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Q15858 (SCN9A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium channel protein type 9 subunit alpha
Alternative name(s):
Neuroendocrine sodium channel
Short name=hNE-Na
Peripheral sodium channel 1
Short name=PN1
Sodium channel protein type IX subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.7
Gene names
Name:SCN9A
Synonyms:NENA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1988 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 Na+ ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na+ channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain By similarity. Ref.1 Ref.8

Subunit structure

The sodium channel consists of a large polypeptide and 2-3 smaller ones. This sequence represents a large polypeptide. Interacts with NEDD4 and NEDD4L By similarity.

Subcellular location

Membrane; Multi-pass membrane protein. Note: In neurite terminals By similarity.

Tissue specificity

Expressed strongly in dorsal root ganglion, with only minor levels elsewhere in the body, smooth muscle cells, MTC cell line and C-cell carcinoma. Isoform 1 is expressed preferentially in the central and peripheral nervous system. Isoform 2 is expressed preferentially in the dorsal root ganglion. Ref.1 Ref.4 Ref.7 Ref.8

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 may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4 By similarity.

Phosphorylation at Ser-1490 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents By similarity.

Involvement in disease

Primary erythermalgia (PERYTHM) [MIM:133020]: Autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17

Congenital indifference to pain autosomal recessive (CIPAR) [MIM:243000]: A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Paroxysmal extreme pain disorder (PEPD) [MIM:167400]: Autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15

Generalized epilepsy with febrile seizures plus 7 (GEFS+7) [MIM:613863]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18

Febrile seizures, familial, 3B (FEB3B) [MIM:613863]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.7/SCN9A subfamily. [View classification]

Contains 1 IQ domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15858-1)

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: Q15858-2)

The sequence of this isoform differs from the canonical sequence as follows:
     200-229: YLTEFVNLGNVSALRTFRVLRALKTISVIP → YVTEFVDLGNVSALRTFRVLRALKTISVIP
Isoform 3 (identifier: Q15858-3)

The sequence of this isoform differs from the canonical sequence as follows:
     648-658: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19881988Sodium channel protein type 9 subunit alpha
PRO_0000048502

Regions

Transmembrane122 – 14524Helical; Name=S1 of repeat I; Potential
Transmembrane154 – 17320Helical; Name=S2 of repeat I; Potential
Transmembrane187 – 20519Helical; Name=S3 of repeat I; Potential
Transmembrane212 – 23120Helical; Voltage-sensor; Name=S4 of repeat I; Potential
Transmembrane248 – 27124Helical; Name=S5 of repeat I; Potential
Transmembrane379 – 40426Helical; Name=S6 of repeat I; Potential
Transmembrane739 – 76325Helical; Name=S1 of repeat II; Potential
Transmembrane775 – 79824Helical; Name=S2 of repeat II; Potential
Transmembrane807 – 82620Helical; Name=S3 of repeat II; Potential
Transmembrane833 – 85220Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Transmembrane869 – 88921Helical; Name=S5 of repeat II; Potential
Transmembrane943 – 96826Helical; Name=S6 of repeat II; Potential
Transmembrane1188 – 121124Helical; Name=S1 of repeat III; Potential
Transmembrane1225 – 125026Helical; Name=S2 of repeat III; Potential
Transmembrane1257 – 127822Helical; Name=S3 of repeat III; Potential
Transmembrane1283 – 130422Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Transmembrane1324 – 135128Helical; Name=S5 of repeat III; Potential
Transmembrane1431 – 145727Helical; Name=S6 of repeat III; Potential
Transmembrane1511 – 153424Helical; Name=S1 of repeat IV; Potential
Transmembrane1546 – 156924Helical; Name=S2 of repeat IV; Potential
Transmembrane1576 – 159924Helical; Name=S3 of repeat IV; Potential
Transmembrane1610 – 163122Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Transmembrane1647 – 166923Helical; Name=S5 of repeat IV; Potential
Transmembrane1736 – 176025Helical; Name=S6 of repeat IV; Potential
Repeat121 – 405285I
Repeat738 – 969232II
Repeat1187 – 1458272III
Repeat1510 – 1761252IV
Domain1889 – 191830IQ

