Nav1.1

Sodium channel, voltage-gated, type I, alpha subunit
Solution structure of the rat Nav1.1 sodium channel inactivation gate.[1] This gate (25 amino acids residues in length) is a small portion of the entire sodium channel (which contains a a total of 2009 amino acids). The inactivation gate is located between repeat domains III and IV of the sodium channel protein.
Available structures PDB 1byy
Identifiers
Symbols	SCN1A; FEB3; GEFSP2; HBSCI; NAC1; Nav1.1; SCN1; SMEI
External IDs	OMIM: 182389 MGI: 98246 HomoloGene: 21375 IUPHAR: Nav1.1 GeneCards: SCN1A Gene
Gene Ontology Molecular function • voltage-gated sodium channel activity • sodium ion binding Cellular component • voltage-gated sodium channel complex • membrane • integral to membrane Biological process • ion transport • sodium ion transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6323	20265
Ensembl	ENSG00000144285	ENSMUSG00000064329
UniProt	P35498	n/a
RefSeq (mRNA)	NM_006920	XM_001001733
RefSeq (protein)	NP_008851	XP_001001733
Location (UCSC)	Chr 2: 166.55 – 166.64 Mb	Chr 2: 66.07 – 66.12 Mb
PubMed search	[1]	[2]

Na_v1.1, also known as the sodium channel, voltage-gated, type I, alpha subunit (SCN1A), is a protein which in humans is encoded by the SCN1A gene.^[2][3][4][5]

Function

The vertebrate sodium channel is a voltage-gated ion channel essential for the generation and propagation of action potentials, chiefly in nerve and muscle. Voltage-sensitive sodium channels are heteromeric complexes consisting of a large central pore-forming glycosylated alpha subunit and 2 smaller auxiliary beta subunits. Functional studies have indicated that the transmembrane alpha subunit of the brain sodium channels is sufficient for expression of functional sodium channels.^[6][7] Brain sodium channel alpha subunits form a gene subfamily with several structurally distinct isoforms clustering on chromosome 2q24, types I, II (Na_v1.2), and III (Na_v1.3). There are also several distinct sodium channel alpha subunit isoforms in skeletal and cardiac muscle (Na_v1.4^[8] and Na_v1.5,^[9] respectively).

Clinical significance

Mutations in the SCNA1 gene cause inherited febrile seizures and GEFS+, type 2.^{[10][11][12][13]}

Patent controversy

On November 29th 2008, The Sydney Morning Herald reported the first evidence of private intellectual property rights over human DNA^[14] having adversely affected medical care. The Melbourne company Genetic Technologies (GTG) controls rights to the gene, and requires royalties for tests on the gene, which can help identify Dravet syndrome. Doctors on the Children's Hospital in Westmead, Australia have told journalists that they would test 50% more infants for the gene, if they could conduct the test on site.

Interactions

Na_v1.1 has been shown to interact with syntrophin, alpha 1.^[15]

See also

• Sodium channel

References

1. ^ PDB 1byy; Rohl CA, Boeckman FA, Baker C, Scheuer T, Catterall WA, Klevit RE (January 1999). "Solution structure of the sodium channel inactivation gate". Biochemistry 38 (3): 855–61. doi:10.1021/bi9823380. PMID 9893979. 
2. ^ "Entrez Gene: SCN1A sodium channel, voltage-gated, type I, alpha subunit". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6323. 
3. ^ Malo MS, Blanchard BJ, Andresen JM, Srivastava K, Chen XN, Li X, Jabs EW, Korenberg JR, Ingram VM (1994). "Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24". Cytogenet. Cell Genet. 67 (3): 178–86. doi:10.1159/000133818. PMID 8062593. 
4. ^ Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, Hirose S, Fukuma G, Mitsudome A, Wada K, Kaneko S (January 2002). "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A". Epilepsy Res. 48 (1–2): 15–23. doi:10.1016/S0920-1211(01)00313-8. PMID 11823106. http://linkinghub.elsevier.com/retrieve/pii/S0920121101003138. 
5. ^ Catterall WA, Goldin AL, Waxman SG (December 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacol. Rev. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098. 
6. ^ Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R (October 1986). "Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes". Proc. Natl. Acad. Sci. U.S.A. 83 (19): 7503–7. doi:10.1073/pnas.83.19.7503. PMC 386747. PMID 2429308. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2429308. 
7. ^ Isom LL (January 2002). "The role of sodium channels in cell adhesion". Front. Biosci. 7: 12–23. doi:10.2741/isom. PMID 11779698. http://www.bioscience.org/2002/v7/d/isom/list.htm. 
8. ^ George AL, Komisarof J, Kallen RG, Barchi RL (February 1992). "Primary structure of the adult human skeletal muscle voltage-dependent sodium channel". Ann. Neurol. 31 (2): 131–7. doi:10.1002/ana.410310203. PMID 1315496. 
9. ^ Gellens ME, George AL, Chen LQ, et al. (January 1992). "Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel". Proc. Natl. Acad. Sci. U.S.A. 89 (2): 554–8. doi:10.1073/pnas.89.2.554. PMC 48277. PMID 1309946. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48277. 
10. ^ Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, Brice A, LeGuern E, Moulard B, Chaigne D, Buresi C, Malafosse A (April 2000). "Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2". Nat. Genet. 24 (4): 343–5. doi:10.1038/74159. PMID 10742094. 
11. ^ Spampanato J, Escayg A, Meisler MH, Goldin AL (October 2001). "Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2". J. Neurosci. 21 (19): 7481–90. PMID 11567038. 
12. ^ Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, Capovilla G, Chiron C, Cristofori G, Elia M, Fontana E, Gaggero R, Granata T, Guerrini R, Loi M, La Selva L, Lispi ML, Matricardi A, Romeo A, Tzolas V, Valseriati D, Veggiotti P, Vigevano F, Vallée L, Dagna Bricarelli F, Bianchi A, Zara F (June 2003). "Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy". Neurology 60 (12): 1961–7. PMID 12821740. 
13. ^ Lossin C. "SCN1A infobase". http://www.scn1a.info/. Retrieved 2009-10-30. "compilation of genetic variations in the SCN1A gene that alter the expression or function of Nav1.1" 
14. ^ Robotham J (2008-11-29). "Sick babies denied treatment in DNA row -". National News. Sidney Morning Herald - smh.com.au. http://www.smh.com.au/news/national/sick-babies-denied-treatment-in-row/2008/11/28/1227491827171.html. Retrieved 2008-12-03. 
15. ^ Gee, S H; Madhavan R, Levinson S R, Caldwell J H, Sealock R, Froehner S C (Jan. 1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". J. Neurosci. (UNITED STATES) 18 (1): 128–37. ISSN 0270-6474. PMID 9412493. 

