ID   SCN8A_MOUSE             Reviewed;        1978 AA.
AC   Q9WTU3; Q3TYI3; Q60828; Q60858; Q62449;
DT   15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   24-JAN-2024, entry version 174.
DE   RecName: Full=Sodium channel protein type 8 subunit alpha;
DE   AltName: Full=Sodium channel protein type VIII subunit alpha;
DE   AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.6;
GN   Name=Scn8a; Synonyms=Nbna1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090 {ECO:0000312|EMBL:AAD20438.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:AAD20438.1};
RX   PubMed=9828131; DOI=10.1006/geno.1998.5550;
RA   Plummer N.W., Galt J., Jones J.M., Burgess D.L., Sprunger L.K.,
RA   Kohrman D.C., Meisler M.H.;
RT   "Exon organization, coding sequence, physical mapping, and polymorphic
RT   intragenic markers for the human neuronal sodium channel gene SCN8A.";
RL   Genomics 54:287-296(1998).
RN   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND DISEASE.
RC   STRAIN=C57BL/6J {ECO:0000269|PubMed:7670495};
RC   TISSUE=Brain {ECO:0000269|PubMed:7670495};
RX   PubMed=7670495; DOI=10.1038/ng0895-461;
RA   Burgess D.L., Kohrman D.C., Galt J., Plummer N.W., Jones J.M., Spear B.,
RA   Meisler M.H.;
RT   "Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor
RT   endplate disease'.";
RL   Nat. Genet. 10:461-465(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-804, AND VARIANT LEU-5.
RC   STRAIN=C57BL/6J; TISSUE=Visual cortex;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 93-205, AND DISEASE.
RC   STRAIN=129/Sv {ECO:0000269|PubMed:8663325};
RC   TISSUE=Brain {ECO:0000269|PubMed:8663325};
RX   PubMed=8663325; DOI=10.1074/jbc.271.29.17576;
RA   Kohrman D.C., Harris J.B., Meisler M.H.;
RT   "Mutation detection in the med and medJ alleles of the sodium channel
RT   Scn8a. Unusual splicing due to a minor class AT-AC intron.";
RL   J. Biol. Chem. 271:17576-17581(1996).
RN   [5] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1411-1686.
RA   Fan Z., Kyle J.W., Makielski J.C.;
RT   "A putative novel Na channel alpha subunit cDNA isolated from mouse NB2a
RT   neuroblastoma cells.";
RL   Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN   [6] {ECO:0000305}
RP   ALTERNATIVE SPLICING (ISOFORMS 1; 4 AND 5).
RC   TISSUE=Brain {ECO:0000269|PubMed:9295353}, and Fetal brain
RC   {ECO:0000269|PubMed:9295353};
RX   PubMed=9295353; DOI=10.1074/jbc.272.38.24008;
RA   Plummer N.W., McBurney M.W., Meisler M.H.;
RT   "Alternative splicing of the sodium channel SCN8A predicts a truncated two-
RT   domain protein in fetal brain and non-neuronal cells.";
RL   J. Biol. Chem. 272:24008-24015(1997).
RN   [7]
RP   INTERACTION WITH NEDD4 AND NEDD4L.
RX   PubMed=15123669; DOI=10.1074/jbc.m402820200;
RA   Fotia A.B., Ekberg J., Adams D.J., Cook D.I., Poronnik P., Kumar S.;
RT   "Regulation of neuronal voltage-gated sodium channels by the ubiquitin-
RT   protein ligases Nedd4 and Nedd4-2.";
RL   J. Biol. Chem. 279:28930-28935(2004).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=19136557; DOI=10.1074/jbc.m801892200;
RA   Carrithers M.D., Chatterjee G., Carrithers L.M., Offoha R., Iheagwara U.,
RA   Rahner C., Graham M., Waxman S.G.;
RT   "Regulation of podosome formation in macrophages by a splice variant of the
RT   sodium channel SCN8A.";
RL   J. Biol. Chem. 284:8114-8126(2009).
RN   [9]
RP   INTERACTION WITH SCORPION TOXIN BMK M1, AND MUTAGENESIS OF ASP-1602.
