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Q99250 (SCN2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SCN2A
Synonyms:NAC2, SCN2A1, SCN2A2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2005 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Subunit structure

Interacts with NEDD4L. Interacts with CALM By similarity. Heterooligomer of a large alpha subunit and a smaller beta subunit. Heterooligomer with SCN4B; disulfide-linked. Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1.

Domain

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.

Post-translational modification

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.

Involvement in disease

Seizures, benign familial infantile 3 (BFIS3) [MIM:607745]: An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10 Ref.13 Ref.16

Epileptic encephalopathy, early infantile, 11 (EIEE11) [MIM:613721]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.17 Ref.18 Ref.19

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.2/SCN2A subfamily. [View classification]

Contains 1 IQ domain.

Sequence caution

The sequence CAA46438.1 differs from that shown. Reason: Frameshift at position 1953.

The sequence CAA46438.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Epilepsy
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processintrinsic apoptotic signaling pathway in response to osmotic stress

Inferred from electronic annotation. Source: Ensembl

myelination

Inferred from sequence or structural similarity. Source: BHF-UCL

neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

sodium ion transmembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

sodium ion transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentT-tubule

Inferred from electronic annotation. Source: Ensembl

axon

Traceable author statement PubMed 16652168. Source: BHF-UCL

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

intercalated disc

Inferred from electronic annotation. Source: Ensembl

intrinsic component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

node of Ranvier

Inferred from sequence or structural similarity. Source: BHF-UCL

paranode region of axon

Inferred from electronic annotation. Source: Ensembl

sodium channel complex

Inferred from sequence or structural similarity. Source: UniProtKB

voltage-gated sodium channel complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionvoltage-gated sodium channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99250-1)

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.
Isoform 2 (identifier: Q99250-2)

Also known as: Neonatal; 6N;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 20052005Sodium channel protein type 2 subunit alpha
PRO_0000048491

Regions

Topological domain1 – 124124Cytoplasmic Potential
Transmembrane125 – 14824Helical; Name=S1 of repeat I; Potential
Topological domain149 – 1568Extracellular Potential
Transmembrane157 – 17620Helical; Name=S2 of repeat I; Potential
Topological domain177 – 18913Cytoplasmic Potential
Transmembrane190 – 20819Helical; Name=S3 of repeat I; Potential
Topological domain209 – 2146Extracellular Potential
Transmembrane215 – 23420Helical; Voltage-sensor; Name=S4 of repeat I; Potential
Topological domain235 – 25016Cytoplasmic Potential
Transmembrane251 – 27424Helical; Name=S5 of repeat I; Potential
Topological domain275 – 401127Extracellular Potential
Transmembrane402 – 42726Helical; Name=S6 of repeat I; Potential
Topological domain428 – 753326Cytoplasmic Potential
Transmembrane754 – 77825Helical; Name=S1 of repeat II; Potential
Topological domain779 – 78911Extracellular Potential
Transmembrane790 – 81324Helical; Name=S2 of repeat II; Potential
Topological domain814 – 8218Cytoplasmic Potential
Transmembrane822 – 84120Helical; Name=S3 of repeat II; Potential
Topological domain842 – 8476Extracellular Potential
Transmembrane848 – 86720Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Topological domain868 – 88316Cytoplasmic Potential
Transmembrane884 – 90421Helical; Name=S5 of repeat II; Potential
Topological domain905 – 95753Extracellular Potential
Transmembrane958 – 98326Helical; Name=S6 of repeat II; Potential
Topological domain984 – 1203220Cytoplasmic Potential
Transmembrane1204 – 122724Helical; Name=S1 of repeat III; Potential
Topological domain1228 – 124013Extracellular Potential
Transmembrane1241 – 126626Helical; Name=S2 of repeat III; Potential
Topological domain1267 – 12726Cytoplasmic Potential
Transmembrane1273 – 129422Helical; Name=S3 of repeat III; Potential
Topological domain1295 – 12984Extracellular Potential
Transmembrane1299 – 132022Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Topological domain1321 – 133919Cytoplasmic Potential
Transmembrane1340 – 136728Helical; Name=S5 of repeat III; Potential
Topological domain1368 – 144679Extracellular Potential
Transmembrane1447 – 147327Helical; Name=S6 of repeat III; Potential
Topological domain1474 – 152653Cytoplasmic Potential
Transmembrane1527 – 155024Helical; Name=S1 of repeat IV; Potential
Topological domain1551 – 156111Extracellular Potential
Transmembrane1562 – 158524Helical; Name=S2 of repeat IV; Potential
Topological domain1586 – 15916Cytoplasmic Potential
Transmembrane1592 – 161524Helical; Name=S3 of repeat IV; Potential
Topological domain1616 – 162510Extracellular Potential
Transmembrane1626 – 164722Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Topological domain1648 – 166215Cytoplasmic Potential
Transmembrane1663 – 168523Helical; Name=S5 of repeat IV; Potential
Topological domain1686 – 175166Extracellular Potential
Transmembrane1752 – 177625Helical; Name=S6 of repeat IV; Potential
Topological domain1777 – 2005229Cytoplasmic Potential
Repeat111 – 456346I
Repeat741 – 1013273II
Repeat1190 – 1504315III
Repeat1513 – 1811299IV
Domain1905 – 193430IQ

