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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.1 Publication

Sites

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136531-MONOMER.
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

HGNCiHGNC:10588. SCN2A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 124CytoplasmicSequence analysisAdd BLAST124
Transmembranei125 – 148Helical; Name=S1 of repeat ISequence analysisAdd BLAST24
Topological domaini149 – 156ExtracellularSequence analysis8
Transmembranei157 – 176Helical; Name=S2 of repeat ISequence analysisAdd BLAST20
Topological domaini177 – 189CytoplasmicSequence analysisAdd BLAST13
Transmembranei190 – 208Helical; Name=S3 of repeat ISequence analysisAdd BLAST19
Topological domaini209 – 214ExtracellularSequence analysis6
Transmembranei215 – 234Helical; Voltage-sensor; Name=S4 of repeat ISequence analysisAdd BLAST20
Topological domaini235 – 250CytoplasmicSequence analysisAdd BLAST16
Transmembranei251 – 274Helical; Name=S5 of repeat ISequence analysisAdd BLAST24
Topological domaini275 – 401ExtracellularSequence analysisAdd BLAST127
Transmembranei402 – 427Helical; Name=S6 of repeat ISequence analysisAdd BLAST26
Topological domaini428 – 753CytoplasmicSequence analysisAdd BLAST326
Transmembranei754 – 778Helical; Name=S1 of repeat IISequence analysisAdd BLAST25
Topological domaini779 – 789ExtracellularSequence analysisAdd BLAST11
Transmembranei790 – 813Helical; Name=S2 of repeat IISequence analysisAdd BLAST24
Topological domaini814 – 821CytoplasmicSequence analysis8
Transmembranei822 – 841Helical; Name=S3 of repeat IISequence analysisAdd BLAST20
Topological domaini842 – 847ExtracellularSequence analysis6
Transmembranei848 – 867Helical; Voltage-sensor; Name=S4 of repeat IISequence analysisAdd BLAST20
Topological domaini868 – 883CytoplasmicSequence analysisAdd BLAST16
Transmembranei884 – 904Helical; Name=S5 of repeat IISequence analysisAdd BLAST21
Topological domaini905 – 957ExtracellularSequence analysisAdd BLAST53
Transmembranei958 – 983Helical; Name=S6 of repeat IISequence analysisAdd BLAST26
Topological domaini984 – 1203CytoplasmicSequence analysisAdd BLAST220
Transmembranei1204 – 1227Helical; Name=S1 of repeat IIISequence analysisAdd BLAST24
Topological domaini1228 – 1240ExtracellularSequence analysisAdd BLAST13
Transmembranei1241 – 1266Helical; Name=S2 of repeat IIISequence analysisAdd BLAST26
Topological domaini1267 – 1272CytoplasmicSequence analysis6
Transmembranei1273 – 1294Helical; Name=S3 of repeat IIISequence analysisAdd BLAST22
Topological domaini1295 – 1298ExtracellularSequence analysis4
Transmembranei1299 – 1320Helical; Voltage-sensor; Name=S4 of repeat IIISequence analysisAdd BLAST22
Topological domaini1321 – 1339CytoplasmicSequence analysisAdd BLAST19
Transmembranei1340 – 1367Helical; Name=S5 of repeat IIISequence analysisAdd BLAST28
Topological domaini1368 – 1446ExtracellularSequence analysisAdd BLAST79
Transmembranei1447 – 1473Helical; Name=S6 of repeat IIISequence analysisAdd BLAST27
Topological domaini1474 – 1526CytoplasmicSequence analysisAdd BLAST53
Transmembranei1527 – 1550Helical; Name=S1 of repeat IVSequence analysisAdd BLAST24
Topological domaini1551 – 1561ExtracellularSequence analysisAdd BLAST11
Transmembranei1562 – 1585Helical; Name=S2 of repeat IVSequence analysisAdd BLAST24
Topological domaini1586 – 1591CytoplasmicSequence analysis6
Transmembranei1592 – 1615Helical; Name=S3 of repeat IVSequence analysisAdd BLAST24
Topological domaini1616 – 1625ExtracellularSequence analysis10
Transmembranei1626 – 1647Helical; Voltage-sensor; Name=S4 of repeat IVSequence analysisAdd BLAST22
Topological domaini1648 – 1662CytoplasmicSequence analysisAdd BLAST15
Transmembranei1663 – 1685Helical; Name=S5 of repeat IVSequence analysisAdd BLAST23
Topological domaini1686 – 1751ExtracellularSequence analysisAdd BLAST66
Transmembranei1752 – 1776Helical; Name=S6 of repeat IVSequence analysisAdd BLAST25
Topological domaini1777 – 2005CytoplasmicSequence analysisAdd BLAST229

