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Protein

Sodium channel protein type 3 subunit alpha

Gene

Scn3a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, forms a sodium-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient (PubMed:29142310). May contribute to the regulation of serotonin/5-hydroxytryptamine release by enterochromaffin cells (PubMed:29142310). In pancreatic endocrine cells, required for both glucagon and glucose-induced insulin secretion (PubMed:25172946).2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-MMU-5576892 Phase 0 - rapid depolarisation

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel protein type 3 subunit alpha
Alternative name(s):
Sodium channel protein brain III subunit alpha
Sodium channel protein type III subunit alpha
Voltage-gated sodium channel subtype III
Voltage-gated sodium channel subunit alpha Nav1.3
Gene namesi
Name:Scn3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:98249 Scn3a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 128CytoplasmicCuratedAdd BLAST128
Transmembranei129 – 147Helical; Name=S1 of repeat IBy similarityAdd BLAST19
Topological domaini148 – 154ExtracellularCurated7
Transmembranei155 – 175Helical; Name=S2 of repeat IBy similarityAdd BLAST21
Topological domaini176 – 189CytoplasmicCuratedAdd BLAST14
Transmembranei190 – 207Helical; Name=S3 of repeat IBy similarityAdd BLAST18
Topological domaini208 – 213ExtracellularCurated6
Transmembranei214 – 230Helical; Name=S4 of repeat IBy similarityAdd BLAST17
Topological domaini231 – 249CytoplasmicCuratedAdd BLAST19
Transmembranei250 – 269Helical; Name=S5 of repeat IBy similarityAdd BLAST20
Topological domaini270 – 368ExtracellularCuratedAdd BLAST99
Intramembranei369 – 393Pore-formingBy similarityAdd BLAST25
Topological domaini394 – 400ExtracellularCurated7
Transmembranei401 – 421Helical; Name=S6 of repeat IBy similarityAdd BLAST21
Topological domaini422 – 711CytoplasmicCuratedAdd BLAST290
Transmembranei712 – 730Helical; Name=S1 of repeat IIBy similarityAdd BLAST19
Topological domaini731 – 741ExtracellularCuratedAdd BLAST11
Transmembranei742 – 761Helical; Name=S2 of repeat IIBy similarityAdd BLAST20
Topological domaini762 – 775CytoplasmicCuratedAdd BLAST14
Transmembranei776 – 795Helical; Name=S3 of repeat IIBy similarityAdd BLAST20
Topological domaini796 – 797ExtracellularCurated2
Transmembranei798 – 815Helical; Name=S4 of repeat IIBy similarityAdd BLAST18
Topological domaini816 – 831CytoplasmicCuratedAdd BLAST16
Transmembranei832 – 850Helical; Name=S5 of repeat IIBy similarityAdd BLAST19
Topological domaini851 – 879ExtracellularCuratedAdd BLAST29
Intramembranei880 – 900Pore-formingBy similarityAdd BLAST21
Topological domaini901 – 913ExtracellularCuratedAdd BLAST13
Transmembranei914 – 934Helical; Name=S6 of repeat IIBy similarityAdd BLAST21
Topological domaini935 – 1158CytoplasmicCuratedAdd BLAST224
Transmembranei1159 – 1177Helical; Name=S1 of repeat IIIBy similarityAdd BLAST19
Topological domaini1178 – 1190ExtracellularCuratedAdd BLAST13
Transmembranei1191 – 1209Helical; Name=S2 of repeat IIIBy similarityAdd BLAST19
Topological domaini1210 – 1223CytoplasmicCuratedAdd BLAST14
Transmembranei1224 – 1242Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini1243 – 1250ExtracellularCurated8
Transmembranei1251 – 1269Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini1270 – 1286CytoplasmicCuratedAdd BLAST17
Transmembranei1287 – 1306Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini1307 – 1355ExtracellularCuratedAdd BLAST49
Intramembranei1356 – 1377Pore-formingBy similarityAdd BLAST22
Topological domaini1378 – 1394ExtracellularCuratedAdd BLAST17
Transmembranei1395 – 1416Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1417 – 1479CytoplasmicCuratedAdd BLAST63
Transmembranei1480 – 1497Helical; Name=S1 of repeat IVBy similarityAdd BLAST18
Topological domaini1498 – 1508ExtracellularCuratedAdd BLAST11
Transmembranei1509 – 1527Helical; Name=S2 of repeat IVBy similarityAdd BLAST19
Topological domaini1528 – 1539CytoplasmicCuratedAdd BLAST12
Transmembranei1540 – 1557Helical; Name=S3 of repeat IVBy similarityAdd BLAST18
Topological domaini1558 – 1570ExtracellularCuratedAdd BLAST13
Transmembranei1571 – 1587Helical; Name=S4 of repeat IVBy similarityAdd BLAST17
Topological domaini1588 – 1606CytoplasmicCuratedAdd BLAST19
Transmembranei1607 – 1624Helical; Name=S5 of repeat IVBy similarityAdd BLAST18
Topological domaini1625 – 1646ExtracellularCuratedAdd BLAST22
Intramembranei1647 – 1669Pore-formingBy similarityAdd BLAST23
Topological domaini1670 – 1699ExtracellularCuratedAdd BLAST30
Transmembranei1700 – 1722Helical; Name=S6 of repeat IVBy similarityAdd BLAST23
Topological domaini1723 – 1947CytoplasmicCuratedAdd BLAST225

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004448991 – 1947Sodium channel protein type 3 subunit alphaAdd BLAST1947

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi211N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi277 ↔ 346By similarity
Glycosylationi290N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi296N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi302N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi307N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi339N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei484PhosphoserineBy similarity1
Modified residuei485PhosphoserineBy similarity1
Modified residuei486PhosphoserineBy similarity1
Disulfide bondi862Interchain; with SCN2B or SCN4BBy similarity
Disulfide bondi862Interchain; with the conotoxin GVIIJ (when the channel is not linked to SCN2B or SCN4B; the bond to SCN2B or SCN4B protects the channel from the inhibition by toxin)By similarity
Disulfide bondi902 ↔ 911By similarity
Glycosylationi1318N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1332N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1453PhosphoserineBy similarity1

Post-translational modificationi

May be ubiquitinated by NEDD4L; which would promote its endocytosis.By similarity
Phosphorylation at Ser-1453 in a highly conserved cytoplasmic loop slows inactivation of the channel and reduces peak sodium currents.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiA2ASI5
PaxDbiA2ASI5
PeptideAtlasiA2ASI5
PRIDEiA2ASI5

PTM databases

iPTMnetiA2ASI5
PhosphoSitePlusiA2ASI5
SwissPalmiA2ASI5

Expressioni

Tissue specificityi

Expressed in enterochromaffin cells in both colon and small bowel (at protein level) (PubMed:29142310). Expressed in pancreatic alpha and beta cells (PubMed:25172946).2 Publications

Developmental stagei

Expressed in the hippocampus at late embryonic stages and during the first week after birth. Down-regulated after postnatal day 7.1 Publication

Gene expression databases

BgeeiENSMUSG00000057182 Expressed in 140 organ(s), highest expression level in central nervous system
ExpressionAtlasiA2ASI5 baseline and differential

Interactioni

Subunit structurei

Heterooligomer of a large alpha subunit and 2-3 smaller beta subunits. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Interacts with NEDD4L.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097647

Structurei

3D structure databases

ProteinModelPortaliA2ASI5
SMRiA2ASI5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati110 – 455ICuratedAdd BLAST346
Repeati693 – 965IICuratedAdd BLAST273
Repeati1140 – 1451IIICuratedAdd BLAST312
Repeati1460 – 1758IVCuratedAdd BLAST299
Domaini1852 – 1881IQPROSITE-ProRule annotationAdd BLAST30

Domaini

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.By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2301 Eukaryota
ENOG410XNP6 LUCA
GeneTreeiENSGT00830000128242
HOGENOMiHOG000231755
HOVERGENiHBG053100
InParanoidiA2ASI5
OMAiHYPMTGQ
OrthoDBiEOG091G00FK
PhylomeDBiA2ASI5
TreeFamiTF323985

Family and domain databases

Gene3Di1.20.120.350, 4 hits
InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR001696 Na_channel_asu
IPR010526 Na_trans_assoc
IPR024583 Na_trans_cytopl
IPR027359 Volt_channel_dom_sf
PfamiView protein in Pfam
PF00520 Ion_trans, 4 hits
PF06512 Na_trans_assoc, 1 hit
PF11933 Na_trans_cytopl, 2 hits
PRINTSiPR00170 NACHANNEL

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: A2ASI5-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAQALLVPPG PESFRLFTRE SLAAIEKRAA EEKAKKPKKE QDIDDENKPK
60 70 80 90 100
PNSDLEAGKN LPFIYGDIPP EMVSEPLEDL DPYYVSKKTF VVLNKGKAIF
110 120 130 140 150
RFSATSALYI LTPLNPVRKI AIKILVHSLF SMLIMCTILT NCVFMTLSNP
160 170 180 190 200
PDWTKNVEYT FTGIYTFESL IKILARGFCL EDFTFLRDPW NWLDFSVIVM
210 220 230 240 250
AYVTEFVDLG NVSALRTFRV LRALKTISVI PGLKTIVGAL IQSVKKLSDV
260 270 280 290 300
MILTVFCLSV FALIGLQLFM GNLRNKCLQW PPSDSAFEIN TTSYFNGTMD
310 320 330 340 350
SNGTFVNVTM STFNWKDYIA DDSHFYVLDG QKDPLLCGNG SDAGQCPEGY
360 370 380 390 400
ICVKAGRNPN YGYTSFDTFS WAFLSLFRLM TQDYWENLYQ LTLRAAGKTY
410 420 430 440 450
MIFFVLVIFL GSFYLVNLIL AVVAMAYEEQ NQATLEEAEQ KEAEFQQMLE
460 470 480 490 500
QLKKQQEEAQ AVAAASAASR DFSGIGGLGE LLESSSEASK LSSKSAKEWR
510 520 530 540 550
NRRKKRRQRE HLEGNHRPEG DRFPKSESED SVKRRSFLFS LDGNPLSGDK
560 570 580 590 600
KLCSPHQSLL SIRGSLFSPR RNSKTSIFSF RGRAKDVGSE NDFADDEHST
610 620 630 640 650
FEDSESRRDS LFVPHRPGER RNSNGTTTET EVRKRRLSSY QISMEMLEDS
660 670 680 690 700
SGRQRAMSIA SILTNTMEEL EESRQKCPPC WYRFANVFLI WDCCDSWLKV
710 720 730 740 750
KHLVNLIVMD PFVDLAITIC IVLNTLFMAM EHYPMTEQFS SVLTVGNLVF
760 770 780 790 800
TGIFTAEMVL KIIAMDPYYY FQEGWNIFDG IIVSLSLMEL GLANVEGLSV
810 820 830 840 850
LRSFRLLRVF KLAKSWPTLN MLIKIIGNSV GALGNLTLVL AIIVFIFAVV
860 870 880 890 900
GMQLFGKSYK ECVCKINEDC KLPRWHMNDF FHSFLIVFRV LCGEWIETMW
910 920 930 940 950
DCMEVAGQTM CLIVFMLVMV IGNLVVLNLF LALLLSSFSS DNLAATDDDN
960 970 980 990 1000
EMNNLQIAVG RMQKGIDYVK NKIRECFRKA FFRKPKVIEI HEGNKIDSCM
1010 1020 1030 1040 1050
SNNTGVVEIS KELNYLKDGN GTTSGVGTGS SVEKYVIDEN DYMSFINNPS
1060 1070 1080 1090 1100
LTVTVPIAVG ESDFENLNTE EFSSESELEE SKEKLNATSS SEGSTVDVAP
1110 1120 1130 1140 1150
PREGEQAEIE PEEDLKPEAC FTEGCIKKFP FCQVSTEEGK GKIWWNLRKT
1160 1170 1180 1190 1200
CYSIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT
1210 1220 1230 1240 1250
YIFILEMLLK WVAYGFQTYF TNAWCWLDFL IVDVSLVSLV ANALGYSELG
1260 1270 1280 1290 1300
AIKSLRTLRA LRPLRALSRF EGMRVVVNAL VGAIPSIMNV LLVCLIFWLI
1310 1320 1330 1340 1350
FSIMGVNLFA GKFYHCVNMT TGSMFDMSEV NNFSDCQALG KQARWKNVKV
1360 1370 1380 1390 1400
NFDNVGAGYL ALLQVATFKG WMDIMYAAVD SRDVKLQPVY EENLYMYLYF
1410 1420 1430 1440 1450
VIFIIFGSFF TLNLFIGVII DNFNQQKKKF GGQDIFMTEE QKKYYNAMKK
1460 1470 1480 1490 1500
LGSKKPQKPI PRPANKFQGM VFDFVTRQVF DISIMILICL NMVTMMVETD
1510 1520 1530 1540 1550
DQSKYMTLVL SRINLVFIVL FTGEFLLKLI SLRYYYFTIG WNIFDFVVVI
1560 1570 1580 1590 1600
LSIVGMFLAE LIEKYFVSPT LFRVIRLARI GRILRLIKGA KGIRTLLFAL
1610 1620 1630 1640 1650
MMSLPALFNI GLLLFLVMFI YAIFGMSNFA YVKKEAGIDD MFNFETFGNS
1660 1670 1680 1690 1700
MICLFQITTS AGWDGLLAPI LNSAPPDCDP DAIHPGSSVK GDCGNPSVGI
1710 1720 1730 1740 1750
FFFVSYIIIS FLVVVNMYIA VILENFSVAT EESAEPLSED DFEMFYEVWE
1760 1770 1780 1790 1800
KFDPDATQFI EFCKLSDFAA ALDPPLLIAK PNKVQLIAMD LPMVSGDRIH
1810 1820 1830 1840 1850
CLDILFAFTK RVLGESGEMD ALRIQMEDRF MASNPSKVSY EPITTTLKRK
1860 1870 1880 1890 1900
QEEVSAAIIQ RNYRCYLLKQ RLKNISNTYD KETIKGRIVL PIKGDMVIDK
1910 1920 1930 1940
LNGNSTPEKT DGSSSTTSPP SYDSVTKPDK EKFEKDKPEK ESKGKEV
Length:1,947
Mass (Da):220,880
Last modified:February 5, 2008 - v1
Checksum:iB5E01EEC78004E15
GO
Isoform 2 (identifier: A2ASI5-2) [UniParc]FASTAAdd to basket
Also known as: CbmNav1.3a

