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1.A.1.10.8
The Voltage-gated Na+ channel α-subunit, Nav1.6, encoded by the Scn8a gene which when defective gives rise to the ENU-induced neurological mutant ataxia3 which gives rise to ataxia, tremors, and juvenile lethality.   75% identical to 1.A.1.10.7. Nav1.6 is the dendritic, voltage-gated sodium channel (responsible for dendritic excitability (Lorincz and Nusser, 2010)). Nav1.6 (SCN8A) interacts with microtubule-associated protein (O'Brien et al., 2012). Scorpion alpha toxins bind at receptor site-3 and inhibit channel inactivation, whereas beta toxins bind at receptor site-4 and shift the voltage-dependent activation toward more hyperpolarizing potentials (Gurevitz, 2012).  Mutations give rise to epileptic encephalopathy and intellectual disability (O'Brien and Meisler 2013).  A gain-of-function mutation gave rise to increased channel activation and infantile epileptic encephalopathy (Estacion et al. 2014). Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination - known as infantile convulsions and paroxysmal choreoathetosis (ICCA) - are related autosomal dominant diseases involving SCN8A (Gardella et al. 2015).  Mutations can lead to chronic movement disorder in the mouse (Jones et al. 2016), and loss of function mutations in humans can lead to intellectual disability without seizures (Wagnon et al. 2017).

Accession Number:Q9UQD0
Protein Name:Sodium channel protein type 8 subunit alpha
Length:1980
Molecular Weight:225280.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:20
Location1 / Topology2 / Orientation3: Cytoplasmic vesicle1
Substrate Na+

Cross database links:

Genevestigator: Q9UQD0
eggNOG: prNOG14675
HEGENOM: HBG358468
RefSeq: NP_055006.1   
Entrez Gene ID: 6334   
Pfam: PF00520    PF00612    PF06512   
OMIM: 600702  gene
KEGG: hsa:6334   

Gene Ontology

GO:0016023 C:cytoplasmic membrane-bounded vesicle
GO:0033268 C:node of Ranvier
GO:0001518 C:voltage-gated sodium channel complex
GO:0005524 F:ATP binding
GO:0005248 F:voltage-gated sodium channel activity
GO:0042552 P:myelination
GO:0007422 P:peripheral nervous system development
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport

References (4)

[1] “Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.”  Plummer N.W.et.al.   9295353
[2] “Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.”  Plummer N.W.et.al.   9828131
[3] “Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.”  Carrithers M.D.et.al.   19136557
[4] “The finished DNA sequence of human chromosome 12.”  Scherer S.E.et.al.   16541075

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 
61:	AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 
121:	IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR 
181:	GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI 
241:	VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF 
301:	DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF 
361:	LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 
421:	TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI 
481:	SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 
541:	SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 
601:	LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG 
661:	GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP 
721:	PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ 
781:	FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL 
841:	SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS 
901:	YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV 
961:	MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ 
1021:	AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID 
1081:	EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK 
1141:	PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF 
1201:	ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF 
1261:	TNAWCWLDFL IVAVSLVSLI ANALGYSELG AIKSLRTLRA LRPLRALSRF EGMRVVVNAL 
1321:	VGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKYHYCFNET SEIRFEIEDV NNKTECEKLM 
1381:	EGNNTEIRWK NVKINFDNVG AGYLALLQVA TFKGWMDIMY AAVDSRKPDE QPKYEDNIYM 
1441:	YIYFVIFIIF GSFFTLNLFI GVIIDNFNQQ KKKFGGQDIF MTEEQKKYYN AMKKLGSKKP 
1501:	QKPIPRPLNK IQGIVFDFVT QQAFDIVIMM LICLNMVTMM VETDTQSKQM ENILYWINLV 
1561:	FVIFFTCECV LKMFALRHYY FTIGWNIFDF VVVILSIVGM FLADIIEKYF VSPTLFRVIR 
1621:	LARIGRILRL IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA 
1681:	GIDDMFNFET FGNSMICLFQ ITTSAGWDGL LLPILNRPPD CSLDKEHPGS GFKGDCGNPS 
1741:	VGIFFFVSYI IISFLIVVNM YIAIILENFS VATEESADPL SEDDFETFYE IWEKFDPDAT 
1801:	QFIEYCKLAD FADALEHPLR VPKPNTIELI AMDLPMVSGD RIHCLDILFA FTKRVLGDSG 
1861:	ELDILRQQME ERFVASNPSK VSYEPITTTL RRKQEEVSAV VLQRAYRGHL ARRGFICKKT 
1921:	TSNKLENGGT HREKKESTPS TASLPSYDSV TKPEKEKQQR AEEGRRERAK RQKEVRESKC