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O88420

- SCN8A_RAT

UniProt

O88420 - SCN8A_RAT

Protein

Sodium channel protein type 8 subunit alpha

Gene

Scn8a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      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 By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi891 – 8988ATPSequence Analysis

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. sodium ion binding Source: RGD
    4. voltage-gated sodium channel activity Source: RGD

    GO - Biological processi

    1. membrane depolarization during action potential Source: RefGenome
    2. myelination Source: BHF-UCL
    3. neuronal action potential Source: RGD
    4. peripheral nervous system development Source: BHF-UCL
    5. sodium ion transmembrane transport Source: GOC
    6. sodium ion transport Source: RGD

    Keywords - Molecular functioni

    Ion channel, Sodium channel, Voltage-gated channel

    Keywords - Biological processi

    Ion transport, Sodium transport, Transport

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding, Sodium

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium channel protein type 8 subunit alpha
    Alternative name(s):
    Peripheral nerve protein type 4
    Short name:
    PN4
    Sodium channel 6
    Short name:
    NaCh6
    Sodium channel protein type VIII subunit alpha
    Voltage-gated sodium channel subunit alpha Nav1.6
    Gene namesi
    Name:Scn8a
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3638. Scn8a.

    Subcellular locationi

    Membrane By similarity; Multi-pass membrane protein By similarity

    GO - Cellular componenti

    1. axon initial segment Source: BHF-UCL
    2. integral component of membrane Source: RGD
    3. node of Ranvier Source: BHF-UCL
    4. plasma membrane Source: RGD
    5. voltage-gated sodium channel complex Source: RGD

    Keywords - Cellular componenti

    Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 19781978Sodium channel protein type 8 subunit alphaPRO_0000390890Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi215 – 2151N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi289 – 2891N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi295 – 2951N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi308 – 3081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi326 – 3261N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1356 – 13561N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1370 – 13701N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1381 – 13811N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1495 – 14951Phosphoserine; by PKCBy similarity

    Post-translational modificationi

    May be ubiquitinated by NEDD4L; which would promote its endocytosis.By similarity
    Phosphorylation at Ser-1495 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO88420.
    PRIDEiO88420.

    PTM databases

    PhosphoSiteiO88420.

    Expressioni

    Tissue specificityi

    Isoform 1 is highly expressed in brain, moderately in spinal cord, and at low levels in dorsal root ganglia, nodose ganglia and superior cervical ganglia. Not detected in sciatic nerve and non-neuronal tissues. Isoform 2 is hardly detectable, if at all, in brain, expressed at low levels in spinal cord and at highest levels in dorsal root ganglia.1 Publication

    Gene expression databases

    GenevestigatoriO88420.

    Interactioni

    Subunit structurei

    Interacts with NEDD4 and NEDD4L By similarity. Interacts with FGF13; may regulate SCN8A activity.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi248327. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliO88420.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 127127CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini152 – 1598ExtracellularSequence Analysis
    Topological domaini180 – 19213CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini212 – 2176ExtracellularSequence Analysis
    Topological domaini238 – 25215CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini278 – 387110ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini414 – 745332CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini771 – 78111ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini806 – 8138CytoplasmicSequence Analysis
    Topological domaini834 – 8396ExtracellularSequence Analysis
    Topological domaini861 – 87515CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini897 – 94953ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini976 – 1191216CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1216 – 122813ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1255 – 12606CytoplasmicSequence Analysis
    Topological domaini1283 – 12864ExtracellularSequence Analysis
    Topological domaini1309 – 132719CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1350 – 143586ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1463 – 151553CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1540 – 155011ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1575 – 15806CytoplasmicSequence Analysis
    Topological domaini1605 – 161410ExtracellularSequence Analysis
    Topological domaini1637 – 165115CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1675 – 173965ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1765 – 1978214CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei128 – 15124Helical; Name=S1 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei160 – 17920Helical; Name=S2 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei193 – 21119Helical; Name=S3 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei218 – 23720Helical; Name=S4 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei253 – 27725Helical; Name=S5 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei388 – 41326Helical; Name=S6 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei746 – 77025Helical; Name=S1 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei782 – 80524Helical; Name=S2 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei814 – 83320Helical; Name=S3 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei840 – 86021Helical; Name=S4 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei876 – 89621Helical; Name=S5 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei950 – 97526Helical; Name=S6 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei1192 – 121524Helical; Name=S1 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1229 – 125426Helical; Name=S2 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1261 – 128222Helical; Name=S3 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1287 – 130822Helical; Name=S4 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1328 – 134922Helical; Name=S5 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1436 – 146227Helical; Name=S6 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1516 – 153924Helical; Name=S1 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1551 – 157424Helical; Name=S2 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1581 – 160424Helical; Name=S3 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1615 – 163622Helical; Name=S4 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1652 – 167423Helical; Name=S5 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1740 – 176425Helical; Name=S6 of repeat IVSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati114 – 442329IAdd
    BLAST
    Repeati733 – 1005273IIAdd
    BLAST
    Repeati1178 – 1493316IIIAdd
    BLAST
    Repeati1502 – 1799298IVAdd
    BLAST
    Domaini1893 – 192230IQPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 IQ domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1226.
    HOGENOMiHOG000231755.
    HOVERGENiHBG053100.
    KOiK04840.
    PhylomeDBiO88420.

