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Q99250

- SCN2A_HUMAN

UniProt

Q99250 - SCN2A_HUMAN

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Protein

Sodium channel protein type 2 subunit alpha

Gene

SCN2A

Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Sitei1489 – 14891Important for channel closureBy similarity

GO - Molecular functioni

  1. voltage-gated sodium channel activity Source: UniProtKB

GO - Biological processi

  1. intrinsic apoptotic signaling pathway in response to osmotic stress Source: Ensembl
  2. membrane depolarization during action potential Source: RefGenome
  3. myelination Source: BHF-UCL
  4. neuronal action potential Source: RefGenome
  5. neuron apoptotic process Source: Ensembl
  6. sodium ion transmembrane transport Source: UniProtKB
  7. sodium ion transport Source: ProtInc
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

ReactomeiREACT_22266. Interaction between L1 and Ankyrins.

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
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:10588. SCN2A.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 124124CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei125 – 14824Helical; Name=S1 of repeat ISequence AnalysisAdd
BLAST
Topological domaini149 – 1568ExtracellularSequence Analysis
Transmembranei157 – 17620Helical; Name=S2 of repeat ISequence AnalysisAdd
BLAST
Topological domaini177 – 18913CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei190 – 20819Helical; Name=S3 of repeat ISequence AnalysisAdd
BLAST
Topological domaini209 – 2146ExtracellularSequence Analysis
Transmembranei215 – 23420Helical; Voltage-sensor; Name=S4 of repeat ISequence AnalysisAdd
BLAST
Topological domaini235 – 25016CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei251 – 27424Helical; Name=S5 of repeat ISequence AnalysisAdd
BLAST
Topological domaini275 – 401127ExtracellularSequence AnalysisAdd
BLAST
Transmembranei402 – 42726Helical; Name=S6 of repeat ISequence AnalysisAdd
BLAST
Topological domaini428 – 753326CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei754 – 77825Helical; Name=S1 of repeat IISequence AnalysisAdd
BLAST
Topological domaini779 – 78911ExtracellularSequence AnalysisAdd
BLAST
Transmembranei790 – 81324Helical; Name=S2 of repeat IISequence AnalysisAdd
BLAST
Topological domaini814 – 8218CytoplasmicSequence Analysis
Transmembranei822 – 84120Helical; Name=S3 of repeat IISequence AnalysisAdd
BLAST
Topological domaini842 – 8476ExtracellularSequence Analysis
Transmembranei848 – 86720Helical; Voltage-sensor; Name=S4 of repeat IISequence AnalysisAdd
BLAST
Topological domaini868 – 88316CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei884 – 90421Helical; Name=S5 of repeat IISequence AnalysisAdd
BLAST
Topological domaini905 – 95753ExtracellularSequence AnalysisAdd
BLAST
Transmembranei958 – 98326Helical; Name=S6 of repeat IISequence AnalysisAdd
BLAST
Topological domaini984 – 1203220CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei1204 – 122724Helical; Name=S1 of repeat IIISequence AnalysisAdd
BLAST
Topological domaini1228 – 124013ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1241 – 126626Helical; Name=S2 of repeat IIISequence AnalysisAdd
BLAST
Topological domaini1267 – 12726CytoplasmicSequence Analysis
Transmembranei1273 – 129422Helical; Name=S3 of repeat IIISequence AnalysisAdd
BLAST
Topological domaini1295 – 12984ExtracellularSequence Analysis
Transmembranei1299 – 132022Helical; Voltage-sensor; Name=S4 of repeat IIISequence AnalysisAdd
BLAST
Topological domaini1321 – 133919CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei1340 – 136728Helical; Name=S5 of repeat IIISequence AnalysisAdd
BLAST
Topological domaini1368 – 144679ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1447 – 147327Helical; Name=S6 of repeat IIISequence AnalysisAdd
BLAST
