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P15389 (SCN5A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:Scn5a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length2019 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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. It is a tetrodotoxin-resistant Na+ channel isoform. Channel inactivation is regulated by intracellular calcium levels By similarity.

Subunit structure

Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2. Interacts with NEDD4, NEDD4L, WWP2 and GPD1L. Interacts with CALM. Interacts with FGF13; the interaction is direct and may regulate SNC5A density at membranes and function By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Strongly expressed in the heart. Also expressed in adult and fetal brain, spinal cord, testis, and at moderate levels in kidney, adrenal gland, lung, skeletal muscle, spleen, stomach and bladder. Isoform 2 is expressed in brain. Ref.3 Ref.4

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.

The IQ domain mediates association with calmodulin By similarity.

Post-translational modification

Regulated through phosphorylation by CaMK2D By similarity.

Ubiquitinated by NEDD4L; which promotes its endocytosis By similarity.

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.

Miscellaneous

Na+ channels in mammalian cardiac membrane have functional properties quite distinct from Na+ channels in nerve and skeletal muscle.

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily. [View classification]

Contains 1 IQ domain.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandCalmodulin-binding
Sodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMGlycoprotein
Methylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrainstem development

Inferred from expression pattern PubMed 22331407. Source: RGD

cellular response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

cerebellum development

Inferred from expression pattern PubMed 22331407. Source: RGD

odontogenesis of dentin-containing tooth

Inferred from expression pattern PubMed 21640979. Source: RGD

positive regulation of action potential

Inferred from mutant phenotype PubMed 22336133. Source: RGD

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 16331678. Source: RGD

positive regulation of heart rate

Inferred from mutant phenotype PubMed 17259145. Source: RGD

response to denervation involved in regulation of muscle adaptation

Inferred from mutant phenotype PubMed 22336133. Source: RGD

sodium ion transmembrane transport

Inferred from mutant phenotype PubMed 12562928. Source: RGD

sodium ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

telencephalon development

Inferred from expression pattern PubMed 22331407. Source: RGD

   Cellular_componentT-tubule

Inferred from direct assay PubMed 15579534. Source: BHF-UCL

integral component of membrane

Inferred from sequence or structural similarity. Source: UniProtKB

intercalated disc

Inferred from direct assay PubMed 15579534PubMed 18180363. Source: BHF-UCL

voltage-gated sodium channel complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionankyrin binding

Inferred from physical interaction PubMed 15579534. Source: BHF-UCL

fibroblast growth factor binding

Inferred from physical interaction PubMed 12401812. Source: RGD

voltage-gated sodium channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P15389-1)

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.
Isoform 2 (identifier: P15389-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1080-1132: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 20192019Sodium channel protein type 5 subunit alpha
PRO_0000048498

