Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P35499 (SCN4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium channel protein type 4 subunit alpha
Alternative name(s):
SkM1
Sodium channel protein skeletal muscle subunit alpha
Sodium channel protein type IV subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.4
Gene names
Name:SCN4A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1836 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.

Subunit structure

Muscle sodium channels contain an alpha subunit and a smaller beta subunit. Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Domain

The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Post-translational modification

Phosphorylation at Ser-1328 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents By similarity.

Involvement in disease

Paramyotonia congenita of von Eulenburg (PMC) [MIM:168300]: An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.18 Ref.21 Ref.27 Ref.28 Ref.35 Ref.36 Ref.38 Ref.41

Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.30 Ref.40 Ref.42 Ref.43

Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.15 Ref.38

Periodic paralysis normokalemic (NKPP) [MIM:170500]: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Ref.34 Ref.42

Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A phenotypically highly variable myotonia aggravated by potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. Myotonia SCN4A-related includes myotonia permanens and myotonia fluctuans. In myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by exercise.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.17 Ref.19 Ref.28 Ref.29 Ref.31 Ref.32 Ref.33 Ref.37 Ref.38 Ref.39

Myasthenic syndrome, congenital, acetazolamide-responsive (CMSAR) [MIM:614198]: A congenital myasthenic syndrome associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.4/SCN4A subfamily. [View classification]

Contains 1 IQ domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 18361836Sodium channel protein type 4 subunit alpha
PRO_0000048495

Regions

Topological domain1 – 128128Cytoplasmic Potential
Transmembrane129 – 15022Helical; Name=S1 of repeat I; Potential
Topological domain151 – 1588Extracellular Potential
Transmembrane159 – 17820Helical; Name=S2 of repeat I; Potential
Topological domain179 – 19012Cytoplasmic Potential
Transmembrane191 – 21020Helical; Name=S3 of repeat I; Potential
Topological domain211 – 2166Extracellular Potential
Transmembrane217 – 23620Helical; Voltage-sensor; Name=S4 of repeat I; Potential
Topological domain237 – 25216Cytoplasmic Potential
Transmembrane253 – 26614Helical; Name=S5 of repeat I; Potential
Topological domain267 – 423157Extracellular Potential
Transmembrane424 – 44926Helical; Name=S6 of repeat I; Potential
Topological domain450 – 573124Cytoplasmic Potential
Transmembrane574 – 59724Helical; Name=S1 of repeat II; Potential
Topological domain598 – 60811Extracellular Potential
Transmembrane609 – 63224Helical; Name=S2 of repeat II; Potential
Topological domain633 – 6408Cytoplasmic Potential
Transmembrane641 – 66020Helical; Name=S3 of repeat II; Potential
Topological domain661 – 6666Extracellular Potential
Transmembrane667 – 68620Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Topological domain687 – 70115Cytoplasmic Potential
Transmembrane702 – 72423Helical; Name=S5 of repeat II; Potential
Topological domain725 – 77652Extracellular Potential
Transmembrane777 – 80226Helical; Name=S6 of repeat II; Potential
Topological domain803 – 1026224Cytoplasmic Potential
Transmembrane1027 – 104923Helical; Name=S1 of repeat III; Potential
Topological domain1050 – 106314Extracellular Potential
Transmembrane1064 – 108926Helical; Name=S2 of repeat III; Potential
Topological domain1090 – 10956Cytoplasmic Potential
Transmembrane1096 – 111621Helical; Name=S3 of repeat III; Potential
Topological domain1117 – 11215Extracellular Potential
Transmembrane1122 – 114322Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Topological domain1144 – 116219Cytoplasmic Potential
Transmembrane1163 – 118422Helical; Name=S5 of repeat III; Potential
Topological domain1185 – 126884Extracellular Potential
Transmembrane1269 – 129527Helical; Name=S6 of repeat III; Potential
Topological domain1296 – 134853Cytoplasmic Potential
Transmembrane1349 – 137224Helical; Name=S1 of repeat IV; Potential
Topological domain1373 – 138311Extracellular Potential
Transmembrane1384 – 140724Helical; Name=S2 of repeat IV; Potential
Topological domain1408 – 14136Cytoplasmic Potential
Transmembrane1414 – 143724Helical; Name=S3 of repeat IV; Potential
Topological domain1438 – 14469Extracellular Potential
Transmembrane1447 – 146923Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Topological domain1470 – 148415Cytoplasmic Potential
Transmembrane1485 – 150723Helical; Name=S5 of repeat IV; Potential
Topological domain1508 – 157366Extracellular Potential
Transmembrane1574 – 159825Helical; Name=S6 of repeat IV; Potential
Topological domain1599 – 1836238Cytoplasmic Potential
Repeat128 – 450323I
Repeat571 – 796226II
Repeat1024 – 1281258III
Repeat1349 – 1595247IV
Domain1727 – 175630IQ

