Protein detail
SCN8A
Sodium channel protein type 8 subunit alpha (Sodium channel protein type VIII subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.6)
Entry name SCN8A | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count 24 | Protein classification |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Sodium channel protein type 8 subunit alpha (Sodium channel protein type VIII subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.6)
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Epilepsy
- Voltage-gated ion channels:Voltage-Gated Sodium Channels
- Transporters:Transporter channels and pores
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
133..151; Helical; Name=S1 of repeat I; 159..179; Helical; Name=S2 of repeat I; 194..211; Helical; Name=S3 of repeat I; 218..234; Helical; Name=S4 of repeat I; 254..273; Helical; Name=S5 of repeat I; 388..408; Helical; Name=S6 of repeat I; 754..772; Helical; Name=S1 of repeat II; 784..803; Helical; Name=S2 of repeat II; 818..837; Helical; Name=S3 of repeat II; 840..857; Helical; Name=S4 of repeat II; 874..892; Helical; Name=S5 of repeat II; 956..976; Helical; Name=S6 of repeat II; 1200..1217; Helical; Name=S1 of repeat III; 1231..1249; Helical; Name=S2 of repeat III; 1264..1282; Helical; Name=S3 of repeat III; 1291..1309; Helical; Name=S4 of repeat III; 1327..1346; Helical; Name=S5 of repeat III; 1439..1460; Helical; Name=S6 of repeat III; 1524..1541; Helical; Name=S1 of repeat IV; 1553..1571; Helical; Name=S2 of repeat IV; 1584..1601; Helical; Name=S3 of repeat IV; 1615..1631; Helical; Name=S4 of repeat IV; 1651..1668; Helical; Name=S5 of repeat IV; 1743..1765; Helical; Name=S6 of repeat IV
Transmembrane Count
24
Ensembl
Entrez Gene Symbol
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Epilepsy
- Voltage-gated ion channels:Voltage-Gated Sodium Channels
- Transporters:Transporter channels and pores
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
- GO:0001518 voltage-gated sodium channel complex
- GO:0002102 podosome
- GO:0005886 plasma membrane
- GO:0016020 membrane
- GO:0030018 Z disc
- GO:0030054 cell junction
- GO:0030424 axon
- GO:0031410 cytoplasmic vesicle
- GO:0033268 node of Ranvier
- GO:0043194 axon initial segment
- GO:0048787 presynaptic active zone membrane
- GO:0070161 anchoring junction
- GO:0098688 parallel fiber to Purkinje cell synapse
- GO:0098839 postsynaptic density membrane
- GO:0098978 glutamatergic synapse
Molecular Function
Biological Process
Reactome
Mediation Categories
Clinical-translation mediationFusion and delivery mediation
Relations & Evidence
Enzyme-Mediated Modification
4 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| SCN8A | CAMK2A | Q9UQM7 | T | 642 | phosphorylation | PhosphoSite | |
| SCN8A | CAMK2A | Q9UQM7 | S | 541 | phosphorylation | PhosphoSite | |
| SCN8A | CAMK2A | Q9UQM7 | S | 561 | phosphorylation | PhosphoSite | |
| SCN8A | CAMK2A | Q9UQM7 | S | 641 | phosphorylation | PhosphoSite |
Ligand-Receptor Signaling
31 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| ion_channel | ion_channel | Almen2009 | No | Yes | No | No | No |
| sodium | ion_channel | Almen2009 | No | Yes | No | No | No |
| voltage_gated | ion_channel | Almen2009 | No | Yes | No | No | No |
| voltage_gated | ion_channel | Surfaceome | No | Yes | No | No | No |
| transporter | transporter | OmniPath | No | Yes | No | No | No |
| ion_channel | ion_channel | OmniPath | No | Yes | No | No | No |
| transmembrane | transmembrane | UniProt_location | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_topology | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_keyword | No | No | No | No | No |
| transmembrane | transmembrane | TopDB | No | No | No | No | No |
Regulatory Interaction Network
13 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| KCC2G | Q13555 | SCN8A | Q9UQD0 | Yes | Yes | No | SIGNOR | SIGNOR:32611770 |
| CALM1 | P0DP23 | SCN8A | Q9UQD0 | Yes | No | Yes | SIGNOR | SIGNOR:11807557 |
| KCC2D | Q13557 | SCN8A | Q9UQD0 | Yes | Yes | No | SIGNOR | SIGNOR:32611770 |
| FGF11 | Q92914 | SCN8A | Q9UQD0 | Yes | No | Yes | SIGNOR | SIGNOR:20679355 |
| GSK3B | P49841 | SCN8A | Q9UQD0 | Yes | Yes | No | SIGNOR | SIGNOR:29642012 |
| CALM2 | P0DP24 | SCN8A | Q9UQD0 | Yes | No | Yes | SIGNOR | SIGNOR:11807557 |
| CALM3 | P0DP25 | SCN8A | Q9UQD0 | Yes | No | Yes | SIGNOR | SIGNOR:11807557 |
| NED4L | Q96PU5 | SCN8A | Q9UQD0 | Yes | No | Yes | SIGNOR | SIGNOR:23778145 |
| FGF12 | P61328 | SCN8A | Q9UQD0 | Yes | No | Yes | SIGNOR | SIGNOR:20679355 |
| FGF13 | Q92913 | SCN8A | Q9UQD0 | Yes | No | Yes | Fantom5_LRdbCellTalkDBHPRD_LRdbiTALKtalklrSIGNORconnectomeDB2020HPRDHPRD_talklrCellinkerLRdbRamilowski2015 | Cellinker:15282281HPRD:15282281LRdb:15282281SIGNOR:20679355CellTalkDB:15282281connectomeDB2020:15282281 |
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Protein Complex Composition
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential Ultracentrifugation | Mass spectrometry | 1 | 24196483 |
Sequence, Structure & Domains
Sequences
Length
1,980
Mass
225,280
Sequence
MAARLLAPPGPDSFKPFTPESLANIERRIAESKLKKPPKADGSHREDDEDSKPKPNSDLEAGKSLPFIYGDIPQGLVAVPLEDFDPYYLTQKTFVVLNRGKTLFRFSATPALYILSPFNLIRRIAIKILIHSVFSMIIMCTILTNCVFMTFSNPPDWSKNVEYTFTGIYTFESLVKIIARGFCIDGFTFLRDPWNWLDFSVIMMAYITEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCVVWPINFNESYLENGTKGFDWEEYINNKTNFYTVPGMLEPLLCGNSSDAGQCPEGYQCMKAGRNPNYGYTSFDTFSWAFLALFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFVGSFYLVNLILAVVAMAYEEQNQATLEEAEQKEAEFKAMLEQLKKQQEEAQAAAMATSAGTVSEDAIEEEGEEGGGSPRSSSEISKLSSKSAKERRNRRKKRKQKELSEGEEKGDPEKVFKSESEDGMRRKAFRLPDNRIGRKFSIMNQSLLSIPGSPFLSRHNSKSSIFSFRGPGRFRDPGSENEFADDEHSTVEESEGRRDSLFIPIRARERRSSYSGYSGYSQGSRSSRIFPSLRRSVKRNSTVDCNGVVSLIGGPGSHIGGRLLPEATTEVEIKKKGPGSLLVSMDQLASYGRKDRINSIMSVVTNTLVEELEESQRKCPPCWYKFANTFLIWECHPYWIKLKEIVNLIVMDPFVDLAITICIVLNTLFMAMEHHPMTPQFEHVLAVGNLVFTGIFTAEMFLKLIAMDPYYYFQEGWNIFDGFIVSLSLMELSLADVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKINQDCELPRWHMHDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDGEMNNLQISVIRIKKGVAWTKLKVHAFMQAHFKQREADEVKPLDELYEKKANCIANHTGADIHRNGDFQKNGNGTTSGIGSSVEKYIIDEDHMSFINNPNLTVRVPIAVGESDFENLNTEDVSSESDPEGSKDKLDDTSSSEGSTIDIKPEVEEVPVEQPEEYLDPDACFTEGCVQRFKCCQVNIEEGLGKSWWILRKTCFLIVEHNWFETFIIFMILLSSGALAFEDIYIEQRKTIRTILEYADKVFTYIFILEMLLKWTAYGFVKFFTNAWCWLDFLIVAVSLVSLIANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKYHYCFNETSEIRFEIEDVNNKTECEKLMEGNNTEIRWKNVKINFDNVGAGYLALLQVATFKGWMDIMYAAVDSRKPDEQPKYEDNIYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPLNKIQGIVFDFVTQQAFDIVIMMLICLNMVTMMVETDTQSKQMENILYWINLVFVIFFTCECVLKMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIFSIFGMSNFAYVKHEAGIDDMFNFETFGNSMICLFQITTSAGWDGLLLPILNRPPDCSLDKEHPGSGFKGDCGNPSVGIFFFVSYIIISFLIVVNMYIAIILENFSVATEESADPLSEDDFETFYEIWEKFDPDATQFIEYCKLADFADALEHPLRVPKPNTIELIAMDLPMVSGDRIHCLDILFAFTKRVLGDSGELDILRQQMEERFVASNPSKVSYEPITTTLRRKQEEVSAVVLQRAYRGHLARRGFICKKTTSNKLENGGTHREKKESTPSTASLPSYDSVTKPEKEKQQRAEEGRRERAKRQKEVRESKC
Alternative Products
Event=Alternative splicing; Named isoforms=5; Name=1; IsoId=Q9UQD0-1; Sequence=Displayed; Name=2; Synonyms=5A; IsoId=Q9UQD0-2; Sequence=VSP_050589, VSP_050590; Name=3; IsoId=Q9UQD0-3; Sequence=VSP_050591; Name=4; Synonyms=18N; IsoId=Q9UQD0-4; Sequence=VSP_050592, VSP_050593; Name=5; Synonyms=Delta18; IsoId=Q9UQD0-5; Sequence=VSP_038651
Alternative Sequence
207; I -> V (in isoform 2); 212; N -> D (in isoform 2); 666; E -> EVKIDKAATDDS (in isoform 3); 1275..1315; Missing (in isoform 5); 1275..1283; SLVSLIANA -> PLNLSGLI (in isoform 4); 1284..1980; Missing (in isoform 4)
3D Structural Models
Turn
57..59; 112..114; 274..277; 302..307; 346..350; 369..371; 397..399; 748..750; 834..836; 872..875; 1302..1305; 1307..1309; 1359..1362; 1367..1369; 1451..1453; 1510..1513; 1573..1575; 1703..1706; 1707..1715; 1718..1720
Helix
19..34; 67..69; 117..119; 122..129; 132..150; 156..158; 159..179; 189..191; 193..207; 216..223; 224..228; 229..233; 237..249; 253..272; 288..290; 309..311; 356..367; 372..383; 385..387; 388..396; 401..443; 722..730; 739..747; 753..770; 779..806; 809..813; 820..832; 840..843; 847..856; 859..871; 876..897; 900..903; 905..907; 922..934; 938..948; 951..979; 981..983; 996..1006; 1179..1196; 1200..1214; 1220..1223; 1226..1254; 1256..1260; 1263..1284; 1290..1296; 1297..1301; 1311..1346; 1373..1379; 1399..1410; 1415..1424; 1438..1440; 1441..1450; 1454..1474; 1483..1496; 1514..1519; 1522..1538; 1548..1572; 1585..1605; 1615..1620; 1621..1631; 1635..1672; 1691..1702; 1739..1772
Beta Strand
60..63; 89..91; 94..97; 103..106; 151..153; 182..187; 208..210; 278..283; 294..297; 326..330; 337..341; 353..355; 815..817; 837..839; 919..921; 986..988; 1176..1178; 1349..1351; 1354..1358; 1386..1391; 1427..1430; 1580..1584; 1673..1676; 1684..1690
3D Structure
Electron microscopy (3)
Domain & Motif Annotations
Compositional Bias
28..61; Basic and acidic residues; 474..486; Low complexity; 489..500; Basic residues; 501..530; Basic and acidic residues; 586..602; Basic and acidic residues; 1938..1949; Polar residues; 1951..1980; Basic and acidic residues
Repeat
114..442; I; 735..1007; II; 1180..1495; III; 1504..1801; IV
Domain (CC)
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
Domain (FT)
1895..1924; IQ
Region
1..20; Disordered; 28..62; Disordered; 446..530; Disordered; 568..602; Disordered; 1107..1148; Disordered; 1922..1980; Disordered
Protein Families
- Sodium channel (TC 1.A.1.10) family
- Nav1.6/SCN8A subfamily
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.
Clinical Relevance
Related Diseases
Biomarker
Phase 1; Phase 2
Drugs
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