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 05-OCT-2010, entry version 111. DE RecName: Full=Sodium channel protein type 4 subunit alpha; DE AltName: Full=SkM1; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS GLY-524; RP ASP-559 AND ASP-1376. RC TISSUE=Skeletal muscle; RX MEDLINE=92246457; 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- RT dependent sodium channel."; RL Ann. Neurol. 31:131-137(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=92134303; PubMed=1310396; DOI=10.1016/0006-291X(92)91802-W; RA Wang J., Rojas C.V., Zhou J., Schwartz L.S., Nicholas H., RA Hoffmann E.P.; RT "Sequence and genomic structure of the human adult skeletal muscle RT sodium channel alpha subunit gene on 17q."; RL Biochem. Biophys. Res. Commun. 182:794-801(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMS-SCNA4 GLU-1442, AND VARIANTS RP LEU-246; GLY-524 AND ASP-559. RX MEDLINE=22684480; 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 MEDLINE=93338444; PubMed=1339144; DOI=10.1093/hmg/1.7.521; RA McClatchey A.I., Lin C.S., Wang J., Hoffman E.P., Rojas C.V., RA Gusella J.F.; RT "The genomic structure of the human skeletal muscle sodium channel RT 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., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA 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 RT the human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1305-1339, AND VARIANTS PMC RP VAL-1306 AND MET-1313. RX MEDLINE=92154689; 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 RT of the skeletal muscle sodium channel gene in paramyotonia RT congenita."; RL Cell 68:769-774(1992). RN [7] RP VARIANT HYPP MET-704. RX MEDLINE=92069747; 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 RT periodic paralysis."; RL Cell 67:1021-1027(1991). RN [8] RP VARIANT HYPP VAL-1592. RX MEDLINE=92065978; 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- RT subunit in hyperkalaemic periodic paralysis."; RL Nature 354:387-389(1991). RN [9] RP VARIANTS PMC PHE-804 AND THR-1156. RX MEDLINE=93265141; 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 RT the skeletal muscle sodium channel."; RL Nat. Genet. 2:148-152(1992). RN [10] RP VARIANTS PMC CYS-1448 AND HIS-1448. RX MEDLINE=92265302; 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 RT channel cause paramyotonia congenita."; RL Neuron 8:891-897(1992). RN [11] RP VARIANT PMC/HYPP ARG-1433. RX MEDLINE=93270429; PubMed=8388676; DOI=10.1002/ana.410330312; RA Ptacek L.J., Gouw L., Kwiecinski H., McManis P., Mendell J.R., RA Barohn R.J., 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 [12] RP VARIANTS PMC ALA-1306; GLU-1306 AND VAL-1306. RX MEDLINE=94141728; PubMed=8308722; RA Lerche H., Heine R., Pika U., George A.L. Jr., Mitrovic N., RA Browatzki M., Weiss T., Rivet-Bastide M., Franke C., Lomonaco M., RA Ricker K., 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 [13] RP VARIANT PMC MET-1589. RX MEDLINE=94061027; 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 [14] RP VARIANT MYOSCN4A VAL-1160. RX PubMed=8058156; 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 RT congenita, paramyotonia congenita, and hyperkalemic periodic RT paralysis."; RL Neurology 44:1500-1503(1994). RN [15] RP VARIANT HYPP 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., RA Hoffman E.P., Ebeid M.R.; RT "Hyperkalemic periodic paralysis with cardiac dysrhythmia: a novel RT sodium channel mutation?"; RL Ann. Neurol. 