ID   KCNK9_HUMAN             Reviewed;         374 AA.
AC   Q9NPC2; Q2M290; Q540F2;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 179.
DE   RecName: Full=Potassium channel subfamily K member 9;
DE   AltName: Full=Acid-sensitive potassium channel protein TASK-3;
DE   AltName: Full=TWIK-related acid-sensitive K(+) channel 3;
DE   AltName: Full=Two pore potassium channel KT3.2;
DE            Short=Two pore K(+) channel KT3.2;
GN   Name=KCNK9; Synonyms=TASK3;
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].
RX   PubMed=10747866; DOI=10.1074/jbc.m000030200;
RA   Rajan S., Wischmeyer E., Liu G.X., Preisig-Mueller R., Daut J.,
RA   Karschin A., Derst C.;
RT   "TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An
RT   extracellular histidine as pH sensor.";
RL   J. Biol. Chem. 275:16650-16657(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Cerebellum;
RX   PubMed=11042359; DOI=10.1016/s0169-328x(00)00183-2;
RA   Chapman C.G., Meadows H.J., Godden R.J., Campbell D.A., Duckworth M.,
RA   Kelsell R.E., Murdock P.R., Randall A.D., Rennie G.I., Gloger I.S.;
RT   "Cloning, localisation and functional expression of a novel human,
RT   cerebellum specific, two pore domain potassium channel.";
RL   Brain Res. Mol. Brain Res. 82:74-83(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=11431495; DOI=10.1152/jn.2001.86.1.130;
RA   Vega-Saenz de Miera E., Lau D.H.P., Zhadina M., Pountney D., Coetzee W.A.,
RA   Rudy B.;
RT   "KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to
RT   TASK-1.";
RL   J. Neurophysiol. 86:130-142(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND OVEREXPRESSION IN BREAST CANCERS.
RX   PubMed=12676587; DOI=10.1016/s1535-6108(03)00054-0;
RA   Mu D., Chen L., Zhang X., See L.-H., Koch C.M., Yen C., Tong J.J.,
RA   Spiegel L., Nguyen K.C.Q., Servoss A., Peng Y., Pei L., Marks J.R.,
RA   Lowe S., Hoey T., Jan L.Y., McCombie W.R., Wigler M.H., Powers S.;
RT   "Genomic amplification and oncogenic properties of the KCNK9 potassium
RT   channel gene.";
RL   Cancer Cell 3:297-302(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Girard C., Lesage F., Tinel N., Lazdunski M.;
RT   "Human Task-3, a novel 2P domain potassium channel related to Task.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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).
RN   [7]
RP   INTERACTION WITH KCNK1, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=23169818; DOI=10.1126/scisignal.2003431;
RA   Plant L.D., Zuniga L., Araki D., Marks J.D., Goldstein S.A.;
RT   "SUMOylation silences heterodimeric TASK potassium channels containing K2P1
RT   subunits in cerebellar granule neurons.";
RL   Sci. Signal. 5:RA84-RA84(2012).
RN   [8]
RP   VARIANT BIBARS ARG-236, AND CHARACTERIZATION OF VARIANT BIBARS ARG-236.
RX   PubMed=18678320; DOI=10.1016/j.ajhg.2008.07.010;
RA   Barel O., Shalev S.A., Ofir R., Cohen A., Zlotogora J., Shorer Z.,
RA   Mazor G., Finer G., Khateeb S., Zilberberg N., Birk O.S.;
RT   "Maternally inherited Birk Barel mental retardation dysmorphism syndrome
RT   caused by a mutation in the genomically imprinted potassium channel
RT   KCNK9.";
RL   Am. J. Hum. Genet. 83:193-199(2008).
RN   [9]
RP   VARIANT BIBARS ARG-236.