Amino acid modifications

Modified residue13281Phosphoserine; by PKC By similarity
Glycosylation2141N-linked (GlcNAc...) Potential
Glycosylation2881N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation2971N-linked (GlcNAc...) Potential
Glycosylation3031N-linked (GlcNAc...) Potential
Glycosylation3151N-linked (GlcNAc...) Potential
Glycosylation3211N-linked (GlcNAc...) Potential
Glycosylation3331N-linked (GlcNAc...) Potential
Glycosylation3621N-linked (GlcNAc...) Potential
Glycosylation11911N-linked (GlcNAc...) Potential
Glycosylation12051N-linked (GlcNAc...) Potential

Natural variations

Natural variant1351M → V.
VAR_001560
Natural variant1411I → V in MYOSCN4A; causes a hyperpolarizing shift of the activation curve; enhances channel slow inactivation. Ref.37
VAR_054934
Natural variant2221R → W in HOKPP2. Ref.40
VAR_054935
Natural variant2251R → W in MYOSCN4A. Ref.38
VAR_065230
Natural variant2461S → L. Ref.3
VAR_017785
Natural variant2701Q → K in PMC. Ref.28 Ref.36
VAR_054936
Natural variant4451V → M in MYOSCN4A. Ref.17 Ref.19 Ref.39
VAR_017786
Natural variant4521E → K in MYOSCN4A; variable phenotype ranging from mild to severe myotonia. Ref.39
VAR_054937
Natural variant5241S → G. Ref.1 Ref.3 Ref.4
Corresponds to variant rs6504191 [ dbSNP | Ensembl ].
VAR_001561
Natural variant5591N → D. Ref.1 Ref.3
Corresponds to variant rs1047705 [ dbSNP | Ensembl ].
VAR_017787
Natural variant6691R → H in HOKPP2. Ref.20 Ref.30
VAR_017788
Natural variant6711F → S in MYOSCN4A. Ref.39
VAR_054938
Natural variant6721R → C in HOKPP2. Ref.30 Ref.40
VAR_054939
Natural variant6721R → G in HOKPP2. Ref.23 Ref.30 Ref.40
VAR_017789
Natural variant6721R → H in HOKPP2. Ref.23 Ref.40 Ref.43
VAR_017790
Natural variant6721R → S in HOKPP2. Ref.24 Ref.25 Ref.40
VAR_017791
Natural variant6751R → G in NKPP. Ref.26
VAR_037104
Natural variant6751R → Q in NKPP. Ref.26 Ref.34
VAR_037105
Natural variant6751R → W in NKPP. Ref.26
VAR_037106
Natural variant6931I → T in PMC. Ref.38
VAR_065231
Natural variant7041T → M in HYPP and PMC. Ref.7 Ref.36 Ref.41
VAR_001562
Natural variant7151A → T in MYOSCN4A. Ref.28
VAR_054940
Natural variant7811V → I in HYPP and NKPP. Ref.15 Ref.34
Corresponds to variant rs62070884 [ dbSNP | Ensembl ].
VAR_054941
Natural variant8041S → F in PMC. Ref.9
VAR_001563
Natural variant8041S → N in MYOSCN4A. Ref.28
VAR_054942
Natural variant8611A → D.
VAR_001564
Natural variant11291R → Q in NKPP and HOKPP2; detected in a family where three affected members manifested hypokalemic periodic paralysis whereas five other patients had normokalemic periodic paralysis. Ref.42
VAR_064987
Natural variant11321R → Q in HOKPP2. Ref.40
VAR_054943
Natural variant11351R → H in HOKPP2. Ref.40
VAR_054944
Natural variant11521A → D in PMC. Ref.27
VAR_022341
Natural variant11561A → T in PMC, MYOSCN4A and HYPP. Ref.9 Ref.38
