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O88420 (SCN8A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 102. 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 8 subunit alpha
Alternative name(s):
Peripheral nerve protein type 4
Short name=PN4
Sodium channel 6
Short name=NaCh6
Sodium channel protein type VIII subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.6
Gene names
Name:Scn8a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1978 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Subunit structure

Interacts with NEDD4 and NEDD4L By similarity. Interacts with FGF13; may regulate SCN8A activity. Ref.2

Subcellular location

Membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Isoform 1 is highly expressed in brain, moderately in spinal cord, and at low levels in dorsal root ganglia, nodose ganglia and superior cervical ganglia. Not detected in sciatic nerve and non-neuronal tissues. Isoform 2 is hardly detectable, if at all, in brain, expressed at low levels in spinal cord and at highest levels in dorsal root ganglia. Ref.1

Post-translational modification

May be ubiquitinated by NEDD4L; which would promote its endocytosis By similarity.

Phosphorylation at Ser-1495 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents By similarity.

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A 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
   LigandATP-binding
Nucleotide-binding
Sodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmembrane depolarization during action potential

Inferred from Biological aspect of Ancestor. Source: RefGenome

myelination

Inferred from expression pattern PubMed 16652168. Source: BHF-UCL

neuronal action potential

Inferred from direct assay PubMed 15664695PubMed 15917456. Source: RGD

peripheral nervous system development

Inferred from expression pattern PubMed 16652168. Source: BHF-UCL

sodium ion transmembrane transport

Inferred from direct assay PubMed 15664695Ref.1. Source: GOC

sodium ion transport

Inferred from direct assay Ref.1. Source: RGD

   Cellular_componentaxon initial segment

Inferred from direct assay PubMed 11724816. Source: BHF-UCL

integral component of membrane

Inferred from direct assay Ref.1. Source: RGD

node of Ranvier

Inferred from direct assay PubMed 16652168. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 17273863. Source: RGD

voltage-gated sodium channel complex

Inferred from direct assay PubMed 15664695. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.2. Source: UniProtKB

sodium ion binding

Inferred from direct assay PubMed 15664695. Source: RGD

voltage-gated sodium channel activity

Inferred from direct assay PubMed 15664695Ref.1. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88420-1)

Also known as: PN4;

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: O88420-2)

Also known as: PN4a;

The sequence of this isoform differs from the canonical sequence as follows:
     664-664: E → EVKIDKAATDS
Note: May be due to competing donor splice site.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19781978Sodium channel protein type 8 subunit alpha
PRO_0000390890

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; Name=S4 of repeat I; Potential
Topological domain238 – 25215Cytoplasmic Potential
Transmembrane253 – 27725Helical; Name=S5 of repeat I; Potential
Topological domain278 – 387110Extracellular Potential
Transmembrane388 – 41326Helical; Name=S6 of repeat I; Potential
Topological domain414 – 745332Cytoplasmic Potential
Transmembrane746 – 77025Helical; Name=S1 of repeat II; Potential
Topological domain771 – 78111Extracellular Potential
Transmembrane782 – 80524Helical; Name=S2 of repeat II; Potential
Topological domain806 – 8138Cytoplasmic Potential
Transmembrane814 – 83320Helical; Name=S3 of repeat II; Potential
Topological domain834 – 8396Extracellular Potential
Transmembrane840 – 86021Helical; Name=S4 of repeat II; Potential
Topological domain861 – 87515Cytoplasmic Potential
Transmembrane876 – 89621Helical; Name=S5 of repeat II; Potential
Topological domain897 – 94953Extracellular Potential
Transmembrane950 – 97526Helical; Name=S6 of repeat II; Potential
Topological domain976 – 1191216Cytoplasmic Potential
Transmembrane1192 – 121524Helical; Name=S1 of repeat III; Potential
Topological domain1216 – 122813Extracellular Potential
Transmembrane1229 – 125426Helical; Name=S2 of repeat III; Potential
Topological domain1255 – 12606Cytoplasmic Potential
Transmembrane1261 – 128222Helical; Name=S3 of repeat III; Potential
Topological domain1283 – 12864Extracellular Potential
Transmembrane1287 – 130822Helical; Name=S4 of repeat III; Potential
Topological domain1309 – 132719Cytoplasmic Potential
Transmembrane1328 – 134922Helical; Name=S5 of repeat III; Potential
Topological domain1350 – 143586Extracellular Potential
Transmembrane1436 – 146227Helical; Name=S6 of repeat III; Potential
Topological domain1463 – 151553Cytoplasmic Potential
Transmembrane1516 – 153924Helical; Name=S1 of repeat IV; Potential
Topological domain1540 – 155011Extracellular Potential
Transmembrane1551 – 157424Helical; Name=S2 of repeat IV; Potential
Topological domain1575 – 15806Cytoplasmic Potential
Transmembrane1581 – 160424Helical; Name=S3 of repeat IV; Potential
Topological domain1605 – 161410Extracellular Potential
Transmembrane1615 – 163622Helical; Name=S4 of repeat IV; Potential
Topological domain1637 – 165115Cytoplasmic Potential
Transmembrane1652 – 167423Helical; Name=S5 of repeat IV; Potential
Topological domain1675 – 173965Extracellular Potential
Transmembrane1740 – 176425Helical; Name=S6 of repeat IV; Potential
Topological domain1765 – 1978214Cytoplasmic Potential
Repeat114 – 442329I
Repeat733 – 1005273II
Repeat1178 – 1493316III
Repeat1502 – 1799298IV
Domain1893 – 192230IQ
Nucleotide binding891 – 8988ATP Potential