Further reading

• Lerche H, Jurkat-Rott K, Lehmann-Horn F (2001). "Ion channels and epilepsy". Am. J. Med. Genet. 106 (2): 146–59. doi:10.1002/ajmg.1582. PMID 11579435. 
• Isom LL (2002). "The role of sodium channels in cell adhesion". Front. Biosci. 7: 12–23. doi:10.2741/isom. PMID 11779698. 
• Kanai K, Hirose S, Oguni H, et al. (2005). "Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity". Neurology 63 (2): 329–34. PMID 15277629. 
• Oguni H, Hayashi K, Osawa M, et al. (2004). "Severe myoclonic epilepsy in infancy: clinical analysis and relation to SCN1A mutations in a Japanese cohort". Advances in neurology 95: 103–17. PMID 15508916. 
• Mulley JC, Scheffer IE, Petrou S, et al. (2006). "SCN1A mutations and epilepsy". Hum. Mutat. 25 (6): 535–42. doi:10.1002/humu.20178. PMID 15880351. 
• Catterall WA, Goldin AL, Waxman SG (2006). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacol. Rev. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098. 
• Lu CM, Han J, Rado TA, Brown GB (1992). "Differential expression of two sodium channel subtypes in human brain". FEBS Lett. 303 (1): 53–8. doi:10.1016/0014-5793(92)80476-W. PMID 1317301. 
• Goldin AL, Snutch T, Lübbert H, et al. (1986). "Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes". Proc. Natl. Acad. Sci. U.S.A. 83 (19): 7503–7. doi:10.1073/pnas.83.19.7503. PMC 386747. PMID 2429308. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=386747. 
• Malo MS, Blanchard BJ, Andresen JM, et al. (1994). "Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24". Cytogenet. Cell Genet. 67 (3): 178–86. doi:10.1159/000133818. PMID 8062593. 
• Peiffer A, Thompson J, Charlier C, et al. (1999). "A locus for febrile seizures (FEB3) maps to chromosome 2q23-24". Ann. Neurol. 46 (4): 671–8. doi:10.1002/1531-8249(199910)46:4<671::AID-ANA20>3.0.CO;2-5. PMID 10514109. 
• Wallace RH, Scheffer IE, Barnett S, et al. (2001). "Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus". Am. J. Hum. Genet. 68 (4): 859–65. doi:10.1086/319516. PMC 1275639. PMID 11254444. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1275639. 
• Escayg A, Heils A, MacDonald BT, et al. (2001). "A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy". Am. J. Hum. Genet. 68 (4): 866–73. doi:10.1086/319524. PMC 1275640. PMID 11254445. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1275640. 
• Whitaker WR, Faull RL, Waldvogel HJ, et al. (2001). "Comparative distribution of voltage-gated sodium channel proteins in human brain". Brain Res. Mol. Brain Res. 88 (1–2): 37–53. doi:10.1016/S0169-328X(00)00289-8. PMID 11295230. 
• Claes L, Del-Favero J, Ceulemans B, et al. (2001). "De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy". Am. J. Hum. Genet. 68 (6): 1327–32. doi:10.1086/320609. PMC 1226119. PMID 11359211. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1226119. 
• Sugawara T, Mazaki-Miyazaki E, Ito M, et al. (2001). "Nav1.1 mutations cause febrile seizures associated with afebrile partial seizures". Neurology 57 (4): 703–5. PMID 11524484. 
• Abou-Khalil B, Ge Q, Desai R, et al. (2003). "Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation". Neurology 57 (12): 2265–72. PMID 11756608. 
• Ito M, Nagafuji H, Okazawa H, et al. (2002). "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A". Epilepsy Res. 48 (1–2): 15–23. doi:10.1016/S0920-1211(01)00313-8. PMID 11823106. 

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hemiplegic Migraine
• GeneReviews/NCBI/NIH/UW entry on SCN1A-Related Seizure Disorders
• MeSH SCN1A+protein,+human

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