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O15554

- KCNN4_HUMAN

UniProt

O15554 - KCNN4_HUMAN

Protein

Intermediate conductance calcium-activated potassium channel protein 4

Gene

KCNN4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Forms a voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin.2 Publications

    GO - Molecular functioni

    1. calcium-activated potassium channel activity Source: BHF-UCL
    2. calmodulin binding Source: RefGenome
    3. Intermediate conductance calcium-activated potassium channel activity Source: RefGenome
    4. protein binding Source: UniProtKB
    5. protein phosphatase binding Source: BHF-UCL

    GO - Biological processi

    1. calcium ion transport Source: BHF-UCL
    2. cell volume homeostasis Source: Ensembl
    3. defense response Source: ProtInc
    4. immune system process Source: UniProtKB-KW
    5. phospholipid translocation Source: Ensembl
    6. positive regulation of protein secretion Source: Ensembl
    7. positive regulation of T cell receptor signaling pathway Source: BHF-UCL
    8. potassium ion export Source: Ensembl
    9. potassium ion transmembrane transport Source: RefGenome
    10. potassium ion transport Source: ProtInc
    11. saliva secretion Source: Ensembl
    12. stabilization of membrane potential Source: BHF-UCL
    13. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel

    Keywords - Biological processi

    Immunity, Ion transport, Transport

    Keywords - Ligandi

    Calmodulin-binding

    Enzyme and pathway databases

    ReactomeiREACT_75896. Ca2+ activated K+ channels.

    Protein family/group databases

    TCDBi1.A.1.16.2. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Intermediate conductance calcium-activated potassium channel protein 4
    Short name:
    SK4
    Short name:
    SKCa 4
    Short name:
    SKCa4
    Alternative name(s):
    IKCa1
    Short name:
    IK1
    KCa3.1
    KCa4
    Putative Gardos channel
    Gene namesi
    Name:KCNN4
    Synonyms:IK1, IKCA1, KCA4, SK4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:6293. KCNN4.

    Subcellular locationi

    GO - Cellular componenti

    1. apical plasma membrane Source: Ensembl
    2. basolateral plasma membrane Source: Ensembl
    3. membrane raft Source: Ensembl
    4. neuronal cell body Source: RefGenome
    5. plasma membrane Source: RefGenome
    6. voltage-gated potassium channel complex Source: BHF-UCL

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi250 – 2501T → S: Loss of sensitivity to triarylmethanes. 1 Publication
    Mutagenesisi275 – 2751V → A: Loss of sensitivity to triarylmethanes. 1 Publication

    Organism-specific databases

    PharmGKBiPA222.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 427427Intermediate conductance calcium-activated potassium channel protein 4PRO_0000155017Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei358 – 3581Phosphohistidine1 Publication

    Post-translational modificationi

    Phosphorylation at His-358 by NDKB activates the channel, and conversely it's dephosphorylation by PHPT1 inhibits the channel.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO15554.
    PaxDbiO15554.
    PRIDEiO15554.

    PTM databases

    PhosphoSiteiO15554.

    Expressioni

    Tissue specificityi

    Widely expressed in non-excitable tissues.

    Inductioni

    Up-regulated by phorbol myristate acetate (PMA) and phytohemagglutinin (PHA) in T-cells.

    Gene expression databases

    ArrayExpressiO15554.
    BgeeiO15554.
    CleanExiHS_KCNN4.
    GenevestigatoriO15554.

    Organism-specific databases

    HPAiHPA053841.
    HPA059622.

    Interactioni

    Subunit structurei

    Heterotetramer of potassium channel proteins Probable. Interacts with MTMR6.2 PublicationsCurated

    Protein-protein interaction databases

    BioGridi109984. 6 interactions.
    DIPiDIP-48598N.
    IntActiO15554. 1 interaction.
    STRINGi9606.ENSP00000262888.

    Structurei

    3D structure databases

    ProteinModelPortaliO15554.
    SMRiO15554. Positions 207-373.
    ModBaseiSearch...
    MobiDBiSearch...

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei241 – 26121Pore-forming; Name=Segment H5Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei29 – 4921Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei59 – 7921Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei108 – 12821Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei143 – 16321Helical; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei207 – 22721Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei265 – 28521Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni286 – 34762Calmodulin-bindingAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG323309.
    HOGENOMiHOG000276908.
    HOVERGENiHBG052241.
    InParanoidiO15554.
    KOiK04945.
    OMAiKCMISIS.
    PhylomeDBiO15554.
    TreeFamiTF315015.