VAR_001565
Natural variant11581P → S in HOKPP2. Ref.22
VAR_017792
Natural variant11601I → V in MYOSCN4A; acetazolamide-responsive myotonia. Ref.14
VAR_017793
Natural variant12931V → I in PMC; without cold paralysis. Ref.16
VAR_001566
Natural variant12971N → K in MYOSCN4A; unusually severe and lethal phenotype with neonatal onset. Ref.33
VAR_054945
Natural variant13061G → A in PMC. Ref.12 Ref.36
VAR_001567
Natural variant13061G → E in MYOSCN4A and PMC; severe. Ref.12 Ref.29 Ref.36 Ref.38
VAR_001568
Natural variant13061G → V in MYOSCN4A and PMC. Ref.6 Ref.12 Ref.39
VAR_001569
Natural variant13101I → N in MYOSCN4A. Ref.28
VAR_054946
Natural variant13131T → M in PMC. Ref.6 Ref.36
VAR_001570
Natural variant13761N → D. Ref.1
Corresponds to variant rs2058194 [ dbSNP | Ensembl ].
VAR_017794
Natural variant14331L → R in PMC and HYPP. Ref.11
VAR_001571
Natural variant14361L → P in PMC. Ref.36
VAR_054947
Natural variant14421V → E in CMSAR. Ref.3
VAR_017795
Natural variant14481R → C in PMC. Ref.10 Ref.36
VAR_001572
Natural variant14481R → H in PMC. Ref.10 Ref.36
VAR_001573
Natural variant14481R → L in PMC. Ref.36
VAR_054948
Natural variant14561G → E in PMC. Ref.18 Ref.21 Ref.36
VAR_037107
Natural variant14731F → S in PMC; accelerates deactivation from the inactivated state and enhances the remobilization of gating charge. Ref.35 Ref.36
VAR_054949
Natural variant14761M → I in MYOSCN4A; highly variable severity. Ref.32 Ref.39
VAR_054950
Natural variant14811A → D in MYOSCN4A; fluctuating cold-induced and exercise-induced stiffness. Ref.31
VAR_054951
Natural variant15891V → M in PMC. Ref.13 Ref.36
VAR_001574
Natural variant15921M → V in HYPP and NKPP. Ref.8 Ref.34
VAR_001575
Natural variant17051F → I in PMC; increases the extent of charge immobilization in response to strong depolarization. Ref.35
VAR_054952

Experimental info

Sequence conflict10 – 112VP → AR in AAA60554. Ref.1
Sequence conflict3711E → K in AAA60554. Ref.1
Sequence conflict3711E → Q in AAB59624. Ref.1
Sequence conflict8701A → G in AAB59624. Ref.1
Sequence conflict1151 – 11522NA → KP in AAB59624. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P35499 [UniParc].

Last modified March 23, 2010. Version 4.
Checksum: FA9A6B81B7C2D50F

FASTA1,836208,061
        10         20         30         40         50         60 
MARPSLCTLV PLGPECLRPF TRESLAAIEQ RAVEEEARLQ RNKQMEIEEP ERKPRSDLEA 

        70         80         90        100        110        120 
GKNLPMIYGD PPPEVIGIPL EDLDPYYSNK KTFIVLNKGK AIFRFSATPA LYLLSPFSVV 

       130        140        150        160        170        180 
RRGAIKVLIH ALFSMFIMIT ILTNCVFMTM SDPPPWSKNV EYTFTGIYTF ESLIKILARG 

       190        200        210        220        230        240 
FCVDDFTFLR DPWNWLDFSV IMMAYLTEFV DLGNISALRT FRVLRALKTI TVIPGLKTIV 

