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Protein

Sodium channel protein type 8 subunit alpha

Gene

SCN8A

Organism
Homo sapiens (Human)
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. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi893 – 900ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • voltage-gated sodium channel activity Source: UniProtKB

GO - Biological processi

  • membrane depolarization during action potential Source: GO_Central
  • myelination Source: BHF-UCL
  • nervous system development Source: ProtInc
  • neuronal action potential Source: GO_Central
  • peripheral nervous system development Source: BHF-UCL
  • sodium ion transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-445095. Interaction between L1 and Ankyrins.
R-HSA-5576892. Phase 0 - rapid depolarisation.

Protein family/group databases

TCDBi1.A.1.10.8. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 8 subunit alpha
Alternative name(s):
Sodium channel protein type VIII subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.6
Gene namesi
Name:SCN8A
Synonyms:MED
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:10596. SCN8A.

Subcellular locationi

Isoform 5 :
  • Cytoplasmic vesicle

  • Note: Some vesicles are localized adjacent to melanoma invadopodia and macrophage podosomes. Does not localize to the plasma membrane.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 127CytoplasmicSequence analysisAdd BLAST127
Transmembranei128 – 151Helical; Name=S1 of repeat ISequence analysisAdd BLAST24
Topological domaini152 – 159ExtracellularSequence analysis8
Transmembranei160 – 179Helical; Name=S2 of repeat ISequence analysisAdd BLAST20
Topological domaini180 – 192CytoplasmicSequence analysisAdd BLAST13
Transmembranei193 – 211Helical; Name=S3 of repeat ISequence analysisAdd BLAST19
Topological domaini212 – 217ExtracellularSequence analysis6
Transmembranei218 – 237Helical; Voltage-sensor; Name=S4 of repeat ISequence analysisAdd BLAST20
Topological domaini238 – 252CytoplasmicSequence analysisAdd BLAST15
Transmembranei253 – 277Helical; Name=S5 of repeat ISequence analysisAdd BLAST25
Topological domaini278 – 387ExtracellularSequence analysisAdd BLAST110
Transmembranei388 – 413Helical; Name=S6 of repeat ISequence analysisAdd BLAST26
Topological domaini414 – 747CytoplasmicSequence analysisAdd BLAST334
Transmembranei748 – 772Helical; Name=S1 of repeat IISequence analysisAdd BLAST25
Topological domaini773 – 783ExtracellularSequence analysisAdd BLAST11
Transmembranei784 – 807Helical; Name=S2 of repeat IISequence analysisAdd BLAST24
Topological domaini808 – 815CytoplasmicSequence analysis8
Transmembranei816 – 835Helical; Name=S3 of repeat IISequence analysisAdd BLAST20
Topological domaini836 – 841ExtracellularSequence analysis6
Transmembranei842 – 862Helical; Voltage-sensor; Name=S4 of repeat IISequence analysisAdd BLAST21
Topological domaini863 – 877CytoplasmicSequence analysisAdd BLAST15
Transmembranei878 – 898Helical; Name=S5 of repeat IISequence analysisAdd BLAST21
Topological domaini899 – 951ExtracellularSequence analysisAdd BLAST53
Transmembranei952 – 977Helical; Name=S6 of repeat IISequence analysisAdd BLAST26
Topological domaini978 – 1193CytoplasmicSequence analysisAdd BLAST216
Transmembranei1194 – 1217Helical; Name=S1 of repeat IIISequence analysisAdd BLAST24
Topological domaini1218 – 1230ExtracellularSequence analysisAdd BLAST13
Transmembranei1231 – 1256Helical; Name=S2 of repeat IIISequence analysisAdd BLAST26
Topological domaini1257 – 1262CytoplasmicSequence analysis6
Transmembranei1263 – 1284Helical; Name=S3 of repeat IIISequence analysisAdd BLAST22
Topological domaini1285 – 1288ExtracellularSequence analysis4
Transmembranei1289 – 1310Helical; Voltage-sensor; Name=S4 of repeat IIISequence analysisAdd BLAST22
Topological domaini1311 – 1329CytoplasmicSequence analysisAdd BLAST19
Transmembranei1330 – 1351Helical; Name=S5 of repeat IIISequence analysisAdd BLAST22
Topological domaini1352 – 1437ExtracellularSequence analysisAdd BLAST86
Transmembranei1438 – 1464Helical; Name=S6 of repeat IIISequence analysisAdd BLAST27
Topological domaini1465 – 1517CytoplasmicSequence analysisAdd BLAST53
Transmembranei1518 – 1541Helical; Name=S1 of repeat IVSequence analysisAdd BLAST24
Topological domaini1542 – 1552ExtracellularSequence analysisAdd BLAST11
Transmembranei1553 – 1576Helical; Name=S2 of repeat IVSequence analysisAdd BLAST24
Topological domaini1577 – 1582CytoplasmicSequence analysis6
Transmembranei1583 – 1606Helical; Name=S3 of repeat IVSequence analysisAdd BLAST24
Topological domaini1607 – 1616ExtracellularSequence analysis10
Transmembranei1617 – 1638Helical; Voltage-sensor; Name=S4 of repeat IVSequence analysisAdd BLAST22
Topological domaini1639 – 1653CytoplasmicSequence analysisAdd BLAST15
Transmembranei1654 – 1676Helical; Name=S5 of repeat IVSequence analysisAdd BLAST23
Topological domaini1677 – 1741ExtracellularSequence analysisAdd BLAST65
Transmembranei1742 – 1766Helical; Name=S6 of repeat IVSequence analysisAdd BLAST25
Topological domaini1767 – 1980CytoplasmicSequence analysisAdd BLAST214

