Q99250 (SCN2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium channel protein type 2 subunit alpha

Alternative name(s):
HBSC II
Sodium channel protein brain II subunit alpha
Sodium channel protein type II subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.2

Gene names

Name:	SCN2A
Synonyms:	NAC2, SCN2A1, SCN2A2

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	2005 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.
Subunit structure	The sodium channel consists of a large polypeptide and 2-3 smaller ones. This sequence represents a large polypeptide. Interacts with NEDD4L By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
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	Seizures, benign familial infantile 3 (BFIS3) [MIM:607745]: An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9 Ref.12 Ref.15 Epileptic encephalopathy, early infantile, 11 (EIEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.16
Sequence similarities	Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.2/SCN2A subfamily. [View classification] Contains 1 IQ domain.
Sequence caution	The sequence CAA46438.1 differs from that shown. Reason: Frameshift at position 1953. The sequence CAA46438.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.

Ontologies

Keywords
Biological process	Ion transport Sodium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Epilepsy
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ion channel Sodium channel Voltage-gated channel
PTM	Glycoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: Compara myelination Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	T-tubule Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc intercalated disc Inferred from electronic annotation. Source: Compara node of Ranvier Inferred from sequence or structural similarity. Source: BHF-UCL paranode region of axon Inferred from electronic annotation. Source: Compara voltage-gated sodium channel complex Inferred from electronic annotation. Source: InterPro
Molecular_function	voltage-gated sodium channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99250-1)

Also known as: Adult; 6A;

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: Q99250-2)

Also known as: Neonatal; 6N;

The sequence of this isoform differs from the canonical sequence as follows:
     209-209: D → N

