Reviewed, UniProtKB/Swiss-Prot Q15858 (SCN9A_HUMAN)

Names and origin

Protein names

Recommended name:
    Sodium channel protein type 9 subunit alpha
Alternative name(s):
    Sodium channel protein type IX subunit alpha
    Voltage-gated sodium channel subunit alpha Nav1.7
    Neuroendocrine sodium channel
      Short name=hNE-Na
    Peripheral sodium channel 1

Gene names

Name:	SCN9A
Synonyms:	NENA, PN1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1988 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
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 while isoform 2 is expressed preferentially in the dorsal root ganglion. Ref.1 Ref.3 Ref.6 Ref.7
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.
Involvement in disease	Defects in SCN9A are the cause of primary erythermalgia [MIM:133020]. It is an autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. Ref.5 Ref.9 Ref.10 Ref.11 Ref.13 Defects in SCN9A are the cause of autosomal recessive congenital indifference to pain [MIM:243000]; also known as channelopathy-associated insensitivity to pain. Affected individuals have a 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. Defects in SCN9A are a cause of paroxysmal extreme pain disorder (PEPD) [MIM:167400]; previously known as familial rectal pain (FRP). PEPD is an 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. Ref.12
Sequence similarities	Belongs to the sodium channel family. Contains 1 IQ domain.