Amino acid modifications

Modified residue14901Phosphoserine; by PKC By similarity
Glycosylation2091N-linked (GlcNAc...) Potential
Glycosylation2831N-linked (GlcNAc...) Potential
Glycosylation13521N-linked (GlcNAc...) Potential
Glycosylation13661N-linked (GlcNAc...) Potential
Glycosylation13751N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence200 – 22930YLTEF…ISVIP → YVTEFVDLGNVSALRTFRVL RALKTISVIP in isoform 2.
VSP_012028
Alternative sequence648 – 65811Missing in isoform 3.
VSP_012029
Natural variant101Q → R in PERYTHM; causes a hyperpolarizing shift of -5.3 mV for the midpoint of activation which is smaller than that seen in other mutations causing early-onset erythromelalgia mutations; also causes a faster rate of activation and slower deactivation compared to wild-type; expression of the mutant protein induced hyperexcitability in dorsal root ganglion neurons but the increase is smaller than that produced by Thr-859. Ref.17
VAR_064595
Natural variant621I → V in FEB3B. Ref.18
VAR_064596
Natural variant1491P → Q in FEB3B. Ref.18
VAR_064597
Natural variant2161F → S in PERYTHM; hyperpolarizes the voltage dependence of activation by 11 mV, accelerates activation, slows deactivation and enhances the response to slow, small depolarizations. Ref.12 Ref.14
VAR_064598
Natural variant2281I → M. Ref.18
Corresponds to variant rs71428908 [ dbSNP | Ensembl ].
VAR_064599
Natural variant2411S → T in PERYTHM. Ref.10
VAR_032014
Natural variant3951N → K in PERYTHM. Ref.12
VAR_064600
Natural variant4061E → K in PERYTHM.
VAR_064601
Natural variant4901S → N. Ref.18
Corresponds to variant rs58022607 [ dbSNP | Ensembl ].
VAR_064602
Natural variant5191E → K. Ref.18
Corresponds to variant rs187453572 [ dbSNP | Ensembl ].
VAR_064603
Natural variant6411N → Y in GEFS+7. Ref.18
VAR_064604
Natural variant6661K → R in GEFS+7; also found in a patient with severe myoclonic epilepsy in infancy. Ref.18
Corresponds to variant rs121908919 [ dbSNP | Ensembl ].
VAR_064605
Natural variant6951I → M. Ref.18
VAR_064606
Natural variant7101C → Y Found in a patient with severe myoclonic epilepsy in infancy. Ref.18
VAR_064607
Natural variant7501I → V. Ref.18
Corresponds to variant rs182650126 [ dbSNP | Ensembl ].
VAR_064608
Natural variant8591I → T in PERYTHM; sporadic; activated at more negative potentials; slower inactivation kinetics than wild-type channels. Ref.6 Ref.9 Ref.12 Ref.17
VAR_019947
Natural variant8691L → F in PERYTHM; causes a hyperpolarizing shift in channel activation, a depolarizing shift of inactivation and an 18-fold increase in deactivation time compared to wild-type; the mean ramp current amplitude in response to slow depolarization is higher in the mutant channels. Ref.12 Ref.13
VAR_064609
Natural variant8691L → H in PERYTHM; activated at more negative potentials; slower inactivation kinetics than wild-type channels. Ref.6 Ref.9 Ref.16
VAR_019948
Natural variant9071R → Q in CIPAR; significant reduction in membrane localization of the mutant protein compared to the wild-type; complete loss of function of the sodium channel. Ref.19
VAR_064610
Natural variant9321M → L.
Corresponds to variant rs12478318 [ dbSNP | Ensembl ].
VAR_030444
Natural variant9431M → L.
Corresponds to variant rs12478318 [ dbSNP | Ensembl ].
VAR_055646
Natural variant10071R → C in PEPD. Ref.15
Corresponds to variant rs121908910 [ dbSNP | Ensembl ].
VAR_032015
Natural variant11341L → F. Ref.18
Corresponds to variant rs200160858 [ dbSNP | Ensembl ].
VAR_064611
Natural variant11611W → R. Ref.1 Ref.2 Ref.12
Corresponds to variant rs6746030 [ dbSNP | Ensembl ].
VAR_019949
Natural variant11711E → Q Found in a patient with severe myoclonic epilepsy in infancy. Ref.18
VAR_064612
Natural variant12781L → V. Ref.18
Corresponds to variant rs180922748 [ dbSNP | Ensembl ].
VAR_064613
Natural variant13091V → D in PEPD. Ref.15
VAR_032016
Natural variant13091V → F in PEPD. Ref.15
VAR_032017
Natural variant13101V → F in PEPD. Ref.15
VAR_032018
Natural variant1381 – 13855Missing in CIPAR; significant reduction in membrane localization of the mutant protein compared to the wild-type; complete loss of function of the sodium channel.
VAR_064614
Natural variant14601F → V in PERYTHM; produces a hyperpolarizing shift in channel activation and a depolarizing shift in steady-state activation. Ref.11
VAR_032019
Natural variant14721I → T in PEPD; reduction in fast inactivation leading to persistent sodium current. Ref.15
VAR_032020
Natural variant14731F → V in PEPD. Ref.15
VAR_032021
Natural variant14751T → I in PEPD; reduction in fast inactivation leading to persistent sodium current. Ref.15
VAR_032022
Natural variant16381M → K in PEPD; reduction in fast inactivation leading to persistent sodium current. Ref.15
VAR_032023
Natural variant19191D → G.
Corresponds to variant rs3750904 [ dbSNP | Ensembl ].
VAR_019950