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2005

2005

Sodium channel protein type 2 subunit alpha

PRO_0000048491

Regions

Transmembrane

125 – 148

24

Helical; Name=S1 of repeat I; Potential

Transmembrane

157 – 176

20

Helical; Name=S2 of repeat I; Potential

Transmembrane

190 – 208

19

Helical; Name=S3 of repeat I; Potential

Transmembrane

215 – 234

20

Helical; Voltage-sensor; Name=S4 of repeat I; Potential

Transmembrane

251 – 274

24

Helical; Name=S5 of repeat I; Potential

Transmembrane

402 – 427

26

Helical; Name=S6 of repeat I; Potential

Transmembrane

754 – 778

25

Helical; Name=S1 of repeat II; Potential

Transmembrane

790 – 813

24

Helical; Name=S2 of repeat II; Potential

Transmembrane

822 – 841

20

Helical; Name=S3 of repeat II; Potential

Transmembrane

848 – 867

20

Helical; Voltage-sensor; Name=S4 of repeat II; Potential

Transmembrane

884 – 904

21

Helical; Name=S5 of repeat II; Potential

Transmembrane

958 – 983

26

Helical; Name=S6 of repeat II; Potential

Transmembrane

1204 – 1227

24

Helical; Name=S1 of repeat III; Potential

Transmembrane

1241 – 1266

26

Helical; Name=S2 of repeat III; Potential

Transmembrane

1273 – 1294

22

Helical; Name=S3 of repeat III; Potential

Transmembrane

1299 – 1320

22

Helical; Voltage-sensor; Name=S4 of repeat III; Potential

Transmembrane

1340 – 1367

28

Helical; Name=S5 of repeat III; Potential

Transmembrane

1447 – 1473

27

Helical; Name=S6 of repeat III; Potential

Transmembrane

1527 – 1550

24

Helical; Name=S1 of repeat IV; Potential

Transmembrane

1562 – 1585

24

Helical; Name=S2 of repeat IV; Potential

Transmembrane

1592 – 1615

24

Helical; Name=S3 of repeat IV; Potential

Transmembrane

1626 – 1647

22

Helical; Voltage-sensor; Name=S4 of repeat IV; Potential

Transmembrane

1663 – 1685

23

Helical; Name=S5 of repeat IV; Potential

Transmembrane

1752 – 1776

25

Helical; Name=S6 of repeat IV; Potential

Repeat

111 – 456

346

I

Repeat

741 – 1013

273

II

Repeat

1190 – 1504

315

III

Repeat

1513 – 1811

299

IV

Domain

1905 – 1934

30

IQ

Amino acid modifications

Glycosylation

212

1

N-linked (GlcNAc...) Potential

Glycosylation

285

1

N-linked (GlcNAc...) Potential

Glycosylation

291

1

N-linked (GlcNAc...) Potential

Glycosylation

297

1

N-linked (GlcNAc...) Potential

Glycosylation

303

1

N-linked (GlcNAc...) Potential

Glycosylation

308

1

N-linked (GlcNAc...) Potential

Glycosylation

340

1

N-linked (GlcNAc...) Potential

Glycosylation

604

1

N-linked (GlcNAc...) Potential

Glycosylation

624

1

N-linked (GlcNAc...) Potential

Glycosylation

883

1

N-linked (GlcNAc...) Potential

Glycosylation

1055

1

N-linked (GlcNAc...) Potential

Glycosylation

1072

1

N-linked (GlcNAc...) Potential

Glycosylation

1136

1

N-linked (GlcNAc...) Potential

Glycosylation

1368

1

N-linked (GlcNAc...) Potential

Glycosylation

1382

1

N-linked (GlcNAc...) Potential

Glycosylation

1393

1

N-linked (GlcNAc...) Potential

Glycosylation

1778

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

209

1

D → N in isoform 2.

VSP_001032

Natural variant

19

1

R → K. Ref.7 Ref.11 Ref.14
Corresponds to variant rs17183814 [ dbSNP | Ensembl ].

VAR_029732

Natural variant

188

1

R → W in BFIS3; mutant channel inactivates more slowly than wild-type whereas the Na(+) channel conductance is not affected. Ref.7

VAR_029733

Natural variant

223

1

R → Q in BFIS3. Ref.12

VAR_029734

Natural variant

252

1

M → V in BFIS3. Ref.15

VAR_065176

Natural variant

261

1

V → M in BFIS3. Ref.15

VAR_065177

Natural variant

263

1

A → V in EIEE11. Ref.16

VAR_065178

Natural variant

328

1

F → V. Ref.13 Ref.14

VAR_064331

Natural variant

385

1

F → Y.
Corresponds to variant rs2228988 [ dbSNP | Ensembl ].

VAR_029735

Natural variant

524

1

R → Q. Ref.7 Ref.14

VAR_029736

Natural variant

575

1

A → V There is no significant effetcs on the voltage-dependence of the channel. Ref.14

VAR_065179

Natural variant

892

1

V → I in BFIS3. Ref.12

VAR_029737

Natural variant

1003

1

L → I in BFIS3. Ref.12

VAR_029738

Natural variant

1211

1

E → K in EIEE11; markedly altered the voltage-dependence of the channel. Ref.14

VAR_065180

Natural variant

1319

1

R → Q in BFIS3. Ref.12

VAR_029739

Natural variant

1330

1

L → F in BFIS3. Ref.9

VAR_029740

Natural variant

1473

1

I → M in EIEE11; markedly altered the voltage-dependence of the channel. Ref.14

VAR_065181

Natural variant

1563

1

L → V in BFIS3. Ref.9

VAR_029741

Natural variant

1902

1

R → T Associated with autism. Ref.11

VAR_029742

Experimental info

Sequence conflict

524

1

R → L in AAA18895. Ref.1

Sequence conflict

1325

1

V → A in AAA18895. Ref.1

Sequence conflict

1768

1

V → L in AAA18895. Ref.1

Sequence conflict

1990

1

K → R in CAA46438. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

2005

Helix Strand Turn

Details...

