ID SCN8A_HUMAN Reviewed; 1980 AA. AC Q9UQD0; B9VWG8; O95788; Q9NYX2; Q9UPB2; DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 24-JAN-2024, entry version 200. DE RecName: Full=Sodium channel protein type 8 subunit alpha; DE AltName: Full=Sodium channel protein type VIII subunit alpha; DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.6; GN Name=SCN8A; Synonyms=MED; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000312|EMBL:BAA78033.1}; RN [1] RP NUCLEOTIDE SEQUENCE (ISOFORM 4). RC TISSUE=Brain, and Fetal brain; RX PubMed=9295353; DOI=10.1074/jbc.272.38.24008; RA Plummer N.W., McBurney M.W., Meisler M.H.; RT "Alternative splicing of the sodium channel SCN8A predicts a truncated two- RT domain protein in fetal brain and non-neuronal cells."; RL J. Biol. Chem. 272:24008-24015(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3). RX PubMed=9828131; DOI=10.1006/geno.1998.5550; RA Plummer N.W., Galt J., Jones J.M., Burgess D.L., Sprunger L.K., RA Kohrman D.C., Meisler M.H.; RT "Exon organization, coding sequence, physical mapping, and polymorphic RT intragenic markers for the human neuronal sodium channel gene SCN8A."; RL Genomics 54:287-296(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC TISSUE=Monocytic leukemia; RX PubMed=19136557; DOI=10.1074/jbc.m801892200; RA Carrithers M.D., Chatterjee G., Carrithers L.M., Offoha R., Iheagwara U., RA Rahner C., Graham M., Waxman S.G.; RT "Regulation of podosome formation in macrophages by a splice variant of the RT sodium channel SCN8A."; RL J. Biol. Chem. 284:8114-8126(2009). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Lin C., Numakura C., Kiyoshi H.; RT "cDNA sequence of human sodium channel, SCN8A."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Jeong S.-Y., Goto J., Kanazawa I.; RT "Cloning of cDNA for human voltage-gated sodium channel alpha subunit, RT SCN8A."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [7] RP INTERACTION WITH FGF13. RX PubMed=15282281; DOI=10.1523/jneurosci.1628-04.2004; RA Wittmack E.K., Rush A.M., Craner M.J., Goldfarb M., Waxman S.G., RA Dib-Hajj S.D.; RT "Fibroblast growth factor homologous factor 2B: association with Nav1.6 and RT selective colocalization at nodes of Ranvier of dorsal root axons."; RL J. Neurosci. 24:6765-6775(2004). RN [8] RP INVOLVEMENT IN CIAT. RX PubMed=16236810; DOI=10.1136/jmg.2005.035667; RA Trudeau M.M., Dalton J.C., Day J.W., Ranum L.P., Meisler M.H.; RT "Heterozygosity for a protein truncation mutation of sodium channel SCN8A RT in a patient with cerebellar atrophy, ataxia, and mental retardation."; RL J. Med. Genet. 43:527-530(2006). RN [9] RP INTERACTION WITH THE CONOTOXIN GVIIJ. RX PubMed=24497506; DOI=10.1073/pnas.1324189111; RA Gajewiak J., Azam L., Imperial J., Walewska A., Green B.R., RA Bandyopadhyay P.K., Raghuraman S., Ueberheide B., Bern M., Zhou H.M., RA Minassian N.A., Hagan R.H., Flinspach M., Liu Y., Bulaj G., Wickenden A.D., RA Olivera B.M., Yoshikami D., Zhang M.M.; RT "A disulfide tether stabilizes the block of sodium channels by the RT conotoxin muO[section sign]-GVIIJ."; RL Proc. Natl. Acad. Sci. U.S.A. 111:2758-2763(2014). RN [10] RP SUBUNIT, INTERACTION WITH THE SPIDER BETA/DELTA-THERAPHOTOXIN-PRE1A, AND RP SITE SER-1574. RX PubMed=28428547; DOI=10.1038/s41598-017-01129-0; RA Wingerd J.S., Mozar C.A., Ussing C.A., Murali S.S., Chin Y.K., RA Cristofori-Armstrong B., Durek T., Gilchrist J., Vaughan C.W., Bosmans F., RA Adams D.J., Lewis R.J., Alewood P.F., Mobli M., Christie M.J., Rash L.D.; RT "The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance of the RT S1-S2 voltage-sensor region for sodium channel subtype selectivity."; RL Sci. Rep. 7:974-988(2017). RN [11] RP FUNCTION, AND INTERACTION WITH FGF13. RX PubMed=33245860; DOI=10.1016/j.ajhg.2020.10.017; RG Genomics England Research Consortium; RA Fry A.E., Marra C., Derrick A.V., Pickrell W.O., Higgins A.T., RA Te Water Naude J., McClatchey M.A., Davies S.J., Metcalfe K.A., Tan H.J., RA Mohanraj R., Avula S., Williams D., Brady L.I., Mesterman R., RA Tarnopolsky M.A., Zhang Y., Yang Y., Wang X., Rees M.I., Goldfarb M., RA Chung S.K.; RT "Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 RT cause an X-linked developmental and epileptic encephalopathy."; RL Am. J. Hum. Genet. 108:176-185(2021). RN [12] RP SUBUNIT. RX PubMed=37117223; DOI=10.1038/s41467-023-37963-2; RA Jami S., Deuis J.R., Klasfauseweh T., Cheng X., Kurdyukov S., Chung F., RA Okorokov A.L., Li S., Zhang J., Cristofori-Armstrong B., Israel M.R., RA Ju R.J., Robinson S.D., Zhao P., Ragnarsson L., Andersson A., Tran P., RA Schendel V., McMahon K.L., Tran H.N.T., Chin Y.K., Zhu Y., Liu J., RA Crawford T., Purushothamvasan S., Habib A.M., Andersson D.A., Rash L.D., RA Wood J.N., Zhao J., Stehbens S.J., Mobli M., Leffler A., Jiang D., RA Cox J.J., Waxman S.G., Dib-Hajj S.D., Gregory Neely G., Durek T., RA Vetter I.; RT "Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 RT function."; RL Nat. Commun. 14:2442-2442(2023). RN [13] {ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) IN COMPLEX WITH SCN1B; RP SCN2B; NA(+) AND INHIBITOR 4,9-ANHYDRO-TETRODOTOXIN, FUNCTION, ACTIVITY RP REGULATION, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-289; ASN-295; RP ASN-308; ASN-326; ASN-1358 AND ASN-1372, AND MUTAGENESIS OF RP 1416-MET-ASP-1417. RX PubMed=36823201; DOI=10.1038/s41467-023-36766-9; RA Li Y., Yuan T., Huang B., Zhou F., Peng C., Li X., Qiu Y., Yang B., RA Zhao Y., Huang Z., Jiang D.; RT "Structure of human NaV1.6 channel reveals Na+ selectivity and pore RT blockade by 4,9-anhydro-tetrodotoxin."; RL Nat. Commun. 14:1030-1030(2023). RN [14] {ECO:0007744|PDB:8FHD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) IN COMPLEX WITH SCN1B, RP FUNCTION, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-295; ASN-308; RP ASN-326; ASN-1358 AND ASN-1372. RX PubMed=36696443; DOI=10.1073/pnas.2220578120; RA Fan X., Huang J., Jin X., Yan N.; RT "Cryo-EM structure of human voltage-gated sodium channel Nav1.6."