GO - Cellular componenti

  • axon initial segment Source: BHF-UCL
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • integral component of membrane Source: ProtInc
  • node of Ranvier Source: BHF-UCL
  • plasma membrane Source: GO_Central
  • voltage-gated sodium channel complex Source: UniProtKB
  • Z disc Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Involvement in diseasei

Cognitive impairment with or without cerebellar ataxia (CIAT)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by markedly delayed cognitive and motor development, attention deficit disorder, and cerebellar ataxia. Features include bilateral esophoria, strabismatic amblyopia, unsustained gaze evoked nystagmus on horizontal gaze, ataxic gait, dysmetria in the upper limbs and dysarthria, with normal strength, tone, and reflexes.
See also OMIM:614306
Epileptic encephalopathy, early infantile, 13 (EIEE13)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. EIEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy.
See also OMIM:614558
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07659858D → N in EIEE13; unknown pathological significance; no effect on channel activity. 1 Publication1
Natural variantiVAR_076599215N → R in EIEE13; unknown pathological significance; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_071674216V → D in EIEE13. 1 Publication1
Natural variantiVAR_072182223R → G in EIEE13; loss of function mutation; reduces channel activity. 1 PublicationCorresponds to variant rs672601319dbSNPEnsembl.1
Natural variantiVAR_076600260F → S in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076601407L → F in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076602410V → L in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076603479E → V in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_072183767T → I in EIEE13; gain-of-function mutation; increases channel activity. 1 Publication1
Natural variantiVAR_071675846F → S in EIEE13. 1 Publication1
Natural variantiVAR_076604850R → Q in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs587780586dbSNPEnsembl.1
Natural variantiVAR_076605890A → T in EIEE13. 2 Publications1
Natural variantiVAR_076606960V → D in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076607984N → K in EIEE13; gain-of-function mutation; increased channel activity. 1 Publication1
Natural variantiVAR_0716761327I → V in EIEE13. 1 Publication1
Natural variantiVAR_0766081331L → V in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs397514738dbSNPEnsembl.1
Natural variantiVAR_0766091451G → S in EIEE13; loss of channel activity. 1 Publication1
Natural variantiVAR_0716771466N → K in EIEE13. 1 PublicationCorresponds to variant rs587777722dbSNPEnsembl.1
Natural variantiVAR_0716781466N → T in EIEE13. 1 PublicationCorresponds to variant rs587777723dbSNPEnsembl.1
Natural variantiVAR_0766101479I → V in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs796053217dbSNPEnsembl.1
Natural variantiVAR_0766111592V → L in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs587780454dbSNPEnsembl.1
Natural variantiVAR_0766121596S → C in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_0766131605I → R in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_0716791617R → Q in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation. 4 PublicationsCorresponds to variant rs587777721dbSNPEnsembl.1
Natural variantiVAR_0716801650A → T in EIEE13. 2 Publications1
Natural variantiVAR_0675391768N → D in EIEE13; gain-of-function mutation; results in increased persistent sodium currents and incomplete channel inactivation. 1 PublicationCorresponds to variant rs202151337dbSNPEnsembl.1
Natural variantiVAR_0766141801Q → E in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_0766151872R → L in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation. 1 PublicationCorresponds to variant rs796053229dbSNPEnsembl.1
Natural variantiVAR_0766161872R → Q in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation. 2 Publications1
Natural variantiVAR_0716811872R → W in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation; no effect on interactions with FGF14, SCN1B, GNB2 and GNG3. 3 PublicationsCorresponds to variant rs796053228dbSNPEnsembl.1
Natural variantiVAR_0766171877N → S in EIEE13 and BFIS5. 1 PublicationCorresponds to variant rs587780455dbSNPEnsembl.1
Seizures, benign familial infantile, 5 (BFIS5)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS5 inheritance is autosomal dominant.
See also OMIM:617080
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0769271483E → K in BFIS5. 1 Publication1
Natural variantiVAR_0766171877N → S in EIEE13 and BFIS5. 1 PublicationCorresponds to variant rs587780455dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi6334.
MalaCardsiSCN8A.
MIMi614306. phenotype.
614558. phenotype.
617080. phenotype.
OpenTargetsiENSG00000196876.
Orphaneti1934. Early infantile epileptic encephalopathy.
PharmGKBiPA35009.