Helix

1792 – 1805

14

Helix

1815 – 1817

3

Helix

1818 – 1824

7

Helix

1837 – 1841

5

Turn

1848 – 1850

3

Beta strand

1851 – 1853

3

Helix

1854 – 1864

11

Turn

1865 – 1869

5

Helix

1872 – 1878

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Adult) (6A) [UniParc]. Last modified November 8, 2002. Version 3. Checksum: 8A421AE6C7ED9A37	FASTA	2,005	227,975
	10 20 30 40 50 60 MAQSVLVPPG PDSFRFFTRE SLAAIEQRIA EEKAKRPKQE RKDEDDENGP KPNSDLEAGK 70 80 90 100 110 120 SLPFIYGDIP PEMVSVPLED LDPYYINKKT FIVLNKGKAI SRFSATPALY ILTPFNPIRK 130 140 150 160 170 180 LAIKILVHSL FNMLIMCTIL TNCVFMTMSN PPDWTKNVEY TFTGIYTFES LIKILARGFC 190 200 210 220 230 240 LEDFTFLRDP WNWLDFTVIT FAYVTEFVDL GNVSALRTFR VLRALKTISV IPGLKTIVGA 250 260 270 280 290 300 LIQSVKKLSD VMILTVFCLS VFALIGLQLF MGNLRNKCLQ WPPDNSSFEI NITSFFNNSL 310 320 330 340 350 360 DGNGTTFNRT VSIFNWDEYI EDKSHFYFLE GQNDALLCGN SSDAGQCPEG YICVKAGRNP 370 380 390 400 410 420 NYGYTSFDTF SWAFLSLFRL MTQDFWENLY QLTLRAAGKT YMIFFVLVIF LGSFYLINLI 430 440 450 460 470 480 LAVVAMAYEE QNQATLEEAE QKEAEFQQML EQLKKQQEEA QAAAAAASAE SRDFSGAGGI 490 500 510 520 530 540 GVFSESSSVA SKLSSKSEKE LKNRRKKKKQ KEQSGEEEKN DRVRKSESED SIRRKGFRFS 550 560 570 580 590 600 LEGSRLTYEK RFSSPHQSLL SIRGSLFSPR RNSRASLFSF RGRAKDIGSE NDFADDEHST 610 620 630 640 650 660 FEDNDSRRDS LFVPHRHGER RHSNVSQASR ASRVLPILPM NGKMHSAVDC NGVVSLVGGP 670 680 690 700 710 720 STLTSAGQLL PEGTTTETEI RKRRSSSYHV SMDLLEDPTS RQRAMSIASI LTNTMEELEE 730 740 750 760 770 780 SRQKCPPCWY KFANMCLIWD CCKPWLKVKH LVNLVVMDPF VDLAITICIV LNTLFMAMEH 790 800 810 820 830 840 YPMTEQFSSV LSVGNLVFTG IFTAEMFLKI IAMDPYYYFQ EGWNIFDGFI VSLSLMELGL 850 860 870 880 890 900 ANVEGLSVLR SFRLLRVFKL AKSWPTLNML IKIIGNSVGA LGNLTLVLAI IVFIFAVVGM 910 920 930 940 950 960 QLFGKSYKEC VCKISNDCEL PRWHMHDFFH SFLIVFRVLC GEWIETMWDC MEVAGQTMCL 970 980 990 1000 1010 1020 TVFMMVMVIG NLVVLNLFLA LLLSSFSSDN LAATDDDNEM NNLQIAVGRM QKGIDFVKRK 1030 1040 1050 1060 1070 1080 IREFIQKAFV RKQKALDEIK PLEDLNNKKD SCISNHTTIE IGKDLNYLKD GNGTTSGIGS 1090 1100 1110 1120 1130 1140 SVEKYVVDES DYMSFINNPS LTVTVPIAVG ESDFENLNTE EFSSESDMEE SKEKLNATSS 1150 1160 1170 1180 1190 1200 SEGSTVDIGA PAEGEQPEVE PEESLEPEAC FTEDCVRKFK CCQISIEEGK GKLWWNLRKT 1210 1220 1230 1240 1250 1260 CYKIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT YIFILEMLLK 1270 1280 1290 1300 1310 1320 WVAYGFQVYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG AIKSLRTLRA LRPLRALSRF 1330 1340 1350 1360 1370 1380 EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCINYT TGEMFDVSVV 1390 1400 1410 1420 1430 1440 NNYSECKALI ESNQTARWKN VKVNFDNVGL GYLSLLQVAT FKGWMDIMYA AVDSRNVELQ 1450 1460 1470 1480 1490 1500 PKYEDNLYMY LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM TEEQKKYYNA 1510 1520 1530 1540 1550 1560 MKKLGSKKPQ KPIPRPANKF QGMVFDFVTK QVFDISIMIL ICLNMVTMMV ETDDQSQEMT 1570 1580 1590 1600 1610 1620 NILYWINLVF IVLFTGECVL KLISLRYYYF TIGWNIFDFV VVILSIVGMF LAELIEKYFV 1630 1640 1650 1660 1670 1680 SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV MFIYAIFGMS 1690 1700 1710 1720 1730 1740 NFAYVKREVG IDDMFNFETF GNSMICLFQI TTSAGWDGLL APILNSGPPD CDPDKDHPGS 1750 1760 1770 1780 1790 1800 SVKGDCGNPS VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL SEDDFEMFYE 1810 1820 1830 1840 1850 1860 VWEKFDPDAT QFIEFAKLSD FADALDPPLL IAKPNKVQLI AMDLPMVSGD RIHCLDILFA 1870 1880 1890 1900 1910 1920 FTKRVLGESG EMDALRIQME ERFMASNPSK VSYEPITTTL KRKQEEVSAI IIQRAYRRYL 1930 1940 1950 1960 1970 1980 LKQKVKKVSS IYKKDKGKEC DGTPIKEDTL IDKLNENSTP EKTDMTPSTT SPPSYDSVTK 1990 2000 PEKEKFEKDK SEKEDKGKDI RESKK