    Family and domain databases

    InterProiIPR013099. 2pore_dom_K_chnl_dom.
    IPR004178. CaM-bd_dom.
    IPR015449. K_chnl_Ca-activ_SK.
    [Graphical view]
    PANTHERiPTHR10153. PTHR10153. 1 hit.
    PfamiPF02888. CaMBD. 1 hit.
    PF07885. Ion_trans_2. 1 hit.
    PF03530. SK_channel. 1 hit.
    [Graphical view]
    SMARTiSM01053. CaMBD. 1 hit.
    [Graphical view]
    SUPFAMiSSF81327. SSF81327. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    O15554-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGGDLVLGLG ALRRRKRLLE QEKSLAGWAL VLAGTGIGLM VLHAEMLWFG    50
    GCSWALYLFL VKCTISISTF LLLCLIVAFH AKEVQLFMTD NGLRDWRVAL 100
    TGRQAAQIVL ELVVCGLHPA PVRGPPCVQD LGAPLTSPQP WPGFLGQGEA 150
    LLSLAMLLRL YLVPRAVLLR SGVLLNASYR SIGALNQVRF RHWFVAKLYM 200
    NTHPGRLLLG LTLGLWLTTA WVLSVAERQA VNATGHLSDT LWLIPITFLT 250
    IGYGDVVPGT MWGKIVCLCT GVMGVCCTAL LVAVVARKLE FNKAEKHVHN 300
    FMMDIQYTKE MKESAARVLQ EAWMFYKHTR RKESHAARRH QRKLLAAINA 350
    FRQVRLKHRK LREQVNSMVD ISKMHMILYD LQQNLSSSHR ALEKQIDTLA 400
    GKLDALTELL STALGPRQLP EPSQQSK 427
    Length:427
    Mass (Da):47,696
    Last modified:January 1, 1998 - v1
    Checksum:i23F9AF66609B410F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti66 – 661S → G in AAK81862. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF000972 mRNA. Translation: AAB82739.1.
    AF022150 mRNA. Translation: AAC23541.1.
    AF022797 mRNA. Translation: AAC51913.1.
    AF033021 mRNA. Translation: AAC36804.1.
    AF305735
    , AF305731, AF305732, AF305733, AF305734 Genomic DNA. Translation: AAG26917.1.
    AF395661 mRNA. Translation: AAK81862.1.
    BT007426 mRNA. Translation: AAP36094.1.
    CH471126 Genomic DNA. Translation: EAW57230.1.
    BC015337 mRNA. Translation: AAH15337.1.
    AF053403 mRNA. Translation: AAC35281.1.
    CCDSiCCDS12630.1.
    RefSeqiNP_002241.1. NM_002250.2.
    UniGeneiHs.10082.

    Genome annotation databases

    EnsembliENST00000262888; ENSP00000262888; ENSG00000104783.
    GeneIDi3783.
    KEGGihsa:3783.
    UCSCiuc002oxl.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF000972 mRNA. Translation: AAB82739.1 .
    AF022150 mRNA. Translation: AAC23541.1 .
    AF022797 mRNA. Translation: AAC51913.1 .
    AF033021 mRNA. Translation: AAC36804.1 .
    AF305735
    , AF305731 , AF305732 , AF305733 , AF305734 Genomic DNA. Translation: AAG26917.1 .
    AF395661 mRNA. Translation: AAK81862.1 .
    BT007426 mRNA. Translation: AAP36094.1 .
    CH471126 Genomic DNA. Translation: EAW57230.1 .
    BC015337 mRNA. Translation: AAH15337.1 .
    AF053403 mRNA. Translation: AAC35281.1 .
    CCDSi CCDS12630.1.
    RefSeqi NP_002241.1. NM_002250.2.
    UniGenei Hs.10082.

    3D structure databases

    ProteinModelPortali O15554.
    SMRi O15554. Positions 207-373.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109984. 6 interactions.
    DIPi DIP-48598N.
    IntActi O15554. 1 interaction.
    STRINGi 9606.ENSP00000262888.

    Chemistry

    BindingDBi O15554.
    ChEMBLi CHEMBL4305.
    DrugBanki DB00257. Clotrimazole.
    DB01159. Halothane.
    DB00468. Quinine.
    GuidetoPHARMACOLOGYi 384.

    Protein family/group databases

    TCDBi 1.A.1.16.2. the voltage-gated ion channel (vic) superfamily.

    PTM databases

    PhosphoSitei O15554.

    Proteomic databases

    MaxQBi O15554.
    PaxDbi O15554.
    PRIDEi O15554.