Chemistry databases

ChEMBLiCHEMBL5202.
DrugBankiDB00313. Valproic Acid.
GuidetoPHARMACOLOGYi583.

Polymorphism and mutation databases

BioMutaiSCN8A.
DMDMi34098756.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000485001 – 1980Sodium channel protein type 8 subunit alphaAdd BLAST1980

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi215N-linked (GlcNAc...)Sequence analysis1
Glycosylationi289N-linked (GlcNAc...)Sequence analysis1
Glycosylationi295N-linked (GlcNAc...)Sequence analysis1
Glycosylationi308N-linked (GlcNAc...)Sequence analysis1
Glycosylationi326N-linked (GlcNAc...)Sequence analysis1
Modified residuei477PhosphoserineBy similarity1
Modified residuei504PhosphoserineBy similarity1
Modified residuei518PhosphoserineBy similarity1
Modified residuei520PhosphoserineBy similarity1
Modified residuei546PhosphoserineBy similarity1
Modified residuei579PhosphoserineBy similarity1
Modified residuei613PhosphoserineBy similarity1
Modified residuei699PhosphoserineBy similarity1
Modified residuei702PhosphoserineBy similarity1
Glycosylationi1358N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1372N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1383N-linked (GlcNAc...)Sequence analysis1
Modified residuei1497Phosphoserine; by PKCBy similarity1

Post-translational modificationi

May be ubiquitinated by NEDD4L; which would promote its endocytosis.By similarity
Phosphorylation at Ser-1497 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9UQD0.
PeptideAtlasiQ9UQD0.
PRIDEiQ9UQD0.

PTM databases

iPTMnetiQ9UQD0.
PhosphoSitePlusiQ9UQD0.

Expressioni

Tissue specificityi

Isoform 5 is expressed in non-neuronal tissues, such as monocytes/macrophages.1 Publication

Gene expression databases

BgeeiENSG00000196876.
CleanExiHS_SCN8A.
ExpressionAtlasiQ9UQD0. baseline and differential.
GenevisibleiQ9UQD0. HS.

Interactioni

Subunit structurei

Interacts with NEDD4 and NEDD4L (By similarity). Interacts with FGF13; may regulate SCN8A activity. Interacts with FGF14, GBG3, GBB2 and SCN1B (PubMed:26900580).By similarity2 Publications

Protein-protein interaction databases

BioGridi112238. 1 interactor.
IntActiQ9UQD0. 1 interactor.
STRINGi9606.ENSP00000346534.

Chemistry databases

BindingDBiQ9UQD0.

