Swiss-Prot entry

ID   KCMB4_HUMAN    STANDARD;      PRT;   210 AA.
AC   Q86W47; Q8IVR3; Q9NPA4; Q9P0G5;
DT   05-JUL-2004 (Rel. 44, Created)
DT   05-JUL-2004 (Rel. 44, Last sequence update)
DT   10-MAY-2005 (Rel. 47, Last annotation update)
DE   Calcium-activated potassium channel beta subunit 4 (Calcium-activated
DE   potassium channel, subfamily M, beta subunit 4) (Maxi K channel beta
DE   subunit 4) (BK channel beta subunit 4) (Slo-beta 4) (K(VCA)beta 4)
DE   (Charybdotoxin receptor beta subunit 4) (BKbeta4) (Hbeta4).
GN   Name=KCNMB4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; 
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; 
OC   Homo. 
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE, FUNCTION, GLYCOSYLATION, AND VARIANT ILE-199.
RX   MEDLINE=20266405; PubMed=10792058 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1073/pnas.100118597;
RA   Meera P., Wallner M., Toro L.;
RT   "A neuronal beta subunit (KCNMB4) makes the large conductance,
RT   voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and
RT   iberiotoxin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:5562-5567(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE, FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=10828459 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1016/S0014-5793(00)01584-2;
RA   Behrens R., Nolting A., Reimann F., Schwarz M., Waldschuetz R.,
RA   Pongs O.;
RT   "hKCNMB3 and hKCNMB4, cloning and characterization of two members of
RT   the large-conductance calcium-activated potassium channel beta subunit
RT   family.";
RL   FEBS Lett. 474:99-106(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE, FUNCTION, INTERACTION WITH KCNMA1, AND TISSUE
RP   SPECIFICITY.
RX   MEDLINE=20158960; PubMed=10692449 [NCBI, ExPASy, EBI, Israel, Japan]; 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
RT   hKCNMB4.";
RL   J. Biol. Chem. 275:6453-6461(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE, AND INTERACTION WITH KCNMA1.
RC   TISSUE=CNS;
RX   MEDLINE=20266164; PubMed=10804197 [NCBI, ExPASy, EBI, Israel, Japan];
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   MEDLINE=22388257; PubMed=12477932 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1073/pnas.242603899;
RA   Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA   Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA   Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA   Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA   Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA   Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA   Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA   Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA   Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA   Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA   Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA   Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA   Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA   Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA   Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA   Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA   Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT   "Generation and initial analysis of more than 15,000 full-length human
RT   and mouse cDNA sequences.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN   [6]
RP   PHOSPHORYLATION, AND MUTAGENESIS OF THR-11; SER-17 AND SER-210.
RX   PubMed=11790768 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.M107682200;
RA   Jin P., Weiger T.M., Wu Y., Levitan I.B.;
RT   "Phosphorylation-dependent functional coupling of hSlo calcium-
RT   dependent 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 [NCBI, ExPASy, EBI, Israel, Japan]; 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 [NCBI, ExPASy, EBI, Israel, Japan];
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).
CC   -!- FUNCTION: Regulatory subunit of the calcium activated potassium
CC       KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and
CC       gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel
CC       diversity. Decreases the gating kinetics and calcium sensitivity
CC       of the KCNMA1 channel, but with fast deactivation kinetics. May
CC       decrease KCNMA1 channel openings at low calcium concentrations but
CC       increases channel openings at high calcium concentrations. Makes
CC       KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin
CC       concentrations.
CC   -!- SUBUNIT: Interacts with KCNMA1 tetramer. There are probably 4
CC       molecules of KCMNB4 per KCNMA1 tetramer.
CC   -!- SUBCELLULAR LOCATION: Integral membrane protein.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in brain. In brain, it
CC       is expressed in the cerebellum, cerebral cortex, medulla, spinal
CC       cord, occipital pole, frontal lobe, temporal lobe, putamen,
CC       amygdala, caudate nucleus, corpus callosum, hippocampus,
CC       substantia nigra and thalamus. Weakly or not expressed in other
CC       tissues.
CC   -!- DOMAIN: Resistance to charybdotoxin (CTX) toxin is mediated by the
CC       extracellular domain.
CC   -!- PTM: Phosphorylated. Phosphorylation modulates its effect on
CC       KCNMA1 activation kinetics.
CC   -!- PTM: N-glycosylated. A highly glycosylated form is promoted by
CC       KCNMA1. Glycosylation, which is not required for the interaction
CC       with KCNMA1 and subcellular location, increases protection against
CC       charybdotoxin.
CC   -!- MISCELLANEOUS: Treatment with okadaic acid reduces its effect on
CC       KCNMA1.
CC   -!- SIMILARITY: Belongs to the KCNMB family.