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2220578120-e2220578120(2023). RN [15] RP VARIANT DEE13 ASP-1768, AND CHARACTERIZATION OF VARIANT DEE13 ASP-1768. RX PubMed=22365152; DOI=10.1016/j.ajhg.2012.01.006; RA Veeramah K.R., O'Brien J.E., Meisler M.H., Cheng X., Dib-Hajj S.D., RA Waxman S.G., Talwar D., Girirajan S., Eichler E.E., Restifo L.L., RA Erickson R.P., Hammer M.F.; RT "de novo pathogenic SCN8A mutation identified by whole-genome sequencing of RT a family quartet affected by infantile epileptic encephalopathy and RT SUDEP."; RL Am. J. Hum. Genet. 90:502-510(2012). RN [16] RP VARIANT DEE13 VAL-1327. RX PubMed=24352161; DOI=10.1177/0883073813511300; RA Vaher U., Noukas M., Nikopensius T., Kals M., Annilo T., Nelis M., RA Ounap K., Reimand T., Talvik I., Ilves P., Piirsoo A., Seppet E., RA Metspalu A., Talvik T.; RT "De novo SCN8A mutation identified by whole-exome sequencing in a boy with RT neonatal epileptic encephalopathy, multiple congenital anomalies, and RT movement disorders."; RL J. Child Neurol. 0:0-0(2013). RN [17] RP VARIANTS DEE13 CYS-662 AND VAL-1279. RX PubMed=23708187; DOI=10.1038/ng.2646; RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J., RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G., RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T., RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N., RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L., RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.; RT "Targeted resequencing in epileptic encephalopathies identifies de novo RT mutations in CHD2 and SYNGAP1."; RL Nat. Genet. 45:825-830(2013). RN [18] RP VARIANTS DEE13 ASP-216; SER-846; LYS-1466; THR-1466; GLN-1617; THR-1650 AND RP TRP-1872. RX PubMed=24888894; DOI=10.1111/epi.12668; RA Ohba C., Kato M., Takahashi S., Lerman-Sagie T., Lev D., Terashima H., RA Kubota M., Kawawaki H., Matsufuji M., Kojima Y., Tateno A., RA Goldberg-Stern H., Straussberg R., Marom D., Leshinsky-Silver E., RA Nakashima M., Nishiyama K., Tsurusaki Y., Miyake N., Tanaka F., RA Matsumoto N., Saitsu H.; RT "Early onset epileptic encephalopathy caused by de novo SCN8A mutations."; RL Epilepsia 55:994-1000(2014). RN [19] RP VARIANT DEE13 GLY-223, AND CHARACTERIZATION OF VARIANT DEE13 GLY-223. RX PubMed=25239001; DOI=10.1016/j.eplepsyres.2014.08.020; RA de Kovel C.G., Meisler M.H., Brilstra E.H., van Berkestijn F.M., Slot R.V., RA van Lieshout S., Nijman I.J., O'Brien J.E., Hammer M.F., Estacion M., RA Waxman S.G., Dib-Hajj S.D., Koeleman B.P.; RT "Characterization of a de novo SCN8A mutation in a patient with epileptic RT encephalopathy."; RL Epilepsy Res. 108:1511-1518(2014). RN [20] RP VARIANT DEE13 ILE-767, AND CHARACTERIZATION OF VARIANT DEE13 ILE-767. RX PubMed=24874546; DOI=10.1016/j.nbd.2014.05.017; RA Estacion M., O'Brien J.E., Conravey A., Hammer M.F., Waxman S.G., RA Dib-Hajj S.D., Meisler M.H.; RT "A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel RT activation in a child with epileptic encephalopathy."; RL Neurobiol. Dis. 69:117-123(2014). RN [21] RP VARIANTS DEE13 PHE-407; GLN-850; THR-890; CYS-1596 AND GLN-1617. RX PubMed=25785782; DOI=10.1111/epi.12925; RA Kong W., Zhang Y., Gao Y., Liu X., Gao K., Xie H., Wang J., Wu Y., RA Zhang Y., Wu X., Jiang Y.; RT "SCN8A mutations in Chinese children with early onset epilepsy and RT intellectual disability."; RL Epilepsia 56:431-438(2015). RN [22] RP VARIANT DEE13 LEU-210. RX PubMed=25818041; DOI=10.1111/epi.12954; RA Mercimek-Mahmutoglu S., Patel J., Cordeiro D., Hewson S., Callen D., RA Donner E.J., Hahn C.D., Kannu P., Kobayashi J., Minassian B.A., Moharir M., RA Siriwardena K., Weiss S.K., Weksberg R., Snead O.C. III; RT "Diagnostic yield of genetic testing in epileptic encephalopathy in RT childhood."; RL Epilepsia 56:707-716(2015). RN [23] RP VARIANTS DEE13 ASN-58; LYS-984 AND SER-1451, AND CHARACTERIZATION OF RP VARIANTS DEE13 ASN-58; LYS-984 AND SER-1451. RX PubMed=25725044; DOI=10.1136/jmedgenet-2014-102813; RA Blanchard M.G., Willemsen M.H., Walker J.B., Dib-Hajj S.D., Waxman S.G., RA Jongmans M.C., Kleefstra T., van de Warrenburg B.P., Praamstra P., RA Nicolai J., Yntema H.G., Bindels R.J., Meisler M.H., Kamsteeg E.J.; RT "De novo gain-of-function and loss-of-function mutations of SCN8A in RT patients with intellectual disabilities and epilepsy."; RL J. Med. Genet. 52:330-337(2015). RN [24] RP VARIANTS DEE13 ARG-215; SER-260; LEU-410; VAL-479; THR-890; ASP-960; RP VAL-1331; VAL-1479; LEU-1592; ARG-1605; GLN-1617; THR-1650; GLU-1801; RP GLN-1872 AND TRP-1872. RX PubMed=25568300; DOI=10.1212/wnl.0000000000001211; RG EuroEPINOMICS RES Consortium CRP; RA Larsen J., Carvill G.L., Gardella E., Kluger G., Schmiedel G., Barisic N., RA Depienne C., Brilstra E., Mang Y., Nielsen J.E., Kirkpatrick M., Goudie D., RA Goldman R., Jaehn J.A., Jepsen B., Gill D., Doecker M., Biskup S., RA McMahon J.M., Koeleman B., Harris M., Braun K., de Kovel C.G., Marini C., RA Specchio N., Djemie T., Weckhuysen S., Tommerup N., Troncoso M., RA Troncoso L., Bevot A., Wolff M., Hjalgrim H., Guerrini R., Scheffer I.E., RA Mefford H.C., Moeller R.S.; RT "The phenotypic spectrum of SCN8A encephalopathy."; RL Neurology 84:480-489(2015). RN [25] RP VARIANT DEE13 SER-1877, AND VARIANT BFIS5 SER-1877. RX PubMed=27210545; DOI=10.1016/j.ejpn.2016.04.015; RA Anand G., Collett-White F., Orsini A., Thomas S., Jayapal S., Trump N., RA Zaiwalla Z., Jayawant S.; RT "Autosomal dominant SCN8A mutation with an unusually mild phenotype."; RL Eur. J. Paediatr. Neurol. 20:761-765(2016). RN [26] RP VARIANTS DEE13 GLN-1617; GLN-1872; LEU-1872 AND TRP-1872, CHARACTERIZATION RP OF VARIANTS DEE13 GLN-1617; GLN-1872; LEU-1872 AND TRP-1872, AND RP INTERACTION WITH FGF14; GBG3; GBB2 AND SCN1B. RX PubMed=26900580; DOI=10.1002/acn3.276; RA Wagnon J.L., Barker B.S., Hounshell J.A., Haaxma C.A., Shealy A., Moss T., RA Parikh S., Messer R.D., Patel M.K., Meisler M.H.; RT "Pathogenic mechanism of recurrent mutations of SCN8A in epileptic RT encephalopathy."; RL Ann. Clin. Transl. Neurol. 