SCN10A

The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Full Name

Sodium Voltage-Gated Channel Alpha Subunit 10

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.

Cellular Location

Cell membrane
It can be translocated to the cell membrane through association with S100A10.

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.

Topology

Cytoplasmic: 1-125
Helical: 126-149
Extracellular: 150-154
Helical: 155-174
Cytoplasmic: 175-187
Helical: 188-206
Extracellular: 207-212
Helical: 213-232
Cytoplasmic: 233-248
Helical: 249-272
Extracellular: 273-341
Pore-forming: 342-366
Extracellular: 367-373
Helical: 374-399
Cytoplasmic: 400-659
Helical: 660-684
Extracellular: 685-695
Helical: 696-719
Cytoplasmic: 720-727
Helical: 728-747
Extracellular: 748-753
Helical: 754-773
Cytoplasmic: 790-810
Helical: 790-810
Extracellular: 811-834
Pore-forming: 835-855
Extracellular: 856-864
Helical: 865-890
Cytoplasmic: 891-1147
Helical: 1148-1171
Extracellular: 1172-1184
Helical: 1185-1210
Cytoplasmic: 1211-1216
Helical: 1217-1238
Extracellular: 1239-1242
Helical: 1243-1264
Cytoplasmic: 1265-1283
Helical: 1284-1311
Extracellular: 1312-1353
Pore-forming: 1354-1375
Extracellular: 1376-1391
Helical: 1392-1418
Cytoplasmic: 1419-1471
Helical: 1472-1495
Extracellular: 1496-1506
Helical: 1507-1530
Cytoplasmic: 1531-1536
Helical: 1537-1560
Extracellular: 1561-1572
Helical: 1573-1594
Cytoplasmic: 1595-1609
Helical: 1610-1632
Extracellular: 1633-1646
Pore-forming: 1647-1669
Extracellular: 1670-1697
Helical: 1698-1722
Cytoplasmic: 1723-1956

PTM

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.