Sites

Site14891Important for channel closure By similarity

Amino acid modifications

Modified residue41Phosphoserine By similarity
Modified residue4681Phosphoserine By similarity
Modified residue4711Phosphoserine By similarity
Modified residue4841Phosphoserine By similarity
Modified residue5281Phosphoserine By similarity
Modified residue5541Phosphoserine By similarity
Modified residue5731Phosphoserine By similarity
Modified residue5761Phosphoserine By similarity
Modified residue6101Phosphoserine By similarity
Modified residue6231Phosphoserine By similarity
Modified residue6861Phosphoserine By similarity
Modified residue6871Phosphoserine By similarity
Modified residue7211Phosphoserine By similarity
Modified residue15061Phosphoserine; by PKC By similarity
Modified residue19301Phosphoserine By similarity
Modified residue19631Phosphothreonine By similarity
Modified residue19661Phosphothreonine By similarity
Modified residue19711Phosphoserine By similarity
Glycosylation2121N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation2971N-linked (GlcNAc...) Potential
Glycosylation3031N-linked (GlcNAc...) Potential
Glycosylation3081N-linked (GlcNAc...) Potential
Glycosylation3401N-linked (GlcNAc...) Potential
Glycosylation13681N-linked (GlcNAc...) Potential
Glycosylation13821N-linked (GlcNAc...) Potential
Glycosylation13931N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence2091D → N in isoform 2.
VSP_001032
Natural variant191R → K. Ref.8 Ref.12 Ref.15
Corresponds to variant rs17183814 [ dbSNP | Ensembl ].
VAR_029732
Natural variant1691E → G in EIEE11. Ref.19
VAR_069996
Natural variant1881R → W in BFIS3; mutant channel inactivates more slowly than wild-type whereas the Na(+) channel conductance is not affected. Ref.8
VAR_029733
Natural variant2121N → D in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_069997
Natural variant2131V → D in EIEE11. Ref.19
VAR_069998
Natural variant2231R → Q in BFIS3. Ref.13
VAR_029734
Natural variant2361T → S in EIEE11. Ref.19
VAR_069999
Natural variant2521M → V in BFIS3. Ref.16
VAR_065176
Natural variant2611V → M in BFIS3. Ref.16
VAR_065177
Natural variant2631A → T in EIEE11. Ref.19
VAR_070000
Natural variant2631A → V in EIEE11. Ref.17 Ref.18
VAR_065178
Natural variant3281F → V. Ref.14 Ref.15
VAR_064331
Natural variant3851F → Y.
Corresponds to variant rs2228988 [ dbSNP | Ensembl ].
VAR_029735
Natural variant5241R → Q. Ref.8 Ref.15
Corresponds to variant rs186154973 [ dbSNP | Ensembl ].
VAR_029736
Natural variant5751A → V There is no significant effetcs on the voltage-dependence of the channel. Ref.15
VAR_065179
Natural variant8531R → Q in EIEE11; phenotype consistent with West syndrome. Ref.19
VAR_070001
Natural variant8761N → T in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_070002
Natural variant8921V → I in BFIS3. Ref.13
VAR_029737
Natural variant9991E → K in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_070003
Natural variant10031L → I in BFIS3. Ref.13
VAR_029738
Natural variant12111E → K in EIEE11; markedly altered the voltage-dependence of the channel. Ref.15
VAR_065180
Natural variant13191R → Q in BFIS3. Ref.13
VAR_029739
Natural variant13231M → V in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_070004
Natural variant13261V → L in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_070005
Natural variant13301L → F in BFIS3. Ref.10
VAR_029740
Natural variant13361S → Y in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_070006
Natural variant13381M → T in EIEE11. Ref.19
VAR_070007
Natural variant14221K → E Probable disease-associated mutation found in a boy with infantile spasms and bitemporal glucose hypometabolism. Ref.20
VAR_070008
Natural variant14731I → M in EIEE11; markedly altered the voltage-dependence of the channel. Ref.15
VAR_065181
Natural variant15631L → V in BFIS3. Ref.10
VAR_029741
Natural variant16231T → N in EIEE11; the disease progresses to West syndrome. Ref.19
VAR_070009
Natural variant16291R → L in EIEE11. Ref.19
VAR_070010
Natural variant19021R → T Associated with autism. Ref.12
VAR_029742