3:114-123(2016). RN [27] RP VARIANT BFIS5 LYS-1483, AND INVOLVEMENT IN BFIS5. RX PubMed=26677014; DOI=10.1002/ana.24580; RA Gardella E., Becker F., Moeller R.S., Schubert J., Lemke J.R., Larsen L.H., RA Eiberg H., Nothnagel M., Thiele H., Altmueller J., Syrbe S., RA Merkenschlager A., Bast T., Steinhoff B., Nuernberg P., Mang Y., RA Bakke Moeller L., Gellert P., Heron S.E., Dibbens L.M., Weckhuysen S., RA Dahl H.A., Biskup S., Tommerup N., Hjalgrim H., Lerche H., Beniczky S., RA Weber Y.G.; RT "Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A RT mutation."; RL Ann. Neurol. 79:428-436(2016). RN [28] RP VARIANTS DEE13 THR-408; SER-1323; VAL-1327; SER-1754 AND PRO-1865. RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263; RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A., RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A., RA Scott R.H.; RT "Improving diagnosis and broadening the phenotypes in early-onset seizure RT and severe developmental delay disorders through gene panel analysis."; RL J. Med. Genet. 53:310-317(2016). RN [29] RP VARIANTS DEE13 PRO-232; GLU-850; MET-891; ARG-1475; ALA-1598; TRP-1872 AND RP SER-1877. RX PubMed=28923014; DOI=10.1186/s12881-017-0460-1; RA Wang J., Gao H., Bao X., Zhang Q., Li J., Wei L., Wu X., Chen Y., Yu S.; RT "SCN8A mutations in Chinese patients with early onset epileptic RT encephalopathy and benign infantile seizures."; RL BMC Med. Genet. 18:104-104(2017). RN [30] RP VARIANTS DEE13 SER-307; GLY-978; ARG-1475; THR-1650 AND TRP-1872, AND RP VARIANT SER-1877. RX PubMed=27864847; DOI=10.1002/humu.23149; RG Clinical Study Group; RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D., RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S., RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.; RT "Diagnostic targeted resequencing in 349 patients with drug-resistant RT pediatric epilepsies identifies causative mutations in 30 different RT genes."; RL Hum. Mutat. 38:216-225(2017). RN [31] RP TISSUE SPECIFICITY. RX PubMed=28842554; DOI=10.1038/s41467-017-00368-z; RA Liu Y., Lai S., Ma W., Ke W., Zhang C., Liu S., Zhang Y., Pei F., Li S., RA Yi M., Shu Y., Shang Y., Liang J., Huang Z.; RT "CDYL suppresses epileptogenesis in mice through repression of axonal RT Nav1.6 sodium channel expression."; RL Nat. Commun. 8:355-355(2017). RN [32] RP FUNCTION, INVOLVEMENT IN MYOCL2, VARIANT MYOCL2 ARG-1719, AND RP CHARACTERIZATION OF VARIANT MYOCL2 ARG-1719. RX PubMed=29726066; DOI=10.1002/humu.23547; RA Wagnon J.L., Mencacci N.E., Barker B.S., Wengert E.R., Bhatia K.P., RA Balint B., Carecchio M., Wood N.W., Patel M.K., Meisler M.H.; RT "Partial loss-of-function of sodium channel SCN8A in familial isolated RT myoclonus."; RL Hum. Mutat. 39:965-969(2018). CC -!- FUNCTION: Mediates the voltage-dependent sodium ion permeability of CC excitable membranes (PubMed:29726066). Assuming opened or closed CC conformations in response to the voltage difference across the CC membrane, the protein forms a sodium-selective channel through which CC Na(+) ions may pass in accordance with their electrochemical gradient. CC {ECO:0000269|PubMed:19136557, ECO:0000269|PubMed:29726066, CC ECO:0000269|PubMed:33245860, ECO:0000269|PubMed:36696443, CC ECO:0000269|PubMed:36823201}. CC -!- FUNCTION: [Isoform 5]: In macrophages and melanoma cells, may CC participate in the control of podosome and invadopodia formation. CC {ECO:0000269|PubMed:29726066}. CC -!- ACTIVITY REGULATION: Inhibited by tetrodotoxin and, more weakly, by its CC metabolite 4,9-ah-tetrodotoxin. {ECO:0000269|PubMed:36823201}. CC -!- SUBUNIT: The voltage-sensitive sodium channel consists of an ion- CC conducting pore-forming alpha subunit regulated by one or more beta-1 CC (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B) subunits. CC Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with CC alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by CC disulfide bonds. Interacts with NEDD4 and NEDD4L (By similarity). CC Interacts with FGF13 (PubMed:33245860). Interacts with FGF14, GBG3, CC GBB2 and SCN1B (PubMed:26900580). Interacts with TMEM233 CC (PubMed:37117223). Interacts with the conotoxin GVIIJ CC (PubMed:24497506). Interacts with the spider beta/delta-theraphotoxin- CC Pre1a (PubMed:28428547). Interacts with CALM1; the interaction CC modulates the inactivation rate of SCN8A (By similarity). CC {ECO:0000250|UniProtKB:Q9WTU3, ECO:0000269|PubMed:15282281, CC ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:26900580, CC ECO:0000269|PubMed:28428547, ECO:0000269|PubMed:33245860, CC ECO:0000269|PubMed:36696443, ECO:0000269|PubMed:36823201, CC ECO:0000305|PubMed:37117223}. CC -!- INTERACTION: CC Q9UQD0; Q92915-2: FGF14; NbExp=3; IntAct=EBI-2682072, EBI-12836320; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19136557}; CC Multi-pass membrane protein {ECO:0000269|PubMed:19136557}. Cell CC projection, axon {ECO:0000250|UniProtKB:Q9WTU3}. Note=Mainly localizes CC to the axon initial segment. {ECO:0000250|UniProtKB:Q9WTU3}. CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasmic vesicle. Note=Some CC vesicles are localized adjacent to melanoma invadopodia and macrophage CC podosomes. Does not localize to the plasma membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1 {ECO:0000269|PubMed:9828131}; CC IsoId=Q9UQD0-1; Sequence=Displayed; CC Name=2 {ECO:0000269|PubMed:9828131}; Synonyms=5A CC {ECO:0000269|PubMed:9828131}; CC IsoId=Q9UQD0-2; Sequence=VSP_050589, VSP_050590; CC Name=3 {ECO:0000269|PubMed:9828131}; CC IsoId=Q9UQD0-3; Sequence=VSP_050591; CC Name=4 {ECO:0000269|PubMed:9295353}; Synonyms=18N CC {ECO:0000269|PubMed:9295353}; CC IsoId=Q9UQD0-4; Sequence=VSP_050592, VSP_050593; CC Name=5; CC IsoId=Q9UQD0-5; Sequence=VSP_038651; CC -!- TISSUE SPECIFICITY: Expressed in the hippocampus with increased CC expression in epileptic tissue compared to normal adjacent tissue (at CC protein level) (PubMed:28842554). Isoform 5: Expressed in non-neuronal CC tissues, such as monocytes/macrophages. {ECO:0000269|PubMed:19136557, CC ECO:0000269|PubMed:28842554}. CC -!- INDUCTION: Up-regulated in the hippocampus after epilepsy. CC {ECO:0000269|PubMed:28842554}. CC -!