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Q9Y5Y9 (SCNAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
Short name=hPN3
Sodium channel protein type X subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.8
Gene names
Name:SCN10A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1956 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 By similarity. Interacts with NEDD4 and NEDD4L.

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 the dorsal root ganglia and sciatic nerve. Ref.1

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 By similarity.

Phosphorylation at Ser-1451 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents By similarity.

Sequence similarities

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

Contains 1 IQ domain.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processAV node cell to bundle of His cell communication

Inferred from mutant phenotype PubMed 20062061. Source: BHF-UCL

bundle of His cell to Purkinje myocyte communication

Inferred from mutant phenotype PubMed 20062061. Source: BHF-UCL

regulation of atrial cardiac muscle cell membrane depolarization

Inferred from mutant phenotype PubMed 20062061PubMed 21041692. Source: BHF-UCL

regulation of cardiac muscle contraction

Inferred from mutant phenotype PubMed 20062061. Source: BHF-UCL

regulation of heart rate

Inferred from mutant phenotype PubMed 20062061PubMed 21041692. Source: BHF-UCL

regulation of ion transmembrane transport

Inferred from direct assay Ref.1. Source: BHF-UCL

sensory perception

Traceable author statement Ref.1. Source: ProtInc

sensory perception of pain

Inferred from electronic annotation. Source: InterPro

sodium ion transmembrane transport

Inferred from direct assay Ref.1. Source: BHF-UCL

sodium ion transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentC-fiber

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

voltage-gated sodium channel complex

Inferred from direct assay Ref.1. Source: BHF-UCL

   Molecular_functionvoltage-gated sodium channel activity

Inferred from direct assay Ref.1. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19561956Sodium channel protein type 10 subunit alpha
PRO_0000048507

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
Transmembrane374 – 39926Helical; 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
Transmembrane1148 – 117124Helical; Name=S1 of repeat III; Potential
Transmembrane1185 – 121026Helical; Name=S2 of repeat III; Potential
Transmembrane1217 – 123822Helical; Name=S3 of repeat III; Potential
Transmembrane1243 – 126422Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Transmembrane1284 – 131128Helical; Name=S5 of repeat III; Potential
Transmembrane1392 – 141827Helical; Name=S6 of repeat III; Potential
Transmembrane1472 – 149524Helical; Name=S1 of repeat IV; Potential
Transmembrane1507 – 153024Helical; Name=S2 of repeat IV; Potential
Transmembrane1537 – 156024Helical; Name=S3 of repeat IV; Potential
Transmembrane1573 – 159422Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Transmembrane1610 – 163223Helical; Name=S5 of repeat IV; Potential
Transmembrane1698 – 172225Helical; Name=S6 of repeat IV; Potential
Repeat125 – 400276I
Repeat659 – 891233II
Repeat1147 – 1419273III
Repeat1471 – 1723253IV
Domain1851 – 188030IQ

Amino acid modifications

Modified residue14511Phosphoserine; by PKC By similarity
Glycosylation2841N-linked (GlcNAc...) Potential
Glycosylation2881N-linked (GlcNAc...) Potential
Glycosylation3121N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Potential
Glycosylation8191N-linked (GlcNAc...) Potential
Glycosylation13121N-linked (GlcNAc...) Potential
Glycosylation13281N-linked (GlcNAc...) Potential
Glycosylation13361N-linked (GlcNAc...) Potential
Glycosylation16861N-linked (GlcNAc...) Potential

Natural variations

Natural variant5091S → P.
Corresponds to variant rs7630989 [ dbSNP | Ensembl ].
VAR_020605
Natural variant5901G → R.
Corresponds to variant rs35332705 [ dbSNP | Ensembl ].
VAR_048696
Natural variant9161R → W Found in a renal cell carcinoma sample; somatic mutation. Ref.3
VAR_064748
Natural variant10731V → A. Ref.1
Corresponds to variant rs6795970 [ dbSNP | Ensembl ].
VAR_020606
Natural variant10921L → P.
Corresponds to variant rs12632942 [ dbSNP | Ensembl ].
VAR_020607
Natural variant17131M → V. Ref.1
Corresponds to variant rs6599241 [ dbSNP | Ensembl ].
VAR_020608

Sequences

Sequence LengthMass (Da)Tools
Q9Y5Y9 [UniParc].

