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Protein

Sodium channel protein type 5 subunit alpha

Gene

Scn5a

Organism
Mus musculus (Mouse)
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 (PubMed:11834499). It is a tetrodotoxin-resistant Na+ channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Ion channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-MMU-5576892. Phase 0 - rapid depolarisation.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 5 subunit alpha
Alternative name(s):
Sodium channel protein cardiac muscle subunit alpha
Sodium channel protein type V subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.5
mH1
Gene namesi
Name:Scn5a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:98251. Scn5a.

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 – 357ExtracellularCuratedAdd BLAST85
Intramembranei358 – 382Pore-formingBy similarityAdd BLAST25
Topological domaini383 – 389ExtracellularCurated7
Transmembranei390 – 410Helical; Name=S6 of repeat IBy similarityAdd BLAST21
Topological domaini411 – 717CytoplasmicCuratedAdd BLAST307
Transmembranei718 – 736Helical; Name=S1 of repeat IIBy similarityAdd BLAST19
Topological domaini737 – 747ExtracellularCuratedAdd BLAST11
Transmembranei748 – 767Helical; Name=S2 of repeat IIBy similarityAdd BLAST20
Topological domaini768 – 781CytoplasmicCuratedAdd BLAST14
Transmembranei782 – 801Helical; Name=S3 of repeat IIBy similarityAdd BLAST20
Topological domaini802 – 803ExtracellularCurated2
Transmembranei804 – 821Helical; Name=S4 of repeat IIBy similarityAdd BLAST18
Topological domaini822 – 837CytoplasmicCuratedAdd BLAST16
Transmembranei838 – 856Helical; Name=S5 of repeat IIBy similarityAdd BLAST19
Topological domaini857 – 885ExtracellularCuratedAdd BLAST29
Intramembranei886 – 906Pore-formingBy similarityAdd BLAST21
Topological domaini907 – 919ExtracellularCuratedAdd BLAST13
Transmembranei920 – 940Helical; Name=S6 of repeat IIBy similarityAdd BLAST21
Topological domaini941 – 1208CytoplasmicCuratedAdd BLAST268
Transmembranei1209 – 1226Helical; Name=S1 of repeat IIIBy similarityAdd BLAST18
Topological domaini1227 – 1239ExtracellularCuratedAdd BLAST13
Transmembranei1240 – 1258Helical; Name=S2 of repeat IIIBy similarityAdd BLAST19
Topological domaini1259 – 1272CytoplasmicCuratedAdd BLAST14
Transmembranei1273 – 1291Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini1292 – 1299ExtracellularCurated8
Transmembranei1300 – 1318Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini1319 – 1335CytoplasmicCuratedAdd BLAST17
Transmembranei1336 – 1355Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini1356 – 1407ExtracellularCuratedAdd BLAST52
Intramembranei1408 – 1429Pore-formingBy similarityAdd BLAST22
Topological domaini1430 – 1446ExtracellularCuratedAdd BLAST17
Transmembranei1447 – 1468Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1469 – 1531CytoplasmicCuratedAdd BLAST63
Transmembranei1532 – 1549Helical; Name=S1 of repeat IVBy similarityAdd BLAST18
Topological domaini1550 – 1560ExtracellularCuratedAdd BLAST11
Transmembranei1561 – 1579Helical; Name=S2 of repeat IVBy similarityAdd BLAST19
Topological domaini1580 – 1591CytoplasmicCuratedAdd BLAST12
Transmembranei1592 – 1609Helical; Name=S3 of repeat IVBy similarityAdd BLAST18
Topological domaini1610 – 1622ExtracellularCuratedAdd BLAST13
Transmembranei1623 – 1639Helical; Name=S4 of repeat IVBy similarityAdd BLAST17
Topological domaini1640 – 1658CytoplasmicCuratedAdd BLAST19
Transmembranei1659 – 1676Helical; Name=S5 of repeat IVBy similarityAdd BLAST18
Topological domaini1677 – 1698ExtracellularCuratedAdd BLAST22
Intramembranei1699 – 1721Pore-formingBy similarityAdd BLAST23
Topological domaini1722 – 1750ExtracellularCuratedAdd BLAST29
Transmembranei1751 – 1773Helical; Name=S6 of repeat IVBy similarityAdd BLAST23
Topological domaini1774 – 2019CytoplasmicCuratedAdd BLAST246

GO - Cellular componenti

  • caveola Source: MGI
  • cell surface Source: BHF-UCL
  • endoplasmic reticulum Source: MGI
  • integral component of membrane Source: UniProtKB
  • intercalated disc Source: BHF-UCL
  • intracellular Source: MGI
  • lateral plasma membrane Source: BHF-UCL
  • plasma membrane Source: MGI
  • sarcolemma Source: MGI
  • sodium channel complex Source: MGI
  • T-tubule Source: MGI
  • voltage-gated sodium channel complex Source: MGI
  • Z disc Source: MGI

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003768951 – 2019Sodium channel protein type 5 subunit alphaAdd BLAST2019

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei36PhosphoserineBy similarity1
Modified residuei38PhosphothreonineBy similarity1
Glycosylationi214N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi280 ↔ 335By similarity
Glycosylationi283N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi288N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi291N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi318N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi328N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei457PhosphoserineCombined sources1
Modified residuei460PhosphoserineBy similarity1
Modified residuei483PhosphoserineBy similarity1
Modified residuei484PhosphoserineCombined sources1
Modified residuei486PhosphothreonineBy similarity1
Modified residuei497PhosphoserineBy similarity1
Modified residuei510PhosphoserineBy similarity1
Modified residuei526Dimethylated arginine; alternateBy similarity1
Modified residuei526Omega-N-methylarginine; alternateCombined sources1
Modified residuei539PhosphoserineCombined sources1
Modified residuei571PhosphoserineBy similarity1
Modified residuei664PhosphoserineBy similarity1
Modified residuei667PhosphoserineBy similarity1
Glycosylationi740N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi803N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi864N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi908 ↔ 917By similarity
Glycosylationi1367N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1376N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1382N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1390N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1505Phosphoserine; by PKCBy similarity1

Post-translational modificationi

Phosphorylation at Ser-1505 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents (By similarity). Regulated through phosphorylation by CaMK2D (PubMed:17124532).By similarity1 Publication
Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2.By similarity
Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 868) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9JJV9.
PRIDEiQ9JJV9.

PTM databases

iPTMnetiQ9JJV9.
PhosphoSitePlusiQ9JJV9.

Expressioni

Tissue specificityi

Expressed in the myocardium.1 Publication

Gene expression databases

BgeeiENSMUSG00000032511.
ExpressionAtlasiQ9JJV9. baseline and differential.
GenevisibleiQ9JJV9. MM.

Interactioni

Subunit structurei

Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 (PubMed:9412493). Interacts with NEDD4, NEDD4L, WWP2 and GPD1L (By similarity). Interacts with CALM (By similarity). Interacts with FGF13; the interaction is direct and may regulate SNC5A density at membranes and function (PubMed:21817159). Interacts with FGF12 and FGF14 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203101. 2 interactors.
DIPiDIP-46142N.
IntActiQ9JJV9. 1 interactor.
MINTiMINT-4130032.
STRINGi10090.ENSMUSP00000066228.

Structurei

3D structure databases

ProteinModelPortaliQ9JJV9.
SMRiQ9JJV9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati113 – 420ICuratedAdd BLAST308
Repeati699 – 971IICuratedAdd BLAST273
Repeati1189 – 1503IIICuratedAdd BLAST315
Repeati1512 – 1809IVCuratedAdd BLAST298
Domaini1903 – 1932IQAdd BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1841 – 1903Interaction with FGF13By similarityAdd BLAST63
Regioni1977 – 1980Interaction with NEDD4, NEDD4L and WWP2By similarity4

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
The IQ domain mediates association with calmodulin.By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
GeneTreeiENSGT00830000128242.
HOGENOMiHOG000231755.
InParanoidiQ9JJV9.
KOiK04838.
TreeFamiTF323985.