Experimental info

Sequence conflict2011L → V in AAT85835. Ref.4
Sequence conflict2011L → V in AAT85833. Ref.4
Sequence conflict2061N → D in AAT85835. Ref.4
Sequence conflict2061N → D in AAT85833. Ref.4
Sequence conflict2671F → S in AAT85834. Ref.4
Sequence conflict3011K → R in AAT85835. Ref.4
Sequence conflict3091S → P in AAT85834. Ref.4
Sequence conflict4201E → G in AAT85834. Ref.4
Sequence conflict4301L → P in AAT85834. Ref.4
Sequence conflict5011S → P in AAT85835. Ref.4
Sequence conflict6101P → T in AAT85835. Ref.4
Sequence conflict6421G → R in AAT85835. Ref.4

Sequences

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

Last modified April 5, 2011. Version 3.
Checksum: 1BAEB8F32EBF5438

FASTA1,988226,372
        10         20         30         40         50         60 
MAMLPPPGPQ SFVHFTKQSL ALIEQRIAER KSKEPKEEKK DDDEEAPKPS SDLEAGKQLP 

        70         80         90        100        110        120 
FIYGDIPPGM VSEPLEDLDP YYADKKTFIV LNKGKTIFRF NATPALYMLS PFSPLRRISI 

       130        140        150        160        170        180 
KILVHSLFSM LIMCTILTNC IFMTMNNPPD WTKNVEYTFT GIYTFESLVK ILARGFCVGE 

       190        200        210        220        230        240 
FTFLRDPWNW LDFVVIVFAY LTEFVNLGNV SALRTFRVLR ALKTISVIPG LKTIVGALIQ 

       250        260        270        280        290        300 
SVKKLSDVMI LTVFCLSVFA LIGLQLFMGN LKHKCFRNSL ENNETLESIM NTLESEEDFR 

