KCNK6_HUMAN
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 03-AUG-2022, entry version 179.
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 (TC
CC 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 GlyGen; Q9Y257; 2 sites.
DR iPTMnet; Q9Y257; -.
DR PhosphoSitePlus; Q9Y257; -.
DR BioMuta; KCNK6; -.
DR DMDM; 13124108; -.
DR jPOST; Q9Y257; -.
DR MassIVE; Q9Y257; -.
DR PaxDb; Q9Y257; -.
DR PeptideAtlas; Q9Y257; -.
DR PRIDE; Q9Y257; -.
DR ProteomicsDB; 85659; -. [Q9Y257-1]
DR Antibodypedia; 30028; 110 antibodies from 24 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 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; SATSNWD; -.
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 1021 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 137 other tissues.
DR ExpressionAtlas; Q9Y257; baseline and differential.
DR Genevisible; Q9Y257; 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: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:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
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 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; PTHR11003; 1.
DR PANTHER; PTHR11003:SF28; PTHR11003:SF28; 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.
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
