KCNKA_HUMAN
ID KCNKA_HUMAN Reviewed; 538 AA.
AC P57789; B2R8T4; B2RCT3; B5TJL4; Q6B014; Q8TDK7; Q8TDK8; Q9HB59;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Potassium channel subfamily K member 10;
DE AltName: Full=Outward rectifying potassium channel protein TREK-2;
DE AltName: Full=TREK-2 K(+) channel subunit;
GN Name=KCNK10; Synonyms=TREK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=10880510; DOI=10.1074/jbc.m002822200;
RA Lesage F., Terrenoire C., Romey G., Lazdunski M.;
RT "Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple
RT regulations by polyunsaturated fatty acids, lysophospholipids and Gs, Gi,
RT and Gq protein-coupled receptors.";
RL J. Biol. Chem. 275:28398-28405(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C).
RX PubMed=11897838; DOI=10.1113/jphysiol.2001.013432;
RA Gu W., Schlichthorl G., Hirsch J.R., Engels H., Karschin C., Karschin A.,
RA Derst C., Steinlein O.K., Daut J.;
RT "Expression pattern and functional characteristics of two novel splice
RT variants of the two-pore-domain potassium channel TREK-2.";
RL J. Physiol. (Lond.) 539:657-668(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C).
RC TISSUE=Brain, Kidney, and Pancreas;
RX PubMed=18516069; DOI=10.1038/bjp.2008.213;
RA Gierten J., Ficker E., Bloehs R., Schlomer K., Kathofer S., Scholz E.,
RA Zitron E., Kiesecker C., Bauer A., Becker R., Katus H.A., Karle C.A.,
RA Thomas D.;
RT "Regulation of two-pore-domain (K2P) potassium leak channels by the
RT tyrosine kinase inhibitor genistein.";
RL Br. J. Pharmacol. 154:1680-1690(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C), AND VARIANT
RP THR-512.
RC TISSUE=Brain, and Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Outward rectifying potassium channel. Produces rapidly
CC activating and non-inactivating outward rectifier K(+) currents.
CC Activated by arachidonic acid and other naturally occurring unsaturated
CC free fatty acids.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A; Synonyms=TREK-2a;
CC IsoId=P57789-1; Sequence=Displayed;
CC Name=B; Synonyms=TREK-2b;
CC IsoId=P57789-4; Sequence=VSP_006697;
CC Name=C; Synonyms=TREK-2c;
CC IsoId=P57789-3; Sequence=VSP_006698;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in pancreas and kidney and to
CC a lower level in brain, testis, colon, and small intestine. Isoform b
CC is strongly expressed in kidney (primarily in the proximal tubule) and
CC pancreas, whereas isoform c is abundantly expressed in brain.
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; AF279890; AAG15191.1; -; mRNA.
DR EMBL; AF385399; AAL95705.1; -; mRNA.
DR EMBL; AF385400; AAL95706.1; -; mRNA.
DR EMBL; EU978938; ACH86097.1; -; mRNA.
DR EMBL; EU978939; ACH86098.1; -; mRNA.
DR EMBL; EU978940; ACH86099.1; -; mRNA.
DR EMBL; EU978941; ACH86100.1; -; mRNA.
DR EMBL; AK313499; BAG36281.1; -; mRNA.
DR EMBL; AK315263; BAG37680.1; -; mRNA.
DR EMBL; AL049834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133279; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81373.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81374.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81375.1; -; Genomic_DNA.
DR EMBL; BC075021; AAH75021.1; -; mRNA.
DR EMBL; BC075022; AAH75022.1; -; mRNA.
DR CCDS; CCDS9880.1; -. [P57789-1]
DR CCDS; CCDS9881.1; -. [P57789-3]
DR CCDS; CCDS9882.1; -. [P57789-4]
DR RefSeq; NP_066984.1; NM_021161.4. [P57789-1]
DR RefSeq; NP_612190.1; NM_138317.2. [P57789-3]
DR RefSeq; NP_612191.1; NM_138318.2. [P57789-4]
DR PDB; 4BW5; X-ray; 3.20 A; A/B/C/D=62-335.
