Q9UQD0 (SCN8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium channel protein type 8 subunit alpha

Alternative name(s):
Sodium channel protein type VIII subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.6

Gene names

Name:	SCN8A
Synonyms:	MED

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	1980 AA.
Sequence status	Complete.
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. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation. Ref.3
Subunit structure	Interacts with NEDD4 and NEDD4L By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Ref.3. Isoform 5: Cytoplasmic vesicle. Note: Some vesicles are localized adjacent to melanoma invadopodia and macrophage podosomes. Does not localize to the plasma membrane. Ref.3
Tissue specificity	Isoform 5 is expressed in non-neuronal tissues, such as monocytes/macrophages. Ref.3
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	May be ubiquitinated by NEDD4L; which would promote its endocytosis By similarity.
Involvement in disease	Defects in SCN8A are the cause of cognitive impairment with or without cerebellar ataxia (CIAT) [MIM:614306]. A disorder characterized by markedly delayed cognitive and motor development, attention deficit disorder, and cerebellar ataxia. Features include bilateral esophoria, strabismatic amblyopia, unsustained gaze evoked nystagmus on horizontal gaze, ataxic gait, dysmetria in the upper limbs and dysarthria, with normal strength, tone, and reflexes. Ref.7
Sequence similarities	Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily. [View classification] Contains 1 IQ domain.

Ontologies

Keywords
Biological process	Ion transport Sodium transport Transport
Cellular component	Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing
Disease	Mental retardation
Domain	Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding Sodium
Molecular function	Ionic channel Sodium channel Voltage-gated channel
PTM	Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Traceable author statement. Source: Reactome myelination Inferred from sequence or structural similarity. Source: BHF-UCL peripheral nervous system development Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell node of Ranvier Inferred from sequence or structural similarity. Source: BHF-UCL voltage-gated sodium channel complex Inferred by curator Ref.2. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated sodium channel activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.2 (identifier: Q9UQD0-1)

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 Ref.2 (identifier: Q9UQD0-2)

Also known as: 5A;

The sequence of this isoform differs from the canonical sequence as follows:
     207-207: I → V
     212-212: N → D

Isoform 3 Ref.2 (identifier: Q9UQD0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     666-666: E → EVKIDKAATDDS

Isoform 4 Ref.1 (identifier: Q9UQD0-4)

Also known as: 18N;

The sequence of this isoform differs from the canonical sequence as follows:
     1275-1283: SLVSLIANA → PLNLSGLI
     1284-1980: Missing.