Amino acid modifications

Modified residue14951Phosphoserine; by PKC By similarity
Glycosylation2151N-linked (GlcNAc...) Potential
Glycosylation2891N-linked (GlcNAc...) Potential
Glycosylation2951N-linked (GlcNAc...) Potential
Glycosylation3081N-linked (GlcNAc...) Potential
Glycosylation3261N-linked (GlcNAc...) Potential
Glycosylation13561N-linked (GlcNAc...) Potential
Glycosylation13701N-linked (GlcNAc...) Potential
Glycosylation13811N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence6641E → EVKIDKAATDS in isoform 2.
VSP_038652

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PN4) [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 9160843C5935B88B

FASTA1,978225,159
        10         20         30         40         50         60 
MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 

        70         80         90        100        110        120 
AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 

       130        140        150        160        170        180 
IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPEWSKN VEYTFTGIYT FESLVKIIAR 

       190        200        210        220        230        240 
GFCIDGFTFL RDPWNWLDFS VIMMAYVTEF VDLGNVSALR TFRVLRALKT ISVIPGLKTI 

       250        260        270        280        290        300 
VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTRGF 

       310        320        330        340        350        360 
DWEEYINNKT NFYMVPGMLE PLLCGNSSDA GQCPEGFQCM KAGRNPNYGY TSFDTFSWAF 

       370        380        390        400        410        420 
LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 

       430        440        450        460        470        480 
TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEDG VGSPRSSSEL 

       490        500        510        520        530        540 
SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 

       550        560        570        580        590        600 
SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 

       610        620        630        640        650        660 
LFIPIRARER RSSYSGYSGY SQCSRSSRIF PSLRRSVKRN STVDCNGVVS LIGPGSHIGR 

       670        680        690        700        710        720 
LLPEATTEVE IKKKGPGSLL VSMDQLASYG RKDRINSIMS VVTNTLVEEL EESQRKCPPC 

       730        740        750        760        770        780 
WYKFANTFLI WECHPYWIKL KEIVNLIVMD PFVDLAITIC IVLNTLFMAM EHHPMTPQFE 

       790        800        810        820        830        840 
HVLAVGNLVF TGIFTAEMFL KLIAMDPYYY FQEGWNIFDG FIVSLSLMEL SLADVEGLSV 

       850        860        870        880        890        900 
LRSFRLLRVF KLAKSWPTLN MLIKIIGNSV GALGNLTLVL AIIVFIFAVV GMQLFGKSYK 

       910        920        930        940        950        960 
ECVCKINQEC KLPRWHMNDF FHSFLIVFRV LCGEWIETMW DCMEVAGQAM CLIVFMMVMV 

       970        980        990       1000       1010       1020 
IGNLVVLNLF LALLLSSFSA DNLAATDDDG EMNNLQISVI RIKKGVAWTK VKVHAFMQAH 

      1030       1040       1050       1060       1070       1080 
FKQREADEVK PLDELYEKKA NCIANHTGVD IHRNGDFQKN GNGTTSGIGS SVEKYIIDED 

      1090       1100       1110       1120       1130       1140 
HMSFINNPNL TVRVPIAVGE SDFENLNTED VSSESDPEGS KDKLDDTSSS EGSTIDIKPE 

      1150       1160       1170       1180       1190       1200 
VEEVPVEQPE EYLDPDACFT EGCVQRFKCC QVNIEEGLGK SWWILRKTCF LIVEHNWFET 