Regions

Topological domain1 – 127127Cytoplasmic Potential
Transmembrane128 – 15124Helical; Name=S1 of repeat I; Potential
Topological domain152 – 1598Extracellular Potential
Transmembrane160 – 17920Helical; Name=S2 of repeat I; Potential
Topological domain180 – 19213Cytoplasmic Potential
Transmembrane193 – 21119Helical; Name=S3 of repeat I; Potential
Topological domain212 – 2176Extracellular Potential
Transmembrane218 – 23720Helical; Voltage-sensor; Name=S4 of repeat I; Potential
Topological domain238 – 25316Cytoplasmic Potential
Transmembrane254 – 27724Helical; Name=S5 of repeat I; Potential
Topological domain278 – 390113Extracellular Potential
Transmembrane391 – 41626Helical; Name=S6 of repeat I; Potential
Topological domain417 – 712296Cytoplasmic Potential
Transmembrane713 – 73725Helical; Name=S1 of repeat II; Potential
Topological domain738 – 74811Extracellular Potential
Transmembrane749 – 77224Helical; Name=S2 of repeat II; Potential
Topological domain773 – 7808Cytoplasmic Potential
Transmembrane781 – 80020Helical; Name=S3 of repeat II; Potential
Topological domain801 – 8066Extracellular Potential
Transmembrane807 – 82620Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Topological domain827 – 84216Cytoplasmic Potential
Transmembrane843 – 86321Helical; Name=S5 of repeat II; Potential
Topological domain864 – 91653Extracellular Potential
Transmembrane917 – 94226Helical; Name=S6 of repeat II; Potential
Topological domain943 – 1202260Cytoplasmic Potential
Transmembrane1203 – 122624Helical; Name=S1 of repeat III; Potential
Topological domain1227 – 123913Extracellular Potential
Transmembrane1240 – 126526Helical; Name=S2 of repeat III; Potential
Topological domain1266 – 12716Cytoplasmic Potential
Transmembrane1272 – 129322Helical; Name=S3 of repeat III; Potential
Topological domain1294 – 12974Extracellular Potential
Transmembrane1298 – 131922Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Topological domain1320 – 133819Cytoplasmic Potential
Transmembrane1339 – 136123Helical; Name=S5 of repeat III; Potential
Topological domain1362 – 144584Extracellular Potential
Transmembrane1446 – 147227Helical; Name=S6 of repeat III; Potential
Topological domain1473 – 152553Cytoplasmic Potential
Transmembrane1526 – 154924Helical; Name=S1 of repeat IV; Potential
Topological domain1550 – 156011Extracellular Potential
Transmembrane1561 – 158424Helical; Name=S2 of repeat IV; Potential
Topological domain1585 – 15906Cytoplasmic Potential
Transmembrane1591 – 161424Helical; Name=S3 of repeat IV; Potential
Topological domain1615 – 162410Extracellular Potential
Transmembrane1625 – 164622Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Topological domain1647 – 166115Cytoplasmic Potential
Transmembrane1662 – 168423Helical; Name=S5 of repeat IV; Potential
Topological domain1685 – 174965Extracellular Potential
Transmembrane1750 – 177425Helical; Name=S6 of repeat IV; Potential
Topological domain1775 – 2019245Cytoplasmic Potential
Domain1903 – 193230IQ
Region1841 – 190363Interaction with FGF13 By similarity
Region1977 – 19804Interaction with NEDD4, NEDD4L and WWP2 By similarity

Amino acid modifications

Modified residue371Phosphoserine By similarity
Modified residue391Phosphothreonine By similarity
Modified residue4581Phosphoserine By similarity
Modified residue4611Phosphoserine By similarity
Modified residue4841Phosphoserine By similarity
Modified residue4851Phosphoserine By similarity
Modified residue4981Phosphoserine By similarity
Modified residue5111Phosphoserine By similarity
Modified residue5271Dimethylated arginine; alternate By similarity
Modified residue5271Omega-N-methylarginine; alternate By similarity
Modified residue5721Phosphoserine By similarity
Modified residue6651Phosphoserine By similarity
Modified residue6681Phosphoserine By similarity
Modified residue15051Phosphoserine; by PKC By similarity
Glycosylation2151N-linked (GlcNAc...) Potential
Glycosylation2841N-linked (GlcNAc...) Potential
Glycosylation2891N-linked (GlcNAc...) Potential
Glycosylation2921N-linked (GlcNAc...) Potential
Glycosylation3191N-linked (GlcNAc...) Potential
Glycosylation3291N-linked (GlcNAc...) Potential
Glycosylation7411N-linked (GlcNAc...) Potential
Glycosylation8041N-linked (GlcNAc...) Potential
Glycosylation8651N-linked (GlcNAc...) Potential
Glycosylation13671N-linked (GlcNAc...) Potential
Glycosylation13761N-linked (GlcNAc...) Potential
Glycosylation13821N-linked (GlcNAc...) Potential
Glycosylation13901N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1080 – 113253Missing in isoform 2.
VSP_037482

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: CFC3B03CEAE708AD

FASTA2,019227,367
        10         20         30         40         50         60 
MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE EAPRPQLDLQ 

        70         80         90        100        110        120 
ASKKLPDLYG NPPRELIGEP LEDLDPFYST QKTFIVLNKG KTIFRFSATN ALYVLSPFHP 

