Scn1a
Domain
The S3b-S4 and S1-S2 loops of repeat IV are targeted by H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b depends on S1-S2 loops of repeat IV (PubMed:27281198).
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
Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:16921370, PubMed:17928448, PubMed:27281198). By regulating the excitability of neurons, ensures that they respond appropriately to synaptic inputs, maintaining the balance between excitation and inhibition in brain neural circuits (PubMed:16921370, PubMed:22914087). Nav1.1 plays a role in controlling the excitability and action potential propagation from somatosensory neurons, thereby contributing to the sensory perception of mechanically-induced pain (PubMed:27281198).
Post-translational modifications
Phosphorylation at Ser-1516 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.1/SCN1A subfamily.
Tissue Specificity
Present in cerebellar Purkinje neurons (at protein level) (PubMed:17928448). Expressed by myelinated, non-C-fiber neurons in sensory ganglia (PubMed:27281198).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
Sodium channel protein type 1 subunit alpha, Sodium channel protein brain I subunit alpha, Sodium channel protein type I subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.1, Scn1a