37:408-411(1995). RN [16] RP VARIANT PMC ILE-1293. RX MEDLINE=96154961; PubMed=8580427; 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 [17] 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 [18] 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 RT channel alpha-subunit (SCN4A) that causes paramyotonia congenita of RT von Eulenburg."; RL Arch. Neurol. 56:692-696(1999). RN [19] 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 RT mutation associated with painful congenital myotonia."; RL FEBS Lett. 448:231-234(1999). RN [20] RP VARIANT HOKPP HIS-669. RX PubMed=10599760; 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 [21] 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 RT new family with paramyotonia congenita."; RL J. Neurol. Neurosurg. Psych. 68:504-507(2000). RN [22] RP VARIANT HOKPP SER-1158. RX PubMed=10851391; RA Sugiura Y., Aoki T., Sugiyama Y., Hida C., Ogata M., Yamamoto T.; RT "Temperature-sensitive sodium channelopathy with heat-induced myotonia RT and cold-induced paralysis."; RL Neurology 54:2179-2181(2000). RN [23] RP VARIANTS HOKPP 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., RA Herzog J., Lerche H., Nicole S., Vale-Santos J., Chauveau D., RA Fontaine B., 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 [24] RP VARIANT HOKPP 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 RT acetazolamide-exacerbated hypokalemic periodic paralysis."; RL Ann. Neurol. 50:417-420(2001). RN [25] RP VARIANT HOKPP SER-672. RX PubMed=11591859; 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 [26] RP VARIANTS NKPP GLY-675; GLN-675 AND TRP-675. RX PubMed=15596759; RA Vicart S., Sternberg D., Fournier E., Ochsner F., Laforet P., RA Kuntzer T., Eymard B., Hainque B., Fontaine B.; RT "New mutations of SCN4A cause a potassium-sensitive normokalemic RT periodic paralysis."; RL Neurology 63:2120-2127(2004). RN [27] 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., RA 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 [28] RP VARIANT PMC LYS-270, AND VARIANTS MYOSCN4A THR-715; ASN-804 AND RP 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 RT mutations causing myotonia."; RL Ann. Neurol. 60:356-365(2006). RN [29] 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 [30] RP VARIANTS HOKPP 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 [31] 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 RT heterozygous A1481D mutation in the SCN4A gene."; RL Muscle Nerve 35:599-606(2007). RN [32] 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 RT in French-Canadians."; RL Neurology 69:1937-1941(2007). RN [33] 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., RA Colombani M., Soichot P., Huet F., Hainque B., Sternberg D., RA Fontaine B., Gouyon J.B., Thauvin-Robinet C.; RT "Severe neonatal non-dystrophic myotonia secondary to a novel mutation RT of the voltage-gated sodium channel (SCN4A) gene."; RL Am. J. Med. Genet. A 146:380-383(2008). RN [34] RP VARIANTS NKPP GLN-675; ILE-781 AND VAL-1592. 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 RT with normokalemic periodic paralysis."; RL Cell. Mol. Neurobiol. 