RX   PubMed=20678086; DOI=10.1042/bj20100517;
RA   He H., Liu Z., Dong B., Zhou J., Zhu H., Ji Y.;
RT   "Molecular determination of selectivity of the site 3 modulator (BmK I) to
RT   sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-
RT   induced neuronal hyperexcitability.";
RL   Biochem. J. 431:289-298(2010).
RN   [10] {ECO:0000305}
RP   VARIANT MEDJO THR-1317, AND VARIANT LEU-5.
RC   STRAIN=DBA/2WyDi {ECO:0000269|PubMed:8815882};
RX   PubMed=8815882; DOI=10.1523/jneurosci.16-19-05993.1996;
RA   Kohrman D.C., Smith M.R., Goldin A.L., Harris J., Meisler M.H.;
RT   "A missense mutation in the sodium channel Scn8a is responsible for
RT   cerebellar ataxia in the mouse mutant jolting.";
RL   J. Neurosci. 16:5993-5999(1996).
RN   [11] {ECO:0000305}
RP   DISEASE.
RX   PubMed=11532991; DOI=10.1093/hmg/10.17.1819;
RA   De Repentigny Y., Cote P.D., Pool M., Bernier G., Girard S., Vidal S.M.,
RA   Kothary R.;
RT   "Pathological and genetic analysis of the degenerating muscle (dmu) mouse:
RT   a new allele of Scn8a.";
RL   Hum. Mol. Genet. 10:1819-1827(2001).
RN   [12]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=28842554; DOI=10.1038/s41467-017-00368-z;
RA   Liu Y., Lai S., Ma W., Ke W., Zhang C., Liu S., Zhang Y., Pei F., Li S.,
RA   Yi M., Shu Y., Shang Y., Liang J., Huang Z.;
RT   "CDYL suppresses epileptogenesis in mice through repression of axonal
RT   Nav1.6 sodium channel expression.";
RL   Nat. Commun. 8:355-355(2017).
RN   [13] {ECO:0007744|PDB:3WFN}
RP   X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1893-1914 IN COMPLEX WITH CALM1,
RP   INTERACTION WITH CALM1, AND MUTAGENESIS OF GLN-1901; ARG-1902; TYR-1904 AND
RP   ARG-1905.
RX   PubMed=23942337; DOI=10.1038/srep02435;
RA   Reddy Chichili V.P., Xiao Y., Seetharaman J., Cummins T.R., Sivaraman J.;
RT   "Structural basis for the modulation of the neuronal voltage-gated sodium
RT   channel NaV1.6 by calmodulin.";
RL   Sci. Rep. 3:2435-2435(2013).
CC   -!- FUNCTION: Mediates the voltage-dependent sodium ion permeability of
CC       excitable membranes. Assuming opened or closed conformations in
CC       response to the voltage difference across the membrane, the protein
CC       forms a sodium-selective channel through which Na(+) ions may pass in
CC       accordance with their electrochemical gradient. In macrophages, isoform
CC       5 may participate in the control of podosome and invadopodia formation.
CC       {ECO:0000269|PubMed:19136557}.
CC   -!- ACTIVITY REGULATION: Inhibited by tetrodotoxin and, more weakly, by its
CC       metabolite 4,9-ah-tetrodotoxin. {ECO:0000250|UniProtKB:Q9UQD0}.
CC   -!- SUBUNIT: The voltage-sensitive sodium channel consists of an ion-
CC       conducting pore-forming alpha subunit regulated by one or more beta-1
CC       (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B) subunits.
CC       Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with
CC       alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by
CC       disulfide bonds. Interacts with FGF13 (By similarity). Interacts with
CC       NEDD4 and NEDD4L (PubMed:15123669). Interacts with FGF14, GBG3, GBB2
CC       and SCN1B (By similarity). Interacts with TMEM233 (By similarity).
CC       Interacts with the conotoxin GVIIJ (By similarity). Interacts with the
CC       scorpion toxin BMK M1 (PubMed:20678086). Interacts with CALM1; the
CC       interaction modulates the inactivation rate of SCN8A (PubMed:23942337).