Isoform 5 (identifier: Q9UQD0-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1275-1315: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1980	1980	Sodium channel protein type 8 subunit alpha		PRO_0000048500
Regions
	Transmembrane	128 – 151	24	Helical; Name=S1 of repeat I; Potential
	Transmembrane	160 – 179	20	Helical; Name=S2 of repeat I; Potential
	Transmembrane	193 – 211	19	Helical; Name=S3 of repeat I; Potential
	Transmembrane	218 – 237	20	Helical; Voltage-sensor; Name=S4 of repeat I; Potential
	Transmembrane	253 – 277	25	Helical; Name=S5 of repeat I; Potential
	Transmembrane	388 – 413	26	Helical; Name=S6 of repeat I; Potential
	Transmembrane	748 – 772	25	Helical; Name=S1 of repeat II; Potential
	Transmembrane	784 – 807	24	Helical; Name=S2 of repeat II; Potential
	Transmembrane	816 – 835	20	Helical; Name=S3 of repeat II; Potential
	Transmembrane	842 – 862	21	Helical; Voltage-sensor; Name=S4 of repeat II; Potential
	Transmembrane	878 – 898	21	Helical; Name=S5 of repeat II; Potential
	Transmembrane	952 – 977	26	Helical; Name=S6 of repeat II; Potential
	Transmembrane	1194 – 1217	24	Helical; Name=S1 of repeat III; Potential
	Transmembrane	1231 – 1256	26	Helical; Name=S2 of repeat III; Potential
	Transmembrane	1263 – 1284	22	Helical; Name=S3 of repeat III; Potential
	Transmembrane	1289 – 1310	22	Helical; Voltage-sensor; Name=S4 of repeat III; Potential
	Transmembrane	1330 – 1351	22	Helical; Name=S5 of repeat III; Potential
	Transmembrane	1438 – 1464	27	Helical; Name=S6 of repeat III; Potential
	Transmembrane	1518 – 1541	24	Helical; Name=S1 of repeat IV; Potential
	Transmembrane	1553 – 1576	24	Helical; Name=S2 of repeat IV; Potential
	Transmembrane	1583 – 1606	24	Helical; Name=S3 of repeat IV; Potential
	Transmembrane	1617 – 1638	22	Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
	Transmembrane	1654 – 1676	23	Helical; Name=S5 of repeat IV; Potential
	Transmembrane	1742 – 1766	25	Helical; Name=S6 of repeat IV; Potential
	Repeat	114 – 442	329	I
	Repeat	735 – 1007	273	II
	Repeat	1180 – 1495	316	III
	Repeat	1504 – 1801	298	IV
	Domain	1895 – 1924	30	IQ
	Nucleotide binding	893 – 900	8	ATP Potential
Amino acid modifications
	Glycosylation	215	1	N-linked (GlcNAc...) Potential
	Glycosylation	289	1	N-linked (GlcNAc...) Potential
	Glycosylation	295	1	N-linked (GlcNAc...) Potential
	Glycosylation	308	1	N-linked (GlcNAc...) Potential
	Glycosylation	326	1	N-linked (GlcNAc...) Potential
	Glycosylation	544	1	N-linked (GlcNAc...) Potential
	Glycosylation	640	1	N-linked (GlcNAc...) Potential
	Glycosylation	877	1	N-linked (GlcNAc...) Potential
	Glycosylation	1047	1	N-linked (GlcNAc...) Potential
	Glycosylation	1064	1	N-linked (GlcNAc...) Potential
	Glycosylation	1091	1	N-linked (GlcNAc...) Potential
	Glycosylation	1358	1	N-linked (GlcNAc...) Potential
	Glycosylation	1372	1	N-linked (GlcNAc...) Potential
	Glycosylation	1383	1	N-linked (GlcNAc...) Potential
	Glycosylation	1768	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	207	1	I → V in isoform 2. Ref.2		VSP_050589
	Alternative sequence	212	1	N → D in isoform 2. Ref.2		VSP_050590
	Alternative sequence	666	1	E → EVKIDKAATDDS in isoform 3. Ref.2		VSP_050591
	Alternative sequence	1275 – 1315	41	Missing in isoform 5.		VSP_038651
	Alternative sequence	1275 – 1283	9	SLVSLIANA → PLNLSGLI in isoform 4. Ref.1		VSP_050592
	Alternative sequence	1284 – 1980	697	Missing in isoform 4. Ref.1		VSP_050593
Experimental info
	Sequence conflict	5	1	L → V in AAF35390. Ref.5
	Sequence conflict	133	1	V → L in AAD15789. Ref.1
	Sequence conflict	257	1	L → M in AAF35390. Ref.5
	Sequence conflict	273	1	F → I in ACM63162. Ref.3
	Sequence conflict	274 – 278	5	MGNLR → HGEPS in AAF35390. Ref.5