Experimental info

Sequence conflict5241R → L in AAA18895. Ref.1
Sequence conflict13251V → A in AAA18895. Ref.1
Sequence conflict17681V → L in AAA18895. Ref.1
Sequence conflict19901K → R in CAA46438. Ref.5

Secondary structure

............... 2005
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Adult) (6A) [UniParc].

Last modified November 8, 2002. Version 3.
Checksum: 8A421AE6C7ED9A37

FASTA2,005227,975
        10         20         30         40         50         60 
MAQSVLVPPG PDSFRFFTRE SLAAIEQRIA EEKAKRPKQE RKDEDDENGP KPNSDLEAGK 

        70         80         90        100        110        120 
SLPFIYGDIP PEMVSVPLED LDPYYINKKT FIVLNKGKAI SRFSATPALY ILTPFNPIRK 

       130        140        150        160        170        180 
LAIKILVHSL FNMLIMCTIL TNCVFMTMSN PPDWTKNVEY TFTGIYTFES LIKILARGFC 

       190        200        210        220        230        240 
LEDFTFLRDP WNWLDFTVIT FAYVTEFVDL GNVSALRTFR VLRALKTISV IPGLKTIVGA 

       250        260        270        280        290        300 
LIQSVKKLSD VMILTVFCLS VFALIGLQLF MGNLRNKCLQ WPPDNSSFEI NITSFFNNSL 

       310        320        330        340        350        360 
DGNGTTFNRT VSIFNWDEYI EDKSHFYFLE GQNDALLCGN SSDAGQCPEG YICVKAGRNP 

       370        380        390        400        410        420 
NYGYTSFDTF SWAFLSLFRL MTQDFWENLY QLTLRAAGKT YMIFFVLVIF LGSFYLINLI 

       430        440        450        460        470        480 
LAVVAMAYEE QNQATLEEAE QKEAEFQQML EQLKKQQEEA QAAAAAASAE SRDFSGAGGI 

       490        500        510        520        530        540 
GVFSESSSVA SKLSSKSEKE LKNRRKKKKQ KEQSGEEEKN DRVRKSESED SIRRKGFRFS 

       550        560        570        580        590        600 
LEGSRLTYEK RFSSPHQSLL SIRGSLFSPR RNSRASLFSF RGRAKDIGSE NDFADDEHST 

       610        620        630        640        650        660 
FEDNDSRRDS LFVPHRHGER RHSNVSQASR ASRVLPILPM NGKMHSAVDC NGVVSLVGGP 

       670        680        690        700        710        720 
STLTSAGQLL PEGTTTETEI RKRRSSSYHV SMDLLEDPTS RQRAMSIASI LTNTMEELEE 

       730        740        750        760        770        780 
SRQKCPPCWY KFANMCLIWD CCKPWLKVKH LVNLVVMDPF VDLAITICIV LNTLFMAMEH 

       790        800        810        820        830        840 
YPMTEQFSSV LSVGNLVFTG IFTAEMFLKI IAMDPYYYFQ EGWNIFDGFI VSLSLMELGL 

       850        860        870        880        890        900 
ANVEGLSVLR SFRLLRVFKL AKSWPTLNML IKIIGNSVGA LGNLTLVLAI IVFIFAVVGM 

       910        920        930        940        950        960 
QLFGKSYKEC VCKISNDCEL PRWHMHDFFH SFLIVFRVLC GEWIETMWDC MEVAGQTMCL 

       970        980        990       1000       1010       1020 
TVFMMVMVIG NLVVLNLFLA LLLSSFSSDN LAATDDDNEM NNLQIAVGRM QKGIDFVKRK 

