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P0DMA5 (SCNAA_ONYTO) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 4. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium channel protein type 10 subunit alpha
Gene names
Name:Scn10a
Synonyms:Sns
OrganismOnychomys torridus (Southern grasshopper mouse)
Taxonomic identifier38674 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeNeotominaeOnychomys

Protein attributes

Sequence length1959 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.1

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. Interacts with NEDD4 and NEDD4L By similarity.

Subcellular location

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

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.

Phosphorylation at Ser-1453 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents By similarity.

Miscellaneous

O.torridus is resistant to the pain-inducing components of the venom of its prey, the bark scorpion (Centruroides sculpturatus). It is most probably due to the unique inhibition by some venom components of the Scn10a sodium-channel in those rodents. Inhibition of Snc10a would, in turn, inhibit sodium currents, block action potential propagation and induce analgesia. Glu-862 plays a central role in that inhibition and its replacement by a Gln, the corresponding amino acid found in the M.musculus ortholog, prevents the inhibition of Snc10a. This would explain why the venom induces pain in M.musculus but not in O.torridus (Ref.1).

Sequence similarities

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

Contains 1 IQ domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19591959Sodium channel protein type 10 subunit alpha
PRO_0000424959

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
Transmembrane660 – 68425Helical; Name=S1 of repeat II; Potential
Transmembrane696 – 71924Helical; Name=S2 of repeat II; Potential
Transmembrane728 – 74720Helical; Name=S3 of repeat II; Potential
Transmembrane754 – 77320Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Transmembrane790 – 81021Helical; Name=S5 of repeat II; Potential
Transmembrane865 – 89026Helical; Name=S6 of repeat II; Potential
Transmembrane1150 – 117324Helical; Name=S1 of repeat III; Potential
Transmembrane1187 – 121226Helical; Name=S2 of repeat III; Potential
Transmembrane1219 – 124022Helical; Name=S3 of repeat III; Potential
Transmembrane1245 – 126622Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Transmembrane1286 – 131328Helical; Name=S5 of repeat III; Potential
Transmembrane1394 – 142027Helical; Name=S6 of repeat III; Potential
Transmembrane1474 – 149724Helical; Name=S1 of repeat IV; Potential
Transmembrane1509 – 153224Helical; Name=S2 of repeat IV; Potential
Transmembrane1539 – 156224Helical; Name=S3 of repeat IV; Potential
Transmembrane1575 – 159622Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Transmembrane1612 – 163423Helical; Name=S5 of repeat IV; Potential
Transmembrane1700 – 172425Helical; Name=S6 of repeat IV; Potential
Repeat125 – 399275I
Repeat659 – 891233II
Repeat1149 – 1421273III
Repeat1473 – 1725253IV
Domain1853 – 188230IQ

Amino acid modifications

Modified residue14531Phosphoserine; by PKC By similarity
Glycosylation2881N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation3341N-linked (GlcNAc...) Potential
Glycosylation8971N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis746 – 7472IA → TS: No effect on inhibition by the venom of Centruroides sculpturatus.
Mutagenesis8591Q → E: Complete loss of inhibition by the venom of Centruroides sculpturatus; when associated with Q-862. Ref.1
Mutagenesis8621E → Q: Almost complete loss of inhibition by the venom of Centruroides sculpturatus. Complete loss of inhibition by the venom of Centruroides sculpturatus; when associated with E-859. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P0DMA5 [UniParc].

Last modified January 22, 2014. Version 1.
Checksum: FE84EC9345B5EB74

FASTA1,959220,523
        10         20         30         40         50         60 
MEFPIGSVGT TNFRRFTPES LAEIEKQIAA HGAAKKARAK HGERKGQDEK PRPQLDLKAC 

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

       130        140        150        160        170        180 
RTAIKVSVHA WFSIFITITI LFNCVCMTQN DLPEKIEYAF TVIYTFEALI KILARGFCLN 

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

       250        260        270        280        290        300 
HSVRKLADVT ILTVFCLSVF ALVGLQLFKG NLKNKCIKRS TDPHNAYNFS SQMADNFYIK 

       310        320        330        340        350        360 
NGTTEPLLCG NGSDAGHCPS GYICLKTSDN PDFNYTSFDS FAWAFLSLFR LMTQDSWERL 

       370        380        390        400        410        420 
YQQTLRASGK MYMVFFVLVI FLGSFYLVNL ILAVVTMAYE EQNQATIAEI EAKEKKFQEA 

       430        440        450        460        470        480 
LEVLQKEQEV LAALGIDTTS LHSHNGSPLA PKNANERKHR IKSRVSEGST DDNRSPQSDP 

       490        500        510        520        530        540 
YNQRRMSFLG LSSGRRRASH SSVFHFRAPS QDVSFPDGIT DDGVFHGDHE SHRSSLLLAR 

       550        560        570        580        590        600 
GAGQAGPLPR SPLASSPNPG PGHREEGQLT APTGELTTGA PEDLALEAAG QKKNFLSAEY 