Topological domaini1474 – 152653CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei1527 – 155024Helical; Name=S1 of repeat IVSequence AnalysisAdd
BLAST
Topological domaini1551 – 156111ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1562 – 158524Helical; Name=S2 of repeat IVSequence AnalysisAdd
BLAST
Topological domaini1586 – 15916CytoplasmicSequence Analysis
Transmembranei1592 – 161524Helical; Name=S3 of repeat IVSequence AnalysisAdd
BLAST
Topological domaini1616 – 162510ExtracellularSequence Analysis
Transmembranei1626 – 164722Helical; Voltage-sensor; Name=S4 of repeat IVSequence AnalysisAdd
BLAST
Topological domaini1648 – 166215CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei1663 – 168523Helical; Name=S5 of repeat IVSequence AnalysisAdd
BLAST
Topological domaini1686 – 175166ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1752 – 177625Helical; Name=S6 of repeat IVSequence AnalysisAdd
BLAST
Topological domaini1777 – 2005229CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axon Source: BHF-UCL
  2. integral component of plasma membrane Source: ProtInc
  3. intercalated disc Source: Ensembl
  4. intrinsic component of plasma membrane Source: UniProtKB
  5. node of Ranvier Source: BHF-UCL
  6. paranode region of axon Source: Ensembl
  7. plasma membrane Source: RefGenome
  8. sodium channel complex Source: UniProtKB
  9. T-tubule Source: Ensembl
  10. 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) [MIM:607745]: An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae.4 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti188 – 1881R → W in BFIS3; mutant channel inactivates more slowly than wild-type whereas the Na(+) channel conductance is not affected. 1 Publication
VAR_029733
Natural varianti223 – 2231R → Q in BFIS3. 1 Publication
VAR_029734
Natural varianti252 – 2521M → V in BFIS3. 1 Publication
VAR_065176
Natural varianti261 – 2611V → M in BFIS3. 1 Publication
VAR_065177
Natural varianti892 – 8921V → I in BFIS3. 1 Publication
VAR_029737
Natural varianti1003 – 10031L → I in BFIS3. 1 Publication
VAR_029738
Natural varianti1319 – 13191R → Q in BFIS3. 1 Publication
VAR_029739
Natural varianti1330 – 13301L → F in BFIS3. 1 Publication
VAR_029740
Natural varianti1563 – 15631L → V in BFIS3. 1 Publication
VAR_029741
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.4 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti169 – 1691E → G in EIEE11. 1 Publication
VAR_069996
Natural varianti212 – 2121N → D in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_069997
Natural varianti213 – 2131V → D in EIEE11. 1 Publication
VAR_069998
Natural varianti236 – 2361T → S in EIEE11. 1 Publication
VAR_069999
Natural varianti263 – 2631A → T in EIEE11. 1 Publication
VAR_070000
Natural varianti263 – 2631A → V in EIEE11. 2 Publications
VAR_065178
Natural varianti853 – 8531R → Q in EIEE11; phenotype consistent with West syndrome. 1 Publication
VAR_070001
Natural varianti876 – 8761N → T in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070002
Natural varianti999 – 9991E → K in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070003
Natural varianti1211 – 12111E → K in EIEE11; markedly altered the voltage-dependence of the channel. 1 Publication
VAR_065180
Natural varianti1323 – 13231M → V in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070004
Natural varianti1326 – 13261V → L in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070005
Natural varianti1336 – 13361S → Y in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070006
Natural varianti1338 – 13381M → T in EIEE11. 1 Publication
VAR_070007
Natural varianti1473 – 14731I → M in EIEE11; markedly altered the voltage-dependence of the channel. 1 Publication
VAR_065181
Natural varianti1623 – 16231T → N in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070009
Natural varianti1629 – 16291R → L in EIEE11. 1 Publication
VAR_070010

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

MIMi607745. phenotype.
613721. phenotype.
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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 20052005Sodium channel protein type 2 subunit alphaPRO_0000048491Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei4 – 41PhosphoserineBy similarity
Glycosylationi212 – 2121N-linked (GlcNAc...)Sequence Analysis
Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence Analysis
Glycosylationi291 – 2911N-linked (GlcNAc...)Sequence Analysis
Glycosylationi297 – 2971N-linked (GlcNAc...)Sequence Analysis
Glycosylationi303 – 3031N-linked (GlcNAc...)Sequence Analysis
Glycosylationi308 – 3081N-linked (GlcNAc...)Sequence Analysis
Glycosylationi340 – 3401N-linked (GlcNAc...)Sequence Analysis
Modified residuei468 – 4681PhosphoserineBy similarity
Modified residuei471 – 4711PhosphoserineBy similarity
Modified residuei484 – 4841PhosphoserineBy similarity
Modified residuei528 – 5281PhosphoserineBy similarity
Modified residuei554 – 5541PhosphoserineBy similarity
Modified residuei573 – 5731PhosphoserineBy similarity
Modified residuei576 – 5761PhosphoserineBy similarity
Modified residuei610 – 6101PhosphoserineBy similarity
Modified residuei623 – 6231PhosphoserineBy similarity
Modified residuei686 – 6861PhosphoserineBy similarity
Modified residuei687 – 6871PhosphoserineBy similarity
Modified residuei721 – 7211PhosphoserineBy similarity
Glycosylationi1368 – 13681N-linked (GlcNAc...)Sequence Analysis
Glycosylationi1382 – 13821N-linked (GlcNAc...)Sequence Analysis
Glycosylationi1393 – 13931N-linked (GlcNAc...)Sequence Analysis
Modified residuei1506 – 15061Phosphoserine; by PKCBy similarity
Modified residuei1930 – 19301PhosphoserineBy similarity
Modified residuei1963 – 19631PhosphothreonineBy similarity
Modified residuei1966 – 19661PhosphothreonineBy similarity
Modified residuei1971 – 19711PhosphoserineBy similarity

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.
PRIDEiQ99250.

PTM databases

PhosphoSiteiQ99250.

Expressioni

Gene expression databases

BgeeiQ99250.
CleanExiHS_SCN2A.
ExpressionAtlasiQ99250. baseline and differential.
GenevestigatoriQ99250.

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. 2 interactions.
IntActiQ99250. 4 interactions.
MINTiMINT-1388751.
STRINGi9606.ENSP00000283256.

Structurei

Secondary structure

1
2005
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1792 – 180514Combined sources
Beta strandi1811 – 18144Combined sources
Turni1815 – 18173Combined sources
Helixi1818 – 18236Combined sources
Turni1827 – 18293Combined sources
Helixi1836 – 18394Combined sources
Beta strandi1845 – 18473Combined sources
Turni1848 – 18503Combined sources
Beta strandi1851 – 18533Combined sources
Helixi1854 – 186613Combined sources
Helixi1870 – 188617Combined sources
Helixi1900 – 192627Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KAVNMR-A1777-1882[»]
4JPZX-ray3.02B/H1777-1937[»]
ProteinModelPortaliQ99250.
SMRiQ99250. Positions 125-270, 755-909, 1204-1474, 1524-1882, 1901-1927.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99250.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati111 – 456346IAdd
BLAST
Repeati741 – 1013273IIAdd
BLAST
Repeati1190 – 1504315IIIAdd
BLAST
Repeati1513 – 1811299IVAdd
BLAST
Domaini1905 – 193430IQPROSITE-ProRule annotationAdd
BLAST

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

eggNOGiCOG1226.
GeneTreeiENSGT00760000118827.
HOVERGENiHBG053100.
InParanoidiQ99250.
KOiK04834.
OMAiKKVSCIY.
OrthoDBiEOG7DJSK9.
PhylomeDBiQ99250.
TreeFamiTF323985.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PfamiPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 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. Align