Ontologies

Keywords
Biological process	Ion transport Sodium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane
Ligand	Sodium
Molecular function	Ionic channel Sodium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	sodium ion transport Ref.1 Traceable author statement. Source: ProtInc
Cellular component	voltage-gated sodium channel complex Inferred from electronic annotation. Source: InterPro
Molecular function	sodium ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated sodium channel activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1988	1988	Sodium channel protein type 9 subunit alpha		PRO_0000048502
Regions
	Transmembrane	122 – 145	24	S1 of repeat I By similarity
	Transmembrane	154 – 173	20	S2 of repeat I By similarity
	Transmembrane	187 – 205	19	S3 of repeat I By similarity
	Transmembrane	212 – 231	20	S4 of repeat I By similarity
	Transmembrane	248 – 271	24	S5 of repeat I By similarity
	Transmembrane	379 – 404	26	S6 of repeat I By similarity
	Transmembrane	739 – 763	25	S1 of repeat II By similarity
	Transmembrane	775 – 798	24	S2 of repeat II By similarity
	Transmembrane	807 – 826	20	S3 of repeat II By similarity
	Transmembrane	833 – 852	20	S4 of repeat II By similarity
	Transmembrane	869 – 889	21	S5 of repeat II By similarity
	Transmembrane	943 – 968	26	S6 of repeat II By similarity
	Transmembrane	1188 – 1211	24	S1 of repeat III By similarity
	Transmembrane	1225 – 1250	26	S2 of repeat III By similarity
	Transmembrane	1257 – 1278	22	S3 of repeat III By similarity
	Transmembrane	1283 – 1304	22	S4 of repeat III By similarity
	Transmembrane	1324 – 1351	28	S5 of repeat III By similarity
	Transmembrane	1431 – 1457	27	S6 of repeat III By similarity
	Transmembrane	1511 – 1534	24	S1 of repeat IV By similarity
	Transmembrane	1546 – 1569	24	S2 of repeat IV By similarity
	Transmembrane	1576 – 1599	24	S3 of repeat IV By similarity
	Transmembrane	1610 – 1631	22	S4 of repeat IV By similarity
	Transmembrane	1647 – 1669	23	S5 of repeat IV By similarity
	Transmembrane	1736 – 1760	25	S6 of repeat IV By similarity
	Repeat	121 – 405	285	I
	Repeat	738 – 969	232	II
	Repeat	1187 – 1458	272	III
	Repeat	1510 – 1761	252	IV
	Domain	1889 – 1918	30	IQ
Amino acid modifications
	Modified residue	1413	1	Phosphotyrosine Ref.8
	Modified residue	1418	1	Phosphoserine Ref.8
	Glycosylation	209	1	N-linked (GlcNAc...) Potential
	Glycosylation	283	1	N-linked (GlcNAc...) Potential
	Glycosylation	1352	1	N-linked (GlcNAc...) Potential
	Glycosylation	1366	1	N-linked (GlcNAc...) Potential
	Glycosylation	1375	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	200 – 229	30	YLTEF…ISVIP → YVTEFVDLGNVSALRTFRVL RALKTISVIP in isoform 2.		VSP_012028
	Alternative sequence	648 – 658	11	Missing in isoform 3.		VSP_012029
	Natural variant	241	1	S → T in primary erythermalgia. Ref.10		VAR_032014
	Natural variant	859	1	I → T in primary erythermalgia; sporadic; activated at more negative potentials; slower inactivation kinetics than wild-type channels. Ref.5 Ref.9		VAR_019947
	Natural variant	869	1	L → H in primary erythermalgia; activated at more negative potentials; slower inactivation kinetics than wild-type channels. Ref.5 Ref.9 Ref.13		VAR_019948
	Natural variant	932	1	M → L: dbSNP rs12478318.		VAR_030444
	Natural variant	943	1	M → L: dbSNP rs12478318.		VAR_055646
	Natural variant	1007	1	R → C in PEPD. Ref.12		VAR_032015
	Natural variant	1161	1	R → W: dbSNP rs6746030.		VAR_019949
	Natural variant	1309	1	V → D in PEPD. Ref.12		VAR_032016
	Natural variant	1309	1	V → F in PEPD. Ref.12		VAR_032017
	Natural variant	1310	1	V → F in PEPD. Ref.12		VAR_032018
	Natural variant	1460	1	F → V in primary erythermalgia; produces a hyperpolarizing shift in channel activation and a depolarizing shift in steady-state activation. Ref.11		VAR_032019
