Channelpedia

Navβ4

Gene: scn4b

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Introduction

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]


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Gene

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

Species NCBI gene ID Chromosome Position
Human 6330 11 19446
Mouse 399548 9 15531
Rat 315611 8 15714

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Transcript

Species NCBI accession Length (nt)
Human NM_174934.4 4487
Mouse NM_001013390.3 4771
Rat NM_001008880.2 4272

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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q8IWT1 228
Mouse Q7M729 228
Rat Q7M730 228

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

PTM
Position
Type

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Structure

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].

Navβ4 predicted AlphaFold size

Species Area (Å2) Reference
Human 6867.81 source
Mouse 5106.10 source
Rat 7443.74 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Expression and Distribution

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


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Function

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]


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Interaction

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]


References

406

816

896

Medeiros-Domingo A et al. SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome.
Circulation, 2007 Jul 10 , 116 (134-42).


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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/259/ , accessed on 2024 Dec 12



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