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Protein

Sodium channel protein type 4 subunit alpha

Gene

Scn4a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 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.1 Publication

GO - Molecular functioni

  • voltage-gated sodium channel activity Source: RGD

GO - Biological processi

  • cation transport Source: RGD
  • choline transport Source: RGD
  • membrane depolarization during action potential Source: GO_Central
  • neuronal action potential Source: GO_Central
  • potassium ion transport Source: RGD
  • sodium ion transport Source: RGD

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):
Mu-1
SkM1
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3636. Scn4a.

Subcellular locationi

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 – 1025CytoplasmicCuratedAdd BLAST230
Transmembranei1026 – 1043Helical; Name=S1 of repeat IIIBy similarityAdd BLAST18
Topological domaini1044 – 1056ExtracellularCuratedAdd BLAST13
Transmembranei1057 – 1075Helical; Name=S2 of repeat IIIBy similarityAdd BLAST19
Topological domaini1076 – 1089CytoplasmicCuratedAdd BLAST14
Transmembranei1090 – 1108Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini1109 – 1116ExtracellularCurated8
Transmembranei1117 – 1135Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini1136 – 1152CytoplasmicCuratedAdd BLAST17
Transmembranei1153 – 1172Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini1173 – 1223ExtracellularCuratedAdd BLAST51
Intramembranei1224 – 1245Pore-formingBy similarityAdd BLAST22
Topological domaini1246 – 1262ExtracellularCuratedAdd BLAST17
Transmembranei1263 – 1284Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1285 – 1347CytoplasmicCuratedAdd BLAST63
Transmembranei1348 – 1365Helical; Name=S1 of repeat IVBy similarityAdd BLAST18
Topological domaini1366 – 1376ExtracellularCuratedAdd BLAST11
Transmembranei1377 – 1395Helical; Name=S2 of repeat IVBy similarityAdd BLAST19
Topological domaini1396 – 1407CytoplasmicCuratedAdd BLAST12
Transmembranei1408 – 1425Helical; Name=S3 of repeat IVBy similarityAdd BLAST18
Topological domaini1426 – 1438ExtracellularCuratedAdd BLAST13
Transmembranei1439 – 1455Helical; Name=S4 of repeat IVBy similarityAdd BLAST17
Topological domaini1456 – 1474CytoplasmicCuratedAdd BLAST19
Transmembranei1475 – 1492Helical; Name=S5 of repeat IVBy similarityAdd BLAST18
Topological domaini1493 – 1514ExtracellularCuratedAdd BLAST22
Intramembranei1515 – 1537Pore-formingBy similarityAdd BLAST23
Topological domaini1538 – 1567ExtracellularCuratedAdd BLAST30
Transmembranei1568 – 1590Helical; Name=S6 of repeat IVBy similarityAdd BLAST23
Topological domaini1591 – 1840CytoplasmicCuratedAdd BLAST250

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1379Y → S: Become sensitive to the spider beta/delta-theraphotoxin-Pre1a, which inhibits inactivation of the channel. 1 Publication1
Mutagenesisi1380N → R: No change in sensitivity to the spider beta/delta-theraphotoxin-Pre1a. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3509.
GuidetoPHARMACOLOGYi581.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000484961 – 1840Sodium channel protein type 4 subunit alphaAdd BLAST1840

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei56Phosphoserine; by PKASequence analysis1
Modified residuei251Phosphoserine; by PKASequence 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
Glycosylationi315N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi327N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi356N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei487PhosphoserineCombined sources1
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
Disulfide bondi763 ↔ 772By similarity
Glycosylationi1198N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1321Phosphoserine; by PKASequence analysis1
Modified residuei1321Phosphoserine; by PKCBy similarity1

Post-translational modificationi

Phosphorylation at Ser-1321 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

PaxDbiP15390.
PRIDEiP15390.

PTM databases

iPTMnetiP15390.
PhosphoSitePlusiP15390.