	Natural variant	1472	1	I → T in PEPD; reduction in fast inactivation leading to persistent sodium current. Ref.12		VAR_032020
	Natural variant	1473	1	F → V in PEPD. Ref.12		VAR_032021
	Natural variant	1475	1	T → I in PEPD; reduction in fast inactivation leading to persistent sodium current. Ref.12		VAR_032022
	Natural variant	1638	1	M → K in PEPD; reduction in fast inactivation leading to persistent sodium current. Ref.12		VAR_032023
	Natural variant	1919	1	D → G: dbSNP rs3750904.		VAR_019950
Experimental info
	Sequence conflict	201	1	L → V in AAT85835. Ref.3
	Sequence conflict	201	1	L → V in AAT85833. Ref.3
	Sequence conflict	206	1	N → D in AAT85835. Ref.3
	Sequence conflict	206	1	N → D in AAT85833. Ref.3
	Sequence conflict	267	1	F → S in AAT85834. Ref.3
	Sequence conflict	301	1	K → R in AAT85835. Ref.3
	Sequence conflict	309	1	S → P in AAT85834. Ref.3
	Sequence conflict	420	1	E → G in AAT85834. Ref.3
	Sequence conflict	430	1	L → P in AAT85834. Ref.3
	Sequence conflict	501	1	S → P in AAT85835. Ref.3
	Sequence conflict	610	1	P → T in AAT85835. Ref.3
	Sequence conflict	642	1	G → R in AAT85835. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 23, 2004. Version 2. Checksum: 875311807A5C506B	FASTA	1,988	226,342
	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 RRFSCCQVNI 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
	Isoform 2. Checksum: 106DCFDE02F78851	FASTA	1,988	226,329
	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 VTEFVDLGNV 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 RRFSCCQVNI 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
	Isoform 3. Checksum: 17D67CBC32BC15FB	FASTA	1,977	225,197
	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 NGQLLPEGTT NQIHKKRRCS 670 680 690 700 710 720 SYLLSEDMLN DPNLRQRAMS RASILTNTVE ELEESRQKCP PWWYRFAHKF LIWNCSPYWI 730 740 750 760 770 780 KFKKCIYFIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTEE FKNVLAIGNL VFTGIFAAEM 790 800 810 820 830 840 VLKLIAMDPY EYFQVGWNIF DSLIVTLSLV ELFLADVEGL SVLRSFRLLR VFKLAKSWPT 850 860 870 880 890 900 LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS YKECVCKIND DCTLPRWHMN 910 920 930 940 950 960 DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVYMMV MVIGNLVVLN LFLALLLSSF 970 980 990 1000 1010 1020 SSDNLTAIEE DPDANNLQIA VTRIKKGINY VKQTLREFIL KAFSKKPKIS REIRQAEDLN 1030 1040 1050 1060 1070 1080 TKKENYISNH TLAEMSKGHN FLKEKDKISG FGSSVDKHLM EDSDGQSFIH NPSLTVTVPI 1090 1100 1110 1120 1130 1140 APGESDLENM NAEELSSDSD SEYSKVRLNR SSSSECSTVD NPLPGEGEEA EAEPMNSDEP 1150 1160 1170 1180 1190 1200 EACFTDGCVR RFSCCQVNIE SGKGKIWWNI RKTCYKIVEH SWFESFIVLM ILLSSGALAF 1210 1220 1230 1240 1250 1260 EDIYIERKKT IKIILEYADK IFTYIFILEM LLKWIAYGYK TYFTNAWCWL DFLIVDVSLV 1270 1280 1290 1300 1310 1320 TLVANTLGYS DLGPIKSLRT LRALRPLRAL SRFEGMRVVV NALIGAIPSI MNVLLVCLIF 1330 1340 1350 1360 1370 1380 WLIFSIMGVN LFAGKFYECI NTTDGSRFPA SQVPNRSECF ALMNVSQNVR WKNLKVNFDN 1390 1400 1410 1420 1430 1440 VGLGYLSLLQ VATFKGWTII MYAAVDSVNV DKQPKYEYSL YMYIYFVVFI IFGSFFTLNL 1450 1460 1470 1480 1490 1500 FIGVIIDNFN QQKKKLGGQD IFMTEEQKKY YNAMKKLGSK KPQKPIPRPG NKIQGCIFDL 1510 1520 1530 1540 1550 1560 VTNQAFDISI MVLICLNMVT MMVEKEGQSQ HMTEVLYWIN VVFIILFTGE CVLKLISLRH 1570 1580 1590 1600 1610 1620 YYFTVGWNIF DFVVVIISIV GMFLADLIET YFVSPTLFRV IRLARIGRIL RLVKGAKGIR 1630 1640 1650 1660 1670 1680 TLLFALMMSL PALFNIGLLL FLVMFIYAIF GMSNFAYVKK EDGINDMFNF ETFGNSMICL 1690 1700 1710 1720 1730 1740 FQITTSAGWD GLLAPILNSK PPDCDPKKVH PGSSVEGDCG NPSVGIFYFV SYIIISFLVV 1750 1760 1770 1780 1790 1800 VNMYIAVILE NFSVATEEST EPLSEDDFEM FYEVWEKFDP DATQFIEFSK LSDFAAALDP 1810 1820 1830 1840 1850 1860 PLLIAKPNKV QLIAMDLPMV SGDRIHCLDI LFAFTKRVLG ESGEMDSLRS QMEERFMSAN 1870 1880 1890 1900 1910 1920 PSKVSYEPIT TTLKRKQEDV SATVIQRAYR RYRLRQNVKN ISSIYIKDGD RDDDLLNKKD 1930 1940 1950 1960 1970 MAFDNVNENS SPEKTDATSS TTSPPSYDSV TKPDKEKYEQ DRTEKEDKGK DSKESKK

