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Protein

Sodium channel protein type 2 subunit alpha

Gene

SCN2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1489Important for channel closureBy similarity1

GO - Molecular functioni

  • voltage-gated sodium channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIon channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-HSA-445095. Interaction between L1 and Ankyrins.
R-HSA-5576892. Phase 0 - rapid depolarisation.
SIGNORiQ99250.

Protein family/group databases

TCDBi1.A.1.10.12. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 2 subunit alpha
Alternative name(s):
HBSC II
Sodium channel protein brain II subunit alpha
Sodium channel protein type II subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.2
Gene namesi
Name:SCN2A
Synonyms:NAC2, SCN2A1, SCN2A2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000136531.13.
HGNCiHGNC:10588. SCN2A.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 129CytoplasmicCuratedAdd BLAST129
Transmembranei130 – 148Helical; Name=S1 of repeat IBy similarityAdd BLAST19
Topological domaini149 – 155ExtracellularCurated7
Transmembranei156 – 176Helical; Name=S2 of repeat IBy similarityAdd BLAST21
Topological domaini177 – 190CytoplasmicCuratedAdd BLAST14
Transmembranei191 – 208Helical; Name=S3 of repeat IBy similarityAdd BLAST18
Topological domaini209 – 214ExtracellularCurated6
Transmembranei215 – 231Helical; Name=S4 of repeat IBy similarityAdd BLAST17
Topological domaini232 – 250CytoplasmicCuratedAdd BLAST19
Transmembranei251 – 270Helical; Name=S5 of repeat IBy similarityAdd BLAST20
Topological domaini271 – 369ExtracellularCuratedAdd BLAST99
Intramembranei370 – 394Pore-formingBy similarityAdd BLAST25
Topological domaini395 – 401ExtracellularCurated7
Transmembranei402 – 422Helical; Name=S6 of repeat IBy similarityAdd BLAST21
Topological domaini423 – 759CytoplasmicCuratedAdd BLAST337
Transmembranei760 – 778Helical; Name=S1 of repeat IIBy similarityAdd BLAST19
Topological domaini779 – 789ExtracellularCuratedAdd BLAST11
Transmembranei790 – 809Helical; Name=S2 of repeat IIBy similarityAdd BLAST20
Topological domaini810 – 823CytoplasmicCuratedAdd BLAST14
Transmembranei824 – 843Helical; Name=S3 of repeat IIBy similarityAdd BLAST20
Topological domaini844 – 845ExtracellularCurated2
Transmembranei846 – 863Helical; Name=S4 of repeat IIBy similarityAdd BLAST18
Topological domaini864 – 879CytoplasmicCuratedAdd BLAST16
Transmembranei880 – 898Helical; Name=S5 of repeat IIBy similarityAdd BLAST19
Topological domaini899 – 927ExtracellularCuratedAdd BLAST29
Intramembranei928 – 948Pore-formingBy similarityAdd BLAST21
Topological domaini949 – 961ExtracellularCuratedAdd BLAST13
Transmembranei962 – 982Helical; Name=S6 of repeat IIBy similarityAdd BLAST21
Topological domaini983 – 1209CytoplasmicCuratedAdd BLAST227
Transmembranei1210 – 1227Helical; Name=S1 of repeat IIIBy similarityAdd BLAST18
Topological domaini1228 – 1240ExtracellularCuratedAdd BLAST13
Transmembranei1241 – 1259Helical; Name=S2 of repeat IIIBy similarityAdd BLAST19
Topological domaini1260 – 1273CytoplasmicCuratedAdd BLAST14
Transmembranei1274 – 1292Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini1293 – 1300ExtracellularCurated8
Transmembranei1301 – 1319Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini1320 – 1336CytoplasmicCuratedAdd BLAST17
Transmembranei1337 – 1356Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini1357 – 1408ExtracellularCuratedAdd BLAST52
Intramembranei1409 – 1430Pore-formingBy similarityAdd BLAST22
Topological domaini1431 – 1447ExtracellularCuratedAdd BLAST17
Transmembranei1448 – 1469Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1470 – 1532CytoplasmicCuratedAdd BLAST63
Transmembranei1533 – 1550Helical; Name=S1 of repeat IVBy similarityAdd BLAST18
Topological domaini1551 – 1561ExtracellularCuratedAdd BLAST11
Transmembranei1562 – 1580Helical; Name=S2 of repeat IVBy similarityAdd BLAST19
Topological domaini1581 – 1592CytoplasmicCuratedAdd BLAST12
Transmembranei1593 – 1610Helical; Name=S3 of repeat IVBy similarityAdd BLAST18
Topological domaini1611 – 1623ExtracellularCuratedAdd BLAST13
Transmembranei1624 – 1640Helical; Name=S4 of repeat IVBy similarityAdd BLAST17
Topological domaini1641 – 1659CytoplasmicCuratedAdd BLAST19
Transmembranei1660 – 1677Helical; Name=S5 of repeat IVBy similarityAdd BLAST18
Topological domaini1678 – 1699ExtracellularCuratedAdd BLAST22
Intramembranei1700 – 1722Pore-formingBy similarityAdd BLAST23
Topological domaini1723 – 1752ExtracellularCuratedAdd BLAST30
Transmembranei1753 – 1775Helical; Name=S6 of repeat IVBy similarityAdd BLAST23
Topological domaini1776 – 2005CytoplasmicCuratedAdd BLAST230

