ID   KCNK6_HUMAN             Reviewed;         313 AA.
AC   Q9Y257; Q9HB47;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=Potassium channel subfamily K member 6;
DE   AltName: Full=Inward rectifying potassium channel protein TWIK-2;
DE   AltName: Full=TWIK-originated similarity sequence;
GN   Name=KCNK6; Synonyms=TOSS, TWIK2;
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 1).
RC   TISSUE=Testis;
RX   PubMed=10359073; DOI=10.1016/s0014-5793(99)00495-0;
RA   Pountney D.J., Gulkarov I., Vega-Saenz de Miera E., Holmes D., Saganich M.,
RA   Rudy B., Artman M., Coetzee W.A.;
RT   "Identification and cloning of TWIK-originated similarity sequence (TOSS):
RT   a novel human 2-pore K+ channel principal subunit.";
RL   FEBS Lett. 450:191-196(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF CYS-53.
RC   TISSUE=Brain;
RX   PubMed=10075682; DOI=10.1074/jbc.274.12.7887;
RA   Chavez R.A., Gray A.T., Zhao B.B., Kindler C.H., Mazurek M.J., Mehta Y.,
RA   Forsayeth J.R., Yost C.S.;
RT   "TWIK-2, a new weak inward rectifying member of the tandem pore domain
RT   potassium channel family.";
RL   J. Biol. Chem. 274:7887-7892(1999).
RN   [3]
RP   ERRATUM OF PUBMED:10075682.
RA   Chavez R.A., Gray A.T., Zhao B.B., Kindler C.H., Mazurek M.J., Mehta Y.,
RA   Forsayeth J.R., Yost C.S.;
RL   J. Biol. Chem. 274:24440-24440(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND CHARACTERIZATION.
RX   PubMed=10887187; DOI=10.1074/jbc.m003755200;
RA   Patel A.J., Maingret F., Magnone V., Fosset M., Lazdunski M., Honore E.;
RT   "TWIK-2, an inactivating 2P domain K+ channel.";
RL   J. Biol. Chem. 275:28722-28730(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE (ISOFORM 1).
RA   Chen A.F., Gray A.T., Chen A.H., Kindler C.H., Mhatre A.N., Yost C.S.,
RA   Lalwani A.K., Smith R.J.H.;
RT   "Genomic structure and mutation screening of the TWIK-2 gene.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Pancreas;
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: Exhibits outward rectification in a physiological K(+)
CC       gradient and mild inward rectification in symmetrical K(+) conditions.
CC   -!- SUBUNIT: Homodimer. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9Y257-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y257-2; Sequence=VSP_006692;
CC   -!- TISSUE SPECIFICITY: Widespread expression, detected in all tissues
CC       tested except for skeletal muscle. Strongest expression in placenta,
CC       pancreas, heart, colon and spleen, lower levels detected in peripheral
CC       blood leukocytes, lung, liver, kidney and thymus. Lowest expression
CC       detected in brain.
CC   -!- MISCELLANEOUS: Inhibited by internal acidification and, to a small
CC       degree, by zinc. Not inhibited by quinine, quinidine or barium.
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; AF134149; AAD22980.1; -; mRNA.
DR   EMBL; AF117708; AAD24000.1; -; mRNA.
DR   EMBL; AF281302; AAG10506.1; -; mRNA.
DR   EMBL; AF281303; AAG10507.1; -; mRNA.
DR   EMBL; AJ297404; CAC15489.1; -; Genomic_DNA.
DR   EMBL; AJ297405; CAC15489.1; JOINED; Genomic_DNA.
DR   EMBL; BC004367; AAH04367.1; -; mRNA.
DR   CCDS; CCDS12513.1; -. [Q9Y257-1]
DR   RefSeq; NP_004814.1; NM_004823.1. [Q9Y257-1]
DR   RefSeq; XP_011525828.1; XM_011527526.1.
DR   AlphaFoldDB; Q9Y257; -.
DR   SMR; Q9Y257; -.
DR   STRING; 9606.ENSP00000263372; -.
DR   DrugBank; DB00308; Ibutilide.
DR   DrugBank; DB00908; Quinidine.
DR   TCDB; 1.A.1.8.3; the voltage-gated ion channel (vic) superfamily.
DR   GlyCosmos; Q9Y257; 2 sites, No reported glycans.
DR   GlyGen; Q9Y257; 2 sites.
DR   iPTMnet; Q9Y257; -.
DR   PhosphoSitePlus; Q9Y257; -.
DR   BioMuta; KCNK6; -.
DR   DMDM; 13124108; -.
DR   jPOST; Q9Y257; -.
DR   MassIVE; Q9Y257; -.
DR   PaxDb; 9606-ENSP00000263372; -.
DR   PeptideAtlas; Q9Y257; -.
DR   ProteomicsDB; 85659; -. [Q9Y257-1]
DR   Antibodypedia; 30028; 132 antibodies from 25 providers.
DR   DNASU; 9424; -.
DR   Ensembl; ENST00000263372.5; ENSP00000263372.2; ENSG00000099337.5. [Q9Y257-1]
DR   GeneID; 9424; -.