       610        620        630        640        650        660 
LNEPFRAQRA MSVVSIMTSV IEELEESKLR CPPCLINLAQ KYLIWECCPK WMKFKMVLFE 

       670        680        690        700        710        720 
LVTDPFAELT ITLCIVVNTI FMAMEHYPMT DAFDAMLQAG NIVFTVFFTM EMAFKIIAFD 

       730        740        750        760        770        780 
PYYYFQKKWN VFDCVIVTVS LLELSIAKKG SLSVLRTFRL LRVFKLAKSW PTLNTLIKII 

       790        800        810        820        830        840 
GNSVGALGNL TFILAIIVFI FALVGKQLLG EDYGCRKDGT ALWNEGQLRW HMCDFFHSFL 

       850        860        870        880        890        900 
VIFRILCGEW IENMWVCMQV SEKSICLILF LTVMVLGNLV VLNLFIALLL NSFSADNLTA 

       910        920        930        940        950        960 
PEDDGEVNNL QVALARTQAF GQRASQAISS YFSSHCRLRW PKVGSQLGVK PSLTSSKAEH 

       970        980        990       1000       1010       1020 
HITADAVNTA VGTSAKPALS GPKEDPRDFI TDANVWVSVP IAEGESDLDE LEEDIEQNSQ 

      1030       1040       1050       1060       1070       1080 
SSWREESPKG QQDQLWQIQR CEDHQVPNSP GSGMSSEDLA SYLGERWKSE ATPQVPAEGV 

      1090       1100       1110       1120       1130       1140 
DDTSSSEGST VDCPDPEEIL KKIPELADDL EEPDDCFTEG CTRHCPCCKV STSKFPWTTG 

      1150       1160       1170       1180       1190       1200 
WQVRKTCYRI VEHSWFESFI IFMILLSSGA LAFEDNYLEQ KPRVKSMLEY TDRVFTFIFV 

      1210       1220       1230       1240       1250       1260 
FEMLLKWVAY GFKKYFTNAW CWLDFLIVNI SLTSLIAKIL DYSDVASLKA LRTLRALRPL 

      1270       1280       1290       1300       1310       1320 
RALSRFEGMR VVVDALVGAI PSIMNVLLVC LIFWLIFSIM GVNLFAGKFS RCIDTSNNPF 

      1330       1340       1350       1360       1370       1380 
SVVNSTIVNN KSECRNQNHT GHFFWVNVKV NFDNVAMGYL ALLQVATFKG WMDIMYAAVD 

      1390       1400       1410       1420       1430       1440 
SREINSQPQW EDNLYMYLYF VVFIIFGGFF TLNLFVGVII DNFNQQKKKL GGQDIFMTEE 

      1450       1460       1470       1480       1490       1500 
QKKYYNAMKK LGSKKPQKPI PRPLNKYQGF VFDIVTRQAF DIIIMVLICL NMITMMVETD 

      1510       1520       1530       1540       1550       1560 
GQSEEKTKIL GRINQFFVAV FTGECVMKMF ALRQYYFTNG WNVFDFIVVI LSIGSLVFSA 

      1570       1580       1590       1600       1610       1620 
ILKSLESYFS PTLFRVIRLA RIGRILRLIR AAKGIRTLLF ALMMSLPALF NIGLLLFLVM 

      1630       1640       1650       1660       1670       1680 
FIYSIFGMAS FANVVEEAGI DDMFNFQTFG NSMLCLFQIT TSAGWDGLLS PILNTGPPYC 

      1690       1700       1710       1720       1730       1740 
DPNLSNNNTS KGNCGSPTVG IVFFTTYIII SFLIVVNMYI AVILENFNVA TEESTEPLSE 

      1750       1760       1770       1780       1790       1800 
DDFDMFYETW EKFDPEATQF IAFSALSDFA DTLSGPLRIP KPNQNILIQM DLPLVPGDKI 

      1810       1820       1830       1840       1850       1860 
HCLDILFAFT KNVLGESGEL DSLKTNMEEK FMATNLSKAS YEPIATTLRW KQEDISATVI 

      1870       1880       1890       1900       1910       1920 
QKAYRSYVLQ RSLTLSNPLR VPRAEDDDAP LPGEGYVTFM ANDSGRLPDK SETTSATSFP 

      1930       1940       1950 
PSYDSVTRGL SDRVNISTSN SMHNEDEVTS KEGDSPGPQ 

« Hide

References

[1]"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: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF 746-ILE-ALA-747; GLN-859 AND GLU-862.

Web resources

Protein Spotlight

A pain soothed - Issue 157 of January 2014

Cross-references

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

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:SF170. PTHR10037:SF170. 1 hit.
PfamPF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameSCNAA_ONYTO
AccessionPrimary (citable) accession number: P0DMA5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 22, 2014
Last sequence update: January 22, 2014
Last modified: April 16, 2014
This is version 4 of the entry and version 1 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

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries