Q86W47 (KCMB4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

KCNMB4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	210 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.2 Ref.3
Subunit structure	Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB4 per KCNMA1 tetramer. Ref.3 Ref.4
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	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. Ref.2 Ref.3
Domain	Resistance to charybdotoxin (CTX) toxin is mediated by the extracellular domain.
Post-translational modification	Phosphorylated. Phosphorylation modulates its effect on KCNMA1 activation kinetics. Ref.6 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. Ref.1 Ref.7
Miscellaneous	Treatment with okadaic acid reduces its effect on KCNMA1.
Sequence similarities	Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB4 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Ion channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome detection of calcium ion Inferred from direct assay Ref.3. Source: UniProtKB regulation of action potential in neuron Inferred from direct assay Ref.3. Source: UniProtKB regulation of neurotransmitter secretion Traceable author statement Ref.3. Source: UniProtKB regulation of vasoconstriction Traceable author statement Ref.3. Source: UniProtKB synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	voltage-gated potassium channel complex Inferred from direct assay Ref.3. Source: UniProtKB
Molecular_function	calcium-activated potassium channel activity Inferred from direct assay Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 210	210	Calcium-activated potassium channel subunit beta-4		PRO_0000187055
Regions
	Topological domain	1 – 19	19	Cytoplasmic Potential
	Transmembrane	20 – 40	21	Helical; Name=1; Potential
	Topological domain	41 – 167	127	Extracellular Potential
	Transmembrane	168 – 188	21	Helical; Name=2; Potential
	Topological domain	189 – 210	22	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	53	1	N-linked (GlcNAc...)
	Glycosylation	90	1	N-linked (GlcNAc...)
Natural variations
	Natural variant	199	1	V → I. Ref.1		VAR_018178
Experimental info
	Mutagenesis	11	1	T → A: Suppresses the effect of okadaic acid and increases activation time constant; when associated with A-17 and A-210. Ref.6
	Mutagenesis	11	1	T → D: Suppresses its effect on KCNMA1 channel activation and on deactivation kinetics; when associated with E-17 and E-210. Ref.6
	Mutagenesis	17	1	S → A: Suppresses the effect of okadaic acid and increases activation time constant; when associated with A-11 and A-210. Ref.6
	Mutagenesis	17	1	S → E: Suppresses its effect on KCNMA1 channel activation and on deactivation kinetics; when associated with D-11 and E-210. Ref.6
	Mutagenesis	53	1	N → A: Loss of N-glycosylation and reduced protection against charybdotoxin; when associated with A-90. Ref.7
	Mutagenesis	90	1	N → A: Loss of N-glycosylation and reduced protection against charybdotoxin; when associated with A-53. Ref.7
	Mutagenesis	210	1	S → A: Suppresses the effect of okadaic acid and increases activation time constant; when associated with A-11 and A-17. Ref.6
	Mutagenesis	210	1	S → E: Suppresses its effect on KCNMA1 channel activation and on deactivation kinetics; when associated with D-11 and E-17. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q86W47 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: A59D56DD034F027A	FASTA	210	23,949
	10 20 30 40 50 60 MAKLRVAYEY TEAEDKSIRL GLFLIISGVV SLFIFGFCWL SPALQDLQAT EANCTVLSVQ 70 80 90 100 110 120 QIGEVFECTF TCGADCRGTS QYPCVQVYVN NSESNSRALL HSDEHQLLTN PKCSYIPPCK 130 140 150 160 170 180 RENQKNLESV MNWQQYWKDE IGSQPFTCYF NQHQRPDDVL LHRTHDEIVL LHCFLWPLVT 190 200 210 FVVGVLIVVL TICAKSLAVK AEAMKKRKFS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00217101.
RefSeq	NP_055320.4. NM_014505.5.
UniGene	Hs.525529.
3D structure databases
ProteinModelPortal	Q86W47.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000258111.
PTM databases
PhosphoSite	Q86W47.
Polymorphism databases
DMDM	46395791.
Proteomic databases
PaxDb	Q86W47.
PRIDE	Q86W47.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258111; ENSP00000258111; ENSG00000135643.
GeneID	27345.
KEGG	hsa:27345.
UCSC	uc001svx.3. human.
Organism-specific databases
CTD	27345.
GeneCards	GC12P070760.
HGNC	HGNC:6289. KCNMB4.
MIM	605223. gene.
neXtProt	NX_Q86W47.
PharmGKB	PA30069.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG83271.
HOGENOM	HOG000113205.
HOVERGEN	HBG052224.
InParanoid	Q86W47.
KO	K04941.
OMA	CFLWPVV.
OrthoDB	EOG4FBHTX.
PhylomeDB	Q86W47.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_604. Hemostasis.
Gene expression databases
Bgee	Q86W47.
CleanEx	HS_KCNMB4.
Genevestigator	Q86W47.
GermOnline	ENSG00000135643. Homo sapiens.
Family and domain databases
InterPro	IPR003930. K_chnl_Ca-activ_BK_bsu. [Graphical view]
PANTHER	PTHR10258. PTHR10258. 1 hit.
Pfam	PF03185. CaKB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KCNMB4. human.
GenomeRNAi	27345.
NextBio	50430.
SOURCE	Search...

Entry information

Entry name

KCMB4_HUMAN

Accession

Primary (citable) accession number: Q86W47
Secondary accession number(s): Q8IVR3, Q9NPA4, Q9P0G5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	March 1, 2004
Last modified:	April 3, 2013
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.