	Isoform 2 (Neonatal) (6N) [UniParc]. Checksum: BDA9D5ADEEB5F780	FASTA	2,005	227,974
	10 20 30 40 50 60 MAQSVLVPPG PDSFRFFTRE SLAAIEQRIA EEKAKRPKQE RKDEDDENGP KPNSDLEAGK 70 80 90 100 110 120 SLPFIYGDIP PEMVSVPLED LDPYYINKKT FIVLNKGKAI SRFSATPALY ILTPFNPIRK 130 140 150 160 170 180 LAIKILVHSL FNMLIMCTIL TNCVFMTMSN PPDWTKNVEY TFTGIYTFES LIKILARGFC 190 200 210 220 230 240 LEDFTFLRDP WNWLDFTVIT FAYVTEFVNL GNVSALRTFR VLRALKTISV IPGLKTIVGA 250 260 270 280 290 300 LIQSVKKLSD VMILTVFCLS VFALIGLQLF MGNLRNKCLQ WPPDNSSFEI NITSFFNNSL 310 320 330 340 350 360 DGNGTTFNRT VSIFNWDEYI EDKSHFYFLE GQNDALLCGN SSDAGQCPEG YICVKAGRNP 370 380 390 400 410 420 NYGYTSFDTF SWAFLSLFRL MTQDFWENLY QLTLRAAGKT YMIFFVLVIF LGSFYLINLI 430 440 450 460 470 480 LAVVAMAYEE QNQATLEEAE QKEAEFQQML EQLKKQQEEA QAAAAAASAE SRDFSGAGGI 490 500 510 520 530 540 GVFSESSSVA SKLSSKSEKE LKNRRKKKKQ KEQSGEEEKN DRVRKSESED SIRRKGFRFS 550 560 570 580 590 600 LEGSRLTYEK RFSSPHQSLL SIRGSLFSPR RNSRASLFSF RGRAKDIGSE NDFADDEHST 610 620 630 640 650 660 FEDNDSRRDS LFVPHRHGER RHSNVSQASR ASRVLPILPM NGKMHSAVDC NGVVSLVGGP 670 680 690 700 710 720 STLTSAGQLL PEGTTTETEI RKRRSSSYHV SMDLLEDPTS RQRAMSIASI LTNTMEELEE 730 740 750 760 770 780 SRQKCPPCWY KFANMCLIWD CCKPWLKVKH LVNLVVMDPF VDLAITICIV LNTLFMAMEH 790 800 810 820 830 840 YPMTEQFSSV LSVGNLVFTG IFTAEMFLKI IAMDPYYYFQ EGWNIFDGFI VSLSLMELGL 850 860 870 880 890 900 ANVEGLSVLR SFRLLRVFKL AKSWPTLNML IKIIGNSVGA LGNLTLVLAI IVFIFAVVGM 910 920 930 940 950 960 QLFGKSYKEC VCKISNDCEL PRWHMHDFFH SFLIVFRVLC GEWIETMWDC MEVAGQTMCL 970 980 990 1000 1010 1020 TVFMMVMVIG NLVVLNLFLA LLLSSFSSDN LAATDDDNEM NNLQIAVGRM QKGIDFVKRK 1030 1040 1050 1060 1070 1080 IREFIQKAFV RKQKALDEIK PLEDLNNKKD SCISNHTTIE IGKDLNYLKD GNGTTSGIGS 1090 1100 1110 1120 1130 1140 SVEKYVVDES DYMSFINNPS LTVTVPIAVG ESDFENLNTE EFSSESDMEE SKEKLNATSS 1150 1160 1170 1180 1190 1200 SEGSTVDIGA PAEGEQPEVE PEESLEPEAC FTEDCVRKFK CCQISIEEGK GKLWWNLRKT 1210 1220 1230 1240 1250 1260 CYKIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT YIFILEMLLK 1270 1280 1290 1300 1310 1320 WVAYGFQVYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG AIKSLRTLRA LRPLRALSRF 1330 1340 1350 1360 1370 1380 EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCINYT TGEMFDVSVV 1390 1400 1410 1420 1430 1440 NNYSECKALI ESNQTARWKN VKVNFDNVGL GYLSLLQVAT FKGWMDIMYA AVDSRNVELQ 1450 1460 1470 1480 1490 1500 PKYEDNLYMY LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM TEEQKKYYNA 1510 1520 1530 1540 1550 1560 MKKLGSKKPQ KPIPRPANKF QGMVFDFVTK QVFDISIMIL ICLNMVTMMV ETDDQSQEMT 1570 1580 1590 1600 1610 1620 NILYWINLVF IVLFTGECVL KLISLRYYYF TIGWNIFDFV VVILSIVGMF LAELIEKYFV 1630 1640 1650 1660 1670 1680 SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV MFIYAIFGMS 1690 1700 1710 1720 1730 1740 NFAYVKREVG IDDMFNFETF GNSMICLFQI TTSAGWDGLL APILNSGPPD CDPDKDHPGS 1750 1760 1770 1780 1790 1800 SVKGDCGNPS VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL SEDDFEMFYE 1810 1820 1830 1840 1850 1860 VWEKFDPDAT QFIEFAKLSD FADALDPPLL IAKPNKVQLI AMDLPMVSGD RIHCLDILFA 1870 1880 1890 1900 1910 1920 FTKRVLGESG EMDALRIQME ERFMASNPSK VSYEPITTTL KRKQEEVSAI IIQRAYRRYL 1930 1940 1950 1960 1970 1980 LKQKVKKVSS IYKKDKGKEC DGTPIKEDTL IDKLNENSTP EKTDMTPSTT SPPSYDSVTK 1990 2000 PEKEKFEKDK SEKEDKGKDI RESKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain." Ahmed C.M., Ware D.H., Lee S.C., Patten C.D., Ferrer-Montiel A.V., Schinder A.F., McPherson J.D., Wagner-Mcpherson C.B., Wasmuth J.J., Evans G.A., Montal M. Proc. Natl. Acad. Sci. U.S.A. 89:8220-8224(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Genomic structures of SCN2A and SCN3A -- candidate genes for deafness at the DFNA16 locus." Kasai N., Fukushima K., Ueki Y., Prasad S., Nosakowski J., Sugata K., Sugata A., Nishizaki K., Meyer N.C., Smith R.J.H. Gene 264:113-122(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[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. , 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]	"Isolation of the 5'-flanking region for human brain sodium channel subtype II alpha-Subunit (SCN2A)." Lu C.-M., Eichelberger J.S., Beckman M.L., Schade S.D., Brown G.B. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
[5]	"Differential expression of two sodium channel subtypes in human brain." Lu C.-M., Han J., Rado T.A., Brown G.B. FEBS Lett. 303:53-58(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1709-1994. Tissue: Brain.
[6]	"Direct amplification of a single dissected chromosomal segment by polymerase chain reaction: a human brain sodium channel gene is on chromosome 2q22-q23." Han J., Lu C.-M., Brown G.B., Rado T.A. Proc. Natl. Acad. Sci. U.S.A. 88:335-339(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1702-1772.
[7]	"A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction." Sugawara T., Tsurubuchi Y., Agarwala K.L., Ito M., Fukuma G., Mazaki-Miyazaki E., Nagafuji H., Noda M., Imoto K., Wada K., Mitsudome A., Kaneko S., Montal M., Nagata K., Hirose S., Yamakawa K. Proc. Natl. Acad. Sci. U.S.A. 98:6384-6389(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BFIS3 TRP-188, CHARACTERIZATION OF VARIANT BFIS3 TRP-188, VARIANTS LYS-19 AND GLN-524.
[8]	Erratum Sugawara T., Tsurubuchi Y., Agarwala K.L., Ito M., Fukuma G., Mazaki-Miyazaki E., Nagafuji H., Noda M., Imoto K., Wada K., Mitsudome A., Kaneko S., Montal M., Nagata K., Hirose S., Yamakawa K. Proc. Natl. Acad. Sci. U.S.A. 98:10515-10515(2001)
[9]	"Sodium-channel defects in benign familial neonatal-infantile seizures." Heron S.E., Crossland K.M., Andermann E., Phillips H.A., Hall A.J., Bleasel A., Shevell M., Mercho S., Seni M.H., Guiot M.C., Mulley J.C., Berkovic S.F., Scheffer I.E. Lancet 360:851-852(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BFIS3 PHE-1330 AND VAL-1563.
