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UniProtKB - O88420 (SCN8A_RAT)

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Protein

Sodium channel protein type 8 subunit alpha

Gene

Scn8a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi891 – 898ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • sodium ion binding Source: RGD
  • voltage-gated ion channel activity Source: UniProtKB-KW
  • voltage-gated sodium channel activity Source: RGD
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • membrane depolarization during action potential Source: GO_Central
  • myelination Source: BHF-UCL
  • neuronal action potential Source: RGD
  • peripheral nervous system development Source: BHF-UCL
  • regulation of ion transmembrane transport Source: UniProtKB-KW
  • sodium ion transport Source: RGD
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionIon channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Sodium transport, Transport
LigandATP-binding, Nucleotide-binding, Sodium

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Scn8a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3638 Scn8a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 132CytoplasmicCuratedAdd BLAST132
Transmembranei133 – 151Helical; Name=S1 of repeat IBy similarityAdd BLAST19
Topological domaini152 – 158ExtracellularCurated7
Transmembranei159 – 179Helical; Name=S2 of repeat IBy similarityAdd BLAST21
Topological domaini180 – 193CytoplasmicCuratedAdd BLAST14
Transmembranei194 – 211Helical; Name=S3 of repeat IBy similarityAdd BLAST18
Topological domaini212 – 217ExtracellularCurated6
Transmembranei218 – 234Helical; Name=S4 of repeat IBy similarityAdd BLAST17
Topological domaini235 – 253CytoplasmicCuratedAdd BLAST19
Transmembranei254 – 273Helical; Name=S5 of repeat IBy similarityAdd BLAST20
Topological domaini274 – 355ExtracellularCuratedAdd BLAST82
Intramembranei356 – 380Pore-formingBy similarityAdd BLAST25
Topological domaini381 – 387ExtracellularCurated7
Transmembranei388 – 408Helical; Name=S6 of repeat IBy similarityAdd BLAST21
Topological domaini409 – 751CytoplasmicCuratedAdd BLAST343
Transmembranei752 – 770Helical; Name=S1 of repeat IIBy similarityAdd BLAST19
Topological domaini771 – 781ExtracellularCuratedAdd BLAST11
Transmembranei782 – 801Helical; Name=S2 of repeat IIBy similarityAdd BLAST20
Topological domaini802 – 815CytoplasmicCuratedAdd BLAST14
Transmembranei816 – 835Helical; Name=S3 of repeat IIBy similarityAdd BLAST20
Topological domaini836 – 837ExtracellularCurated2
Transmembranei838 – 855Helical; Name=S4 of repeat IIBy similarityAdd BLAST18
Topological domaini856 – 871CytoplasmicCuratedAdd BLAST16
Transmembranei872 – 890Helical; Name=S5 of repeat IIBy similarityAdd BLAST19
Topological domaini891 – 919ExtracellularCuratedAdd BLAST29
Intramembranei920 – 940Pore-formingBy similarityAdd BLAST21
Topological domaini941 – 953ExtracellularCuratedAdd BLAST13
Transmembranei954 – 974Helical; Name=S6 of repeat IIBy similarityAdd BLAST21
Topological domaini975 – 1197CytoplasmicCuratedAdd BLAST223
Transmembranei1198 – 1215Helical; Name=S1 of repeat IIIBy similarityAdd BLAST18
Topological domaini1216 – 1228ExtracellularCuratedAdd BLAST13
Transmembranei1229 – 1247Helical; Name=S2 of repeat IIIBy similarityAdd BLAST19
Topological domaini1248 – 1261CytoplasmicCuratedAdd BLAST14
Transmembranei1262 – 1280Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini1281 – 1288ExtracellularCurated8
Transmembranei1289 – 1307Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini1308 – 1324CytoplasmicCuratedAdd BLAST17
Transmembranei1325 – 1344Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini1345 – 1397ExtracellularCuratedAdd BLAST53
Intramembranei1398 – 1419Pore-formingBy similarityAdd BLAST22
Topological domaini1420 – 1436ExtracellularCuratedAdd BLAST17
Transmembranei1437 – 1458Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1459 – 1521CytoplasmicCuratedAdd BLAST63
Transmembranei1522 – 1539Helical; Name=S1 of repeat IVBy similarityAdd BLAST18
Topological domaini1540 – 1550ExtracellularCuratedAdd BLAST11
Transmembranei1551 – 1569Helical; Name=S2 of repeat IVBy similarityAdd BLAST19
Topological domaini1570 – 1581CytoplasmicCuratedAdd BLAST12
Transmembranei1582 – 1599Helical; Name=S3 of repeat IVBy similarityAdd BLAST18
Topological domaini1600 – 1612ExtracellularCuratedAdd BLAST13
Transmembranei1613 – 1629Helical; Name=S4 of repeat IVBy similarityAdd BLAST17
Topological domaini1630 – 1648CytoplasmicCuratedAdd BLAST19
Transmembranei1649 – 1666Helical; Name=S5 of repeat IVBy similarityAdd BLAST18
Topological domaini1667 – 1688ExtracellularCuratedAdd BLAST22
Intramembranei1689 – 1711Pore-formingBy similarityAdd BLAST23
Topological domaini1712 – 1740ExtracellularCuratedAdd BLAST29
Transmembranei1741 – 1763Helical; Name=S6 of repeat IVBy similarityAdd BLAST23
Topological domaini1764 – 1978CytoplasmicCuratedAdd BLAST215