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Seizures, benign familial infantile, 3 (BFIS3)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant.
See also OMIM:607745
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029733188R → W in BFIS3; mutant channel inactivates more slowly than wild-type whereas the Na(+) channel conductance is not affected. 1 PublicationCorresponds to variant dbSNP:rs121917748Ensembl.1
Natural variantiVAR_072745208V → E in BFIS3. 1 Publication1
Natural variantiVAR_029734223R → Q in BFIS3; increased voltage-gated sodium channel activity; modified voltage dependence of activation and inactivation; gain of function. 3 PublicationsCorresponds to variant dbSNP:rs121917752Ensembl.1
Natural variantiVAR_078455240A → S in BFIS3. 1 Publication1
Natural variantiVAR_065176252M → V in BFIS3; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function. 1 PublicationCorresponds to variant dbSNP:rs387906687Ensembl.1
Natural variantiVAR_065177261V → M in BFIS3; increased voltage-gated sodium channel activity; faster recovery from inactivation; gain of function. 1 Publication1
Natural variantiVAR_078458430E → Q in BFIS3; unknown pathological significance. 1 Publication1
Natural variantiVAR_029737892V → I in BFIS3. 1 PublicationCorresponds to variant dbSNP:rs121917751Ensembl.1
Natural variantiVAR_0784681001N → K in BFIS3. 2 Publications1
Natural variantiVAR_0297381003L → I in BFIS3. 1 PublicationCorresponds to variant dbSNP:rs121917754Ensembl.1
Natural variantiVAR_0297391319R → Q in BFIS3; modified voltage-gated sodium channel activity; modified voltage dependence of activation and inactivation. 4 PublicationsCorresponds to variant dbSNP:rs121917753Ensembl.1
Natural variantiVAR_0787401321E → K in BFIS3; unknown pathological significance. 1 Publication1
Natural variantiVAR_0297401330L → F in BFIS3; increased voltage-gated sodium channel activity; decreased overall channel availability during repetitive stimulation; gain of function; no effect on kinetics of activation or inactivation; no effect on voltage dependence of activation. 3 PublicationsCorresponds to variant dbSNP:rs121917749Ensembl.1
Natural variantiVAR_0787461531Q → K in BFIS3; unknown pathological significance. 1 Publication1
Natural variantiVAR_0297411563L → V in BFIS3; increased voltage-gated sodium channel activity; impaired fast inactivation; gain of function; no effect on kinetics of activation or inactivation; no effect on voltage dependence of activation. 3 PublicationsCorresponds to variant dbSNP:rs121917750Ensembl.1
Natural variantiVAR_0784781589Y → C in BFIS3; increased voltage-gated sodium channel activity; depolarized shift of steady-state inactivation; increased persistent sodium current; slower fast inactivation; accelerated recovery of fast inactivation; gain of function. 1 Publication1
Natural variantiVAR_0784801596I → S in BFIS3; unknown pathological significance. 1 Publication1
Natural variantiVAR_0787471641K → N in BFIS3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs767224097Ensembl.1
Epileptic encephalopathy, early infantile, 11 (EIEE11)21 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
See also OMIM:613721
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078451132N → K in EIEE11. 1 Publication1
Natural variantiVAR_078452136M → I in EIEE11. 2 Publications1
Natural variantiVAR_069996169E → G in EIEE11. 2 Publications1
Natural variantiVAR_078730211G → D in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_069997212N → D in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_069998213V → D in EIEE11. 1 Publication1
Natural variantiVAR_078454218T → K in EIEE11; unknown pathological significance. 1 Publication1
Natural variantiVAR_078731220R → G in EIEE11. 1 Publication1
Natural variantiVAR_069999236T → S in EIEE11. 1 Publication1
Natural variantiVAR_078196251V → I in EIEE11. 1 Publication1
Natural variantiVAR_070000263A → T in EIEE11. 1 Publication1
