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P15389

- SCN5A_RAT

UniProt

P15389 - SCN5A_RAT

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Protein

Sodium channel protein type 5 subunit alpha

Gene
Scn5a
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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. It is a tetrodotoxin-resistant Na+ channel isoform. Channel inactivation is regulated by intracellular calcium levels By similarity.

GO - Molecular functioni

  1. ankyrin binding Source: BHF-UCL
  2. fibroblast growth factor binding Source: RGD
  3. protein binding Source: BHF-UCL
  4. voltage-gated sodium channel activity Source: UniProtKB

GO - Biological processi

  1. brainstem development Source: RGD
  2. cellular response to calcium ion Source: UniProtKB
  3. cerebellum development Source: RGD
  4. membrane depolarization during action potential Source: RefGenome
  5. neuronal action potential Source: RefGenome
  6. odontogenesis of dentin-containing tooth Source: RGD
  7. positive regulation of action potential Source: RGD
  8. positive regulation of epithelial cell proliferation Source: RGD
  9. positive regulation of heart rate Source: RGD
  10. response to denervation involved in regulation of muscle adaptation Source: RGD
  11. sodium ion transmembrane transport Source: RGD
  12. sodium ion transport Source: UniProtKB
  13. telencephalon development Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calmodulin-binding, Sodium

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
Gene namesi
Name:Scn5a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3637. Scn5a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 127127Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei128 – 15124Helical; Name=S1 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini152 – 1598Extracellular Reviewed prediction
Transmembranei160 – 17920Helical; Name=S2 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini180 – 19213Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei193 – 21119Helical; Name=S3 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini212 – 2176Extracellular Reviewed prediction
Transmembranei218 – 23720Helical; Voltage-sensor; Name=S4 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini238 – 25316Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei254 – 27724Helical; Name=S5 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini278 – 390113Extracellular Reviewed predictionAdd
BLAST
Transmembranei391 – 41626Helical; Name=S6 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini417 – 712296Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei713 – 73725Helical; Name=S1 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini738 – 74811Extracellular Reviewed predictionAdd
BLAST
Transmembranei749 – 77224Helical; Name=S2 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini773 – 7808Cytoplasmic Reviewed prediction
Transmembranei781 – 80020Helical; Name=S3 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini801 – 8066Extracellular Reviewed prediction
Transmembranei807 – 82620Helical; Voltage-sensor; Name=S4 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini827 – 84216Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei843 – 86321Helical; Name=S5 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini864 – 91653Extracellular Reviewed predictionAdd
BLAST
Transmembranei917 – 94226Helical; Name=S6 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini943 – 1202260Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1203 – 122624Helical; Name=S1 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1227 – 123913Extracellular Reviewed predictionAdd
BLAST
Transmembranei1240 – 126526Helical; Name=S2 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1266 – 12716Cytoplasmic Reviewed prediction
Transmembranei1272 – 129322Helical; Name=S3 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1294 – 12974Extracellular Reviewed prediction
Transmembranei1298 – 131922Helical; Voltage-sensor; Name=S4 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1320 – 133819Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1339 – 136123Helical; Name=S5 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1362 – 144584Extracellular Reviewed predictionAdd
BLAST
Transmembranei1446 – 147227Helical; Name=S6 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1473 – 152553Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1526 – 154924Helical; Name=S1 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1550 – 156011Extracellular Reviewed predictionAdd
BLAST
Transmembranei1561 – 158424Helical; Name=S2 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1585 – 15906Cytoplasmic Reviewed prediction
Transmembranei1591 – 161424Helical; Name=S3 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1615 – 162410Extracellular Reviewed prediction
Transmembranei1625 – 164622Helical; Voltage-sensor; Name=S4 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1647 – 166115Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1662 – 168423Helical; Name=S5 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1685 – 174965Extracellular Reviewed predictionAdd
BLAST
Transmembranei1750 – 177425Helical; Name=S6 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1775 – 2019245Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB
  2. intercalated disc Source: BHF-UCL
  3. T-tubule Source: BHF-UCL
  4. voltage-gated sodium channel complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 20192019Sodium channel protein type 5 subunit alphaPRO_0000048498Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei37 – 371Phosphoserine By similarity
Modified residuei39 – 391Phosphothreonine By similarity
Glycosylationi215 – 2151N-linked (GlcNAc...) Reviewed prediction
Glycosylationi284 – 2841N-linked (GlcNAc...) Reviewed prediction
Glycosylationi289 – 2891N-linked (GlcNAc...) Reviewed prediction
Glycosylationi292 – 2921N-linked (GlcNAc...) Reviewed prediction
Glycosylationi319 – 3191N-linked (GlcNAc...) Reviewed prediction
Glycosylationi329 – 3291N-linked (GlcNAc...) Reviewed prediction
Modified residuei458 – 4581Phosphoserine By similarity
Modified residuei461 – 4611Phosphoserine By similarity
Modified residuei484 – 4841Phosphoserine By similarity
Modified residuei485 – 4851Phosphoserine By similarity
Modified residuei498 – 4981Phosphoserine By similarity
Modified residuei511 – 5111Phosphoserine By similarity
Modified residuei527 – 5271Dimethylated arginine; alternate By similarity
Modified residuei527 – 5271Omega-N-methylarginine; alternate By similarity
Modified residuei572 – 5721Phosphoserine By similarity
Modified residuei665 – 6651Phosphoserine By similarity
Modified residuei668 – 6681Phosphoserine By similarity
Glycosylationi741 – 7411N-linked (GlcNAc...) Reviewed prediction
Glycosylationi804 – 8041N-linked (GlcNAc...) Reviewed prediction
Glycosylationi865 – 8651N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1367 – 13671N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1376 – 13761N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1382 – 13821N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1390 – 13901N-linked (GlcNAc...) Reviewed prediction
Modified residuei1505 – 15051Phosphoserine; by PKC By similarity