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2752
GuidetoPHARMACOLOGYi583

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003908901 – 1978Sodium channel protein type 8 subunit alphaAdd BLAST1978

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi215N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi281 ↔ 333By similarity
Glycosylationi289N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi295N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi308N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi326N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei518PhosphoserineCombined sources1
Modified residuei520PhosphoserineCombined sources1
Disulfide bondi902Interchain; with SCN2B or SCN4BBy similarity
Disulfide bondi902Interchain; 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 bondi942 ↔ 951By similarity
Glycosylationi1356N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1370N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1381N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1495Phosphoserine; by PKCBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO88420
PRIDEiO88420

PTM databases

CarbonylDBiO88420
iPTMnetiO88420
PhosphoSitePlusiO88420

Expressioni

Tissue specificityi

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.1 Publication

Interactioni

Subunit structurei

The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B). Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by disulfide bonds. Interacts with NEDD4 and NEDD4L (By similarity). Interacts with FGF13 (PubMed:15282281). Interacts with FGF14, GBG3, GBB2 and SCN1B (By similarity). Interacts with the conotoxin GVIIJ (PubMed:24497506).By similarity2 Publications

Protein-protein interaction databases

BioGridi248327, 1 interactor
STRINGi10116.ENSRNOP00000008160

Chemistry databases

BindingDBiO88420

Structurei

3D structure databases

ProteinModelPortaliO88420
SMRiO88420
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati114 – 442ICuratedAdd BLAST329
Repeati733 – 1005IICuratedAdd BLAST273
Repeati1178 – 1493IIICuratedAdd BLAST316
Repeati1502 – 1799IVCuratedAdd BLAST298
Domaini1893 – 1922IQPROSITE-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

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily. [View classification]Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2301 Eukaryota
ENOG410XNP6 LUCA
HOGENOMiHOG000231755
HOVERGENiHBG053100
InParanoidiO88420
KOiK04840
PhylomeDBiO88420

