SCN4A_HUMAN
ID SCN4A_HUMAN Reviewed; 1836 AA.
AC P35499; Q15478; Q16447; Q7Z6B1;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 4.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Sodium channel protein type 4 subunit alpha;
DE AltName: Full=SkM1 {ECO:0000303|PubMed:1315496};
DE AltName: Full=Sodium channel protein skeletal muscle subunit alpha;
DE AltName: Full=Sodium channel protein type IV subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.4;
GN Name=SCN4A;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS GLY-524; ASP-559 AND
RP ASP-1376.
RC TISSUE=Skeletal muscle;
RX PubMed=1315496; DOI=10.1002/ana.410310203;
RA George A.L. Jr., Komisarof J., Kallen R.G., Barchi R.L.;
RT "Primary structure of the adult human skeletal muscle voltage-dependent
RT sodium channel.";
RL Ann. Neurol. 31:131-137(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1310396; DOI=10.1016/0006-291x(92)91802-w;
RA Wang J., Rojas C.V., Zhou J., Schwartz L.S., Nicholas H., Hoffmann E.P.;
RT "Sequence and genomic structure of the human adult skeletal muscle sodium
RT channel alpha subunit gene on 17q.";
RL Biochem. Biophys. Res. Commun. 182:794-801(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, VARIANT CMS16
RP GLU-1442, VARIANTS LEU-246; GLY-524 AND ASP-559, CHARACTERIZATION OF
RP VARIANT CMS16 GLU-1442, AND CHARACTERIZATION OF VARIANT LEU-246.
RX PubMed=12766226; DOI=10.1073/pnas.1230273100;
RA Tsujino A., Maertens C., Ohno K., Shen X.-M., Fukuda T., Harper C.M.,
RA Cannon S.C., Engel A.G.;
RT "Myasthenic syndrome caused by mutation of the SCN4A sodium channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7377-7382(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-524.
RX PubMed=1339144; DOI=10.1093/hmg/1.7.521;
RA McClatchey A.I., Lin C.S., Wang J., Hoffman E.P., Rojas C.V., Gusella J.F.;
RT "The genomic structure of the human skeletal muscle sodium channel gene.";
RL Hum. Mol. Genet. 1:521-527(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1305-1339, AND VARIANTS PMC VAL-1306
RP AND MET-1313.
RX PubMed=1310898; DOI=10.1016/0092-8674(92)90151-2;
RA McClatchey A.I., van den Bergh P., Pericak-Vance M.A., Raskind W.,
RA Verellen C., McKenna-Yasek D., Rao K., Haines J.L., Bird T.,
RA Brown R.H. Jr., Gusella J.F.;
RT "Temperature-sensitive mutations in the III-IV cytoplasmic loop region of
RT the skeletal muscle sodium channel gene in paramyotonia congenita.";
RL Cell 68:769-774(1992).
RN [7]
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 [8]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP SCN1B.
RX PubMed=29992740; DOI=10.1002/humu.23589;
RA Baroni D., Picco C., Moran O.;
RT "A mutation of SCN1B associated with GEFS+ causes functional and maturation
RT defects of the voltage-dependent sodium channel.";
RL Hum. Mutat. 39:1402-1415(2018).
RN [9] {ECO:0007744|PDB:6AGF}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH SCN1B,
RP FUNCTION, ACTIVITY REGULATION, TOPOLOGY, SUBCELLULAR LOCATION, SUBUNIT,
RP DOMAIN, GLYCOSYLATION AT ASN-362 AND ASN-1205, AND DISULFIDE BONDS.
RX PubMed=30190309; DOI=10.1126/science.aau2486;
RA Pan X., Li Z., Zhou Q., Shen H., Wu K., Huang X., Chen J., Zhang J.,
RA Zhu X., Lei J., Xiong W., Gong H., Xiao B., Yan N.;
RT "Structure of the human voltage-gated sodium channel Nav1.4 in complex with
RT beta1.";
RL Science 362:0-0(2018).
RN [10]
RP VARIANT HYPP MET-704.
RX PubMed=1659948; DOI=10.1016/0092-8674(91)90374-8;
RA Ptacek L.J., George A.L. Jr., Griggs R.C., Tawil R., Kallen R.G.,
RA Barchi R.L., Robertson M., Leppert M.F.;
RT "Identification of a mutation in the gene causing hyperkalemic periodic
RT paralysis.";
RL Cell 67:1021-1027(1991).
RN [11]
RP VARIANT HYPP VAL-1592.
RX PubMed=1659668; DOI=10.1038/354387a0;
RA Rojas C.V., Wang J., Schwartz L.S., Hoffman E.P., Powell B.R.,
RA Brown R.H. Jr.;
RT "A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in
RT hyperkalaemic periodic paralysis.";
RL Nature 354:387-389(1991).
RN [12]
RP VARIANTS PMC PHE-804 AND THR-1156.
RX PubMed=1338909; DOI=10.1038/ng1092-148;
RA McClatchey A.I., McKenna-Yasek D., Cros D., Worthen H.G., Kuncl R.W.,
RA Desilva S.M., Cornblath D.R., Gusella J.F., Brown R.H. Jr.;
RT "Novel mutations in families with unusual and variable disorders of the
RT skeletal muscle sodium channel.";
RL Nat. Genet. 2:148-152(1992).
RN [13]
RP VARIANTS PMC CYS-1448 AND HIS-1448.
RX PubMed=1316765; DOI=10.1016/0896-6273(92)90203-p;
RA Ptacek L.J., George A.L. Jr., Barchi R.L., Griggs R.C., Riggs J.E.,
RA Robertson M., Leppert M.F.;
RT "Mutations in an S4 segment of the adult skeletal muscle sodium channel
RT cause paramyotonia congenita.";
RL Neuron 8:891-897(1992).
RN [14]
RP VARIANT PMC/HYPP ARG-1433.
RX PubMed=8388676; DOI=10.1002/ana.410330312;
RA Ptacek L.J., Gouw L., Kwiecinski H., McManis P., Mendell J.R., Barohn R.J.,
RA George A.L. Jr., Barchi R.L., Robertson M., Leppert M.F.;
RT "Sodium channel mutations in paramyotonia congenita and hyperkalemic
RT periodic paralysis.";
RL Ann. Neurol. 33:300-307(1993).
RN [15]
RP VARIANTS PMC ALA-1306; GLU-1306 AND VAL-1306.
RX PubMed=8308722; DOI=10.1113/jphysiol.1993.sp019843;
RA Lerche H., Heine R., Pika U., George A.L. Jr., Mitrovic N., Browatzki M.,
RA Weiss T., Rivet-Bastide M., Franke C., Lomonaco M., Ricker K.,
RA Lehmann-Horn F.;
RT "Human sodium channel myotonia: slowed channel inactivation due to
RT substitutions for a glycine within the III-IV linker.";
RL J. Physiol. (Lond.) 470:13-22(1993).
RN [16]
RP VARIANT PMC MET-1589.
RX PubMed=8242056; DOI=10.1093/hmg/2.9.1349;
RA Heine R., Pika U., Lehmann-Horn F.;
RT "A novel SCN4A mutation causing myotonia aggravated by cold and
RT potassium.";
RL Hum. Mol. Genet. 2:1349-1353(1993).
RN [17]
RP VARIANT MYOSCN4A VAL-1160.
RX PubMed=8058156; DOI=10.1212/wnl.44.8.1500;
RA Ptacek L.J., Tawil R., Griggs R.C., Meola G., McManis P., Barohn R.J.,
RA Mendell J.R., Harris C., Spitzer R., Santiago F., Leppert M.F.;
RT "Sodium channel mutations in acetazolamide-responsive myotonia congenita,
RT paramyotonia congenita, and hyperkalemic periodic paralysis.";
RL Neurology 44:1500-1503(1994).
RN [18]
RP VARIANT ILE-781.
RX PubMed=7695243; DOI=10.1002/ana.410370320;
RA Baquero J.L., Ayala R.A., Wang J., Curless R.G., Feero W.G., Hoffman E.P.,
RA Ebeid M.R.;
RT "Hyperkalemic periodic paralysis with cardiac dysrhythmia: a novel sodium
RT channel mutation?";
RL Ann. Neurol. 37:408-411(1995).
RN [19]
RP VARIANT PMC ILE-1293.
RX PubMed=8580427; DOI=10.1097/00001756-199510010-00012;
RA Koch M.C., Baumbach K., George A.L. Jr., Ricker K.;
RT "Paramyotonia congenita without paralysis on exposure to cold: a novel
RT mutation in the SCN4A gene (Val1293Ile).";
RL NeuroReport 6:2001-2004(1995).
RN [20]
RP VARIANT ILE-781.