      1210       1220       1230       1240       1250       1260 
FIIFMILLSS GALAFEDIYI EQRKTIRTIL EYADKVFTYI FILEMLLKWT AYGFVKFFTN 

      1270       1280       1290       1300       1310       1320 
AWCWLDFLIV AVSLVSLIAN ALGYSELGAI KSLRTLRALR PLRALSRFEG MRVVVNALVG 

      1330       1340       1350       1360       1370       1380 
AIPSIMNVLL VCLIFWLIFS IMGVNLFAGK YHYCFNETSE IRFEIDIVNN KTDCEKLMEG 

      1390       1400       1410       1420       1430       1440 
NSTEIRWKNV KINFDNVGAG YLALLQVATF KGWMDIMYAA VDSRKPDEQP DYEGNIYMYI 

      1450       1460       1470       1480       1490       1500 
YFVIFIIFGS FFTLNLFIGV IIDNFNQQKK KFGGQDIFMT EEQKKYYNAM KKLGSKKPQK 

      1510       1520       1530       1540       1550       1560 
PIPRPLNKIQ GIVFDFVTQQ AFDIVIMMLI CLNMVTMMVE TDTQSKQMEN ILYWINLVFV 

      1570       1580       1590       1600       1610       1620 
IFFTCECVLK MFALRHYYFT IGWNIFDFVV VILSIVGMFL ADIIEKYFVS PTLFRVIRLA 

      1630       1640       1650       1660       1670       1680 
RIGRILRLIK GAKGIRTLLF ALMMSLPALF NIGLLLFLVM FIFSIFGMSN FAYVKHEAGI 

      1690       1700       1710       1720       1730       1740 
DDMFNFETFG NSMICLFQIT TSAGWDGLLL PILNRPPDCS LDKEHPGSGF KGDCGNPSVG 

      1750       1760       1770       1780       1790       1800 
IFFFVSYIII SFLIVVNMYI AIILENFSVA TEESADPLSE DDFETFYEIW EKFDPDATQF 

      1810       1820       1830       1840       1850       1860 
IEYCKLADFA DALEHPLRVP KPNTIELIAM DLPMVSGDRI HCLDILFAFT KRVLGDSGEL 

      1870       1880       1890       1900       1910       1920 
DILRQQMEER FVASNPSKVS YEPITTTLRR KQEEVSAVVL QRAYRGHLAR RGFICRKMAS 

      1930       1940       1950       1960       1970 
NKLENGGTHR DKKESTPSTA SLPSYDSVTK PDKEKQQRAE EGRRERAKRQ KEVRESKC 

« Hide

Isoform 2 (PN4a) [UniParc].

Checksum: C1F7D87FDC266C8F
Show »

FASTA1,988226,188

References

[1]"Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia."
Dietrich P.S., McGivern J.G., Delgado S.G., Koch B.D., Eglen R.M., Hunter J.C., Sangameswaran L.
J. Neurochem. 70:2262-2272(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Tissue: Spinal ganglion.
[2]"Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons."
Wittmack E.K., Rush A.M., Craner M.J., Goldfarb M., Waxman S.G., Dib-Hajj S.D.
J. Neurosci. 24:6765-6775(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGF13.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF049239 mRNA. Translation: AAC26014.1.
AF049240 mRNA. Translation: AAC26015.1.
RefSeqNP_062139.2. NM_019266.2. [O88420-1]
UniGeneRn.91216.

3D structure databases

ProteinModelPortalO88420.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248327. 1 interaction.

Chemistry

BindingDBO88420.
ChEMBLCHEMBL2752.
GuidetoPHARMACOLOGY583.

PTM databases

PhosphoSiteO88420.

Proteomic databases

PaxDbO88420.
PRIDEO88420.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID29710.
KEGGrno:29710.
UCSCRGD:3638. rat. [O88420-1]

Organism-specific databases

CTD6334.
RGD3638. Scn8a.

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231755.
HOVERGENHBG053100.
KOK04840.
PhylomeDBO88420.

Gene expression databases

GenevestigatorO88420.

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.
IPR008054. Na_channel_a8su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PfamPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF00612. IQ. 1 hit.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
PR01667. NACHANNEL8.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
PROSITEPS50096. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio610139.
PROO88420.

Entry information

Entry nameSCN8A_RAT
AccessionPrimary (citable) accession number: O88420
Secondary accession number(s): O88421
Entry history
Integrated into UniProtKB/Swiss-Prot: January 19, 2010
Last sequence update: November 1, 1998
Last modified: June 11, 2014
This is version 102 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