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   27-MAR-2024, entry version 153.
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   EMDB; EMD-21025; -.
DR   EMDB; EMD-21028; -.
DR   SMR; Q86W47; -.
DR   BioGRID; 118157; 4.
DR   IntAct; Q86W47; 3.
DR   STRING; 9606.ENSP00000258111; -.
DR   BindingDB; Q86W47; -.
DR   ChEMBL; CHEMBL4523376; -.
DR   DrugBank; DB02587; Colforsin.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB01054; Nitrendipine.
DR   DrugBank; DB00721; Procaine.
DR   DrugBank; DB00867; Ritodrine.
DR   DrugBank; DB09089; Trimebutine.
DR   GlyCosmos; Q86W47; 2 sites, No reported glycans.
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; 9606-ENSP00000258111; -.
DR   PeptideAtlas; Q86W47; -.
DR   ProteomicsDB; 70115; -.
DR   Pumba; Q86W47; -.
DR   ABCD; Q86W47; 1 sequenced antibody.
DR   Antibodypedia; 29474; 206 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   AGR; HGNC:6289; -.
DR   CTD; 27345; -.
DR   DisGeNET; 27345; -.
DR   GeneCards; KCNMB4; -.
DR   HGNC; HGNC:6289; KCNMB4.
DR   HPA; ENSG00000135643; Tissue enhanced (brain).
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; RGTAQYP; -.
DR   OrthoDB; 3976732at2759; -.
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 1158 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 150 other cell types or tissues.
DR   ExpressionAtlas; Q86W47; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0099508; F:voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl.
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; CALCIUM-ACTIVATED POTASSIUM CHANNEL SUBUNIT BETA; 1.
DR   PANTHER; PTHR10258:SF3; CALCIUM-ACTIVATED POTASSIUM CHANNEL SUBUNIT BETA-4; 1.
DR   Pfam; PF03185; CaKB; 1.
DR   Genevisible; Q86W47; HS.
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
FT                   A-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
FT                   A-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
FT                   A-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
//