Natural variantiVAR_065178263A → V in EIEE11; also found in a patient with neonatal epilepsy with late-onset episodic ataxia; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function. 4 PublicationsCorresponds to variant dbSNP:rs387906686Ensembl.1
Natural variantiVAR_078457430E → G in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs796053183Ensembl.1
Natural variantiVAR_070001853R → Q in EIEE11; phenotype consistent with West syndrome. 1 PublicationCorresponds to variant dbSNP:rs794727152Ensembl.1
Natural variantiVAR_078460856R → L in EIEE11. 1 Publication1
Natural variantiVAR_078735873I → M in EIEE11. 1 Publication1
Natural variantiVAR_070002876N → T in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_078197896A → V in EIEE11. 1 Publication1
Natural variantiVAR_078461905K → N in EIEE11. 2 PublicationsCorresponds to variant dbSNP:rs796053119Ensembl.1
Natural variantiVAR_078463928F → C in EIEE11; mild form with ataxia. 2 Publications1
Natural variantiVAR_078736987S → I in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs796053124Ensembl.1
Natural variantiVAR_070003999E → K in EIEE11; the disease progresses to West syndrome. 2 PublicationsCorresponds to variant dbSNP:rs796053126Ensembl.1
Natural variantiVAR_078737999E → V in EIEE11. 1 Publication1
Natural variantiVAR_0651801211E → K in EIEE11; markedly altered channel voltage-dependence. 1 PublicationCorresponds to variant dbSNP:rs387906684Ensembl.1
Natural variantiVAR_0787381260K → E in EIEE11. 1 Publication1
Natural variantiVAR_0787391260K → Q in EIEE11. 1 Publication1
Natural variantiVAR_0734291312R → T in EIEE11; modified voltage-gated sodium channel activity; activated with lowered voltage sensitivity; disturbed fast and slow inactivation. 3 Publications1
Natural variantiVAR_0781981316A → V in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs796053130Ensembl.1
Natural variantiVAR_0700041323M → V in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0784721326V → D in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs796053131Ensembl.1
Natural variantiVAR_0700051326V → L in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700061336S → Y in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700071338M → T in EIEE11. 1 Publication1
Natural variantiVAR_0784731342L → P in EIEE11. 3 PublicationsCorresponds to variant dbSNP:rs796053134Ensembl.1
Natural variantiVAR_0781991344C → Y in EIEE11. 1 Publication1
Natural variantiVAR_0787421398 – 2005Missing in EIEE11. 1 PublicationAdd BLAST608
Natural variantiVAR_0787431435 – 2005Missing in EIEE11. 1 PublicationAdd BLAST571
Natural variantiVAR_0651811473I → M in EIEE11; increased voltage-gated sodium channel activity; markedly altered the voltage-dependence of the channel; gain of function. 1 PublicationCorresponds to variant dbSNP:rs387906685Ensembl.1
Natural variantiVAR_0787441479Q → P in EIEE11. 1 Publication1
Natural variantiVAR_0784761522G → A in found in a patient with neonatal epilepsy with late-onset episodic ataxia and EIEE11; unknown pathological significance; no effect voltage-gated sodium channel activity; higher current density when associated with G-1882; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs147522594Ensembl.1
Natural variantiVAR_0782001548M → T in EIEE11. 1 Publication1
Natural variantiVAR_0784791593G → R in EIEE11. 1 Publication1
Natural variantiVAR_0700091623T → N in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700101629R → L in EIEE11. 1 Publication1
Natural variantiVAR_0784821634G → V in EIEE11. 1 Publication1
Natural variantiVAR_0787481650L → P in EIEE11. 1 Publication1
Natural variantiVAR_0784831660L → W in EIEE11. 1 Publication1
Natural variantiVAR_0787501829L → F in EIEE11. 1 Publication1
Natural variantiVAR_0787511853H → R in EIEE11. 1 Publication1
Natural variantiVAR_0784861882R → L in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs794727444Ensembl.1
Natural variantiVAR_0782011882R → Q in EIEE11. 4 PublicationsCorresponds to variant dbSNP:rs794727444Ensembl.1
Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neruon excitability are associated with ASD.1 Publication