[10]	Erratum Heron S.E., Crossland K.M., Andermann E., Phillips H.A., Hall A.J., Bleasel A., Shevell M., Mercho S., Seni M.H., Guiot M.C., Mulley J.C., Berkovic S.F., Scheffer I.E. Lancet 360:1520-1520(2002)
[11]	"Sodium channels SCN1A, SCN2A and SCN3A in familial autism." Weiss L.A., Escayg A., Kearney J.A., Trudeau M., MacDonald B.T., Mori M., Reichert J., Buxbaum J.D., Meisler M.H. Mol. Psychiatry 8:186-194(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-19 AND THR-1902.
[12]	"Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy." Berkovic S.F., Heron S.E., Giordano L., Marini C., Guerrini R., Kaplan R.E., Gambardella A., Steinlein O.K., Grinton B.E., Dean J.T., Bordo L., Hodgson B.L., Yamamoto T., Mulley J.C., Zara F., Scheffer I.E. Ann. Neurol. 55:550-557(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BFIS3 GLN-223; ILE-892; ILE-1003 AND GLN-1319.
[13]	"A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in infancy (SMEI) inherited from a father with febrile seizures." Kimura K., Sugawara T., Mazaki-Miyazaki E., Hoshino K., Nomura Y., Tateno A., Hachimori K., Yamakawa K., Segawa M. Brain Dev. 27:424-430(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VAL-328.
[14]	"De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies." Ogiwara I., Ito K., Sawaishi Y., Osaka H., Mazaki E., Inoue I., Montal M., Hashikawa T., Shike T., Fujiwara T., Inoue Y., Kaneda M., Yamakawa K. Neurology 73:1046-1053(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIEE11 LYS-1211 AND MET-1473, VARIANTS LYS-19; VAL-328; GLN-524 AND VAL-575, CHARACTERIZATION OF VARIANTS EIEE11 LYS-1211 AND MET-1473, CHARACTERIZATION OF VARIANT VAL-575.
[15]	"Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy." Liao Y., Deprez L., Maljevic S., Pitsch J., Claes L., Hristova D., Jordanova A., Ala-Mello S., Bellan-Koch A., Blazevic D., Schubert S., Thomas E.A., Petrou S., Becker A.J., De Jonghe P., Lerche H. Brain 133:1403-1414(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BFIS3 VAL-252 AND MET-261.
[16]	"SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain." Liao Y., Anttonen A.K., Liukkonen E., Gaily E., Maljevic S., Schubert S., Bellan-Koch A., Petrou S., Ahonen V.E., Lerche H., Lehesjoki A.E. Neurology 75:1454-1458(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EIEE11 VAL-263.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M94055 mRNA. Translation: AAA18895.1.
AF059683 Genomic DNA. Translation: AAC14574.1.
AF327246 , AF327226, AF327227, AF327228, AF327229, AF327230, AF327231, AF327232, AF327233, AF327234, AF327235, AF327236, AF327237, AF327238, AF327239, AF327240, AF327241, AF327242, AF327243, AF327244, AF327245 Genomic DNA. Translation: AAG53413.1.
AF327246 , AF327226, AF327227, AF327228, AF327229, AF327230, AF327231, AF327232, AF327233, AF327234, AF327235, AF327236, AF327237, AF327238, AF327239, AF327240, AF327241, AF327242, AF327243, AF327244, AF327245 Genomic DNA. Translation: AAG53412.1.
AC011303 Genomic DNA. Translation: AAY14971.1.
AC013438 Genomic DNA. No translation available.
X65361 mRNA. Translation: CAA46438.1. Sequence problems.
M91804 mRNA. No translation available.
M55662 Genomic DNA. Translation: AAB65854.2.

