SCN10A
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.
Function
Tetrodotoxin-resistant channel that 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. Plays a role in neuropathic pain mechanisms.
Involvement in disease
Episodic pain syndrome, familial, 2
FEPS2
An autosomal dominant neurologic disorder characterized by adult-onset of paroxysmal pain mainly affecting the distal lower extremities.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated by NEDD4L; which promotes its endocytosis.
Phosphorylation at Ser-1451 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 816) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.8/SCN10A subfamily.
Tissue Specificity
Expressed in the dorsal root ganglia and sciatic nerve.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- It can be translocated to the cell membrane through association with S100A10.
Alternative names
Sodium channel protein type 10 subunit alpha, Peripheral nerve sodium channel 3, Sodium channel protein type X subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.8, PN3, hPN3, SCN10A