Structure and chromosomal localization of the beta2 subunit of the human brain sodium channel.

ABSTRACT

The beta2 subunit of rat brain voltage-gated sodium channels modulates their cell-surface expression and gating. It is a 33 kDa glycoprotein with a single transmembrane segment and an immunoglobulin-like fold resembling those of cell adhesion molecules in the extracellular domain. Here we report the cDNA sequence and genomic localization of the gene encoding the human beta2 subunit. The mature human beta2 protein has 89% amino acid sequence identity to rat beta2 and has four conserved consensus sites for N-linked glycosylation. The extracellular cysteine residues which are predicted to form the disulfide linkage in the immunoglobulin-like fold are also conserved, indicating that the overall structure is preserved between these two species. Using fluorescent in situ hybridization (FISH), we localized the beta2 gene to human chromosome 11q3. Mutations in this region of chromosome 11 in Charcot-Marie-Tooth syndrome type 4B and in other neurological diseases cause abnormal myelination and neurological deficits. The similarity of beta2 to cell adhesion molecules, including myelin protein p0, and its chromosomal location at 11q23 suggest a potential role in these demyelinating diseases.