The sequence of this isoform differs from the canonical sequence as follows:
     624-624: N → NVSQ

Show »
Length:1,950
Mass (Da):221,195
Checksum:i3BAC44B08B9B8D39
GO
Isoform 3 (identifier: A2ASI5-3) [UniParc]FASTAAdd to basket
Also known as: CbmNav1.3b

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: D → S
     624-624: N → NVSQ

Show »
Length:1,950
Mass (Da):221,167
Checksum:i783A81360E03112F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6U9Y2F6U9Y2_MOUSE
Sodium channel protein type 3 subun...
Scn3a
122Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti494K → R1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_059662208D → S in isoform 3. 1
Alternative sequenceiVSP_059663624N → NVSQ in isoform 2 and isoform 3. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
KM373689 mRNA Translation: AIW80041.1
KM373690 mRNA Translation: AIW80042.1
AL772235 Genomic DNA No translation available.
AL928621 Genomic DNA No translation available.
CCDSiCCDS50596.1 [A2ASI5-1]
RefSeqiNP_061202.3, NM_018732.3 [A2ASI5-1]
XP_011237695.1, XM_011239393.1
XP_017172210.1, XM_017316721.1
UniGeneiMm.330256

Genome annotation databases

EnsembliENSMUST00000066432; ENSMUSP00000065023; ENSMUSG00000057182 [A2ASI5-1]
ENSMUST00000100069; ENSMUSP00000097647; ENSMUSG00000057182 [A2ASI5-1]
GeneIDi20269
UCSCiuc012bwa.1 mouse [A2ASI5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
KM373689 mRNA Translation: AIW80041.1
KM373690 mRNA Translation: AIW80042.1
AL772235 Genomic DNA No translation available.
AL928621 Genomic DNA No translation available.
CCDSiCCDS50596.1 [A2ASI5-1]
RefSeqiNP_061202.3, NM_018732.3 [A2ASI5-1]
XP_011237695.1, XM_011239393.1
XP_017172210.1, XM_017316721.1
UniGeneiMm.330256

3D structure databases

ProteinModelPortaliA2ASI5
SMRiA2ASI5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097647

PTM databases

iPTMnetiA2ASI5
PhosphoSitePlusiA2ASI5
SwissPalmiA2ASI5

Proteomic databases

MaxQBiA2ASI5
PaxDbiA2ASI5
PeptideAtlasiA2ASI5
PRIDEiA2ASI5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000066432; ENSMUSP00000065023; ENSMUSG00000057182 [A2ASI5-1]
ENSMUST00000100069; ENSMUSP00000097647; ENSMUSG00000057182 [A2ASI5-1]
GeneIDi20269
UCSCiuc012bwa.1 mouse [A2ASI5-1]

Organism-specific databases

CTDi6328
MGIiMGI:98249 Scn3a

Phylogenomic databases

eggNOGiKOG2301 Eukaryota
ENOG410XNP6 LUCA
GeneTreeiENSGT00830000128242
HOGENOMiHOG000231755
HOVERGENiHBG053100
InParanoidiA2ASI5
OMAiHYPMTGQ
OrthoDBiEOG091G00FK
PhylomeDBiA2ASI5
TreeFamiTF323985

Enzyme and pathway databases

ReactomeiR-MMU-5576892 Phase 0 - rapid depolarisation

Miscellaneous databases

SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000057182 Expressed in 140 organ(s), highest expression level in central nervous system
ExpressionAtlasiA2ASI5 baseline and differential

Family and domain databases

Gene3Di1.20.120.350, 4 hits
InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR001696 Na_channel_asu
IPR010526 Na_trans_assoc
IPR024583 Na_trans_cytopl
IPR027359 Volt_channel_dom_sf
PfamiView protein in Pfam
PF00520 Ion_trans, 4 hits
PF06512 Na_trans_assoc, 1 hit
PF11933 Na_trans_cytopl, 2 hits
PRINTSiPR00170 NACHANNEL
ProtoNetiSearch...

Entry informationi

Entry nameiSCN3A_MOUSE
AccessioniPrimary (citable) accession number: A2ASI5
Secondary accession number(s): A0A0R5RP23, A0A0R5RP41
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 18, 2018
Last sequence update: February 5, 2008
Last modified: November 7, 2018
This is version 95 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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