Description: Homo sapiens potassium large conductance calcium-activated channel, subfamily M, beta member 4 (KCNMB4), mRNA. RefSeq Summary (NM_014505): MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Transcript (Including UTRs) Position: hg19 chr12:70,760,062-70,828,072 Size: 68,011 Total Exon Count: 3 Strand: + Coding Region Position: hg19 chr12:70,760,515-70,824,433 Size: 63,919 Coding Exon Count: 3
ID:KCMB4_HUMAN DESCRIPTION: RecName: Full=Calcium-activated potassium channel subunit beta-4; AltName: Full=BK channel subunit beta-4; Short=BKbeta4; Short=Hbeta4; AltName: Full=Calcium-activated potassium channel, subfamily M subunit beta-4; AltName: Full=Charybdotoxin receptor subunit beta-4; AltName: Full=K(VCA)beta-4; AltName: Full=Maxi K channel subunit beta-4; AltName: Full=Slo-beta-4; 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. SUBUNIT: Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB4 per KCNMA1 tetramer. 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. DOMAIN: Resistance to charybdotoxin (CTX) toxin is mediated by the extracellular domain. PTM: Phosphorylated. Phosphorylation modulates its effect on KCNMA1 activation kinetics. PTM: 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. MISCELLANEOUS: Treatment with okadaic acid reduces its effect on KCNMA1. SIMILARITY: Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB4 subfamily.
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): KCNMB4 CDC HuGE Published Literature: KCNMB4 Positive Disease Associations: Blood Pressure Related Studies:
Blood Pressure Daniel Levy et al. BMC medical genetics 2007, Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness., BMC medical genetics.
[PubMed 17903302]
These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q86W47
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001508 action potential GO:0005513 detection of calcium ion GO:0006811 ion transport GO:0006813 potassium ion transport GO:0007268 chemical synaptic transmission GO:0019228 neuronal action potential GO:0019229 regulation of vasoconstriction GO:0046928 regulation of neurotransmitter secretion GO:0071805 potassium ion transmembrane transport
Cellular Component: GO:0005886 plasma membrane GO:0005887 integral component of plasma membrane GO:0008076 voltage-gated potassium channel complex GO:0016020 membrane GO:0016021 integral component of membrane
Descriptions from all associated GenBank mRNAs
AF160967 - Homo sapiens large-conductance calcium-activated potassium channel beta subunit (KCNMB4) mRNA, complete cds. BC042446 - Homo sapiens potassium large conductance calcium-activated channel, subfamily M, beta member 4, mRNA (cDNA clone MGC:9933 IMAGE:3873518), complete cds. BC050621 - Homo sapiens potassium large conductance calcium-activated channel, subfamily M, beta member 4, mRNA (cDNA clone MGC:60089 IMAGE:5552807), complete cds. AF215891 - Homo sapiens large conductance calcium-dependent potassium ion channel beta 4 subunit mRNA, complete cds. AF170917 - Homo sapiens calcium-activated potassium channel beta 4 subunit (KCNMB4) mRNA, complete cds. KJ893642 - Synthetic construct Homo sapiens clone ccsbBroadEn_03036 KCNMB4 gene, encodes complete protein. AF207992 - Homo sapiens large-conductance calcium-activated potassium channel beta subunit (KCNMB4) mRNA, complete cds. JD365813 - Sequence 346837 from Patent EP1572962. JD391586 - Sequence 372610 from Patent EP1572962. JD442475 - Sequence 423499 from Patent EP1572962. JD181024 - Sequence 162048 from Patent EP1572962. JD461531 - Sequence 442555 from Patent EP1572962. JD341690 - Sequence 322714 from Patent EP1572962. JD341691 - Sequence 322715 from Patent EP1572962. JD200762 - Sequence 181786 from Patent EP1572962. JD210553 - Sequence 191577 from Patent EP1572962. JD332971 - Sequence 313995 from Patent EP1572962. JD209205 - Sequence 190229 from Patent EP1572962. JD180137 - Sequence 161161 from Patent EP1572962. JD086103 - Sequence 67127 from Patent EP1572962. JD244648 - Sequence 225672 from Patent EP1572962. JD243007 - Sequence 224031 from Patent EP1572962. JD511167 - Sequence 492191 from Patent EP1572962. JD044635 - Sequence 25659 from Patent EP1572962. AK054684 - Homo sapiens cDNA FLJ30122 fis, clone BRACE1000087. JD333399 - Sequence 314423 from Patent EP1572962. BC037898 - Homo sapiens cDNA clone IMAGE:5275948. BC047427 - Homo sapiens cDNA clone IMAGE:5275947. JD428266 - Sequence 409290 from Patent EP1572962. JD550267 - Sequence 531291 from Patent EP1572962. JD234107 - Sequence 215131 from Patent EP1572962. JD234108 - Sequence 215132 from Patent EP1572962. JD293164 - Sequence 274188 from Patent EP1572962. JD270476 - Sequence 251500 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04270 - Vascular smooth muscle contraction
Reactome (by CSHL, EBI, and GO)
Protein Q86W47 (Reactome details) participates in the following event(s):