       250        260        270        280        290        300 
GALIQSVKKL SDVMILTVFC LSVFALVGLQ LFMGNLRQKC VRWPPPFNDT NTTWYSNDTW 

       310        320        330        340        350        360 
YGNDTWYGNE MWYGNDSWYA NDTWNSHASW ATNDTFDWDA YISDEGNFYF LEGSNDALLC 

       370        380        390        400        410        420 
GNSSDAGHCP EGYECIKTGR NPNYGYTSYD TFSWAFLALF RLMTQDYWEN LFQLTLRAAG 

       430        440        450        460        470        480 
KTYMIFFVVI IFLGSFYLIN LILAVVAMAY AEQNEATLAE DKEKEEEFQQ MLEKFKKHQE 

       490        500        510        520        530        540 
ELEKAKAAQA LEGGEADGDP AHGKDCNGSL DTSQGEKGAP RQSSSGDSGI SDAMEELEEA 

       550        560        570        580        590        600 
HQKCPPWWYK CAHKVLIWNC CAPWLKFKNI IHLIVMDPFV DLGITICIVL NTLFMAMEHY 

       610        620        630        640        650        660 
PMTEHFDNVL TVGNLVFTGI FTAEMVLKLI AMDPYEYFQQ GWNIFDSIIV TLSLVELGLA 

       670        680        690        700        710        720 
NVQGLSVLRS FRLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII VFIFAVVGMQ 

       730        740        750        760        770        780 
LFGKSYKECV CKIALDCNLP RWHMHDFFHS FLIVFRILCG EWIETMWDCM EVAGQAMCLT 

       790        800        810        820        830        840 
VFLMVMVIGN LVVLNLFLAL LLSSFSADSL AASDEDGEMN NLQIAIGRIK LGIGFAKAFL 

       850        860        870        880        890        900 
LGLLHGKILS PKDIMLSLGE ADGAGEAGEA GETAPEDEKK EPPEEDLKKD NHILNHMGLA 

       910        920        930        940        950        960 
DGPPSSLELD HLNFINNPYL TIQVPIASEE SDLEMPTEEE TDTFSEPEDS KKPPQPLYDG 

       970        980        990       1000       1010       1020 
NSSVCSTADY KPPEEDPEEQ AEENPEGEQP EECFTEACVQ RWPCLYVDIS QGRGKKWWTL 

      1030       1040       1050       1060       1070       1080 
RRACFKIVEH NWFETFIVFM ILLSSGALAF EDIYIEQRRV IRTILEYADK VFTYIFIMEM 

      1090       1100       1110       1120       1130       1140 
LLKWVAYGFK VYFTNAWCWL DFLIVDVSII SLVANWLGYS ELGPIKSLRT LRALRPLRAL 

      1150       1160       1170       1180       1190       1200 
SRFEGMRVVV NALLGAIPSI MNVLLVCLIF WLIFSIMGVN LFAGKFYYCI NTTTSERFDI 

      1210       1220       1230       1240       1250       1260 
SEVNNKSECE SLMHTGQVRW LNVKVNYDNV GLGYLSLLQV ATFKGWMDIM YAAVDSREKE 

      1270       1280       1290       1300       1310       1320 
EQPQYEVNLY MYLYFVIFII FGSFFTLNLF IGVIIDNFNQ QKKKLGGKDI FMTEEQKKYY 

      1330       1340       1350       1360       1370       1380 
NAMKKLGSKK PQKPIPRPQN KIQGMVYDLV TKQAFDITIM ILICLNMVTM MVETDNQSQL 

      1390       1400       1410       1420       1430       1440 
KVDILYNINM IFIIIFTGEC VLKMLALRQY YFTVGWNIFD FVVVILSIVG LALSDLIQKY 

      1450       1460       1470       1480       1490       1500 
FVSPTLFRVI RLARIGRVLR LIRGAKGIRT LLFALMMSLP ALFNIGLLLF LVMFIYSIFG 

      1510       1520       1530       1540       1550       1560 
MSNFAYVKKE SGIDDMFNFE TFGNSIICLF EITTSAGWDG LLNPILNSGP PDCDPNLENP 