Post-translational modificationi

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.

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP15389.
PRIDEiP15389.

PTM databases

PhosphoSiteiP15389.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

GenevestigatoriP15389.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

DIPiDIP-60063N.

Structurei

3D structure databases

ProteinModelPortaliP15389.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1903 – 193230IQAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1841 – 190363Interaction with FGF13 By similarityAdd
BLAST
Regioni1977 – 19804Interaction with NEDD4, NEDD4L and WWP2 By similarity

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.
The IQ domain mediates association with calmodulin By similarity.

Sequence similaritiesi

Contains 1 IQ domain.

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1226.
HOGENOMiHOG000231755.
HOVERGENiHBG053100.
KOiK04838.
PhylomeDBiP15389.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. 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]
PfamiPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
PR01666. NACHANNEL5.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P15389-1) [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

MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE     50
EAPRPQLDLQ ASKKLPDLYG NPPRELIGEP LEDLDPFYST QKTFIVLNKG 100
KTIFRFSATN ALYVLSPFHP VRRAAVKILV HSLFSMLIMC TILTNCVFMA 150
QHDPPPWTKY VEYTFTAIYT FESLVKILAR GFCLHAFTFL RDPWNWLDFS 200
VIVMAYTTEF VDLGNVSALR TFRVLRALKT ISVISGLKTI VGALIQSVKK 250
LADVMVLTVF CLSVFALIGL QLFMGNLRHK CVRNFTELNG TNGSVEADGL 300
VWNSLDVYLN DPANYLLKNG TTDVLLCGNS SDAGTCPEGY RCLKAGENPD 350
HGYTSFDSFA WAFLALFRLM TQDCWERLYQ QTLRSAGKIY MIFFMLVIFL 400
GSFYLVNLIL AVVAMAYEEQ NQATIAETEE KEKRFQEAME MLKKEHEALT 450
IRGVDTVSRS SLEMSPLAPV TNHERKSKRR KRLSSGTEDG GDDRLPKSDS 500
EDGPRALNQL SLTHGLSRTS MRPRSSRGSI FTFRRRDQGS EADFADDENS 550
TAGESESHRT SLLVPWPLRH PSAQGQPGPG ASAPGYVLNG KRNSTVDCNG 600
VVSLLGAGDA EATSPGSYLL RPMVLDRPPD TTTPSEEPGG PQMLTPQAPC 650
ADGFEEPGAR QRALSAVSVL TSALEELEES HRKCPPCWNR FAQHYLIWEC 700
CPLWMSIKQK VKFVVMDPFA DLTITMCIVL NTLFMALEHY NMTAEFEEML 750
QVGNLVFTGI FTAEMTFKII ALDPYYYFQQ GWNIFDSIIV ILSLMELGLS 800
RMGNLSVLRS FRLLRVFKLA KSWPTLNTLI KIIGNSVGAL GNLTLVLAII 850
VFIFAVVGMQ LFGKNYSELR HRISDSGLLP RWHMMDFFHA FLIIFRILCG 900
EWIETMWDCM EVSGQSLCLL VFLLVMVIGN LVVLNLFLAL LLSSFSADNL 950
TAPDEDGEMN NLQLALARIQ RGLRFVKRTT WDFCCGILRR RPKKPAALAT 1000
HSQLPSCITA PRSPPPPEVE KVPPARKETR FEEDKRPGQG TPGDSEPVCV 1050
PIAVAESDTE DQEEDEENSL GTEEESSKQE SQVVSGGHEP YQEPRAWSQV 1100
SETTSSEAGA STSQADWQQE QKTEPQAPGC GETPEDSYSE GSTADMTNTA 1150
DLLEQIPDLG EDVKDPEDCF TEGCVRRCPC CMVDTTQSPG KVWWRLRKTC 1200
YRIVEHSWFE TFIIFMILLS SGALAFEDIY LEERKTIKVL LEYADKMFTY 1250
VFVLEMLLKW VAYGFKKYFT NAWCWLDFLI VDVSLVSLVA NTLGFAEMGP 1300
IKSLRTLRAL RPLRALSRFE GMRVVVNALV GAIPSIMNVL LVCLIFWLIF 1350
SIMGVNLFAG KFGRCINQTE GDLPLNYTIV NNKSECESFN VTGELYWTKV 1400