DR PDB; 4XDJ; X-ray; 3.80 A; A/B/C/D=62-335.
DR PDB; 4XDK; X-ray; 3.60 A; A/B/C/D=62-335.
DR PDB; 4XDL; X-ray; 3.50 A; A/B/C/D=62-335.
DR PDBsum; 4BW5; -.
DR PDBsum; 4XDJ; -.
DR PDBsum; 4XDK; -.
DR PDBsum; 4XDL; -.
DR AlphaFoldDB; P57789; -.
DR SMR; P57789; -.
DR BioGRID; 119924; 1.
DR DIP; DIP-44050N; -.
DR IntAct; P57789; 1.
DR STRING; 9606.ENSP00000312811; -.
DR BindingDB; P57789; -.
DR ChEMBL; CHEMBL2331041; -.
DR DrugCentral; P57789; -.
DR GuidetoPHARMACOLOGY; 521; -.
DR GlyGen; P57789; 3 sites.
DR iPTMnet; P57789; -.
DR PhosphoSitePlus; P57789; -.
DR BioMuta; KCNK10; -.
DR DMDM; 13431412; -.
DR jPOST; P57789; -.
DR PaxDb; P57789; -.
DR PeptideAtlas; P57789; -.
DR PRIDE; P57789; -.
DR ProteomicsDB; 57038; -. [P57789-1]
DR ProteomicsDB; 57039; -. [P57789-3]
DR ProteomicsDB; 57040; -. [P57789-4]
DR Antibodypedia; 13325; 214 antibodies from 26 providers.
DR DNASU; 54207; -.
DR Ensembl; ENST00000312350.9; ENSP00000310568.5; ENSG00000100433.16. [P57789-4]
DR Ensembl; ENST00000319231.10; ENSP00000312811.5; ENSG00000100433.16. [P57789-3]
DR Ensembl; ENST00000340700.9; ENSP00000343104.5; ENSG00000100433.16. [P57789-1]
DR GeneID; 54207; -.
DR KEGG; hsa:54207; -.
DR MANE-Select; ENST00000319231.10; ENSP00000312811.5; NM_138317.3; NP_612190.1. [P57789-3]
DR UCSC; uc001xwm.4; human. [P57789-1]
DR CTD; 54207; -.
DR DisGeNET; 54207; -.
DR GeneCards; KCNK10; -.
DR HGNC; HGNC:6273; KCNK10.
DR HPA; ENSG00000100433; Tissue enhanced (brain, intestine, stomach).
DR MIM; 605873; gene.
DR neXtProt; NX_P57789; -.
DR OpenTargets; ENSG00000100433; -.
DR PharmGKB; PA30053; -.
DR VEuPathDB; HostDB:ENSG00000100433; -.
DR eggNOG; KOG1418; Eukaryota.
DR GeneTree; ENSGT00940000156147; -.
DR HOGENOM; CLU_022504_10_0_1; -.
DR InParanoid; P57789; -.
DR OMA; MNWYKPL; -.
DR OrthoDB; 616474at2759; -.
DR PhylomeDB; P57789; -.
DR TreeFam; TF313947; -.
DR PathwayCommons; P57789; -.
DR Reactome; R-HSA-1299503; TWIK related potassium channel (TREK).
DR Reactome; R-HSA-5576886; Phase 4 - resting membrane potential.
DR SignaLink; P57789; -.
DR BioGRID-ORCS; 54207; 7 hits in 1057 CRISPR screens.
DR ChiTaRS; KCNK10; human.
DR GeneWiki; KCNK10; -.
DR GenomeRNAi; 54207; -.
DR Pharos; P57789; Tclin.
DR PRO; PR:P57789; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P57789; protein.
DR Bgee; ENSG00000100433; Expressed in cerebellar vermis and 120 other tissues.
DR ExpressionAtlas; P57789; baseline and differential.
