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Protein

Sodium channel protein type 4 subunit alpha

Gene

SCN4A

Organism
Equus caballus (Horse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 4 subunit alpha
Alternative name(s):
Sodium channel protein skeletal muscle subunit alpha
Sodium channel protein type IV subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.4
Gene namesi
Name:SCN4A
OrganismiEquus caballus (Horse)
Taxonomic identifieri9796 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus
Proteomesi
  • UP000002281 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 128128CytoplasmicSequence analysisAdd
BLAST
Transmembranei129 – 15022Helical; Name=S1 of repeat ISequence analysisAdd
BLAST
Topological domaini151 – 1588ExtracellularSequence analysis
Transmembranei159 – 17820Helical; Name=S2 of repeat ISequence analysisAdd
BLAST
Topological domaini179 – 19012CytoplasmicSequence analysisAdd
BLAST
Transmembranei191 – 21020Helical; Name=S3 of repeat ISequence analysisAdd
BLAST
Topological domaini211 – 2166ExtracellularSequence analysis
Transmembranei217 – 23620Helical; Voltage-sensor; Name=S4 of repeat ISequence analysisAdd
BLAST
Topological domaini237 – 25216CytoplasmicSequence analysisAdd
BLAST
Transmembranei253 – 26614Helical; Name=S5 of repeat ISequence analysisAdd
BLAST
Topological domaini267 – 417151ExtracellularSequence analysisAdd
BLAST
Transmembranei418 – 44326Helical; Name=S6 of repeat ISequence analysisAdd
BLAST
Topological domaini444 – 567124CytoplasmicSequence analysisAdd
BLAST
Transmembranei568 – 59124Helical; Name=S1 of repeat IISequence analysisAdd
BLAST
Topological domaini592 – 60211ExtracellularSequence analysisAdd
BLAST
Transmembranei603 – 62624Helical; Name=S2 of repeat IISequence analysisAdd
BLAST
Topological domaini627 – 6348CytoplasmicSequence analysis
Transmembranei635 – 65420Helical; Name=S3 of repeat IISequence analysisAdd
BLAST
Topological domaini655 – 6606ExtracellularSequence analysis
Transmembranei661 – 68020Helical; Voltage-sensor; Name=S4 of repeat IISequence analysisAdd
BLAST
Topological domaini681 – 69515CytoplasmicSequence analysisAdd
BLAST
Transmembranei696 – 71823Helical; Name=S5 of repeat IISequence analysisAdd
BLAST
Topological domaini719 – 77052ExtracellularSequence analysisAdd
BLAST
Transmembranei771 – 79626Helical; Name=S6 of repeat IISequence analysisAdd
BLAST
Topological domaini797 – 1023227CytoplasmicSequence analysisAdd
BLAST
Transmembranei1024 – 104623Helical; Name=S1 of repeat IIISequence analysisAdd
BLAST
Topological domaini1047 – 106014ExtracellularSequence analysisAdd
BLAST
Transmembranei1061 – 108626Helical; Name=S2 of repeat IIISequence analysisAdd
BLAST
Topological domaini1087 – 10926CytoplasmicSequence analysis
Transmembranei1093 – 111321Helical; Name=S3 of repeat IIISequence analysisAdd
BLAST
Topological domaini1114 – 11185ExtracellularSequence analysis
Transmembranei1119 – 114022Helical; Voltage-sensor; Name=S4 of repeat IIISequence analysisAdd
BLAST
Topological domaini1141 – 115919CytoplasmicSequence analysisAdd
BLAST
Transmembranei1160 – 118122Helical; Name=S5 of repeat IIISequence analysisAdd
BLAST
Topological domaini1182 – 126584ExtracellularSequence analysisAdd
BLAST
Transmembranei1266 – 129227Helical; Name=S6 of repeat IIISequence analysisAdd
BLAST
Topological domaini1293 – 134553CytoplasmicSequence analysisAdd
BLAST
Transmembranei1346 – 136924Helical; Name=S1 of repeat IVSequence analysisAdd
BLAST
Topological domaini1370 – 138011ExtracellularSequence analysisAdd
BLAST
Transmembranei1381 – 140424Helical; Name=S2 of repeat IVSequence analysisAdd
BLAST
Topological domaini1405 – 14106CytoplasmicSequence analysis
Transmembranei1411 – 143424Helical; Name=S3 of repeat IVSequence analysisAdd
BLAST
Topological domaini1435 – 14439ExtracellularSequence analysis
Transmembranei1444 – 146623Helical; Voltage-sensor; Name=S4 of repeat IVSequence analysisAdd
BLAST
Topological domaini1467 – 148115CytoplasmicSequence analysisAdd
BLAST
Transmembranei1482 – 150423Helical; Name=S5 of repeat IVSequence analysisAdd
BLAST
Topological domaini1505 – 157066ExtracellularSequence analysisAdd
BLAST
Transmembranei1571 – 159525Helical; Name=S6 of repeat IVSequence analysisAdd
BLAST
Topological domaini1596 – 1834239CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in SCN4A are the cause of periodic paralysis hyperkalemic (HYPP). HYPP is an autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. HYPP is frequently found in Quarter Horses, the most popular equine breed in the United States.

