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Q6QIY3 (SCNAA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Scn10a
Synonyms:Sns
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1958 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Subunit structure

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 By similarity. Interacts with NEDD4 and NEDD4L. Ref.4

Subcellular location

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

Tissue specificity

Expressed in dorsal root ganglion and trigeminal ganglion.

Domain

The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Post-translational modification

Ubiquitinated by NEDD4L; which promotes its endocytosis Probable. Ref.4

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.

Miscellaneous

Mus musculus is sensitive to the pain-inducing components of the bark scorpion (Centruroides sculpturatus) venom while Onychomys torridus is not. Gln-861 may account for the difference between both rodents and its replacement by a glutamate, the corresponding amino acid found in the Onychomys torridus ortholog, allows inhibition of Snc10a by the venom, which in turn, inhibits sodium currents, blocks action potential propagation and may induce analgesia (Ref.5).

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.8/SCN10A subfamily. [View classification]

Contains 1 IQ domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6QIY3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q6QIY3-2)

Also known as: Nav1.8c;

The sequence of this isoform differs from the canonical sequence as follows:
     1030-1030: Missing.
Isoform 3 (identifier: Q6QIY3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1435: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19581958Sodium channel protein type 10 subunit alpha
PRO_0000048508

Regions

Transmembrane126 – 14924Helical; Name=S1 of repeat I; Potential
Transmembrane155 – 17420Helical; Name=S2 of repeat I; Potential
Transmembrane188 – 20619Helical; Name=S3 of repeat I; Potential
Transmembrane213 – 23220Helical; Voltage-sensor; Name=S4 of repeat I; Potential
Transmembrane249 – 27224Helical; Name=S5 of repeat I; Potential
Transmembrane373 – 39826Helical; Name=S6 of repeat I; Potential
Transmembrane659 – 68325Helical; Name=S1 of repeat II; Potential
Transmembrane695 – 71824Helical; Name=S2 of repeat II; Potential
Transmembrane727 – 74620Helical; Name=S3 of repeat II; Potential
Transmembrane753 – 77220Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Transmembrane789 – 80921Helical; Name=S5 of repeat II; Potential
Transmembrane864 – 88926Helical; Name=S6 of repeat II; Potential
Transmembrane1149 – 117224Helical; Name=S1 of repeat III; Potential
Transmembrane1186 – 121126Helical; Name=S2 of repeat III; Potential
Transmembrane1218 – 123922Helical; Name=S3 of repeat III; Potential
Transmembrane1244 – 126522Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Transmembrane1285 – 131228Helical; Name=S5 of repeat III; Potential
Transmembrane1393 – 141927Helical; Name=S6 of repeat III; Potential
Transmembrane1473 – 149624Helical; Name=S1 of repeat IV; Potential
Transmembrane1508 – 153124Helical; Name=S2 of repeat IV; Potential
Transmembrane1538 – 156124Helical; Name=S3 of repeat IV; Potential
Transmembrane1574 – 159522Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Transmembrane1611 – 163323Helical; Name=S5 of repeat IV; Potential
Transmembrane1699 – 172325Helical; Name=S6 of repeat IV; Potential
Repeat125 – 399275I
Repeat658 – 890233II
Repeat1148 – 1420273III
Repeat1472 – 1724253IV
Domain1852 – 188130IQ

Amino acid modifications

Modified residue14521Phosphoserine; by PKC By similarity
Glycosylation2791N-linked (GlcNAc...) Potential
Glycosylation2881N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation3341N-linked (GlcNAc...) Potential
Glycosylation13231N-linked (GlcNAc...) Potential
Glycosylation13291N-linked (GlcNAc...) Potential
Glycosylation13371N-linked (GlcNAc...) Potential
Glycosylation15001N-linked (GlcNAc...) Potential
Glycosylation16871N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 14351435Missing in isoform 3.
VSP_012256
Alternative sequence10301Missing in isoform 2.
VSP_012257

Experimental info

Mutagenesis8611Q → E: Sensitive to inhibition by some components of the venom of Centruroides sculpturatus. Ref.5
Mutagenesis19221Y → A: No regulation by NEDD4L. Ref.4

Sequences

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

Last modified December 21, 2004. Version 2.
Checksum: 24830634E86490FF

FASTA1,958220,552
        10         20         30         40         50         60 
MEFPFGSVGT TNFRRFTPES LAEIEKQIAA HRAAKKGRPK QRGQKDKSEK PRPQLDLKAC 

        70         80         90        100        110        120 
NQLPRFYGEL PAELVGEPLE DLDPFYSTHR TFIVLDKSRT ISRFSATWAL WLFSPFNLIR 