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 (PubMed:24497506).By similarity1 Publication

Protein-protein interaction databases

BioGridi247751. 1 interactor.
STRINGi10116.ENSRNOP00000016841.

Chemistry databases

BindingDBiP15390.

Structurei

Secondary structure

11840
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1569 – 1594Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JR0NMR-A1567-1594[»]
ProteinModelPortaliP15390.
SMRiP15390.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati113 – 448ICuratedAdd BLAST336
Repeati554 – 826IICuratedAdd BLAST273
Repeati1006 – 1319IIICuratedAdd BLAST314
Repeati1328 – 1626IVCuratedAdd BLAST299
Domaini1720 – 1749IQPROSITE-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

eggNOGiENOG410INF8. Eukaryota.
COG1226. LUCA.
HOGENOMiHOG000231755.
HOVERGENiHBG053100.
InParanoidiP15390.
KOiK04837.
PhylomeDBiP15390.

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.

P15390-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASSSLPNLV PPGPHCLRPF TPESLAAIEQ RAVEEEARLQ RNKQMEIEEP
60 70 80 90 100
ERKPRSDLEA GKNLPLIYGD PPPEVIGIPL EDLDPYYSDK KTFIVLNKGK
110 120 130 140 150
AIFRFSATPA LYLLSPFSIV RRVAIKVLIH ALFSMFIMIT ILTNCVFMTM
160 170 180 190 200
SNPPSWSKHV EYTFTGIYTF ESLIKMLARG FCIDDFTFLR DPWNWLDFSV
210 220 230 240 250
ITMAYVTEFV DLGNISALRT FRVLRALKTI TVIPGLKTIV GALIQSVKKL
260 270 280 290 300
SDVMILTVFC LSVFALVGLQ LFMGNLRQKC VRWPPPMNDT NTTWYGNDTW
310 320 330 340 350
YSNDTWYGND TWYINDTWNS QESWAGNSTF DWEAYINDEG NFYFLEGSND
360 370 380 390 400
ALLCGNSSDA GHCPEGYECI KAGRNPNYGY TSYDTFSWAF LALFRLMTQD
410 420 430 440 450
YWENLFQLTL RAAGKTYMIF FVVIIFLGSF YLINLILAVV AMAYAEQNEA
460 470 480 490 500
TLAEDQEKEE EFQQMLEKYK KHQEELEKAK AAQALESGEE ADGDPTHNKD
510 520 530 540 550
CNGSLDASGE KGPPRPSCSA DSAISDAMEE LEEAHQKCPP WWYKCAHKVL
560 570 580 590 600
IWNCCAPWVK FKHIIYLIVM DPFVDLGITI CIVLNTLFMA MEHYPMTEHF
610 620 630 640 650
DNVLSVGNLV FTGIFTAEMV LKLIAMDPYE YFQQGWNIFD SFIVTLSLVE
660 670 680 690 700
LGLANVQGLS VLRSFRLLRV FKLAKSWPTL NMLIKIIGNS VGALGNLTLV
710 720 730 740 750
LAIIVFIFAV VGMQLFGKSY KECVCKIASD CNLPRWHMND FFHSFLIVFR
760 770 780 790 800
ILCGEWIETM WDCMEVAGQA MCLTVFLMVM VIGNLVVLNL FLALLLSSFS
810 820 830 840 850
ADSLAASDED GEMNNLQIAI GRIKWGIGFA KTFLLGLLRG KILSPKEIIL
860 870 880 890 900
SLGEPGGAGE NAEESTPEDE KKEPPPEDKE LKDNHILNHV GLTDGPRSSI
910 920 930 940 950
ELDHLNFINN PYLTIQVPIA SEESDLEMPT EEETDAFSEP EDIKKPLQPL
960 970 980 990 1000
YDGNSSVCST ADYKPPEEDP EEQAEENPEG EQPEECFTEA CVKRCPCLYV
1010 1020 1030 1040 1050
DISQGRGKMW WTLRRACFKI VEHNWFETFI VFMILLSSGA LAFEDIYIEQ
1060 1070 1080 1090 1100
RRVIRTILEY ADKVFTYIFI LEMLLKWVAY GFKVYFTNAW CWLDFLIVDV
1110 1120 1130 1140 1150
SIISLVANWL GYSELGPIKS LRTLRALRPL RALSRFEGMR VVVNALLGAI
1160 1170 1180 1190 1200
PSIMNVLLVC LIFWLIFSIM GVNLFAGKFY YCVNTTTSER FDISVVNNKS
1210 1220 1230 1240 1250
ESESLMYTGQ VRWMNVKVNY DNVGLGYLSL LQVATFKGWM DIMYAAVDSR
1260 1270 1280 1290 1300
EKEEQPHYEV NLYMYLYFVI FIIFGSFFTL NLFIGVIIDN FNQQKKKFGG
1310 1320 1330 1340 1350
KDIFMTEEQK KYYNAMKKLG SKKPQKPIPR PQNKIQGMVY DFVTKQVFDI
1360 1370 1380 1390 1400
SIMILICLNM VTMMVETDDQ SQLKVDILYN INMVFIIIFT GECVLKMFAL
1410 1420 1430 1440 1450
RHYYFTIGWN IFDFVVVILS IVGLALSDLI QKYFVSPTLF RVIRLARIGR
1460 1470 1480 1490 1500
VLRLIRGAKG IRTLLFALMM SLPALFNIGL LLFLVMFIYS IFGMSNFAYV
1510 1520 1530 1540 1550
KKESGIDDMF NFETFGNSII CLFEITTSAG WDGLLNPILN SGPPDCDPTL
1560 1570 1580 1590 1600
ENPGTNVRGD CGNPSIGICF FCSYIIISFL IVVNMYIAII LENFNVATEE
1610 1620 1630 1640 1650
SSEPLSEDDF EMFYETWEKF DPDATQFIDY SRLSDFVDTL QEPLKIAKPN
1660 1670 1680 1690 1700
KIKLITLDLP MVPGDKIHCL DILFALTKEV LGDSGEMDAL KQTMEEKFMA
1710 1720 1730 1740 1750
ANPSKVSYEP ITTTLKRKQE EVCAIKIQRA YRRHLLQRSV KQASYMYRHS
1760 1770 1780 1790 1800
QDGNDDGAPE KEGLLANTMN KMYGHEKEGD GVQSQGEEEK ASTEDAGPTV
1810 1820 1830 1840
EPEPTSSSDT ALTPSPPPLP PSSSPPQGQT VRPGVKESLV
Length:1,840
Mass (Da):208,867
Last modified:April 1, 1990 - v1
Checksum:iC5DC09D93DD9FAD6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti120V → I in strain: COP; prostatic cancer cell lines. 1 Publication1
Natural varianti916Q → H in strain: COP; prostatic cancer cell lines. 1 Publication1
Natural varianti1202S → C in strain: COP; prostatic cancer cell lines. 1 Publication1
Natural varianti1257H → D in strain: COP; prostatic cancer cell lines. 1 Publication1
Natural varianti1755D → G in strain: COP; prostatic cancer cell lines. 1 Publication1
Natural varianti1803E → K in strain: COP; prostatic cancer cell lines. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M26643 mRNA. Translation: AAA41682.1.
Y17153 mRNA. Translation: CAA76659.1.
PIRiJN0007. CHRTM1.
RefSeqiNP_037310.1. NM_013178.1.
UniGeneiRn.9700.

Genome annotation databases

GeneIDi25722.
KEGGirno:25722.
UCSCiRGD:3636. rat.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSCN4A_RAT
AccessioniPrimary (citable) accession number: P15390
Secondary accession number(s): O70611
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: August 30, 2017
This is version 142 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families