Family and domain databases

Gene3Di1.20.120.350, 4 hits
InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR000048 IQ_motif_EF-hand-BS
IPR008054 Na_channel_a8su
IPR001696 Na_channel_asu
IPR010526 Na_trans_assoc
IPR024583 Na_trans_cytopl
IPR027359 Volt_channel_dom_sf
PfamiView protein in Pfam
PF00520 Ion_trans, 4 hits
PF00612 IQ, 1 hit
PF06512 Na_trans_assoc, 1 hit
PF11933 Na_trans_cytopl, 1 hit
PRINTSiPR00170 NACHANNEL
PR01667 NACHANNEL8
SMARTiView protein in SMART
SM00015 IQ, 1 hit
PROSITEiView protein in PROSITE
PS50096 IQ, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O88420-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED 
        60         70         80         90        100
SKPKPNSDLE AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG 
       110        120        130        140        150
KTLFRFSATP ALYILSPFNL IRRIAIKILI HSVFSMIIMC TILTNCVFMT 
       160        170        180        190        200
FSNPPEWSKN VEYTFTGIYT FESLVKIIAR GFCIDGFTFL RDPWNWLDFS 
       210        220        230        240        250
VIMMAYVTEF VDLGNVSALR TFRVLRALKT ISVIPGLKTI VGALIQSVKK 
       260        270        280        290        300
LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTRGF 
       310        320        330        340        350
DWEEYINNKT NFYMVPGMLE PLLCGNSSDA GQCPEGFQCM KAGRNPNYGY 
       360        370        380        390        400
TSFDTFSWAF LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF 
       410        420        430        440        450
YLVNLILAVV AMAYEEQNQA TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA 
       460        470        480        490        500
MATSAGTVSE DAIEEEGEDG VGSPRSSSEL SKLSSKSAKE RRNRRKKRKQ 
       510        520        530        540        550
KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF SIMNQSLLSI 
       560        570        580        590        600
PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 
       610        620        630        640        650
LFIPIRARER RSSYSGYSGY SQCSRSSRIF PSLRRSVKRN STVDCNGVVS 
       660        670        680        690        700
LIGPGSHIGR LLPEATTEVE IKKKGPGSLL VSMDQLASYG RKDRINSIMS 
       710        720        730        740        750
VVTNTLVEEL EESQRKCPPC WYKFANTFLI WECHPYWIKL KEIVNLIVMD 
       760        770        780        790        800
PFVDLAITIC IVLNTLFMAM EHHPMTPQFE HVLAVGNLVF TGIFTAEMFL 
       810        820        830        840        850
KLIAMDPYYY FQEGWNIFDG FIVSLSLMEL SLADVEGLSV LRSFRLLRVF 
       860        870        880        890        900
KLAKSWPTLN MLIKIIGNSV GALGNLTLVL AIIVFIFAVV GMQLFGKSYK 
       910        920        930        940        950
ECVCKINQEC KLPRWHMNDF FHSFLIVFRV LCGEWIETMW DCMEVAGQAM 
       960        970        980        990       1000
CLIVFMMVMV IGNLVVLNLF LALLLSSFSA DNLAATDDDG EMNNLQISVI 
      1010       1020       1030       1040       1050
RIKKGVAWTK VKVHAFMQAH FKQREADEVK PLDELYEKKA NCIANHTGVD 
      1060       1070       1080       1090       1100
IHRNGDFQKN GNGTTSGIGS SVEKYIIDED HMSFINNPNL TVRVPIAVGE 
      1110       1120       1130       1140       1150
SDFENLNTED VSSESDPEGS KDKLDDTSSS EGSTIDIKPE VEEVPVEQPE 
      1160       1170       1180       1190       1200
EYLDPDACFT EGCVQRFKCC QVNIEEGLGK SWWILRKTCF LIVEHNWFET 
      1210       1220       1230       1240       1250
FIIFMILLSS GALAFEDIYI EQRKTIRTIL EYADKVFTYI FILEMLLKWT 
      1260       1270       1280       1290       1300
AYGFVKFFTN AWCWLDFLIV AVSLVSLIAN ALGYSELGAI KSLRTLRALR 
      1310       1320       1330       1340       1350
PLRALSRFEG MRVVVNALVG AIPSIMNVLL VCLIFWLIFS IMGVNLFAGK 
      1360       1370       1380       1390       1400
YHYCFNETSE IRFEIDIVNN KTDCEKLMEG NSTEIRWKNV KINFDNVGAG 
      1410       1420       1430       1440       1450
YLALLQVATF KGWMDIMYAA VDSRKPDEQP DYEGNIYMYI YFVIFIIFGS 
      1460       1470       1480       1490       1500
FFTLNLFIGV IIDNFNQQKK KFGGQDIFMT EEQKKYYNAM KKLGSKKPQK 
      1510       1520       1530       1540       1550
PIPRPLNKIQ GIVFDFVTQQ AFDIVIMMLI CLNMVTMMVE TDTQSKQMEN 
      1560       1570       1580       1590       1600
ILYWINLVFV IFFTCECVLK MFALRHYYFT IGWNIFDFVV VILSIVGMFL 
      1610       1620       1630       1640       1650
ADIIEKYFVS PTLFRVIRLA RIGRILRLIK GAKGIRTLLF ALMMSLPALF 
      1660       1670       1680       1690       1700
NIGLLLFLVM FIFSIFGMSN FAYVKHEAGI DDMFNFETFG NSMICLFQIT 
      1710       1720       1730       1740       1750
TSAGWDGLLL PILNRPPDCS LDKEHPGSGF KGDCGNPSVG IFFFVSYIII 
      1760       1770       1780       1790       1800
SFLIVVNMYI AIILENFSVA TEESADPLSE DDFETFYEIW EKFDPDATQF 
      1810       1820       1830       1840       1850
IEYCKLADFA DALEHPLRVP KPNTIELIAM DLPMVSGDRI HCLDILFAFT 
      1860       1870       1880       1890       1900
KRVLGDSGEL DILRQQMEER FVASNPSKVS YEPITTTLRR KQEEVSAVVL 
      1910       1920       1930       1940       1950
QRAYRGHLAR RGFICRKMAS NKLENGGTHR DKKESTPSTA SLPSYDSVTK 
      1960       1970 
PDKEKQQRAE EGRRERAKRQ KEVRESKC
Length:1,978
Mass (Da):225,159
Last modified:November 1, 1998 - v1
Checksum:i9160843C5935B88B
GO
Isoform 2 (identifier: O88420-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:1,988
Mass (Da):226,188
Checksum:iC1F7D87FDC266C8F
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038652664E → EVKIDKAATDS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF049239 mRNA Translation: AAC26014.1
AF049240 mRNA Translation: AAC26015.1
RefSeqiNP_062139.2, NM_019266.2 [O88420-1]
UniGeneiRn.91216

Genome annotation databases

GeneIDi29710
KEGGirno:29710
UCSCiRGD:3638 rat [O88420-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSCN8A_RAT
AccessioniPrimary (citable) accession number: O88420
Secondary accession number(s): O88421
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 19, 2010
Last sequence update: November 1, 1998
Last modified: May 23, 2018
This is version 123 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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