CC   --------------------------------------------------------------------------
CC   This Swiss-Prot entry is copyright. It is produced through a collaboration
CC   between  the Swiss Institute of Bioinformatics  and the  EMBL outstation -
CC   the European Bioinformatics Institute.  There are no  restrictions on  its
CC   use as long as its content is in no way modified and this statement is not
CC   removed.
CC   --------------------------------------------------------------------------
DR   EMBL; AF160967; AAF69805.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR   EMBL; AF170917; AAF89699.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR   EMBL; AF207992; AAF28333.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR   EMBL; AF215891; AAF75596.1; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR   EMBL; BC042446; AAH42446.2; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR   EMBL; BC050621; AAH50621.2; -; mRNA. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR   Ensembl; ENSG00000135643; Homo_sapiens
DR   HGNC; HGNC:6289; KCNMB4.
DR   CleanEx; HGNC:6289; KCNMB4.
DR   MIM; 605223; -. [NCBI / EBI]
DR   GeneCards; KCNMB4.
DR   GeneLynx; KCNMB4.
DR   GenAtlas; KCNMB4.
DR   SOURCE; KCNMB4.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IDA.
DR   GO; GO:0015269; F:calcium-activated potassium channel activity; IDA.
DR   GO; GO:0015459; F:potassium channel regulator activity; TAS.
DR   GO; GO:0005515; F:protein binding; IDA.
DR   GO; GO:0005513; P:calcium ion sensing; IDA.
DR   GO; GO:0019228; P:generation of action potential; IDA.
DR   GO; GO:0006813; P:potassium ion transport; IDA.
DR   GO; GO:0001508; P:regulation of action potential; IDA.
DR   GO; GO:0046928; P:regulation of neurotransmitter secretion; TAS.
DR   GO; GO:0019229; P:regulation of vasoconstriction; TAS.
DR   GO; GO:0007268; P:synaptic transmission; TAS.
DR   InterPro; IPR003930; BK_channel_beta.
DR   InterPro; Graphical view of domain structure.
DR   PANTHER; PTHR10258; BK_channel_beta; 1.
DR   Pfam; PF03185; CaKB; 1.
DR   Pfam; Graphical view of domain structure.
DR   CMR; Q86W47.
DR   ProDom [Domain structure / List of seq. sharing at least 1 domain]
DR   HOVERGEN [Family / Alignment / Tree]
DR   BLOCKS; Q86W47.
DR   ProtoNet; Q86W47.
DR   ProtoMap; Q86W47.
DR   PRESAGE; Q86W47.
DR   DIP; Q86W47.
DR   ModBase; Q86W47.
DR   SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW   Glycoprotein; Ion transport; Ionic channel; Phosphorylation;
KW   Polymorphism; Transmembrane; Transport.
FT   TOPO_DOM      1     19       Cytoplasmic (Potential).
FT   TRANSMEM     20     40       1 (Potential).
FT   TOPO_DOM     41    167       Extracellular (Potential).
FT   TRANSMEM    168    188       2 (Potential).
FT   TOPO_DOM    189    210       Cytoplasmic (Potential).
FT   CARBOHYD     53     53       N-linked (GlcNAc...).
FT   CARBOHYD     90     90       N-linked (GlcNAc...).
FT   VARIANT     199    199       V -> I.
FT                                /FTId=VAR_018178.
FT   MUTAGEN      11     11       T->A: Suppresses the effect of okadaic
FT                                acid and increases activation time
FT                                constant; when associated with A-17 and
FT                                A-210.
FT   MUTAGEN      11     11       T->D: Suppresses its effect on KCNMA1
FT                                channel activation and on deactivation
FT                                kinetics; when associated with E-17 and
FT                                E-210.
FT   MUTAGEN      17     17       S->A: Suppresses the effect of okadaic
FT                                acid and increases activation time
FT                                constant; when associated with A-11 and
FT                                A-210.
FT   MUTAGEN      17     17       S->E: Suppresses its effect on KCNMA1
FT                                channel activation and on deactivation
FT                                kinetics; when associated with D-11 and
FT                                E-210.
FT   MUTAGEN      53     53       N->A: Loss of N-glycosylation and reduced
FT                                protection against charybdotoxin; when
FT                                associated with A-90.
FT   MUTAGEN      90     90       N->A: Loss of N-glycosylation and reduced
FT                                pr$otection against charybdotoxin; when
FT                                associated with A-53.
FT   MUTAGEN     210    210       S->A: Suppresses the effect of okadaic
FT                                acid and increases activation time
FT                                constant; when associated with A-11 and
FT                                A-17.
FT   MUTAGEN     210    210       S->E: Suppresses its effect on KCNMA1
FT                                channel activation and on deactivation
FT                                kinetics; when associated with D-11 and
FT                                E-17.
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
//