SCNBA Human Protein

Voltage-gated sodium channels are membrane protein complexes that play a fundamental role in the rising phase of the action potential in most excitable cells. Alpha subunits, such as SCN11A, mediate voltage-dependent gating and conductance, while auxiliary beta subunits regulate the kinetic properties of the channel and facilitate membrane localization of the complex. Aberrant expression patterns or mutations of alpha subunits underlie a number of disorders. Each alpha subunit consists of 4 domains connected by 3 intracellular loops; each domain consists of 6 transmembrane segments and intra- and extracellular linkers.[supplied by OMIM, Apr 2004]

Function: This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization. Ref.1 Ref.3

Subunit structure: The voltage-resistant sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more auxiliary subunits SCN1B, SCN2B and SCN3B.

Subcellular location: Membrane; Multi-pass membrane protein

By similarity.

Tissue specificity: Expressed in the dorsal root ganglia and trigeminal ganglia, olfactory bulb, hippocampus, cerebellar cortex, spinal cord, spleen, small intestine and placenta. Ref.2 Ref.5

Domain: The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Post-translational modification: Phosphorylation at Ser-1341 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents

By similarity.

Sequence similarities: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.9/SCN11A subfamily. [View classification]