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O14649

- KCNK3_HUMAN

UniProt

O14649 - KCNK3_HUMAN

Protein

Potassium channel subfamily K member 3

Gene

KCNK3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward.1 Publication

    GO - Molecular functioni

    1. ion channel activity Source: UniProt
    2. open rectifier potassium channel activity Source: Ensembl
    3. potassium channel activity Source: ProtInc
    4. potassium ion leak channel activity Source: UniProtKB
    5. S100 protein binding Source: UniProt

    GO - Biological processi

    1. brain development Source: Ensembl
    2. cellular response to hypoxia Source: Ensembl
    3. cellular response to zinc ion Source: Ensembl
    4. cochlea development Source: Ensembl
    5. ion transmembrane transport Source: UniProt
    6. negative regulation of cytosolic calcium ion concentration Source: Ensembl
    7. potassium ion transport Source: ProtInc
    8. response to drug Source: Ensembl
    9. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel, Potassium channel, Voltage-gated channel

    Keywords - Biological processi

    Ion transport, Potassium transport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_75899. TWIK-releated acid-sensitive K+ channel (TASK).

    Protein family/group databases

    TCDBi1.A.1.9.2. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Potassium channel subfamily K member 3
    Alternative name(s):
    Acid-sensitive potassium channel protein TASK-1
    TWIK-related acid-sensitive K(+) channel 1
    Two pore potassium channel KT3.1
    Short name:
    Two pore K(+) channel KT3.1
    Gene namesi
    Name:KCNK3
    Synonyms:TASK, TASK1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:6278. KCNK3.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. plasma membrane Source: UniProt

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Pulmonary hypertension, primary, 4 (PPH4) [MIM:615344]: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti8 – 81T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
    VAR_070126
    Natural varianti97 – 971G → R in PPH4; loss of function. 1 Publication
    VAR_070127
    Natural varianti182 – 1821E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
    VAR_070128
    Natural varianti192 – 1921Y → C in PPH4; loss of function. 1 Publication
    VAR_070129
    Natural varianti203 – 2031G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
    VAR_070130
    Natural varianti221 – 2211V → L in PPH4; loss of function. 1 Publication
    VAR_070131

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi98 – 981H → N: Greatly reduces pH sensitivity. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi615344. phenotype.
    Orphaneti275777. Heritable pulmonary arterial hypertension.
    275766. Idiopathic pulmonary arterial hypertension.
    PharmGKBiPA30060.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 394394Potassium channel subfamily K member 3PRO_0000101744Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiO14649.
    PRIDEiO14649.

    PTM databases

    PhosphoSiteiO14649.

    Expressioni

    Tissue specificityi

    Widespread expression in adult. Strongest expression in pancreas and placenta. Lower expression in brain, lung, prostate, heart, kidney, uterus, small intestine and colon.

    Gene expression databases

    ArrayExpressiO14649.
    BgeeiO14649.
    CleanExiHS_KCNK3.
    GenevestigatoriO14649.

    Organism-specific databases

    HPAiHPA026658.

    Interactioni

    Protein-protein interaction databases

    BioGridi109978. 3 interactions.
    MINTiMINT-1645466.
    STRINGi9606.ENSP00000306275.

    Structurei

    3D structure databases

    ProteinModelPortaliO14649.
    SMRiO14649. Positions 18-242.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 88CytoplasmicSequence Analysis
    Topological domaini129 – 15830CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini244 – 394151CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei78 – 10124Pore-forming; Name=Pore-forming 1Sequence AnalysisAdd
    BLAST
    Intramembranei184 – 20724Pore-forming; Name=Pore-forming 2Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 2921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei108 – 12821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei159 – 17921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei223 – 24321HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG259548.
    HOGENOMiHOG000231463.
    HOVERGENiHBG052239.
    InParanoidiO14649.
    KOiK04914.
    OMAiCSGTQRS.
    OrthoDBiEOG7B05DC.
    PhylomeDBiO14649.
    TreeFamiTF313947.

    Family and domain databases

    InterProiIPR003280. 2pore_dom_K_chnl.
    IPR013099. 2pore_dom_K_chnl_dom.
    IPR003092. 2pore_dom_K_chnl_TASK.
    IPR005406. KCNK3.
    [Graphical view]
    PfamiPF07885. Ion_trans_2. 2 hits.
    [Graphical view]
    PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
    PRINTSiPR01333. 2POREKCHANEL.
    PR01584. TASK1CHANNEL.
    PR01095. TASKCHANNEL.

    Sequencei

    Sequence statusi: Complete.

    O14649-1 [UniParc]FASTAAdd to Basket

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    MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA    50
    RYNLSQGGYE ELERVVLRLK PHKAGVQWRF AGSFYFAITV ITTIGYGHAA 100
    PSTDGGKVFC MFYALLGIPL TLVMFQSLGE RINTLVRYLL HRAKKGLGMR 150
    RADVSMANMV LIGFFSCIST LCIGAAAFSH YEHWTFFQAY YYCFITLTTI 200
    GFGDYVALQK DQALQTQPQY VAFSFVYILT GLTVIGAFLN LVVLRFMTMN 250
    AEDEKRDAEH RALLTRNGQA GGGGGGGSAH TTDTASSTAA AGGGGFRNVY 300
    AEVLHFQSMC SCLWYKSREK LQYSIPMIIP RDLSTSDTCV EQSHSSPGGG 350
    GRYSDTPSRR CLCSGAPRSA ISSVSTGLHS LSTFRGLMKR RSSV 394
    Length:394
    Mass (Da):43,518
    Last modified:January 1, 1998 - v1
    Checksum:i9FF4C8266F615FB7
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti8 – 81T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
    VAR_070126
    Natural varianti97 – 971G → R in PPH4; loss of function. 1 Publication
    VAR_070127
    Natural varianti182 – 1821E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
    VAR_070128
    Natural varianti192 – 1921Y → C in PPH4; loss of function. 1 Publication
    VAR_070129
    Natural varianti203 – 2031G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
    VAR_070130
    Natural varianti221 – 2211V → L in PPH4; loss of function. 1 Publication
    VAR_070131

