SCN8A_MOUSE
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 03-AUG-2022, entry version 166.
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
RC Fetal brain {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 -!- 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). Beta-1
CC (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha,
CC 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 the conotoxin GVIIJ (By
CC similarity). Interacts with the scorpion toxin BMK M1
CC (PubMed:20678086). Interacts with CALM1; the interaction modulates the
CC 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 GlyGen; Q9WTU3; 8 sites.
DR iPTMnet; Q9WTU3; -.
DR PhosphoSitePlus; Q9WTU3; -.
DR SwissPalm; Q9WTU3; -.
DR MaxQB; Q9WTU3; -.
DR PaxDb; Q9WTU3; -.
DR PRIDE; Q9WTU3; -.
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 CTD; 6334; -.
DR MGI; MGI:103169; Scn8a.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; Q9WTU3; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q9WTU3; -.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR BioGRID-ORCS; 20273; 0 hits in 76 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:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; 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:0034706; C:sodium channel complex; IPI:MGI.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
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:0019228; P:neuronal action potential; ISO:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
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; 1.20.120.350; -; 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.
DR InterPro; IPR024583; Na_trans_cytopl.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 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 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; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW 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 891..898
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
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 942..951
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
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 BMK M1."
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