CC       {ECO:0000250|UniProtKB:O88420, ECO:0000250|UniProtKB:Q9UQD0,
CC       ECO:0000269|PubMed:15123669, ECO:0000269|PubMed:20678086,
CC       ECO:0000269|PubMed:23942337}.
CC   -!- INTERACTION:
CC       Q9WTU3; P14873: Map1b; NbExp=7; IntAct=EBI-6396042, EBI-764653;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19136557};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:19136557}. Cell
CC       projection, axon {ECO:0000269|PubMed:28842554}. Note=Mainly localizes
CC       to the axon initial segment. {ECO:0000269|PubMed:28842554}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1 {ECO:0000269|PubMed:9295353, ECO:0000269|PubMed:9828131};
CC       Synonyms=18A {ECO:0000269|PubMed:9295353};
CC         IsoId=Q9WTU3-1; Sequence=Displayed;
CC       Name=2 {ECO:0000269|PubMed:7670495};
CC         IsoId=Q9WTU3-2; Sequence=VSP_050594;
CC       Name=3 {ECO:0000269|PubMed:9828131};
CC         IsoId=Q9WTU3-3; Sequence=VSP_050595;
CC       Name=4 {ECO:0000269|PubMed:9295353}; Synonyms=18N
CC       {ECO:0000269|PubMed:9295353};
CC         IsoId=Q9WTU3-4; Sequence=VSP_050596, VSP_050597;
CC       Name=5 {ECO:0000269|PubMed:9295353};
CC         IsoId=Q9WTU3-5; Sequence=VSP_050598;
CC   -!- TISSUE SPECIFICITY: Expressed in the hippocampus (at protein level)
CC       (PubMed:28842554). Expressed in brain, cerebellum and spinal cord.
CC       Isoform 5: May be expressed in non-neuronal tissues, such as peritoneal
CC       macrophages. {ECO:0000269|PubMed:19136557, ECO:0000269|PubMed:28842554,
CC       ECO:0000269|PubMed:7670495}.
CC   -!- DOMAIN: The sequence contains 4 internal repeats, each with 5
CC       hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged
CC       segment (S4). Segments S4 are probably the voltage-sensors and are
CC       characterized by a series of positively charged amino acids at every
CC       third position. {ECO:0000305}.
CC   -!- PTM: May be ubiquitinated by NEDD4L; which would promote its
CC       endocytosis. {ECO:0000250}.
CC   -!- PTM: Phosphorylation at Ser-1495 by PKC in a highly conserved
CC       cytoplasmic loop slows inactivation of the sodium channel and reduces
CC       peak sodium currents. {ECO:0000250}.
CC   -!- DISEASE: Note=Defects in Scn8a are the cause of motor endplate disease
CC       (med). Med is a recessive neuromuscular disorder that is characterized
CC       by lack of signal transmission at the neuromuscular junction, excess
CC       preterminal arborization and degeneration of cerebellar Purkinje cells.
CC       It produces early onset progressive paralysis of hind limbs, severe
CC       muscle atrophy and juvenile lethality.
CC   -!- DISEASE: Note=Defects in Scn8a are the cause of the jolting mutant
CC       (medjo), a mild form of motor endplate disease which is characterized
CC       by the absence of spontaneous, regular, simple discharges from Purkinje
CC       cells. After 3 weeks of age, jolting mice are unsteady and have wide-
CC       based gait and a rhythmical tremor of head and neck induced by
CC       attempted movement. {ECO:0000269|PubMed:7670495,
CC       ECO:0000269|PubMed:8815882}.
CC   -!- DISEASE: Note=Defects in Scn8a are a cause of degenerating muscle
CC       (dmu). Dmu is an autosomal recessive neuromuscular disorder that is
CC       characterized by skeletal and cardiac muscle degeneration. It produces
CC       early onset progressive loss of mobility of the hind limbs and
CC       subsequent lethality in the first month of life.
CC       {ECO:0000269|PubMed:11532991, ECO:0000305|PubMed:8663325}.
CC   -!- MISCELLANEOUS: [Isoform 2]: Due to aberrant splicing. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC       Nav1.6/SCN8A subfamily. {ECO:0000305}.
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DR   EMBL; AF049617; AAD20438.1; -; mRNA.
DR   EMBL; U26707; AAC52242.1; -; mRNA.
DR   EMBL; AK158609; BAE34580.1; -; mRNA.
DR   EMBL; U59964; AAC52708.1; -; Genomic_DNA.
DR   EMBL; U59963; AAC52708.1; JOINED; Genomic_DNA.
DR   EMBL; U23158; AAA65599.1; -; mRNA.
DR   CCDS; CCDS57011.1; -. [Q9WTU3-1]
DR   RefSeq; NP_001070967.1; NM_001077499.2.
DR   RefSeq; NP_035453.2; NM_011323.3.
DR   PDB; 3WFN; X-ray; 1.95 A; B/C/D/E=1893-1914.
DR   PDBsum; 3WFN; -.
DR   AlphaFoldDB; Q9WTU3; -.
DR   SMR; Q9WTU3; -.
DR   BioGRID; 203103; 8.
DR   IntAct; Q9WTU3; 2.
DR   MINT; Q9WTU3; -.
DR   STRING; 10090.ENSMUSP00000080842; -.
DR   BindingDB; Q9WTU3; -.
DR   ChEMBL; CHEMBL1914275; -.
DR   GuidetoPHARMACOLOGY; 583; -.
DR   GlyCosmos; Q9WTU3; 8 sites, No reported glycans.
DR   GlyGen; Q9WTU3; 8 sites.
DR   iPTMnet; Q9WTU3; -.
DR   PhosphoSitePlus; Q9WTU3; -.
DR   SwissPalm; Q9WTU3; -.
DR   MaxQB; Q9WTU3; -.
DR   PaxDb; 10090-ENSMUSP00000080842; -.
DR   ProteomicsDB; 253416; -. [Q9WTU3-1]
DR   ProteomicsDB; 253417; -. [Q9WTU3-2]
DR   ProteomicsDB; 253418; -. [Q9WTU3-3]
DR   ProteomicsDB; 253419; -. [Q9WTU3-4]
DR   ProteomicsDB; 253420; -. [Q9WTU3-5]
DR   ABCD; Q9WTU3; 1 sequenced antibody.
DR   DNASU; 20273; -.
DR   GeneID; 20273; -.
DR   KEGG; mmu:20273; -.
DR   AGR; MGI:103169; -.
DR   CTD; 6334; -.
DR   MGI; MGI:103169; Scn8a.
DR   eggNOG; KOG2301; Eukaryota.
DR   InParanoid; Q9WTU3; -.
DR   OrthoDB; 1110761at2759; -.
DR   PhylomeDB; Q9WTU3; -.
DR   BioGRID-ORCS; 20273; 0 hits in 81 CRISPR screens.
DR   ChiTaRS; Scn8a; mouse.
DR   PRO; PR:Q9WTU3; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q9WTU3; Protein.
DR   GO; GO:0030424; C:axon; ISO:MGI.
DR   GO; GO:0043194; C:axon initial segment; ISO:MGI.
DR   GO; GO:0030054; C:cell junction; ISO:MGI.
DR   GO; GO:0030425; C:dendrite; IDA:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR   GO; GO:0033268; C:node of Ranvier; IDA:BHF-UCL.
DR   GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI.
DR   GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI.
DR   GO; GO:0034706; C:sodium channel complex; IPI:MGI.
DR   GO; GO:0001518; C:voltage-gated sodium channel complex; ISS:UniProtKB.
DR   GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0031402; F:sodium ion binding; ISS:UniProtKB.
DR   GO; GO:0005248; F:voltage-gated sodium channel activity; ISS:UniProtKB.
DR   GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR   GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR   GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR   GO; GO:0007517; P:muscle organ development; IMP:MGI.
DR   GO; GO:0021675; P:nerve development; IMP:MGI.
DR   GO; GO:0019228; P:neuronal action potential; ISO:MGI.
DR   GO; GO:0009636; P:response to toxic substance; IDA:MGI.
DR   GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006814; P:sodium ion transport; ISO:MGI.
DR   CDD; cd13433; Na_channel_gate; 1.
DR   Gene3D; 1.10.287.70; -; 4.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   Gene3D; 1.20.5.1190; iswi atpase; 1.
