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Q99250

- SCN2A_HUMAN

UniProt

Q99250 - SCN2A_HUMAN

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
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 3 (08 Nov 2002)
      Previous versions | rss
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    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

    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

    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

    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 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.
    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

    ArrayExpressiQ99250.
    BgeeiQ99250.
    CleanExiHS_SCN2A.
    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 – 180514
    Beta strandi1811 – 18144
    Turni1815 – 18173
    Helixi1818 – 18236
    Turni1827 – 18293
    Helixi1836 – 18394
    Beta strandi1845 – 18473
    Turni1848 – 18503
    Beta strandi1851 – 18533
    Helixi1854 – 186613
    Helixi1870 – 188617
    Helixi1900 – 192627

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2KAVNMR-A1777-1882[»]
    4JPZX-ray3.02B/H1777-1937[»]
    ProteinModelPortaliQ99250.
    SMRiQ99250. Positions 131-270, 769-983, 1197-1474, 1524-1932.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ99250.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 124124CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini149 – 1568ExtracellularSequence Analysis
    Topological domaini177 – 18913CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini209 – 2146ExtracellularSequence Analysis
    Topological domaini235 – 25016CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini275 – 401127ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini428 – 753326CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini779 – 78911ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini814 – 8218CytoplasmicSequence Analysis
    Topological domaini842 – 8476ExtracellularSequence Analysis
    Topological domaini868 – 88316CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini905 – 95753ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini984 – 1203220CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1228 – 124013ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1267 – 12726CytoplasmicSequence Analysis
    Topological domaini1295 – 12984ExtracellularSequence Analysis
    Topological domaini1321 – 133919CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1368 – 144679ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1474 – 152653CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1551 – 156111ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1586 – 15916CytoplasmicSequence Analysis
    Topological domaini1616 – 162510ExtracellularSequence Analysis
    Topological domaini1648 – 166215CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1686 – 175166ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1777 – 2005229CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei125 – 14824Helical; Name=S1 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei157 – 17620Helical; Name=S2 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei190 – 20819Helical; Name=S3 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei215 – 23420Helical; Voltage-sensor; Name=S4 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei251 – 27424Helical; Name=S5 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei402 – 42726Helical; Name=S6 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei754 – 77825Helical; Name=S1 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei790 – 81324Helical; Name=S2 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei822 – 84120Helical; Name=S3 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei848 – 86720Helical; Voltage-sensor; Name=S4 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei884 – 90421Helical; Name=S5 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei958 – 98326Helical; Name=S6 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei1204 – 122724Helical; Name=S1 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1241 – 126626Helical; Name=S2 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1273 – 129422Helical; Name=S3 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1299 – 132022Helical; Voltage-sensor; Name=S4 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1340 – 136728Helical; Name=S5 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1447 – 147327Helical; Name=S6 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1527 – 155024Helical; Name=S1 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1562 – 158524Helical; Name=S2 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1592 – 161524Helical; Name=S3 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1626 – 164722Helical; Voltage-sensor; Name=S4 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1663 – 168523Helical; Name=S5 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1752 – 177625Helical; Name=S6 of repeat IVSequence AnalysisAdd
    BLAST

    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.
    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

    MAQSVLVPPG PDSFRFFTRE SLAAIEQRIA EEKAKRPKQE RKDEDDENGP     50
    KPNSDLEAGK SLPFIYGDIP PEMVSVPLED LDPYYINKKT FIVLNKGKAI 100
    SRFSATPALY ILTPFNPIRK LAIKILVHSL FNMLIMCTIL TNCVFMTMSN 150
    PPDWTKNVEY TFTGIYTFES LIKILARGFC LEDFTFLRDP WNWLDFTVIT 200
    FAYVTEFVDL GNVSALRTFR VLRALKTISV IPGLKTIVGA LIQSVKKLSD 250
    VMILTVFCLS VFALIGLQLF MGNLRNKCLQ WPPDNSSFEI NITSFFNNSL 300
    DGNGTTFNRT VSIFNWDEYI EDKSHFYFLE GQNDALLCGN SSDAGQCPEG 350
    YICVKAGRNP NYGYTSFDTF SWAFLSLFRL MTQDFWENLY QLTLRAAGKT 400
    YMIFFVLVIF LGSFYLINLI LAVVAMAYEE QNQATLEEAE QKEAEFQQML 450
    EQLKKQQEEA QAAAAAASAE SRDFSGAGGI GVFSESSSVA SKLSSKSEKE 500
    LKNRRKKKKQ KEQSGEEEKN DRVRKSESED SIRRKGFRFS LEGSRLTYEK 550
    RFSSPHQSLL SIRGSLFSPR RNSRASLFSF RGRAKDIGSE NDFADDEHST 600
    FEDNDSRRDS LFVPHRHGER RHSNVSQASR ASRVLPILPM NGKMHSAVDC 650
    NGVVSLVGGP STLTSAGQLL PEGTTTETEI RKRRSSSYHV SMDLLEDPTS 700
    RQRAMSIASI LTNTMEELEE SRQKCPPCWY KFANMCLIWD CCKPWLKVKH 750
    LVNLVVMDPF VDLAITICIV LNTLFMAMEH YPMTEQFSSV LSVGNLVFTG 800
    IFTAEMFLKI IAMDPYYYFQ EGWNIFDGFI VSLSLMELGL ANVEGLSVLR 850
    SFRLLRVFKL AKSWPTLNML IKIIGNSVGA LGNLTLVLAI IVFIFAVVGM 900
    QLFGKSYKEC VCKISNDCEL PRWHMHDFFH SFLIVFRVLC GEWIETMWDC 950
    MEVAGQTMCL TVFMMVMVIG NLVVLNLFLA LLLSSFSSDN LAATDDDNEM 1000
    NNLQIAVGRM QKGIDFVKRK IREFIQKAFV RKQKALDEIK PLEDLNNKKD 1050
    SCISNHTTIE IGKDLNYLKD GNGTTSGIGS SVEKYVVDES DYMSFINNPS 1100
    LTVTVPIAVG ESDFENLNTE EFSSESDMEE SKEKLNATSS SEGSTVDIGA 1150
    PAEGEQPEVE PEESLEPEAC FTEDCVRKFK CCQISIEEGK GKLWWNLRKT 1200
    CYKIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT 1250
    YIFILEMLLK WVAYGFQVYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG 1300
    AIKSLRTLRA LRPLRALSRF EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI 1350
    FSIMGVNLFA GKFYHCINYT TGEMFDVSVV NNYSECKALI ESNQTARWKN 1400
    VKVNFDNVGL GYLSLLQVAT FKGWMDIMYA AVDSRNVELQ PKYEDNLYMY 1450
    LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM TEEQKKYYNA 1500
    MKKLGSKKPQ KPIPRPANKF QGMVFDFVTK QVFDISIMIL ICLNMVTMMV 1550
    ETDDQSQEMT NILYWINLVF IVLFTGECVL KLISLRYYYF TIGWNIFDFV 1600
    VVILSIVGMF LAELIEKYFV SPTLFRVIRL ARIGRILRLI KGAKGIRTLL 1650
    FALMMSLPAL FNIGLLLFLV MFIYAIFGMS NFAYVKREVG IDDMFNFETF 1700
    GNSMICLFQI TTSAGWDGLL APILNSGPPD CDPDKDHPGS SVKGDCGNPS 1750
    VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL SEDDFEMFYE 1800
    VWEKFDPDAT QFIEFAKLSD FADALDPPLL IAKPNKVQLI AMDLPMVSGD 1850
    RIHCLDILFA FTKRVLGESG EMDALRIQME ERFMASNPSK VSYEPITTTL 1900
    KRKQEEVSAI IIQRAYRRYL LKQKVKKVSS IYKKDKGKEC DGTPIKEDTL 1950
    IDKLNENSTP EKTDMTPSTT SPPSYDSVTK PEKEKFEKDK SEKEDKGKDI 2000
    RESKK 2005
    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.
    The sequence CAA46438.1 differs from that shown. Reason: Frameshift at position 1953.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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 131-270, 769-983, 1197-1474, 1524-1932.
    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 CHEMBL2331043.
    DrugBanki DB00555. Lamotrigine.
    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 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.
    PharmGKBi PA35004.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1226.
    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

    ArrayExpressi Q99250.
    Bgeei Q99250.
    CleanExi HS_SCN2A.
    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

    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: October 1, 2014
    This is version 156 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