RX   PubMed=27151206; DOI=10.1002/ajmg.a.37740;
RA   Graham J.M. Jr., Zadeh N., Kelley M., Tan E.S., Liew W., Tan V.,
RA   Deardorff M.A., Wilson G.N., Sagi-Dain L., Shalev S.A.;
RT   "KCNK9 imprinting syndrome-further delineation of a possible treatable
RT   disorder.";
RL   Am. J. Med. Genet. A 170:2632-2637(2016).
RN   [10]
RP   VARIANT BIBARS ASP-237.
RX   PubMed=30690205; DOI=10.1016/j.ejmg.2019.01.009;
RA   Sediva M., Lassuthova P., Zamecnik J., Sedlackova L., Seeman P.,
RA   Haberlova J.;
RT   "Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome.";
RL   Eur. J. Med. Genet. 63:103619-103619(2020).
CC   -!- FUNCTION: pH-dependent, voltage-insensitive, background potassium
CC       channel protein. {ECO:0000269|PubMed:11042359,
CC       ECO:0000269|PubMed:11431495, ECO:0000269|PubMed:23169818}.
CC   -!- SUBUNIT: Homodimer (Probable). Heterodimer with KCNK1.
CC       {ECO:0000269|PubMed:23169818, ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Mainly found in the cerebellum. Also found in
CC       adrenal gland, kidney and lung. {ECO:0000269|PubMed:11042359,
CC       ECO:0000269|PubMed:11431495}.
CC   -!- DISEASE: Birk-Barel syndrome (BIBARS) [MIM:612292]: A syndrome
CC       characterized by intellectual disability, hypotonia, hyperactivity, and
CC       facial dysmorphism. BIBARS transmission pattern is consistent with
CC       autosomal dominant inheritance with paternal imprinting.
CC       {ECO:0000269|PubMed:18678320, ECO:0000269|PubMed:27151206,
CC       ECO:0000269|PubMed:30690205}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: Inhibited by phorbol 12-myristate 13-acetate (PMA).
CC       TASK-3 current is strongly decreased in the presence of an
CC       extracellular pH inferior to 7.0.
CC   -!- MISCELLANEOUS: Overexpressed in a high proportion of breast cancers.
CC       May confer resistance to growth factor deprivation and hypoxia, thereby
CC       promoting tumor cell survival in poorly oxygenated areas of solid
CC       tumors.
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; AF212829; AAF63708.1; -; mRNA.
DR   EMBL; AF248241; AAG31730.1; -; mRNA.
DR   EMBL; AF257080; AAG33126.1; -; mRNA.
DR   EMBL; AY190605; AAO38739.1; -; mRNA.
DR   EMBL; AF279809; AAF85982.1; -; mRNA.
DR   EMBL; BC075079; AAH75079.1; -; mRNA.
DR   EMBL; BC075080; AAH75080.1; -; mRNA.
DR   EMBL; BC112063; AAI12064.1; -; mRNA.
DR   EMBL; BC112065; AAI12066.1; -; mRNA.
DR   CCDS; CCDS6377.1; -.
DR   RefSeq; NP_001269463.1; NM_001282534.1.
DR   RefSeq; XP_011515404.1; XM_011517102.2.
DR   PDB; 3P1N; X-ray; 1.40 A; P=369-374.
DR   PDB; 3P1O; X-ray; 1.90 A; P=369-374.
DR   PDB; 3P1P; X-ray; 1.95 A; P=369-374.
DR   PDB; 3P1Q; X-ray; 1.70 A; P=369-374.
DR   PDB; 3P1R; X-ray; 1.70 A; P=369-374.
DR   PDB; 3P1S; X-ray; 1.65 A; P=369-374.
DR   PDB; 3SMK; X-ray; 2.10 A; P=369-374.
DR   PDB; 3SML; X-ray; 1.90 A; P=370-374.
DR   PDB; 3SMM; X-ray; 2.00 A; P=369-374.
DR   PDB; 3SMN; X-ray; 2.00 A; P=369-374.
DR   PDB; 3SMO; X-ray; 1.80 A; P=369-374.