RX PubMed=9266738; DOI=10.1002/ana.410420219;
RA Green D.S., Hayward L.J., George A.L. Jr., Cannon S.C.;
RT "A proposed mutation, Val781Ile, associated with hyperkalemic periodic
RT paralysis and cardiac dysrhythmia is a benign polymorphism.";
RL Ann. Neurol. 42:253-256(1997).
RN [21]
RP VARIANT MYOSCN4A MET-445.
RX PubMed=9392583; DOI=10.1002/ana.410420520;
RA Rosenfeld J., Sloan-Brown K., George A.L. Jr.;
RT "A novel muscle sodium channel mutation causes painful congenital
RT myotonia.";
RL Ann. Neurol. 42:811-814(1997).
RN [22]
RP VARIANT PMC GLU-1456.
RX PubMed=10369308; DOI=10.1001/archneur.56.6.692;
RA Sasaki R., Takano H., Kamakura K., Kaida K., Hirata A., Saito M.,
RA Tanaka H., Kuzuhara S., Tsuji S.;
RT "A novel mutation in the gene for the adult skeletal muscle sodium channel
RT alpha-subunit (SCN4A) that causes paramyotonia congenita of von
RT Eulenburg.";
RL Arch. Neurol. 56:692-696(1999).
RN [23]
RP VARIANT MYOSCN4A MET-445.
RX PubMed=10218481; DOI=10.1016/s0014-5793(99)00338-5;
RA Wang D.W., VanDeCarr D., Ruben P.C., George A.L. Jr., Bennett P.B.;
RT "Functional consequences of a domain 1/S6 segment sodium channel mutation
RT associated with painful congenital myotonia.";
RL FEBS Lett. 448:231-234(1999).
RN [24]
RP VARIANT HOKPP2 HIS-669.
RX PubMed=10599760; DOI=10.1212/wnl.53.9.1932;
RA Bulman D.E., Scoggan K.A., van Oene M.D., Nicolle M.W., Hahn A.F.,
RA Tollar L.L., Ebers G.C.;
RT "A novel sodium channel mutation in a family with hypokalemic periodic
RT paralysis.";
RL Neurology 53:1932-1936(1999).
RN [25]
RP VARIANT PMC GLU-1456.
RX PubMed=10727489; DOI=10.1136/jnnp.68.4.504;
RA Davies N.P., Eunson L.H., Gregory R.P., Mills K.R., Morrison P.J.,
RA Hanna M.G.;
RT "Clinical, electrophysiological, and molecular genetic studies in a new
RT family with paramyotonia congenita.";
RL J. Neurol. Neurosurg. Psych. 68:504-507(2000).
RN [26]
RP VARIANT HOKPP2 SER-1158.
RX PubMed=10851391; DOI=10.1212/wnl.54.11.2179;
RA Sugiura Y., Aoki T., Sugiyama Y., Hida C., Ogata M., Yamamoto T.;
RT "Temperature-sensitive sodium channelopathy with heat-induced myotonia and
RT cold-induced paralysis.";
RL Neurology 54:2179-2181(2000).
RN [27]
RP VARIANTS HOKPP2 GLY-672 AND HIS-672.
RX PubMed=10944223; DOI=10.1073/pnas.97.17.9549;
RA Jurkat-Rott K., Mitrovic N., Hang C., Kouzmekine A., Iaizzo P., Herzog J.,
RA Lerche H., Nicole S., Vale-Santos J., Chauveau D., Fontaine B.,
RA Lehmann-Horn F.;
RT "Voltage-sensor sodium channel mutations cause hypokalemic periodic
RT paralysis type 2 by enhanced inactivation and reduced current.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9549-9554(2000).
RN [28]
RP VARIANT HOKPP2 SER-672.
RX PubMed=11558801; DOI=10.1002/ana.1144;
RA Bendahhou S., Cummins T.R., Griggs R.C., Fu Y.H., Ptacek L.J.;
RT "Sodium channel inactivation defects are associated with acetazolamide-
RT exacerbated hypokalemic periodic paralysis.";
RL Ann. Neurol. 50:417-420(2001).
RN [29]
RP VARIANT HOKPP2 SER-672.
RX PubMed=11591859; DOI=10.1212/wnl.57.7.1323;
RA Davies N.P., Eunson L.H., Samuel M., Hanna M.G.;
RT "Sodium channel gene mutations in hypokalemic periodic paralysis: an
RT uncommon cause in the UK.";
RL Neurology 57:1323-1325(2001).
RN [30]
RP VARIANTS PMC MET-1313 AND CYS-1448, CHARACTERIZATION OF VARIANTS PMC
RP MET-1313 AND CYS-1448, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15318338; DOI=10.1002/mus.20080;
RA Dice M.S., Abbruzzese J.L., Wheeler J.T., Groome J.R., Fujimoto E.,
RA Ruben P.C.;
RT "Temperature-sensitive defects in paramyotonia congenita mutants R1448C and
RT T1313M.";
RL Muscle Nerve 30:277-288(2004).
RN [31]
RP VARIANTS NKPP GLY-675; GLN-675 AND TRP-675.
RX PubMed=15596759; DOI=10.1212/01.wnl.0000145768.09934.ec;
RA Vicart S., Sternberg D., Fournier E., Ochsner F., Laforet P., Kuntzer T.,
RA Eymard B., Hainque B., Fontaine B.;
RT "New mutations of SCN4A cause a potassium-sensitive normokalemic periodic
RT paralysis.";
RL Neurology 63:2120-2127(2004).
RN [32]
RP VARIANT PMC ASP-1152.
RX PubMed=15790667; DOI=10.1113/jphysiol.2004.081018;
RA Bouhours M., Luce S., Sternberg D., Willer J.-C., Fontaine B., Tabti N.;
RT "A1152D mutation of the Na+ channel causes paramyotonia congenita and
RT emphasizes the role of DIII/S4-S5 linker in fast inactivation.";
RL J. Physiol. (Lond.) 565:415-427(2005).
RN [33]
RP VARIANT PMC LYS-270, AND VARIANTS MYOSCN4A THR-715; ASN-804 AND ASN-1310.
RX PubMed=16786525; DOI=10.1002/ana.20905;
RA Fournier E., Viala K., Gervais H., Sternberg D., Arzel-Hezode M.,
RA Laforet P., Eymard B., Tabti N., Willer J.-C., Vial C., Fontaine B.;
RT "Cold extends electromyography distinction between ion channel mutations
RT causing myotonia.";
RL Ann. Neurol. 60:356-365(2006).
RN [34]
RP VARIANT HOKPP2 GLN-1132, CHARACTERIZATION OF VARIANT HOKPP2 GLN-1132,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16890191; DOI=10.1016/j.bbrc.2006.07.101;
RA Carle T., Lhuillier L., Luce S., Sternberg D., Devuyst O., Fontaine B.,
RA Tabti N.;
RT "Gating defects of a novel Na+ channel mutant causing hypokalemic periodic
RT paralysis.";
RL Biochem. Biophys. Res. Commun. 348:653-661(2006).
RN [35]
RP VARIANT MYOSCN4A GLU-1306.
RX PubMed=16832098; DOI=10.1212/01.wnl.0000223838.88872.da;
RA Colding-Joergensen E., Duno M., Vissing J.;
RT "Autosomal dominant monosymptomatic myotonia permanens.";
RL Neurology 67:153-155(2006).
RN [36]
RP VARIANTS HOKPP2 HIS-669; CYS-672 AND GLY-672.
RX PubMed=18162704; DOI=10.3346/jkms.2007.22.6.946;
RA Kim J.-B., Kim M.-H., Lee S.J., Kim D.-J., Lee B.C.;
RT "The genotype and clinical phenotype of Korean patients with familial
RT hypokalemic periodic paralysis.";
RL J. Korean Med. Sci. 22:946-951(2007).
RN [37]
RP VARIANT MYOSCN4A ASP-1481.
RX PubMed=17212350; DOI=10.1002/mus.20733;
RA Schoser B.G.H., Schroeder J.M., Grimm T., Sternberg D., Kress W.;
RT "A large German kindred with cold-aggravated myotonia and a heterozygous
RT A1481D mutation in the SCN4A gene.";
RL Muscle Nerve 35:599-606(2007).
RN [38]
RP VARIANT MYOSCN4A ILE-1476.
RX PubMed=17998485; DOI=10.1212/01.wnl.0000290831.08585.2c;
RA Rossignol E., Mathieu J., Thiffault I., Tetreault M., Dicaire M.J.,
RA Chrestian N., Dupre N., Puymirat J., Brais B.;
RT "A novel founder SCN4A mutation causes painful cold-induced myotonia in
RT French-Canadians.";
RL Neurology 69:1937-1941(2007).