       130        140        150        160        170        180 
VRRAAVKILV HSLFSMLIMC TILTNCVFMA QHDPPPWTKY VEYTFTAIYT FESLVKILAR 

       190        200        210        220        230        240 
GFCLHAFTFL RDPWNWLDFS VIVMAYTTEF VDLGNVSALR TFRVLRALKT ISVISGLKTI 

       250        260        270        280        290        300 
VGALIQSVKK LADVMVLTVF CLSVFALIGL QLFMGNLRHK CVRNFTELNG TNGSVEADGL 

       310        320        330        340        350        360 
VWNSLDVYLN DPANYLLKNG TTDVLLCGNS SDAGTCPEGY RCLKAGENPD HGYTSFDSFA 

       370        380        390        400        410        420 
WAFLALFRLM TQDCWERLYQ QTLRSAGKIY MIFFMLVIFL GSFYLVNLIL AVVAMAYEEQ 

       430        440        450        460        470        480 
NQATIAETEE KEKRFQEAME MLKKEHEALT IRGVDTVSRS SLEMSPLAPV TNHERKSKRR 

       490        500        510        520        530        540 
KRLSSGTEDG GDDRLPKSDS EDGPRALNQL SLTHGLSRTS MRPRSSRGSI FTFRRRDQGS 

       550        560        570        580        590        600 
EADFADDENS TAGESESHRT SLLVPWPLRH PSAQGQPGPG ASAPGYVLNG KRNSTVDCNG 

       610        620        630        640        650        660 
VVSLLGAGDA EATSPGSYLL RPMVLDRPPD TTTPSEEPGG PQMLTPQAPC ADGFEEPGAR 

       670        680        690        700        710        720 
QRALSAVSVL TSALEELEES HRKCPPCWNR FAQHYLIWEC CPLWMSIKQK VKFVVMDPFA 

       730        740        750        760        770        780 
DLTITMCIVL NTLFMALEHY NMTAEFEEML QVGNLVFTGI FTAEMTFKII ALDPYYYFQQ 

       790        800        810        820        830        840 
GWNIFDSIIV ILSLMELGLS RMGNLSVLRS FRLLRVFKLA KSWPTLNTLI KIIGNSVGAL 

       850        860        870        880        890        900 
GNLTLVLAII VFIFAVVGMQ LFGKNYSELR HRISDSGLLP RWHMMDFFHA FLIIFRILCG 

       910        920        930        940        950        960 
EWIETMWDCM EVSGQSLCLL VFLLVMVIGN LVVLNLFLAL LLSSFSADNL TAPDEDGEMN 

       970        980        990       1000       1010       1020 
NLQLALARIQ RGLRFVKRTT WDFCCGILRR RPKKPAALAT HSQLPSCITA PRSPPPPEVE 

      1030       1040       1050       1060       1070       1080 
KVPPARKETR FEEDKRPGQG TPGDSEPVCV PIAVAESDTE DQEEDEENSL GTEEESSKQE 

      1090       1100       1110       1120       1130       1140 
SQVVSGGHEP YQEPRAWSQV SETTSSEAGA STSQADWQQE QKTEPQAPGC GETPEDSYSE 

      1150       1160       1170       1180       1190       1200 
GSTADMTNTA DLLEQIPDLG EDVKDPEDCF TEGCVRRCPC CMVDTTQSPG KVWWRLRKTC 

      1210       1220       1230       1240       1250       1260 
YRIVEHSWFE TFIIFMILLS SGALAFEDIY LEERKTIKVL LEYADKMFTY VFVLEMLLKW 

      1270       1280       1290       1300       1310       1320 
VAYGFKKYFT NAWCWLDFLI VDVSLVSLVA NTLGFAEMGP IKSLRTLRAL RPLRALSRFE 

      1330       1340       1350       1360       1370       1380 
GMRVVVNALV GAIPSIMNVL LVCLIFWLIF SIMGVNLFAG KFGRCINQTE GDLPLNYTIV 

      1390       1400       1410       1420       1430       1440 
NNKSECESFN VTGELYWTKV KVNFDNVGAG YLALLQVATF KGWMDIMYAA VDSRGYEEQP 

      1450       1460       1470       1480       1490       1500 
QWEDNLYMYI YFVVFIIFGS FFTLNLFIGV IIDNFNQQKK KLGGQDIFMT EEQKKYYNAM 

      1510       1520       1530       1540       1550       1560 
KKLGSKKPQK PIPRPLNKYQ GFIFDIVTKQ AFDVTIMFLI CLNMVTMMVE TDDQSPEKVN 

      1570       1580       1590       1600       1610       1620 
ILAKINLLFV AIFTGECIVK MAALRHYYFT NSWNIFDFVV VILSIVGTVL SDIIQKYFFS 

      1630       1640       1650       1660       1670       1680 
PTLFRVIRLA RIGRILRLIR GAKGIRTLLF ALMMSLPALF NIGLLLFLVM FIYSIFGMAN 

      1690       1700       1710       1720       1730       1740 
FAYVKWEAGI DDMFNFQTFA NSMLCLFQIT TSAGWDGLLS PILNTGPPYC DPNLPNSNGS 

      1750       1760       1770       1780       1790       1800 
RGNCGSPAVG ILFFTTYIII SFLIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW 

      1810       1820       1830       1840       1850       1860 
EKFDPEATQF IEYLALSDFA DALSEPLRIA KPNQISLINM DLPMVSGDRI HCMDILFAFT 

      1870       1880       1890       1900       1910       1920 
KRVLGESGEM DALKIQMEEK FMAANPSKIS YEPITTTLRR KHEEVSATVI QRAFRRHLLQ 

      1930       1940       1950       1960       1970       1980 
RSVKHASFLF RQQAGGSGLS DEDAPEREGL IAYMMNGNFS RRSAPLSSSS ISSTSFPPSY 

      1990       2000       2010 
DSVTRATSDN LPVRASDYSR SEDLADFPPS PDRDRESIV 

« Hide

Isoform 2 [UniParc].

Checksum: E4AC1FB7CF825647
Show »

FASTA1,966221,706

References

[1]"Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform."
Rogart R.B., Cribbs L.L., Muglia L.K., Kephart D.D., Kaiser M.W.
Proc. Natl. Acad. Sci. U.S.A. 86:8170-8174(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[2]"Characterisation of the novel voltage-gated Na+ channel rNav1.5a isolated from the rat hippocampal progenitor stem cell line HiB5."
Korsgaard M.P.G., Christophersen P., Ahring P.K., Olesen S.
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: Sprague-Dawley.
[3]"New variants of Nav1.5/SCN5A encode Na+ channels in the brain."
Wang J., Ou S.-W., Wang Y.-J., Zong Z.-H., Lin L., Kameyama M., Kameyama A.
J. Neurogenet. 22:57-75(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[4]"Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain."
Wang J., Ou S.-W., Wang Y.-J., Kameyama M., Kameyama A., Zong Z.-H.
Neurosci. Res. 64:339-347(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M27902 mRNA. Translation: AAA42114.1.
AF353637 mRNA. Translation: AAK38884.1.
PIRA33996.
RefSeqNP_001153634.1. NM_001160162.1.
NP_037257.1. NM_013125.2.
UniGeneRn.32074.

3D structure databases

ProteinModelPortalP15389.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-60063N.

Chemistry

BindingDBP15389.
ChEMBLCHEMBL3866.
GuidetoPHARMACOLOGY582.

PTM databases

PhosphoSiteP15389.

Proteomic databases

PaxDbP15389.
PRIDEP15389.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25665.
KEGGrno:25665.
UCSCRGD:3637. rat. [P15389-1]

Organism-specific databases

CTD6331.
RGD3637. Scn5a.

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231755.
HOVERGENHBG053100.
KOK04838.
PhylomeDBP15389.

Gene expression databases

GenevestigatorP15389.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR008053. Na_channel_a5su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PfamPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
PR01666. NACHANNEL5.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio607581.
PROP15389.

Entry information

Entry nameSCN5A_RAT
AccessionPrimary (citable) accession number: P15389
Secondary accession number(s): Q925G6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: April 16, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families