DR   Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 4.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR   InterPro; IPR008054; Na_channel_a8su.
DR   InterPro; IPR001696; Na_channel_asu.
DR   InterPro; IPR044564; Na_chnl_inactivation_gate.
DR   InterPro; IPR010526; Na_trans_assoc_dom.
DR   InterPro; IPR024583; Na_trans_cytopl.
DR   InterPro; IPR043203; VGCC_Ca_Na.
DR   InterPro; IPR027359; Volt_channel_dom_sf.
DR   PANTHER; PTHR10037:SF23; SODIUM CHANNEL PROTEIN TYPE 8 SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR10037; VOLTAGE-GATED CATION CHANNEL CALCIUM AND SODIUM; 1.
DR   Pfam; PF00520; Ion_trans; 4.
DR   Pfam; PF00612; IQ; 1.
DR   Pfam; PF06512; Na_trans_assoc; 1.
DR   Pfam; PF11933; Na_trans_cytopl; 1.
DR   PRINTS; PR00170; NACHANNEL.
DR   PRINTS; PR01667; NACHANNEL8.
DR   SMART; SM00015; IQ; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 4.
DR   PROSITE; PS50096; IQ; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW   Cell projection; Disease variant; Disulfide bond; Glycoprotein;
KW   Ion channel; Ion transport; Membrane; Metal-binding; Nucleotide-binding;
KW   Phosphoprotein; Reference proteome; Repeat; Sodium; Sodium channel;
KW   Sodium transport; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation; Voltage-gated channel.
FT   CHAIN           1..1978
FT                   /note="Sodium channel protein type 8 subunit alpha"
FT                   /id="PRO_0000048501"
FT   TOPO_DOM        1..132
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        133..151
FT                   /note="Helical; Name=S1 of repeat I"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        152..158
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        159..179
FT                   /note="Helical; Name=S2 of repeat I"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        180..193
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        194..211
FT                   /note="Helical; Name=S3 of repeat I"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        212..217
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        218..234
FT                   /note="Helical; Name=S4 of repeat I"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        235..253
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        254..273
FT                   /note="Helical; Name=S5 of repeat I"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        274..355
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        356..380
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        381..387
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        388..408
FT                   /note="Helical; Name=S6 of repeat I"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        409..751
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        752..770
FT                   /note="Helical; Name=S1 of repeat II"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        771..781
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        782..801
FT                   /note="Helical; Name=S2 of repeat II"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        802..815
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        816..835
FT                   /note="Helical; Name=S3 of repeat II"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        836..837
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        838..855
FT                   /note="Helical; Name=S4 of repeat II"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        856..871
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        872..890
FT                   /note="Helical; Name=S5 of repeat II"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        891..919
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        920..940
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        941..953
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        954..974
FT                   /note="Helical; Name=S6 of repeat II"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        975..1197
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1198..1215
FT                   /note="Helical; Name=S1 of repeat III"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1216..1228
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1229..1247
FT                   /note="Helical; Name=S2 of repeat III"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1248..1261
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1262..1280
FT                   /note="Helical; Name=S3 of repeat III"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1281..1288
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1289..1307
FT                   /note="Helical; Name=S4 of repeat III"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1308..1324
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1325..1344
FT                   /note="Helical; Name=S5 of repeat III"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1345..1397
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        1398..1419
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1420..1436
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1437..1458
FT                   /note="Helical; Name=S6 of repeat III"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1459..1521
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1522..1539
FT                   /note="Helical; Name=S1 of repeat IV"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1540..1550
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1551..1569
FT                   /note="Helical; Name=S2 of repeat IV"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1570..1581
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1582..1599
FT                   /note="Helical; Name=S3 of repeat IV"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1600..1612
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1613..1629
