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Protein

Sodium channel protein type 8 subunit alpha

Gene

Scn8a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 sodium channel activity Source: RGD

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
  • sodium ion transport Source: RGD

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3638. Scn8a.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein By similarity

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

GO - Cellular componenti

  • axon initial segment Source: BHF-UCL
  • integral component of membrane Source: RGD
  • node of Ranvier Source: BHF-UCL
  • plasma membrane Source: RGD
  • voltage-gated sodium channel complex Source: RGD

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 residuei477PhosphoserineBy similarity1
Modified residuei504PhosphoserineBy similarity1
Modified residuei518PhosphoserineCombined sources1
Modified residuei520PhosphoserineCombined sources1
Modified residuei546PhosphoserineBy similarity1
Modified residuei579PhosphoserineBy similarity1
Modified residuei613PhosphoserineBy similarity1
Modified residuei697PhosphoserineBy similarity1
Modified residuei700PhosphoserineBy similarity1
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

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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
HOGENOMiHOG000231755.
HOVERGENiHBG053100.
InParanoidiO88420.
KOiK04840.
PhylomeDBiO88420.

Family and domain databases

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.
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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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 10, 2017
This is version 118 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