Family and domain databases

InterProiView protein in InterPro
IPR005821. Ion_trans_dom.
IPR008053. Na_channel_a5su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
IPR024583. Na_trans_cytopl.
PfamiView protein in Pfam
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
PF11933. Na_trans_cytopl. 1 hit.
PRINTSiPR00170. NACHANNEL.
PR01666. NACHANNEL5.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9JJV9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSATSQ ESREGLPEEE
60 70 80 90 100
APRPQLDLQA SKKLPDLYGN PPRELIGEPL EDLDPFYSTQ KTFIVLNKGK
110 120 130 140 150
TIFRFSATNA LYVLSPFHPV RRAAVKILVH SLFSMLIMCT ILTNCVFMAQ
160 170 180 190 200
HDPPPWTKYV EYTFTAIYTF ESLVKILARG FCLHAFTFLR DPWNWLDFSV
210 220 230 240 250
IVMAYTTEFV DLGNVSALRT FRVLRALKTI SVISGLKTIV GALIQSVKKL
260 270 280 290 300
ADVMVLTVFC LSVFALIGLQ LFMGNLRHKC VRNFTELNGT NGSVEADGIV
310 320 330 340 350
WNSLDVYLND PANYLLKNGT TDVLLCGNSS DAGTCPEGYR CLKAGENPDH
360 370 380 390 400
GYTSFDSFAW AFLALFRLMT QDCWERLYQQ TLRSAGKIYM IFFMLVIFLG
410 420 430 440 450
SFYLVNLILA VVAMAYEEQN QATIAETEEK EKRFQEAMEM LKKEHEALTI
460 470 480 490 500
RGVDTVSRSS LEMSPLAPVT NHERRSKRRK RLSSGTEDGG DDRLPKSDSE
510 520 530 540 550
DGPRALNQLS LTHGLSRTSM RPRSSRGSIF TFRRRDQGSE ADFADDENST
560 570 580 590 600
AGESESHRTS LLVPWPLRRP STQGQPGFGT SAPGHVLNGK RNSTVDCNGV
610 620 630 640 650
VSLLGAGDAE ATSPGSHLLR PIVLDRPPDT TTPSEEPGGP QMLTPQAPCA
660 670 680 690 700
DGFEEPGARQ RALSAVSVLT SALEELEESH RKCPPCWNRF AQHYLIWECC
710 720 730 740 750
PLWMSIKQKV KFVVMDPFAD LTITMCIVLN TLFMALEHYN MTAEFEEMLQ
760 770 780 790 800
VGNLVFTGIF TAEMTFKIIA LDPYYYFQQG WNIFDSIIVI LSLMELGLSR
810 820 830 840 850
MGNLSVLRSF RLLRVFKLAK SWPTLNTLIK IIGNSVGALG NLTLVLAIIV
860 870 880 890 900
FIFAVVGMQL FGKNYSELRH RISDSGLLPR WHMMDFFHAF LIIFRILCGE
910 920 930 940 950
WIETMWDCME VSGQSLCLLV FLLVMVIGNL VVLNLFLALL LSSFSADNLT
960 970 980 990 1000
APDEDGEMNN LQLALARIQR GLRFVKRTTW DFCCGLLRRR PKKPAALATH
1010 1020 1030 1040 1050
SQLPSCIAAP RSPPPPEVEK APPARKETRF EEDKRPGQGT PGDTEPVCVP
1060 1070 1080 1090 1100
IAVAESDTDD QEEDEENSLG TEEEESSKQE SQVVSGGHEP PQEPRAWSQV
1110 1120 1130 1140 1150
SETTSSEAEA STSQADWQQE REAEPRAPGC GETPEDSYSE GSTADMTNTA
1160 1170 1180 1190 1200
DLLEQIPDLG EDVKDPEDCF TEGCVRRCPC CMVDTTQAPG KVWWRLRKTC
1210 1220 1230 1240 1250
YRIVEHSWFE TFIIFMILLS SGALAFEDIY LEERKTIKVL LEYADKMFTY
1260 1270 1280 1290 1300
VFVLEMLLKW VAYGFKKYFT NAWCWLDFLI VDVSLVSLVA NTLGFAEMGP
1310 1320 1330 1340 1350
IKSLRTLRAL RPLRALSRFE GMRVVVNALV GAIPSIMNVL LVCLIFWLIF
1360 1370 1380 1390 1400
SIMGVNLFAG KFGRCINQTE GDLPLNYTIV NNKSECESFN VTGELYWTKV
1410 1420 1430 1440 1450
KVNFDNVGAG YLALLQVATF KGWMDIMYAA VDSRGYEEQP QWEDNLYMYI
1460 1470 1480 1490 1500
YFVVFIIFGS FFTLNLFIGV IIDNFNQQKK KLGGQDIFMT EEQKKYYNAM
1510 1520 1530 1540 1550
KKLGSKKPQK PIPRPLNKYQ GFIFDIVTKQ AFDVTIMFLI CLNMVTMMVE
1560 1570 1580 1590 1600
TDDQSPEKVN ILAKINLLFV AIFTGECIVK MAALRHYYFT NSWNIFDFVV
1610 1620 1630 1640 1650
VILSIVGTVL SDIIQKYFFS PTLFRVIRLA RIGRILRLIR GAKGIRTLLF
1660 1670 1680 1690 1700
ALMMSLPALF NIGLLLFLVM FIYSIFGMAN FAYVKWEAGI DDMFNFQTFA
1710 1720 1730 1740 1750
NSMLCLFQIT TSAGWDGLLS PILNTGPPYC DPNLPNSNGS RGNCGSPAVG
1760 1770 1780 1790 1800
ILFFTTYIII SFLIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW
1810 1820 1830 1840 1850
EKFDPEATQF IEYLALSDFA DALSEPLRIA KPNQISLINM DLPMVSGDRI
1860 1870 1880 1890 1900
HCMDILFAFT KRVLGESGEM DALKIQMEEK FMAANPSKIS YEPITTTLRR
1910 1920 1930 1940 1950
KHEEVSATVI QRAFRRHLLQ RSVKHASFLF RQQAGSSGLS DEDAPEREGL
1960 1970 1980 1990 2000
IAYMMNENFS RRSGPLSSSS ISSTSFPPSY DSVTRATSDN LPVRASDYSR
2010
SEDLADFPPS PDRDRESIV
Length:2,019
Mass (Da):227,576
Last modified:July 27, 2011 - v2
Checksum:i5A3BC3C191859E79
GO
Isoform 2 (identifier: Q9JJV9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     206-211: TTEFVD → VSENIK