      1570       1580       1590       1600       1610       1620 
GTSVKGDCGN PSIGICFFCS YIIISFLIVV NMYIAIILEN FNVATEESSE PLGEDDFEMF 

      1630       1640       1650       1660       1670       1680 
YETWEKFDPD ATQFIAYSRL SDFVDTLQEP LRIAKPNKIK LITLDLPMVP GDKIHCLDIL 

      1690       1700       1710       1720       1730       1740 
FALTKEVLGD SGEMDALKQT MEEKFMAANP SKVSYEPITT TLKRKHEEVC AIKIQRAYRR 

      1750       1760       1770       1780       1790       1800 
HLLQRSMKQA SYMYRHSHDG SGDDAPEKEG LLANTMSKMY GHENGNSSSP SPEEKGEAGD 

      1810       1820       1830 
AGPTMGLMPI SPSDTAWPPA PPPGQTVRPG VKESLV 

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of the adult human skeletal muscle voltage-dependent sodium channel."
George A.L. Jr., Komisarof J., Kallen R.G., Barchi R.L.
Ann. Neurol. 31:131-137(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS GLY-524; ASP-559 AND ASP-1376.
Tissue: Skeletal muscle.
[2]"Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q."
Wang J., Rojas C.V., Zhou J., Schwartz L.S., Nicholas H., Hoffmann E.P.
Biochem. Biophys. Res. Commun. 182:794-801(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Myasthenic syndrome caused by mutation of the SCN4A sodium channel."
Tsujino A., Maertens C., Ohno K., Shen X.-M., Fukuda T., Harper C.M., Cannon S.C., Engel A.G.
Proc. Natl. Acad. Sci. U.S.A. 100:7377-7382(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMSAR GLU-1442, VARIANTS LEU-246; GLY-524 AND ASP-559.
[4]"The genomic structure of the human skeletal muscle sodium channel gene."
McClatchey A.I., Lin C.S., Wang J., Hoffman E.P., Rojas C.V., Gusella J.F.
Hum. Mol. Genet. 1:521-527(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-524.
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita."
McClatchey A.I., van den Bergh P., Pericak-Vance M.A., Raskind W., Verellen C., McKenna-Yasek D., Rao K., Haines J.L., Bird T., Brown R.H. Jr., Gusella J.F.
Cell 68:769-774(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1305-1339, VARIANTS PMC VAL-1306 AND MET-1313.
[7]"Identification of a mutation in the gene causing hyperkalemic periodic paralysis."
Ptacek L.J., George A.L. Jr., Griggs R.C., Tawil R., Kallen R.G., Barchi R.L., Robertson M., Leppert M.F.
Cell 67:1021-1027(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPP MET-704.
[8]"A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis."
Rojas C.V., Wang J., Schwartz L.S., Hoffman E.P., Powell B.R., Brown R.H. Jr.
Nature 354:387-389(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPP VAL-1592.
[9]"Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel."
McClatchey A.I., McKenna-Yasek D., Cros D., Worthen H.G., Kuncl R.W., Desilva S.M., Cornblath D.R., Gusella J.F., Brown R.H. Jr.
Nat. Genet. 2:148-152(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PMC PHE-804 AND THR-1156.
[10]"Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita."
Ptacek L.J., George A.L. Jr., Barchi R.L., Griggs R.C., Riggs J.E., Robertson M., Leppert M.F.
Neuron 8:891-897(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PMC CYS-1448 AND HIS-1448.
[11]"Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis."
Ptacek L.J., Gouw L., Kwiecinski H., McManis P., Mendell J.R., Barohn R.J., George A.L. Jr., Barchi R.L., Robertson M., Leppert M.F.
Ann. Neurol. 33:300-307(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC/HYPP ARG-1433.
[12]"Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker."
Lerche H., Heine R., Pika U., George A.L. Jr., Mitrovic N., Browatzki M., Weiss T., Rivet-Bastide M., Franke C., Lomonaco M., Ricker K., Lehmann-Horn F.
J. Physiol. (Lond.) 470:13-22(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PMC ALA-1306; GLU-1306 AND VAL-1306.
[13]"A novel SCN4A mutation causing myotonia aggravated by cold and potassium."
Heine R., Pika U., Lehmann-Horn F.
Hum. Mol. Genet. 2:1349-1353(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC MET-1589.
[14]"Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis."
Ptacek L.J., Tawil R., Griggs R.C., Meola G., McManis P., Barohn R.J., Mendell J.R., Harris C., Spitzer R., Santiago F., Leppert M.F.