IPI

IPI00220666.
IPI00305036.

PIR

A46269.
I59194.

RefSeq

NP_001035232.1. NM_001040142.1.
NP_001035233.1. NM_001040143.1.
NP_066287.2. NM_021007.2.

UniGene

Hs.93485.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KAV	NMR	-	A	1777-1882	[»]

ProteinModelPortal

Q99250.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99250. 3 interactions.

MINT

MINT-1388751.

STRING

9606.ENSP00000283256.

PTM databases

PhosphoSite

Q99250.

Polymorphism databases

DMDM

25014053.

Proteomic databases

PaxDb

Q99250.

PRIDE

Q99250.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000283256; ENSP00000283256; ENSG00000136531.
ENST00000357398; ENSP00000349973; ENSG00000136531.
ENST00000375427; ENSP00000364576; ENSG00000136531.
ENST00000375437; ENSP00000364586; ENSG00000136531.

GeneID

6326.

KEGG

hsa:6326.

UCSC

uc002udc.3. human.
uc002ude.3. human.

Organism-specific databases

CTD

6326.

GeneCards

GC02P166095.

H-InvDB

HIX0029932.

HGNC

HGNC:10588. SCN2A.

HPA

CAB022567.

MIM

182390. gene.
607745. phenotype.
613721. phenotype.

neXtProt

NX_Q99250.

Orphanet

140927. Benign familial neonatal-infantile seizures.
1934. Early infantile epileptic encephalopathy.
36387. Generalized epilepsy with febrile seizures-plus context.

PharmGKB

PA35004.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1226.

HOVERGEN

HBG053100.

InParanoid

Q99250.

KO

K04834.

OMA

EDPTARQ.

OrthoDB

EOG4Z36CT.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

Q99250.

Bgee

Q99250.

CleanEx

HS_SCN2A.

Genevestigator

Q99250.

GermOnline

ENSG00000136531. Homo sapiens.

Family and domain databases

InterPro

IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]

Pfam

PF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]

PRINTS

PR00170. NACHANNEL.

SMART

SM00015. IQ. 1 hit.
[Graphical view]

PROSITE

PS50096. IQ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q99250.

ChEMBL

CHEMBL4187.

ChiTaRS

SCN2A. human.

DrugBank

DB00555. Lamotrigine.

EvolutionaryTrace

Q99250.

GenomeRNAi

6326.

NextBio

24550.

SOURCE

Search...

Entry information

Entry name

SCN2A_HUMAN

Accession

Primary (citable) accession number: Q99250
Secondary accession number(s): A6NC14 , A6NIQ5, Q14472, Q53T77, Q9BZC9, Q9BZD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 8, 2002
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 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.