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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

Keywordsi

Molecular functionIon channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

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

  • Cell membrane By similarity; Multi-pass membrane protein By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 131CytoplasmicCuratedAdd BLAST131
Transmembranei132 – 150Helical; Name=S1 of repeat IBy similarityAdd BLAST19
Topological domaini151 – 157ExtracellularCurated7
Transmembranei158 – 178Helical; Name=S2 of repeat IBy similarityAdd BLAST21
Topological domaini179 – 192CytoplasmicCuratedAdd BLAST14
Transmembranei193 – 210Helical; Name=S3 of repeat IBy similarityAdd BLAST18
Topological domaini211 – 216ExtracellularCurated6
Transmembranei217 – 233Helical; Name=S4 of repeat IBy similarityAdd BLAST17
Topological domaini234 – 252CytoplasmicCuratedAdd BLAST19
Transmembranei253 – 272Helical; Name=S5 of repeat IBy similarityAdd BLAST20
Topological domaini273 – 385ExtracellularCuratedAdd BLAST113
Intramembranei386 – 410Pore-formingBy similarityAdd BLAST25
Topological domaini411 – 417ExtracellularCurated7
Transmembranei418 – 438Helical; Name=S6 of repeat IBy similarityAdd BLAST21
Topological domaini439 – 572CytoplasmicCuratedAdd BLAST134
Transmembranei573 – 591Helical; Name=S1 of repeat IIBy similarityAdd BLAST19
Topological domaini592 – 602ExtracellularCuratedAdd BLAST11
Transmembranei603 – 622Helical; Name=S2 of repeat IIBy similarityAdd BLAST20
Topological domaini623 – 636CytoplasmicCuratedAdd BLAST14
Transmembranei637 – 656Helical; Name=S3 of repeat IIBy similarityAdd BLAST20
Topological domaini657 – 658ExtracellularCurated2
Transmembranei659 – 676Helical; Name=S4 of repeat IIBy similarityAdd BLAST18
Topological domaini677 – 692CytoplasmicCuratedAdd BLAST16
Transmembranei693 – 711Helical; Name=S5 of repeat IIBy similarityAdd BLAST19
Topological domaini712 – 740ExtracellularCuratedAdd BLAST29
Intramembranei741 – 761Pore-formingBy similarityAdd BLAST21
Topological domaini762 – 774ExtracellularCuratedAdd BLAST13
Transmembranei775 – 795Helical; Name=S6 of repeat IIBy similarityAdd BLAST21
Topological domaini796 – 1029CytoplasmicCuratedAdd BLAST234
Transmembranei1030 – 1047Helical; Name=S1 of repeat IIIBy similarityAdd BLAST18
Topological domaini1048 – 1060ExtracellularCuratedAdd BLAST13
Transmembranei1061 – 1079Helical; Name=S2 of repeat IIIBy similarityAdd BLAST19
Topological domaini1080 – 1093CytoplasmicCuratedAdd BLAST14
Transmembranei1094 – 1112Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini1113 – 1120ExtracellularCurated8
Transmembranei1121 – 1139Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini1140 – 1156CytoplasmicCuratedAdd BLAST17
Transmembranei1157 – 1176Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini1177 – 1227ExtracellularCuratedAdd BLAST51
Intramembranei1228 – 1249Pore-formingBy similarityAdd BLAST22
Topological domaini1250 – 1266ExtracellularCuratedAdd BLAST17
Transmembranei1267 – 1288Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1289 – 1351CytoplasmicCuratedAdd BLAST63
Transmembranei1352 – 1369Helical; Name=S1 of repeat IVBy similarityAdd BLAST18
Topological domaini1370 – 1380ExtracellularCuratedAdd BLAST11
Transmembranei1381 – 1399Helical; Name=S2 of repeat IVBy similarityAdd BLAST19
Topological domaini1400 – 1411CytoplasmicCuratedAdd BLAST12
Transmembranei1412 – 1429Helical; Name=S3 of repeat IVBy similarityAdd BLAST18
Topological domaini1430 – 1442ExtracellularCuratedAdd BLAST13
Transmembranei1443 – 1459Helical; Name=S4 of repeat IVBy similarityAdd BLAST17
Topological domaini1460 – 1478CytoplasmicCuratedAdd BLAST19
Transmembranei1479 – 1496Helical; Name=S5 of repeat IVBy similarityAdd BLAST18
Topological domaini1497 – 1518ExtracellularCuratedAdd BLAST22
Intramembranei1519 – 1541Pore-formingBy similarityAdd BLAST23
Topological domaini1542 – 1571ExtracellularCuratedAdd BLAST30
Transmembranei1572 – 1594Helical; Name=S6 of repeat IVBy similarityAdd BLAST23
Topological domaini1595 – 1834CytoplasmicCuratedAdd BLAST240

GO - Cellular componenti

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.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003713151 – 1834Sodium channel protein type 4 subunit alphaAdd BLAST1834

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi214N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi280 ↔ 363By similarity
Glycosylationi288N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi291N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi297N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi303N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi309N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi327N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi356N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi723Interchain; with SCN2B or SCN4BBy similarity
Disulfide bondi723Interchain; with the conotoxin GVIIJ (when the channel is not linked to SCN2B or SCN4B; the bond to SCN2B or SCN4B protects the channel from the inhibition by toxin)By similarity
Glycosylationi1188N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1202N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1325Phosphoserine; by PKCBy similarity1

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

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiQ28371.

Interactioni

Subunit structurei

Muscle sodium channels contain an alpha subunit and a smaller beta subunit. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2. Interacts with the conotoxin GVIIJ.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ28371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati113 – 448ICuratedAdd BLAST336
Repeati554 – 826IICuratedAdd BLAST273
Repeati1010 – 1323IIICuratedAdd BLAST314
Repeati1332 – 1630IVCuratedAdd BLAST299
Domaini1724 – 1753IQPROSITE-ProRule annotationAdd BLAST30

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.Curated

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

InParanoidiQ28371.
KOiK04837.

Family and domain databases

InterProiView protein in InterPro
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR008052. Na_channel_a4su_mammal.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
PfamiView protein in Pfam
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
PRINTSiPR00170. NACHANNEL.
PR01665. NACHANNEL4.
PROSITEiView protein in PROSITE
PS50096. IQ. 1 hit.

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)DescriptionActionsGraphical viewLength
Natural varianti1416F → L in HYPP; found in a Quarter Horse lineage segregating the disease. 1 Publication1

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.

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.

Entry informationi

Entry nameiSCN4A_HORSE
AccessioniPrimary (citable) accession number: Q28371
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: November 1, 1996
Last modified: May 10, 2017
This is version 96 of the entry and version 1 of the sequence. See 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