Last modified September 2, 2008. Version 2.
Checksum: 4A4A2C5E135B6685

FASTA1,956220,626
        10         20         30         40         50         60 
MEFPIGSLET NNFRRFTPES LVEIEKQIAA KQGTKKAREK HREQKDQEEK PRPQLDLKAC 

        70         80         90        100        110        120 
NQLPKFYGEL PAELIGEPLE DLDPFYSTHR TFMVLNKGRT ISRFSATRAL WLFSPFNLIR 

       130        140        150        160        170        180 
RTAIKVSVHS WFSLFITVTI LVNCVCMTRT DLPEKIEYVF TVIYTFEALI KILARGFCLN 

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

       250        260        270        280        290        300 
HSVKKLADVT ILTIFCLSVF ALVGLQLFKG NLKNKCVKND MAVNETTNYS SHRKPDIYIN 

       310        320        330        340        350        360 
KRGTSDPLLC GNGSDSGHCP DGYICLKTSD NPDFNYTSFD SFAWAFLSLF RLMTQDSWER 

       370        380        390        400        410        420 
LYQQTLRTSG KIYMIFFVLV IFLGSFYLVN LILAVVTMAY EEQNQATTDE IEAKEKKFQE 

       430        440        450        460        470        480 
ALEMLRKEQE VLAALGIDTT SLHSHNGSPL TSKNASERRH RIKPRVSEGS TEDNKSPRSD 

       490        500        510        520        530        540 
PYNQRRMSFL GLASGKRRAS HGSVFHFRSP GRDISLPEGV TDDGVFPGDH ESHRGSLLLG 

       550        560        570        580        590        600 
GGAGQQGPLP RSPLPQPSNP DSRHGEDEHQ PPPTSELAPG AVDVSAFDAG QKKTFLSAEY 

       610        620        630        640        650        660 
LDEPFRAQRA MSVVSIITSV LEELEESEQK CPPCLTSLSQ KYLIWDCCPM WVKLKTILFG 

       670        680        690        700        710        720 
LVTDPFAELT ITLCIVVNTI FMAMEHHGMS PTFEAMLQIG NIVFTIFFTA EMVFKIIAFD 

       730        740        750        760        770        780 
PYYYFQKKWN IFDCIIVTVS LLELGVAKKG SLSVLRSFRL LRVFKLAKSW PTLNTLIKII 

       790        800        810        820        830        840 
GNSVGALGNL TIILAIIVFV FALVGKQLLG ENYRNNRKNI SAPHEDWPRW HMHDFFHSFL 

       850        860        870        880        890        900 
IVFRILCGEW IENMWACMEV GQKSICLILF LTVMVLGNLV VLNLFIALLL NSFSADNLTA 

       910        920        930        940        950        960 
PEDDGEVNNL QVALARIQVF GHRTKQALCS FFSRSCPFPQ PKAEPELVVK LPLSSSKAEN 

       970        980        990       1000       1010       1020 
HIAANTARGS SGGLQAPRGP RDEHSDFIAN PTVWVSVPIA EGESDLDDLE DDGGEDAQSF 

      1030       1040       1050       1060       1070       1080 
QQEVIPKGQQ EQLQQVERCG DHLTPRSPGT GTSSEDLAPS LGETWKDESV PQVPAEGVDD 

      1090       1100       1110       1120       1130       1140 
TSSSEGSTVD CLDPEEILRK IPELADDLEE PDDCFTEGCI RHCPCCKLDT TKSPWDVGWQ 

      1150       1160       1170       1180       1190       1200 
VRKTCYRIVE HSWFESFIIF MILLSSGSLA FEDYYLDQKP TVKALLEYTD RVFTFIFVFE 

      1210       1220       1230       1240       1250       1260 
MLLKWVAYGF KKYFTNAWCW LDFLIVNISL ISLTAKILEY SEVAPIKALR TLRALRPLRA 

      1270       1280       1290       1300       1310       1320 
LSRFEGMRVV VDALVGAIPS IMNVLLVCLI FWLIFSIMGV NLFAGKFWRC INYTDGEFSL 

      1330       1340       1350       1360       1370       1380 
VPLSIVNNKS DCKIQNSTGS FFWVNVKVNF DNVAMGYLAL LQVATFKGWM DIMYAAVDSR 

      1390       1400       1410       1420       1430       1440 
EVNMQPKWED NVYMYLYFVI FIIFGGFFTL NLFVGVIIDN FNQQKKKLGG QDIFMTEEQK 

      1450       1460       1470       1480       1490       1500 
KYYNAMKKLG SKKPQKPIPR PLNKFQGFVF DIVTRQAFDI TIMVLICLNM ITMMVETDDQ 

      1510       1520       1530       1540       1550       1560 
SEEKTKILGK INQFFVAVFT GECVMKMFAL RQYYFTNGWN VFDFIVVVLS IASLIFSAIL 

      1570       1580       1590       1600       1610       1620 
KSLQSYFSPT LFRVIRLARI GRILRLIRAA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI 

      1630       1640       1650       1660       1670       1680 
YSIFGMSSFP HVRWEAGIDD MFNFQTFANS MLCLFQITTS AGWDGLLSPI LNTGPPYCDP 

      1690       1700       1710       1720       1730       1740 
NLPNSNGTRG DCGSPAVGII FFTTYIIISF LIMVNMYIAV ILENFNVATE ESTEPLSEDD 

      1750       1760       1770       1780       1790       1800 
FDMFYETWEK FDPEATQFIT FSALSDFADT LSGPLRIPKP NRNILIQMDL PLVPGDKIHC 

      1810       1820       1830       1840       1850       1860 
LDILFAFTKN VLGESGELDS LKANMEEKFM ATNLSKSSYE PIATTLRWKQ EDISATVIQK 

      1870       1880       1890       1900       1910       1920 
AYRSYVLHRS MALSNTPCVP RAEEEAASLP DEGFVAFTAN ENCVLPDKSE TASATSFPPS 

      1930       1940       1950 
YESVTRGLSD RVNMRTSSSI QNEDEATSME LIAPGP 

« Hide

References

« Hide 'large scale' references
[1]"A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A."
Rabert D.K., Koch B.D., Ilnicka M., Obernolte R.A., Naylor S.L., Herman R.C., Eglen R.M., Hunter J.C., Sangameswaran L.
Pain 78:107-114(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION, TISSUE SPECIFICITY, VARIANTS ALA-1073 AND VAL-1713.
Tissue: Spinal ganglion.
[2]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-916.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF117907 mRNA. Translation: AAD30863.1.
AC116038 Genomic DNA. No translation available.
AC137625 Genomic DNA. No translation available.
RefSeqNP_006505.2. NM_006514.2.
UniGeneHs.250443.

3D structure databases

ProteinModelPortalQ9Y5Y9.
SMRQ9Y5Y9. Positions 120-407, 668-891, 1148-1425, 1478-1871.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000390600.

Chemistry

BindingDBQ9Y5Y9.
ChEMBLCHEMBL2331043.
DrugBankDB01086. Benzocaine.
DB00297. Bupivacaine.
DB01161. Chloroprocaine.
DB00907. Cocaine.
DB00527. Dibucaine.
DB00645. Dyclonine.
DB00473. Hexylcaine.
DB01002. Levobupivacaine.
DB00281. Lidocaine.
DB00961. Mepivacaine.
DB00892. Oxybuprocaine.
DB00721. Procaine.
DB00807. Proparacaine.
DB00296. Ropivacaine.
GuidetoPHARMACOLOGY585.

PTM databases

PhosphoSiteQ9Y5Y9.

Polymorphism databases

DMDM205371821.

Proteomic databases

PaxDbQ9Y5Y9.
PRIDEQ9Y5Y9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000449082; ENSP00000390600; ENSG00000185313.
GeneID6336.
KEGGhsa:6336.
UCSCuc003ciq.3. human.

Organism-specific databases

CTD6336.
GeneCardsGC03M038713.
H-InvDBHIX0030722.
HGNCHGNC:10582. SCN10A.
HPACAB022171.
MIM604427. gene.
neXtProtNX_Q9Y5Y9.
Orphanet88642. Channelopathy-associated congenital insensitivity to pain.
46348. Paroxysmal extreme pain disorder.
90026. Primary erythermalgia.
306577. Sodium channelopathy-related small fiber neuropathy.
PharmGKBPA35000.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231755.
HOVERGENHBG053100.
InParanoidQ9Y5Y9.
KOK04842.
OMANIVFTVF.
OrthoDBEOG7DJSK9.
PhylomeDBQ9Y5Y9.
TreeFamTF323985.

Gene expression databases

BgeeQ9Y5Y9.
CleanExHS_SCN10A.
GenevestigatorQ9Y5Y9.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
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.
ProtoNetSearch...

Other

GeneWikiSCN10A.
GenomeRNAi6336.
NextBio24604.
PROQ9Y5Y9.
SOURCESearch...

Entry information

Entry nameSCNAA_HUMAN
AccessionPrimary (citable) accession number: Q9Y5Y9
Secondary accession number(s): A6NDQ1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: September 2, 2008
Last modified: April 16, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM