
[KCNK1 HOHO1 KCNO1 TWIK1] Potassium channel subfamily K member 1 (Inward rectifying potassium channel protein TWIK-1) (Potassium channel K2P1) (Potassium channel KCNO1)
[Kcnk1] Potassium channel subfamily K member 1 (Inward rectifying potassium channel protein TWIK-1) (rTWIK) (Potassium channel K2P1)
[KCNK6 TOSS TWIK2] Potassium channel subfamily K member 6 (Inward rectifying potassium channel protein TWIK-2) (TWIK-originated similarity sequence)
[KCNK5 TASK2] Potassium channel subfamily K member 5 (Acid-sensitive potassium channel protein TASK-2) (TWIK-related acid-sensitive K(+) channel 2)
[Kcnk1] Potassium channel subfamily K member 1 (Inward rectifying potassium channel protein TWIK-1)
[Kcnk3 Ctbak Task Task1] Potassium channel subfamily K member 3 (Acid-sensitive potassium channel protein TASK-1) (Cardiac two pore background K(+) channel) (TWIK-related acid-sensitive K(+) channel 1) (Two pore potassium channel KT3.1) (Two pore K(+) channel KT3.1) (cTBAK-1)
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[Kcnc2] Potassium voltage-gated channel subfamily C member 2 (Potassium channel voltage-gated Shaw-related subfamily C member 2) (Shaw-like potassium channel) (Voltage-gated potassium channel subunit Kv3.2)
[KCNA4 KCNA4L] Potassium voltage-gated channel subfamily A member 4 (HPCN2) (Voltage-gated K(+) channel HuKII) (Voltage-gated potassium channel HBK4) (Voltage-gated potassium channel HK1) (Voltage-gated potassium channel subunit Kv1.4)
[KCNH2 ERG ERG1 HERG] Potassium voltage-gated channel subfamily H member 2 (Eag homolog) (Ether-a-go-go-related gene potassium channel 1) (ERG-1) (Eag-related protein 1) (Ether-a-go-go-related protein 1) (H-ERG) (hERG-1) (hERG1) (Voltage-gated potassium channel subunit Kv11.1)
[Kcnh2 Erg Merg1] Potassium voltage-gated channel subfamily H member 2 (Ether-a-go-go-related gene potassium channel 1) (ERG-1) (Eag-related protein 1) (Ether-a-go-go-related protein 1) (MERG) (Voltage-gated potassium channel subunit Kv11.1)
[Kcne2] Potassium voltage-gated channel subfamily E member 2 (MinK-related peptide 1) (Minimum potassium ion channel-related peptide 1) (Potassium channel subunit beta MiRP1)
[Kcnd2] Potassium voltage-gated channel subfamily D member 2 (RK5) (Shal1) (Voltage-gated potassium channel subunit Kv4.2)
[Kcnd2 Kiaa1044 MNCb-7013] Potassium voltage-gated channel subfamily D member 2 (Voltage-gated potassium channel subunit Kv4.2)
[KCNK1] Potassium channel subfamily K member 1 (Inward rectifying potassium channel protein TWIK-1)
[Kcnb1] Potassium voltage-gated channel subfamily B member 1 (Delayed rectifier potassium channel 1) (DRK1) (Voltage-gated potassium channel subunit Kv2.1)
[Kcnh2 Erg] Potassium voltage-gated channel subfamily H member 2 (Ether-a-go-go-related gene potassium channel 1) (ERG-1) (Eag-related protein 1) (Ether-a-go-go-related protein 1) (RERG) (r-ERG) (Voltage-gated potassium channel subunit Kv11.1)
[Kcnh7 Erg3] Potassium voltage-gated channel subfamily H member 7 (Ether-a-go-go-related gene potassium channel 3) (ERG-3) (Eag-related protein 3) (Ether-a-go-go-related protein 3) (Voltage-gated potassium channel subunit Kv11.3)
[KCNA2] Potassium voltage-gated channel subfamily A member 2 (NGK1) (Voltage-gated K(+) channel HuKIV) (Voltage-gated potassium channel HBK5) (Voltage-gated potassium channel subunit Kv1.2)
[KCNE2] Potassium voltage-gated channel subfamily E member 2 (MinK-related peptide 1) (Minimum potassium ion channel-related peptide 1) (Potassium channel subunit beta MiRP1)
[KCNA1] Potassium voltage-gated channel subfamily A member 1 (Voltage-gated K(+) channel HuKI) (Voltage-gated potassium channel HBK1) (Voltage-gated potassium channel subunit Kv1.1)
[Kcne2] Potassium voltage-gated channel subfamily E member 2 (MinK-related peptide 1) (Minimum potassium ion channel-related peptide 1) (Potassium channel subunit beta MiRP1)
[KCND2 KIAA1044] Potassium voltage-gated channel subfamily D member 2 (Voltage-gated potassium channel subunit Kv4.2)
[Kcna4] Potassium voltage-gated channel subfamily A member 4 (Voltage-gated potassium channel subunit Kv1.4)
[Kcnh6 Erg2] Potassium voltage-gated channel subfamily H member 6 (Ether-a-go-go-related gene potassium channel 2) (ERG-2) (Eag-related protein 2) (Ether-a-go-go-related protein 2) (Voltage-gated potassium channel subunit Kv11.2)
[KCNC1] Potassium voltage-gated channel subfamily C member 1 (NGK2) (Voltage-gated potassium channel subunit Kv3.1) (Voltage-gated potassium channel subunit Kv4)
[Kcnu1 Kcnma3 Ksper Slo3] Potassium channel subfamily U member 1 (Calcium-activated potassium channel subunit alpha-3) (Calcium-activated potassium channel, subfamily M subunit alpha-3) (Pore-forming subunit of the sperm-specific alkalization activated K(+) current) (KSper) (Slowpoke homolog 3) (mSlo3) (pH-sensitive maxi potassium channel)
[KCNQ1 KCNA8 KCNA9 KVLQT1] Potassium voltage-gated channel subfamily KQT member 1 (IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1) (KQT-like 1) (Voltage-gated potassium channel subunit Kv7.1)
[KCNJ5 GIRK4] G protein-activated inward rectifier potassium channel 4 (GIRK-4) (Cardiac inward rectifier) (CIR) (Heart KATP channel) (Inward rectifier K(+) channel Kir3.4) (IRK-4) (KATP-1) (Potassium channel, inwardly rectifying subfamily J member 5)

Bibliography :
[30290154] Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome.