Navβ4

The protein encoded by the gene SCN4B in humans is one of several sodium channel beta subunits, type IV. These subunits interact with voltage-gated alpha subunits to change sodium channel kinetics. The encoded transmembrane protein forms interchain disulfide bonds with SCN2A. Defects in this gene are a cause of long QT syndrome type 10 (LQT10). Three protein-coding and one non-coding transcript variant have been found for this gene.

http://www.ncbi.nlm.nih.gov/gene/6330 http://rgd.mcw.edu

The sodium channel beta 4 subunit is most highly related to the beta 2 subunit, although it also shares substantial sequence similarity with beta 1 and beta 3. Its distinct localization and function indicate that it may differentially affect sodium channel protein–protein interactions and physiological function in the neurons and other cell types in which it is expressed. [406]

The protein encoded by the gene SCN4B in humans is one of several sodium channel beta subunits, type IV. These subunits interact with voltage-gated alpha subunits to change sodium channel kinetics. The encoded transmembrane protein forms interchain disulfide bonds with SCN2A. Defects in this gene are a cause of long QT syndrome type 10 (LQT10). Three protein-coding and one non-coding transcript variant have been found for this gene.

http://www.ncbi.nlm.nih.gov/gene/6330

http://rgd.mcw.edu

Like the b1–b3 subunits, b4 (beta-4) contains a cleaved signal sequence, an extracellular Ig-like fold, a transmembrane segment, and a short intracellular C-terminal tail. Under nonreducing conditions, b4 has a molecular mass exceeding 250 kDa because of its covalent linkage to Nav1.2a, whereas on reduction, it migrates with a molecular mass of 38 kDa, similar to the mature glycosylated forms of the other b subunits. [406].

b4 is widely distributed in neurons in the brain, spinal cord, and some sensory neurons. [406]

Nav-beta subunits play a critical role in cell adhesion, signal transduction, channel expression at the plasma membrane, and voltage dependence of channel gating. [897], [816]

SCN4B-encoded Nav-beta-4 is a LQT3-susceptibility gene. Long-QT syndrome (LQTS) represents the prototypic cardiac channelopathy that affects 1 in 3000 individuals and is characterized by QT prolongation, abnormal ventricular repolarization, and increased propensity for sudden cardiac death as a result of its trademark dysrhythmia of torsade de pointes. [896]

b4 is most similar to the b2 subunit (35% identity), and, like the b2 subunit, the Ig-like fold of b4 contains an unpaired cysteine that may interact with the alpha-subunit. [406]

Coexpression of b4 with brain Nav1.2a and skeletal muscle Nav1.4 alpha subunits in tsA-201 cells resulted in a negative shift in the voltage dependence of channel activation, which overrode the opposite effects of b1 and b3 subunits when they were present. [406]