RN [39]
RP VARIANT MYOSCN4A LYS-1297.
RX PubMed=18203179; DOI=10.1002/ajmg.a.32141;
RA Gay S., Dupuis D., Faivre L., Masurel-Paulet A., Labenne M., Colombani M.,
RA Soichot P., Huet F., Hainque B., Sternberg D., Fontaine B., Gouyon J.B.,
RA Thauvin-Robinet C.;
RT "Severe neonatal non-dystrophic myotonia secondary to a novel mutation of
RT the voltage-gated sodium channel (SCN4A) gene.";
RL Am. J. Med. Genet. A 146:380-383(2008).
RN [40]
RP VARIANTS NKPP GLN-675 AND VAL-1592, AND VARIANT ILE-781.
RX PubMed=18046642; DOI=10.1007/s10571-007-9231-4;
RA Xiuhai G., Weiping W., Ke Z., Hongbin W., Yiling S., Yanling M.;
RT "Mutations of sodium channel alpha-subunit genes in Chinese patients with
RT normokalemic periodic paralysis.";
RL Cell. Mol. Neurobiol. 28:653-661(2008).
RN [41]
RP CHARACTERIZATION OF VARIANTS PMC SER-1473 AND ILE-1705, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18690054; DOI=10.4161/chan.2.1.6051;
RA Groome J.R., Larsen M.F., Coonts A.;
RT "Differential effects of paramyotonia congenita mutations F1473S and F1705I
RT on sodium channel gating.";
RL Channels 2:39-50(2008).
RN [42]
RP VARIANTS PMC LYS-270; MET-704; ALA-1306; GLU-1306; MET-1313; PRO-1436;
RP CYS-1448; HIS-1448; LEU-1448; GLU-1456; SER-1473 AND MET-1589.
RX PubMed=18166706; DOI=10.1212/01.wnl.0000287069.21162.94;
RA Matthews E., Tan S.V., Fialho D., Sweeney M.G., Sud R., Haworth A.,
RA Stanley E., Cea G., Davis M.B., Hanna M.G.;
RT "What causes paramyotonia in the United Kingdom? Common and new SCN4A
RT mutations revealed.";
RL Neurology 70:50-53(2008).
RN [43]
RP VARIANT HOKPP2 SER-1158, CHARACTERIZATION OF VARIANT HOKPP2 SER-1158,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17898326; DOI=10.1212/01.wnl.0000265397.70057.d8;
RA Webb J., Cannon S.C.;
RT "Cold-induced defects of sodium channel gating in atypical periodic
RT paralysis plus myotonia.";
RL Neurology 70:755-761(2008).
RN [44]
RP VARIANT MYOSCN4A VAL-141, AND CHARACTERIZATION OF VARIANT MYOSCN4A VAL-141.
RX PubMed=19015483; DOI=10.1212/01.wnl.0000335168.86248.55;
RA Petitprez S., Tiab L., Chen L., Kappeler L., Rosler K.M., Schorderet D.,
RA Abriel H., Burgunder J.M.;
RT "A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to
RT sodium channel myotonia.";
RL Neurology 71:1669-1675(2008).
RN [45]
RP VARIANTS MYOSCN4A TRP-225; THR-1156 AND GLU-1306, VARIANT PMC THR-693, AND
RP VARIANT HYPP THR-1156.
RX PubMed=20076800; DOI=10.3988/jcn.2009.5.4.186;
RA Lee S.C., Kim H.S., Park Y.E., Choi Y.C., Park K.H., Kim D.S.;
RT "Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium
RT channelopathy.";
RL J. Clin. Neurol. 5:186-191(2009).
RN [46]
RP VARIANT MYOSCN4A GLU-1633, CHARACTERIZATION OF VARIANT MYOSCN4A GLU-1633,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19347921; DOI=10.1002/mus.21155;
RA Kubota T., Kinoshita M., Sasaki R., Aoike F., Takahashi M.P., Sakoda S.,
RA Hirose K.;
RT "New mutation of the Na channel in the severe form of potassium-aggravated
RT myotonia.";
RL Muscle Nerve 39:666-673(2009).
RN [47]
RP VARIANTS MYOSCN4A MET-445; LYS-452; SER-671; VAL-1306 AND ILE-1476.
RX PubMed=18337100; DOI=10.1016/j.nmd.2008.01.007;
RA Dupre N., Chrestian N., Bouchard J.-P., Rossignol E., Brunet D.,
RA Sternberg D., Brais B., Mathieu J., Puymirat J.;
RT "Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia
RT in French-Canadians.";
RL Neuromuscul. Disord. 19:330-334(2009).
RN [48]
RP VARIANTS HOKPP2 TRP-222; CYS-672; GLY-672; HIS-672; SER-672; GLN-1132 AND
RP HIS-1135.
RX PubMed=19118277; DOI=10.1212/01.wnl.0000342387.65477.46;
RA Matthews E., Labrum R., Sweeney M.G., Sud R., Haworth A., Chinnery P.F.,
RA Meola G., Schorge S., Kullmann D.M., Davis M.B., Hanna M.G.;
RT "Voltage sensor charge loss accounts for most cases of hypokalemic periodic
RT paralysis.";
RL Neurology 72:1544-1547(2009).
RN [49]
RP VARIANT PMC MET-704.
RX PubMed=19077043; DOI=10.1111/j.1440-1789.2008.00985.x;
RA Luan X., Chen B., Liu Y., Zheng R., Zhang W., Yuan Y.;
RT "Tubular aggregates in paralysis periodica paramyotonica with T704M
RT mutation of SCN4A.";
RL Neuropathology 29:579-584(2009).
RN [50]
RP VARIANT NKPP GLN-1129, AND VARIANT HOKPP2 GLN-1129.
RX PubMed=20522878; DOI=10.1136/jnnp.2009.177451;
RA Hong D., Luan X., Chen B., Zheng R., Zhang W., Wang Z., Yuan Y.;
RT "Both hypokalaemic and normokalaemic periodic paralysis in different
RT members of a single family with novel R1129Q mutation in SCN4A gene.";
RL J. Neurol. Neurosurg. Psych. 81:703-704(2010).
RN [51]
RP VARIANT HOKPP2 HIS-672.
RX PubMed=21043388;
RA Incecik F., Herguner M.O., Altunbasak S., Lehman-Horn F.;
RT "Hypokalemic periodic paralysis due to the SCN4A R672H mutation in a
RT Turkish family.";
RL Turk. J. Pediatr. 52:409-410(2010).
RN [52]
RP VARIANTS HOKPP2 CYS-1135 AND HIS-1135, AND CHARACTERIZATION OF VARIANTS
RP HOKPP2 CYS-1135 AND HIS-1135.
RX PubMed=24549961; DOI=10.1093/brain/awu015;
RA Groome J.R., Lehmann-Horn F., Fan C., Wolf M., Winston V., Merlini L.,
RA Jurkat-Rott K.;
RT "NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4
RT movement during recovery.";
RL Brain 137:998-1008(2014).
RN [53]
RP VARIANT CMS16 HIS-1457, CHARACTERIZATION OF VARIANT CMS16 HIS-1457,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25707578; DOI=10.1002/ana.24389;
RA Arnold W.D., Feldman D.H., Ramirez S., He L., Kassar D., Quick A.,
RA Klassen T.L., Lara M., Nguyen J., Kissel J.T., Lossin C., Maselli R.A.;
RT "Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic
RT syndrome.";
RL Ann. Neurol. 77:840-850(2015).
RN [54]
RP INVOLVEMENT IN FETAL HYPOKINESIA AND CONGENITAL MYOPATHY, VARIANTS HIS-104;
RP LYS-203; TRP-225; THR-382; ASN-1069; CYS-1135 AND PHE-1209,
RP CHARACTERIZATION OF VARIANTS HIS-104; LYS-203; TRP-225; THR-382; ASN-1069
RP AND PHE-1209, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26700687; DOI=10.1093/brain/awv352;
RA Zaharieva I.T., Thor M.G., Oates E.C., van Karnebeek C., Hendson G.,
RA Blom E., Witting N., Rasmussen M., Gabbett M.T., Ravenscroft G.,
RA Sframeli M., Suetterlin K., Sarkozy A., D'Argenzio L., Hartley L.,
RA Matthews E., Pitt M., Vissing J., Ballegaard M., Krarup C., Sloerdahl A.,
RA Halvorsen H., Ye X.C., Zhang L.H., Loekken N., Werlauff U., Abdelsayed M.,
RA Davis M.R., Feng L., Phadke R., Sewry C.A., Morgan J.E., Laing N.G.,
RA Vallance H., Ruben P., Hanna M.G., Lewis S., Kamsteeg E.J., Maennikkoe R.,
RA Muntoni F.;
RT "Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or
RT 'classical' congenital myopathy.";
RL Brain 139:674-691(2016).