    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.
    IPR008054. Na_channel_a8su.
    IPR001696. Na_channel_asu.
    IPR010526. Na_trans_assoc.
    [Graphical view]
    PfamiPF11933. DUF3451. 1 hit.
    PF00520. Ion_trans. 4 hits.
    PF00612. IQ. 1 hit.
    PF06512. Na_trans_assoc. 1 hit.
    [Graphical view]
    PRINTSiPR00170. NACHANNEL.
    PR01667. NACHANNEL8.
    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: O88420-1) [UniParc]FASTAAdd to Basket

    Also known as: PN4

    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

    MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED     50
    SKPKPNSDLE AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG 100
    KTLFRFSATP ALYILSPFNL IRRIAIKILI HSVFSMIIMC TILTNCVFMT 150
    FSNPPEWSKN VEYTFTGIYT FESLVKIIAR GFCIDGFTFL RDPWNWLDFS 200
    VIMMAYVTEF VDLGNVSALR TFRVLRALKT ISVIPGLKTI VGALIQSVKK 250
    LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTRGF 300
    DWEEYINNKT NFYMVPGMLE PLLCGNSSDA GQCPEGFQCM KAGRNPNYGY 350
    TSFDTFSWAF LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF 400
    YLVNLILAVV AMAYEEQNQA TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA 450
    MATSAGTVSE DAIEEEGEDG VGSPRSSSEL SKLSSKSAKE RRNRRKKRKQ 500
    KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF SIMNQSLLSI 550
    PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 600
    LFIPIRARER RSSYSGYSGY SQCSRSSRIF PSLRRSVKRN STVDCNGVVS 650
    LIGPGSHIGR LLPEATTEVE IKKKGPGSLL VSMDQLASYG RKDRINSIMS 700
    VVTNTLVEEL EESQRKCPPC WYKFANTFLI WECHPYWIKL KEIVNLIVMD 750
    PFVDLAITIC IVLNTLFMAM EHHPMTPQFE HVLAVGNLVF TGIFTAEMFL 800
    KLIAMDPYYY FQEGWNIFDG FIVSLSLMEL SLADVEGLSV LRSFRLLRVF 850
    KLAKSWPTLN MLIKIIGNSV GALGNLTLVL AIIVFIFAVV GMQLFGKSYK 900
    ECVCKINQEC KLPRWHMNDF FHSFLIVFRV LCGEWIETMW DCMEVAGQAM 950
    CLIVFMMVMV IGNLVVLNLF LALLLSSFSA DNLAATDDDG EMNNLQISVI 1000
    RIKKGVAWTK VKVHAFMQAH FKQREADEVK PLDELYEKKA NCIANHTGVD 1050
    IHRNGDFQKN GNGTTSGIGS SVEKYIIDED HMSFINNPNL TVRVPIAVGE 1100
    SDFENLNTED VSSESDPEGS KDKLDDTSSS EGSTIDIKPE VEEVPVEQPE 1150
    EYLDPDACFT EGCVQRFKCC QVNIEEGLGK SWWILRKTCF LIVEHNWFET 1200
    FIIFMILLSS GALAFEDIYI EQRKTIRTIL EYADKVFTYI FILEMLLKWT 1250
    AYGFVKFFTN AWCWLDFLIV AVSLVSLIAN ALGYSELGAI KSLRTLRALR 1300
    PLRALSRFEG MRVVVNALVG AIPSIMNVLL VCLIFWLIFS IMGVNLFAGK 1350
    YHYCFNETSE IRFEIDIVNN KTDCEKLMEG NSTEIRWKNV KINFDNVGAG 1400
    YLALLQVATF KGWMDIMYAA VDSRKPDEQP DYEGNIYMYI YFVIFIIFGS 1450
    FFTLNLFIGV IIDNFNQQKK KFGGQDIFMT EEQKKYYNAM KKLGSKKPQK 1500
    PIPRPLNKIQ GIVFDFVTQQ AFDIVIMMLI CLNMVTMMVE TDTQSKQMEN 1550
    ILYWINLVFV IFFTCECVLK MFALRHYYFT IGWNIFDFVV VILSIVGMFL 1600
    ADIIEKYFVS PTLFRVIRLA RIGRILRLIK GAKGIRTLLF ALMMSLPALF 1650
    NIGLLLFLVM FIFSIFGMSN FAYVKHEAGI DDMFNFETFG NSMICLFQIT 1700
    TSAGWDGLLL PILNRPPDCS LDKEHPGSGF KGDCGNPSVG IFFFVSYIII 1750
    SFLIVVNMYI AIILENFSVA TEESADPLSE DDFETFYEIW EKFDPDATQF 1800
    IEYCKLADFA DALEHPLRVP KPNTIELIAM DLPMVSGDRI HCLDILFAFT 1850
    KRVLGDSGEL DILRQQMEER FVASNPSKVS YEPITTTLRR KQEEVSAVVL 1900
    QRAYRGHLAR RGFICRKMAS NKLENGGTHR DKKESTPSTA SLPSYDSVTK 1950
    PDKEKQQRAE EGRRERAKRQ KEVRESKC 1978
    Length:1,978
    Mass (Da):225,159
    Last modified:November 1, 1998 - v1
    Checksum:i9160843C5935B88B
    GO
    Isoform 2 (identifier: O88420-2) [UniParc]FASTAAdd to Basket