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi6326.
MalaCardsiSCN2A.
MIMi607745. phenotype.
613721. phenotype.
OpenTargetsiENSG00000136531.
Orphaneti306. Benign familial infantile epilepsy.
140927. Benign familial neonatal-infantile seizures.
33069. Dravet syndrome.
1934. Early infantile epileptic encephalopathy.
36387. Generalized epilepsy with febrile seizures-plus.
3451. West syndrome.
PharmGKBiPA35004.

Chemistry databases

ChEMBLiCHEMBL4187.
DrugBankiDB00555. Lamotrigine.
DB00818. Propofol.
DB05232. Tetrodotoxin.
DB00313. Valproic Acid.
DB00909. Zonisamide.
GuidetoPHARMACOLOGYi579.

Polymorphism and mutation databases

BioMutaiSCN2A.
DMDMi25014053.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000484911 – 2005Sodium channel protein type 2 subunit alphaAdd BLAST2005

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4PhosphoserineBy similarity1
Glycosylationi212N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi278 ↔ 347By similarity
Glycosylationi285N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi291N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi297N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi303N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi308N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi340N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei468PhosphoserineBy similarity1
Modified residuei471PhosphoserineBy similarity1
Modified residuei484PhosphoserineBy similarity1
Modified residuei526PhosphoserineBy similarity1
Modified residuei528PhosphoserineBy similarity1
Modified residuei531PhosphoserineBy similarity1
Modified residuei553PhosphoserineBy similarity1
Modified residuei554PhosphoserineBy similarity1
Modified residuei558PhosphoserineBy similarity1
Modified residuei573PhosphoserineBy similarity1
Modified residuei576PhosphoserineBy similarity1
Modified residuei589PhosphoserineBy similarity1
Modified residuei610PhosphoserineBy similarity1
Modified residuei623PhosphoserineBy similarity1
Modified residuei686PhosphoserineBy similarity1
Modified residuei687PhosphoserineBy similarity1
Modified residuei721PhosphoserineBy similarity1
Disulfide bondi910Interchain; with SCN2B or SCN4BBy similarity
Disulfide bondi910Interchain; with the conotoxin GVIIJ (when the channel is not linked to SCN2B or SCN4B; the bond to SCN2B or SCN4B protects the channel from the inhibition by toxin)By similarity
Disulfide bondi950 ↔ 959By similarity
Glycosylationi1368N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1382N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1393N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1506Phosphoserine; by PKCBy similarity1
Modified residuei1930PhosphoserineBy similarity1
Modified residuei1943PhosphothreonineBy similarity1
Modified residuei1963PhosphothreonineBy similarity1
Modified residuei1966PhosphothreonineBy similarity1
Modified residuei1971PhosphoserineBy similarity1

Post-translational modificationi

May be ubiquitinated by NEDD4L; which would promote its endocytosis.By similarity
Phosphorylation at Ser-1506 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ99250.
PeptideAtlasiQ99250.
PRIDEiQ99250.