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18341834Sodium channel protein type 4 subunit alphaPRO_0000371315Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi214 – 2141N-linked (GlcNAc...)Sequence analysis
Glycosylationi288 – 2881N-linked (GlcNAc...)Sequence analysis
Glycosylationi291 – 2911N-linked (GlcNAc...)Sequence analysis
Glycosylationi297 – 2971N-linked (GlcNAc...)Sequence analysis
Glycosylationi303 – 3031N-linked (GlcNAc...)Sequence analysis
Glycosylationi309 – 3091N-linked (GlcNAc...)Sequence analysis
Glycosylationi327 – 3271N-linked (GlcNAc...)Sequence analysis
Glycosylationi356 – 3561N-linked (GlcNAc...)Sequence analysis
Glycosylationi1188 – 11881N-linked (GlcNAc...)Sequence analysis
Glycosylationi1202 – 12021N-linked (GlcNAc...)Sequence analysis
Modified residuei1325 – 13251Phosphoserine; by PKCBy similarity

Post-translational modificationi

Phosphorylation at Ser-1325 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiQ28371.

Interactioni

Subunit structurei

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ28371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati113 – 448336ICuratedAdd
BLAST
Repeati554 – 826273IICuratedAdd
BLAST
Repeati1010 – 1323314IIICuratedAdd
BLAST
Repeati1332 – 1630299IVCuratedAdd
BLAST
Domaini1724 – 175330IQPROSITE-ProRule annotationAdd
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 IQ domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