GO - Cellular componenti

  • axon Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • intrinsic component of plasma membrane Source: UniProtKB
  • node of Ranvier Source: BHF-UCL
  • sodium channel complex Source: UniProtKB
  • voltage-gated sodium channel complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Seizures, benign familial infantile, 3 (BFIS3)5 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 rs121917748dbSNPEnsembl.1
Natural variantiVAR_072745208V → E in BFIS3. 1 Publication1
Natural variantiVAR_029734223R → Q in BFIS3. 1 PublicationCorresponds to variant rs121917752dbSNPEnsembl.1
Natural variantiVAR_065176252M → V in BFIS3. 1 PublicationCorresponds to variant rs387906687dbSNPEnsembl.1
Natural variantiVAR_065177261V → M in BFIS3. 1 Publication1
Natural variantiVAR_029737892V → I in BFIS3. 1 PublicationCorresponds to variant rs121917751dbSNPEnsembl.1
Natural variantiVAR_0297381003L → I in BFIS3. 1 PublicationCorresponds to variant rs121917754dbSNPEnsembl.1
Natural variantiVAR_0297391319R → Q in BFIS3. 1 PublicationCorresponds to variant rs121917753dbSNPEnsembl.1
Natural variantiVAR_0297401330L → F in BFIS3. 1 PublicationCorresponds to variant rs121917749dbSNPEnsembl.1
Natural variantiVAR_0297411563L → V in BFIS3. 1 PublicationCorresponds to variant rs121917750dbSNPEnsembl.1
Epileptic encephalopathy, early infantile, 11 (EIEE11)5 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_069996169E → G in EIEE11. 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_069999236T → S in EIEE11. 1 Publication1
Natural variantiVAR_070000263A → T in EIEE11. 1 Publication1
Natural variantiVAR_065178263A → V in EIEE11. 2 PublicationsCorresponds to variant rs387906686dbSNPEnsembl.1
Natural variantiVAR_070001853R → Q in EIEE11; phenotype consistent with West syndrome. 1 PublicationCorresponds to variant rs794727152dbSNPEnsembl.1
Natural variantiVAR_070002876N → T in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_070003999E → K in EIEE11; the disease progresses to West syndrome. 1 PublicationCorresponds to variant rs796053126dbSNPEnsembl.1
Natural variantiVAR_0651801211E → K in EIEE11; markedly altered the voltage-dependence of the channel. 1 PublicationCorresponds to variant rs387906684dbSNPEnsembl.1
Natural variantiVAR_0734291312R → T in EIEE11. 1 Publication1
Natural variantiVAR_0700041323M → V in EIEE11; the disease progresses to West syndrome. 1 Publication1
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_0651811473I → M in EIEE11; markedly altered the voltage-dependence of the channel. 1 PublicationCorresponds to variant rs387906685dbSNPEnsembl.1
Natural variantiVAR_0700091623T → N in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700101629R → L in EIEE11. 1 Publication1

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.
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...)Sequence analysis1
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Glycosylationi291N-linked (GlcNAc...)Sequence analysis1
Glycosylationi297N-linked (GlcNAc...)Sequence analysis1
Glycosylationi303N-linked (GlcNAc...)Sequence analysis1
Glycosylationi308N-linked (GlcNAc...)Sequence analysis1
Glycosylationi340N-linked (GlcNAc...)Sequence 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
Glycosylationi1368N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1382N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1393N-linked (GlcNAc...)Sequence 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

Interacts with NEDD4L. Interacts with CALM (By similarity). Heterooligomer of a large alpha subunit and a smaller beta subunit. Heterooligomer with SCN4B; disulfide-linked.By similarity1 Publication

Protein-protein interaction databases

BioGridi112231. 1 interactor.
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.

Sequence similaritiesi

Contains 1 IQ domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
IPR024583. Na_trans_cytopl.
[Graphical view]
PfamiPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
PF11933. Na_trans_cytopl. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]
PROSITEiPS50096. IQ. 1 hit.
[Graphical view]

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.