    Protocols and materials databases

    DNASUi 3783.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000262888 ; ENSP00000262888 ; ENSG00000104783 .
    GeneIDi 3783.
    KEGGi hsa:3783.
    UCSCi uc002oxl.3. human.

    Organism-specific databases

    CTDi 3783.
    GeneCardsi GC19M044270.
    HGNCi HGNC:6293. KCNN4.
    HPAi HPA053841.
    HPA059622.
    MIMi 602754. gene.
    neXtProti NX_O15554.
    PharmGKBi PA222.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG323309.
    HOGENOMi HOG000276908.
    HOVERGENi HBG052241.
    InParanoidi O15554.
    KOi K04945.
    OMAi KCMISIS.
    PhylomeDBi O15554.
    TreeFami TF315015.

    Enzyme and pathway databases

    Reactomei REACT_75896. Ca2+ activated K+ channels.

    Miscellaneous databases

    GeneWikii KCNN4.
    GenomeRNAii 3783.
    NextBioi 14849.
    PROi O15554.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15554.
    Bgeei O15554.
    CleanExi HS_KCNN4.
    Genevestigatori O15554.

    Family and domain databases

    InterProi IPR013099. 2pore_dom_K_chnl_dom.
    IPR004178. CaM-bd_dom.
    IPR015449. K_chnl_Ca-activ_SK.
    [Graphical view ]
    PANTHERi PTHR10153. PTHR10153. 1 hit.
    Pfami PF02888. CaMBD. 1 hit.
    PF07885. Ion_trans_2. 1 hit.
    PF03530. SK_channel. 1 hit.
    [Graphical view ]
    SMARTi SM01053. CaMBD. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81327. SSF81327. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "hSK4, a member of a novel subfamily of calcium-activated potassium channels."
      Joiner W.J., Wang L.-Y., Tang M.D., Kaczmarek L.K.
      Proc. Natl. Acad. Sci. U.S.A. 94:11013-11018(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Pancreas.
    3. "A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes."
      Logsdon N.J., Kang J., Togo J.A., Christian E.P., Aiyar J.
      J. Biol. Chem. 272:32723-32726(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lymph node.
    4. "Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia."
      Ghanshani S., Coleman M., Gustavsson P., Wu A.C., Gargus J.J., Gutman G.A., Dahl N., Mohrenweiser H., Chandy K.G.
      Genomics 51:160-161(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences."
      Ghanshani S., Wulff H., Miller M.J., Rohm H., Neben A., Gutman G.A., Cahalan M.D., Chandy K.G.
      J. Biol. Chem. 275:37137-37149(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "Characterization of calcium-activated potassium channels in human myometrium."
      Mazzone J.N., Kaiser R.A., Buxton I.L.O.
      Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Myometrium.
    7. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Prostate.
    10. "hIK1 (putative Gardos channel) PCR product amplified from the K562 human erythroleukemic cell line."
      Golding S., Culliford S.J., Ellory J.C.
      Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 227-367.
    11. "Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1."
      Fanger C.M., Ghanshani S., Logsdon N.J., Rauer H., Kalman K., Zhou J., Beckingham K., Chandy K.G., Cahalan M.D., Aiyar J.
      J. Biol. Chem. 274:5746-5754(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CALMODULIN.
    12. "Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1."
      Wulff H., Gutman G.A., Cahalan M.D., Chandy K.G.
      J. Biol. Chem. 276:32040-32045(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF THR-250 AND VAL-275.
    13. "The phosphatidylinositol 3-phosphate phosphatase myotubularin-related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1."
      Srivastava S., Li Z., Lin L., Liu G., Ko K., Coetzee W.A., Skolnik E.Y.
      Mol. Cell. Biol. 25:3630-3638(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MTMR6.
    14. "Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells."
      Srivastava S., Li Z., Ko K., Choudhury P., Albaqumi M., Johnson A.K., Yan Y., Backer J.M., Unutmaz D., Coetzee W.A., Skolnik E.Y.
      Mol. Cell 24:665-675(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT HIS-358.
    15. "Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1."
      Srivastava S., Zhdanova O., Di L., Li Z., Albaqumi M., Wulff H., Skolnik E.Y.
      Proc. Natl. Acad. Sci. U.S.A. 105:14442-14446(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INHIBITIVE DEPHOSPHORYLATION BY PTHP1.
    16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiKCNN4_HUMAN
    AccessioniPrimary (citable) accession number: O15554
    Secondary accession number(s): Q53XR4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 16, 2001
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 132 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3