       310        320        330        340        350        360 
KYFYYLEGSK DALLCGFSTD SGQCPEGYTC VKIGRNPDYG YTSFDTFSWA FLALFRLMTQ 

       370        380        390        400        410        420 
DYWENLYQQT LRAAGKTYMI FFVVVIFLGS FYLINLILAV VAMAYEEQNQ ANIEEAKQKE 

       430        440        450        460        470        480 
LEFQQMLDRL KKEQEEAEAI AAAAAEYTSI RRSRIMGLSE SSSETSKLSS KSAKERRNRR 

       490        500        510        520        530        540 
KKKNQKKLSS GEEKGDAEKL SKSESEDSIR RKSFHLGVEG HRRAHEKRLS TPNQSPLSIR 

       550        560        570        580        590        600 
GSLFSARRSS RTSLFSFKGR GRDIGSETEF ADDEHSIFGD NESRRGSLFV PHRPQERRSS 

       610        620        630        640        650        660 
NISQASRSPP MLPVNGKMHS AVDCNGVVSL VDGRSALMLP NGQLLPEVII DKATSDDSGT 

       670        680        690        700        710        720 
TNQIHKKRRC SSYLLSEDML NDPNLRQRAM SRASILTNTV EELEESRQKC PPWWYRFAHK 

       730        740        750        760        770        780 
FLIWNCSPYW IKFKKCIYFI VMDPFVDLAI TICIVLNTLF MAMEHHPMTE EFKNVLAIGN 

       790        800        810        820        830        840 
LVFTGIFAAE MVLKLIAMDP YEYFQVGWNI FDSLIVTLSL VELFLADVEG LSVLRSFRLL 

       850        860        870        880        890        900 
RVFKLAKSWP TLNMLIKIIG NSVGALGNLT LVLAIIVFIF AVVGMQLFGK SYKECVCKIN 

       910        920        930        940        950        960 
DDCTLPRWHM NDFFHSFLIV FRVLCGEWIE TMWDCMEVAG QAMCLIVYMM VMVIGNLVVL 

       970        980        990       1000       1010       1020 
NLFLALLLSS FSSDNLTAIE EDPDANNLQI AVTRIKKGIN YVKQTLREFI LKAFSKKPKI 

      1030       1040       1050       1060       1070       1080 
SREIRQAEDL NTKKENYISN HTLAEMSKGH NFLKEKDKIS GFGSSVDKHL MEDSDGQSFI 

      1090       1100       1110       1120       1130       1140 
HNPSLTVTVP IAPGESDLEN MNAEELSSDS DSEYSKVRLN RSSSSECSTV DNPLPGEGEE 

      1150       1160       1170       1180       1190       1200 
AEAEPMNSDE PEACFTDGCV WRFSCCQVNI ESGKGKIWWN IRKTCYKIVE HSWFESFIVL 

      1210       1220       1230       1240       1250       1260 
MILLSSGALA FEDIYIERKK TIKIILEYAD KIFTYIFILE MLLKWIAYGY KTYFTNAWCW 

      1270       1280       1290       1300       1310       1320 
LDFLIVDVSL VTLVANTLGY SDLGPIKSLR TLRALRPLRA LSRFEGMRVV VNALIGAIPS 

      1330       1340       1350       1360       1370       1380 
IMNVLLVCLI FWLIFSIMGV NLFAGKFYEC INTTDGSRFP ASQVPNRSEC FALMNVSQNV 

      1390       1400       1410       1420       1430       1440 
RWKNLKVNFD NVGLGYLSLL QVATFKGWTI IMYAAVDSVN VDKQPKYEYS LYMYIYFVVF 

      1450       1460       1470       1480       1490       1500 
IIFGSFFTLN LFIGVIIDNF NQQKKKLGGQ DIFMTEEQKK YYNAMKKLGS KKPQKPIPRP 

      1510       1520       1530       1540       1550       1560 
GNKIQGCIFD LVTNQAFDIS IMVLICLNMV TMMVEKEGQS QHMTEVLYWI NVVFIILFTG 

