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Q86W47

- KCMB4_HUMAN

UniProt

Q86W47 - KCMB4_HUMAN

Protein

Calcium-activated potassium channel subunit beta-4

Gene

KCNMB4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 2 (01 Mar 2004)
      Previous versions | rss
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    Functioni

    Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.3 Publications

    GO - Molecular functioni

    1. calcium-activated potassium channel activity Source: UniProtKB
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. action potential Source: UniProtKB
    2. blood coagulation Source: Reactome
    3. detection of calcium ion Source: UniProtKB
    4. neuronal action potential Source: UniProtKB
    5. potassium ion transmembrane transport Source: GOC
    6. potassium ion transport Source: UniProtKB
    7. regulation of neurotransmitter secretion Source: UniProtKB
    8. regulation of vasoconstriction Source: UniProtKB
    9. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel

    Keywords - Biological processi

    Ion transport, Transport

    Enzyme and pathway databases

    ReactomeiREACT_23767. cGMP effects.
    REACT_75896. Ca2+ activated K+ channels.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Calcium-activated potassium channel subunit beta-4
    Alternative name(s):
    BK channel subunit beta-4
    Short name:
    BKbeta4
    Short name:
    Hbeta4
    Calcium-activated potassium channel, subfamily M subunit beta-4
    Charybdotoxin receptor subunit beta-4
    K(VCA)beta-4
    Maxi K channel subunit beta-4
    Slo-beta-4
    Gene namesi
    Name:KCNMB4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:6289. KCNMB4.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: UniProtKB
    2. plasma membrane Source: Reactome
    3. voltage-gated potassium channel complex Source: UniProtKB

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi11 – 111T → A: Suppresses the effect of okadaic acid and increases activation time constant; when associated with A-17 and A-210. 1 Publication
    Mutagenesisi11 – 111T → D: Suppresses its effect on KCNMA1 channel activation and on deactivation kinetics; when associated with E-17 and E-210. 1 Publication
    Mutagenesisi17 – 171S → A: Suppresses the effect of okadaic acid and increases activation time constant; when associated with A-11 and A-210. 1 Publication
    Mutagenesisi17 – 171S → E: Suppresses its effect on KCNMA1 channel activation and on deactivation kinetics; when associated with D-11 and E-210. 1 Publication
    Mutagenesisi53 – 531N → A: Loss of N-glycosylation and reduced protection against charybdotoxin; when associated with A-90. 1 Publication
    Mutagenesisi90 – 901N → A: Loss of N-glycosylation and reduced protection against charybdotoxin; when associated with A-53. 1 Publication
    Mutagenesisi210 – 2101S → A: Suppresses the effect of okadaic acid and increases activation time constant; when associated with A-11 and A-17. 1 Publication
    Mutagenesisi210 – 2101S → E: Suppresses its effect on KCNMA1 channel activation and on deactivation kinetics; when associated with D-11 and E-17. 1 Publication

    Organism-specific databases

    PharmGKBiPA30069.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 210210Calcium-activated potassium channel subunit beta-4PRO_0000187055Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi53 – 531N-linked (GlcNAc...)
    Glycosylationi90 – 901N-linked (GlcNAc...)

    Post-translational modificationi

    Phosphorylated. Phosphorylation modulates its effect on KCNMA1 activation kinetics.1 Publication
    N-glycosylated. A highly glycosylated form is promoted by KCNMA1. Glycosylation, which is not required for the interaction with KCNMA1 and subcellular location, increases protection against charybdotoxin.2 Publications

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ86W47.
    PRIDEiQ86W47.

    PTM databases

    PhosphoSiteiQ86W47.

    Expressioni

    Tissue specificityi

    Predominantly expressed in brain. In brain, it is expressed in the cerebellum, cerebral cortex, medulla, spinal cord, occipital pole, frontal lobe, temporal lobe, putamen, amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra and thalamus. Weakly or not expressed in other tissues.2 Publications

    Gene expression databases

    BgeeiQ86W47.
    CleanExiHS_KCNMB4.
    GenevestigatoriQ86W47.

    Interactioni

    Subunit structurei

    Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB4 per KCNMA1 tetramer.2 Publications

    Protein-protein interaction databases

    STRINGi9606.ENSP00000258111.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86W47.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1919CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini41 – 167127ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini189 – 21022CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei20 – 4021Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei168 – 18821Helical; Name=2Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domaini

    Resistance to charybdotoxin (CTX) toxin is mediated by the extracellular domain.

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG83271.
    HOGENOMiHOG000113205.
    HOVERGENiHBG052224.
    InParanoidiQ86W47.
    KOiK04941.
    OMAiHEAPRKE.
    OrthoDBiEOG77WWDC.
    PhylomeDBiQ86W47.
    TreeFamiTF328589.

    Family and domain databases

    InterProiIPR003930. K_chnl_Ca-activ_BK_bsu.
    [Graphical view]
    PANTHERiPTHR10258. PTHR10258. 1 hit.
    PfamiPF03185. CaKB. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q86W47-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAKLRVAYEY TEAEDKSIRL GLFLIISGVV SLFIFGFCWL SPALQDLQAT    50
    EANCTVLSVQ QIGEVFECTF TCGADCRGTS QYPCVQVYVN NSESNSRALL 100
    HSDEHQLLTN PKCSYIPPCK RENQKNLESV MNWQQYWKDE IGSQPFTCYF 150
    NQHQRPDDVL LHRTHDEIVL LHCFLWPLVT FVVGVLIVVL TICAKSLAVK 200
    AEAMKKRKFS 210
    Length:210
    Mass (Da):23,949
    Last modified:March 1, 2004 - v2
    Checksum:iA59D56DD034F027A
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti199 – 1991V → I.1 Publication
    VAR_018178

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF160967 mRNA. Translation: AAF69805.1.
    AF170917 mRNA. Translation: AAF89699.1.
    AF207992 mRNA. Translation: AAF28333.1.
    AF215891 mRNA. Translation: AAF75596.1.
    BC042446 mRNA. Translation: AAH42446.2.
    BC050621 mRNA. Translation: AAH50621.2.
    CCDSiCCDS8997.1.
    RefSeqiNP_055320.4. NM_014505.5.
    UniGeneiHs.525529.