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF006823 mRNA. Translation: AAC51777.1.
    AF065163 mRNA. Translation: AAG29340.1.
    AC015977 Genomic DNA. Translation: AAY24312.1.
    CH471053 Genomic DNA. Translation: EAX00678.1.
    CH471053 Genomic DNA. Translation: EAX00679.1.
    CCDSiCCDS1727.1.
    RefSeqiNP_002237.1. NM_002246.2.
    UniGeneiHs.645288.

    Genome annotation databases

    EnsembliENST00000302909; ENSP00000306275; ENSG00000171303.
    GeneIDi3777.
    KEGGihsa:3777.
    UCSCiuc002rhn.2. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF006823 mRNA. Translation: AAC51777.1 .
    AF065163 mRNA. Translation: AAG29340.1 .
    AC015977 Genomic DNA. Translation: AAY24312.1 .
    CH471053 Genomic DNA. Translation: EAX00678.1 .
    CH471053 Genomic DNA. Translation: EAX00679.1 .
    CCDSi CCDS1727.1.
    RefSeqi NP_002237.1. NM_002246.2.
    UniGenei Hs.645288.

    3D structure databases

    ProteinModelPortali O14649.
    SMRi O14649. Positions 18-242.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109978. 3 interactions.
    MINTi MINT-1645466.
    STRINGi 9606.ENSP00000306275.

    Chemistry

    ChEMBLi CHEMBL2321613.
    GuidetoPHARMACOLOGYi 515.

    Protein family/group databases

    TCDBi 1.A.1.9.2. the voltage-gated ion channel (vic) superfamily.

    PTM databases

    PhosphoSitei O14649.

    Proteomic databases

    PaxDbi O14649.
    PRIDEi O14649.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302909 ; ENSP00000306275 ; ENSG00000171303 .
    GeneIDi 3777.
    KEGGi hsa:3777.
    UCSCi uc002rhn.2. human.

    Organism-specific databases

    CTDi 3777.
    GeneCardsi GC02P026827.
    HGNCi HGNC:6278. KCNK3.
    HPAi HPA026658.
    MIMi 603220. gene.
    615344. phenotype.
    neXtProti NX_O14649.
    Orphaneti 275777. Heritable pulmonary arterial hypertension.
    275766. Idiopathic pulmonary arterial hypertension.
    PharmGKBi PA30060.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG259548.
    HOGENOMi HOG000231463.
    HOVERGENi HBG052239.
    InParanoidi O14649.
    KOi K04914.
    OMAi CSGTQRS.
    OrthoDBi EOG7B05DC.
    PhylomeDBi O14649.
    TreeFami TF313947.

    Enzyme and pathway databases

    Reactomei REACT_75899. TWIK-releated acid-sensitive K+ channel (TASK).

    Miscellaneous databases

    GeneWikii KCNK3.
    GenomeRNAii 3777.
    NextBioi 14819.
    PROi O14649.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14649.
    Bgeei O14649.
    CleanExi HS_KCNK3.
    Genevestigatori O14649.

    Family and domain databases

    InterProi IPR003280. 2pore_dom_K_chnl.
    IPR013099. 2pore_dom_K_chnl_dom.
    IPR003092. 2pore_dom_K_chnl_TASK.
    IPR005406. KCNK3.
    [Graphical view ]
    Pfami PF07885. Ion_trans_2. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF038061. K_channel_subfamily_K_type. 1 hit.
    PRINTSi PR01333. 2POREKCHANEL.
    PR01584. TASK1CHANNEL.
    PR01095. TASKCHANNEL.
    ProtoNeti Search...

    Publicationsi

    1. "TASK, a human background K+ channel to sense external pH variations near physiological pH."
      Duprat F., Lesage F., Fink M., Reyes R., Heurteaux C., Lazdunski M.
      EMBO J. 16:5464-5471(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
      Tissue: Kidney.
    2. "Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3."
      Lopes C.M.B., Gallagher P.G., Buck M.E., Butler M.H., Goldstein S.A.N.
      J. Biol. Chem. 275:16969-16978(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Heart.
    3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Inhalational anesthetics activate two-pore-domain background K+ channels."
      Patel A.J., Honore E., Lesage F., Fink M., Romey G., Lazdunski M.
      Nat. Neurosci. 2:422-426(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVATION.
    6. "TASK-5, a novel member of the tandem pore K+ channel family."
      Ashmole I., Goodwin P.A., Stanfield P.R.
      Pflugers Arch. 442:828-833(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF HIS-98.
    7. Cited for: VARIANTS PPH4 LYS-8; ARG-97; LYS-182; CYS-192; ASP-203 AND LEU-221, CHARACTERIZATION OF VARIANTS PPH4 LYS-8; ARG-97; LYS-182; CYS-192; ASP-203 AND LEU-221.

    Entry informationi

    Entry nameiKCNK3_HUMAN
    AccessioniPrimary (citable) accession number: O14649
    Secondary accession number(s): Q53SU2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 125 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Inhibited by external acidification. Activated by halothane and isoflurane.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3