      1570       1580       1590       1600       1610       1620 
ECVLKLISLR HYYFTVGWNI FDFVVVIISI VGMFLADLIE TYFVSPTLFR VIRLARIGRI 

      1630       1640       1650       1660       1670       1680 
LRLVKGAKGI RTLLFALMMS LPALFNIGLL LFLVMFIYAI FGMSNFAYVK KEDGINDMFN 

      1690       1700       1710       1720       1730       1740 
FETFGNSMIC LFQITTSAGW DGLLAPILNS KPPDCDPKKV HPGSSVEGDC GNPSVGIFYF 

      1750       1760       1770       1780       1790       1800 
VSYIIISFLV VVNMYIAVIL ENFSVATEES TEPLSEDDFE MFYEVWEKFD PDATQFIEFS 

      1810       1820       1830       1840       1850       1860 
KLSDFAAALD PPLLIAKPNK VQLIAMDLPM VSGDRIHCLD ILFAFTKRVL GESGEMDSLR 

      1870       1880       1890       1900       1910       1920 
SQMEERFMSA NPSKVSYEPI TTTLKRKQED VSATVIQRAY RRYRLRQNVK NISSIYIKDG 

      1930       1940       1950       1960       1970       1980 
DRDDDLLNKK DMAFDNVNEN SSPEKTDATS STTSPPSYDS VTKPDKEKYE QDRTEKEDKG 


KDSKESKK 

« Hide

Isoform 2 [UniParc].

Checksum: 8C9066AD56148C02
Show »

FASTA1,988226,359
Isoform 3 [UniParc].

Checksum: 8B2BD5CF665F11A8
Show »

