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Q62968

- SCNAA_RAT

UniProt

Q62968 - SCNAA_RAT

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Protein
Sodium channel protein type 10 subunit alpha
Gene
Scn10a, Sns
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Tetrodotoxin-resistant channel that 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 sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.3 Publications

GO - Molecular functioni

  1. protein binding Source: UniProtKB
  2. voltage-gated sodium channel activity Source: RGD
Complete GO annotation...

GO - Biological processi

  1. membrane depolarization during action potential Source: RefGenome
  2. neuronal action potential Source: RefGenome
  3. odontogenesis of dentin-containing tooth Source: RGD
  4. sensory perception of pain Source: RGD
  5. sodium ion transmembrane transport Source: GOC
  6. sodium ion transport Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Protein family/group databases

TCDBi1.A.1.10.6. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 10 subunit alpha
Alternative name(s):
Peripheral nerve sodium channel 3
Short name:
PN3
Sensory neuron sodium channel
Sodium channel protein type X subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.8
Gene namesi
Name:Scn10a
Synonyms:Sns
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3629. Scn10a.

Subcellular locationi

Membrane; Multi-pass membrane protein By similarity
Note: It can be translocated to the extracellular membrane through association with S100A10.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei126 – 14924Helical; Name=S1 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei155 – 17420Helical; Name=S2 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei188 – 20619Helical; Name=S3 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei213 – 23220Helical; Voltage-sensor; Name=S4 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei249 – 27224Helical; Name=S5 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei373 – 39826Helical; Name=S6 of repeat I; Reviewed prediction
Add
BLAST
Transmembranei659 – 68325Helical; Name=S1 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei695 – 71824Helical; Name=S2 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei727 – 74620Helical; Name=S3 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei753 – 77220Helical; Voltage-sensor; Name=S4 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei789 – 80921Helical; Name=S5 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei864 – 88926Helical; Name=S6 of repeat II; Reviewed prediction
Add
BLAST
Transmembranei1149 – 117224Helical; Name=S1 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1186 – 121126Helical; Name=S2 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1218 – 123922Helical; Name=S3 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1244 – 126522Helical; Voltage-sensor; Name=S4 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1285 – 131228Helical; Name=S5 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1393 – 141927Helical; Name=S6 of repeat III; Reviewed prediction
Add
BLAST
Transmembranei1473 – 149624Helical; Name=S1 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1508 – 153124Helical; Name=S2 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1538 – 156124Helical; Name=S3 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1574 – 159522Helical; Voltage-sensor; Name=S4 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1611 – 163323Helical; Name=S5 of repeat IV; Reviewed prediction
Add
BLAST
Transmembranei1699 – 172325Helical; Name=S6 of repeat IV; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. clathrin complex Source: RGD
  2. integral component of membrane Source: RGD
  3. plasma membrane Source: RefGenome
  4. voltage-gated sodium channel complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 19561956Sodium channel protein type 10 subunit alpha
PRO_0000048509Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi279 – 2791N-linked (GlcNAc...) Reviewed prediction
Glycosylationi288 – 2881N-linked (GlcNAc...) Reviewed prediction
Glycosylationi311 – 3111N-linked (GlcNAc...) Reviewed prediction
Glycosylationi334 – 3341N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1323 – 13231N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1329 – 13291N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1337 – 13371N-linked (GlcNAc...) Reviewed prediction
Modified residuei1452 – 14521Phosphoserine; by PKC By similarity
Glycosylationi1687 – 16871N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Ubiquitinated by NEDD4L; which promotes its endocytosis By similarity.
Phosphorylation at Ser-1452 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

PaxDbiQ62968.
PRIDEiQ62968.

PTM databases

PhosphoSiteiQ62968.

Expressioni

Tissue specificityi

Expressed in dorsal root ganglia, trigeminal ganglia, nodose ganglia and sciatic nerve.3 Publications

Developmental stagei

Expressed in dorsal root ganglia at 15 dpc onwards.1 Publication

Inductioni

Down-regulated after axotomy in dorsal root ganglia.1 Publication

Gene expression databases

GenevestigatoriQ62968.