DR Genevisible; P57789; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; TAS:ProtInc.
DR GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0030322; P:stabilization of membrane potential; IBA:GO_Central.
DR InterPro; IPR003280; 2pore_dom_K_chnl.
DR InterPro; IPR003976; 2pore_dom_K_chnl_TREK.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR11003; PTHR11003; 1.
DR Pfam; PF07885; Ion_trans_2; 2.
DR PRINTS; PR01333; 2POREKCHANEL.
DR PRINTS; PR01499; TREKCHANNEL.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..538
FT /note="Potassium channel subfamily K member 10"
FT /id="PRO_0000101758"
FT TOPO_DOM 1..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 154..180
FT /note="Pore-forming; Name=Pore-forming 1"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 263..294
FT /note="Pore-forming; Name=Pore-forming 2"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 412..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 510..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..538
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..12
FT /note="MFFLYTDFFLSL -> MEDGFKGDRTEGCRSDS (in isoform B)"
FT /evidence="ECO:0000303|PubMed:11897838,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:18516069"
FT /id="VSP_006697"
FT VAR_SEQ 1..12
FT /note="MFFLYTDFFLSL -> MKFPIETPRKQVNWDPK (in isoform C)"
FT /evidence="ECO:0000303|PubMed:11897838,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:18516069"
FT /id="VSP_006698"
FT VARIANT 70
FT /note="K -> Q (in dbSNP:rs398263)"
FT /id="VAR_060216"
FT VARIANT 512
FT /note="A -> T (in dbSNP:rs17762463)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_052428"
FT CONFLICT 529
FT /note="E -> G (in Ref. 2; AAL95705/AAL95706)"
FT /evidence="ECO:0000305"
FT HELIX 69..115
FT /evidence="ECO:0007829|PDB:4BW5"
FT HELIX 121..136
FT /evidence="ECO:0007829|PDB:4BW5"
FT TURN 145..148
FT /evidence="ECO:0007829|PDB:4XDL"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:4BW5"
FT HELIX 154..165
FT /evidence="ECO:0007829|PDB:4BW5"
FT HELIX 178..222
FT /evidence="ECO:0007829|PDB:4BW5"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:4XDL"
FT HELIX 232..247
FT /evidence="ECO:0007829|PDB:4BW5"
FT HELIX 249..258
FT /evidence="ECO:0007829|PDB:4BW5"
FT HELIX 263..274
FT /evidence="ECO:0007829|PDB:4BW5"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:4BW5"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4XDL"
FT HELIX 296..325
FT /evidence="ECO:0007829|PDB:4BW5"
SQ SEQUENCE 538 AA; 59765 MW; 8EA615B08D147FBC CRC64;
MFFLYTDFFL SLVAVPAAAP VCQPKSATNG QPPAPAPTPT PRLSISSRAT VVARMEGTSQ
GGLQTVMKWK TVVAIFVVVV VYLVTGGLVF RALEQPFESS QKNTIALEKA EFLRDHVCVS
PQELETLIQH ALDADNAGVS PIGNSSNNSS HWDLGSAFFF AGTVITTIGY GNIAPSTEGG
KIFCILYAIF GIPLFGFLLA GIGDQLGTIF GKSIARVEKV FRKKQVSQTK IRVISTILFI
LAGCIVFVTI PAVIFKYIEG WTALESIYFV VVTLTTVGFG DFVAGGNAGI NYREWYKPLV
WFWILVGLAY FAAVLSMIGD WLRVLSKKTK EEVGEIKAHA AEWKANVTAE FRETRRRLSV
EIHDKLQRAA TIRSMERRRL GLDQRAHSLD MLSPEKRSVF AALDTGRFKA SSQESINNRP
NNLRLKGPEQ LNKHGQGASE DNIINKFGST SRLTKRKNKD LKKTLPEDVQ KIYKTFRNYS
LDEEKKEEET EKMCNSDNSS TAMLTDCIQQ HAELENGMIP TDTKDREPEN NSLLEDRN
