FUNCTION: SwissProt: Q15858 # 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 Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
SIZE: 1988 amino acids; 226342 Da
SUBUNIT: The sodium channel consists of a large polypeptide and 2- 3 smaller ones. This sequence represents a large polypeptide. Interacts with NEDD4 and NEDD4L (By similarity).
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Note=In neurite terminals (By similarity).
TISSUE SPECIFICITY: Expressed strongly in dorsal root ganglion, with only minor levels elsewhere in the body, smooth muscle cells, MTC cell line and C-cell carcinoma. Isoform 1 is expressed preferentially in the central and peripheral nervous system while isoform 2 is expressed preferentially in the dorsal root ganglion.
DOMAIN: SwissProt: Q15858 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.
PTM: Ubiquitinated by NEDD4L; which may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4 (By similarity).
DISEASE: SwissProt: Q15858 # Defects in SCN9A are the cause of primary erythermalgia [MIM:133020]. It is an autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. & Defects in SCN9A are the cause of autosomal recessive congenital indifference to pain [MIM:243000]; also known as channelopathy-associated insensitivity to pain. Affected individuals have a congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating. & Defects in SCN9A are a cause of paroxysmal extreme pain disorder (PEPD) [MIM:167400]; previously known as familial rectal pain (FRP). PEPD is an autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing.
SIMILARITY: Belongs to the sodium channel family. & Contains 1 IQ domain.