Interactioni

Subunit structurei

The channel consists of an ion conducting pore forming alpha-subunit regulated by one or more associated auxiliary subunits SCN1B, SCN2B and SCN3B; electrophysiological properties may vary depending on the type of the associated beta subunits. Found in a number of complexes with PRX, DYNLT1 and PDZD2. Interacts with proteins such as FSTL1, PRX, DYNLT1, PDZD2, S100A10 and many others. Interacts with NEDD4 and NEDD4L.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dynlt1Q9Z3362EBI-1800320,EBI-920359
PrxQ634252EBI-1800320,EBI-1800492
S100a10P059434EBI-1800320,EBI-1800351

Protein-protein interaction databases

IntActiQ62968. 23 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ62968.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati125 – 399275I
Add
BLAST
Repeati658 – 890233II
Add
BLAST
Repeati1148 – 1420273III
Add
BLAST
Repeati1472 – 1724253IV
Add
BLAST
Domaini1852 – 188130IQ
Add
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.

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1226.
HOGENOMiHOG000231755.
HOVERGENiHBG053100.
InParanoidiQ62968.
KOiK04842.
PhylomeDBiQ62968.
TreeFamiTF323985.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR028809. Na_channel_a10su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PANTHERiPTHR10037:SF23. PTHR10037:SF23. 1 hit.
PfamiPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSiPR00170. NACHANNEL.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q62968-1) [UniParc]FASTAAdd to Basket

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

MELPFASVGT TNFRRFTPES LAEIEKQIAA HRAAKKARTK HRGQEDKGEK     50
PRPQLDLKAC NQLPKFYGEL PAELVGEPLE DLDPFYSTHR TFMVLNKSRT 100
ISRFSATWAL WLFSPFNLIR RTAIKVSVHS WFSIFITITI LVNCVCMTRT 150
DLPEKVEYVF TVIYTFEALI KILARGFCLN EFTYLRDPWN WLDFSVITLA 200
YVGAAIDLRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI HSVRKLADVT 250
ILTVFCLSVF ALVGLQLFKG NLKNKCIRNG TDPHKADNLS SEMAEYIFIK 300
PGTTDPLLCG NGSDAGHCPG GYVCLKTPDN PDFNYTSFDS FAWAFLSLFR 350
LMTQDSWERL YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE 400
EQSQATIAEI EAKEKKFQEA LEVLQKEQEV LAALGIDTTS LQSHSGSPLA 450
SKNANERRPR VKSRVSEGST DDNRSPQSDP YNQRRMSFLG LSSGRRRASH 500
GSVFHFRAPS QDISFPDGIT DDGVFHGDQE SRRGSILLGR GAGQTGPLPR 550
SPLPQSPNPG RRHGEEGQLG VPTGELTAGA PEGPALDTTG QKSFLSAGYL 600
NEPFRAQRAM SVVSIMTSVI EELEESKLKC PPCLISFAQK YLIWECCPKW 650
RKFKMALFEL VTDPFAELTI TLCIVVNTVF MAMEHYPMTD AFDAMLQAGN 700
IVFTVFFTME MAFKIIAFDP YYYFQKKWNI FDCVIVTVSL LELSASKKGS 750
LSVLRTFRLL RVFKLAKSWP TLNTLIKIIG NSVGALGNLT FILAIIVFIF 800
ALVGKQLLSE DYGCRKDGVS VWNGEKLRWH MCDFFHSFLV VFRILCGEWI 850
ENMWVCMEVS QKSICLILFL TVMVLGNLVV LNLFIALLLN SFSADNLTAP 900
EDDGEVNNLQ LALARIQVLG HRASRAIASY ISSHCRFRWP KVETQLGMKP 950
PLTSSEAKNH IATDAVSAAV GNLTKPALSS PKENHGDFIT DPNVWVSVPI 1000
AEGESDLDEL EEDMEQASQS SWQEEDPKGQ QEQLPQVQKC ENHQAARSPA 1050
SMMSSEDLAP YLGESWKRKD SPQVPAEGVD DTSSSEGSTV DCPDPEEILR 1100
KIPELADDLD EPDDCFTEGC TRRCPCCNVN TSKSPWATGW QVRKTCYRIV 1150
EHSWFESFII FMILLSSGAL AFEDNYLEEK PRVKSVLEYT DRVFTFIFVF 1200
EMLLKWVAYG FKKYFTNAWC WLDFLIVNIS LTSLIAKILE YSDVASIKAL 1250
RTLRALRPLR ALSRFEGMRV VVDALVGAIP SIMNVLLVCL IFWLIFSIMG 1300
VNLFAGKFSK CVDTRNNPFS NVNSTMVNNK SECHNQNSTG HFFWVNVKVN 1350
FDNVAMGYLA LLQVATFKGW MDIMYAAVDS GEINSQPNWE NNLYMYLYFV 1400
VFIIFGGFFT LNLFVGVIID NFNQQKKKLG GQDIFMTEEQ KKYYNAMKKL 1450
GSKKPQKPIP RPLNKYQGFV FDIVTRQAFD IIIMVLICLN MITMMVETDE 1500
QGEEKTKVLG RINQFFVAVF TGECVMKMFA LRQYYFTNGW NVFDFIVVIL 1550
SIGSLLFSAI LKSLENYFSP TLFRVIRLAR IGRILRLIRA AKGIRTLLFA 1600
LMMSLPALFN IGLLLFLVMF IYSIFGMASF ANVVDEAGID DMFNFKTFGN 1650
SMLCLFQITT SAGWDGLLSP ILNTGPPYCD PNLPNSNGSR GNCGSPAVGI 1700
IFFTTYIIIS FLIVVNMYIA VILENFNVAT EESTEPLSED DFDMFYETWE 1750
KFDPEATQFI AFSALSDFAD TLSGPLRIPK PNQNILIQMD LPLVPGDKIH 1800
CLDILFAFTK NVLGESGELD SLKTNMEEKF MATNLSKASY EPIATTLRWK 1850
QEDLSATVIQ KAYRSYMLHR SLTLSNTLHV PRAEEDGVSL PGEGYVTFMA 1900
NSGLPDKSET ASATSFPPSY DSVTRGLSDR ANINPSSSMQ NEDEVAAKEG 1950
NSPGPQ 1956
Length:1,956
Mass (Da):219,733
Last modified:November 1, 1996 - v1
Checksum:i8FC58EDAD263AC67
GO
Isoform 2 (identifier: Q62968-2) [UniParc]FASTAAdd to Basket

Also known as: Nav1.8c

The sequence of this isoform differs from the canonical sequence as follows:
     1030-1030: Missing.

Show »
Length:1,955
Mass (Da):219,605
Checksum:i4C6677DF46388F43
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1030 – 10301Missing in isoform 2.
VSP_012258

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti59 – 591A → D in CAA63095. 1 Publication
Sequence conflicti432 – 4321A → E in CAA63095. 1 Publication
Sequence conflicti520 – 5201T → TP in CAA63095. 1 Publication
Sequence conflicti587 – 5871D → H in CAA63095. 1 Publication
Sequence conflicti757 – 7571F → L in CAA63095. 1 Publication
Sequence conflicti938 – 9381R → H in CAA63095. 1 Publication
Sequence conflicti1896 – 18961V → I in CAA63095. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X92184 mRNA. Translation: CAA63095.1.
U53833 Genomic DNA. Translation: AAC52619.1.
AJ623271 mRNA. Translation: CAF25041.1.
PIRiS68453.
RefSeqiNP_058943.1. NM_017247.1.
XP_006244144.1. XM_006244082.1. [Q62968-2]
UniGeneiRn.10246.

Genome annotation databases

GeneIDi29571.
KEGGirno:29571.
UCSCiRGD:3629. rat. [Q62968-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X92184 mRNA. Translation: CAA63095.1 .
U53833 Genomic DNA. Translation: AAC52619.1 .
AJ623271 mRNA. Translation: CAF25041.1 .
PIRi S68453.
RefSeqi NP_058943.1. NM_017247.1.
XP_006244144.1. XM_006244082.1. [Q62968-2 ]
UniGenei Rn.10246.

3D structure databases

ProteinModelPortali Q62968.
ModBasei Search...

Protein-protein interaction databases

IntActi Q62968. 23 interactions.

Chemistry

BindingDBi Q62968.
ChEMBLi CHEMBL4017.
GuidetoPHARMACOLOGYi 585.

Protein family/group databases

TCDBi 1.A.1.10.6. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSitei Q62968.

Proteomic databases

PaxDbi Q62968.
PRIDEi Q62968.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 29571.
KEGGi rno:29571.
UCSCi RGD:3629. rat. [Q62968-1 ]

Organism-specific databases

CTDi 6336.
RGDi 3629. Scn10a.

Phylogenomic databases

eggNOGi COG1226.
HOGENOMi HOG000231755.
HOVERGENi HBG053100.
InParanoidi Q62968.
KOi K04842.
PhylomeDBi Q62968.
TreeFami TF323985.

Miscellaneous databases

NextBioi 609654.
PROi Q62968.

Gene expression databases

Genevestigatori Q62968.

Family and domain databases

Gene3Di 1.20.120.350. 4 hits.
InterProi IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR028809. Na_channel_a10su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view ]
PANTHERi PTHR10037:SF23. PTHR10037:SF23. 1 hit.
Pfami PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view ]
PRINTSi PR00170. NACHANNEL.
ProtoNeti Search...

Publicationsi

  1. "A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons."
    Akopian A.N., Sivilotti L., Wood J.N.
    Nature 379:257-262(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION.
    Tissue: Spinal ganglion.
  2. "Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons."
    Sangameswaran L., Delgado S.G., Fish L.M., Koch B.D., Jakeman L.B., Stewart G.R., Sze P., Hunter J.C., Eglen R.M., Herman R.C.
    J. Biol. Chem. 271:5953-5956(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION.
    Strain: Sprague-Dawley.
    Tissue: Spinal ganglion.
  3. "Role of auxiliary beta1-, beta2-, and beta3-subunits and their interaction with Na(v)1.8 voltage-gated sodium channel."
    Vijayaragavan K., Powell A.J., Kinghorn I.J., Chahine M.
    Biochem. Biophys. Res. Commun. 319:531-540(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), INTERACTION WITH SCN1B; SCN2B AND SCN3B.
    Strain: Sprague-Dawley.
    Tissue: Spinal ganglion.
  4. "Novel isoforms of the sodium channels Nav1.8 and Nav1.5 are produced by a conserved mechanism in mouse and rat."
    Kerr N.C.H., Holmes F.E., Wynick D.
    J. Biol. Chem. 279:24826-24833(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 963-1097 (ISOFORMS 1 AND 2).
    Strain: Wistar.
    Tissue: Spinal ganglion and Trigeminal ganglion.
  5. "Unilateral nerve injury down-regulates mRNA for Na+ channel SCN10A bilaterally in rat dorsal root ganglia."
    Oaklander A.L., Belzberg A.J.
    Brain Res. Mol. Brain Res. 52:162-165(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  6. "Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons."
    Benn S.C., Costigan M., Tate S., Fitzgerald M., Woolf C.J.
    J. Neurosci. 21:6077-6085(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  7. "Annexin II light chain regulates sensory neuron-specific sodium channel expression."
    Okuse K., Malik-Hall M., Baker M.D., Poon W.-Y.L., Kong H., Chao M.V., Wood J.N.
    Nature 417:653-656(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH S100A10.
  8. "Sensory neuron proteins interact with the intracellular domains of sodium channel NaV1.8."
    Malik-Hall M., Poon W.-Y.L., Baker M.D., Wood J.N., Okuse K.
    Brain Res. Mol. Brain Res. 110:298-304(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FSTL1; PRX; DYNLT1 AND PDZD2, IDENTIFICATION IN COMPLEXES WITH PRX; DYNLT1 AND PDZD2.
  9. "Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain."
    Gold M.S., Weinreich D., Kim C.-S., Wang R., Treanor J., Porreca F., Lai J.
    J. Neurosci. 23:158-166(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PAIN.

Entry informationi

Entry nameiSCNAA_RAT
AccessioniPrimary (citable) accession number: Q62968
Secondary accession number(s): Q63554, Q6EWG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 1, 1996
Last modified: June 11, 2014
This is version 111 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

Similar proteinsi