FT                   /note="Helical; Name=S4 of repeat IV"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1630..1648
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1649..1666
FT                   /note="Helical; Name=S5 of repeat IV"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1667..1688
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        1689..1711
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1712..1740
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1741..1763
FT                   /note="Helical; Name=S6 of repeat IV"
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   TOPO_DOM        1764..1978
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   REPEAT          114..442
FT                   /note="I"
FT                   /evidence="ECO:0000305"
FT   REPEAT          733..1005
FT                   /note="II"
FT                   /evidence="ECO:0000305"
FT   REPEAT          1178..1493
FT                   /note="III"
FT                   /evidence="ECO:0000305"
FT   REPEAT          1502..1799
FT                   /note="IV"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          1893..1922
FT                   /note="IQ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00116,
FT                   ECO:0000305"
FT   REGION          1..20
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          28..62
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          446..530
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          576..597
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1105..1146
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1924..1978
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        28..57
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        500..530
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1114..1129
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1948..1978
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         371
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   BINDING         373
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   BINDING         891..898
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255"
FT   BINDING         937
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   BINDING         1411
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   MOD_RES         518
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O88420"
FT   MOD_RES         520
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O88420"
FT   MOD_RES         1495
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000250|UniProtKB:Q15858"
FT   CARBOHYD        215
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        308
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        326
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1356
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1370
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1381
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        281..333
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   DISULFID        902
FT                   /note="Interchain; with SCN2B or SCN4B"
FT                   /evidence="ECO:0000250|UniProtKB:P04775"
FT   DISULFID        902
FT                   /note="Interchain; with the conotoxin GVIIJ (when the
FT                   channel is not linked to SCN2B or SCN4B; the bond to SCN2B
FT                   or SCN4B protects the channel from the inhibition by
FT                   toxin)"
FT                   /evidence="ECO:0000250|UniProtKB:P04775"
FT   DISULFID        904..910
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   DISULFID        942..951
FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT   DISULFID        1354..1374
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   DISULFID        1719..1734
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQD0"
FT   VAR_SEQ         428..673
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7670495"
FT                   /id="VSP_050594"
FT   VAR_SEQ         664
FT                   /note="E -> EVKIDKAATDS (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9828131"
FT                   /id="VSP_050595"
FT   VAR_SEQ         1272..1312
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:9295353"
FT                   /id="VSP_050598"
FT   VAR_SEQ         1273..1280
FT                   /note="SLVSLIAN -> PLSLSGLI (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:9295353"
FT                   /id="VSP_050596"
FT   VAR_SEQ         1281..1978
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:9295353"
FT                   /id="VSP_050597"
FT   VARIANT         5
FT                   /note="V -> L"
FT                   /evidence="ECO:0000269|PubMed:16141072,
FT                   ECO:0000269|PubMed:8815882"
FT   VARIANT         1317
FT                   /note="A -> T (in medjo)"
FT                   /evidence="ECO:0000269|PubMed:8815882"
FT   MUTAGEN         1602
FT                   /note="D->E: Decrease in sensitivity to the scorpion toxin
FT                   BMKM1."
FT                   /evidence="ECO:0000269|PubMed:20678086"
FT   MUTAGEN         1901
FT                   /note="Q->A: Decreases interaction with CALM1 in the
FT                   absence of calcium."
FT                   /evidence="ECO:0000269|PubMed:23942337"
FT   MUTAGEN         1902
FT                   /note="R->A: Decreases interaction with CALM1 in the
FT                   presence and absence of calcium and reduces rate of channel
FT                   inactivation."
FT                   /evidence="ECO:0000269|PubMed:23942337"
FT   MUTAGEN         1904
FT                   /note="Y->A: Decreases interaction with CALM1 in the
FT                   presence and absence of calcium and reduces rate of channel
FT                   inactivation."
FT                   /evidence="ECO:0000269|PubMed:23942337"
FT   MUTAGEN         1905
FT                   /note="R->A: Decreases interaction with CALM1 in the
FT                   absence of calcium."