Show »
Length:2,019
Mass (Da):227,554
Checksum:iE382EEFD025079F9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti215V → L in BAE27966 (PubMed:16141072).Curated1
Sequence conflicti215V → L in BAE27800 (PubMed:16141072).Curated1
Sequence conflicti234S → P in BAE27966 (PubMed:16141072).Curated1
Sequence conflicti234S → P in BAE27800 (PubMed:16141072).Curated1
Sequence conflicti1008 – 1009AA → TT in CAB70096 (PubMed:11834499).Curated2
Sequence conflicti1078K → KQ in BAE27966 (PubMed:16141072).Curated1
Sequence conflicti1078K → KQ in BAE27800 (PubMed:16141072).Curated1
Sequence conflicti1133T → S in CAB70096 (PubMed:11834499).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037444206 – 211TTEFVD → VSENIK in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ271477 mRNA. Translation: CAB70096.1.
AK147254 mRNA. Translation: BAE27800.1.
AK147517 mRNA. Translation: BAE27966.1.
AC121922 Genomic DNA. No translation available.
AC171201 Genomic DNA. No translation available.
RefSeqiNP_001240789.1. NM_001253860.1.
NP_067519.2. NM_021544.4.
UniGeneiMm.103584.

Genome annotation databases

EnsembliENSMUST00000120420; ENSMUSP00000113272; ENSMUSG00000032511. [Q9JJV9-1]
GeneIDi20271.
KEGGimmu:20271.
UCSCiuc009sbc.2. mouse. [Q9JJV9-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSCN5A_MOUSE
AccessioniPrimary (citable) accession number: Q9JJV9
Secondary accession number(s): E9Q1D2, Q3UH91
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2009
Last sequence update: July 27, 2011
Last modified: August 30, 2017
This is version 122 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families