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POTASSIUM CHANNEL, CALCIUM-ACTIVATED, LARGE CONDUCTANCE, SUBFAMILY M, BETA MEMBER 3; KCNMB3

POTASSIUM CHANNEL, CALCIUM-ACTIVATED, LARGE CONDUCTANCE, SUBFAMILY M, BETA MEMBER 3; KCNMB3

HGNC Approved Gene Symbol: KCNMB3Cytogenetic location: 3q26.32 Genomic coordinates (GRCh38): 3:179,239,702-179,267,049 (from NCBI)▼ DescriptionThe KCNMB3 gen...

HGNC Approved Gene Symbol: KCNMB3

Cytogenetic location: 3q26.32 Genomic coordinates (GRCh38): 3:179,239,702-179,267,049 (from NCBI)

▼ Description

The KCNMB3 gene encodes a family of 4 large conductance, calcium-activated potassium (BK) beta subunits which arise by alternative splicing and have distinct effects on the functional properties of BK currents, channel kinetics, voltage dependence, and rectification properties (Uebele et al., 2000).

▼ Cloning and Expression

By exon trapping and searching an EST database, Riazi et al. (1999) identified a cDNA encoding KCNMB3. KCNMB3 encodes a predicted 275-amino acid protein. Northern blot analysis detected 2.0- and 5.3-kb KCNMB3 transcripts, with highest expression in pancreas; a 3.1-kb transcript was also detected in most tissues.

By searching EST databases, Brenner et al. (2000) and Behrens et al. (2000) identified cDNAs encoding KCNMB3. The sequence reported by Brenner et al. (2000) lacks amino acids 2 through 19 in the sequences reported by Riazi et al. (1999) and Behrens et al. (2000). Sequence analysis predicted that the KCNMB3 protein contains 2 transmembrane domains and an extracellular domain containing an N-glycosylation site and 4 cys residues. Northern blot analysis by Brenner et al. (2000) detected a testis-specific 3.0-kb KCNMB3 transcript, as well as a weakly expressed 4.0-kb transcript in most nonneural tissues. RNA dot blot analysis by Behrens et al. (2000) detected weak expression of KCNMB3 in most tissues tested. Functional analysis indicated that KCNMB3 may slightly decrease the activation time of KCNMA1 currents (Brenner et al., 2000).

Uebele et al. (2000) determined that KCNMB3 encodes a family of 4 related subunits, KCNMB3a (277 amino acids), KCNMB3b (257 amino acids), KCNMB3c (275 amino acids), and KCNMB3d (279 amino acids), that arise from alternative splicing. The subunits vary only in their cytoplasmic N-terminal sequences and share 256 C-terminal amino acids. RT-PCR analysis showed that KCNMB3a has a relatively restricted distribution (spleen, placenta, pancreas, kidney, and heart), while the other variants are more widely expressed. KCNMB3c was notably abundant in pancreas. In situ hybridization analysis demonstrated that KCNMB3c expression is restricted to pancreatic beta cells. Coexpression of KCNMB3a, -b, and -c with KCNMA1 resulted in partial inactivation of activating currents; KCNMB3d did not induce detectable inactivation.

▼ Gene Structure

Using genomic sequence analysis, Uebele et al. (2000) determined that the KCNMB3 gene contains 6 exons, 3 of which (1a, 1b, and 1c/d) encode sequences unique to each of the splice variants.

▼ Mapping

By FISH and somatic cell hybrid analysis, Riazi et al. (1999) mapped the KCNMB3 gene to chromosome 3q26.3-q27. Uebele et al. (2000) also mapped the KCNMB3 gene to 3q26.3-q27.1, in close proximity to KCNMB2, by radiation hybrid and FISH analysis.

▼ Gene Family

The large conductance, calcium-activated potassium (BK) channel is a member of the Shaker-related 6-transmembrane domain potassium channel superfamily that is sensitive to voltage and calcium. BK channels are composed of a pore-forming alpha subunit (KCNMA1, or HSLO; 600150) and, in some tissues, a beta subunit. The beta-1 subunit (KCNMB1; 603951) is expressed predominantly in smooth muscle cells, whereas the beta-2 subunit (KCNMB2; 605214) is expressed in endocrine tissue, such as adrenal chromaffin cells (summary by Behrens et al., 2000).

Tags: 3q26.32