FASTA1,977225,227

References

« Hide 'large scale' references
[1]"Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells."
Klugbauer N., Lacinova L., Flockerzi V., Hofmann F.
EMBO J. 14:1084-1090(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION, TISSUE SPECIFICITY, VARIANT ARG-1161.
Tissue: Thyroid.
[2]"An SCN9A channelopathy causes congenital inability to experience pain."
Cox J.J., Reimann F., Nicholas A.K., Thornton G., Roberts E., Springell K., Karbani G., Jafri H., Mannan J., Raashid Y., Al-Gazali L., Hamamy H., Valente E.M., Gorman S., Williams R., McHale D.P., Wood J.N., Gribble F.M., Woods C.G.
Nature 444:894-898(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INVOLVEMENT IN CONGENITAL INSENSITIVITY TO PAIN, CHARACTERIZATION, VARIANT ARG-1161.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Expression of alternatively spliced sodium channel alpha-subunit genes: unique splicing patterns are observed in dorsal root ganglia."
Raymond C.K., Castle J.C., Garrett-Engele P.W., Armour C.D., Kan Z.G., Tsinoremas N.T., Johnson J.M.
J. Biol. Chem. 279:46234-46241(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 136-674 (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
Tissue: Spinal ganglion.
[5]"Upregulation of voltage-gated Na+ channel expression and metastatic potential in human breast cancer: correlative studies on cell lines and biopsy tissues."
Diss J.K.J., Fraser S.P., Coombes R.C., Djamgoz M.B.A.
Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-264 AND 1340-1400.
[6]"Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia."
Yang Y., Wang Y., Li S., Xu Z., Li H., Ma L., Fan J., Bu D., Liu B., Fan Z., Wu G., Jin J., Ding B., Zhu X., Shen Y.
J. Med. Genet. 41:171-174(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 840-958, VARIANTS PERYTHM THR-859 AND HIS-869.
[7]"A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia."
Sangameswaran L., Fish L.M., Koch B.D., Rabert D.K., Delgado S.G., Ilnicka M., Jakeman L.B., Novakovic S., Wong K., Sze P., Tzoumaka E., Stewart G.R., Herman R.C., Chan H., Eglen R.M., Hunter J.C.
J. Biol. Chem. 272:14805-14809(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Voltage-gated sodium channel expressed in cultured human smooth muscle cells: involvement of SCN9A."
Jo T., Nagata T., Iida H., Imuta H., Iwasawa K., Ma J., Hara K., Omata M., Nagai R., Takizawa H., Nagase T., Nakajima T.
FEBS Lett. 567:339-343(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION, TISSUE SPECIFICITY.
[9]"Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy."
Cummins T.R., Dib-Hajj S.D., Waxman S.G.
J. Neurosci. 24:8232-8236(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PERYTHM THR-859 AND HIS-869.
[10]"Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha subunit Nav1.7."
Michiels J.J., te Morsche R.H.M., Jansen J.B.M.J., Drenth J.P.H.
Arch. Neurol. 62:1587-1590(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PERYTHM THR-241.
[11]"Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons."
Dib-Hajj S.D., Rush A.M., Cummins T.R., Hisama F.M., Novella S., Tyrrell L., Marshall L., Waxman S.G.
Brain 128:1847-1854(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PERYTHM VAL-1460, CHARACTERIZATION OF VARIANT PERYTHM VAL-1460.
[12]"SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels."
Drenth J.P., te Morsche R.H., Guillet G., Taieb A., Kirby R.L., Jansen J.B.
J. Invest. Dermatol. 124:1333-1338(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PERYTHM SER-216; LYS-395; THR-859 AND PHE-869, VARIANT ARG-1161.
[13]"Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7."
Han C., Rush A.M., Dib-Hajj S.D., Li S., Xu Z., Wang Y., Tyrrell L., Wang X., Yang Y., Waxman S.G.
Ann. Neurol. 59:553-558(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PERYTHM PHE-869, CHARACTERIZATION OF VARIANT PERYTHM PHE-869.
[14]"Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy."
Choi J.S., Dib-Hajj S.D., Waxman S.G.
Neurology 67:1563-1567(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PERYTHM SER-216.
[15]"SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes."
Fertleman C.R., Baker M.D., Parker K.A., Moffatt S., Elmslie F.V., Abrahamsen B., Ostman J., Klugbauer N., Wood J.N., Gardiner R.M., Rees M.
Neuron 52:767-774(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEPD CYS-1007; PHE-1309; ASP-1309; PHE-1310; THR-1472; VAL-1473; ILE-1475 AND LYS-1638, CHARACTERIZATION OF VARIANTS PEPD THR-1472; ILE-1475 AND LYS-1638.
[16]"A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons."
Rush A.M., Dib-Hajj S.D., Liu S., Cummins T.R., Black J.A., Waxman S.G.
Proc. Natl. Acad. Sci. U.S.A. 103:8245-8250(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PERYTHM HIS-869.
[17]"Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation."
Han C., Dib-Hajj S.D., Lin Z., Li Y., Eastman E.M., Tyrrell L., Cao X., Yang Y., Waxman S.G.
Brain 132:1711-1722(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PERYTHM ARG-10, CHARACTERIZATION OF VARIANTS PERYTHM ARG-10 AND THR-859.
[18]"A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome."
Singh N.A., Pappas C., Dahle E.J., Claes L.R., Pruess T.H., De Jonghe P., Thompson J., Dixon M., Gurnett C., Peiffer A., White H.S., Filloux F., Leppert M.F.
PLoS Genet. 5:E1000649-E1000649(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GEFS+7 TYR-641 AND ARG-666, VARIANTS FEB3B VAL-62 AND GLN-149, VARIANTS MET-228; ASN-490; LYS-519; MET-695; TYR-710; VAL-750; PHE-1134; GLN-1171 AND VAL-1278.
[19]"Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations."
Cox J.J., Sheynin J., Shorer Z., Reimann F., Nicholas A.K., Zubovic L., Baralle M., Wraige E., Manor E., Levy J., Woods C.G., Parvari R.
Hum. Mutat. 31:E1670-E1686(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CIPAR GLN-907 AND 1381-ARG--LEU-1385 DEL, CHARACTERIZATION OF VARIANTS CIPAR GLN-907 AND 1381-ARG--LEU-1385 DEL.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