RN [55]
RP VARIANT LEU-72, CHARACTERIZATION OF VARIANT LEU-72, AND INVOLVEMENT IN DM2.
RX PubMed=25660391; DOI=10.1016/j.nmd.2015.01.006;
RA Bugiardini E., Rivolta I., Binda A., Soriano Caminero A., Cirillo F.,
RA Cinti A., Giovannoni R., Botta A., Cardani R., Wicklund M.P., Meola G.;
RT "SCN4A mutation as modifying factor of myotonic dystrophy type 2
RT phenotype.";
RL Neuromuscul. Disord. 25:301-307(2015).
RN [56]
RP VARIANT MYOSCN4A LEU-1290.
RX PubMed=27653901; DOI=10.1016/j.jns.2016.08.030;
RA Kato H., Kokunai Y., Dalle C., Kubota T., Madokoro Y., Yuasa H., Uchida Y.,
RA Ikeda T., Mochizuki H., Nicole S., Fontaine B., Takahashi M.P., Mitake S.;
RT "A case of non-dystrophic myotonia with concomitant mutations in the SCN4A
RT and CLCN1 genes.";
RL J. Neurol. Sci. 369:254-258(2016).
RN [57]
RP VARIANT ILE-781.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
RN [58]
RP VARIANT CMS16 TRP-1454, CHARACTERIZATION OF VARIANT CMS16 TRP-1454,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26659129; DOI=10.1212/wnl.0000000000002264;
RA Habbout K., Poulin H., Rivier F., Giuliano S., Sternberg D., Fontaine B.,
RA Eymard B., Morales R.J., Echenne B., King L., Hanna M.G., Maennikkoe R.,
RA Chahine M., Nicole S., Bendahhou S.;
RT "A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with
RT periodic paralysis.";
RL Neurology 86:161-169(2016).
CC -!- FUNCTION: Pore-forming subunit of a voltage-gated sodium channel
CC complex through which Na(+) ions pass in accordance with their
CC electrochemical gradient. Alternates between resting, activated and
CC inactivated states (PubMed:12766226, PubMed:29992740, PubMed:30190309,
CC PubMed:15318338, PubMed:16890191, PubMed:18690054, PubMed:17898326,
CC PubMed:19347921, PubMed:25707578, PubMed:26700687). Required for normal
CC muscle fiber excitability, normal muscle contraction and relaxation
CC cycles, and constant muscle strength in the presence of fluctuating
CC K(+) levels (PubMed:12766226, PubMed:15318338, PubMed:16890191,
CC PubMed:19347921, PubMed:25707578, PubMed:26700687, PubMed:26659129).
CC {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:15318338,
CC ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326,
CC ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19347921,
CC ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129,
CC ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:29992740,
CC ECO:0000269|PubMed:30190309}.
CC -!- ACTIVITY REGULATION: Channel activity is regulated by the ancillary
CC beta subunit SCN1B (PubMed:29992740). SCN1B strongly enhances the
CC presence of the pore-forming alpha subunit at the cell surface
CC (PubMed:29992740, PubMed:30190309). Interaction with SCN1B is required
CC for rapid channel inactivation and rapid recovery after inactivation,
CC and prevents decrease of channel activity in response to repetitive,
CC high-frequency depolarizations (By similarity). The channel is
CC inhibited by tetrodotoxin and saxitoxin (PubMed:30190309).
CC {ECO:0000250|UniProtKB:P15390, ECO:0000269|PubMed:29992740,
CC ECO:0000269|PubMed:30190309}.
CC -!- SUBUNIT: Component of a voltage-sensitive sodium channel complex that
CC consists of an ion-conducting pore-forming alpha subunit and one or
CC more regulatory beta subunits (PubMed:29992740, PubMed:30190309).
CC Interacts with SCN1B (PubMed:29992740, PubMed:30190309). Heterooligomer
CC with SCN2B or SCN4B; disulfide-linked (By similarity). Interacts with
CC the PDZ domain of the syntrophins SNTA1, SNTB1 and SNTB2 (By
CC similarity). Interacts with the conotoxin GVIIJ (PubMed:24497506).
CC {ECO:0000250|UniProtKB:P04775, ECO:0000250|UniProtKB:Q9ER60,
CC ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:29992740,
CC ECO:0000269|PubMed:30190309}.
CC -!- INTERACTION:
CC P35499; Q07699-1: SCN1B; NbExp=2; IntAct=EBI-16813249, EBI-20974499;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12766226,
CC ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:16890191,
CC ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18690054,
CC ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:25707578,
CC ECO:0000269|PubMed:26659129, ECO:0000269|PubMed:26700687,
CC ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:30190309}.
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|PubMed:30190309}.
CC -!- PTM: Phosphorylation at Ser-1328 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: Paramyotonia congenita of von Eulenburg (PMC) [MIM:168300]: An
CC autosomal dominant channelopathy characterized by myotonia, increased
CC by exposure to cold, intermittent flaccid paresis, not necessarily
CC dependent on cold or myotonia, lability of serum potassium, non-
CC progressive nature and lack of atrophy or hypertrophy of muscles. In
CC some patients, myotonia is not increased by cold exposure (paramyotonia
CC without cold paralysis). Patients may have a combination phenotype of
CC PMC and HYPP. {ECO:0000269|PubMed:10369308,
CC ECO:0000269|PubMed:10727489, ECO:0000269|PubMed:1310898,
CC ECO:0000269|PubMed:1316765, ECO:0000269|PubMed:1338909,
CC ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:15790667,
CC ECO:0000269|PubMed:16786525, ECO:0000269|PubMed:18166706,
CC ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19077043,
CC ECO:0000269|PubMed:20076800, ECO:0000269|PubMed:8242056,
CC ECO:0000269|PubMed:8308722, ECO:0000269|PubMed:8388676,
CC ECO:0000269|PubMed:8580427}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An
CC autosomal dominant disorder manifested by episodic flaccid generalized
CC muscle weakness associated with falls of serum potassium levels.
CC {ECO:0000269|PubMed:10599760, ECO:0000269|PubMed:10851391,
CC ECO:0000269|PubMed:10944223, ECO:0000269|PubMed:11558801,
CC ECO:0000269|PubMed:11591859, ECO:0000269|PubMed:16890191,
CC ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18162704,
CC ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:20522878,
CC ECO:0000269|PubMed:21043388, ECO:0000269|PubMed:24549961}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An
CC autosomal dominant channelopathy characterized by episodic flaccid
CC generalized muscle weakness associated with high levels of serum
CC potassium. Concurrence of myotonia is found in HYPP patients.
CC {ECO:0000269|PubMed:1659668, ECO:0000269|PubMed:1659948,
CC ECO:0000269|PubMed:20076800}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Periodic paralysis normokalemic (NKPP) [MIM:170500]: A
CC disorder closely related to hyperkalemic periodic paralysis, but marked
CC by a lack of alterations in potassium levels during attacks of muscle
CC weakness. {ECO:0000269|PubMed:15596759, ECO:0000269|PubMed:18046642,
CC ECO:0000269|PubMed:20522878}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A
CC phenotypically highly variable myotonia aggravated by potassium
CC loading, and sometimes by cold. Myotonia is characterized by sustained
CC muscle tensing that prevents muscles from relaxing normally. It causes
CC muscle stiffness that can interfere with movement. In some people the
CC stiffness is very mild, while in other cases it may be severe enough to
CC interfere with walking, running, and other activities of daily life.
CC Myotonia SCN4A-related includes myotonia permanens and myotonia
CC fluctuans. In myotonia permanens, the myotonia is generalized and there
CC is a hypertrophy of the muscle, particularly in the neck and the
CC shoulder. Attacks of severe muscle stiffness of the thoracic muscles
CC may be life threatening due to impaired ventilation. In myotonia
CC fluctuans, the muscle stiffness may fluctuate from day to day, provoked
CC by exercise. {ECO:0000269|PubMed:10218481, ECO:0000269|PubMed:16786525,
CC ECO:0000269|PubMed:16832098, ECO:0000269|PubMed:17212350,
CC ECO:0000269|PubMed:17998485, ECO:0000269|PubMed:18203179,
CC ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:19015483,
CC ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:20076800,
CC ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:8058156,
CC ECO:0000269|PubMed:9392583}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myasthenic syndrome, congenital, 16 (CMS16) [MIM:614198]: A
CC form of congenital myasthenic syndrome, a group of disorders
CC characterized by failure of neuromuscular transmission, including pre-
CC synaptic, synaptic, and post-synaptic disorders that are not of
CC autoimmune origin. Clinical features are easy fatigability and muscle
CC weakness. CMS16 is characterized by fatigable generalized weakness and
CC recurrent attacks of respiratory and bulbar paralysis since birth. The
CC fatigable weakness involves lid-elevator, external ocular, facial, limb
CC and truncal muscles and an decremental response of the compound muscle
CC action potential on repetitive stimulation.
CC {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:25707578,
CC ECO:0000269|PubMed:26659129}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=SCN4A mutations are the cause of an autosomal recessive
CC neuromuscular disorder characterized by severe fetal hypokinesia,
CC neonatal hypotonia and congenital myopathy of variable severity. The
CC most severe clinical features include reduced or absent fetal
CC movements, in-utero upper and lower limb contractures, talipes and
CC hydrops, and intrauterine or early postnatal death. Mildly affected
CC patients present with generalized hypotonia and weakness at birth or
CC within the first few days of life, mild-to-moderate facial muscle
CC weakness without ptosis, significant early respiratory and feeding
CC difficulties, and skeletal abnormalities of the spine and palate.
CC Symptoms improve over time in patients who survive infancy, resulting
CC in gain of muscle strength and motor skills and concomitant resolution
CC of early respiratory and feeding difficulties. In contrast to other
CC SCN4A-related channelopathies, affected individuals manifest in-utero
CC or neonatal onset of permanent muscle weakness, rather than later-onset
CC episodic muscle weakness. {ECO:0000269|PubMed:26700687}.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.4/SCN4A subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=SCN4A entry;
CC URL="https://en.wikipedia.org/wiki/SCN4A";
CC ---------------------------------------------------------------------------
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DR EMBL; M81758; AAA60554.1; -; mRNA.
DR EMBL; L04236; AAB59624.1; -; Genomic_DNA.
DR EMBL; L04216; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04217; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04218; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04219; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04220; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04221; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04222; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04223; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04224; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04225; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04226; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04227; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04228; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04229; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04230; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04231; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04232; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04233; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04234; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; L04235; AAB59624.1; JOINED; Genomic_DNA.
DR EMBL; AY212253; AAO83647.1; -; mRNA.
DR EMBL; L01983; AAA75557.1; ALT_SEQ; Genomic_DNA.
DR EMBL; L01962; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01963; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01964; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01965; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01966; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01967; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01968; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01969; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01970; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01971; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01972; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01973; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01974; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01975; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01976; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01977; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01978; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01979; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01980; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01981; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; L01982; AAA75557.1; JOINED; Genomic_DNA.
DR EMBL; AC127029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; S82622; AAB21450.2; -; Genomic_DNA.
DR CCDS; CCDS45761.1; -.
DR PIR; I51964; I51964.
DR PIR; I54323; I54323.
DR PIR; I64893; I64893.
DR PIR; JS0648; JS0648.
DR RefSeq; NP_000325.4; NM_000334.4.
DR PDB; 6AGF; EM; 3.20 A; A=1-1836.
DR PDB; 6MBA; X-ray; 1.80 A; A=1599-1764.
DR PDB; 6MC9; X-ray; 3.30 A; A=1599-1754.
DR PDBsum; 6AGF; -.
DR PDBsum; 6MBA; -.
DR PDBsum; 6MC9; -.
DR AlphaFoldDB; P35499; -.
DR SMR; P35499; -.
DR BioGRID; 112234; 89.
DR IntAct; P35499; 7.
DR STRING; 9606.ENSP00000396320; -.
DR BindingDB; P35499; -.
DR ChEMBL; CHEMBL2072; -.
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; DB00586; Diclofenac.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB01195; Flecainide.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB00281; Lidocaine.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB13154; Parachlorophenol.
DR DrugBank; DB11186; Pentoxyverine.
DR DrugBank; DB09345; Pramocaine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB09342; Propoxycaine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB09085; Tetracaine.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; P35499; -.
DR GuidetoPHARMACOLOGY; 581; -.
DR TCDB; 1.A.1.10.4; the voltage-gated ion channel (vic) superfamily.
DR GlyConnect; 1752; 2 N-Linked glycans (2 sites).
DR GlyGen; P35499; 13 sites, 3 N-linked glycans (2 sites).
DR iPTMnet; P35499; -.
DR PhosphoSitePlus; P35499; -.
DR BioMuta; SCN4A; -.
DR DMDM; 292495096; -.
DR EPD; P35499; -.
DR MassIVE; P35499; -.
DR PaxDb; P35499; -.
DR PeptideAtlas; P35499; -.
DR PRIDE; P35499; -.
DR ProteomicsDB; 55071; -.
DR ABCD; P35499; 3 sequenced antibodies.
DR Antibodypedia; 57204; 87 antibodies from 21 providers.
DR DNASU; 6329; -.
DR Ensembl; ENST00000435607.3; ENSP00000396320.1; ENSG00000007314.12.
DR GeneID; 6329; -.
DR KEGG; hsa:6329; -.
DR MANE-Select; ENST00000435607.3; ENSP00000396320.1; NM_000334.4; NP_000325.4.
DR UCSC; uc002jds.1; human.
DR CTD; 6329; -.
DR DisGeNET; 6329; -.
DR GeneCards; SCN4A; -.
DR GeneReviews; SCN4A; -.
DR HGNC; HGNC:10591; SCN4A.
DR HPA; ENSG00000007314; Group enriched (skeletal muscle, tongue).
DR MalaCards; SCN4A; -.
DR MIM; 168300; phenotype.
DR MIM; 170500; phenotype.
DR MIM; 603967; gene.
DR MIM; 608390; phenotype.
DR MIM; 613345; phenotype.
DR MIM; 614198; phenotype.
DR neXtProt; NX_P35499; -.
DR OpenTargets; ENSG00000007314; -.
DR Orphanet; 99736; Acetazolamide-responsive myotonia.
DR Orphanet; 682; Hyperkalemic periodic paralysis.
DR Orphanet; 681; Hypokalemic periodic paralysis.
DR Orphanet; 99734; Myotonia fluctuans.
DR Orphanet; 99735; Myotonia permanens.
DR Orphanet; 684; Paramyotonia congenita of Von Eulenburg.
DR Orphanet; 98913; Postsynaptic congenital myasthenic syndromes.
DR PharmGKB; PA35006; -.
DR VEuPathDB; HostDB:ENSG00000007314; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000159417; -.
DR HOGENOM; CLU_000540_5_0_1; -.
DR InParanoid; P35499; -.
DR OMA; CCAPWMK; -.
DR OrthoDB; 56920at2759; -.
DR PhylomeDB; P35499; -.
DR TreeFam; TF323985; -.
DR PathwayCommons; P35499; -.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR SignaLink; P35499; -.
DR SIGNOR; P35499; -.
DR BioGRID-ORCS; 6329; 16 hits in 1066 CRISPR screens.
DR ChiTaRS; SCN4A; human.
DR GeneWiki; Nav1.4; -.
DR GenomeRNAi; 6329; -.
DR Pharos; P35499; Tclin.
DR PRO; PR:P35499; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P35499; protein.
DR Bgee; ENSG00000007314; Expressed in hindlimb stylopod muscle and 107 other tissues.
DR Genevisible; P35499; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:UniProtKB.
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:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0100001; P:regulation of skeletal muscle contraction by action potential; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; TAS:ProtInc.
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; IPR008052; Na_channel_a4su_mammal.
DR InterPro; IPR001696; Na_channel_asu.
DR InterPro; IPR044564; Na_chnl_inactivation_gate.
DR InterPro; IPR010526; Na_trans_assoc.
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; PF06512; Na_trans_assoc; 1.
DR PRINTS; PR00170; NACHANNEL.