DR   KEGG; hsa:9424; -.
DR   MANE-Select; ENST00000263372.5; ENSP00000263372.2; NM_004823.3; NP_004814.1.
DR   UCSC; uc002oic.4; human. [Q9Y257-1]
DR   AGR; HGNC:6281; -.
DR   CTD; 9424; -.
DR   DisGeNET; 9424; -.
DR   GeneCards; KCNK6; -.
DR   HGNC; HGNC:6281; KCNK6.
DR   HPA; ENSG00000099337; Low tissue specificity.
DR   MIM; 603939; gene.
DR   neXtProt; NX_Q9Y257; -.
DR   OpenTargets; ENSG00000099337; -.
DR   PharmGKB; PA30063; -.
DR   VEuPathDB; HostDB:ENSG00000099337; -.
DR   eggNOG; KOG1418; Eukaryota.
DR   GeneTree; ENSGT00940000160509; -.
DR   HOGENOM; CLU_022504_6_0_1; -.
DR   InParanoid; Q9Y257; -.
DR   OMA; IERPMED; -.
DR   OrthoDB; 600333at2759; -.
DR   PhylomeDB; Q9Y257; -.
DR   TreeFam; TF313947; -.
DR   PathwayCommons; Q9Y257; -.
DR   Reactome; R-HSA-1299308; Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK).
DR   Reactome; R-HSA-5576886; Phase 4 - resting membrane potential.
DR   BioGRID-ORCS; 9424; 7 hits in 1071 CRISPR screens.
DR   ChiTaRS; KCNK6; human.
DR   GeneWiki; KCNK6; -.
DR   GenomeRNAi; 9424; -.
DR   Pharos; Q9Y257; Tbio.
DR   PRO; PR:Q9Y257; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9Y257; Protein.
DR   Bgee; ENSG00000099337; Expressed in lower esophagus mucosa and 139 other cell types or tissues.
DR   ExpressionAtlas; Q9Y257; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; TAS:ProtInc.
DR   GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR   GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
DR   GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IEA:Ensembl.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR   GO; GO:0060075; P:regulation of resting membrane potential; IEA:Ensembl.
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; IPR003092; 2pore_dom_K_chnl_TASK.
DR   InterPro; IPR005408; 2pore_dom_K_chnl_TWIK.
DR   InterPro; IPR005409; 2pore_dom_K_chnl_TWIK2.
DR   InterPro; IPR013099; K_chnl_dom.
DR   PANTHER; PTHR11003:SF28; POTASSIUM CHANNEL SUBFAMILY K MEMBER 6; 1.
DR   PANTHER; PTHR11003; POTASSIUM CHANNEL, SUBFAMILY K; 1.
DR   Pfam; PF07885; Ion_trans_2; 2.
DR   PIRSF; PIRSF038061; K_channel_subfamily_K_type; 1.
DR   PRINTS; PR01333; 2POREKCHANEL.
DR   PRINTS; PR01587; TWIK2CHANNEL.
DR   PRINTS; PR01586; TWIKCHANNEL.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 2.
DR   Genevisible; Q9Y257; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Glycoprotein; Ion channel; Ion transport; Membrane;
KW   Potassium; Potassium channel; Potassium transport; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..313
FT                   /note="Potassium channel subfamily K member 6"
FT                   /id="PRO_0000101750"
FT   TOPO_DOM        1..4
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        5..25
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        90..115
FT                   /note="Pore-forming; Name=Pore-forming 1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        121..141
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        142..172
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        173..193
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        199..223
FT                   /note="Pore-forming; Name=Pore-forming 2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        236..256
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        257..313
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          288..313
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        294..313
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        85
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..134
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10887187"
FT                   /id="VSP_006692"
FT   VARIANT         150
FT                   /note="T -> I (in dbSNP:rs35762773)"
FT                   /id="VAR_052426"
FT   VARIANT         240
FT                   /note="V -> I (in dbSNP:rs35496032)"
FT                   /id="VAR_059842"
FT   VARIANT         259
FT                   /note="V -> M (in dbSNP:rs34989303)"
FT                   /id="VAR_052427"
FT   MUTAGEN         53
FT                   /note="C->A: No channel activity."
FT                   /evidence="ECO:0000269|PubMed:10075682"
SQ   SEQUENCE   313 AA;  33747 MW;  1379382DFB0575DE CRC64;
     MRRGALLAGA LAAYAAYLVL GALLVARLEG PHEARLRAEL ETLRAQLLQR SPCVAAPALD
     AFVERVLAAG RLGRVVLANA SGSANASDPA WDFASALFFA STLITTVGYG YTTPLTDAGK
     AFSIAFALLG VPTTMLLLTA SAQRLSLLLT HVPLSWLSMR WGWDPRRAAC WHLVALLGVV
     VTVCFLVPAV IFAHLEEAWS FLDAFYFCFI SLSTIGLGDY VPGEAPGQPY RALYKVLVTV
     YLFLGLVAMV LVLQTFRHVS DLHGLTELIL LPPPCPASFN ADEDDRVDIL GPQPESHQQL
     SASSHTDYAS IPR
//