SCN8A_HUMAN
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 03-AUG-2022, entry version 192.
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 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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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}.
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 -!- 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). Beta-1
CC (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha,
CC 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 the conotoxin GVIIJ
CC (PubMed:24497506). 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 -!- 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}.
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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 AlphaFoldDB; Q9UQD0; -.
DR SMR; Q9UQD0; -.
DR BioGRID; 112238; 5.
DR IntAct; Q9UQD0; 4.
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; 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 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; Q9UQD0; -.
DR PeptideAtlas; Q9UQD0; -.
DR PRIDE; 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; 219 antibodies from 29 providers.
DR DNASU; 6334; -.
DR Ensembl; ENST00000354534.11; ENSP00000346534.4; ENSG00000196876.18. [Q9UQD0-1]
DR Ensembl; ENST00000355133.7; ENSP00000347255.4; ENSG00000196876.18. [Q9UQD0-5]
DR Ensembl; ENST00000545061.5; ENSP00000440360.1; ENSG00000196876.18. [Q9UQD0-5]
DR Ensembl; ENST00000599343.5; ENSP00000476447.3; ENSG00000196876.18. [Q9UQD0-3]
DR Ensembl; ENST00000627620.5; ENSP00000487583.2; ENSG00000196876.18. [Q9UQD0-2]
DR Ensembl; ENST00000662684.1; ENSP00000499636.1; ENSG00000196876.18. [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 CTD; 6334; -.
DR DisGeNET; 6334; -.
DR GeneCards; SCN8A; -.
DR GeneReviews; SCN8A; -.
DR HGNC; HGNC:10596; SCN8A.
DR HPA; ENSG00000196876; Tissue enriched (brain).
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; 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; CIAKYKC; -.
DR OrthoDB; 172471at2759; -.
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; 12 hits in 1069 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 148 other tissues.
DR ExpressionAtlas; Q9UQD0; baseline and differential.
DR Genevisible; Q9UQD0; HS.
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:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB.
DR GO; GO:0086010; P:membrane depolarization during action potential; 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; IBA:GO_Central.
DR GO; GO:0007422; P:peripheral nervous system development; ISS:BHF-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; NAS:UniProtKB.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 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.
DR InterPro; IPR024583; Na_trans_cytopl.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 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 PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasmic vesicle; Disease variant; Disulfide bond; Epilepsy;
KW Glycoprotein; Intellectual disability; Ion channel; Ion transport;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Sodium; Sodium channel; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation; 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 893..900
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
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:0000255"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 944..953
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
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; unknown pathological significance;
FT no effect 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; unknown pathological significance;
FT requires 2 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; unknown pathological significance;
FT dbSNP:rs879255697)"
FT /evidence="ECO:0000269|PubMed:25568300"
FT /id="VAR_076600"
FT VARIANT 307
FT /note="N -> S (in DEE13; unknown pathological significance;
FT dbSNP:rs1057519557)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078202"
FT VARIANT 407
FT /note="L -> F (in DEE13; unknown pathological significance;
FT dbSNP:rs879255698)"
FT /evidence="ECO:0000269|PubMed:25785782"
FT /id="VAR_076601"
FT VARIANT 408
FT /note="A -> T (in DEE13; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078753"
FT VARIANT 410
FT /note="V -> L (in DEE13; unknown pathological significance;
FT dbSNP:rs879255699)"
FT /evidence="ECO:0000269|PubMed:25568300"
FT /id="VAR_076602"
FT VARIANT 479
FT /note="E -> V (in DEE13; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25568300"
FT /id="VAR_076603"
FT VARIANT 662
FT /note="R -> C (in DEE13; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological
FT 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; unknown pathological 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; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs587780454)"
FT /evidence="ECO:0000269|PubMed:25568300"
FT /id="VAR_076611"
FT VARIANT 1596
FT /note="S -> C (in DEE13; unknown pathological 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; unknown pathological
FT 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; unknown pathological
FT 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; unknown pathological significance;
FT dbSNP:rs879255710)"
FT /evidence="ECO:0000269|PubMed:25568300"
FT /id="VAR_076614"
FT VARIANT 1865
FT /note="L -> P (in DEE13; unknown pathological
FT 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 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