PTM databases

iPTMnetiQ99250.
PhosphoSitePlusiQ99250.

Expressioni

Gene expression databases

BgeeiENSG00000136531.
CleanExiHS_SCN2A.
ExpressionAtlasiQ99250. baseline and differential.
GenevisibleiQ99250. HS.

Organism-specific databases

HPAiCAB022567.

Interactioni

Subunit structurei

Heterooligomer of a large alpha subunit and a smaller beta subunit. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Interacts with NEDD4L. Interacts with CALM. Interacts with the conotoxin GVIIJ (PubMed:24497506). Interacts with the conotoxin GVIIJ (PubMed:24497506). Interacts with the spider beta/delta-theraphotoxin-Pre1a (PubMed:28428547).3 Publications

Protein-protein interaction databases

CORUMiQ99250.
IntActiQ99250. 4 interactors.
MINTiMINT-1388751.
STRINGi9606.ENSP00000283256.

Chemistry databases

BindingDBiQ99250.

Structurei

Secondary structure

12005
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1792 – 1805Combined sources14
Beta strandi1811 – 1814Combined sources4
Turni1815 – 1817Combined sources3
Helixi1818 – 1823Combined sources6
Turni1827 – 1829Combined sources3
Helixi1836 – 1839Combined sources4
Beta strandi1845 – 1847Combined sources3
Turni1848 – 1850Combined sources3
Beta strandi1851 – 1853Combined sources3
Helixi1854 – 1866Combined sources13
Helixi1870 – 1886Combined sources17
Helixi1900 – 1926Combined sources27

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KAVNMR-A1777-1882[»]
4JPZX-ray3.02B/H1777-1937[»]
ProteinModelPortaliQ99250.
SMRiQ99250.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99250.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati111 – 456ICuratedAdd BLAST346
Repeati741 – 1013IICuratedAdd BLAST273
Repeati1190 – 1504IIICuratedAdd BLAST315
Repeati1513 – 1811IVCuratedAdd BLAST299
Domaini1905 – 1934IQPROSITE-ProRule annotationAdd BLAST30

Domaini

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.Curated

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410INF8. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00830000128242.
HOVERGENiHBG053100.
InParanoidiQ99250.
KOiK04834.
OMAiILPMNGK.
OrthoDBiEOG091G00FK.
PhylomeDBiQ99250.
TreeFamiTF323985.