      1030       1040       1050       1060       1070       1080 
IREFIQKAFV RKQKALDEIK PLEDLNNKKD SCISNHTTIE IGKDLNYLKD GNGTTSGIGS 

      1090       1100       1110       1120       1130       1140 
SVEKYVVDES DYMSFINNPS LTVTVPIAVG ESDFENLNTE EFSSESDMEE SKEKLNATSS 

      1150       1160       1170       1180       1190       1200 
SEGSTVDIGA PAEGEQPEVE PEESLEPEAC FTEDCVRKFK CCQISIEEGK GKLWWNLRKT 

      1210       1220       1230       1240       1250       1260 
CYKIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT YIFILEMLLK 

      1270       1280       1290       1300       1310       1320 
WVAYGFQVYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG AIKSLRTLRA LRPLRALSRF 

      1330       1340       1350       1360       1370       1380 
EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCINYT TGEMFDVSVV 

      1390       1400       1410       1420       1430       1440 
NNYSECKALI ESNQTARWKN VKVNFDNVGL GYLSLLQVAT FKGWMDIMYA AVDSRNVELQ 

      1450       1460       1470       1480       1490       1500 
PKYEDNLYMY LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM TEEQKKYYNA 

      1510       1520       1530       1540       1550       1560 
MKKLGSKKPQ KPIPRPANKF QGMVFDFVTK QVFDISIMIL ICLNMVTMMV ETDDQSQEMT 

      1570       1580       1590       1600       1610       1620 
NILYWINLVF IVLFTGECVL KLISLRYYYF TIGWNIFDFV VVILSIVGMF LAELIEKYFV 

      1630       1640       1650       1660       1670       1680 
SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV MFIYAIFGMS 

      1690       1700       1710       1720       1730       1740 
NFAYVKREVG IDDMFNFETF GNSMICLFQI TTSAGWDGLL APILNSGPPD CDPDKDHPGS 

      1750       1760       1770       1780       1790       1800 
SVKGDCGNPS VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL SEDDFEMFYE 

      1810       1820       1830       1840       1850       1860 
VWEKFDPDAT QFIEFAKLSD FADALDPPLL IAKPNKVQLI AMDLPMVSGD RIHCLDILFA 

      1870       1880       1890       1900       1910       1920 
FTKRVLGESG EMDALRIQME ERFMASNPSK VSYEPITTTL KRKQEEVSAI IIQRAYRRYL 

      1930       1940       1950       1960       1970       1980 
LKQKVKKVSS IYKKDKGKEC DGTPIKEDTL IDKLNENSTP EKTDMTPSTT SPPSYDSVTK 

      1990       2000 
PEKEKFEKDK SEKEDKGKDI RESKK 

« Hide

Isoform 2 (Neonatal) (6N) [UniParc].

Checksum: BDA9D5ADEEB5F780
Show »

