Q9Y5Y9 (SCNAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1956 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This protein 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. It is a tetrodotoxin-resistant sodium channel isoform. Its electrophysiological properties vary depending on the type of the associated beta subunits (in vitro). Plays a role in neuropathic pain mechanisms By similarity. Ref.1
Subunit structure	The voltage-resistant sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more associated auxiliary subunits SCN1B, SCN2B and SCN3B. 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.
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 process	Ion transport Sodium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ion channel Sodium channel Voltage-gated channel
PTM	Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	AV 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 odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara 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 sensory perception Traceable author statement Ref.1. Source: ProtInc sensory perception of pain Inferred from electronic annotation. Source: Compara
Cellular_component	clathrin complex Inferred from electronic annotation. Source: Compara voltage-gated sodium channel complex Inferred from direct assay Ref.1. Source: BHF-UCL
Molecular_function	voltage-gated sodium channel activity Inferred from direct assay Ref.1. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1956	1956	Sodium channel protein type 10 subunit alpha		PRO_0000048507
Regions
	Transmembrane	126 – 149	24	Helical; Name=S1 of repeat I; Potential
	Transmembrane	155 – 174	20	Helical; Name=S2 of repeat I; Potential
	Transmembrane	188 – 206	19	Helical; Name=S3 of repeat I; Potential
	Transmembrane	213 – 232	20	Helical; Voltage-sensor; Name=S4 of repeat I; Potential
	Transmembrane	249 – 272	24	Helical; Name=S5 of repeat I; Potential
	Transmembrane	374 – 399	26	Helical; Name=S6 of repeat I; Potential
	Transmembrane	660 – 684	25	Helical; Name=S1 of repeat II; Potential
	Transmembrane	696 – 719	24	Helical; Name=S2 of repeat II; Potential
	Transmembrane	728 – 747	20	Helical; Name=S3 of repeat II; Potential
	Transmembrane	754 – 773	20	Helical; Voltage-sensor; Name=S4 of repeat II; Potential
	Transmembrane	790 – 810	21	Helical; Name=S5 of repeat II; Potential
	Transmembrane	865 – 890	26	Helical; Name=S6 of repeat II; Potential
	Transmembrane	1148 – 1171	24	Helical; Name=S1 of repeat III; Potential
	Transmembrane	1185 – 1210	26	Helical; Name=S2 of repeat III; Potential
	Transmembrane	1217 – 1238	22	Helical; Name=S3 of repeat III; Potential
	Transmembrane	1243 – 1264	22	Helical; Voltage-sensor; Name=S4 of repeat III; Potential
	Transmembrane	1284 – 1311	28	Helical; Name=S5 of repeat III; Potential
	Transmembrane	1392 – 1418	27	Helical; Name=S6 of repeat III; Potential
	Transmembrane	1472 – 1495	24	Helical; Name=S1 of repeat IV; Potential
	Transmembrane	1507 – 1530	24	Helical; Name=S2 of repeat IV; Potential
	Transmembrane	1537 – 1560	24	Helical; Name=S3 of repeat IV; Potential
	Transmembrane	1573 – 1594	22	Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
	Transmembrane	1610 – 1632	23	Helical; Name=S5 of repeat IV; Potential
	Transmembrane	1698 – 1722	25	Helical; Name=S6 of repeat IV; Potential
	Repeat	125 – 400	276	I
	Repeat	659 – 891	233	II
	Repeat	1147 – 1419	273	III
	Repeat	1471 – 1723	253	IV
	Domain	1851 – 1880	30	IQ
Amino acid modifications
	Glycosylation	284	1	N-linked (GlcNAc...) Potential
	Glycosylation	288	1	N-linked (GlcNAc...) Potential
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	335	1	N-linked (GlcNAc...) Potential
	Glycosylation	819	1	N-linked (GlcNAc...) Potential
	Glycosylation	1312	1	N-linked (GlcNAc...) Potential
	Glycosylation	1328	1	N-linked (GlcNAc...) Potential
	Glycosylation	1336	1	N-linked (GlcNAc...) Potential
	Glycosylation	1686	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	509	1	S → P. Corresponds to variant rs7630989 [ dbSNP | Ensembl ].		VAR_020605
	Natural variant	590	1	G → R. Corresponds to variant rs35332705 [ dbSNP | Ensembl ].		VAR_048696
	Natural variant	916	1	R → W Found in a renal cell carcinoma sample; somatic mutation. Ref.3		VAR_064748
	Natural variant	1073	1	V → A. Ref.1 Corresponds to variant rs6795970 [ dbSNP | Ensembl ].		VAR_020606
	Natural variant	1092	1	L → P. Corresponds to variant rs12632942 [ dbSNP | Ensembl ].		VAR_020607
	Natural variant	1713	1	M → V. Ref.1 Corresponds to variant rs6599241 [ dbSNP | Ensembl ].		VAR_020608

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5Y9 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 4A4A2C5E135B6685	FASTA	1,956	220,626
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00872541.
RefSeq	NP_006505.2. NM_006514.2.
UniGene	Hs.250443.
3D structure databases
ProteinModelPortal	Q9Y5Y9.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000390600.
PTM databases
PhosphoSite	Q9Y5Y9.
Polymorphism databases
DMDM	205371821.
Proteomic databases
PaxDb	Q9Y5Y9.
PRIDE	Q9Y5Y9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000449082; ENSP00000390600; ENSG00000185313.
GeneID	6336.
KEGG	hsa:6336.
UCSC	uc003ciq.3. human.
Organism-specific databases
CTD	6336.
GeneCards	GC03M038713.
H-InvDB	HIX0030722.
HGNC	HGNC:10582. SCN10A.
HPA	CAB022171.
MIM	604427. gene.
neXtProt	NX_Q9Y5Y9.
PharmGKB	PA35000.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1226.
HOGENOM	HOG000231755.
HOVERGEN	HBG053100.
InParanoid	Q9Y5Y9.
KO	K04842.
OMA	CCPTWVK.
OrthoDB	EOG4229HT.
Gene expression databases
Bgee	Q9Y5Y9.
CleanEx	HS_SCN10A.
Genevestigator	Q9Y5Y9.
GermOnline	ENSG00000185313. Homo sapiens.
Family and domain databases
InterPro	IPR005821. Ion_trans_dom. IPR001696. Na_channel_asu. IPR010526. Na_trans_assoc. [Graphical view]
Pfam	PF00520. Ion_trans. 4 hits. PF06512. Na_trans_assoc. 1 hit. [Graphical view]
PRINTS	PR00170. NACHANNEL.
PROSITE	PS50096. IQ. False negative. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9Y5Y9.
ChEMBL	CHEMBL5451.
DrugBank	DB01086. 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.
GenomeRNAi	6336.
NextBio	24604.
SOURCE	Search...

Entry information

Entry name

SCNAA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.