Family and domain databases

InterProiView protein in InterPro
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
IPR024583. Na_trans_cytopl.
PfamiView protein in Pfam
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
PF11933. Na_trans_cytopl. 1 hit.
PRINTSiPR00170. NACHANNEL.
SMARTiView protein in SMART
SM00015. IQ. 1 hit.
PROSITEiView protein in PROSITE
PS50096. IQ. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99250-1) [UniParc]FASTAAdd to basket
Also known as: Adult, 6A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MAQSVLVPPG PDSFRFFTRE SLAAIEQRIA EEKAKRPKQE RKDEDDENGP
60 70 80 90 100
KPNSDLEAGK SLPFIYGDIP PEMVSVPLED LDPYYINKKT FIVLNKGKAI
110 120 130 140 150
SRFSATPALY ILTPFNPIRK LAIKILVHSL FNMLIMCTIL TNCVFMTMSN
160 170 180 190 200
PPDWTKNVEY TFTGIYTFES LIKILARGFC LEDFTFLRDP WNWLDFTVIT
210 220 230 240 250
FAYVTEFVDL GNVSALRTFR VLRALKTISV IPGLKTIVGA LIQSVKKLSD
260 270 280 290 300
VMILTVFCLS VFALIGLQLF MGNLRNKCLQ WPPDNSSFEI NITSFFNNSL
310 320 330 340 350
DGNGTTFNRT VSIFNWDEYI EDKSHFYFLE GQNDALLCGN SSDAGQCPEG
360 370 380 390 400
YICVKAGRNP NYGYTSFDTF SWAFLSLFRL MTQDFWENLY QLTLRAAGKT
410 420 430 440 450
YMIFFVLVIF LGSFYLINLI LAVVAMAYEE QNQATLEEAE QKEAEFQQML
460 470 480 490 500
EQLKKQQEEA QAAAAAASAE SRDFSGAGGI GVFSESSSVA SKLSSKSEKE
510 520 530 540 550
LKNRRKKKKQ KEQSGEEEKN DRVRKSESED SIRRKGFRFS LEGSRLTYEK
560 570 580 590 600
RFSSPHQSLL SIRGSLFSPR RNSRASLFSF RGRAKDIGSE NDFADDEHST
610 620 630 640 650
FEDNDSRRDS LFVPHRHGER RHSNVSQASR ASRVLPILPM NGKMHSAVDC
660 670 680 690 700
NGVVSLVGGP STLTSAGQLL PEGTTTETEI RKRRSSSYHV SMDLLEDPTS
710 720 730 740 750
RQRAMSIASI LTNTMEELEE SRQKCPPCWY KFANMCLIWD CCKPWLKVKH
760 770 780 790 800
LVNLVVMDPF VDLAITICIV LNTLFMAMEH YPMTEQFSSV LSVGNLVFTG
810 820 830 840 850
IFTAEMFLKI IAMDPYYYFQ EGWNIFDGFI VSLSLMELGL ANVEGLSVLR
860 870 880 890 900
SFRLLRVFKL AKSWPTLNML IKIIGNSVGA LGNLTLVLAI IVFIFAVVGM
910 920 930 940 950
QLFGKSYKEC VCKISNDCEL PRWHMHDFFH SFLIVFRVLC GEWIETMWDC
960 970 980 990 1000
MEVAGQTMCL TVFMMVMVIG NLVVLNLFLA LLLSSFSSDN LAATDDDNEM
1010 1020 1030 1040 1050
NNLQIAVGRM QKGIDFVKRK IREFIQKAFV RKQKALDEIK PLEDLNNKKD
1060 1070 1080 1090 1100
SCISNHTTIE IGKDLNYLKD GNGTTSGIGS SVEKYVVDES DYMSFINNPS
1110 1120 1130 1140 1150
LTVTVPIAVG ESDFENLNTE EFSSESDMEE SKEKLNATSS SEGSTVDIGA
1160 1170 1180 1190 1200
PAEGEQPEVE PEESLEPEAC FTEDCVRKFK CCQISIEEGK GKLWWNLRKT
1210 1220 1230 1240 1250
CYKIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT
1260 1270 1280 1290 1300
YIFILEMLLK WVAYGFQVYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG
1310 1320 1330 1340 1350
AIKSLRTLRA LRPLRALSRF EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI
1360 1370 1380 1390 1400
FSIMGVNLFA GKFYHCINYT TGEMFDVSVV NNYSECKALI ESNQTARWKN
1410 1420 1430 1440 1450
VKVNFDNVGL GYLSLLQVAT FKGWMDIMYA AVDSRNVELQ PKYEDNLYMY
1460 1470 1480 1490 1500
LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM TEEQKKYYNA
1510 1520 1530 1540 1550
MKKLGSKKPQ KPIPRPANKF QGMVFDFVTK QVFDISIMIL ICLNMVTMMV
1560 1570 1580 1590 1600
ETDDQSQEMT NILYWINLVF IVLFTGECVL KLISLRYYYF TIGWNIFDFV
1610 1620 1630 1640 1650
VVILSIVGMF LAELIEKYFV SPTLFRVIRL ARIGRILRLI KGAKGIRTLL
1660 1670 1680 1690 1700
FALMMSLPAL FNIGLLLFLV MFIYAIFGMS NFAYVKREVG IDDMFNFETF
1710 1720 1730 1740 1750
GNSMICLFQI TTSAGWDGLL APILNSGPPD CDPDKDHPGS SVKGDCGNPS
1760 1770 1780 1790 1800
VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL SEDDFEMFYE
1810 1820 1830 1840 1850
VWEKFDPDAT QFIEFAKLSD FADALDPPLL IAKPNKVQLI AMDLPMVSGD
1860 1870 1880 1890 1900
RIHCLDILFA FTKRVLGESG EMDALRIQME ERFMASNPSK VSYEPITTTL
1910 1920 1930 1940 1950
KRKQEEVSAI IIQRAYRRYL LKQKVKKVSS IYKKDKGKEC DGTPIKEDTL
1960 1970 1980 1990 2000
IDKLNENSTP EKTDMTPSTT SPPSYDSVTK PEKEKFEKDK SEKEDKGKDI