Structurei

3D structure databases

ProteinModelPortaliQ9UQD0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati114 – 442ICuratedAdd BLAST329
Repeati735 – 1007IICuratedAdd BLAST273
Repeati1180 – 1495IIICuratedAdd BLAST316
Repeati1504 – 1801IVCuratedAdd BLAST298
Domaini1895 – 1924IQPROSITE-ProRule annotationCuratedAdd 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

Contains 1 IQ domain.PROSITE-ProRule annotationCurated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
GeneTreeiENSGT00830000128242.
HOGENOMiHOG000231755.
HOVERGENiHBG053100.
InParanoidiQ9UQD0.
KOiK04840.
OMAiGFICKKT.
OrthoDBiEOG091G00FK.
PhylomeDBiQ9UQD0.
TreeFamiTF323985.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
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.
[Graphical view]
PfamiPF00520. Ion_trans. 4 hits.
PF00612. IQ. 1 hit.
PF06512. Na_trans_assoc. 1 hit.
PF11933. Na_trans_cytopl. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
PR01667. NACHANNEL8.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]
PROSITEiPS50096. IQ. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9UQD0-1) [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

        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
FSNPPDWSKN VEYTFTGIYT FESLVKIIAR GFCIDGFTFL RDPWNWLDFS
210 220 230 240 250
VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI VGALIQSVKK
260 270 280 290 300
LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF
310 320 330 340 350
DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM 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 DAIEEEGEEG GGSPRSSSEI 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 SQGSRSSRIF PSLRRSVKRN STVDCNGVVS
660 670 680 690 700
LIGGPGSHIG GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI
710 720 730 740 750
MSVVTNTLVE ELEESQRKCP PCWYKFANTF LIWECHPYWI KLKEIVNLIV
760 770 780 790 800
MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ FEHVLAVGNL VFTGIFTAEM
810 820 830 840 850
FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL SVLRSFRLLR
860 870 880 890 900
VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS
910 920 930 940 950
YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ
960 970 980 990 1000
AMCLIVFMMV MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS
1010 1020 1030 1040 1050
VIRIKKGVAW TKLKVHAFMQ AHFKQREADE VKPLDELYEK KANCIANHTG
1060 1070 1080 1090 1100
ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID EDHMSFINNP NLTVRVPIAV
1110 1120 1130 1140 1150
GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK PEVEEVPVEQ
1160 1170 1180 1190 1200
PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF
1210 1220 1230 1240 1250
ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK
1260 1270 1280 1290 1300
WTAYGFVKFF TNAWCWLDFL IVAVSLVSLI ANALGYSELG AIKSLRTLRA
1310 1320 1330 1340 1350
LRPLRALSRF EGMRVVVNAL VGAIPSIMNV LLVCLIFWLI FSIMGVNLFA
1360 1370 1380 1390 1400
GKYHYCFNET SEIRFEIEDV NNKTECEKLM EGNNTEIRWK NVKINFDNVG
1410 1420 1430 1440 1450
AGYLALLQVA TFKGWMDIMY AAVDSRKPDE QPKYEDNIYM YIYFVIFIIF
1460 1470 1480 1490 1500
GSFFTLNLFI GVIIDNFNQQ KKKFGGQDIF MTEEQKKYYN AMKKLGSKKP
1510 1520 1530 1540 1550
QKPIPRPLNK IQGIVFDFVT QQAFDIVIMM LICLNMVTMM VETDTQSKQM
1560 1570 1580 1590 1600
ENILYWINLV FVIFFTCECV LKMFALRHYY FTIGWNIFDF VVVILSIVGM
1610 1620 1630 1640 1650
FLADIIEKYF VSPTLFRVIR LARIGRILRL IKGAKGIRTL LFALMMSLPA
1660 1670 1680 1690 1700
LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA GIDDMFNFET FGNSMICLFQ
1710 1720 1730 1740 1750
ITTSAGWDGL LLPILNRPPD CSLDKEHPGS GFKGDCGNPS VGIFFFVSYI
1760 1770 1780 1790 1800
IISFLIVVNM YIAIILENFS VATEESADPL SEDDFETFYE IWEKFDPDAT
1810 1820 1830 1840 1850
QFIEYCKLAD FADALEHPLR VPKPNTIELI AMDLPMVSGD RIHCLDILFA
1860 1870 1880 1890 1900
FTKRVLGDSG ELDILRQQME ERFVASNPSK VSYEPITTTL RRKQEEVSAV
1910 1920 1930 1940 1950
VLQRAYRGHL ARRGFICKKT TSNKLENGGT HREKKESTPS TASLPSYDSV
1960 1970 1980
TKPEKEKQQR AEEGRRERAK RQKEVRESKC
Length:1,980
Mass (Da):225,280
Last modified:May 1, 2000 - v1
Checksum:i0EFC7BFB137FD4F0
GO
Isoform 21 Publication (identifier: Q9UQD0-2) [UniParc]FASTAAdd to basket
Also known as: 5A1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     207-207: I → V
     212-212: N → D