KVNFDNVGAG YLALLQVATF KGWMDIMYAA VDSRGYEEQP QWEDNLYMYI 1450
YFVVFIIFGS FFTLNLFIGV IIDNFNQQKK KLGGQDIFMT EEQKKYYNAM 1500
KKLGSKKPQK PIPRPLNKYQ GFIFDIVTKQ AFDVTIMFLI CLNMVTMMVE 1550
TDDQSPEKVN ILAKINLLFV AIFTGECIVK MAALRHYYFT NSWNIFDFVV 1600
VILSIVGTVL SDIIQKYFFS PTLFRVIRLA RIGRILRLIR GAKGIRTLLF 1650
ALMMSLPALF NIGLLLFLVM FIYSIFGMAN FAYVKWEAGI DDMFNFQTFA 1700
NSMLCLFQIT TSAGWDGLLS PILNTGPPYC DPNLPNSNGS RGNCGSPAVG 1750
ILFFTTYIII SFLIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW 1800
EKFDPEATQF IEYLALSDFA DALSEPLRIA KPNQISLINM DLPMVSGDRI 1850
HCMDILFAFT KRVLGESGEM DALKIQMEEK FMAANPSKIS YEPITTTLRR 1900
KHEEVSATVI QRAFRRHLLQ RSVKHASFLF RQQAGGSGLS DEDAPEREGL 1950
IAYMMNGNFS RRSAPLSSSS ISSTSFPPSY DSVTRATSDN LPVRASDYSR 2000
SEDLADFPPS PDRDRESIV 2019
Length:2,019
Mass (Da):227,367
Last modified:April 1, 1990 - v1
Checksum:iCFC3B03CEAE708AD
GO
Isoform 2 (identifier: P15389-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:1,966
Mass (Da):221,706
Checksum:iE4AC1FB7CF825647
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1080 – 113253Missing in isoform 2. VSP_037482Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M27902 mRNA. Translation: AAA42114.1.
AF353637 mRNA. Translation: AAK38884.1.
PIRiA33996.
RefSeqiNP_001153634.1. NM_001160162.1. [P15389-2]
NP_037257.1. NM_013125.2. [P15389-1]
UniGeneiRn.32074.

Genome annotation databases

GeneIDi25665.
KEGGirno:25665.
UCSCiRGD:3637. rat. [P15389-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M27902 mRNA. Translation: AAA42114.1 .
AF353637 mRNA. Translation: AAK38884.1 .
PIRi A33996.
RefSeqi NP_001153634.1. NM_001160162.1. [P15389-2 ]
NP_037257.1. NM_013125.2. [P15389-1 ]
UniGenei Rn.32074.

3D structure databases

ProteinModelPortali P15389.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-60063N.

Chemistry

BindingDBi P15389.
ChEMBLi CHEMBL3866.
GuidetoPHARMACOLOGYi 582.

PTM databases

PhosphoSitei P15389.

Proteomic databases

PaxDbi P15389.
PRIDEi P15389.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25665.
KEGGi rno:25665.
UCSCi RGD:3637. rat. [P15389-1 ]

Organism-specific databases

CTDi 6331.
RGDi 3637. Scn5a.

Phylogenomic databases

eggNOGi COG1226.
HOGENOMi HOG000231755.
HOVERGENi HBG053100.
KOi K04838.
PhylomeDBi P15389.

Miscellaneous databases

NextBioi 607581.
PROi P15389.

Gene expression databases

Genevestigatori P15389.

Family and domain databases

Gene3Di 1.20.120.350. 4 hits.
InterProi IPR027359. 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 ]
Pfami PF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view ]
PRINTSi PR00170. NACHANNEL.
PR01666. NACHANNEL5.
SMARTi SM00015. IQ. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiSCN5A_RAT
AccessioniPrimary (citable) accession number: P15389
Secondary accession number(s): Q925G6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: June 11, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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