RESKK
Length:2,005
Mass (Da):227,975
Last modified:November 8, 2002 - v3
Checksum:i8A421AE6C7ED9A37
GO
Isoform 2 (identifier: Q99250-2) [UniParc]FASTAAdd to basket
Also known as: Neonatal, 6N

The sequence of this isoform differs from the canonical sequence as follows:
     209-209: D → N

Show »
Length:2,005
Mass (Da):227,974
Checksum:iBDA9D5ADEEB5F780
GO

Sequence cautioni

The sequence CAA46438 differs from that shown. Contaminating sequence. Sequence of unknown origin in the C-terminal part.Curated
The sequence CAA46438 differs from that shown. Reason: Frameshift at position 1953.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti524R → L in AAA18895 (PubMed:1325650).Curated1
Sequence conflicti1325V → A in AAA18895 (PubMed:1325650).Curated1
Sequence conflicti1768V → L in AAA18895 (PubMed:1325650).Curated1
Sequence conflicti1990K → R in CAA46438 (PubMed:1317301).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07844812D → N Probable disease-associated mutation found in a patient with autism spectrum disorder; decreased voltage-gated sodium channel activity; faster channel inactivation; loss of fucntion. 1 Publication1
Natural variantiVAR_02973219R → K5 PublicationsCorresponds to variant dbSNP:rs17183814Ensembl.1
Natural variantiVAR_07844982D → G Probable disease-associated mutation found in a patient with autism spectrum disorder; decreased voltage-gated sodium channel activity; decreased expression; loss of function. 1 Publication1
Natural variantiVAR_078450102 – 2005Missing Probable disease-associated mutation found in a patient with intractable epilepsy and severe mental decline; non-conducting; loss of voltage-gated sodium channel activity; dominant-negatif. 1 PublicationAdd BLAST1904
Natural variantiVAR_078451132N → K in EIEE11. 1 Publication1
Natural variantiVAR_078452136M → I in EIEE11. 2 Publications1
Natural variantiVAR_078453169 – 2005Missing Found in a patient with schizofrenia; unknown pathological significance. 1 PublicationAdd BLAST1837
Natural variantiVAR_069996169E → G in EIEE11. 2 Publications1
Natural variantiVAR_075572172I → V Found in a patient with non-specific acute encephalopathy; unknown pathological significance. 1 Publication1
Natural variantiVAR_029733188R → W in BFIS3; mutant channel inactivates more slowly than wild-type whereas the Na(+) channel conductance is not affected. 1 PublicationCorresponds to variant dbSNP:rs121917748Ensembl.1
Natural variantiVAR_078195191W → G Probable disease-associated mutation found in a patient with drug-resistant focal epilepsy. 1 Publication1
Natural variantiVAR_072745208V → E in BFIS3. 1 Publication1
Natural variantiVAR_078730211G → D in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_069997212N → D in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_069998213V → D in EIEE11. 1 Publication1
Natural variantiVAR_078454218T → K in EIEE11; unknown pathological significance. 1 Publication1
Natural variantiVAR_078731220R → G in EIEE11. 1 Publication1
Natural variantiVAR_029734223R → Q in BFIS3; increased voltage-gated sodium channel activity; modified voltage dependence of activation and inactivation; gain of function. 3 PublicationsCorresponds to variant dbSNP:rs121917752Ensembl.1
Natural variantiVAR_069999236T → S in EIEE11. 1 Publication1
Natural variantiVAR_078455240A → S in BFIS3. 1 Publication1
Natural variantiVAR_078196251V → I in EIEE11. 1 Publication1
Natural variantiVAR_065176252M → V in BFIS3; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function. 1 PublicationCorresponds to variant dbSNP:rs387906687Ensembl.1
Natural variantiVAR_065177261V → M in BFIS3; increased voltage-gated sodium channel activity; faster recovery from inactivation; gain of function. 1 Publication1