28:653-661(2008). RN [35] RP CHARACTERIZATION OF VARIANTS PMC SER-1473 AND ILE-1705. RX PubMed=18690054; RA Groome J.R., Larsen M.F., Coonts A.; RT "Differential effects of paramyotonia congenita mutations F1473S and RT F1705I on sodium channel gating."; RL Channels 2:39-50(2008). RN [36] 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 [37] RP VARIANT MYOSCN4A VAL-141, AND CHARACTERIZATION OF VARIANT MYOSCN4A RP 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., RA Schorderet D., Abriel H., Burgunder J.M.; RT "A novel dominant mutation of the Nav1.4 alpha-subunit domain I RT leading to sodium channel myotonia."; RL Neurology 71:1669-1675(2008). RN [38] 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 RT myotonia in French-Canadians."; RL Neuromuscul. Disord. 19:330-334(2009). RN [39] RP VARIANTS HOKPP TRP-222; CYS-672; GLY-672; HIS-672; SER-672; GLN-1132 RP AND 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., RA Chinnery P.F., Meola G., Schorge S., Kullmann D.M., Davis M.B., RA Hanna M.G.; RT "Voltage sensor charge loss accounts for most cases of hypokalemic RT periodic paralysis."; RL Neurology 72:1544-1547(2009). RN [40] 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). CC -!- FUNCTION: This protein mediates the voltage-dependent sodium ion CC permeability of excitable membranes. Assuming opened or closed CC conformations in response to the voltage difference across the CC membrane, the protein forms a sodium-selective channel through CC which Na(+) ions may pass in accordance with their electrochemical CC gradient. This sodium channel may be present in both denervated CC and innervated skeletal muscle. CC -!- SUBUNIT: Muscle sodium channels contain an alpha subunit and a CC smaller beta subunit. Interacts with the PDZ domain of the CC syntrophin SNTA1, SNTB1 and SNTB2 (By similarity). CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. 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 CC every third position. CC -!- DISEASE: Defects in SCN4A are the cause of paramyotonia congenita CC of von Eulenburg (PMC) [MIM:168300]. PMC is an autosomal dominant CC channelopathy characterized by myotonia, increased by exposure to CC cold, intermittent flaccid paresis, not necessarily dependent on CC cold or myotonia, lability of serum potassium, nonprogressive CC nature and lack of atrophy or hypertrophy of muscles. In some CC patients, myotonia is not increased by cold exposure (paramyotonia CC without cold paralysis). Patients may have a combination phenotype CC of PMC and HYPP. CC -!- DISEASE: Defects in SCN4A are a cause of periodic paralysis CC hypokalemic (HOKPP) [MIM:170400]; also designated HYPOPP. HOKPP is CC an autosomal dominant disorder manifested by episodic flaccid CC generalized muscle weakness associated with falls of serum CC potassium levels. CC -!- DISEASE: Defects in SCN4A are the cause of periodic paralysis CC hyperkalemic (HYPP) [MIM:170500]. HYPP is an autosomal dominant CC channelopathy characterized by episodic flaccid generalized muscle CC weakness associated with high levels of serum potassium. CC Concurrence of myotonia is found in HYPP patients. CC -!- DISEASE: Defects in SCN4A are the cause of periodic paralysis CC normokalemic (NKPP) [MIM:170500]. NKPP is a disorder closely CC related to hyperkalemic periodic paralysis, but marked by a lack CC of alterations in potassium levels during attacks of muscle CC weakness. CC -!- DISEASE: Defects in SCN4A are the cause of myotonia SCN4A-related CC (MYOSCN4A) [MIM:608390]. Myotonia is characterized by sustained CC muscle tensing that prevents muscles from relaxing normally. CC Myotonia causes muscle stiffness that can interfere with movement. CC In some people the stiffness is very mild, while in other cases it CC may be severe enough to interfere with walking, running, and other CC activities of daily life. MYOSCN4A is a phenotypically highly CC variable myotonia aggravated by potassium loading, and often by CC cold. MYOSCN4A includes myotonia permanens and myotonia fluctuans. CC In myotonia permanens, the myotonia is generalized and there is a CC hypertrophy of the muscle, particularly in the neck and the CC shoulder. Attacks of severe muscle stiffness of the thoracic CC muscles may be life threatening due to impaired ventilation. In CC myotonia fluctuans, the muscle stiffness may fluctuate from day to CC day, provoked by exercise. CC -!- DISEASE: Defects in SCN4A are the cause of a congenital myasthenic CC syndrome SCNA4-related (CMS-SCNA4) [MIM:603967]. CMS-SCNA4 is a CC congenital myasthenic syndrome associated with fatigable CC generalized weakness and recurrent attacks of respiratory and CC bulbar paralysis since birth. The fatigable weakness involves lid- CC elevator, external ocular, facial, limb and truncal muscles and an CC decremental response of the compound muscle action potential on CC repetitive stimulation. CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. CC Nav1.4/SCN4A subfamily. CC -!- SIMILARITY: Contains 1 IQ domain. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN4A"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=SCN4A entry; CC URL="http://en.wikipedia.org/wiki/SCN4A"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- 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 IPI; IPI00292393; -. DR PIR; I51964; I51964. DR PIR; I54323; I54323. DR PIR; I64893; I64893. DR PIR; JS0648; JS0648. DR RefSeq; NP_000325.4; -. DR UniGene; Hs.46038; -. DR ProteinModelPortal; P35499; -. DR STRING; P35499; -. DR TCDB; 1.A.1.10.4; voltage-gated ion channel (VIC) superfamily. DR PRIDE; P35499; -. DR Ensembl; ENST00000006839; ENSP00000006839; ENSG00000007314. DR Ensembl; ENST00000435607; ENSP00000396320; ENSG00000007314. DR GeneID; 6329; -. DR KEGG; hsa:6329; -. DR UCSC; uc002jds.1; human. DR CTD; 6329; -. DR GeneCards; GC17M062015; -. DR H-InvDB; HIX0039131; -. DR HGNC; HGNC:10591; SCN4A. DR MIM; 168300; phenotype. DR MIM; 170400; phenotype. DR MIM; 170500; phenotype. DR MIM; 603967; gene+phenotype. DR MIM; 608390; phenotype. DR Orphanet; 590; Congenital myasthenic syndromes. DR Orphanet; 682; Hyperkalemic periodic paralysis. DR Orphanet; 681; Hypokalemic periodic paralysis. DR Orphanet; 99736; Myotonia congenita acetazolamide responsive. 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 Orphanet; 612; Potassium aggravated myotonia. DR PharmGKB; PA35006; -. DR HOGENOM; HBG358468; -. DR HOVERGEN; HBG053100; -. DR InParanoid; P35499; -. DR OMA; GPECLRP; -. DR PhylomeDB; P35499; -. DR Reactome; REACT_18266; Axon guidance. DR DrugBank; DB00555; Lamotrigine. DR NextBio; 24570; -. DR ArrayExpress; P35499; -. DR Bgee; P35499; -. DR CleanEx; HS_SCN4A; -. DR Genevestigator; P35499; -. DR GermOnline; ENSG00000007314; Homo sapiens. DR GO; GO:0001518; C:voltage-gated sodium channel complex; IEA:InterPro. DR GO; GO:0005248; F:voltage-gated sodium channel activity; TAS:ProtInc. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR InterPro; IPR005821; Ion_trans. DR InterPro; IPR000048; IQ_motif_EF-hand-BS. DR InterPro; IPR008052; Na_channel_a4su. DR InterPro; IPR001696; Na_channel_asu. DR InterPro; IPR010526; Na_trans_assoc. DR Pfam; PF00520; Ion_trans; 4. DR Pfam; PF06512; Na_trans_assoc; 1. DR PRINTS; PR00170; NACHANNEL. DR PRINTS; PR01665; NACHANNEL4. DR SMART; SM00015; IQ; 1. DR PROSITE; PS50096; IQ; 1. PE 1: Evidence at protein level; KW Complete proteome; Congenital myasthenic syndrome; Disease mutation; KW Glycoprotein; Ion transport; Ionic channel; Membrane; Phosphoprotein; KW Polymorphism; Repeat; Sodium; Sodium channel; Sodium transport; KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1 1836 Sodium channel protein type 4 subunit FT alpha. FT /FTId=PRO_0000048495. FT TRANSMEM 129 150 Helical; Name=S1 of repeat I; FT (Potential). FT TRANSMEM 159 178 Helical; Name=S2 of repeat I; FT (Potential). FT TRANSMEM 191 210 Helical; Name=S3 of repeat I; FT (Potential). FT TRANSMEM 217 236 Helical; Voltage-sensor; Name=S4 of FT repeat I; (Potential). FT TRANSMEM 253 266 Helical; Name=S5 of repeat I; FT (Potential). FT TRANSMEM 424 449 Helical; Name=S6 of repeat I; FT (Potential). FT TRANSMEM 574 597 Helical; Name=S1 of repeat II; FT (Potential). FT TRANSMEM 609 632 Helical; Name=S2 of repeat II; FT (Potential). FT TRANSMEM 641 660 Helical; Name=S3 of repeat II; FT (Potential). FT TRANSMEM 667 686 Helical; Voltage-sensor; Name=S4 of FT repeat II; (Potential). FT TRANSMEM 702 724 Helical; Name=S5 of repeat II; FT (Potential). FT TRANSMEM 777 802 Helical; Name=S6 of repeat II; FT (Potential). FT TRANSMEM 1027 1049 Helical; Name=S1 of repeat III; FT (Potential). FT TRANSMEM 1064 1089 Helical; Name=S2 of repeat III; FT (Potential). FT TRANSMEM 1096 1116 Helical; Name=S3 of repeat III; FT (Potential). FT TRANSMEM 1122 1143 Helical; Voltage-sensor; Name=S4 of FT repeat III; (Potential). FT TRANSMEM 1163 1184 Helical; Name=S5 of repeat III; FT (Potential). FT TRANSMEM 1269 1295 Helical; Name=S6 of repeat III; FT (Potential). FT TRANSMEM 1349 1372 Helical; Name=S1 of repeat IV; FT (Potential). FT TRANSMEM 1384 1407 Helical; Name=S2 of repeat IV; FT (Potential). FT TRANSMEM 1414 1437 Helical; Name=S3 of repeat IV; FT (Potential). FT TRANSMEM 1447 1469 Helical; Voltage-sensor; Name=S4 of FT repeat IV; (Potential). FT TRANSMEM 1485 1507 Helical; Name=S5 of repeat IV; FT (Potential). FT TRANSMEM 1574 1598 Helical; Name=S6 of repeat IV; FT (Potential). FT REPEAT 128 450 I. FT REPEAT 571 796 II. FT REPEAT 1024 1281 III. FT REPEAT 1349 1595 IV. FT DOMAIN 1727 1756 IQ. FT CARBOHYD 214 214 N-linked (GlcNAc...) (Potential). FT CARBOHYD 288 288 N-linked (GlcNAc...) (Potential). FT CARBOHYD 291 291 N-linked (GlcNAc...) (Potential). FT CARBOHYD 297 297 N-linked (GlcNAc...) (Potential). FT CARBOHYD 303 303 N-linked (GlcNAc...) (Potential). FT CARBOHYD 315 315 N-linked (GlcNAc...) (Potential). FT CARBOHYD 321 321 N-linked (GlcNAc...) (Potential). FT CARBOHYD 333 333 N-linked (GlcNAc...) (Potential). FT CARBOHYD 362 362 N-linked (GlcNAc...) (Potential). FT CARBOHYD 507 507 N-linked (GlcNAc...) (Potential). FT CARBOHYD 961 961 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1191 1191 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1205 1205 N-linked (GlcNAc...) (Potential). FT VARIANT 135 135 M -> V. FT /FTId=VAR_001560. FT VARIANT 141 141 I -> V (in MYOSCN4A; causes a FT hyperpolarizing shift of the activation FT curve; enhances channel slow FT inactivation). FT /FTId=VAR_054934. FT VARIANT 222 222 R -> W (in HOKPP). FT /FTId=VAR_054935. FT VARIANT 246 246 S -> L. FT /FTId=VAR_017785. FT VARIANT 270 270 Q -> K (in PMC). FT /FTId=VAR_054936. FT VARIANT 445 445 V -> M (in MYOSCN4A). FT /FTId=VAR_017786. FT VARIANT 452 452 E -> K (in MYOSCN4A; variable phenotype FT ranging from mild to severe myotonia). FT /FTId=VAR_054937. FT VARIANT 524 524 S -> G (in dbSNP:rs6504191). FT /FTId=VAR_001561. FT VARIANT 559 559 N -> D (in dbSNP:rs1047705). FT /FTId=VAR_017787. FT VARIANT 669 669 R -> H (in HOKPP). FT /FTId=VAR_017788. FT VARIANT 671 671 F -> S (in MYOSCN4A). FT /FTId=VAR_054938. FT VARIANT 672 672 R -> C (in HOKPP). FT /FTId=VAR_054939. FT VARIANT 672 672 R -> G (in HOKPP). FT /FTId=VAR_017789. FT VARIANT 672 672 R -> H (in HOKPP). FT /FTId=VAR_017790. FT VARIANT 672 672 R -> S (in HOKPP). FT /FTId=VAR_017791. FT VARIANT 675 675 R -> G (in NKPP). FT /FTId=VAR_037104. FT VARIANT 675 675 R -> Q (in NKPP). FT /FTId=VAR_037105. FT VARIANT 675 675 R -> W (in NKPP). FT /FTId=VAR_037106. FT VARIANT 704 704 T -> M (in HYPP and PMC). FT /FTId=VAR_001562. FT VARIANT 715 715 A -> T (in MYOSCN4A). FT /FTId=VAR_054940. FT VARIANT 781 781 V -> I (in HYPP and NKPP). FT /FTId=VAR_054941. FT VARIANT 804 804 S -> F (in PMC). FT /FTId=VAR_001563. FT VARIANT 804 804 S -> N (in MYOSCN4A). FT /FTId=VAR_054942. FT VARIANT 861 861 A -> D. FT /FTId=VAR_001564. FT VARIANT 1132 1132 R -> Q (in HOKPP). FT /FTId=VAR_054943. FT VARIANT 1135 1135 R -> H (in HOKPP). FT /FTId=VAR_054944. FT VARIANT 1152 1152 A -> D (in PMC). FT /FTId=VAR_022341. FT VARIANT 1156 1156 A -> T (in PMC and HYPP). FT /FTId=VAR_001565. FT VARIANT 1158 1158 P -> S (in HOKPP). FT /FTId=VAR_017792. FT VARIANT 1160 1160 I -> V (in MYOSCN4A; acetazolamide- FT responsive myotonia). FT /FTId=VAR_017793. FT VARIANT 1293 1293 V -> I (in PMC; without cold paralysis). FT /FTId=VAR_001566. FT VARIANT 1297 1297 N -> K (in MYOSCN4A; unusually severe and FT lethal phenotype with neonatal onset). FT /FTId=VAR_054945. FT VARIANT 1306 1306 G -> A (in PMC). FT /FTId=VAR_001567. FT VARIANT 1306 1306 G -> E (in MYOSCN4A and PMC; severe). FT /FTId=VAR_001568. FT VARIANT 1306 1306 G -> V (in MYOSCN4A and PMC). FT /FTId=VAR_001569. FT VARIANT 1310 1310 I -> N (in MYOSCN4A). FT /FTId=VAR_054946. FT VARIANT 1313 1313 T -> M (in PMC). FT /FTId=VAR_001570. FT VARIANT 1376 1376 N -> D (in dbSNP:rs2058194). FT /FTId=VAR_017794. FT VARIANT 1433 1433 L -> R (in PMC and HYPP). FT /FTId=VAR_001571. FT VARIANT 1436 1436 L -> P (in PMC). FT /FTId=VAR_054947. FT VARIANT 1442 1442 V -> E (in CMS-SCNA4). FT /FTId=VAR_017795. FT VARIANT 1448 1448 R -> C (in PMC). FT /FTId=VAR_001572. FT VARIANT 1448 1448 R -> H (in PMC). FT /FTId=VAR_001573. FT VARIANT 1448 1448 R -> L (in PMC). FT /FTId=VAR_054948. FT VARIANT 1456 1456 G -> E (in PMC). FT /FTId=VAR_037107. FT VARIANT 1473 1473 F -> S (in PMC; accelerates deactivation FT from the inactivated state and enhances FT the remobilization of gating charge). FT /FTId=VAR_054949. FT VARIANT 1476 1476 M -> I (in MYOSCN4A; highly variable FT severity). FT /FTId=VAR_054950. FT VARIANT 1481 1481 A -> D (in MYOSCN4A; fluctuating cold- FT induced and exercise-induced stiffness). FT /FTId=VAR_054951. FT VARIANT 1589 1589 V -> M (in PMC). FT /FTId=VAR_001574. FT VARIANT 1592 1592 M -> V (in HYPP and NKPP). FT /FTId=VAR_001575. FT VARIANT 1705 1705 F -> I (in PMC; increases the extent of FT charge immobilization in response to FT strong depolarization). FT /FTId=VAR_054952. FT CONFLICT 10 11 VP -> AR (in Ref. 1; AAA60554). FT CONFLICT 371 371 E -> K (in Ref. 1; AAA60554). FT CONFLICT 371 371 E -> Q (in Ref. 1; AAB59624). FT CONFLICT 870 870 A -> G (in Ref. 1; AAB59624). FT CONFLICT 1151 1152 NA -> KP (in Ref. 1; AAB59624). 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 //