DR PRINTS; PR01665; NACHANNEL4.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Congenital myasthenic syndrome;
KW Disease variant; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..1836
FT /note="Sodium channel protein type 4 subunit alpha"
FT /id="PRO_0000048495"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 132..150
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 151..157
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 158..178
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 179..192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 193..210
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 211..216
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 217..233
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 234..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 253..272
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 273..391
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT INTRAMEM 392..416
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 417..423
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 424..444
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 445..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 579..597
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 598..608
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 609..628
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 629..642
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 643..662
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 663..664
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 665..682
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 683..698
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 699..717
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 718..746
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT INTRAMEM 747..767
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 768..778
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 779..797
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 798..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1033..1050
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1051..1063
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1064..1082
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1083..1096
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1097..1115
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1116..1123
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1124..1142
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1143..1159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1160..1179
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1180..1230
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT INTRAMEM 1231..1252
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1253..1269
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1270..1291
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1292..1354
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1355..1372
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1373..1383
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1384..1402
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1403..1414
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1415..1432
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1433..1445
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1446..1462
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1463..1481
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1482..1499
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1500..1521
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT INTRAMEM 1522..1544
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1545..1574
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 1575..1597
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 1598..1836
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT REPEAT 113..454
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 560..832
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1013..1326
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1335..1633
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1727..1756
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 39..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 493..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 863..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..992
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1310..1312
FT /note="Important for rapid channel inactivation"
FT /evidence="ECO:0000250|UniProtKB:P15390"
FT REGION 1778..1836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 507..530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 872..886
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 975..990
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1779..1793
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 407
FT /note="Important for inhibition by tetrodotoxin"
FT /evidence="ECO:0000250|UniProtKB:P15390"
FT MOD_RES 1328
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT CARBOHYD 1191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT DISULFID 280..360
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT DISULFID 369..375
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT DISULFID 729
FT /note="Interchain; with SCN2B or SCN4B"
FT /evidence="ECO:0000250|UniProtKB:P04775"
FT DISULFID 729
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 731..737
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT DISULFID 769..778
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT DISULFID 1189..1209
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT DISULFID 1553..1568
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0007744|PDB:6AGF"
FT VARIANT 72
FT /note="P -> L (found in a patient with severe dystrophia
FT myotonica 2 (DM2) carrying a pathogenic CCTG repeat
FT expansion in CNBP; unknown pathological significance; may
FT act as a disease modifier; changes the voltage-gated sodium
FT channel activity; increases membrane hyperexcitability;
FT decreases channel fast inactivation; dbSNP:rs1303471186)"
FT /evidence="ECO:0000269|PubMed:25660391"
FT /id="VAR_074598"
FT VARIANT 104
FT /note="R -> H (probable disease-associated variant found in
FT patients with severe fetal hypokinesia or congenital
FT myopathy; complete loss of sodium channel function;
FT dbSNP:rs1248025530)"
FT /evidence="ECO:0000269|PubMed:26700687"
FT /id="VAR_075430"
FT VARIANT 135
FT /note="M -> V"
FT /id="VAR_001560"
FT VARIANT 141
FT /note="I -> V (in MYOSCN4A; causes a hyperpolarizing shift
FT of the activation curve; enhances channel slow
FT inactivation; dbSNP:rs121908561)"
FT /evidence="ECO:0000269|PubMed:19015483"
FT /id="VAR_054934"
FT VARIANT 203
FT /note="M -> K (probable disease-associated variant found in
FT patients with severe fetal hypokinesia or congenital
FT myopathy; impaired sodium channel function;
FT dbSNP:rs933258893)"
FT /evidence="ECO:0000269|PubMed:26700687"
FT /id="VAR_075431"
FT VARIANT 222
FT /note="R -> W (in HOKPP2; dbSNP:rs527236148)"
FT /evidence="ECO:0000269|PubMed:19118277"
FT /id="VAR_054935"
FT VARIANT 225
FT /note="R -> W (in MYOSCN4A; also found in patients with
FT severe fetal hypokinesia or congenital myopathy; impaired
FT sodium channel function; dbSNP:rs764718003)"
FT /evidence="ECO:0000269|PubMed:20076800,
FT ECO:0000269|PubMed:26700687"
FT /id="VAR_065230"
FT VARIANT 246
FT /note="S -> L (no significant effect on channel activity;
FT dbSNP:rs80338951)"
FT /evidence="ECO:0000269|PubMed:12766226"
FT /id="VAR_017785"
FT VARIANT 270
FT /note="Q -> K (in PMC; dbSNP:rs1597985462)"
FT /evidence="ECO:0000269|PubMed:16786525,
FT ECO:0000269|PubMed:18166706"
FT /id="VAR_054936"
FT VARIANT 382
FT /note="P -> T (probable disease-associated variant found in
FT patients with severe fetal hypokinesia or congenital
FT myopathy; complete loss of sodium channel function)"
FT /evidence="ECO:0000269|PubMed:26700687"
FT /id="VAR_075432"
FT VARIANT 445
FT /note="V -> M (in MYOSCN4A; dbSNP:rs121908552)"
FT /evidence="ECO:0000269|PubMed:10218481,
FT ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:9392583"
FT /id="VAR_017786"
FT VARIANT 452
FT /note="E -> K (in MYOSCN4A; variable phenotype ranging from
FT mild to severe myotonia; dbSNP:rs372631097)"
FT /evidence="ECO:0000269|PubMed:18337100"
FT /id="VAR_054937"
FT VARIANT 524
FT /note="S -> G (in dbSNP:rs6504191)"
FT /evidence="ECO:0000269|PubMed:12766226,
FT ECO:0000269|PubMed:1315496, ECO:0000269|PubMed:1339144"
FT /id="VAR_001561"
FT VARIANT 559
FT /note="N -> D (in dbSNP:rs1047705)"
FT /evidence="ECO:0000269|PubMed:12766226,
FT ECO:0000269|PubMed:1315496"
FT /id="VAR_017787"
FT VARIANT 669
FT /note="R -> H (in HOKPP2; dbSNP:rs80338784)"
FT /evidence="ECO:0000269|PubMed:10599760,
FT ECO:0000269|PubMed:18162704"
FT /id="VAR_017788"
FT VARIANT 671
FT /note="F -> S (in MYOSCN4A)"
FT /evidence="ECO:0000269|PubMed:18337100"
FT /id="VAR_054938"
FT VARIANT 672
FT /note="R -> C (in HOKPP2; dbSNP:rs80338785)"
FT /evidence="ECO:0000269|PubMed:18162704,
FT ECO:0000269|PubMed:19118277"
FT /id="VAR_054939"
FT VARIANT 672
FT /note="R -> G (in HOKPP2; dbSNP:rs80338785)"
FT /evidence="ECO:0000269|PubMed:10944223,
FT ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277"
FT /id="VAR_017789"
FT VARIANT 672
FT /note="R -> H (in HOKPP2; dbSNP:rs80338788)"
FT /evidence="ECO:0000269|PubMed:10944223,
FT ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:21043388"
FT /id="VAR_017790"
FT VARIANT 672
FT /note="R -> S (in HOKPP2; dbSNP:rs80338785)"
FT /evidence="ECO:0000269|PubMed:11558801,
FT ECO:0000269|PubMed:11591859, ECO:0000269|PubMed:19118277"
FT /id="VAR_017791"
FT VARIANT 675
FT /note="R -> G (in NKPP; dbSNP:rs121908556)"
FT /evidence="ECO:0000269|PubMed:15596759"
FT /id="VAR_037104"
FT VARIANT 675
FT /note="R -> Q (in NKPP; dbSNP:rs121908557)"
FT /evidence="ECO:0000269|PubMed:15596759,
FT ECO:0000269|PubMed:18046642"
FT /id="VAR_037105"
FT VARIANT 675
FT /note="R -> W (in NKPP; dbSNP:rs121908556)"
FT /evidence="ECO:0000269|PubMed:15596759"
FT /id="VAR_037106"
FT VARIANT 693
FT /note="I -> T (in PMC; dbSNP:rs80338956)"
FT /evidence="ECO:0000269|PubMed:20076800"
FT /id="VAR_065231"
FT VARIANT 704
FT /note="T -> M (in HYPP and PMC; dbSNP:rs80338957)"
FT /evidence="ECO:0000269|PubMed:1659948,
FT ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:19077043"
FT /id="VAR_001562"
FT VARIANT 715
FT /note="A -> T (in MYOSCN4A; dbSNP:rs749400108)"
FT /evidence="ECO:0000269|PubMed:16786525"
FT /id="VAR_054940"
FT VARIANT 781
FT /note="V -> I (voltage-gated sodium channel activity is not
FT affected and channel activation as well as fast and slow
FT inactivation curves are normal; dbSNP:rs62070884)"
FT /evidence="ECO:0000269|PubMed:18046642,
FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:7695243,
FT ECO:0000269|PubMed:9266738"
FT /id="VAR_054941"
FT VARIANT 804
FT /note="S -> F (in PMC; dbSNP:rs121908546)"
FT /evidence="ECO:0000269|PubMed:1338909"
FT /id="VAR_001563"
FT VARIANT 804
FT /note="S -> N (in MYOSCN4A)"
FT /evidence="ECO:0000269|PubMed:16786525"
FT /id="VAR_054942"
FT VARIANT 861
FT /note="A -> D"
FT /id="VAR_001564"
FT VARIANT 1069
FT /note="D -> N (probable disease-associated variant found in
FT patients with severe fetal hypokinesia or congenital
FT myopathy; impaired sodium channel function;
FT dbSNP:rs373150395)"
FT /evidence="ECO:0000269|PubMed:26700687"
FT /id="VAR_075433"
FT VARIANT 1129
FT /note="R -> Q (in NKPP and HOKPP2; detected in a family
FT where three affected members manifested hypokalemic
FT periodic paralysis whereas five other patients had
FT normokalemic periodic paralysis; dbSNP:rs527236149)"
FT /evidence="ECO:0000269|PubMed:20522878"
FT /id="VAR_064987"
FT VARIANT 1132
FT /note="R -> Q (in HOKPP2; changes the voltage-gated sodium
FT channel activity; increases membrane hypoexcitability;
FT increases channel activation and both fast and slow channel
FT inactivation; dbSNP:rs80338789)"
FT /evidence="ECO:0000269|PubMed:16890191,
FT ECO:0000269|PubMed:19118277"
FT /id="VAR_054943"
FT VARIANT 1135
FT /note="R -> C (in HOKPP2; also found in patients with
FT severe fetal hypokinesia or congenital myopathy; increased
FT depolarization tendency at normal and reduced extracellular
FT potassium and reduced amplitude and rise time of action
FT potentials; dbSNP:rs1287863349)"
FT /evidence="ECO:0000269|PubMed:24549961,
FT ECO:0000269|PubMed:26700687"
FT /id="VAR_075434"
FT VARIANT 1135
FT /note="R -> H (in HOKPP2; increased depolarization tendency
FT at normal and reduced extracellular potassium and reduced
FT amplitude and rise time of action potentials;
FT dbSNP:rs527236150)"
FT /evidence="ECO:0000269|PubMed:19118277,
FT ECO:0000269|PubMed:24549961"
FT /id="VAR_054944"
FT VARIANT 1152
FT /note="A -> D (in PMC)"
FT /evidence="ECO:0000269|PubMed:15790667"
FT /id="VAR_022341"
FT VARIANT 1156
FT /note="A -> T (in PMC, MYOSCN4A and HYPP;
FT dbSNP:rs80338958)"
FT /evidence="ECO:0000269|PubMed:1338909,
FT ECO:0000269|PubMed:20076800"
FT /id="VAR_001565"
FT VARIANT 1158
FT /note="P -> S (in HOKPP2; atypical phenotype with heat-
FT induced myotonia and cold-induced paralysis with
FT hypokalemia; changes the voltage-gated sodium channel
FT activity; increases channel activation and slow
FT inactivation at low temperature; dbSNP:rs121908555)"
FT /evidence="ECO:0000269|PubMed:10851391,
FT ECO:0000269|PubMed:17898326"
FT /id="VAR_017792"
FT VARIANT 1160
FT /note="I -> V (in MYOSCN4A; acetazolamide-responsive
FT myotonia; dbSNP:rs121908549)"
FT /evidence="ECO:0000269|PubMed:8058156"
FT /id="VAR_017793"
FT VARIANT 1209
FT /note="C -> F (probable disease-associated variant found in
FT patients with severe fetal hypokinesia or congenital
FT myopathy; complete loss of sodium channel function)"
FT /evidence="ECO:0000269|PubMed:26700687"
FT /id="VAR_075435"
FT VARIANT 1290
FT /note="F -> L (in MYOSCN4A; enhances voltage-gated sodium
FT channel activation inducing membrane hyperexcitability)"
FT /evidence="ECO:0000269|PubMed:27653901"
FT /id="VAR_079519"
FT VARIANT 1293
FT /note="V -> I (in PMC; without cold paralysis;
FT dbSNP:rs121908551)"
FT /evidence="ECO:0000269|PubMed:8580427"
FT /id="VAR_001566"
FT VARIANT 1297
FT /note="N -> K (in MYOSCN4A; unusually severe and lethal
FT phenotype with neonatal onset; dbSNP:rs121908560)"
FT /evidence="ECO:0000269|PubMed:18203179"
FT /id="VAR_054945"
FT VARIANT 1306
FT /note="G -> A (in PMC; dbSNP:rs80338792)"
FT /evidence="ECO:0000269|PubMed:18166706,
FT ECO:0000269|PubMed:8308722"
FT /id="VAR_001567"
FT VARIANT 1306
FT /note="G -> E (in MYOSCN4A and PMC; severe;
FT dbSNP:rs80338792)"
FT /evidence="ECO:0000269|PubMed:16832098,
FT ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:20076800,
FT ECO:0000269|PubMed:8308722"
FT /id="VAR_001568"
FT VARIANT 1306
FT /note="G -> V (in MYOSCN4A and PMC; dbSNP:rs80338792)"
FT /evidence="ECO:0000269|PubMed:1310898,
FT ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:8308722"
FT /id="VAR_001569"
FT VARIANT 1310
FT /note="I -> N (in MYOSCN4A; dbSNP:rs1567817380)"
FT /evidence="ECO:0000269|PubMed:16786525"
FT /id="VAR_054946"
FT VARIANT 1313
FT /note="T -> M (in PMC; changes the voltage-gated sodium
FT channel activity; increases membrane hyperexcitability at
FT low temperature; decreases channel activation,
FT deactivation, fast inactivation and recovery delay from
FT fast inactivation; dbSNP:rs121908547)"
FT /evidence="ECO:0000269|PubMed:1310898,
FT ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:18166706"
FT /id="VAR_001570"
FT VARIANT 1376
FT /note="N -> D (in dbSNP:rs2058194)"
FT /evidence="ECO:0000269|PubMed:1315496"
FT /id="VAR_017794"
FT VARIANT 1433
FT /note="L -> R (in PMC and HYPP; dbSNP:rs121908550)"
FT /evidence="ECO:0000269|PubMed:8388676"
FT /id="VAR_001571"
FT VARIANT 1436
FT /note="L -> P (in PMC; dbSNP:rs1598405334)"
FT /evidence="ECO:0000269|PubMed:18166706"
FT /id="VAR_054947"
FT VARIANT 1442
FT /note="V -> E (in CMS16; leads to fast inactivation;
FT dbSNP:rs121908553)"
FT /evidence="ECO:0000269|PubMed:12766226"
FT /id="VAR_017795"
FT VARIANT 1448
FT /note="R -> C (in PMC; changes the voltage-gated sodium
FT channel activity; increases membrane hyperexcitability at
FT low temperature; decreases channel activation,
FT deactivation, fast inactivation and recovery delay from
FT fast inactivation; dbSNP:rs121908544)"
FT /evidence="ECO:0000269|PubMed:1316765,
FT ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:18166706"
FT /id="VAR_001572"
FT VARIANT 1448
FT /note="R -> H (in PMC; dbSNP:rs121908545)"
FT /evidence="ECO:0000269|PubMed:1316765,
FT ECO:0000269|PubMed:18166706"
FT /id="VAR_001573"
FT VARIANT 1448
FT /note="R -> L (in PMC; dbSNP:rs121908545)"
FT /evidence="ECO:0000269|PubMed:18166706"
FT /id="VAR_054948"
FT VARIANT 1454
FT /note="R -> W (in CMS16; leads to hyperpolarization of the
FT steady-state fast inactivation, slow recovery from
FT inactivation and reduces the channel ability to activate in
FT response to repetitive stimulating pulses;
FT dbSNP:rs879253789)"
FT /evidence="ECO:0000269|PubMed:26659129"
FT /id="VAR_075436"
FT VARIANT 1456
FT /note="G -> E (in PMC; dbSNP:rs121908554)"
FT /evidence="ECO:0000269|PubMed:10369308,
FT ECO:0000269|PubMed:10727489, ECO:0000269|PubMed:18166706"
FT /id="VAR_037107"
FT VARIANT 1457
FT /note="R -> H (in CMS16; enhanced fast inactivation and
FT slowed recovery from fast inactivation; dbSNP:rs863225046)"
FT /evidence="ECO:0000269|PubMed:25707578"
FT /id="VAR_075437"
FT VARIANT 1473
FT /note="F -> S (in PMC; accelerates deactivation from the
FT inactivated state and enhances the remobilization of gating
FT charge)"
FT /evidence="ECO:0000269|PubMed:18166706,
FT ECO:0000269|PubMed:18690054"
FT /id="VAR_054949"
FT VARIANT 1476
FT /note="M -> I (in MYOSCN4A; highly variable severity;
FT dbSNP:rs121908559)"
FT /evidence="ECO:0000269|PubMed:17998485,
FT ECO:0000269|PubMed:18337100"
FT /id="VAR_054950"
FT VARIANT 1481
FT /note="A -> D (in MYOSCN4A; fluctuating cold-induced and
FT exercise-induced stiffness; dbSNP:rs763893717)"
FT /evidence="ECO:0000269|PubMed:17212350"
FT /id="VAR_054951"
FT VARIANT 1589
FT /note="V -> M (in PMC; dbSNP:rs121908548)"