- DOMAIN: The sequence contains 4 internal repeats, each with 5 CC hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged CC segment (S4). Segments S4 are probably the voltage-sensors and are CC characterized by a series of positively charged amino acids at every CC third position. {ECO:0000305}. CC -!- PTM: May be ubiquitinated by NEDD4L; which would promote its CC endocytosis. {ECO:0000250}. CC -!- PTM: Phosphorylation at Ser-1497 by PKC in a highly conserved CC cytoplasmic loop slows inactivation of the sodium channel and reduces CC peak sodium currents. {ECO:0000250}. CC -!- DISEASE: Cognitive impairment with or without cerebellar ataxia (CIAT) CC [MIM:614306]: A disorder characterized by markedly delayed cognitive CC and motor development, attention deficit disorder, and cerebellar CC ataxia. Features include bilateral esophoria, strabismatic amblyopia, CC unsustained gaze evoked nystagmus on horizontal gaze, ataxic gait, CC dysmetria in the upper limbs and dysarthria, with normal strength, CC tone, and reflexes. {ECO:0000269|PubMed:16236810}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 13 (DEE13) CC [MIM:614558]: A form of epilepsy characterized by frequent tonic CC seizures or spasms beginning in infancy with a specific EEG finding of CC suppression-burst patterns, characterized by high-voltage bursts CC alternating with almost flat suppression phases. Patients may progress CC to West syndrome, which is characterized by tonic spasms with CC clustering, arrest of psychomotor development, and hypsarrhythmia on CC EEG. DEE13 is a severe form consisting of early-onset seizures, CC features of autism, intellectual disability, ataxia, and sudden CC unexplained death in epilepsy. {ECO:0000269|PubMed:22365152, CC ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24352161, CC ECO:0000269|PubMed:24874546, ECO:0000269|PubMed:24888894, CC ECO:0000269|PubMed:25239001, ECO:0000269|PubMed:25568300, CC ECO:0000269|PubMed:25725044, ECO:0000269|PubMed:25785782, CC ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26900580, CC ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27210545, CC ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28923014}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Seizures, benign familial infantile, 5 (BFIS5) [MIM:617080]: A CC form of benign familial infantile epilepsy, a neurologic disorder CC characterized by afebrile seizures occurring in clusters during the CC first year of life, without neurologic sequelae. BFIS5 inheritance is CC autosomal dominant. {ECO:0000269|PubMed:26677014, CC ECO:0000269|PubMed:27210545}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myoclonus, familial, 2 (MYOCL2) [MIM:618364]: An autosomal CC dominant neurologic disorder characterized by upper limb isolated CC myoclonus without seizures or cognitive impairment. MYOCL2 is a non- CC progressive disease with onset in the first decade of life. CC {ECO:0000269|PubMed:29726066}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. CC Nav1.6/SCN8A subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF050736; AAD15789.1; -; Genomic_DNA. DR EMBL; AF050711; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050712; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050713; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050714; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050715; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050716; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050717; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050718; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050719; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050720; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050721; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050722; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050723; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050724; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050725; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050726; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050727; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050728; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050729; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050730; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050731; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050732; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050733; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050734; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF050735; AAD15789.1; JOINED; Genomic_DNA. DR EMBL; AF049618; AAD20439.1; -; Genomic_DNA. DR EMBL; FJ611941; ACM63162.1; -; mRNA. DR EMBL; AB027567; BAA78033.1; -; mRNA. DR EMBL; AF225988; AAF35390.1; -; mRNA. DR EMBL; AC013421; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025097; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068987; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC140060; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS44891.1; -. [Q9UQD0-1] DR CCDS; CCDS53794.1; -. [Q9UQD0-5] DR CCDS; CCDS81692.1; -. [Q9UQD0-2] DR RefSeq; NP_001171455.1; NM_001177984.2. [Q9UQD0-5] DR RefSeq; NP_001317189.1; NM_001330260.1. [Q9UQD0-2] DR RefSeq; NP_055006.1; NM_014191.3. [Q9UQD0-1] DR RefSeq; XP_006719619.1; XM_006719556.3. DR RefSeq; XP_011536953.1; XM_011538651.2. DR RefSeq; XP_016875283.1; XM_017019794.1. DR PDB; 8FHD; EM; 3.10 A; A=1-1980. DR PDB; 8GZ1; EM; 3.40 A; B=1-1980. DR PDB; 8GZ2; EM; 3.30 A; B=1-1980. DR PDBsum; 8FHD; -. DR PDBsum; 8GZ1; -. DR PDBsum; 8GZ2; -. DR AlphaFoldDB; Q9UQD0; -. DR EMDB; EMD-29082; -. DR EMDB; EMD-34387; -. DR EMDB; EMD-34388; -. DR SMR; Q9UQD0; -. DR BioGRID; 112238; 7. DR IntAct; Q9UQD0; 2. DR STRING; 9606.ENSP00000346534; -. DR BindingDB; Q9UQD0; -. DR ChEMBL; CHEMBL5202; -. DR DrugBank; DB09088; Amylocaine. DR DrugBank; DB13746; Bioallethrin. DR DrugBank; DB05541; Brivaracetam. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB01161; Chloroprocaine. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB13269; Dichlorobenzyl alcohol. DR DrugBank; DB13961; Fish oil. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB00776; Oxcarbazepine. DR DrugBank; DB11186; Pentoxyverine. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB09345; Pramocaine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB09342; Propoxycaine. DR DrugBank; DB00243; Ranolazine. DR DrugBank; DB09085; Tetracaine. DR DrugBank; DB05232; Tetrodotoxin. DR DrugBank; DB00273; Topiramate. DR DrugBank; DB00313; Valproic acid. DR DrugCentral; Q9UQD0; -. DR GuidetoPHARMACOLOGY; 583; -. DR TCDB; 1.A.1.10.8; the voltage-gated ion channel (vic) superfamily. DR GlyConnect; 1754; 1 N-Linked glycan (1 site). DR GlyCosmos; Q9UQD0; 8 sites, No reported glycans. DR GlyGen; Q9UQD0; 8 sites. DR iPTMnet; Q9UQD0; -. DR PhosphoSitePlus; Q9UQD0; -. DR SwissPalm; Q9UQD0; -. DR BioMuta; SCN8A; -. DR DMDM; 34098756; -. DR EPD; Q9UQD0; -. DR MassIVE; Q9UQD0; -. DR PaxDb; 9606-ENSP00000346534; -. DR PeptideAtlas; Q9UQD0; -. DR ProteomicsDB; 85544; -. [Q9UQD0-1] DR ProteomicsDB; 85545; -. [Q9UQD0-2] DR ProteomicsDB; 85546; -. [Q9UQD0-3] DR ProteomicsDB; 85547; -. [Q9UQD0-4] DR ProteomicsDB; 85548; -. [Q9UQD0-5] DR ABCD; Q9UQD0; 1 sequenced antibody. DR Antibodypedia; 26454; 237 antibodies from 29 providers. DR DNASU; 6334; -. DR Ensembl; ENST00000354534.11; ENSP00000346534.4; ENSG00000196876.19. [Q9UQD0-1] DR Ensembl; ENST00000355133.7; ENSP00000347255.4; ENSG00000196876.19. [Q9UQD0-5] DR Ensembl; ENST00000545061.5; ENSP00000440360.1; ENSG00000196876.19. [Q9UQD0-5] DR Ensembl; ENST00000599343.5; ENSP00000476447.3; ENSG00000196876.19. [Q9UQD0-3] DR Ensembl; ENST00000627620.5; ENSP00000487583.2; ENSG00000196876.19. [Q9UQD0-2] DR Ensembl; ENST00000662684.1; ENSP00000499636.1; ENSG00000196876.19. [Q9UQD0-2] DR GeneID; 6334; -. DR KEGG; hsa:6334; -. DR MANE-Select; ENST00000627620.5; ENSP00000487583.2; NM_001330260.2; NP_001317189.1. [Q9UQD0-2] DR UCSC; uc001ryw.4; human. [Q9UQD0-1] DR AGR; HGNC:10596; -. DR CTD; 6334; -. DR DisGeNET; 6334; -. DR GeneCards; SCN8A; -. DR GeneReviews; SCN8A; -. DR HGNC; HGNC:10596; SCN8A. DR HPA; ENSG00000196876; Group enriched (brain, pituitary gland, retina). DR MalaCards; SCN8A; -. DR MIM; 600702; gene. DR MIM; 614306; phenotype. DR MIM; 614558; phenotype. DR MIM; 617080; phenotype. DR MIM; 618364; phenotype. DR neXtProt; NX_Q9UQD0; -. DR OpenTargets; ENSG00000196876; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR Orphanet; 306; Benign familial infantile epilepsy. DR Orphanet; 31709; Infantile convulsions and choreoathetosis. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR PharmGKB; PA35009; -. DR VEuPathDB; HostDB:ENSG00000196876; -. DR eggNOG; KOG2301; Eukaryota. DR GeneTree; ENSGT00940000156263; -. DR InParanoid; Q9UQD0; -. DR OMA; YNDSNFY; -. DR OrthoDB; 1110761at2759; -. DR PhylomeDB; Q9UQD0; -. DR TreeFam; TF323985; -. DR PathwayCommons; Q9UQD0; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation. DR SignaLink; Q9UQD0; -. DR SIGNOR; Q9UQD0; -. DR BioGRID-ORCS; 6334; 13 hits in 1149 CRISPR screens. DR ChiTaRS; SCN8A; human. DR GeneWiki; SCN8A; -. DR GenomeRNAi; 6334; -. DR Pharos; Q9UQD0; Tclin. DR PRO; PR:Q9UQD0; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9UQD0; Protein. DR Bgee; ENSG00000196876; Expressed in Brodmann (1909) area 23 and 149 other cell types or tissues. DR ExpressionAtlas; Q9UQD0; baseline and differential. DR GO; GO:0030424; C:axon; ISS:ARUK-UCL. DR GO; GO:0043194; C:axon initial segment; ISS:BHF-UCL. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL. DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0098839; C:postsynaptic density membrane; IEA:Ensembl. DR GO; GO:0048787; C:presynaptic active zone membrane; IEA:Ensembl. DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central. DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:UniProtKB. DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IBA:GO_Central. DR GO; GO:0031402; F:sodium ion binding; IDA:UniProtKB. DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB. DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0042552; P:myelination; ISS:BHF-UCL. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl. DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl. DR GO; GO:0007422; P:peripheral nervous system development; ISS:BHF-UCL. DR GO; GO:0006814; P:sodium ion transport; NAS:UniProtKB. DR CDD; cd13433; Na_channel_gate; 1. DR Gene3D; 1.10.287.70; -; 4. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 1.20.5.1190; iswi atpase; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 4. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR000048; IQ_motif_EF-hand-BS. DR InterPro; IPR008054; Na_channel_a8su. DR InterPro; IPR001696; Na_channel_asu. DR InterPro; IPR044564; Na_chnl_inactivation_gate. DR InterPro; IPR010526; Na_trans_assoc_dom. DR InterPro; IPR024583; Na_trans_cytopl. DR InterPro; IPR043203; VGCC_Ca_Na. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR10037:SF23; SODIUM CHANNEL PROTEIN TYPE 8 SUBUNIT ALPHA; 1. DR PANTHER; PTHR10037; VOLTAGE-GATED CATION CHANNEL CALCIUM AND SODIUM; 1. DR Pfam; PF00520; Ion_trans; 4. DR Pfam; PF00612; IQ; 1. DR Pfam; PF06512; Na_trans_assoc; 1. DR Pfam; PF11933; Na_trans_cytopl; 1. DR PRINTS; PR00170; NACHANNEL. DR PRINTS; PR01667; NACHANNEL8. DR SMART; SM00015; IQ; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR PROSITE; PS50096; IQ; 1. DR Genevisible; Q9UQD0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Cell projection; Cytoplasmic vesicle; Disease variant; Disulfide bond; KW Epilepsy; Glycoprotein; Intellectual disability; Ion channel; KW Ion transport; Membrane; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation; KW Voltage-gated channel. FT CHAIN 1..1980 FT /note="Sodium channel protein type 8 subunit alpha" FT /id="PRO_0000048500" FT TOPO_DOM 1..132 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 133..151 FT /note="Helical; Name=S1 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 152..158 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 159..179 FT /note="Helical; Name=S2 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 