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Na+ channel protein type 10 subunit alpha; Na+ channel protein type X subunit alpha; voltage-gated Na+ channel subunit alpha Nav1.8; peripheral nerve Na+ channel 3; hPN3 (SCN10A, PN3)

Function: - mediates voltage-dependent Na+ permeability of excitable membranes - assumes opened or closed conformation in response to voltage difference across the membrane - forms a Na+-selective channel through which Na+ may pass in accordance with their electrochemical gradient - tetrodotoxin-resistant Na+ channel isoform - electrophysiological properties vary depending on the type of the associated beta subunits (in vitro) - ubiquitinated by NEDD4L; which promotes its endocytosis - voltage-resistant Na+ channel consists of an ion conducting pore forming alpha-subunit regulated by one or more associated auxiliary subunits SCN1B, SCN2B & SCN3B - found in a number of complexes with PRX, TCTEL1 & PDZD2 - interacts with proteins such as FSTL1, PRX, TCTEL1, PDZD2, S100A10 & many others (putative). interacts with NEDD4 & NEDD4L Structure: - contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) & one positively charged segment (S4) - segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every third position - belongs to the Na+ channel family - contains 1 IQ domain Compartment: - membrane - translocated to extracellular membrane through association with S100A10 (putative) Expression: - expressed in the dorsal root ganglia & sciatic nerve Pathology: - plays a role in neuropathic pain mechanisms (putative) Pharmacology: - VX-548, an oral, highly selective inhibitor of NaV1.8 (SCN10A) [3]

General

glycoprotein voltage-dependent Na+ channel protein alpha subunit transmembrane 22 protein

Properties

SIZE: entity length = 1956 aa MW = 221 kD COMPARTMENT: cellular membrane MOTIF: consensus repeat {125-400} MOTIF: transmembrane domain {126-149} transmembrane domain {155-174} transmembrane domain {188-206} transmembrane domain {213-232} transmembrane domain {249-272} N-glycosylation site {N284} N-glycosylation site {N288} N-glycosylation site {N312} N-glycosylation site {N335} transmembrane domain {374-399} consensus repeat {659-891} MOTIF: transmembrane domain {660-684} transmembrane domain {696-719} transmembrane domain {728-747} transmembrane domain {754-773} transmembrane domain {790-810} N-glycosylation site {N819} transmembrane domain {865-890} consensus repeat {1147-1419} MOTIF: transmembrane domain {1148-1171} transmembrane domain {1185-1210} transmembrane domain {1217-1238} transmembrane domain {1243-1264} transmembrane domain {1284-1311} N-glycosylation site {N1312} N-glycosylation site {N1328} N-glycosylation site {N1336} transmembrane domain {1392-1418} consensus repeat {1471-1723} MOTIF: transmembrane domain {1472-1495} transmembrane domain {1507-1530} transmembrane domain {1537-1560} transmembrane domain {1573-1594} transmembrane domain {1610-1632} N-glycosylation site {N1686} transmembrane domain {1698-1722} IQ motif {1851-1880}

Database Correlations

OMIM 604427 UniProt Q9Y5Y9 PFAM correlations Entrez Gene 6336 Kegg hsa:6336

References

  1. UniProt :accession Q9Y5Y9
  2. Rabert DK, Koch BD, Ilnicka M et al A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. Pain. 1998 Nov;78(2):107-114. PMID: 9839820
  3. Jones J, Correll DJ, Lechner SM et al Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. N Engl J Med. 2023 Aug 3;389(5):393-405. PMID: 37530822 Clinical Trial.