FASTA2,005227,974

References

« Hide 'large scale' references
[1]"Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain."
Ahmed C.M., Ware D.H., Lee S.C., Patten C.D., Ferrer-Montiel A.V., Schinder A.F., McPherson J.D., Wagner-Mcpherson C.B., Wasmuth J.J., Evans G.A., Montal M.
Proc. Natl. Acad. Sci. U.S.A. 89:8220-8224(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION.
Tissue: Brain.
[2]"Genomic structures of SCN2A and SCN3A -- candidate genes for deafness at the DFNA16 locus."
Kasai N., Fukushima K., Ueki Y., Prasad S., Nosakowski J., Sugata K., Sugata A., Nishizaki K., Meyer N.C., Smith R.J.H.
Gene 264:113-122(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Isolation of the 5'-flanking region for human brain sodium channel subtype II alpha-Subunit (SCN2A)."
Lu C.-M., Eichelberger J.S., Beckman M.L., Schade S.D., Brown G.B.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
[5]"Differential expression of two sodium channel subtypes in human brain."
Lu C.-M., Han J., Rado T.A., Brown G.B.
FEBS Lett. 303:53-58(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1709-1994.
Tissue: Brain.
[6]"Direct amplification of a single dissected chromosomal segment by polymerase chain reaction: a human brain sodium channel gene is on chromosome 2q22-q23."
Han J., Lu C.-M., Brown G.B., Rado T.A.
Proc. Natl. Acad. Sci. U.S.A. 88:335-339(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1702-1772.
[7]"Crystallographic insights into sodium-channel modulation by the beta4 subunit."
Gilchrist J., Das S., Van Petegem F., Bosmans F.
Proc. Natl. Acad. Sci. U.S.A. 110:E5016-E5024(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SCN4B.
[8]"A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction."
Sugawara T., Tsurubuchi Y., Agarwala K.L., Ito M., Fukuma G., Mazaki-Miyazaki E., Nagafuji H., Noda M., Imoto K., Wada K., Mitsudome A., Kaneko S., Montal M., Nagata K., Hirose S., Yamakawa K.
Proc. Natl. Acad. Sci. U.S.A. 98:6384-6389(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BFIS3 TRP-188, CHARACTERIZATION OF VARIANT BFIS3 TRP-188, VARIANTS LYS-19 AND GLN-524.
[9]Erratum
Sugawara T., Tsurubuchi Y., Agarwala K.L., Ito M., Fukuma G., Mazaki-Miyazaki E., Nagafuji H., Noda M., Imoto K., Wada K., Mitsudome A., Kaneko S., Montal M., Nagata K., Hirose S., Yamakawa K.
Proc. Natl. Acad. Sci. U.S.A. 98:10515-10515(2001)
[10]"Sodium-channel defects in benign familial neonatal-infantile seizures."
Heron S.E., Crossland K.M., Andermann E., Phillips H.A., Hall A.J., Bleasel A., Shevell M., Mercho S., Seni M.H., Guiot M.C., Mulley J.C., Berkovic S.F., Scheffer I.E.
Lancet 360:851-852(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BFIS3 PHE-1330 AND VAL-1563.
[11]Erratum
Heron S.E., Crossland K.M., Andermann E., Phillips H.A., Hall A.J., Bleasel A., Shevell M., Mercho S., Seni M.H., Guiot M.C., Mulley J.C., Berkovic S.F., Scheffer I.E.
Lancet 360:1520-1520(2002)
[12]"Sodium channels SCN1A, SCN2A and SCN3A in familial autism."
Weiss L.A., Escayg A., Kearney J.A., Trudeau M., MacDonald B.T., Mori M., Reichert J., Buxbaum J.D., Meisler M.H.
Mol. Psychiatry 8:186-194(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-19 AND THR-1902.
[13]"Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy."
Berkovic S.F., Heron S.E., Giordano L., Marini C., Guerrini R., Kaplan R.E., Gambardella A., Steinlein O.K., Grinton B.E., Dean J.T., Bordo L., Hodgson B.L., Yamamoto T., Mulley J.C., Zara F., Scheffer I.E.
Ann. Neurol. 55:550-557(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BFIS3 GLN-223; ILE-892; ILE-1003 AND GLN-1319.
[14]"A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in infancy (SMEI) inherited from a father with febrile seizures."
Kimura K., Sugawara T., Mazaki-Miyazaki E., Hoshino K., Nomura Y., Tateno A., Hachimori K., Yamakawa K., Segawa M.
Brain Dev. 27:424-430(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-328.
[15]"De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies."
Ogiwara I., Ito K., Sawaishi Y., Osaka H., Mazaki E., Inoue I., Montal M., Hashikawa T., Shike T., Fujiwara T., Inoue Y., Kaneda M., Yamakawa K.
Neurology 73:1046-1053(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE11 LYS-1211 AND MET-1473, VARIANTS LYS-19; VAL-328; GLN-524 AND VAL-575, CHARACTERIZATION OF VARIANTS EIEE11 LYS-1211 AND MET-1473, CHARACTERIZATION OF VARIANT VAL-575.
[16]"Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy."
Liao Y., Deprez L., Maljevic S., Pitsch J., Claes L., Hristova D., Jordanova A., Ala-Mello S., Bellan-Koch A., Blazevic D., Schubert S., Thomas E.A., Petrou S., Becker A.J., De Jonghe P., Lerche H.
Brain 133:1403-1414(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BFIS3 VAL-252 AND MET-261.
[17]"SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain."
Liao Y., Anttonen A.K., Liukkonen E., Gaily E., Maljevic S., Schubert S., Bellan-Koch A., Petrou S., Ahonen V.E., Lerche H., Lehesjoki A.E.
Neurology 75:1454-1458(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EIEE11 VAL-263.
[18]"Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings."
Touma M., Joshi M., Connolly M.C., Grant P.E., Hansen A.R., Khwaja O., Berry G.T., Kinney H.C., Poduri A., Agrawal P.B.
Epilepsia 54:E81-E85(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EIEE11 VAL-263.
[19]"Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome."
Nakamura K., Kato M., Osaka H., Yamashita S., Nakagawa E., Haginoya K., Tohyama J., Okuda M., Wada T., Shimakawa S., Imai K., Takeshita S., Ishiwata H., Lev D., Lerman-Sagie T., Cervantes-Barragan D.E., Villarroel C.E., Ohfu M. expand/collapse author list , Writzl K., Gnidovec Strazisar B., Hirabayashi S., Chitayat D., Myles Reid D., Nishiyama K., Kodera H., Nakashima M., Tsurusaki Y., Miyake N., Hayasaka K., Matsumoto N., Saitsu H.
Neurology 81:992-998(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE11 GLY-169; ASP-212; ASP-213; SER-236; THR-263; GLN-853; THR-876; LYS-999; VAL-1323; LEU-1326; TYR-1336; THR-1338; ASN-1623 AND LEU-1629.
[20]"SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism."
Sundaram S.K., Chugani H.T., Tiwari V.N., Huq A.H.
Pediatr. Neurol. 49:46-49(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-1422.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M94055 mRNA. Translation: AAA18895.1.
AF059683 Genomic DNA. Translation: AAC14574.1.
AF327246 expand/collapse EMBL AC list , 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 expand/collapse EMBL AC list , 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.
PIRA46269.
I59194.
RefSeqNP_001035232.1. NM_001040142.1.
NP_001035233.1. NM_001040143.1.
NP_066287.2. NM_021007.2.
XP_005246807.1. XM_005246750.2.
XP_005246808.1. XM_005246751.2.
XP_005246810.1. XM_005246753.1.
UniGeneHs.93485.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KAVNMR-A1777-1882[»]
ProteinModelPortalQ99250.
SMRQ99250. Positions 131-270, 366-424, 769-983, 1204-1480, 1524-1932.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112231. 2 interactions.
IntActQ99250. 4 interactions.
MINTMINT-1388751.
STRING9606.ENSP00000283256.

Chemistry

BindingDBQ99250.
ChEMBLCHEMBL4187.
DrugBankDB00555. Lamotrigine.
GuidetoPHARMACOLOGY579.

Protein family/group databases

TCDB1.A.1.10.12. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ99250.

Polymorphism databases

DMDM25014053.

Proteomic databases

PaxDbQ99250.
PRIDEQ99250.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000283256; ENSP00000283256; ENSG00000136531. [Q99250-1]
ENST00000357398; ENSP00000349973; ENSG00000136531. [Q99250-2]
ENST00000375427; ENSP00000364576; ENSG00000136531. [Q99250-2]
ENST00000375437; ENSP00000364586; ENSG00000136531. [Q99250-1]
GeneID6326.
KEGGhsa:6326.
UCSCuc002udc.3. human. [Q99250-1]
uc002ude.3. human. [Q99250-2]

Organism-specific databases

CTD6326.
GeneCardsGC02P166095.
H-InvDBHIX0029932.
HGNCHGNC:10588. SCN2A.
HPACAB022567.
MIM182390. gene.
607745. phenotype.
613721. phenotype.
neXtProtNX_Q99250.
Orphanet306. Benign familial infantile seizures.
140927. Benign familial neonatal-infantile seizures.
33069. Dravet syndrome.
1934. Early infantile epileptic encephalopathy.
36387. Generalized epilepsy with febrile seizures-plus context.
3451. West syndrome.
PharmGKBPA35004.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOVERGENHBG053100.
InParanoidQ99250.
KOK04834.
OMAKKVSCIY.
OrthoDBEOG7DJSK9.
PhylomeDBQ99250.
TreeFamTF323985.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ99250.
BgeeQ99250.
CleanExHS_SCN2A.
GenevestigatorQ99250.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR028805. Na_channel_a2su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PANTHERPTHR10037:SF134. PTHR10037:SF134. 1 hit.
PfamPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
PROSITEPS50096. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSCN2A. human.
EvolutionaryTraceQ99250.
GeneWikiNav1.2.
GenomeRNAi6326.
NextBio24550.
PROQ99250.
SOURCESearch...

Entry information

Entry nameSCN2A_HUMAN
AccessionPrimary (citable) accession number: Q99250
Secondary accession number(s): A6NC14 expand/collapse secondary AC list , A6NIQ5, Q14472, Q53T77, Q9BZC9, Q9BZD0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 8, 2002
Last modified: April 16, 2014
This is version 151 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM