KCMB4_HUMAN
ID KCMB4_HUMAN Reviewed; 210 AA.
AC Q86W47; Q8IVR3; Q9NPA4; Q9P0G5;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Calcium-activated potassium channel subunit beta-4;
DE AltName: Full=BK channel subunit beta-4;
DE Short=BKbeta4;
DE Short=Hbeta4;
DE AltName: Full=Calcium-activated potassium channel, subfamily M subunit beta-4;
DE AltName: Full=Charybdotoxin receptor subunit beta-4;
DE AltName: Full=K(VCA)beta-4;
DE AltName: Full=Maxi K channel subunit beta-4;
DE AltName: Full=Slo-beta-4;
GN Name=KCNMB4;
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], FUNCTION, GLYCOSYLATION, AND VARIANT ILE-199.
RX PubMed=10792058; DOI=10.1073/pnas.100118597;
RA Meera P., Wallner M., Toro L.;
RT "A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and
RT Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5562-5567(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10828459; DOI=10.1016/s0014-5793(00)01584-2;
RA Behrens R., Nolting A., Reimann F., Schwarz M., Waldschuetz R., Pongs O.;
RT "hKCNMB3 and hKCNMB4, cloning and characterization of two members of the
RT large-conductance calcium-activated potassium channel beta subunit
RT family.";
RL FEBS Lett. 474:99-106(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH KCNMA1, AND TISSUE
RP SPECIFICITY.
RX PubMed=10692449; DOI=10.1074/jbc.275.9.6453;
RA Brenner R., Jegla T.J., Wickenden A., Liu Y., Aldrich R.W.;
RT "Cloning and functional characterization of novel large conductance
RT calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.";
RL J. Biol. Chem. 275:6453-6461(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH KCNMA1.
RC TISSUE=CNS;
RX PubMed=10804197; DOI=10.1523/jneurosci.20-10-03563.2000;
RA Weiger T.M., Holmqvist M.H., Levitan I.B., Clark F.T., Sprague S.,
RA Huang W.-J., Ge P., Wang C., Lawson D., Jurman M.E., Glucksmann M.A.,
RA Silos-Santiago I., DiStefano P.S., Curtis R.;
RT "A novel nervous system beta subunit that downregulates human large
RT conductance calcium-dependent potassium channels.";
RL J. Neurosci. 20:3563-3570(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Lymph;
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 [6]
RP PHOSPHORYLATION, AND MUTAGENESIS OF THR-11; SER-17 AND SER-210.
RX PubMed=11790768; DOI=10.1074/jbc.m107682200;
RA Jin P., Weiger T.M., Wu Y., Levitan I.B.;
RT "Phosphorylation-dependent functional coupling of hSlo calcium-dependent
RT potassium channel and its hbeta 4 subunit.";
RL J. Biol. Chem. 277:10014-10020(2002).
RN [7]
RP GLYCOSYLATION, AND MUTAGENESIS OF ASN-53 AND ASN-90.
RX PubMed=12223479; DOI=10.1074/jbc.m205795200;
RA Jin P., Weiger T.M., Levitan I.B.;
RT "Reciprocal modulation between the alpha and beta 4 subunits of hSlo
RT calcium-dependent potassium channels.";
RL J. Biol. Chem. 277:43724-43729(2002).
RN [8]
RP REVIEW.
RX PubMed=12136044; DOI=10.1152/nips.01387.2002;
RA Orio P., Rojas P., Ferreira G., Latorre R.;
RT "New disguises for an old channel: MaxiK channel beta-subunits.";
RL News Physiol. Sci. 17:156-161(2002).
RN [9]
RP INTERACTION WITH FMR1.
RX PubMed=25561520; DOI=10.1073/pnas.1423094112;
RA Myrick L.K., Deng P.Y., Hashimoto H., Oh Y.M., Cho Y., Poidevin M.J.,
RA Suhl J.A., Visootsak J., Cavalli V., Jin P., Cheng X., Warren S.T.,
RA Klyachko V.A.;
RT "Independent role for presynaptic FMRP revealed by an FMR1 missense
RT mutation associated with intellectual disability and seizures.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:949-956(2015).
CC -!- FUNCTION: Regulatory subunit of the calcium activated potassium KCNMA1
CC (maxiK) channel. Modulates the calcium sensitivity and gating kinetics
CC of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases
CC the gating kinetics and calcium sensitivity of the KCNMA1 channel, but
CC with fast deactivation kinetics. May decrease KCNMA1 channel openings
CC at low calcium concentrations but increases channel openings at high
CC calcium concentrations. Makes KCNMA1 channel resistant to 100 nM
CC charybdotoxin (CTX) toxin concentrations. {ECO:0000269|PubMed:10692449,
CC ECO:0000269|PubMed:10792058, ECO:0000269|PubMed:10828459}.
CC -!- SUBUNIT: Interacts with KCNMA1 tetramer (PubMed:10692449,
CC PubMed:10804197). There are probably 4 molecules of KCMNB4 per KCNMA1
CC tetramer (PubMed:10692449, PubMed:10804197). Interacts with FMR1 (via
CC N-terminus) (PubMed:25561520). {ECO:0000269|PubMed:10692449,
CC ECO:0000269|PubMed:10804197, ECO:0000269|PubMed:25561520}.
CC -!- INTERACTION:
CC Q86W47; P21145: MAL; NbExp=3; IntAct=EBI-19112227, EBI-3932027;
CC Q86W47; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-19112227, EBI-12070086;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain. In brain, it is
CC expressed in the cerebellum, cerebral cortex, medulla, spinal cord,
CC occipital pole, frontal lobe, temporal lobe, putamen, amygdala, caudate
CC nucleus, corpus callosum, hippocampus, substantia nigra and thalamus.
CC Weakly or not expressed in other tissues. {ECO:0000269|PubMed:10692449,
CC ECO:0000269|PubMed:10828459}.
CC -!- DOMAIN: Resistance to charybdotoxin (CTX) toxin is mediated by the
CC extracellular domain.
CC -!- PTM: Phosphorylated. Phosphorylation modulates its effect on KCNMA1
CC activation kinetics. {ECO:0000269|PubMed:11790768}.
CC -!- PTM: N-glycosylated. A highly glycosylated form is promoted by KCNMA1.
CC Glycosylation, which is not required for the interaction with KCNMA1
CC and subcellular location, increases protection against charybdotoxin.
CC {ECO:0000269|PubMed:10792058, ECO:0000269|PubMed:12223479}.
CC -!- MISCELLANEOUS: Treatment with okadaic acid reduces its effect on
CC KCNMA1.
CC -!- SIMILARITY: Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB4
CC subfamily. {ECO:0000305}.
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DR EMBL; AF160967; AAF69805.1; -; mRNA.
DR EMBL; AF170917; AAF89699.1; -; mRNA.
DR EMBL; AF207992; AAF28333.1; -; mRNA.
DR EMBL; AF215891; AAF75596.1; -; mRNA.
DR EMBL; BC042446; AAH42446.2; -; mRNA.
DR EMBL; BC050621; AAH50621.2; -; mRNA.
DR CCDS; CCDS8997.1; -.
DR RefSeq; NP_055320.4; NM_014505.5.
DR PDB; 5Y7L; NMR; -; A=45-166.
DR PDB; 6V22; EM; 3.20 A; E/F/G/H=1-210.
DR PDB; 6V35; EM; 3.50 A; E/F/G/H=1-210.
DR PDBsum; 5Y7L; -.
DR PDBsum; 6V22; -.
DR PDBsum; 6V35; -.
DR AlphaFoldDB; Q86W47; -.
DR SMR; Q86W47; -.
DR BioGRID; 118157; 4.
DR IntAct; Q86W47; 3.
DR STRING; 9606.ENSP00000258111; -.
DR BindingDB; Q86W47; -.
DR ChEMBL; CHEMBL4523376; -.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB09089; Trimebutine.
DR GlyGen; Q86W47; 2 sites.
DR iPTMnet; Q86W47; -.
DR PhosphoSitePlus; Q86W47; -.
DR SwissPalm; Q86W47; -.
DR BioMuta; KCNMB4; -.
DR DMDM; 46395791; -.
DR MassIVE; Q86W47; -.
DR PaxDb; Q86W47; -.
DR PeptideAtlas; Q86W47; -.
DR PRIDE; Q86W47; -.
DR ProteomicsDB; 70115; -.
DR ABCD; Q86W47; 1 sequenced antibody.
DR Antibodypedia; 29474; 181 antibodies from 30 providers.
DR DNASU; 27345; -.
DR Ensembl; ENST00000258111.5; ENSP00000258111.4; ENSG00000135643.5.
DR GeneID; 27345; -.
DR KEGG; hsa:27345; -.
DR MANE-Select; ENST00000258111.5; ENSP00000258111.4; NM_014505.6; NP_055320.4.
DR UCSC; uc001svx.4; human.
DR CTD; 27345; -.
DR DisGeNET; 27345; -.
DR GeneCards; KCNMB4; -.
DR HGNC; HGNC:6289; KCNMB4.
DR HPA; ENSG00000135643; Group enriched (adrenal gland, brain, choroid plexus).
DR MIM; 605223; gene.
DR neXtProt; NX_Q86W47; -.
DR OpenTargets; ENSG00000135643; -.
DR PharmGKB; PA30069; -.
DR VEuPathDB; HostDB:ENSG00000135643; -.
DR eggNOG; ENOG502QR4Z; Eukaryota.
DR GeneTree; ENSGT00950000183039; -.
DR HOGENOM; CLU_085739_0_0_1; -.
DR InParanoid; Q86W47; -.
DR OMA; SVMTWQQ; -.
DR OrthoDB; 1178937at2759; -.
DR PhylomeDB; Q86W47; -.
DR TreeFam; TF328589; -.
DR PathwayCommons; Q86W47; -.
DR Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR Reactome; R-HSA-418457; cGMP effects.
DR SignaLink; Q86W47; -.
DR BioGRID-ORCS; 27345; 15 hits in 1078 CRISPR screens.
DR ChiTaRS; KCNMB4; human.
DR GeneWiki; KCNMB4; -.
DR GenomeRNAi; 27345; -.
DR Pharos; Q86W47; Tbio.
DR PRO; PR:Q86W47; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86W47; protein.
DR Bgee; ENSG00000135643; Expressed in endothelial cell and 148 other tissues.
DR ExpressionAtlas; Q86W47; baseline and differential.
DR Genevisible; Q86W47; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IBA:GO_Central.
DR GO; GO:0001508; P:action potential; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0005513; P:detection of calcium ion; IDA:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; TAS:UniProtKB.
DR GO; GO:0019229; P:regulation of vasoconstriction; TAS:UniProtKB.
DR InterPro; IPR003930; K_chnl_Ca-activ_BK_bsu.
DR PANTHER; PTHR10258; PTHR10258; 1.
DR Pfam; PF03185; CaKB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..210
FT /note="Calcium-activated potassium channel subunit beta-4"
FT /id="PRO_0000187055"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..40
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 41..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT VARIANT 199
FT /note="V -> I"
FT /evidence="ECO:0000269|PubMed:10792058"
FT /id="VAR_018178"
FT MUTAGEN 11
FT /note="T->A: Suppresses the effect of okadaic acid and
FT increases activation time constant; when associated with A-
FT 17 and A-210."
FT /evidence="ECO:0000269|PubMed:11790768"
FT MUTAGEN 11
FT /note="T->D: Suppresses its effect on KCNMA1 channel
FT activation and on deactivation kinetics; when associated
FT with E-17 and E-210."
FT /evidence="ECO:0000269|PubMed:11790768"
FT MUTAGEN 17
FT /note="S->A: Suppresses the effect of okadaic acid and
FT increases activation time constant; when associated with A-
FT 11 and A-210."
FT /evidence="ECO:0000269|PubMed:11790768"
FT MUTAGEN 17
FT /note="S->E: Suppresses its effect on KCNMA1 channel
FT activation and on deactivation kinetics; when associated
FT with D-11 and E-210."
FT /evidence="ECO:0000269|PubMed:11790768"
FT MUTAGEN 53
FT /note="N->A: Loss of N-glycosylation and reduced protection
FT against charybdotoxin; when associated with A-90."
FT /evidence="ECO:0000269|PubMed:12223479"
FT MUTAGEN 90
FT /note="N->A: Loss of N-glycosylation and reduced protection
FT against charybdotoxin; when associated with A-53."
FT /evidence="ECO:0000269|PubMed:12223479"
FT MUTAGEN 210
FT /note="S->A: Suppresses the effect of okadaic acid and
FT increases activation time constant; when associated with A-
FT 11 and A-17."
FT /evidence="ECO:0000269|PubMed:11790768"
FT MUTAGEN 210
FT /note="S->E: Suppresses its effect on KCNMA1 channel
FT activation and on deactivation kinetics; when associated
FT with D-11 and E-17."
FT /evidence="ECO:0000269|PubMed:11790768"
FT HELIX 12..38
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 40..48
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 49..61
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:5Y7L"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:6V35"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:5Y7L"
FT STRAND 85..94
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 123..139
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:6V22"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 155..162
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 169..203
FT /evidence="ECO:0007829|PDB:6V22"
SQ SEQUENCE 210 AA; 23949 MW; A59D56DD034F027A CRC64;
MAKLRVAYEY TEAEDKSIRL GLFLIISGVV SLFIFGFCWL SPALQDLQAT EANCTVLSVQ
QIGEVFECTF TCGADCRGTS QYPCVQVYVN NSESNSRALL HSDEHQLLTN PKCSYIPPCK
RENQKNLESV MNWQQYWKDE IGSQPFTCYF NQHQRPDDVL LHRTHDEIVL LHCFLWPLVT
FVVGVLIVVL TICAKSLAVK AEAMKKRKFS