SCN9A entry

Protein Spotlight

Silent pain - Issue 102 of February 2009

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X82835 mRNA. Translation: CAA58042.1.
DQ857292 mRNA. Translation: ABI51981.1.
AC074101 Genomic DNA. No translation available.
AC107082 Genomic DNA. No translation available.
AC108146 Genomic DNA. No translation available.
AY682084 mRNA. Translation: AAT85833.1.
AY682085 mRNA. Translation: AAT85834.1.
AY682086 mRNA. Translation: AAT85835.1.
AJ310882 mRNA. Translation: CAC84550.1.
AJ310883 mRNA. Translation: CAC84551.1.
AJ310897 mRNA. Translation: CAC84537.1.
AJ580918 Genomic DNA. Translation: CAE45644.1.
AJ580919 Genomic DNA. Translation: CAE45645.1.
PIRS54771.
RefSeqNP_002968.1. NM_002977.3.
XP_005246814.1. XM_005246757.1.
UniGeneHs.439145.

3D structure databases

ProteinModelPortalQ15858.
SMRQ15858. Positions 1761-1916.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ15858.
ChEMBLCHEMBL4296.
DrugBankDB00555. Lamotrigine.
DB00281. Lidocaine.
GuidetoPHARMACOLOGY584.

Protein family/group databases

TCDB1.A.1.10.5. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ15858.

Polymorphism databases

DMDM327478559.

Proteomic databases

PaxDbQ15858.
PRIDEQ15858.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000409435; ENSP00000386330; ENSG00000169432. [Q15858-1]
ENST00000409672; ENSP00000386306; ENSG00000169432. [Q15858-3]
ENST00000454569; ENSP00000413212; ENSG00000169432.
GeneID6335.
KEGGhsa:6335.
UCSCuc010fpl.3. human. [Q15858-3]

Organism-specific databases

CTD6335.
GeneCardsGC02M167051.
HGNCHGNC:10597. SCN9A.
HPACAB013679.
MIM133020. phenotype.
167400. phenotype.
243000. phenotype.
603415. gene.
613863. phenotype.
neXtProtNX_Q15858.
Orphanet88642. Channelopathy-associated congenital insensitivity to pain.
33069. Dravet syndrome.
1956. Erythromelalgia.
36387. Generalized epilepsy with febrile seizures-plus context.
970. Hereditary sensory and autonomic neuropathy type 2.
46348. Paroxysmal extreme pain disorder.
90026. Primary erythermalgia.
306577. Sodium channelopathy-related small fiber neuropathy.
PharmGKBPA35010.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOVERGENHBG053100.
KOK04841.
OrthoDBEOG7DJSK9.
PhylomeDBQ15858.
TreeFamTF323985.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ15858.
BgeeQ15858.
CleanExHS_SCN9A.
GenevestigatorQ15858.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
IPR028803. SCN9A.
[Graphical view]
PANTHERPTHR10037:SF28. PTHR10037:SF28. 1 hit.
PfamPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNav1.7.
GenomeRNAi6335.
NextBio24600.
PROQ15858.
SOURCESearch...

Entry information

Entry nameSCN9A_HUMAN
AccessionPrimary (citable) accession number: Q15858
Secondary accession number(s): A1BUH5 expand/collapse secondary AC list , Q6B4R9, Q6B4S0, Q6B4S1, Q70HX1, Q70HX2, Q8WTU1, Q8WWN4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: April 5, 2011
Last modified: April 16, 2014
This is version 130 of the entry and version 3 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

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

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 2

Human chromosome 2: entries, gene names and cross-references to MIM