Show »
Length:1,980
Mass (Da):225,267
Checksum:i0510CF3CC31892F0
GO
Isoform 31 Publication (identifier: Q9UQD0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     666-666: E → EVKIDKAATDDS

Show »
Length:1,991
Mass (Da):226,424
Checksum:i8C830A4CA55C69DE
GO
Isoform 41 Publication (identifier: Q9UQD0-4) [UniParc]FASTAAdd to basket
Also known as: 18N1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1275-1283: SLVSLIANA → PLNLSGLI
     1284-1980: Missing.

Show »
Length:1,282
Mass (Da):145,118
Checksum:i43D3C2BD00DD44E5
GO
Isoform 5 (identifier: Q9UQD0-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1275-1315: Missing.

Show »
Length:1,939
Mass (Da):220,798
Checksum:i3E44D910D3897BC4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5L → V in AAF35390 (Ref. 5) Curated1
Sequence conflicti133V → L in AAD15789 (PubMed:9295353).Curated1
Sequence conflicti257L → M in AAF35390 (Ref. 5) Curated1
Sequence conflicti273F → I in ACM63162 (PubMed:19136557).Curated1
Sequence conflicti274 – 278MGNLR → HGEPS in AAF35390 (Ref. 5) Curated5
Sequence conflicti453T → N in AAF35390 (Ref. 5) Curated1
Sequence conflicti477S → F in AAF35390 (Ref. 5) Curated1
Sequence conflicti483L → I in AAF35390 (Ref. 5) Curated1
Sequence conflicti492R → S in AAF35390 (Ref. 5) Curated1
Sequence conflicti504S → F in AAF35390 (Ref. 5) Curated1
Sequence conflicti547 – 548LL → MF in AAF35390 (Ref. 5) Curated2
Sequence conflicti1416M → V in ACM63162 (PubMed:19136557).Curated1
Sequence conflicti1445V → I in AAD15789 (PubMed:9295353).Curated1
Sequence conflicti1519V → I in AAD15789 (PubMed:9295353).Curated1
Sequence conflicti1702T → A in AAF35390 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07659858D → N in EIEE13; unknown pathological significance; no effect on channel activity. 1 Publication1
Natural variantiVAR_076599215N → R in EIEE13; unknown pathological significance; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_071674216V → D in EIEE13. 1 Publication1
Natural variantiVAR_072182223R → G in EIEE13; loss of function mutation; reduces channel activity. 1 PublicationCorresponds to variant rs672601319dbSNPEnsembl.1
Natural variantiVAR_076600260F → S in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076601407L → F in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076602410V → L in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076603479E → V in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_072183767T → I in EIEE13; gain-of-function mutation; increases channel activity. 1 Publication1
Natural variantiVAR_071675846F → S in EIEE13. 1 Publication1
Natural variantiVAR_076604850R → Q in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs587780586dbSNPEnsembl.1
Natural variantiVAR_076605890A → T in EIEE13. 2 Publications1
Natural variantiVAR_076606960V → D in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_076607984N → K in EIEE13; gain-of-function mutation; increased channel activity. 1 Publication1
Natural variantiVAR_0716761327I → V in EIEE13. 1 Publication1
Natural variantiVAR_0766081331L → V in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs397514738dbSNPEnsembl.1
Natural variantiVAR_0766091451G → S in EIEE13; loss of channel activity. 1 Publication1
Natural variantiVAR_0716771466N → K in EIEE13. 1 PublicationCorresponds to variant rs587777722dbSNPEnsembl.1
Natural variantiVAR_0716781466N → T in EIEE13. 1 PublicationCorresponds to variant rs587777723dbSNPEnsembl.1
Natural variantiVAR_0766101479I → V in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs796053217dbSNPEnsembl.1
Natural variantiVAR_0769271483E → K in BFIS5. 1 Publication1
Natural variantiVAR_0766111592V → L in EIEE13; unknown pathological significance. 1 PublicationCorresponds to variant rs587780454dbSNPEnsembl.1
Natural variantiVAR_0766121596S → C in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_0766131605I → R in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_0716791617R → Q in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation. 4 PublicationsCorresponds to variant rs587777721dbSNPEnsembl.1
Natural variantiVAR_0716801650A → T in EIEE13. 2 Publications1
Natural variantiVAR_0675391768N → D in EIEE13; gain-of-function mutation; results in increased persistent sodium currents and incomplete channel inactivation. 1 PublicationCorresponds to variant rs202151337dbSNPEnsembl.1
Natural variantiVAR_0766141801Q → E in EIEE13; unknown pathological significance. 1 Publication1
Natural variantiVAR_0766151872R → L in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation. 1 PublicationCorresponds to variant rs796053229dbSNPEnsembl.1
Natural variantiVAR_0766161872R → Q in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation. 2 Publications1
Natural variantiVAR_0716811872R → W in EIEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation; no effect on interactions with FGF14, SCN1B, GNB2 and GNG3. 3 PublicationsCorresponds to variant rs796053228dbSNPEnsembl.1
Natural variantiVAR_0766171877N → S in EIEE13 and BFIS5. 1 PublicationCorresponds to variant rs587780455dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_050589207I → V in isoform 2. 1 Publication1
Alternative sequenceiVSP_050590212N → D in isoform 2. 1 Publication1
Alternative sequenceiVSP_050591666E → EVKIDKAATDDS in isoform 3. 1 Publication1
Alternative sequenceiVSP_0386511275 – 1315Missing in isoform 5. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_0505921275 – 1283SLVSLIANA → PLNLSGLI in isoform 4. 1 Publication9
Alternative sequenceiVSP_0505931284 – 1980Missing in isoform 4. 1 PublicationAdd BLAST697