References

	« Hide 'large scale' referencesShow '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: 7720699] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION, TISSUE SPECIFICITY. 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: 17167479] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INVOLVEMENT IN CONGENITAL INSENSITIVITY TO PAIN, CHARACTERIZATION.
[3]	"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: 15302875] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 136-674 (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY. Tissue: Spinal ganglion.
[4]	"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.
[5]	"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: 14985375] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 840-958, VARIANTS PRIMARY ERYTHERMALGIA THR-859 AND HIS-869.
[6]	"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: 9169448] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"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: 15178348] [Abstract] Cited for: FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION, TISSUE SPECIFICITY.
[8]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1413 AND SER-1418, MASS SPECTROMETRY. Tissue: Epithelium.
[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: 15385606] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS PRIMARY ERYTHERMALGIA 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: 16216943] [Abstract] Cited for: VARIANT PRIMARY ERYTHERMALGIA 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: 15958509] [Abstract] Cited for: VARIANT PRIMARY ERYTHERMALGIA VAL-1460, CHARACTERIZATION OF VARIANT PRIMARY ERYTHERMALGIA VAL-1460.
[12]	"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: 17145499] [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.
[13]	"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: 16702558] [Abstract] Cited for: CHARACTERIZATION OF VARIANT PRIMARY ERYTHERMALGIA HIS-869.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

SCN9A entry

Protein Spotlight

Silent pain - Issue 102 of February 2009

Cross-references

Sequence databases
EMBLGenBankDDBJ	X82835 mRNA. Translation: CAA58042.1. DQ857292 mRNA. Translation: ABI51981.1. 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.
IPI	IPI00154944. IPI00479414. IPI00745570.
PIR	S54771.
RefSeq	NP_002968.1.
UniGene	Hs.439145
3D structure databases
HSSP	HSSP built from PDB template 1BYY based on UniProtKB P04775.
ModBase	Search...
Protein family/group databases
TCDB	1.A.1.10.5. voltage-gated ion channel (VIC) superfamily.
Proteomic databases
PRIDE	Q15858.
Genome annotation databases
Ensembl	ENSG00000169432. Homo sapiens. [Contig view]
GeneID	6335.
KEGG	hsa:6335.
Organism-specific databases
GeneCards	GC02M166763.
H-InvDB	HIX0029861.
HGNC	HGNC:10597. SCN9A.
HPA	CAB013679.
MIM	133020. phenotype. 167400. phenotype. 243000. phenotype. 603415. gene.
Orphanet	88642. Congenital indifference to pain. 1956. Erythromelalgia. 46348. Paroxysmal extreme pain disorder. 90026. Primary erythermalgia.
PharmGKB	PA35010.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q15858.
Gene expression databases
ArrayExpress	Q15858.
Bgee	Q15858.
CleanEx	HS_SCN9A.
GermOnline	ENSG00000169432. Homo sapiens.
Family and domain databases
InterPro	IPR005821. Ion_trans. IPR000048. IQ_CaM_bd_region. IPR001696. Na_channel. IPR010526. Na_trans_assoc. [Graphical view]
Pfam	PF00520. Ion_trans. 4 hits. PF00612. IQ. 1 hit. PF06512. Na_trans_assoc. 1 hit. [Graphical view]
PRINTS	PR00170. NACHANNEL.
SMART	SM00015. IQ. 1 hit. [Graphical view]
PROSITE	PS50096. IQ. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00555. Lamotrigine. DB00281. Lidocaine.
NextBio	24600.
SOURCE	Search...

Entry information

Entry name

SCN9A_HUMAN

Accession

Primary (citable) accession number: Q15858
Secondary accession number(s): A1BUH5 , Q6B4R9, Q6B4S0, Q6B4S1, Q70HX1, Q70HX2, Q8WTU1, Q8WWN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	November 23, 2004
Last modified:	May 26, 2009
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)