« Hide

        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_02973219R → K.3 PublicationsCorresponds to variant rs17183814dbSNPEnsembl.1
Natural variantiVAR_069996169E → G in EIEE11. 1 Publication1
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 rs121917748dbSNPEnsembl.1
Natural variantiVAR_072745208V → E in BFIS3. 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_029734223R → Q in BFIS3. 1 PublicationCorresponds to variant rs121917752dbSNPEnsembl.1
Natural variantiVAR_069999236T → S in EIEE11. 1 Publication1
Natural variantiVAR_065176252M → V in BFIS3. 1 PublicationCorresponds to variant rs387906687dbSNPEnsembl.1
Natural variantiVAR_065177261V → M in BFIS3. 1 Publication1
Natural variantiVAR_070000263A → T in EIEE11. 1 Publication1
Natural variantiVAR_065178263A → V in EIEE11. 2 PublicationsCorresponds to variant rs387906686dbSNPEnsembl.1
Natural variantiVAR_073428322D → N.1 Publication1
Natural variantiVAR_064331328F → V Found in a patient with acute encephalopathy with biphasic seizures and late reduced diffusion; unknown pathological significance. 4 PublicationsCorresponds to variant rs781204054dbSNPEnsembl.1
Natural variantiVAR_029735385F → Y.Corresponds to variant rs2228988dbSNPEnsembl.1
Natural variantiVAR_029736524R → Q.2 PublicationsCorresponds to variant rs186154973dbSNPEnsembl.1
Natural variantiVAR_065179575A → V There is no significant effetcs on the voltage-dependence of the channel. 1 Publication1
Natural variantiVAR_070001853R → Q in EIEE11; phenotype consistent with West syndrome. 1 PublicationCorresponds to variant rs794727152dbSNPEnsembl.1
Natural variantiVAR_070002876N → T in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_029737892V → I in BFIS3. 1 PublicationCorresponds to variant rs121917751dbSNPEnsembl.1
Natural variantiVAR_070003999E → K in EIEE11; the disease progresses to West syndrome. 1 PublicationCorresponds to variant rs796053126dbSNPEnsembl.1
Natural variantiVAR_0297381003L → I in BFIS3. 1 PublicationCorresponds to variant rs121917754dbSNPEnsembl.1
Natural variantiVAR_0651801211E → K in EIEE11; markedly altered the voltage-dependence of the channel. 1 PublicationCorresponds to variant rs387906684dbSNPEnsembl.1
Natural variantiVAR_0734291312R → T in EIEE11. 1 Publication1
Natural variantiVAR_0297391319R → Q in BFIS3. 1 PublicationCorresponds to variant rs121917753dbSNPEnsembl.1
Natural variantiVAR_0700041323M → V in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700051326V → L in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0297401330L → F in BFIS3. 1 PublicationCorresponds to variant rs121917749dbSNPEnsembl.1
Natural variantiVAR_0700061336S → Y in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700071338M → T in EIEE11. 1 Publication1
Natural variantiVAR_0700081422K → E Probable disease-associated mutation found in a boy with infantile spasms and bitemporal glucose hypometabolism. 1 PublicationCorresponds to variant rs796053137dbSNPEnsembl.1
Natural variantiVAR_0651811473I → M in EIEE11; markedly altered the voltage-dependence of the channel. 1 PublicationCorresponds to variant rs387906685dbSNPEnsembl.1
Natural variantiVAR_0297411563L → V in BFIS3. 1 PublicationCorresponds to variant rs121917750dbSNPEnsembl.1
Natural variantiVAR_0700091623T → N in EIEE11; the disease progresses to West syndrome. 1 Publication1
Natural variantiVAR_0700101629R → L in EIEE11. 1 Publication1
Natural variantiVAR_0297421902R → T Associated with autism. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001032209D → N in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94055 mRNA. Translation: AAA18895.1.
AF059683 Genomic DNA. Translation: AAC14574.1.
AF327246
, AF327226, AF327227, AF327228, AF327229, AF327230, AF327231, AF327232, AF327233, AF327234, AF327235, AF327236, AF327237, AF327238, AF327239, AF327240, AF327241, AF327242, AF327243, AF327244, AF327245 Genomic DNA. Translation: AAG53413.1.
AF327246
, AF327226, AF327227, AF327228, AF327229, AF327230, AF327231, AF327232, AF327233, AF327234, AF327235, AF327236, AF327237, AF327238, AF327239, AF327240, AF327241, AF327242, AF327243, AF327244, AF327245 Genomic DNA. Translation: AAG53412.1.
AC011303 Genomic DNA. Translation: AAY14971.1.
AC013438 Genomic DNA. No translation available.
X65361 mRNA. Translation: CAA46438.1. Sequence problems.
M91804 mRNA. No translation available.
M55662 Genomic DNA. Translation: AAB65854.2.
CCDSiCCDS33313.1. [Q99250-2]
CCDS33314.1. [Q99250-1]
PIRiA46269.
I59194.
RefSeqiNP_001035232.1. NM_001040142.1. [Q99250-1]
NP_001035233.1. NM_001040143.1. [Q99250-2]
NP_066287.2. NM_021007.2. [Q99250-1]
XP_005246810.1. XM_005246753.3. [Q99250-2]
XP_016860144.1. XM_017004655.1. [Q99250-1]
XP_016860145.1. XM_017004656.1. [Q99250-1]
XP_016860146.1. XM_017004657.1. [Q99250-2]
UniGeneiHs.93485.