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF050736
, AF050711, AF050712, AF050713, AF050714, AF050715, AF050716, AF050717, AF050718, AF050719, AF050720, AF050721, AF050722, AF050723, AF050724, AF050725, AF050726, AF050727, AF050728, AF050729, AF050730, AF050731, AF050732, AF050733, AF050734, AF050735 Genomic DNA. Translation: AAD15789.1.
AF049618 Genomic DNA. Translation: AAD20439.1.
FJ611941 mRNA. Translation: ACM63162.1.
AB027567 mRNA. Translation: BAA78033.1.
AF225988 mRNA. Translation: AAF35390.1.
AC013421 Genomic DNA. No translation available.
AC025097 Genomic DNA. No translation available.
AC068987 Genomic DNA. No translation available.
AC140060 Genomic DNA. No translation available.
CCDSiCCDS44891.1. [Q9UQD0-1]
CCDS53794.1. [Q9UQD0-5]
CCDS81692.1. [Q9UQD0-2]
RefSeqiNP_001171455.1. NM_001177984.2. [Q9UQD0-5]
NP_001317189.1. NM_001330260.1.
NP_055006.1. NM_014191.3. [Q9UQD0-1]
XP_006719619.1. XM_006719556.3. [Q9UQD0-2]
XP_011536953.1. XM_011538651.2. [Q9UQD0-2]
XP_016875283.1. XM_017019794.1. [Q9UQD0-1]
UniGeneiHs.436550.
Hs.710638.

Genome annotation databases

EnsembliENST00000354534; ENSP00000346534; ENSG00000196876. [Q9UQD0-1]
ENST00000355133; ENSP00000347255; ENSG00000196876. [Q9UQD0-5]
ENST00000545061; ENSP00000440360; ENSG00000196876. [Q9UQD0-5]
ENST00000599343; ENSP00000476447; ENSG00000196876. [Q9UQD0-3]
ENST00000627620; ENSP00000487583; ENSG00000196876. [Q9UQD0-2]
GeneIDi6334.
KEGGihsa:6334.
UCSCiuc001ryw.4. human. [Q9UQD0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF050736
, AF050711, AF050712, AF050713, AF050714, AF050715, AF050716, AF050717, AF050718, AF050719, AF050720, AF050721, AF050722, AF050723, AF050724, AF050725, AF050726, AF050727, AF050728, AF050729, AF050730, AF050731, AF050732, AF050733, AF050734, AF050735 Genomic DNA. Translation: AAD15789.1.
AF049618 Genomic DNA. Translation: AAD20439.1.
FJ611941 mRNA. Translation: ACM63162.1.
AB027567 mRNA. Translation: BAA78033.1.
AF225988 mRNA. Translation: AAF35390.1.
AC013421 Genomic DNA. No translation available.
AC025097 Genomic DNA. No translation available.
AC068987 Genomic DNA. No translation available.
AC140060 Genomic DNA. No translation available.
CCDSiCCDS44891.1. [Q9UQD0-1]
CCDS53794.1. [Q9UQD0-5]
CCDS81692.1. [Q9UQD0-2]
RefSeqiNP_001171455.1. NM_001177984.2. [Q9UQD0-5]
NP_001317189.1. NM_001330260.1.
NP_055006.1. NM_014191.3. [Q9UQD0-1]
XP_006719619.1. XM_006719556.3. [Q9UQD0-2]
XP_011536953.1. XM_011538651.2. [Q9UQD0-2]
XP_016875283.1. XM_017019794.1. [Q9UQD0-1]
UniGeneiHs.436550.
Hs.710638.

3D structure databases

ProteinModelPortaliQ9UQD0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112238. 1 interactor.
IntActiQ9UQD0. 1 interactor.
STRINGi9606.ENSP00000346534.

Chemistry databases

BindingDBiQ9UQD0.
ChEMBLiCHEMBL5202.
DrugBankiDB00313. Valproic Acid.
GuidetoPHARMACOLOGYi583.

Protein family/group databases

TCDBi1.A.1.10.8. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetiQ9UQD0.
PhosphoSitePlusiQ9UQD0.

Polymorphism and mutation databases

BioMutaiSCN8A.
DMDMi34098756.

Proteomic databases

PaxDbiQ9UQD0.
PeptideAtlasiQ9UQD0.
PRIDEiQ9UQD0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000354534; ENSP00000346534; ENSG00000196876. [Q9UQD0-1]
ENST00000355133; ENSP00000347255; ENSG00000196876. [Q9UQD0-5]
ENST00000545061; ENSP00000440360; ENSG00000196876. [Q9UQD0-5]
ENST00000599343; ENSP00000476447; ENSG00000196876. [Q9UQD0-3]
ENST00000627620; ENSP00000487583; ENSG00000196876. [Q9UQD0-2]
GeneIDi6334.
KEGGihsa:6334.
UCSCiuc001ryw.4. human. [Q9UQD0-1]

Organism-specific databases

CTDi6334.
DisGeNETi6334.
GeneCardsiSCN8A.
HGNCiHGNC:10596. SCN8A.
MalaCardsiSCN8A.
MIMi600702. gene.
614306. phenotype.
614558. phenotype.
617080. phenotype.
neXtProtiNX_Q9UQD0.
OpenTargetsiENSG00000196876.
Orphaneti1934. Early infantile epileptic encephalopathy.
PharmGKBiPA35009.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
GeneTreeiENSGT00830000128242.
HOGENOMiHOG000231755.
HOVERGENiHBG053100.
InParanoidiQ9UQD0.
KOiK04840.
OMAiGFICKKT.
OrthoDBiEOG091G00FK.
PhylomeDBiQ9UQD0.
TreeFamiTF323985.

Enzyme and pathway databases

ReactomeiR-HSA-445095. Interaction between L1 and Ankyrins.
R-HSA-5576892. Phase 0 - rapid depolarisation.

Miscellaneous databases

ChiTaRSiSCN8A. human.
GeneWikiiSCN8A.
GenomeRNAii6334.
PROiQ9UQD0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196876.
CleanExiHS_SCN8A.
ExpressionAtlasiQ9UQD0. baseline and differential.
GenevisibleiQ9UQD0. HS.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
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.
[Graphical view]
PfamiPF00520. Ion_trans. 4 hits.
PF00612. IQ. 1 hit.
PF06512. Na_trans_assoc. 1 hit.
PF11933. Na_trans_cytopl. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
PR01667. NACHANNEL8.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]
PROSITEiPS50096. IQ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSCN8A_HUMAN
AccessioniPrimary (citable) accession number: Q9UQD0
Secondary accession number(s): B9VWG8
, O95788, Q9NYX2, Q9UPB2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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.