FT /evidence="ECO:0000269|PubMed:18166706,
FT ECO:0000269|PubMed:8242056"
FT /id="VAR_001574"
FT VARIANT 1592
FT /note="M -> V (in HYPP and NKPP; dbSNP:rs80338962)"
FT /evidence="ECO:0000269|PubMed:1659668,
FT ECO:0000269|PubMed:18046642"
FT /id="VAR_001575"
FT VARIANT 1633
FT /note="Q -> E (in MYOSCN4A; changes the voltage-gated
FT sodium channel activity; increases membrane
FT hyperexcitability; decreases channel fast inactivation)"
FT /evidence="ECO:0000269|PubMed:19347921"
FT /id="VAR_074581"
FT VARIANT 1705
FT /note="F -> I (in PMC; increases the extent of charge
FT immobilization in response to strong depolarization;
FT dbSNP:rs1064794243)"
FT /evidence="ECO:0000269|PubMed:18690054"
FT /id="VAR_054952"
FT CONFLICT 10..11
FT /note="VP -> AR (in Ref. 1; AAA60554)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="E -> K (in Ref. 1; AAA60554)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="E -> Q (in Ref. 1; AAB59624)"
FT /evidence="ECO:0000305"
FT CONFLICT 870
FT /note="A -> G (in Ref. 1; AAB59624)"
FT /evidence="ECO:0000305"
FT CONFLICT 1151..1152
FT /note="NA -> KP (in Ref. 1; AAB59624)"
FT /evidence="ECO:0000305"
FT HELIX 121..128
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 133..147
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 158..179
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 184..188
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 228..232
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 236..243
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 245..248
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 251..272
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 338..342
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 362..366
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 373..377
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 392..397
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 400..403
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 408..419
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 424..433
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 434..438
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 439..453
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 455..462
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 561..576
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 577..580
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 581..595
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 604..631
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 634..639
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 641..659
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 668..670
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 672..680
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 686..697
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 698..702
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 703..726
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 730..732
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 744..746
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 747..759
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 764..772
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 775..802
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1015..1028
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1031..1046
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1053..1055
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1060..1078
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1081..1087
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1090..1093
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1095..1097
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1098..1116
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1117..1119
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 1123..1129
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1130..1141
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1144..1153
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1154..1156
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1157..1182
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1188..1191
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 1192..1194
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 1200..1202
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1206..1209
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1210..1212
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1218..1221
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1230..1241
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1246..1255
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1269..1271
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1272..1281
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1284..1304
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1305..1309
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1316..1324
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 1325..1328
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1341..1343
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1347..1350
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1354..1362
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1365..1371
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1379..1404
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 1408..1413
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1415..1439
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1444..1446
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1447..1450
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1451..1463
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1468..1503
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1504..1506
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1515..1521
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1522..1531
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1532..1534
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1538..1542
FT /evidence="ECO:0007829|PDB:6AGF"
FT TURN 1543..1545
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 1549..1553
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1571..1605
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 1614..1627
FT /evidence="ECO:0007829|PDB:6MBA"
FT STRAND 1633..1636
FT /evidence="ECO:0007829|PDB:6MBA"
FT HELIX 1637..1639
FT /evidence="ECO:0007829|PDB:6MBA"
FT HELIX 1640..1646
FT /evidence="ECO:0007829|PDB:6MBA"
FT TURN 1649..1651
FT /evidence="ECO:0007829|PDB:6MBA"
FT HELIX 1658..1663
FT /evidence="ECO:0007829|PDB:6MBA"
FT STRAND 1667..1669
FT /evidence="ECO:0007829|PDB:6MBA"
FT TURN 1670..1672
FT /evidence="ECO:0007829|PDB:6MBA"
FT STRAND 1673..1675
FT /evidence="ECO:0007829|PDB:6MBA"
FT HELIX 1676..1688
FT /evidence="ECO:0007829|PDB:6MBA"
FT HELIX 1692..1705
FT /evidence="ECO:0007829|PDB:6MBA"
FT STRAND 1718..1720
FT /evidence="ECO:0007829|PDB:6MBA"
FT HELIX 1721..1745
FT /evidence="ECO:0007829|PDB:6MBA"
SQ SEQUENCE 1836 AA; 208061 MW; FA9A6B81B7C2D50F CRC64;
MARPSLCTLV PLGPECLRPF TRESLAAIEQ RAVEEEARLQ RNKQMEIEEP ERKPRSDLEA
GKNLPMIYGD PPPEVIGIPL EDLDPYYSNK KTFIVLNKGK AIFRFSATPA LYLLSPFSVV
RRGAIKVLIH ALFSMFIMIT ILTNCVFMTM SDPPPWSKNV EYTFTGIYTF ESLIKILARG
FCVDDFTFLR DPWNWLDFSV IMMAYLTEFV DLGNISALRT FRVLRALKTI TVIPGLKTIV
GALIQSVKKL SDVMILTVFC LSVFALVGLQ LFMGNLRQKC VRWPPPFNDT NTTWYSNDTW
YGNDTWYGNE MWYGNDSWYA NDTWNSHASW ATNDTFDWDA YISDEGNFYF LEGSNDALLC
GNSSDAGHCP EGYECIKTGR NPNYGYTSYD TFSWAFLALF RLMTQDYWEN LFQLTLRAAG
KTYMIFFVVI IFLGSFYLIN LILAVVAMAY AEQNEATLAE DKEKEEEFQQ MLEKFKKHQE
ELEKAKAAQA LEGGEADGDP AHGKDCNGSL DTSQGEKGAP RQSSSGDSGI SDAMEELEEA
HQKCPPWWYK CAHKVLIWNC CAPWLKFKNI IHLIVMDPFV DLGITICIVL NTLFMAMEHY
PMTEHFDNVL TVGNLVFTGI FTAEMVLKLI AMDPYEYFQQ GWNIFDSIIV TLSLVELGLA
NVQGLSVLRS FRLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII VFIFAVVGMQ
LFGKSYKECV CKIALDCNLP RWHMHDFFHS FLIVFRILCG EWIETMWDCM EVAGQAMCLT
VFLMVMVIGN LVVLNLFLAL LLSSFSADSL AASDEDGEMN NLQIAIGRIK LGIGFAKAFL
LGLLHGKILS PKDIMLSLGE ADGAGEAGEA GETAPEDEKK EPPEEDLKKD NHILNHMGLA
DGPPSSLELD HLNFINNPYL TIQVPIASEE SDLEMPTEEE TDTFSEPEDS KKPPQPLYDG
NSSVCSTADY KPPEEDPEEQ AEENPEGEQP EECFTEACVQ RWPCLYVDIS QGRGKKWWTL
RRACFKIVEH NWFETFIVFM ILLSSGALAF EDIYIEQRRV IRTILEYADK VFTYIFIMEM
LLKWVAYGFK VYFTNAWCWL DFLIVDVSII SLVANWLGYS ELGPIKSLRT LRALRPLRAL
SRFEGMRVVV NALLGAIPSI MNVLLVCLIF WLIFSIMGVN LFAGKFYYCI NTTTSERFDI
SEVNNKSECE SLMHTGQVRW LNVKVNYDNV GLGYLSLLQV ATFKGWMDIM YAAVDSREKE
EQPQYEVNLY MYLYFVIFII FGSFFTLNLF IGVIIDNFNQ QKKKLGGKDI FMTEEQKKYY
NAMKKLGSKK PQKPIPRPQN KIQGMVYDLV TKQAFDITIM ILICLNMVTM MVETDNQSQL
KVDILYNINM IFIIIFTGEC VLKMLALRQY YFTVGWNIFD FVVVILSIVG LALSDLIQKY
FVSPTLFRVI RLARIGRVLR LIRGAKGIRT LLFALMMSLP ALFNIGLLLF LVMFIYSIFG
MSNFAYVKKE SGIDDMFNFE TFGNSIICLF EITTSAGWDG LLNPILNSGP PDCDPNLENP
GTSVKGDCGN PSIGICFFCS YIIISFLIVV NMYIAIILEN FNVATEESSE PLGEDDFEMF
YETWEKFDPD ATQFIAYSRL SDFVDTLQEP LRIAKPNKIK LITLDLPMVP GDKIHCLDIL
FALTKEVLGD SGEMDALKQT MEEKFMAANP SKVSYEPITT TLKRKHEEVC AIKIQRAYRR
HLLQRSMKQA SYMYRHSHDG SGDDAPEKEG LLANTMSKMY GHENGNSSSP SPEEKGEAGD
AGPTMGLMPI SPSDTAWPPA PPPGQTVRPG VKESLV