	Sequence conflict	453	1	T → N in AAF35390. Ref.5
	Sequence conflict	477	1	S → F in AAF35390. Ref.5
	Sequence conflict	483	1	L → I in AAF35390. Ref.5
	Sequence conflict	492	1	R → S in AAF35390. Ref.5
	Sequence conflict	504	1	S → F in AAF35390. Ref.5
	Sequence conflict	547 – 548	2	LL → MF in AAF35390. Ref.5
	Sequence conflict	1416	1	M → V in ACM63162. Ref.3
	Sequence conflict	1445	1	V → I in AAD15789. Ref.1
	Sequence conflict	1519	1	V → I in AAD15789. Ref.1
	Sequence conflict	1702	1	T → A in AAF35390. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 0EFC7BFB137FD4F0	FASTA	1,980	225,280
	10 20 30 40 50 60 MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 70 80 90 100 110 120 AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 130 140 150 160 170 180 IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR 190 200 210 220 230 240 GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI 250 260 270 280 290 300 VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF 310 320 330 340 350 360 DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF 370 380 390 400 410 420 LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 430 440 450 460 470 480 TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI 490 500 510 520 530 540 SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 550 560 570 580 590 600 SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 610 620 630 640 650 660 LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG 670 680 690 700 710 720 GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP 730 740 750 760 770 780 PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ 790 800 810 820 830 840 FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL 850 860 870 880 890 900 SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS 910 920 930 940 950 960 YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV 970 980 990 1000 1010 1020 MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ 1030 1040 1050 1060 1070 1080 AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID 1090 1100 1110 1120 1130 1140 EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK 1150 1160 1170 1180 1190 1200 PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF 1210 1220 1230 1240 1250 1260 ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF 1270 1280 1290 1300 1310 1320 TNAWCWLDFL IVAVSLVSLI ANALGYSELG AIKSLRTLRA LRPLRALSRF EGMRVVVNAL 1330 1340 1350 1360 1370 1380 VGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKYHYCFNET SEIRFEIEDV NNKTECEKLM 1390 1400 1410 1420 1430 1440 EGNNTEIRWK NVKINFDNVG AGYLALLQVA TFKGWMDIMY AAVDSRKPDE QPKYEDNIYM 1450 1460 1470 1480 1490 1500 YIYFVIFIIF GSFFTLNLFI GVIIDNFNQQ KKKFGGQDIF MTEEQKKYYN AMKKLGSKKP 1510 1520 1530 1540 1550 1560 QKPIPRPLNK IQGIVFDFVT QQAFDIVIMM LICLNMVTMM VETDTQSKQM ENILYWINLV 1570 1580 1590 1600 1610 1620 FVIFFTCECV LKMFALRHYY FTIGWNIFDF VVVILSIVGM FLADIIEKYF VSPTLFRVIR 1630 1640 1650 1660 1670 1680 LARIGRILRL IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA 1690 1700 1710 1720 1730 1740 GIDDMFNFET FGNSMICLFQ ITTSAGWDGL LLPILNRPPD CSLDKEHPGS GFKGDCGNPS 1750 1760 1770 1780 1790 1800 VGIFFFVSYI IISFLIVVNM YIAIILENFS VATEESADPL SEDDFETFYE IWEKFDPDAT 1810 1820 1830 1840 1850 1860 QFIEYCKLAD FADALEHPLR VPKPNTIELI AMDLPMVSGD RIHCLDILFA FTKRVLGDSG 1870 1880 1890 1900 1910 1920 ELDILRQQME ERFVASNPSK VSYEPITTTL RRKQEEVSAV VLQRAYRGHL ARRGFICKKT 1930 1940 1950 1960 1970 1980 TSNKLENGGT HREKKESTPS TASLPSYDSV TKPEKEKQQR AEEGRRERAK RQKEVRESKC
	Isoform 2 (5A) [UniParc]. Checksum: 0510CF3CC31892F0	FASTA	1,980	225,267
	10 20 30 40 50 60 MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 70 80 90 100 110 120 AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 130 140 150 160 170 180 IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR 190 200 210 220 230 240 GFCIDGFTFL RDPWNWLDFS VIMMAYVTEF VDLGNVSALR TFRVLRALKT ISVIPGLKTI 250 260 270 280 290 300 VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF 310 320 330 340 350 360 DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF 370 380 390 400 410 420 LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 430 440 450 460 470 480 TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI 490 500 510 520 530 540 SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 550 560 570 580 590 600 SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 610 620 630 640 650 660 LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG 670 680 690 700 710 720 GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP 730 740 750 760 770 780 PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ 790 800 810 820 830 840 FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL 850 860 870 880 890 900 SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS 910 920 930 940 950 960 YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV 970 980 990 1000 1010 1020 MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ 1030 1040 1050 1060 1070 1080 AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID 1090 1100 1110 1120 1130 1140 EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK 1150 1160 1170 1180 1190 1200 PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF 1210 1220 1230 1240 1250 1260 ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF 1270 1280 1290 1300 1310 1320 TNAWCWLDFL IVAVSLVSLI ANALGYSELG AIKSLRTLRA LRPLRALSRF EGMRVVVNAL 1330 1340 1350 1360 1370 1380 VGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKYHYCFNET SEIRFEIEDV NNKTECEKLM 1390 1400 1410 1420 1430 1440 EGNNTEIRWK NVKINFDNVG AGYLALLQVA TFKGWMDIMY AAVDSRKPDE QPKYEDNIYM 1450 1460 1470 1480 1490 1500 YIYFVIFIIF GSFFTLNLFI GVIIDNFNQQ KKKFGGQDIF MTEEQKKYYN AMKKLGSKKP 1510 1520 1530 1540 1550 1560 QKPIPRPLNK IQGIVFDFVT QQAFDIVIMM LICLNMVTMM VETDTQSKQM ENILYWINLV 1570 1580 1590 1600 1610 1620 FVIFFTCECV LKMFALRHYY FTIGWNIFDF VVVILSIVGM FLADIIEKYF VSPTLFRVIR 1630 1640 1650 1660 1670 1680 LARIGRILRL IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA 1690 1700 1710 1720 1730 1740 GIDDMFNFET FGNSMICLFQ ITTSAGWDGL LLPILNRPPD CSLDKEHPGS GFKGDCGNPS 1750 1760 1770 1780 1790 1800 VGIFFFVSYI IISFLIVVNM YIAIILENFS VATEESADPL SEDDFETFYE IWEKFDPDAT 1810 1820 1830 1840 1850 1860 QFIEYCKLAD FADALEHPLR VPKPNTIELI AMDLPMVSGD RIHCLDILFA FTKRVLGDSG 1870 1880 1890 1900 1910 1920 ELDILRQQME ERFVASNPSK VSYEPITTTL RRKQEEVSAV VLQRAYRGHL ARRGFICKKT 1930 1940 1950 1960 1970 1980 TSNKLENGGT HREKKESTPS TASLPSYDSV TKPEKEKQQR AEEGRRERAK RQKEVRESKC
	Isoform 3 [UniParc]. Checksum: 8C830A4CA55C69DE	FASTA	1,991	226,424
	10 20 30 40 50 60 MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 70 80 90 100 110 120 AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 130 140 150 160 170 180 IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR 190 200 210 220 230 240 GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI 250 260 270 280 290 300 VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF 310 320 330 340 350 360 DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF 370 380 390 400 410 420 LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 430 440 450 460 470 480 TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI 490 500 510 520 530 540 SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 550 560 570 580 590 600 SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 610 620 630 640 650 660 LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG 670 680 690 700 710 720 GRLLPEVKID KAATDDSATT EVEIKKKGPG SLLVSMDQLA SYGRKDRINS IMSVVTNTLV 730 740 750 760 770 780 EELEESQRKC PPCWYKFANT FLIWECHPYW IKLKEIVNLI VMDPFVDLAI TICIVLNTLF 790 800 810 820 830 840 MAMEHHPMTP QFEHVLAVGN LVFTGIFTAE MFLKLIAMDP YYYFQEGWNI FDGFIVSLSL 850 860 870 880 890 900 MELSLADVEG LSVLRSFRLL RVFKLAKSWP TLNMLIKIIG NSVGALGNLT LVLAIIVFIF 910 920 930 940 950 960 AVVGMQLFGK SYKECVCKIN QDCELPRWHM HDFFHSFLIV FRVLCGEWIE TMWDCMEVAG 970 980 990 1000 1010 1020 QAMCLIVFMM VMVIGNLVVL NLFLALLLSS FSADNLAATD DDGEMNNLQI SVIRIKKGVA 1030 1040 1050 1060 1070 1080 WTKLKVHAFM QAHFKQREAD EVKPLDELYE KKANCIANHT GADIHRNGDF QKNGNGTTSG 1090 1100 1110 1120 1130 1140 IGSSVEKYII DEDHMSFINN PNLTVRVPIA VGESDFENLN TEDVSSESDP EGSKDKLDDT 1150 1160 1170 1180 1190 1200 SSSEGSTIDI KPEVEEVPVE QPEEYLDPDA CFTEGCVQRF KCCQVNIEEG LGKSWWILRK 1210 1220 1230 1240 1250 1260 TCFLIVEHNW FETFIIFMIL LSSGALAFED IYIEQRKTIR TILEYADKVF TYIFILEMLL 1270 1280 1290 1300 1310 1320 KWTAYGFVKF FTNAWCWLDF LIVAVSLVSL IANALGYSEL GAIKSLRTLR ALRPLRALSR 1330 1340 1350 1360 1370 1380 FEGMRVVVNA LVGAIPSIMN VLLVCLIFWL IFSIMGVNLF AGKYHYCFNE TSEIRFEIED 1390 1400 1410 1420 1430 1440 VNNKTECEKL MEGNNTEIRW KNVKINFDNV GAGYLALLQV ATFKGWMDIM YAAVDSRKPD 1450 1460 1470 1480 1490 1500 EQPKYEDNIY MYIYFVIFII FGSFFTLNLF IGVIIDNFNQ QKKKFGGQDI FMTEEQKKYY 1510 1520 1530 1540 1550 1560 NAMKKLGSKK PQKPIPRPLN KIQGIVFDFV TQQAFDIVIM MLICLNMVTM MVETDTQSKQ 1570 1580 1590 1600 1610 1620 MENILYWINL VFVIFFTCEC VLKMFALRHY YFTIGWNIFD FVVVILSIVG MFLADIIEKY 1630 1640 1650 1660 1670 1680 FVSPTLFRVI RLARIGRILR LIKGAKGIRT LLFALMMSLP ALFNIGLLLF LVMFIFSIFG 1690 1700 1710 1720 1730 1740 MSNFAYVKHE AGIDDMFNFE TFGNSMICLF QITTSAGWDG LLLPILNRPP DCSLDKEHPG 1750 1760 1770 1780 1790 1800 SGFKGDCGNP SVGIFFFVSY IIISFLIVVN MYIAIILENF SVATEESADP LSEDDFETFY 1810 1820 1830 1840 1850 1860 EIWEKFDPDA TQFIEYCKLA DFADALEHPL RVPKPNTIEL IAMDLPMVSG DRIHCLDILF 1870 1880 1890 1900 1910 1920 AFTKRVLGDS GELDILRQQM EERFVASNPS KVSYEPITTT LRRKQEEVSA VVLQRAYRGH 1930 1940 1950 1960 1970 1980 LARRGFICKK TTSNKLENGG THREKKESTP STASLPSYDS VTKPEKEKQQ RAEEGRRERA 1990 KRQKEVRESK C
	Isoform 4 (18N) [UniParc]. Checksum: 43D3C2BD00DD44E5	FASTA	1,282	145,118
	10 20 30 40 50 60 MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 70 80 90 100 110 120 AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 130 140 150 160 170 180 IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR 190 200 210 220 230 240 GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI 250 260 270 280 290 300 VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF 310 320 330 340 350 360 DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF 370 380 390 400 410 420 LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 430 440 450 460 470 480 TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI 490 500 510 520 530 540 SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 550 560 570 580 590 600 SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 610 620 630 640 650 660 LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG 670 680 690 700 710 720 GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP 730 740 750 760 770 780 PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ 790 800 810 820 830 840 FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL 850 860 870 880 890 900 SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS 910 920 930 940 950 960 YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV 970 980 990 1000 1010 1020 MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ 1030 1040 1050 1060 1070 1080 AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID 1090 1100 1110 1120 1130 1140 EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK 1150 1160 1170 1180 1190 1200 PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF 1210 1220 1230 1240 1250 1260 ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF 1270 1280 TNAWCWLDFL IVAVPLNLSG LI
	Isoform 5 [UniParc]. Checksum: 3E44D910D3897BC4	FASTA	1,939	220,798
	10 20 30 40 50 60 MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE 70 80 90 100 110 120 AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL 130 140 150 160 170 180 IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR 190 200 210 220 230 240 GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI 250 260 270 280 290 300 VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF 310 320 330 340 350 360 DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF 370 380 390 400 410 420 LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA 430 440 450 460 470 480 TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI 490 500 510 520 530 540 SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF 550 560 570 580 590 600 SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS 610 620 630 640 650 660 LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG 670 680 690 700 710 720 GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP 730 740 750 760 770 780 PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ 790 800 810 820 830 840 FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL 850 860 870 880 890 900 SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS 910 920 930 940 950 960 YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV 970 980 990 1000 1010 1020 MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ 1030 1040 1050 1060 1070 1080 AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID 1090 1100 1110 1120 1130 1140 EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK 1150 1160 1170 1180 1190 1200 PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF 1210 1220 1230 1240 1250 1260 ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF 1270 1280 1290 1300 1310 1320 TNAWCWLDFL IVAVVVNALV GAIPSIMNVL LVCLIFWLIF SIMGVNLFAG KYHYCFNETS 1330 1340 1350 1360 1370 1380 EIRFEIEDVN NKTECEKLME GNNTEIRWKN VKINFDNVGA GYLALLQVAT FKGWMDIMYA 1390 1400 1410 1420 1430 1440 AVDSRKPDEQ PKYEDNIYMY IYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM 1450 1460 1470 1480 1490 1500 TEEQKKYYNA MKKLGSKKPQ KPIPRPLNKI QGIVFDFVTQ QAFDIVIMML ICLNMVTMMV 1510 1520 1530 1540 1550 1560 ETDTQSKQME NILYWINLVF VIFFTCECVL KMFALRHYYF TIGWNIFDFV VVILSIVGMF 1570 1580 1590 1600 1610 1620 LADIIEKYFV SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV 1630 1640 1650 1660 1670 1680 MFIFSIFGMS NFAYVKHEAG IDDMFNFETF GNSMICLFQI TTSAGWDGLL LPILNRPPDC 1690 1700 1710 1720 1730 1740 SLDKEHPGSG FKGDCGNPSV GIFFFVSYII ISFLIVVNMY IAIILENFSV ATEESADPLS 1750 1760 1770 1780 1790 1800 EDDFETFYEI WEKFDPDATQ FIEYCKLADF ADALEHPLRV PKPNTIELIA MDLPMVSGDR 1810 1820 1830 1840 1850 1860 IHCLDILFAF TKRVLGDSGE LDILRQQMEE RFVASNPSKV SYEPITTTLR RKQEEVSAVV 1870 1880 1890 1900 1910 1920 LQRAYRGHLA RRGFICKKTT SNKLENGGTH REKKESTPST ASLPSYDSVT KPEKEKQQRA 1930 EEGRRERAKR QKEVRESKC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells." Plummer N.W., McBurney M.W., Meisler M.H. J. Biol. Chem. 272:24008-24015(1997) [PubMed: 9295353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 4). Tissue: Brain and Fetal brain.
[2]	"Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A." Plummer N.W., Galt J., Jones J.M., Burgess D.L., Sprunger L.K., Kohrman D.C., Meisler M.H. Genomics 54:287-296(1998) [PubMed: 9828131] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
[3]	"Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A." Carrithers M.D., Chatterjee G., Carrithers L.M., Offoha R., Iheagwara U., Rahner C., Graham M., Waxman S.G. J. Biol. Chem. 284:8114-8126(2009) [PubMed: 19136557] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Monocytic leukemia.
[4]	"cDNA sequence of human sodium channel, SCN8A." Lin C., Numakura C., Kiyoshi H. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Cloning of cDNA for human voltage-gated sodium channel alpha subunit, SCN8A." Jeong S.-Y., Goto J., Kanazawa I. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., 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., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation." Trudeau M.M., Dalton J.C., Day J.W., Ranum L.P., Meisler M.H. J. Med. Genet. 43:527-530(2006) [PubMed: 16236810] [Abstract] Cited for: INVOLVEMENT IN CIAT.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF050736 , AF050711, AF050712, AF050713, AF050714, AF050715, AF050716, AF050717, AF050718, AF050719, AF050720, AF050721, AF050722, AF050723, AF050724, AF050725, AF050726, AF050727, AF050728, AF050729, AF050730, AF050731, AF050732, AF050733, AF050734, AF050735 Genomic DNA. Translation: AAD15789.1. AF049618 Genomic DNA. Translation: AAD20439.1. FJ611941 mRNA. Translation: ACM63162.1. AB027567 mRNA. Translation: BAA78033.1. AF225988 mRNA. Translation: AAF35390.1. AC013421 Genomic DNA. No translation available. AC025097 Genomic DNA. No translation available. AC068987 Genomic DNA. No translation available. AC140060 Genomic DNA. No translation available.
IPI	IPI00183041. IPI00337743. IPI00337744. IPI00337745. IPI00954952.
RefSeq	NP_001171455.1. NM_001177984.1. NP_055006.1. NM_014191.2.
UniGene	Hs.710638.
3D structure databases
ProteinModelPortal	Q9UQD0.
SMR	Q9UQD0. Positions 741-979, 1188-1350, 1510-1872.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UQD0. 1 interaction.
STRING	Q9UQD0.
Protein family/group databases
TCDB	1.A.1.10.8. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	Q9UQD0.
Polymorphism databases
DMDM	34098756.
Proteomic databases
PRIDE	Q9UQD0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354534; ENSP00000346534; ENSG00000196876.
GeneID	6334.
KEGG	hsa:6334.
UCSC	uc001ryw.1. human.
Organism-specific databases
CTD	6334.
GeneCards	GC12P052007.
H-InvDB	HIX0036666.
HGNC	HGNC:10596. SCN8A.
HPA	CAB022169.
MIM	600702. gene. 614306. phenotype.
neXtProt	NX_Q9UQD0.
PharmGKB	PA35009.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14675.
GeneTree	ENSGT00560000076721.
HOGENOM	HBG358468.
HOVERGEN	HBG053100.
OMA	LNKIQGI.
OrthoDB	EOG40S0DS.
PhylomeDB	Q9UQD0.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q9UQD0.
Bgee	Q9UQD0.
CleanEx	HS_SCN8A.
Genevestigator	Q9UQD0.
GermOnline	ENSG00000196876. Homo sapiens.
Family and domain databases
InterPro	IPR024583. DUF3451. IPR005821. Ion_trans. IPR000048. IQ_motif_EF-hand-BS. IPR008054. Na_channel_a8su. IPR001696. Na_channel_asu. IPR010526. Na_trans_assoc. [Graphical view]
KO	K04840.
Pfam	PF11933. DUF3451. 1 hit. PF00520. Ion_trans. 4 hits. PF00612. IQ. 1 hit. PF06512. Na_trans_assoc. 1 hit. [Graphical view]
PRINTS	PR00170. NACHANNEL. PR01667. NACHANNEL8.
SMART	SM00015. IQ. 1 hit. [Graphical view]
PROSITE	PS50096. IQ. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00555. Lamotrigine.
NextBio	24596.
SOURCE	Search...

Entry information

Entry name

SCN8A_HUMAN

Accession

Primary (citable) accession number: Q9UQD0
Secondary accession number(s): B9VWG8 , O95788, Q9NYX2, Q9UPB2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 98 of the entry and version 1 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.