Neurology 44:1500-1503(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A VAL-1160.
[15]"Hyperkalemic periodic paralysis with cardiac dysrhythmia: a novel sodium channel mutation?"
Baquero J.L., Ayala R.A., Wang J., Curless R.G., Feero W.G., Hoffman E.P., Ebeid M.R.
Ann. Neurol. 37:408-411(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPP ILE-781.
[16]"Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in the SCN4A gene (Val1293Ile)."
Koch M.C., Baumbach K., George A.L. Jr., Ricker K.
NeuroReport 6:2001-2004(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC ILE-1293.
[17]"A novel muscle sodium channel mutation causes painful congenital myotonia."
Rosenfeld J., Sloan-Brown K., George A.L. Jr.
Ann. Neurol. 42:811-814(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A MET-445.
[18]"A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg."
Sasaki R., Takano H., Kamakura K., Kaida K., Hirata A., Saito M., Tanaka H., Kuzuhara S., Tsuji S.
Arch. Neurol. 56:692-696(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC GLU-1456.
[19]"Functional consequences of a domain 1/S6 segment sodium channel mutation associated with painful congenital myotonia."
Wang D.W., VanDeCarr D., Ruben P.C., George A.L. Jr., Bennett P.B.
FEBS Lett. 448:231-234(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A MET-445.
[20]"A novel sodium channel mutation in a family with hypokalemic periodic paralysis."
Bulman D.E., Scoggan K.A., van Oene M.D., Nicolle M.W., Hahn A.F., Tollar L.L., Ebers G.C.
Neurology 53:1932-1936(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HOKPP2 HIS-669.
[21]"Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita."
Davies N.P., Eunson L.H., Gregory R.P., Mills K.R., Morrison P.J., Hanna M.G.
J. Neurol. Neurosurg. Psych. 68:504-507(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC GLU-1456.
[22]"Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis."
Sugiura Y., Aoki T., Sugiyama Y., Hida C., Ogata M., Yamamoto T.
Neurology 54:2179-2181(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HOKPP2 SER-1158.
[23]"Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current."
Jurkat-Rott K., Mitrovic N., Hang C., Kouzmekine A., Iaizzo P., Herzog J., Lerche H., Nicole S., Vale-Santos J., Chauveau D., Fontaine B., Lehmann-Horn F.
Proc. Natl. Acad. Sci. U.S.A. 97:9549-9554(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HOKPP2 GLY-672 AND HIS-672.
[24]"Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis."
Bendahhou S., Cummins T.R., Griggs R.C., Fu Y.H., Ptacek L.J.
Ann. Neurol. 50:417-420(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HOKPP2 SER-672.
[25]"Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK."
Davies N.P., Eunson L.H., Samuel M., Hanna M.G.
Neurology 57:1323-1325(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HOKPP2 SER-672.
[26]"New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis."
Vicart S., Sternberg D., Fournier E., Ochsner F., Laforet P., Kuntzer T., Eymard B., Hainque B., Fontaine B.
Neurology 63:2120-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NKPP GLY-675; GLN-675 AND TRP-675.
[27]"A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4-S5 linker in fast inactivation."
Bouhours M., Luce S., Sternberg D., Willer J.-C., Fontaine B., Tabti N.
J. Physiol. (Lond.) 565:415-427(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC ASP-1152.
[28]"Cold extends electromyography distinction between ion channel mutations causing myotonia."
Fournier E., Viala K., Gervais H., Sternberg D., Arzel-Hezode M., Laforet P., Eymard B., Tabti N., Willer J.-C., Vial C., Fontaine B.
Ann. Neurol. 60:356-365(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC LYS-270, VARIANTS MYOSCN4A THR-715; ASN-804 AND ASN-1310.
[29]"Autosomal dominant monosymptomatic myotonia permanens."
Colding-Joergensen E., Duno M., Vissing J.
Neurology 67:153-155(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A GLU-1306.
[30]"The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis."
