SCNM1 (sodium channel modifier 1) is an accessory component of the U1 splicesome protein complex. It interacts with the spliceosomal Sm and U1-70K proteins and has a direct role in splicing []. It was originally identified as a disease modifier gene required for efficient splicing of a mutant splice donor site in the sodium channel Scn8a [].
This entry represents the C-terminal acidic region of eukaryotic sodium channel modifier protein 1 (SCNM1). Deletion of this region affects the splicing and normal activity of the sodium channel Nav1.6 from gene Scn8a []. SCNM1 belongs to the U1C subfamily of RNA binding proteins that is commonly found in RNA-processing proteins, suggesting that SCNM1 is involved in splicing activities. SCNM1 and LUC7L2 associate with the mammalian spliceosomal subunit U1 snRNP [].
Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in mostelectrically excitable cells []. They may exist in 3 states []: the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.There are nine pore-forming alpha subunit of voltage-gated sodium channels consisting of four membrane-embedded homologous domains (I-IV), each consisting of six α-helical segments (S1-S6), three cytoplasmic loops connecting the domains, and a cytoplasmic C-terminal tail. The S6 segments of the four domains form the inner surface of the pore, while the S4 segments bear clusters of basic residues that constitute the channel's voltage sensors [, , ].Sodium channel protein type 8 subunit alpha (SCN8A) encodes the voltage-gated Na+ channel alpha 8 subunit and is strongly expressed in Purkinje cells. Sodium currents are known to generatethe rising phase and the prolonged plateau phase of cerebellar purkinje cell action potentials. Experiments in mice with mutated SCN8A subunits suggest its involvement in the persistent sodium current responsible for the prolonged plateau phase []. SCN8A is abundantly expressed throughout the CNS and in the spinal cord. Mutations in this protein have been related to a number of neurological disorders, including paralysis, ataxia and dystonia [, , , ].This entry represents a conserved region found towards the N terminus of the protein, which defines the alpha 8 subunits and distinguishes them from other members of the voltage-gated Na+ channel superfamily. For entries containing other members of this superfamily see , , .
