SCN1A_MOUSE
ID SCN1A_MOUSE Reviewed; 2009 AA.
AC A2APX8; A2APX6; A2APX7; Q68V28;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Sodium channel protein type 1 subunit alpha;
DE AltName: Full=Sodium channel protein brain I subunit alpha;
DE AltName: Full=Sodium channel protein type I subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.1;
GN Name=Scn1a {ECO:0000312|MGI:MGI:98246};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1489-1708.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=15746173; DOI=10.1113/jphysiol.2004.079681;
RA Haufe V., Camacho J.A., Dumaine R., Guenther B., Bollensdorff C.,
RA von Banchet G.S., Benndorf K., Zimmer T.;
RT "Expression pattern of neuronal and skeletal muscle voltage-gated Na+
RT channels in the developing mouse heart.";
RL J. Physiol. (Lond.) 564:683-696(2005).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16921370; DOI=10.1038/nn1754;
RA Yu F.H., Mantegazza M., Westenbroek R.E., Robbins C.A., Kalume F.,
RA Burton K.A., Spain W.J., McKnight G.S., Scheuer T., Catterall W.A.;
RT "Reduced sodium current in GABAergic interneurons in a mouse model of
RT severe myoclonic epilepsy in infancy.";
RL Nat. Neurosci. 9:1142-1149(2006).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17928448; DOI=10.1523/jneurosci.2162-07.2007;
RA Kalume F., Yu F.H., Westenbroek R.E., Scheuer T., Catterall W.A.;
RT "Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice:
RT implications for ataxia in severe myoclonic epilepsy in infancy.";
RL J. Neurosci. 27:11065-11074(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-551, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP MUTAGENESIS OF ARG-1648.
RX PubMed=20100831; DOI=10.1074/jbc.m109.078568;
RA Martin M.S., Dutt K., Papale L.A., Dube C.M., Dutton S.B., de Haan G.,
RA Shankar A., Tufik S., Meisler M.H., Baram T.Z., Goldin A.L., Escayg A.;
RT "Altered function of the SCN1A voltage-gated sodium channel leads to gamma-
RT aminobutyric acid-ergic (GABAergic) interneuron abnormalities.";
RL J. Biol. Chem. 285:9823-9834(2010).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22914087; DOI=10.1038/nature11356;
RA Han S., Tai C., Westenbroek R.E., Yu F.H., Cheah C.S., Potter G.B.,
RA Rubenstein J.L., Scheuer T., de la Iglesia H.O., Catterall W.A.;
RT "Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-
RT mediated neurotransmission.";
RL Nature 489:385-390(2012).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=22908258; DOI=10.1073/pnas.1211591109;
RA Cheah C.S., Yu F.H., Westenbroek R.E., Kalume F.K., Oakley J.C.,
RA Potter G.B., Rubenstein J.L., Catterall W.A.;
RT "Specific deletion of NaV1.1 sodium channels in inhibitory interneurons
RT causes seizures and premature death in a mouse model of Dravet syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:14646-14651(2012).
RN [9]
RP MUTAGENESIS OF ARG-1648.
RX PubMed=26694226; DOI=10.1111/gbb.12281;
RA Sawyer N.T., Helvig A.W., Makinson C.D., Decker M.J., Neigh G.N.,
RA Escayg A.;
RT "Scn1a dysfunction alters behavior but not the effect of stress on seizure
RT response.";
RL Genes Brain Behav. 15:335-347(2016).
RN [10]
RP FUNCTION, ACTIVITY REGULATION, DOMAIN, AND TISSUE SPECIFICITY.
RX PubMed=27281198; DOI=10.1038/nature17976;
RA Osteen J.D., Herzig V., Gilchrist J., Emrick J.J., Zhang C., Wang X.,
RA Castro J., Garcia-Caraballo S., Grundy L., Rychkov G.Y., Weyer A.D.,
RA Dekan Z., Undheim E.A., Alewood P., Stucky C.L., Brierley S.M.,
RA Basbaum A.I., Bosmans F., King G.F., Julius D.;
RT "Selective spider toxins reveal a role for the Nav1.1 channel in mechanical
RT pain.";
RL Nature 534:494-499(2016).
CC -!- FUNCTION: Mediates the voltage-dependent sodium ion permeability of
CC excitable membranes (PubMed:16921370, PubMed:17928448,
CC PubMed:27281198). Assuming opened or closed conformations in response
CC to the voltage difference across the membrane, the protein forms a
CC sodium-selective channel through which Na(+) ions may pass in
CC accordance with their electrochemical gradient. Plays a key role in
CC brain, probably by regulating the moment when neurotransmitters are
CC released in neurons (PubMed:16921370, PubMed:22914087). Involved in
CC sensory perception of mechanical pain: activation in somatosensory
CC neurons induces pain without neurogenic inflammation and produces
CC hypersensitivity to mechanical, but not thermal stimuli
CC (PubMed:27281198). {ECO:0000269|PubMed:16921370,
CC ECO:0000269|PubMed:17928448, ECO:0000269|PubMed:22914087,
CC ECO:0000269|PubMed:27281198}.
CC -!- ACTIVITY REGULATION: Inactivation of this channel is specifically
CC inhibited by the spider toxins Hm1a and Hm1b (H.maculata, AC P60992 and
CC AC P0DOC5) in somatosensory neurons to elicit acute pain and mechanical
CC allodynia (PubMed:27281198). {ECO:0000269|PubMed:16921370,
CC ECO:0000269|PubMed:27281198}.
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. Interacts with the conotoxin
CC GVIIJ. {ECO:0000250|UniProtKB:P04774, ECO:0000250|UniProtKB:P35498}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35498};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A2APX8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2APX8-2; Sequence=VSP_058553;
CC Name=3;
CC IsoId=A2APX8-3; Sequence=VSP_058552;
CC -!- TISSUE SPECIFICITY: Present in cerebellar Purkinje neurons (at protein
CC level) (PubMed:17928448). Expressed by myelinated, non-C-fiber neurons
CC in sensory ganglia (PubMed:27281198). {ECO:0000269|PubMed:17928448,
CC ECO:0000269|PubMed:27281198}.
CC -!- DOMAIN: The S3b-S4 and S1-S2 loops of repeat IV are targeted by
CC H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation
CC of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b
CC depends on S1-S2 loops of repeat IV (PubMed:27281198).
CC {ECO:0000269|PubMed:27281198}.
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: Phosphorylation at Ser-1516 by PKC in a highly conserved
CC cytoplasmic loop slows inactivation of the sodium channel and reduces
CC peak sodium currents. {ECO:0000250|UniProtKB:P04775}.
CC -!- DISRUPTION PHENOTYPE: Homozygous mice display severe seizures and
CC premature death on postnatal day 15 (PubMed:16921370). Mice show severe
CC motor deficits, including irregularity of stride length during
CC locomotion, impaired motor reflexes in grasping and mild tremor in
CC limbs when immobile, consistent with cerebellar dysfunction
CC (PubMed:16921370). Heterozygous mice exhibit autistic-like behavior,
CC characterized by hyperactivity, stereotyped behaviors, social
CC interaction deficits and impaired context-dependent spatial memory
CC (PubMed:22914087). Defects are caused by caused by impaired GABAergic
CC neurotransmission (PubMed:22914087). Conditional knockout in forebrain
CC GABAergic neurons leads to premature death caused by generalized tonic-
CC clonic seizures in heterozygous mice (PubMed:22908258).
CC {ECO:0000269|PubMed:16921370, ECO:0000269|PubMed:22908258,
CC ECO:0000269|PubMed:22914087}.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.1/SCN1A subfamily. {ECO:0000305}.
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DR EMBL; AL844526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928726; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJ810515; CAH17959.1; -; mRNA.
DR CCDS; CCDS38131.1; -. [A2APX8-2]
DR CCDS; CCDS84530.1; -. [A2APX8-1]
DR RefSeq; NP_001300926.1; NM_001313997.1. [A2APX8-1]
DR RefSeq; NP_061203.2; NM_018733.2. [A2APX8-2]
DR RefSeq; XP_006499090.1; XM_006499027.3. [A2APX8-1]
DR RefSeq; XP_006499091.1; XM_006499028.3. [A2APX8-2]
DR AlphaFoldDB; A2APX8; -.
DR SMR; A2APX8; -.
DR STRING; 10090.ENSMUSP00000076697; -.
DR BindingDB; A2APX8; -.
DR ChEMBL; CHEMBL4523103; -.
DR GlyConnect; 2718; 1 N-Linked glycan (1 site).
DR GlyGen; A2APX8; 5 sites, 1 N-linked glycan (1 site).
DR iPTMnet; A2APX8; -.
DR PhosphoSitePlus; A2APX8; -.
DR SwissPalm; A2APX8; -.
DR MaxQB; A2APX8; -.
DR PRIDE; A2APX8; -.
DR ProteomicsDB; 256931; -. [A2APX8-1]
DR ProteomicsDB; 256932; -. [A2APX8-2]
DR ProteomicsDB; 256933; -. [A2APX8-3]
DR ABCD; A2APX8; 3 sequenced antibodies.
DR Antibodypedia; 47608; 219 antibodies from 32 providers.
DR DNASU; 20265; -.
DR Ensembl; ENSMUST00000077489; ENSMUSP00000076697; ENSMUSG00000064329. [A2APX8-2]
DR Ensembl; ENSMUST00000094951; ENSMUSP00000092558; ENSMUSG00000064329. [A2APX8-3]
DR Ensembl; ENSMUST00000112366; ENSMUSP00000107985; ENSMUSG00000064329. [A2APX8-1]
DR Ensembl; ENSMUST00000112371; ENSMUSP00000107990; ENSMUSG00000064329. [A2APX8-2]
DR GeneID; 20265; -.
DR KEGG; mmu:20265; -.
DR UCSC; uc033hnf.1; mouse.
DR CTD; 6323; -.
DR MGI; MGI:98246; Scn1a.
DR VEuPathDB; HostDB:ENSMUSG00000064329; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000154224; -.
DR InParanoid; A2APX8; -.
DR OMA; KTELTMS; -.
DR OrthoDB; 56920at2759; -.
DR PhylomeDB; A2APX8; -.
DR TreeFam; TF323985; -.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR BioGRID-ORCS; 20265; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Scn1a; mouse.
DR PRO; PR:A2APX8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2APX8; protein.
DR Bgee; ENSMUSG00000064329; Expressed in facial nucleus and 115 other tissues.
DR ExpressionAtlas; A2APX8; baseline and differential.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0043194; C:axon initial segment; IDA:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0014704; C:intercalated disc; IDA: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:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0034706; C:sodium channel complex; IPI:MGI.
DR GO; GO:0030315; C:T-tubule; IDA: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: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; IDA:UniProtKB.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; ISO:MGI.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IMP:MGI.
DR GO; GO:0019228; P:neuronal action potential; IMP:MGI.
DR GO; GO:0019227; P:neuronal action potential propagation; IMP:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IDA:UniProtKB.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR008051; Na_channel_a1su.
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; PF06512; Na_trans_assoc; 1.
DR Pfam; PF11933; Na_trans_cytopl; 1.
DR PRINTS; PR00170; NACHANNEL.
DR PRINTS; PR01664; NACHANNEL1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Sodium; Sodium channel; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..2009
FT /note="Sodium channel protein type 1 subunit alpha"
FT /id="PRO_0000437536"
FT TOPO_DOM 1..128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 129..147
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 148..154
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 155..175
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 176..189
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 190..207
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 208..213
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 214..230
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 231..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 250..269
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 270..367
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 368..392
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 393..399
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 400..420
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 421..768
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 769..787
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 788..798
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 799..818
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 819..832
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 833..852
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 853..854
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 855..872
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 873..888
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 889..907
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 908..936
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 937..957
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 958..970
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 971..991
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 992..1219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1220..1237
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1238..1250
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1251..1269
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1270..1283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1284..1302
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1303..1310
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1311..1329
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1330..1346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1347..1366
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1367..1418
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1419..1440
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1441..1457
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1458..1479
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1480..1542
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1543..1560
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1561..1571
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1572..1590
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1591..1602
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1603..1620
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1621..1633
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1634..1650
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1651..1669
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1670..1687
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1688..1709
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1710..1732
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1733..1762
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1763..1785
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1786..2009
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 110..454
FT /note="I"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT REPEAT 750..1022
FT /note="II"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT REPEAT 1200..1514
FT /note="III"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT REPEAT 1523..1821
FT /note="IV"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT DOMAIN 1915..1944
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 28..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 584..627
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1129..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1561..1571
FT /note="S1-S2 loop of repeat IV"
FT /evidence="ECO:0000269|PubMed:27281198"
FT REGION 1619..1636
FT /note="S3b-S4 loop of repeat IV"
FT /evidence="ECO:0000269|PubMed:27281198"
FT REGION 1984..2009
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..52
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 455..489
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..528
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..620
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1990..2009
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 607
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04774"
FT MOD_RES 1516
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P04775"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 277..345
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 919
FT /note="Interchain; with SCN2B or SCN4B"
FT /evidence="ECO:0000250|UniProtKB:P04775"
FT DISULFID 919
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 959..968
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT VAR_SEQ 654..681
FT /note="Missing (in isoform 3)"
FT /id="VSP_058552"
FT VAR_SEQ 671..681
FT /note="Missing (in isoform 2)"
FT /id="VSP_058553"
FT MUTAGEN 1648
FT /note="R->H: Homozygous mice display spontaneous
FT generalized seizures and premature death between P16 and
FT P26. Heterozygous mice show infrequent spontaneous
FT seizures, increased susceptibility to chemically and
FT hyperthermia-induced generalized seizures and sleep
FT abnormalities. Heterozygous mice also show deficits in
FT social behavior, spatial memory, cued fear conditioning,
FT pre-pulse inhibition and risk assessment."
FT /evidence="ECO:0000269|PubMed:20100831,
FT ECO:0000269|PubMed:26694226"
SQ SEQUENCE 2009 AA; 228800 MW; A373BA0B710C501E CRC64;
MEQTVLVPPG PDSFNFFTRE SLAAIERRIA EEKAKNPKPD KKDDDENGPK PNSDLEAGKN
LPFIYGDIPP EMVSEPLEDL DPYYINKKTF IVLNKGKAIF RFSATSALYI LTPFNPLRKI
AIKILVHSLF SMLIMCTILT NCVFMTMSNP PDWTKNVEYT FTGIYTFESL IKIIARGFCL
EDFTFLRDPW NWLDFTVITF AYVTEFVDLG NVSALRTFRV LRALKTISVI PGLKTIVGAL
IQSVKKLSDV MILTVFCLSV FALIGLQLFM GNLRNKCVQW PPTNASLEEH SIEKNITMDY
NGTLVNETVF EFDWKSYIQD SRYHYFLEGV LDALLCGNSS DAGQCPEGYM CVKAGRNPNY
GYTSFDTFSW AFLSLFRLMT QDFWENLYQL TLRAAGKTYM IFFVLVIFLG SFYLINLILA
VVAMAYEEQN QATLEEAEQK EAEFQQMLEQ LKKQQEAAQQ AAATTASEHS REPSAAGRLS
DSSSEASKLS SKSAKERRNR RKKRKQKEQS GGEEKDDDEF HKSESEDSIR RKGFRFSIEG
NRLTYEKRYS SPHQSLLSIR GSLFSPRRNS RTSLFSFRGR AKDVGSENDF ADDEHSTFED
NESRRDSLFV PRRHGERRNS NLSQTSRSSR MLAVFPANGK MHSTVDCNGV VSLVGGPSVP
TSPVGQLLPE VIIDKPATDD NGTTTETEMR KRRSSSFHVS MDFLEDPSQR QRAMSIASIL
TNTVEELEES RQKCPPCWYK FSNIFLIWDC SPYWLKVKHI VNLVVMDPFV DLAITICIVL
NTLFMAMEHY PMTEHFNHVL TVGNLVFTGI FTAEMFLKII AMDPYYYFQE GWNIFDGFIV
TLSLVELGLA NVEGLSVLRS FRLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII
VFIFAVVGMQ LFGKSYKDCV CKIATDCKLP RWHMNDFFHS FLIVFRVLCG EWIETMWDCM
EVAGQAMCLT VFMMVMVIGN LVVLNLFLAL LLSSFSADNL AATDDDNEMN NLQIAVDRMH
KGIAYVKRKI YEFIQQSFVK KQKILDEIKP LDDLNNRKDN CISNHTTEIG KDLDCLKDVN
GTTSGIGTGS SVEKYIIDES DYMSFINNPS LTVTVPIAVG ESDFENLNTE DFSSESDLEE
SKEKLNESSS SSEGSTVDIG APAEEQPVIE PEETLEPEAC FTEGCVQRFK CCQISVEEGR
GKQWWNLRRT CFRIVEHNWF ETFIVFMILL SSGALAFEDI YIDQRKTIKT MLEYADKVFT
YIFILEMLLK WVAYGYQTYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG AIKSLRTLRA
LRPLRALSRF EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCVNTT
TGDIFEISEV NNHSDCLKLI ERNETARWKN VKVNFDNVGF GYLSLLQVAT FKGWMDIMYA
AVDSRNVELQ PKYEESLYMY LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM
TEEQKKYYNA MKKLGSKKPQ KPIPRPGNKF QGMVFDFVTR QVFDISIMIL ICLNMVTMMV
ETDDQSDYVT SILSRINLVF IVLFTGECVL KLISLRHYYF TIGWNIFDFV VVILSIVGMF
LAELIEKYFV SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV
MFIYAIFGMS NFAYVKREVG IDDMFNFETF GNSMICLFQI TTSAGWDGLL APILNSKPPD
CDPNKVNPGS SVKGDCGNPS VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL
SEDDFEMFYE VWEKFDPDAT QFMEFEKLSQ FAAALEPPLN LPQPNKLQLI AMDLPMVSGD
RIHCLDILFA FTKRVLGESG EMDALRIQME ERFMASNPSK VSYQPITTTL KRKQEEVSAV
IIQRAYRRHL LKRTVKQASF TYNKNKLKGG ANLLVKEDML IDRINENSIT EKTDLTMSTA
ACPPSYDRVT KPIVEKHEQE GKDEKAKGK