InParanoidiQ28371.
KOiK04837.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. 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]
PANTHERiPTHR10037:SF223. PTHR10037:SF223. 2 hits.
PfamiPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
PR01665. NACHANNEL4.
PROSITEiPS50096. IQ. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q28371-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASSSLPNLV PLGPESLRPF TRASLAAIER RALEEEARLQ RNKQMEIQET
60 70 80 90 100
ERNARSDLEA GKNLPLIYGD PPPEVIGIPL EDLDPYYSNK KTFIVLNKGK
110 120 130 140 150
AIFRFSATPA LYMLSPFSII RRSAIKVLIH SLFSMFIMIT ILPNCVVMTM
160 170 180 190 200
SDPPPWPIHV ENTFTGINTF ESLIKMLARG FCIDDFTFLR DPWNWLDFSV
210 220 230 240 250
IMMAYLTEFV DLGNISALRT FRVLRALKTI TVIPGLKTIV GALIQSVKKL
260 270 280 290 300
SDVMILTVFC LSVFALVGLQ LFMGNLRQKC VRWPQPFNDT NTTWYGNDTW
310 320 330 340 350
YSNDTWNSND TWSSNDMWNS HESMASNYTF DWDAYINDEG NFYFLEGAKD
360 370 380 390 400
ALLCGNSSDA GHCPEGYKCI KTGRNPNYGY TSHDTFSWAF LALFRLMIQD
410 420 430 440 450
YWENLFQLTL RAAGKTYMIF FVVIIFLGSF YLINLILAVV TMAYAEQNEA
460 470 480 490 500
TLAEDQEKEE EFQQMMEKFQ KQQEELEKAK ADQALEGGEA GGDPAHSKDC
510 520 530 540 550
NGSLDTSPGE KGPPRQSCSA DSGVSDAMEE LEEAHQKCPP WWYKCAHKVL
560 570 580 590 600
IWNCCTPWVK FKNIIHLIVM DPFVDLGITI CIVLNTLFMA MEHYPMTEHF
610 620 630 640 650
DKVLTVGNLV FTGIFTAEMV LKLIALDPYE YFQQGWNVFD SIIVTLSWVE
660 670 680 690 700
LGLVNVKGLS VLRSFRLVRS LKLAKSWPTL NMFIRIIGNS GGGLGNLTLV
710 720 730 740 750
LAIIVVNFSV VGMQLFGKNY KECVCKNASD CALPRWKMCD FFHSFLIVLR
760 770 780 790 800
ILCGEWIEPM WGFMEVAGQA MFLTVLLMVM VNGNLVDLDL FLALLLNPLN
810 820 830 840 850
SDNLSASDED GEMNNLQISS WPIKLGICFA NAFLLGLLHG KILSPKDIML
860 870 880 890 900
SLGDPGEAGE AGEAEESAPE DEKKEPPPED DDKDLKKDNH ILNHMGLVDG
910 920 930 940 950
TPTSIELDHL NFINNPYLTI HVPIASEESD LEMPTEEETD TFSEPEDGKK
960 970 980 990 1000
PLQPLDGNSS VCSTADYKPP EEDPEEQAEE NPEGEQPEEC FTEACVQRFP
1010 1020 1030 1040 1050
CLSVDISQGR GKMWWTLRRA CFKIVEHHWF KTFNSSLILL NSGTLAFEDI
1060 1070 1080 1090 1100
YIEQRRVIRT ILEYADKVFT YIFIMEMLLK WVAYGFKVYF TNAWCWLDFL
1110 1120 1130 1140 1150
IVDVSIISLV ANWLGYSELG PIKSLRTLRA LRPLRALSRF EGMRVVVNAL
1160 1170 1180 1190 1200
LGAIPSIMNV LLVCLIFWVI FSIMGVNLFA AKIYYFINTT TSERFDISGV
1210 1220 1230 1240 1250
NNKSECESLI HTGQVRWLNV KVNYDNVGLG YLSLLQVATF KGWMDIMYSA
1260 1270 1280 1290 1300
VDSREQEEQP QYEVNIYMYL YFVIFIIFGS FFTINSLIRL IIVNFNQQKK
1310 1320 1330 1340 1350
KLGGKDIFMT EEQKKYYNAM KKLGSKKPQK PIPRPQNKIQ GMVYDFVTKQ
1360 1370 1380 1390 1400
VFDITIMILI CLNMVTMMVE TDDQSQLKVD ILYNINMVFI IVFTGECVLK
1410 1420 1430 1440 1450
MFALRQNYFT VGWNIFDFVV VILSIVGLAL SDLIQKYFVS PTLFRVIRLA
1460 1470 1480 1490 1500
RIGRVLRLIR GAKGIRTLLF ALMMSLPALF NIGLLLILVM FIYSIFGMSN
1510 1520 1530 1540 1550
FAYVKKESGI DDMFNFETFG NSIICLFEIT TSAGWDGLLN PILNSGPPDC
1560 1570 1580 1590 1600
DPTLENPGTS VRGDCGNPSI GICFFCSYII ISFLIVVNMY IAIILENFNV
1610 1620 1630 1640 1650
ATEESSDPLG EDDFEIFFEK WEKFGPDATQ FIDYSRLSDF VDTLQEPLRI
1660 1670 1680 1690 1700
AKPNKIKLIT LDLPMVPGDK IHCLDILFAL TKEVLGDSGE MDALKETMEE
1710 1720 1730 1740 1750
KFMAANPSKV SYEPITTTLK RKQEEVCAIK IQRAYRRHLL QRSVKQASYM
1760 1770 1780 1790 1800
YRHSQDGSGD GAPEKEGLIA NTMSKMYGRE NGNSGVQNKG EERGSTGDAG
1810 1820 1830
PTMGLTPINP SDSALPPSPP PGLPLHPGVK ESLV
Length:1,834
Mass (Da):207,487
Last modified:November 1, 1996 - v1
Checksum:i01D62B25CD577D97
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1416 – 14161F → L in HYPP; found in a Quarter Horse lineage segregating the disease. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25990 mRNA. Translation: AAA67366.1.
RefSeqiNP_001075230.1. NM_001081761.1.
UniGeneiEca.13094.

Genome annotation databases

GeneIDi100049793.
KEGGiecb:100049793.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25990 mRNA. Translation: AAA67366.1.
RefSeqiNP_001075230.1. NM_001081761.1.
UniGeneiEca.13094.

3D structure databases

ProteinModelPortaliQ28371.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiQ28371.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100049793.
KEGGiecb:100049793.

Organism-specific databases

CTDi6329.

Phylogenomic databases

InParanoidiQ28371.
KOiK04837.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. 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]
PANTHERiPTHR10037:SF223. PTHR10037:SF223. 2 hits.
PfamiPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
PR01665. NACHANNEL4.
PROSITEiPS50096. IQ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Stephan D.A., Wang J., Spier S., Hoffman E.P.
    Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. "Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding."
    Rudolph J.A., Spier S.J., Byrns G., Rojas C.V., Bernoco D., Hoffman E.P.
    Nat. Genet. 2:144-147(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN HYPP, VARIANT HYPP LEU-1416.

Entry informationi

Entry nameiSCN4A_HORSE
AccessioniPrimary (citable) accession number: Q28371
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.