FT   CONFLICT        207
FT                   /note="V -> I (in Ref. 3; BAE34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        212
FT                   /note="D -> N (in Ref. 3; BAE34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        554
FT                   /note="P -> T (in Ref. 3; BAE34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        596
FT                   /note="G -> D (in Ref. 3; BAE34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1498
FT                   /note="P -> A (in Ref. 5; AAA65599)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1504
FT                   /note="R -> E (in Ref. 5; AAA65599)"
FT                   /evidence="ECO:0000305"
FT   HELIX           1893..1912
FT                   /evidence="ECO:0007829|PDB:3WFN"
SQ   SEQUENCE   1978 AA;  225141 MW;  9EA4A8E610707220 CRC64;
     MAARVLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE
     AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL
     IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPEWSKN VEYTFTGIYT FESLVKIIAR
     GFCIDGFTFL RDPWNWLDFS VIMMAYVTEF VDLGNVSALR TFRVLRALKT ISVIPGLKTI
     VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTRGF
     DWEEYINNKT NFYMVPGMLE PLLCGNSSDA GQCPEGFQCM KAGRNPNYGY TSFDTFSWAF
     LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA
     TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEDG VGSPRSSSEL
     SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF
     SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS
     LFIPIRARER RSSYSGYSGY SQCSRSSRIF PSLRRSVKRN STVDCNGVVS LIGPGSHIGR
     LLPEATTEVE IKKKGPGSLL VSMEQLASYG RKDRINSIMS VVTNTLVEEL EESQRKCPPC
     WYKFANTFLI WECHPYWIKL KEIVNLIVMD PFVDLAITIC IVLNTLFMAM EHHPMTPQFE
     HVLAVGNLVF TGIFTAEMFL KLIAMDPYYY FQEGWNIFDG FIVSLSLMEL GLADVEGLSV
     LRSFRLLRVF KLAKSWPTLN MLIKIIGNSV GALGNLTLVL AIIVFIFAVV GMQLFGKSYK
     ECVCKISQEC KLPRWHMNDF FHSFLIVFRV LCGEWIETMW DCMEVAGQAM CLIVFMMVMV
     IGNLVVLNLF LALLLSSFSA DNLAATDDDG EMNNLQISVI RIKKGVAWAK VKVHAFMQAH
     FKQREADEVK PLDELYEKKA NCIANHTGVD IHRNGDFQKN GNGTTSGIGS SVEKYIIDED
     HMSFINNPNL TVRVPIAVGE SDFENLNTED VSSESDPEGS KDKLDDTSSS EGSTIDIKPE
     VEEVPVEQPE EYLDPDACFT EGCVQRFKCC QVNIEEGLGK SWWILRKTCF LIVEHNWFET
     FIIFMILLSS GALAFEDIYI EQRKTIRTIL EYADKVFTYI FILEMLLKWT AYGFVKFFTN
     AWCWLDFLIV AVSLVSLIAN ALGYSELGAI KSLRTLRALR PLRALSRFEG MRVVVNALVG
     AIPSIMNVLL VCLIFWLIFS IMGVNLFAGK YHYCFNETSE IRFEIDEVNN KTDCEKLMEG
     NNTEIRWKNV KINFDNVGAG YLALLQVATF KGWMDIMYAA VDSRKPDEQP DYEGNIYMYI
     YFVIFIIFGS FFTLNLFIGV IIDNFNQQKK KFGGQDIFMT EEQKKYYNAM KKLGSKKPQK
     PIPRPLNKIQ GIVFDFVTQQ AFDIVIMMLI CLNMVTMMVE TDTQSKQMEN ILYWINLVFV
     IFFTCECVLK MFALRHYYFT IGWNIFDFVV VILSIVGMFL ADIIEKYFVS PTLFRVIRLA
     RIGRILRLIK GAKGIRTLLF ALMMSLPALF NIGLLLFLVM FIFSIFGMSN FAYVKHEAGI
     DDMFNFETFG NSMICLFQIT TSAGWDGLLL PILNRPPDCS LDKEHPGSGF KGDCGNPSVG
     IFFFVSYIII SFLIVVNMYI AIILENFSVA TEESADPLSE DDFETFYEIW EKFDPDATQF
     IEYCKLADFA DALEHPLRVP KPNTIELIAM DLPMVSGDRI HCLDILFAFT KRVLGDSGEL
     DILRQQMEER FVASNPSKVS YEPITTTLRR KQEEVSAVVL QRAYRGHLAR RGFICRKITS
     NKLENGGTHR EKKESTPSTA SLPSYDSVTK PDKEKQQRAE EGRRERAKRQ KEVRESKC
//