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   24-JAN-2024, entry version 182.
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
CC       (TC 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   GlyCosmos; P57789; 3 sites, No reported glycans.
DR   GlyGen; P57789; 3 sites.
DR   iPTMnet; P57789; -.
DR   PhosphoSitePlus; P57789; -.
DR   BioMuta; KCNK10; -.
DR   DMDM; 13431412; -.
DR   jPOST; P57789; -.
DR   MassIVE; P57789; -.
DR   PaxDb; 9606-ENSP00000312811; -.
DR   PeptideAtlas; P57789; -.
DR   ProteomicsDB; 57038; -. [P57789-1]
DR   ProteomicsDB; 57039; -. [P57789-3]
DR   ProteomicsDB; 57040; -. [P57789-4]
DR   Antibodypedia; 13325; 242 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   AGR; HGNC:6273; -.
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; 600333at2759; -.
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; 9 hits in 1135 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 121 other cell types or tissues.
DR   ExpressionAtlas; P57789; baseline and differential.
DR   GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW.
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:0007165; P:signal transduction; NAS:ProtInc.
DR   GO; GO:0030322; P:stabilization of membrane potential; IBA:GO_Central.
DR   Gene3D; 1.10.287.70; -; 1.
DR   InterPro; IPR003280; 2pore_dom_K_chnl.
DR   InterPro; IPR003976; 2pore_dom_K_chnl_TREK.
DR   InterPro; IPR013099; K_chnl_dom.
DR   PANTHER; PTHR11003:SF32; POTASSIUM CHANNEL SUBFAMILY K MEMBER 10; 1.
DR   PANTHER; PTHR11003; POTASSIUM CHANNEL, SUBFAMILY K; 1.
DR   Pfam; PF07885; Ion_trans_2; 2.
DR   PRINTS; PR01333; 2POREKCHANEL.
DR   PRINTS; PR01499; TREKCHANNEL.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 2.
DR   Genevisible; P57789; HS.
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
//