Genome annotation databases

EnsembliENST00000283256; ENSP00000283256; ENSG00000136531. [Q99250-1]
ENST00000375427; ENSP00000364576; ENSG00000136531. [Q99250-2]
ENST00000375437; ENSP00000364586; ENSG00000136531. [Q99250-1]
ENST00000631182; ENSP00000486885; ENSG00000136531. [Q99250-2]
ENST00000636071; ENSP00000490107; ENSG00000136531. [Q99250-2]
ENST00000637266; ENSP00000490866; ENSG00000136531. [Q99250-1]
GeneIDi6326.
KEGGihsa:6326.
UCSCiuc002udc.4. human. [Q99250-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94055 mRNA. Translation: AAA18895.1.
AF059683 Genomic DNA. Translation: AAC14574.1.
AF327246
, AF327226, AF327227, AF327228, AF327229, AF327230, AF327231, AF327232, AF327233, AF327234, AF327235, AF327236, AF327237, AF327238, AF327239, AF327240, AF327241, AF327242, AF327243, AF327244, AF327245 Genomic DNA. Translation: AAG53413.1.
AF327246
, AF327226, AF327227, AF327228, AF327229, AF327230, AF327231, AF327232, AF327233, AF327234, AF327235, AF327236, AF327237, AF327238, AF327239, AF327240, AF327241, AF327242, AF327243, AF327244, AF327245 Genomic DNA. Translation: AAG53412.1.
AC011303 Genomic DNA. Translation: AAY14971.1.
AC013438 Genomic DNA. No translation available.
X65361 mRNA. Translation: CAA46438.1. Sequence problems.
M91804 mRNA. No translation available.
M55662 Genomic DNA. Translation: AAB65854.2.
CCDSiCCDS33313.1. [Q99250-2]
CCDS33314.1. [Q99250-1]
PIRiA46269.
I59194.
RefSeqiNP_001035232.1. NM_001040142.1. [Q99250-1]
NP_001035233.1. NM_001040143.1. [Q99250-2]
NP_066287.2. NM_021007.2. [Q99250-1]
XP_005246810.1. XM_005246753.3. [Q99250-2]
XP_016860144.1. XM_017004655.1. [Q99250-1]
XP_016860145.1. XM_017004656.1. [Q99250-1]
XP_016860146.1. XM_017004657.1. [Q99250-2]
UniGeneiHs.93485.

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...

Protein-protein interaction databases

BioGridi112231. 1 interactor.
IntActiQ99250. 4 interactors.
MINTiMINT-1388751.
STRINGi9606.ENSP00000283256.

Chemistry databases

BindingDBiQ99250.
ChEMBLiCHEMBL4187.
DrugBankiDB00555. Lamotrigine.
DB00818. Propofol.
DB00313. Valproic Acid.
DB00909. Zonisamide.
GuidetoPHARMACOLOGYi579.

Protein family/group databases

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

PTM databases

iPTMnetiQ99250.
PhosphoSitePlusiQ99250.

Polymorphism and mutation databases

BioMutaiSCN2A.
DMDMi25014053.

Proteomic databases

PaxDbiQ99250.
PeptideAtlasiQ99250.
PRIDEiQ99250.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000283256; ENSP00000283256; ENSG00000136531. [Q99250-1]
ENST00000375427; ENSP00000364576; ENSG00000136531. [Q99250-2]
ENST00000375437; ENSP00000364586; ENSG00000136531. [Q99250-1]
ENST00000631182; ENSP00000486885; ENSG00000136531. [Q99250-2]
ENST00000636071; ENSP00000490107; ENSG00000136531. [Q99250-2]
ENST00000637266; ENSP00000490866; ENSG00000136531. [Q99250-1]
GeneIDi6326.
KEGGihsa:6326.
UCSCiuc002udc.4. human. [Q99250-1]

Organism-specific databases

CTDi6326.
DisGeNETi6326.
GeneCardsiSCN2A.
H-InvDBHIX0029932.
HGNCiHGNC:10588. SCN2A.
HPAiCAB022567.
MalaCardsiSCN2A.
MIMi182390. gene.
607745. phenotype.
613721. phenotype.
neXtProtiNX_Q99250.
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.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136531-MONOMER.
ReactomeiR-HSA-445095. Interaction between L1 and Ankyrins.
R-HSA-5576892. Phase 0 - rapid depolarisation.
SIGNORiQ99250.

Miscellaneous databases

ChiTaRSiSCN2A. human.
EvolutionaryTraceiQ99250.
GeneWikiiNav1.2.
GenomeRNAii6326.
PROiQ99250.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
IPR024583. Na_trans_cytopl.
[Graphical view]
PfamiPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
PF11933. Na_trans_cytopl. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]
PROSITEiPS50096. IQ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSCN2A_HUMAN
AccessioniPrimary (citable) accession number: Q99250
Secondary accession number(s): A6NC14
, A6NIQ5, Q14472, Q53T77, Q9BZC9, Q9BZD0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 8, 2002
Last modified: November 2, 2016
This is version 177 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.