    Also known as: PN4a

    The sequence of this isoform differs from the canonical sequence as follows:
         664-664: E → EVKIDKAATDS

    Note: May be due to competing donor splice site.

    Show »
    Length:1,988
    Mass (Da):226,188
    Checksum:iC1F7D87FDC266C8F
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei664 – 6641E → EVKIDKAATDS in isoform 2. 1 PublicationVSP_038652

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF049239 mRNA. Translation: AAC26014.1.
    AF049240 mRNA. Translation: AAC26015.1.
    RefSeqiNP_062139.2. NM_019266.2. [O88420-1]
    UniGeneiRn.91216.

    Genome annotation databases

    GeneIDi29710.
    KEGGirno:29710.
    UCSCiRGD:3638. rat. [O88420-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF049239 mRNA. Translation: AAC26014.1 .
    AF049240 mRNA. Translation: AAC26015.1 .
    RefSeqi NP_062139.2. NM_019266.2. [O88420-1 ]
    UniGenei Rn.91216.

    3D structure databases

    ProteinModelPortali O88420.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 248327. 1 interaction.

    Chemistry

    BindingDBi O88420.
    ChEMBLi CHEMBL2752.
    GuidetoPHARMACOLOGYi 583.

    PTM databases

    PhosphoSitei O88420.

    Proteomic databases

    PaxDbi O88420.
    PRIDEi O88420.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 29710.
    KEGGi rno:29710.
    UCSCi RGD:3638. rat. [O88420-1 ]

    Organism-specific databases

    CTDi 6334.
    RGDi 3638. Scn8a.

    Phylogenomic databases

    eggNOGi COG1226.
    HOGENOMi HOG000231755.
    HOVERGENi HBG053100.
    KOi K04840.
    PhylomeDBi O88420.

    Miscellaneous databases

    NextBioi 610139.
    PROi O88420.

    Gene expression databases

    Genevestigatori O88420.

    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.
    IPR008054. Na_channel_a8su.
    IPR001696. Na_channel_asu.
    IPR010526. Na_trans_assoc.
    [Graphical view ]
    Pfami PF11933. DUF3451. 1 hit.
    PF00520. Ion_trans. 4 hits.
    PF00612. IQ. 1 hit.
    PF06512. Na_trans_assoc. 1 hit.
    [Graphical view ]
    PRINTSi PR00170. NACHANNEL.
    PR01667. NACHANNEL8.
    SMARTi SM00015. IQ. 1 hit.
    [Graphical view ]
    PROSITEi PS50096. IQ. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia."
      Dietrich P.S., McGivern J.G., Delgado S.G., Koch B.D., Eglen R.M., Hunter J.C., Sangameswaran L.
      J. Neurochem. 70:2262-2272(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
      Tissue: Spinal ganglion.
    2. "Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons."
      Wittmack E.K., Rush A.M., Craner M.J., Goldfarb M., Waxman S.G., Dib-Hajj S.D.
      J. Neurosci. 24:6765-6775(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FGF13.

    Entry informationi

    Entry nameiSCN8A_RAT
    AccessioniPrimary (citable) accession number: O88420
    Secondary accession number(s): O88421
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 19, 2010
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 103 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3