180..193 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 194..211 FT /note="Helical; Name=S3 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 212..217 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 218..234 FT /note="Helical; Name=S4 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 235..253 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 254..273 FT /note="Helical; Name=S5 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 274..355 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 356..380 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 381..387 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 388..408 FT /note="Helical; Name=S6 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 409..753 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 754..772 FT /note="Helical; Name=S1 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 773..783 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 784..803 FT /note="Helical; Name=S2 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 804..817 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 818..837 FT /note="Helical; Name=S3 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 838..839 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 840..857 FT /note="Helical; Name=S4 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 858..873 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 874..892 FT /note="Helical; Name=S5 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 893..921 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 922..942 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 943..955 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 956..976 FT /note="Helical; Name=S6 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 977..1199 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1200..1217 FT /note="Helical; Name=S1 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1218..1230 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1231..1249 FT /note="Helical; Name=S2 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1250..1263 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1264..1282 FT /note="Helical; Name=S3 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1283..1290 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1291..1309 FT /note="Helical; Name=S4 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1310..1326 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1327..1346 FT /note="Helical; Name=S5 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1347..1399 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 1400..1421 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1422..1438 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1439..1460 FT /note="Helical; Name=S6 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1461..1523 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1524..1541 FT /note="Helical; Name=S1 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1542..1552 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1553..1571 FT /note="Helical; Name=S2 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1572..1583 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1584..1601 FT /note="Helical; Name=S3 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1602..1614 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1615..1631 FT /note="Helical; Name=S4 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1632..1650 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1651..1668 FT /note="Helical; Name=S5 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1669..1690 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 1691..1713 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1714..1742 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1743..1765 FT /note="Helical; Name=S6 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1766..1980 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REPEAT 114..442 FT /note="I" FT /evidence="ECO:0000305" FT REPEAT 735..1007 FT /note="II" FT /evidence="ECO:0000305" FT REPEAT 1180..1495 FT /note="III" FT /evidence="ECO:0000305" FT REPEAT 1504..1801 FT /note="IV" FT /evidence="ECO:0000305" FT DOMAIN 1895..1924 FT /note="IQ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116, FT ECO:0000305" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 28..62 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 446..530 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 568..602 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1107..1148 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1922..1980 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 28..57 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 500..530 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 575..602 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1116..1131 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1950..1980 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 371 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:36823201, FT ECO:0007744|PDB:8GZ1" FT BINDING 373 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:36823201, FT ECO:0007744|PDB:8GZ1" FT BINDING 893..900 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT BINDING 939 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:36823201, FT ECO:0007744|PDB:8GZ1" FT BINDING 1413 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:36823201, FT ECO:0007744|PDB:8GZ1" FT MOD_RES 518 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88420" FT MOD_RES 520 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88420" FT MOD_RES 1497 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000250|UniProtKB:Q15858" FT CARBOHYD 215 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 289 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36823201, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT CARBOHYD 295 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0000312|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT CARBOHYD 308 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0000312|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT CARBOHYD 326 FT /note="N-linked (GlcNAc...) (high mannose) asparagine" FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0007744|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT CARBOHYD 1358 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0000312|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT CARBOHYD 1372 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0000312|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT CARBOHYD 1383 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 281..333 FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT DISULFID 904 FT /note="Interchain; with SCN2B or SCN4B" FT /evidence="ECO:0000250|UniProtKB:P04775" FT DISULFID 904 FT /note="Interchain; with the conotoxin GVIIJ (when the FT channel is not linked to SCN2B or SCN4B; the bond to SCN2B FT or SCN4B protects the channel from the inhibition by FT toxin)" FT /evidence="ECO:0000250|UniProtKB:P04775" FT DISULFID 906..912 FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0007744|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT DISULFID 944..953 FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0007744|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT DISULFID 1356..1376 FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0007744|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT DISULFID 1721..1736 FT /evidence="ECO:0000269|PubMed:36696443, FT ECO:0000269|PubMed:36823201, ECO:0007744|PDB:8FHD, FT ECO:0007744|PDB:8GZ1, ECO:0007744|PDB:8GZ2" FT VAR_SEQ 207 FT /note="I -> V (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9828131" FT /id="VSP_050589" FT VAR_SEQ 212 FT /note="N -> D (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9828131" FT /id="VSP_050590" FT VAR_SEQ 666 FT /note="E -> EVKIDKAATDDS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9828131" FT /id="VSP_050591" FT VAR_SEQ 1275..1315 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:19136557" FT /id="VSP_038651" FT VAR_SEQ 1275..1283 FT /note="SLVSLIANA -> PLNLSGLI (in isoform 4)" FT /evidence="ECO:0000303|PubMed:9295353" FT /id="VSP_050592" FT VAR_SEQ 1284..1980 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:9295353" FT /id="VSP_050593" FT VARIANT 58 FT /note="D -> N (in DEE13; uncertain significance; no effect FT on channel activity)" FT /evidence="ECO:0000269|PubMed:25725044" FT /id="VAR_076598" FT VARIANT 210 FT /note="F -> L (in DEE13)" FT /evidence="ECO:0000269|PubMed:25818041" FT /id="VAR_078752" FT VARIANT 215 FT /note="N -> R (in DEE13; uncertain significance; requires 2 FT nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076599" FT VARIANT 216 FT /note="V -> D (in DEE13; dbSNP:rs879255696)" FT /evidence="ECO:0000269|PubMed:24888894" FT /id="VAR_071674" FT VARIANT 223 FT /note="R -> G (in DEE13; loss of function mutation; reduces FT channel activity; dbSNP:rs672601319)" FT /evidence="ECO:0000269|PubMed:25239001" FT /id="VAR_072182" FT VARIANT 232 FT /note="S -> P (in DEE13)" FT /evidence="ECO:0000269|PubMed:28923014" FT /id="VAR_079722" FT VARIANT 260 FT /note="F -> S (in DEE13; uncertain significance; FT dbSNP:rs879255697)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076600" FT VARIANT 307 FT /note="N -> S (in DEE13; uncertain significance; FT dbSNP:rs1057519557)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078202" FT VARIANT 407 FT /note="L -> F (in DEE13; uncertain significance; FT dbSNP:rs879255698)" FT /evidence="ECO:0000269|PubMed:25785782" FT /id="VAR_076601" FT VARIANT 408 FT /note="A -> T (in DEE13; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078753" FT VARIANT 410 FT /note="V -> L (in DEE13; uncertain significance; FT dbSNP:rs879255699)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076602" FT VARIANT 479 FT /note="E -> V (in DEE13; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076603" FT VARIANT 662 FT /note="R -> C (in DEE13; uncertain significance; FT dbSNP:rs76222829)" FT /evidence="ECO:0000269|PubMed:23708187" FT /id="VAR_078612" FT VARIANT 767 FT /note="T -> I (in DEE13; gain-of-function mutation; FT increases channel activity; dbSNP:rs797045013)" FT /evidence="ECO:0000269|PubMed:24874546" FT /id="VAR_072183" FT VARIANT 846 FT /note="F -> S (in DEE13; dbSNP:rs879255700)" FT /evidence="ECO:0000269|PubMed:24888894" FT /id="VAR_071675" FT VARIANT 850 FT /note="R -> E (in DEE13; requires 2 nucleotide FT substitutions)" FT /evidence="ECO:0000269|PubMed:28923014" FT /id="VAR_079723" FT VARIANT 850 FT /note="R -> Q (in DEE13; uncertain significance; FT dbSNP:rs587780586)" FT /evidence="ECO:0000269|PubMed:25785782" FT /id="VAR_076604" FT VARIANT 890 FT /note="A -> T (in DEE13; dbSNP:rs879255702)" FT /evidence="ECO:0000269|PubMed:25568300, FT ECO:0000269|PubMed:25785782" FT /id="VAR_076605" FT VARIANT 891 FT /note="V -> M (in DEE13; dbSNP:rs1592149793)" FT /evidence="ECO:0000269|PubMed:28923014" FT /id="VAR_079724" FT VARIANT 960 FT /note="V -> D (in DEE13; uncertain significance; FT dbSNP:rs879255703)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076606" FT VARIANT 978 FT /note="S -> G (in DEE13; dbSNP:rs1057519540)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078203" FT VARIANT 984 FT /note="N -> K (in DEE13; gain-of-function mutation; FT increased channel activity; dbSNP:rs876657399)" FT /evidence="ECO:0000269|PubMed:25725044" FT /id="VAR_076607" FT VARIANT 1279 FT /note="L -> V (in DEE13)" FT /evidence="ECO:0000269|PubMed:23708187" FT /id="VAR_078613" FT VARIANT 1323 FT /note="A -> S (in DEE13; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078754" FT VARIANT 1327 FT /note="I -> V (in DEE13; dbSNP:rs879255704)" FT /evidence="ECO:0000269|PubMed:24352161, FT ECO:0000269|PubMed:26993267" FT /id="VAR_071676" FT VARIANT 1331 FT /note="L -> V (in DEE13; uncertain significance; FT dbSNP:rs397514738)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076608" FT VARIANT 1451 FT /note="G -> S (in DEE13; loss of channel activity; FT dbSNP:rs863223345)" FT /evidence="ECO:0000269|PubMed:25725044" FT /id="VAR_076609" FT VARIANT 1466 FT /note="N -> K (in DEE13; dbSNP:rs587777722)" FT /evidence="ECO:0000269|PubMed:24888894" FT /id="VAR_071677" FT VARIANT 1466 FT /note="N -> T (in DEE13; dbSNP:rs587777723)" FT /evidence="ECO:0000269|PubMed:24888894" FT /id="VAR_071678" FT VARIANT 1475 FT /note="G -> R (in DEE13; dbSNP:rs796053216)" FT /evidence="ECO:0000269|PubMed:27864847, FT ECO:0000269|PubMed:28923014" FT /id="VAR_078204" FT VARIANT 1479 FT /note="I -> V (in DEE13; uncertain significance; FT dbSNP:rs796053217)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076610" FT VARIANT 1483 FT /note="E -> K (in BFIS5; dbSNP:rs879255652)" FT /evidence="ECO:0000269|PubMed:26677014" FT /id="VAR_076927" FT VARIANT 1592 FT /note="V -> L (in DEE13; uncertain significance; FT dbSNP:rs587780454)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076611" FT VARIANT 1596 FT /note="S -> C (in DEE13; uncertain significance; FT dbSNP:rs879255705)" FT /evidence="ECO:0000269|PubMed:25785782" FT /id="VAR_076612" FT VARIANT 1598 FT /note="V -> A (in DEE13)" FT /evidence="ECO:0000269|PubMed:28923014" FT /id="VAR_079725" FT VARIANT 1605 FT /note="I -> R (in DEE13; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076613" FT VARIANT 1617 FT /note="R -> Q (in DEE13; gain-of-function mutation; FT increased channel activity; impaired channel inactivation; FT dbSNP:rs587777721)" FT /evidence="ECO:0000269|PubMed:24888894, FT ECO:0000269|PubMed:25568300, ECO:0000269|PubMed:25785782, FT ECO:0000269|PubMed:26900580" FT /id="VAR_071679" FT VARIANT 1650 FT /note="A -> T (in DEE13; dbSNP:rs879255709)" FT /evidence="ECO:0000269|PubMed:24888894, FT ECO:0000269|PubMed:25568300, ECO:0000269|PubMed:27864847" FT /id="VAR_071680" FT VARIANT 1719 FT /note="P -> R (in MYOCL2; decreased channel activity; FT results in significantly reduced inward sodium current FT without changes of voltage-dependent channel activation and FT inactivation; dbSNP:rs1565934070)" FT /evidence="ECO:0000269|PubMed:29726066" FT /id="VAR_082076" FT VARIANT 1754 FT /note="F -> S (in DEE13; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078755" FT VARIANT 1768 FT /note="N -> D (in DEE13; gain-of-function mutation; results FT in increased persistent sodium currents and incomplete FT channel inactivation; dbSNP:rs202151337)" FT /evidence="ECO:0000269|PubMed:22365152" FT /id="VAR_067539" FT VARIANT 1801 FT /note="Q -> E (in DEE13; uncertain significance; FT dbSNP:rs879255710)" FT /evidence="ECO:0000269|PubMed:25568300" FT /id="VAR_076614" FT VARIANT 1865 FT /note="L -> P (in DEE13; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078756" FT VARIANT 1872 FT /note="R -> L (in DEE13; gain-of-function mutation; FT increased channel activity; impaired channel inactivation; FT dbSNP:rs796053229)" FT /evidence="ECO:0000269|PubMed:26900580" FT /id="VAR_076615" FT VARIANT 1872 FT /note="R -> Q (in DEE13; gain-of-function mutation; FT increased channel activity; impaired channel inactivation; FT dbSNP:rs796053229)" FT /evidence="ECO:0000269|PubMed:25568300, FT ECO:0000269|PubMed:26900580" FT /id="VAR_076616" FT VARIANT 1872 FT /note="R -> W (in DEE13; gain-of-function mutation; FT increased channel activity; impaired channel inactivation; FT no effect on interactions with FGF14, SCN1B, GNB2 and GNG3; FT dbSNP:rs796053228)" FT /evidence="ECO:0000269|PubMed:24888894, FT ECO:0000269|PubMed:25568300, ECO:0000269|PubMed:26900580, FT ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28923014" FT /id="VAR_071681" FT VARIANT 1877 FT /note="N -> S (in DEE13 and BFIS5; also found in a patient FT with drug-resistant focal epilepsy and mild intellectual FT disability; dbSNP:rs587780455)" FT /evidence="ECO:0000269|PubMed:27210545, FT ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28923014" FT /id="VAR_076617" FT MUTAGEN 1416..1417 FT /note="MD->TI: Reduced inhibition by FT 4,9-anhydro-tetrodotoxin." FT /evidence="ECO:0000269|PubMed:36823201" FT CONFLICT 5 FT /note="L -> V (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 133 FT /note="V -> L (in Ref. 1; AAD15789)" FT /evidence="ECO:0000305" FT CONFLICT 257 FT /note="L -> M (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 273 FT /note="F -> I (in Ref. 3; ACM63162)" FT /evidence="ECO:0000305" FT CONFLICT 274..278 FT /note="MGNLR -> HGEPS (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 453 FT /note="T -> N (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="S -> F (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="L -> I (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 492 FT /note="R -> S (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 504 FT /note="S -> F (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 547..548 FT /note="LL -> MF (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" FT CONFLICT 1416 FT /note="M -> V (in Ref. 3; ACM63162)" FT /evidence="ECO:0000305" FT CONFLICT 1445 FT /note="V -> I (in Ref. 1; AAD15789)" FT /evidence="ECO:0000305" FT CONFLICT 1519 FT /note="V -> I (in Ref. 1; AAD15789)" FT /evidence="ECO:0000305" FT CONFLICT 1702 FT /note="T -> A (in Ref. 5; AAF35390)" FT /evidence="ECO:0000305" SQ SEQUENCE 1980 AA; 225280 MW; 0EFC7BFB137FD4F0 CRC64; MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF TNAWCWLDFL IVAVSLVSLI ANALGYSELG AIKSLRTLRA LRPLRALSRF EGMRVVVNAL VGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKYHYCFNET SEIRFEIEDV NNKTECEKLM EGNNTEIRWK NVKINFDNVG AGYLALLQVA TFKGWMDIMY AAVDSRKPDE QPKYEDNIYM YIYFVIFIIF GSFFTLNLFI GVIIDNFNQQ KKKFGGQDIF MTEEQKKYYN AMKKLGSKKP QKPIPRPLNK IQGIVFDFVT QQAFDIVIMM LICLNMVTMM VETDTQSKQM ENILYWINLV FVIFFTCECV LKMFALRHYY FTIGWNIFDF VVVILSIVGM FLADIIEKYF VSPTLFRVIR LARIGRILRL IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA GIDDMFNFET FGNSMICLFQ ITTSAGWDGL LLPILNRPPD CSLDKEHPGS GFKGDCGNPS VGIFFFVSYI IISFLIVVNM YIAIILENFS VATEESADPL SEDDFETFYE IWEKFDPDAT QFIEYCKLAD FADALEHPLR VPKPNTIELI AMDLPMVSGD RIHCLDILFA FTKRVLGDSG ELDILRQQME ERFVASNPSK VSYEPITTTL RRKQEEVSAV VLQRAYRGHL ARRGFICKKT TSNKLENGGT HREKKESTPS TASLPSYDSV TKPEKEKQQR AEEGRRERAK RQKEVRESKC //