Kim J.-B., Kim M.-H., Lee S.J., Kim D.-J., Lee B.C.
J. Korean Med. Sci. 22:946-951(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HOKPP2 HIS-669; CYS-672 AND GLY-672.
[31]"A large German kindred with cold-aggravated myotonia and a heterozygous A1481D mutation in the SCN4A gene."
Schoser B.G.H., Schroeder J.M., Grimm T., Sternberg D., Kress W.
Muscle Nerve 35:599-606(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A ASP-1481.
[32]"A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians."
Rossignol E., Mathieu J., Thiffault I., Tetreault M., Dicaire M.J., Chrestian N., Dupre N., Puymirat J., Brais B.
Neurology 69:1937-1941(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A ILE-1476.
[33]"Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene."
Gay S., Dupuis D., Faivre L., Masurel-Paulet A., Labenne M., Colombani M., Soichot P., Huet F., Hainque B., Sternberg D., Fontaine B., Gouyon J.B., Thauvin-Robinet C.
Am. J. Med. Genet. A 146:380-383(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A LYS-1297.
[34]"Mutations of sodium channel alpha-subunit genes in Chinese patients with normokalemic periodic paralysis."
Xiuhai G., Weiping W., Ke Z., Hongbin W., Yiling S., Yanling M.
Cell. Mol. Neurobiol. 28:653-661(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NKPP GLN-675; ILE-781 AND VAL-1592.
[35]"Differential effects of paramyotonia congenita mutations F1473S and F1705I on sodium channel gating."
Groome J.R., Larsen M.F., Coonts A.
Channels 2:39-50(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PMC SER-1473 AND ILE-1705.
[36]"What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed."
Matthews E., Tan S.V., Fialho D., Sweeney M.G., Sud R., Haworth A., Stanley E., Cea G., Davis M.B., Hanna M.G.
Neurology 70:50-53(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PMC LYS-270; MET-704; ALA-1306; GLU-1306; MET-1313; PRO-1436; CYS-1448; HIS-1448; LEU-1448; GLU-1456; SER-1473 AND MET-1589.
[37]"A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia."
Petitprez S., Tiab L., Chen L., Kappeler L., Rosler K.M., Schorderet D., Abriel H., Burgunder J.M.
Neurology 71:1669-1675(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MYOSCN4A VAL-141, CHARACTERIZATION OF VARIANT MYOSCN4A VAL-141.
[38]"Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy."
Lee S.C., Kim H.S., Park Y.E., Choi Y.C., Park K.H., Kim D.S.
J. Clin. Neurol. 5:186-191(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MYOSCN4A TRP-225; THR-1156 AND GLU-1306, VARIANT PMC THR-693, VARIANT HYPP THR-1156.
[39]"Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians."
Dupre N., Chrestian N., Bouchard J.-P., Rossignol E., Brunet D., Sternberg D., Brais B., Mathieu J., Puymirat J.
Neuromuscul. Disord. 19:330-334(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MYOSCN4A MET-445; LYS-452; SER-671; VAL-1306 AND ILE-1476.
[40]"Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis."
Matthews E., Labrum R., Sweeney M.G., Sud R., Haworth A., Chinnery P.F., Meola G., Schorge S., Kullmann D.M., Davis M.B., Hanna M.G.
Neurology 72:1544-1547(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HOKPP2 TRP-222; CYS-672; GLY-672; HIS-672; SER-672; GLN-1132 AND HIS-1135.
[41]"Tubular aggregates in paralysis periodica paramyotonica with T704M mutation of SCN4A."
Luan X., Chen B., Liu Y., Zheng R., Zhang W., Yuan Y.
Neuropathology 29:579-584(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PMC MET-704.
[42]"Both hypokalaemic and normokalaemic periodic paralysis in different members of a single family with novel R1129Q mutation in SCN4A gene."
Hong D., Luan X., Chen B., Zheng R., Zhang W., Wang Z., Yuan Y.
J. Neurol. Neurosurg. Psych. 81:703-704(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NKPP GLN-1129, VARIANT HOKPP2 GLN-1129.
[43]"Hypokalemic periodic paralysis due to the SCN4A R672H mutation in a Turkish family."
Incecik F., Herguner M.O., Altunbasak S., Lehman-Horn F.
Turk. J. Pediatr. 52:409-410(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HOKPP2 HIS-672.
+Additional computationally mapped references.