DR   PDB; 3SP5; X-ray; 1.80 A; P=369-374.
DR   PDB; 3SPR; X-ray; 1.99 A; P=369-374.
DR   PDB; 3UX0; X-ray; 1.75 A; P=369-374.
DR   PDB; 4FR3; X-ray; 1.90 A; P=369-374.
DR   PDB; 6GHP; X-ray; 1.95 A; P=368-374.
DR   PDBsum; 3P1N; -.
DR   PDBsum; 3P1O; -.
DR   PDBsum; 3P1P; -.
DR   PDBsum; 3P1Q; -.
DR   PDBsum; 3P1R; -.
DR   PDBsum; 3P1S; -.
DR   PDBsum; 3SMK; -.
DR   PDBsum; 3SML; -.
DR   PDBsum; 3SMM; -.
DR   PDBsum; 3SMN; -.
DR   PDBsum; 3SMO; -.
DR   PDBsum; 3SP5; -.
DR   PDBsum; 3SPR; -.
DR   PDBsum; 3UX0; -.
DR   PDBsum; 4FR3; -.
DR   PDBsum; 6GHP; -.
DR   AlphaFoldDB; Q9NPC2; -.
DR   SMR; Q9NPC2; -.
DR   BioGRID; 119456; 2.
DR   STRING; 9606.ENSP00000498198; -.
DR   BindingDB; Q9NPC2; -.
DR   ChEMBL; CHEMBL2321614; -.
DR   DrugBank; DB00561; Doxapram.
DR   DrugBank; DB01159; Halothane.
DR   DrugCentral; Q9NPC2; -.
DR   TCDB; 1.A.1.9.11; the voltage-gated ion channel (vic) superfamily.
DR   GlyCosmos; Q9NPC2; 1 site, No reported glycans.
DR   GlyGen; Q9NPC2; 1 site.
DR   iPTMnet; Q9NPC2; -.
DR   PhosphoSitePlus; Q9NPC2; -.
DR   BioMuta; KCNK9; -.
DR   DMDM; 13431426; -.
DR   MassIVE; Q9NPC2; -.
DR   PaxDb; 9606-ENSP00000430676; -.
DR   PeptideAtlas; Q9NPC2; -.
DR   Antibodypedia; 27582; 134 antibodies from 22 providers.
DR   DNASU; 51305; -.
DR   Ensembl; ENST00000303015.2; ENSP00000302166.1; ENSG00000169427.8.
DR   Ensembl; ENST00000520439.3; ENSP00000430676.1; ENSG00000169427.8.
DR   Ensembl; ENST00000522317.5; ENSP00000429847.1; ENSG00000169427.8.
DR   Ensembl; ENST00000648164.1; ENSP00000498198.1; ENSG00000169427.8.
DR   Ensembl; ENST00000650269.1; ENSP00000496915.1; ENSG00000169427.8.
DR   GeneID; 51305; -.
DR   KEGG; hsa:51305; -.
DR   MANE-Select; ENST00000520439.3; ENSP00000430676.1; NM_001282534.2; NP_001269463.1.
DR   UCSC; uc003yvg.3; human.
DR   AGR; HGNC:6283; -.
DR   CTD; 51305; -.
DR   DisGeNET; 51305; -.
DR   GeneCards; KCNK9; -.
DR   GeneReviews; KCNK9; -.
DR   HGNC; HGNC:6283; KCNK9.
DR   HPA; ENSG00000169427; Tissue enriched (brain).
DR   MalaCards; KCNK9; -.
DR   MIM; 605874; gene.
DR   MIM; 612292; phenotype.
DR   neXtProt; NX_Q9NPC2; -.
DR   OpenTargets; ENSG00000169427; -.
DR   Orphanet; 166108; Intellectual disability, Birk-Barel type.
DR   PharmGKB; PA30065; -.
DR   VEuPathDB; HostDB:ENSG00000169427; -.
DR   eggNOG; KOG4404; Eukaryota.
DR   GeneTree; ENSGT00940000159791; -.
DR   HOGENOM; CLU_022504_4_0_1; -.
DR   InParanoid; Q9NPC2; -.
DR   OMA; TAWFGQV; -.
DR   OrthoDB; 600333at2759; -.
DR   PhylomeDB; Q9NPC2; -.
DR   TreeFam; TF313947; -.
DR   PathwayCommons; Q9NPC2; -.
DR   Reactome; R-HSA-1299316; TWIK-releated acid-sensitive K+ channel (TASK).
DR   Reactome; R-HSA-5576886; Phase 4 - resting membrane potential.
DR   SignaLink; Q9NPC2; -.
DR   SIGNOR; Q9NPC2; -.
DR   BioGRID-ORCS; 51305; 13 hits in 1151 CRISPR screens.
DR   EvolutionaryTrace; Q9NPC2; -.
DR   GeneWiki; KCNK9; -.
DR   GenomeRNAi; 51305; -.
DR   Pharos; Q9NPC2; Tclin.
DR   PRO; PR:Q9NPC2; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q9NPC2; Protein.
DR   Bgee; ENSG00000169427; Expressed in cerebellar hemisphere and 111 other cell types or tissues.
DR   ExpressionAtlas; Q9NPC2; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR   GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR   GO; GO:0005267; F:potassium channel activity; IDA:MGI.
DR   GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IDA:MGI.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006813; P:potassium ion transport; NAS:UniProtKB.
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; IPR013099; K_chnl_dom.
DR   InterPro; IPR005407; KCNK9.
DR   PANTHER; PTHR11003:SF75; POTASSIUM CHANNEL SUBFAMILY K MEMBER 9; 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; PR01585; TASK3CHANNEL.
DR   PRINTS; PR01095; TASKCHANNEL.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 2.
DR   Genevisible; Q9NPC2; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disease variant; Glycoprotein;
KW   Intellectual disability; Ion channel; Ion transport; Membrane; Potassium;
KW   Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..374
FT                   /note="Potassium channel subfamily K member 9"
FT                   /id="PRO_0000101754"
FT   TOPO_DOM        1..8
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        9..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        30..88
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        89..101
FT                   /note="Pore-forming; Name=Pore-forming 1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        102..107
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        108..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        129..158
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        159..179
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        180..194
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        195..207
FT                   /note="Pore-forming; Name=Pore-forming 2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        208..218
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        219..239
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        240..374
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        53
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         236
FT                   /note="G -> R (in BIBARS; inactive; dbSNP:rs121908332)"
FT                   /evidence="ECO:0000269|PubMed:18678320,
FT                   ECO:0000269|PubMed:27151206"
FT                   /id="VAR_054373"
FT   VARIANT         237
FT                   /note="A -> D (in BIBARS)"
FT                   /evidence="ECO:0000269|PubMed:30690205"
FT                   /id="VAR_084510"
SQ   SEQUENCE   374 AA;  42264 MW;  8A19EAEE5A4D7F38 CRC64;
     MKRQNVRTLS LIVCTFTYLL VGAAVFDALE SDHEMREEEK LKAEEIRIKG KYNISSEDYR
     QLELVILQSE PHRAGVQWKF AGSFYFAITV ITTIGYGHAA PGTDAGKAFC MFYAVLGIPL
     TLVMFQSLGE RMNTFVRYLL KRIKKCCGMR NTDVSMENMV TVGFFSCMGT LCIGAAAFSQ
     CEEWSFFHAY YYCFITLTTI GFGDYVALQT KGALQKKPLY VAFSFMYILV GLTVIGAFLN
     LVVLRFLTMN SEDERRDAEE RASLAGNRNS MVIHIPEEPR PSRPRYKADV PDLQSVCSCT
     CYRSQDYGGR SVAPQNSFSA KLAPHYFHSI SYKIEEISPS TLKNSLFPSP ISSISPGLHS
     FTDHQRLMKR RKSV
//