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 CAA46438.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.Curated
The sequence CAA46438.1 differs from that shown. Reason: Frameshift at position 1953. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti524 – 5241R → L in AAA18895. (PubMed:1325650)Curated
Sequence conflicti1325 – 13251V → A in AAA18895. (PubMed:1325650)Curated
Sequence conflicti1768 – 17681V → L in AAA18895. (PubMed:1325650)Curated
Sequence conflicti1990 – 19901K → R in CAA46438. (PubMed:1317301)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191R → K.3 Publications
Corresponds to variant rs17183814 [ dbSNP | Ensembl ].
VAR_029732
Natural varianti169 – 1691E → G in EIEE11. 1 Publication
VAR_069996
Natural varianti188 – 1881R → W in BFIS3; mutant channel inactivates more slowly than wild-type whereas the Na(+) channel conductance is not affected. 1 Publication
VAR_029733
Natural varianti212 – 2121N → D in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_069997
Natural varianti213 – 2131V → D in EIEE11. 1 Publication
VAR_069998
Natural varianti223 – 2231R → Q in BFIS3. 1 Publication
VAR_029734
Natural varianti236 – 2361T → S in EIEE11. 1 Publication
VAR_069999
Natural varianti252 – 2521M → V in BFIS3. 1 Publication
VAR_065176
Natural varianti261 – 2611V → M in BFIS3. 1 Publication
VAR_065177
Natural varianti263 – 2631A → T in EIEE11. 1 Publication
VAR_070000
Natural varianti263 – 2631A → V in EIEE11. 2 Publications
VAR_065178
Natural varianti328 – 3281F → V.2 Publications
VAR_064331
Natural varianti385 – 3851F → Y.
Corresponds to variant rs2228988 [ dbSNP | Ensembl ].
VAR_029735
Natural varianti524 – 5241R → Q.2 Publications
Corresponds to variant rs186154973 [ dbSNP | Ensembl ].
VAR_029736
Natural varianti575 – 5751A → V There is no significant effetcs on the voltage-dependence of the channel. 1 Publication
VAR_065179
Natural varianti853 – 8531R → Q in EIEE11; phenotype consistent with West syndrome. 1 Publication
VAR_070001
Natural varianti876 – 8761N → T in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070002
Natural varianti892 – 8921V → I in BFIS3. 1 Publication
VAR_029737
Natural varianti999 – 9991E → K in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070003
Natural varianti1003 – 10031L → I in BFIS3. 1 Publication
VAR_029738
Natural varianti1211 – 12111E → K in EIEE11; markedly altered the voltage-dependence of the channel. 1 Publication
VAR_065180
Natural varianti1319 – 13191R → Q in BFIS3. 1 Publication
VAR_029739
Natural varianti1323 – 13231M → V in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070004
Natural varianti1326 – 13261V → L in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070005
Natural varianti1330 – 13301L → F in BFIS3. 1 Publication
VAR_029740
Natural varianti1336 – 13361S → Y in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070006
Natural varianti1338 – 13381M → T in EIEE11. 1 Publication
VAR_070007
Natural varianti1422 – 14221K → E Probable disease-associated mutation found in a boy with infantile spasms and bitemporal glucose hypometabolism. 1 Publication
VAR_070008
Natural varianti1473 – 14731I → M in EIEE11; markedly altered the voltage-dependence of the channel. 1 Publication
VAR_065181
Natural varianti1563 – 15631L → V in BFIS3. 1 Publication
VAR_029741
Natural varianti1623 – 16231T → N in EIEE11; the disease progresses to West syndrome. 1 Publication
VAR_070009
Natural varianti1629 – 16291R → L in EIEE11. 1 Publication
VAR_070010
Natural varianti1902 – 19021R → T Associated with autism. 1 Publication
VAR_029742

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei209 – 2091D → N in isoform 2. CuratedVSP_001032

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_005246807.1. XM_005246750.2. [Q99250-1]
XP_005246808.1. XM_005246751.2. [Q99250-1]
XP_005246810.1. XM_005246753.1. [Q99250-2]
UniGeneiHs.93485.

Genome annotation databases

EnsembliENST00000283256; ENSP00000283256; ENSG00000136531. [Q99250-1]
ENST00000375427; ENSP00000364576; ENSG00000136531. [Q99250-2]
ENST00000375437; ENSP00000364586; ENSG00000136531. [Q99250-1]
GeneIDi6326.
KEGGihsa:6326.
UCSCiuc002udc.3. human. [Q99250-1]
uc002ude.3. human. [Q99250-2]

Polymorphism databases

DMDMi25014053.

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 .
CCDSi CCDS33313.1. [Q99250-2 ]
CCDS33314.1. [Q99250-1 ]
PIRi A46269.
I59194.
RefSeqi NP_001035232.1. NM_001040142.1. [Q99250-1 ]
NP_001035233.1. NM_001040143.1. [Q99250-2 ]
NP_066287.2. NM_021007.2. [Q99250-1 ]
XP_005246807.1. XM_005246750.2. [Q99250-1 ]
XP_005246808.1. XM_005246751.2. [Q99250-1 ]
XP_005246810.1. XM_005246753.1. [Q99250-2 ]
UniGenei Hs.93485.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2KAV NMR - A 1777-1882 [» ]
4JPZ X-ray 3.02 B/H 1777-1937 [» ]
ProteinModelPortali Q99250.
SMRi Q99250. Positions 125-270, 755-909, 1204-1474, 1524-1882, 1901-1927.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112231. 2 interactions.
IntActi Q99250. 4 interactions.
MINTi MINT-1388751.
STRINGi 9606.ENSP00000283256.

Chemistry

BindingDBi Q99250.
ChEMBLi CHEMBL2096682.
DrugBanki DB00555. Lamotrigine.
DB00818. Propofol.
DB00313. Valproic Acid.
DB00909. Zonisamide.
GuidetoPHARMACOLOGYi 579.

Protein family/group databases

TCDBi 1.A.1.10.12. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSitei Q99250.

Polymorphism databases

DMDMi 25014053.

Proteomic databases

PaxDbi Q99250.
PRIDEi Q99250.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000283256 ; ENSP00000283256 ; ENSG00000136531 . [Q99250-1 ]
ENST00000375427 ; ENSP00000364576 ; ENSG00000136531 . [Q99250-2 ]
ENST00000375437 ; ENSP00000364586 ; ENSG00000136531 . [Q99250-1 ]
GeneIDi 6326.
KEGGi hsa:6326.
UCSCi uc002udc.3. human. [Q99250-1 ]
uc002ude.3. human. [Q99250-2 ]

Organism-specific databases

CTDi 6326.
GeneCardsi GC02P166095.
H-InvDB HIX0029932.
HGNCi HGNC:10588. SCN2A.
HPAi CAB022567.
MIMi 182390. gene.
607745. phenotype.
613721. phenotype.
neXtProti NX_Q99250.
Orphaneti 306. 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.
PharmGKBi PA35004.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1226.
GeneTreei ENSGT00760000118827.
HOVERGENi HBG053100.
InParanoidi Q99250.
KOi K04834.
OMAi KKVSCIY.
OrthoDBi EOG7DJSK9.
PhylomeDBi Q99250.
TreeFami TF323985.

Enzyme and pathway databases

Reactomei REACT_22266. Interaction between L1 and Ankyrins.

Miscellaneous databases

ChiTaRSi SCN2A. human.
EvolutionaryTracei Q99250.
GeneWikii Nav1.2.
GenomeRNAii 6326.
NextBioi 24550.
PROi Q99250.
SOURCEi Search...

Gene expression databases

Bgeei Q99250.
CleanExi HS_SCN2A.
ExpressionAtlasi Q99250. baseline and differential.
Genevestigatori Q99250.

Family and domain databases

Gene3Di 1.20.120.350. 4 hits.
InterProi IPR027359. Channel_four-helix_dom.
IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view ]
Pfami PF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view ]
PRINTSi PR00170. NACHANNEL.
SMARTi SM00015. IQ. 1 hit.
[Graphical view ]
PROSITEi PS50096. IQ. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: VARIANTS BFIS3 PHE-1330 AND VAL-1563.
  10. Cited for: VARIANTS LYS-19 AND THR-1902.
  11. Cited for: VARIANTS BFIS3 GLN-223; ILE-892; ILE-1003 AND GLN-1319.
  12. "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.
  13. "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.
  14. Cited for: VARIANTS BFIS3 VAL-252 AND MET-261.
  15. "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.
  16. "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.
  17. 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.
  18. "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.

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 26, 2014
This is version 158 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

External Data

Dasty 3