Natural variantiVAR_070000263A → T in EIEE11. 1 Publication1
Natural variantiVAR_065178263A → V in EIEE11; also found in a patient with neonatal epilepsy with late-onset episodic ataxia; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function. 4 PublicationsCorresponds to variant dbSNP:rs387906686Ensembl.1
Natural variantiVAR_073428322D → N Found in a patient with Dravet syndrome; unknown pathological significance. 2 Publications1
Natural variantiVAR_064331328F → V Found in a patient with acute encephalopathy with biphasic seizures, late reduced diffusion and in a patient with Dravet syndrome; unknown pathological significance. 5 PublicationsCorresponds to variant dbSNP:rs781204054Ensembl.1
Natural variantiVAR_078456379R → H Probable disease-associated mutation found in a patient with autism spectrum disorder; loss of voltage-gated sodium channel activity; non-conducting; no dominant-negatif effect. 1 Publication1
Natural variantiVAR_029735385F → Y. Corresponds to variant dbSNP:rs2228988Ensembl.1
Natural variantiVAR_078457430E → G in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs796053183Ensembl.1
Natural variantiVAR_078458430E → Q in BFIS3; unknown pathological significance. 1 Publication1
Natural variantiVAR_029736524R → Q2 PublicationsCorresponds to variant dbSNP:rs186154973Ensembl.1
Natural variantiVAR_065179575A → V Polymorphism; there is no significant effects on the voltage-dependence of the channel. 1 Publication1
Natural variantiVAR_078732583 – 2005Missing Probable disease-associated mutation found in a patient with autism spectrum disorder. 1 PublicationAdd BLAST1423
Natural variantiVAR_078733649D → N Found in a patient with Dravet syndrome; unknown pathological significance. 1 Publication1
Natural variantiVAR_078734674T → K Probable disease-associated mutation found in a patient with autism spectrum disorder. 1 Publication1
Natural variantiVAR_078459850R → P Found in a patient with schizofrenia; unknown pathological significance. 1 Publication1
Natural variantiVAR_070001853R → Q in EIEE11; phenotype consistent with West syndrome. 1 PublicationCorresponds to variant dbSNP:rs794727152Ensembl.1
Natural variantiVAR_078460856R → L in EIEE11. 1 Publication1
Natural variantiVAR_078735873I → M in EIEE11. 1 Publication1
Natural variantiVAR_070002876N → T in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_029737892V → I in BFIS3. 1 PublicationCorresponds to variant dbSNP:rs121917751Ensembl.1
Natural variantiVAR_078197896A → V in EIEE11. 1 Publication1
Natural variantiVAR_078461905K → N in EIEE11. 2 PublicationsCorresponds to variant dbSNP:rs796053119Ensembl.1
Natural variantiVAR_078462908K → R Found in a patient with schizofrenia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs2228980Ensembl.1
Natural variantiVAR_078463928F → C in EIEE11; mild form with ataxia. 2 Publications1
Natural variantiVAR_078464937R → C Probable disease-associated mutation found in a patient with autism spectrum disorder; loss of voltage-gated sodium channel activity; non-conducting. 1 PublicationCorresponds to variant dbSNP:rs796053197Ensembl.1
Natural variantiVAR_078465937R → H Probable disease-associated mutation found in a patient with autism spectrum disorder; loss of voltage-gated sodium channel activity; non-conducting. 1 Publication1
Natural variantiVAR_078466959 – 2005Missing Probable disease-associated mutation found in a patient with autism spectrum disorder; loss of voltage-gated sodium channel activity; non-conducting. 1 PublicationAdd BLAST1047
Natural variantiVAR_078467976N → K Found in a patient with autism; unknown pathological significance. 1 Publication1
Natural variantiVAR_078736987S → I in EIEE11. 1 PublicationCorresponds to variant dbSNP:rs796053124Ensembl.1