    Genome annotation databases

    EnsembliENST00000258111; ENSP00000258111; ENSG00000135643.
    GeneIDi27345.
    KEGGihsa:27345.
    UCSCiuc001svx.3. human.

    Polymorphism databases

    DMDMi46395791.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF160967 mRNA. Translation: AAF69805.1 .
    AF170917 mRNA. Translation: AAF89699.1 .
    AF207992 mRNA. Translation: AAF28333.1 .
    AF215891 mRNA. Translation: AAF75596.1 .
    BC042446 mRNA. Translation: AAH42446.2 .
    BC050621 mRNA. Translation: AAH50621.2 .
    CCDSi CCDS8997.1.
    RefSeqi NP_055320.4. NM_014505.5.
    UniGenei Hs.525529.

    3D structure databases

    ProteinModelPortali Q86W47.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000258111.

    PTM databases

    PhosphoSitei Q86W47.

    Polymorphism databases

    DMDMi 46395791.

    Proteomic databases

    PaxDbi Q86W47.
    PRIDEi Q86W47.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000258111 ; ENSP00000258111 ; ENSG00000135643 .
    GeneIDi 27345.
    KEGGi hsa:27345.
    UCSCi uc001svx.3. human.

    Organism-specific databases

    CTDi 27345.
    GeneCardsi GC12P070760.
    HGNCi HGNC:6289. KCNMB4.
    MIMi 605223. gene.
    neXtProti NX_Q86W47.
    PharmGKBi PA30069.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG83271.
    HOGENOMi HOG000113205.
    HOVERGENi HBG052224.
    InParanoidi Q86W47.
    KOi K04941.
    OMAi HEAPRKE.
    OrthoDBi EOG77WWDC.
    PhylomeDBi Q86W47.
    TreeFami TF328589.

    Enzyme and pathway databases

    Reactomei REACT_23767. cGMP effects.
    REACT_75896. Ca2+ activated K+ channels.

    Miscellaneous databases

    ChiTaRSi KCNMB4. human.
    GeneWikii KCNMB4.
    GenomeRNAii 27345.
    NextBioi 50430.
    PROi Q86W47.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q86W47.
    CleanExi HS_KCNMB4.
    Genevestigatori Q86W47.

    Family and domain databases

    InterProi IPR003930. K_chnl_Ca-activ_BK_bsu.
    [Graphical view ]
    PANTHERi PTHR10258. PTHR10258. 1 hit.
    Pfami PF03185. CaKB. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin."
      Meera P., Wallner M., Toro L.
      Proc. Natl. Acad. Sci. U.S.A. 97:5562-5567(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, GLYCOSYLATION, VARIANT ILE-199.
    2. "hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family."
      Behrens R., Nolting A., Reimann F., Schwarz M., Waldschuetz R., Pongs O.
      FEBS Lett. 474:99-106(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    3. "Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4."
      Brenner R., Jegla T.J., Wickenden A., Liu Y., Aldrich R.W.
      J. Biol. Chem. 275:6453-6461(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH KCNMA1, TISSUE SPECIFICITY.
    4. "A novel nervous system beta subunit that downregulates human large conductance calcium-dependent potassium channels."
      Weiger T.M., Holmqvist M.H., Levitan I.B., Clark F.T., Sprague S., Huang W.-J., Ge P., Wang C., Lawson D., Jurman M.E., Glucksmann M.A., Silos-Santiago I., DiStefano P.S., Curtis R.
      J. Neurosci. 20:3563-3570(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH KCNMA1.
      Tissue: CNS.
    5. "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: Eye and Lymph.
    6. "Phosphorylation-dependent functional coupling of hSlo calcium-dependent potassium channel and its hbeta 4 subunit."
      Jin P., Weiger T.M., Wu Y., Levitan I.B.
      J. Biol. Chem. 277:10014-10020(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, MUTAGENESIS OF THR-11; SER-17 AND SER-210.
    7. "Reciprocal modulation between the alpha and beta 4 subunits of hSlo calcium-dependent potassium channels."
      Jin P., Weiger T.M., Levitan I.B.
      J. Biol. Chem. 277:43724-43729(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION, MUTAGENESIS OF ASN-53 AND ASN-90.
    8. "New disguises for an old channel: MaxiK channel beta-subunits."
      Orio P., Rojas P., Ferreira G., Latorre R.
      News Physiol. Sci. 17:156-161(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiKCMB4_HUMAN
    AccessioniPrimary (citable) accession number: Q86W47
    Secondary accession number(s): Q8IVR3, Q9NPA4, Q9P0G5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 13, 2004
    Last sequence update: March 1, 2004
    Last modified: October 1, 2014
    This is version 94 of the entry and version 2 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

    Treatment with okadaic acid reduces its effect on KCNMA1.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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