       130        140        150        160        170        180 
RTAIKVSVHS WFSIFITVTI LVNCVCMTRT DLPEKLEYAF TVVYTFEALI KILARGFCLN 

       190        200        210        220        230        240 
EFTYLRDPWN WLDFSVITLA YVGAAIDLRG ISGLRTFRVL RALKTVSVIP GLKVIVGALI 

       250        260        270        280        290        300 
HSVRKLADVT ILTVFCLSVF ALVGLQLFKG NLKNKCIKNG TDPHKADNLS SEMAGDIFIK 

       310        320        330        340        350        360 
PGTTDPLLCG NGSDAGHCPN DYVCRKTSDN PDFNYTSFDS FAWAFLSLFR LMTQDSWERL 

       370        380        390        400        410        420 
YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE EQSQATIAEI EAKEKKFKEA 

       430        440        450        460        470        480 
LEVLQKEQEV LAALGIDTTS LYSHNGSPLA PKNANERRPR VKSRMSEGST DDNRSLQSDP 

       490        500        510        520        530        540 
YNQRRMSFLG LSSGRRRASH SSVFHFRAPS QDVSFPDGIL DDGVFHGDQE SRRSSILLGR 

       550        560        570        580        590        600 
GAGQAGPLPR SPLPQSPNPG PRRGEEGQRG VPTGELATGA PEGPALDAAG QKNFLSADYL 

       610        620        630        640        650        660 
NEPFRAQRAM SVVSIMTSVI EELEESKLKC PPCLISLAQK YLIWECCPKW KKFKMVLFEL 

       670        680        690        700        710        720 
VTDPFAELTI TLCIVVNTVF MAMEHYPMTD AFDAMLQAGN IVFTVFFTME MAFKIIAFDP 

       730        740        750        760        770        780 
YYYFQKKWNI FDCVIVTVSL LELSTSKKGS LSVLRTFRLL RVFKLAKSWP TLNMLIKIIG 

       790        800        810        820        830        840 
NSVGALGNLT FILAIIVFIF ALVGKQLLSE NYGCRRDGIS VWNGERLRWH MCDFFHSFLV 

       850        860        870        880        890        900 
VFRILCGEWI ENMWVCMEVS QDYICLTLFL TVMVLGNLVV LNLFIALLLN SFSADNLTAP 

       910        920        930        940        950        960 
EDDGEVNNLQ VALARIQVFG HRASRAITSY IRSHCRLRWP KVETQLGMKP PLTSCKAENH 

       970        980        990       1000       1010       1020 
IATDAVNAAV GNLAKPALGG PKENHGDFIT DPNVWVSVPI AEGESDLDEL EEDVEHASQS 

      1030       1040       1050       1060       1070       1080 
SWQEESPKGQ QELLQQVQKC EDHQAARSPP SGMSSEDLAP YLGERWQREE SPRVPAEGVD 

      1090       1100       1110       1120       1130       1140 
DTSSSEGSTV DCPDPEEILR KIPELAEELD EPDDCFPEGC TRRCPCCKVN TSKFPWATGW 

      1150       1160       1170       1180       1190       1200 
QVRKTCYRIV EHSWFESFII FMILLSSGAL AFEDNYLEEK PRVKSVLEYT DRVFTFIFVF 

      1210       1220       1230       1240       1250       1260 
EMLLKWVAYG FKKYFTNAWC WLDFLIVNIS LTSLIAKILE YSDVASIKAL RTLRALRPLR 

      1270       1280       1290       1300       1310       1320 
ALSRFEGMRV VVDALVGAIP SIMNVLLVCL IFWLIFSIMG VNLFAGKFSR CVDTRSNPFS 

      1330       1340       1350       1360       1370       1380 
VVNSTFVTNK SDCYNQNNTG HFFWVNVKVN FDNVAMGYLA LLQVATFKGW MDIMYAAVDS 

      1390       1400       1410       1420       1430       1440 
RDINSQPNWE ESLYMYLYFV VFIIFGGFFT LNLFVGVIID NFNQQKKKLG GQDIFMTEEQ 

      1450       1460       1470       1480       1490       1500 
KKYYNAMKKL GSKKPQKPIP RPLNKYQGFV FDIVTRQAFD IIIMALICLN MITMMVETDN 

      1510       1520       1530       1540       1550       1560 
QSEEKTKVLG RINQFFVAVF TGECVMKMFA LRQYYFTNGW NVFDFIVVIL SISSLLFSAI 

      1570       1580       1590       1600       1610       1620 
LSSLESYFSP TLLRVIRLAR IGRILRLIRA AKGIRTLLFA LMMSLPALFN IGLLLFLVMF 