Web resources

Wikipedia

SCN4A entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M81758 mRNA. Translation: AAA60554.1.
L04236 expand/collapse EMBL AC list , L04216, L04217, L04218, L04219, L04220, L04221, L04222, L04223, L04224, L04225, L04226, L04227, L04228, L04229, L04230, L04231, L04232, L04233, L04234, L04235 Genomic DNA. Translation: AAB59624.1.
AY212253 mRNA. Translation: AAO83647.1.
L01983 expand/collapse EMBL AC list , L01962, L01963, L01964, L01965, L01966, L01967, L01968, L01969, L01970, L01971, L01972, L01973, L01974, L01975, L01976, L01977, L01978, L01979, L01980, L01981, L01982 Genomic DNA. Translation: AAA75557.1. Sequence problems.
AC127029 Genomic DNA. No translation available.
S82622 Genomic DNA. Translation: AAB21450.2.
CCDSCCDS45761.1.
PIRI51964.
I54323.
I64893.
JS0648.
RefSeqNP_000325.4. NM_000334.4.
XP_005257623.1. XM_005257566.2.
UniGeneHs.46038.

3D structure databases

ProteinModelPortalP35499.
SMRP35499. Positions 131-272, 588-802, 1020-1296, 1346-1597, 1602-1754.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112234. 4 interactions.
STRING9606.ENSP00000396320.

Chemistry

ChEMBLCHEMBL2331043.
DrugBankDB00555. Lamotrigine.
GuidetoPHARMACOLOGY581.

Protein family/group databases

TCDB1.A.1.10.4. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteP35499.

Polymorphism databases

DMDM292495096.

Proteomic databases

PaxDbP35499.
PRIDEP35499.

Protocols and materials databases

DNASU6329.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000435607; ENSP00000396320; ENSG00000007314.
GeneID6329.
KEGGhsa:6329.
UCSCuc002jds.1. human.

Organism-specific databases

CTD6329.
GeneCardsGC17M062015.
GeneReviewsSCN4A.
H-InvDBHIX0039131.
HGNCHGNC:10591. SCN4A.
HPAHPA053992.
MIM168300. phenotype.
170500. phenotype.
603967. gene.
608390. phenotype.
613345. phenotype.
614198. phenotype.
neXtProtNX_P35499.
Orphanet99736. Acetazolamide-responsive myotonia.
682. Hyperkalemic periodic paralysis.
681. Hypokalemic periodic paralysis.
99734. Myotonia fluctuans.
99735. Myotonia permanens.
684. Paramyotonia congenita of Von Eulenburg.
98913. Postsynaptic congenital myasthenic syndromes.
PharmGKBPA35006.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231755.
HOVERGENHBG053100.
InParanoidP35499.
KOK04837.
PhylomeDBP35499.
TreeFamTF323985.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressP35499.
BgeeP35499.
CleanExHS_SCN4A.
GenevestigatorP35499.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR028826. Na_channel_a4su.
IPR008052. Na_channel_a4su_mammal.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PANTHERPTHR10037:SF193. PTHR10037:SF193. 1 hit.
PfamPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
PR01665. NACHANNEL4.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
PROSITEPS50096. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNav1.4.
GenomeRNAi6329.
NextBio24570.
PROP35499.
SOURCESearch...

Entry information

Entry nameSCN4A_HUMAN
AccessionPrimary (citable) accession number: P35499
Secondary accession number(s): Q15478, Q16447, Q7Z6B1
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: March 23, 2010
Last modified: July 9, 2014
This is version 150 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM