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Protein

Calcium-activated potassium channel subunit beta-4

Gene

KCNMB4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. potassium channel regulator activity Source: GO_Central

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
Complete GO annotation...

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 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6289. KCNMB4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1919CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei20 – 4021Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini41 – 167127ExtracellularSequence AnalysisAdd
BLAST
Transmembranei168 – 18821Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini189 – 21022CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

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.

Chemistry

DrugBankiDB01110. Miconazole.
DB00721. Procaine.

Polymorphism and mutation databases

BioMutaiKCNMB4.
DMDMi46395791.

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...

Family & Domainsi

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG83271.
GeneTreeiENSGT00390000015997.
HOGENOMiHOG000113205.
HOVERGENiHBG052224.
InParanoidiQ86W47.
KOiK04941.
OMAiYVPPCER.
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

        10         20         30         40         50
MAKLRVAYEY TEAEDKSIRL GLFLIISGVV SLFIFGFCWL SPALQDLQAT
60 70 80 90 100
EANCTVLSVQ QIGEVFECTF TCGADCRGTS QYPCVQVYVN NSESNSRALL
110 120 130 140 150
HSDEHQLLTN PKCSYIPPCK RENQKNLESV MNWQQYWKDE IGSQPFTCYF
160 170 180 190 200
NQHQRPDDVL LHRTHDEIVL LHCFLWPLVT FVVGVLIVVL TICAKSLAVK
210
AEAMKKRKFS
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:
EMBLi
GenBanki
DDBJi
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 and mutation databases

BioMutaiKCNMB4.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ86W47.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000258111.

Chemistry

DrugBankiDB01110. Miconazole.
DB00721. Procaine.

PTM databases

PhosphoSiteiQ86W47.

Polymorphism and mutation databases

BioMutaiKCNMB4.
DMDMi46395791.

Proteomic databases

PaxDbiQ86W47.
PRIDEiQ86W47.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi27345.
GeneCardsiGC12P070760.
HGNCiHGNC:6289. KCNMB4.
MIMi605223. gene.
neXtProtiNX_Q86W47.
PharmGKBiPA30069.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG83271.
GeneTreeiENSGT00390000015997.
HOGENOMiHOG000113205.
HOVERGENiHBG052224.
InParanoidiQ86W47.
KOiK04941.
OMAiYVPPCER.
OrthoDBiEOG77WWDC.
PhylomeDBiQ86W47.
TreeFamiTF328589.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiKCNMB4. human.
GeneWikiiKCNMB4.
GenomeRNAii27345.
NextBioi50430.
PROiQ86W47.
SOURCEiSearch...

Gene expression databases

BgeeiQ86W47.
CleanExiHS_KCNMB4.
GenevestigatoriQ86W47.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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: April 29, 2015
This is version 98 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.