      1630       1640       1650       1660       1670       1680 
IYSIFGMASF ANVIDEAGID DMFNFKTFGN SMLCLFQITT SAGWDGLLSP ILNTGPPYCD 

      1690       1700       1710       1720       1730       1740 
PNRPNSNGSK GNCGSPAVGI LFFTTYIIIS FLIVVNMYIA VILENFNVAT EESTEPLSED 

      1750       1760       1770       1780       1790       1800 
DFDMFYETWE KFDPEATQFI AFSALSDFAD TLSGPLRIPK PNQNILIQMD LPLVPGDKIH 

      1810       1820       1830       1840       1850       1860 
CLDILFAFTK NVLGESGELD SLKTNMEEKF MATNLSKASY EPIATTLRCK QEDISATIIQ 

      1870       1880       1890       1900       1910       1920 
KAYRNYMLQR SLMLSNPLHV PRAEEDGVSL PREGYVTFMA NDNGGLPDKS ETASATSFPP 

      1930       1940       1950 
SYDSVTRGLS DRANISTSSS MQNEDEVTAK EGKSPGPQ 

« Hide

Isoform 2 (Nav1.8c) [UniParc].

Checksum: 23426D535A65601D
Show »

FASTA1,957220,424
Isoform 3 [UniParc].

Checksum: D9DB3D0D96A3C622
Show »

FASTA52358,512

References

[1]"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 [GENOMIC DNA / MRNA] OF 943-1090 (ISOFORMS 1 AND 2).
Strain: 129P2.
Tissue: Spinal ganglion and Trigeminal ganglion.
[2]"Mouse sodium channel clone BC in pSB+."
Jover E., Shah V.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 3).
Strain: C3H.
[3]"cDNA cloning of the mouse sensory neuron specific sodium channel Nav1.8 (Scn10a)."
Puhl H.L. III, King M.M., Ikeda S.R.
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2).
Strain: CD-1.
Tissue: Spinal ganglion.
[4]"Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2."
Fotia A.B., Ekberg J., Adams D.J., Cook D.I., Poronnik P., Kumar S.
J. Biol. Chem. 279:28930-28935(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4 AND NEDD4L, PROBABLE UBIQUITINATION, MUTAGENESIS OF TYR-1922.
[5]"Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin."
Rowe A.H., Xiao Y., Rowe M.P., Cummins T.R., Zakon H.H.
Science 342:441-446(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLN-861.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ622906 Genomic DNA. Translation: CAF22039.1.
AJ623269 mRNA. Translation: CAF25039.1.
AJ623270 mRNA. Translation: CAF25040.1.
L42342 mRNA. Translation: AAA68000.1.
AY538273 mRNA. Translation: AAS45602.1.
CCDSCCDS57716.1. [Q6QIY3-1]
RefSeqNP_033160.2. NM_009134.3. [Q6QIY3-2]
XP_006512052.1. XM_006511989.1. [Q6QIY3-1]
XP_006512053.1. XM_006511990.1. [Q6QIY3-1]
XP_006512054.1. XM_006511991.1. [Q6QIY3-1]
UniGeneMm.247042.
Mm.455125.
Mm.489505.

3D structure databases

ProteinModelPortalQ6QIY3.
SMRQ6QIY3. Positions 156-268, 667-890, 1149-1420, 1470-1872.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203097. 2 interactions.
STRING10090.ENSMUSP00000081845.

Chemistry

BindingDBQ6QIY3.
ChEMBLCHEMBL5158.

PTM databases

PhosphoSiteQ6QIY3.

Proteomic databases

PaxDbQ6QIY3.
PRIDEQ6QIY3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID20264.
KEGGmmu:20264.
UCSCuc009sbf.2. mouse. [Q6QIY3-3]
uc009sbg.3. mouse. [Q6QIY3-2]
uc009sbh.3. mouse. [Q6QIY3-1]

Organism-specific databases

CTD6336.
MGIMGI:108029. Scn10a.

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231755.
HOVERGENHBG053100.
InParanoidQ6QIY3.
KOK04842.
PhylomeDBQ6QIY3.

Gene expression databases

BgeeQ6QIY3.
CleanExMM_SCN10A.
GenevestigatorQ6QIY3.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR028809. Na_channel_a10su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PANTHERPTHR10037:SF23. PTHR10037:SF23. 1 hit.
PfamPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio297931.
PROQ6QIY3.
SOURCESearch...

Entry information

Entry nameSCNAA_MOUSE
AccessionPrimary (citable) accession number: Q6QIY3
Secondary accession number(s): Q62243 expand/collapse secondary AC list , Q6EWG7, Q6KCH7, Q703F9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: December 21, 2004
Last modified: July 9, 2014
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot