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1.A.1.10.1
Voltage-sensitive Na+ channel, NaV1.7 (Cox et al., 2006). The human orthologue, SCN3A or Nav1.3, when mutated causes cryptogenic pediatric partial epilepsy (Holland et al., 2008; Zaman et al. 2020). Batrachotoxin (BTX) is a steroidal alkaloid neurotoxin that activates NaV channels through interacting with transmembrane domain-I-segment 6 (IS6) of these channels. Ginsenoside inhibits BTX binding (Lee et al. 2008). VGSCs are heterotrimeric complexes consisting of a single pore-forming alpha subunit joined by two beta subunits, a noncovalently linked beta1 or beta3 and a covalently linked beta2 or beta4 subunit (Hull and Isom 2017).  The binding mode and functional components of the analgesic-antitumour peptide from Buthus martensii Karsch to human voltage-gated sodium channel 1.7 have been characterized (Zhao et al. 2019). Dvorak et al. 2021 developed allosteric modulators of ion channels by targeting their PPI interfaces, particularly in the C-terminal domain of the Nav, with auxiliary proteins. Fenestrations are key functional regions of Nav that modulate drug binding, lipid binding, and influence gating behaviors (Gamal El-Din and Lenaeus 2022). Compartment-specific localizations and trafficking mechanisms for VGSCs are regulated separately to modulate membrane excitability in the brain (Liu et al. 2022). Naview is a library for drawing and annotating voltage-gated sodium channel membrane diagrams (Afonso et al. 2022). Deltamethrin (DLT) is a type-II pyrethroid ester insecticide used in agricultural and domestic applications as well as in public health. Exposure to DLT produced a differential and dose-dependent stimulation of peak Na+ currents, Conversely, tefluthrin (Tef), a type-I pyrethroid insecticide, accentuates I(Na) with a slowing in inactivation time course of the current (Lin et al. 2022). MicroRNA-335-5p suppresses voltage-gated sodium channel expression and may be a target for seizure control (Heiland et al. 2023).  Voltage-gated sodium channels are enhancing factors in the metastasis of metastatic prostate cancer cells (Yildirim-Kahriman 2023). Decreasing microtubule detyrosination modulates Nav1.5 subcellular distribution and restores sodium current in Mdx cardiomyocytes (Nasilli et al. 2024).  Multiple gating processes are associated with the distal end of TMS6 of domain II in Nav channels (Chen et al. 2025).

Accession Number:P08104
Protein Name:SCN3A aka Voltage-gated sodium channel subtype III
Length:1951
Molecular Weight:221387.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:22
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate sodium(1+)

Cross database links:

RefSeq: NP_037251.1   
Entrez Gene ID: 497770   
Pfam: PF00520    PF06512   
KEGG: rno:497770   

Gene Ontology

GO:0030424 C:axon
GO:0043025 C:neuronal cell body
GO:0001518 C:voltage-gated sodium channel complex
GO:0005516 F:calmodulin binding
GO:0031402 F:sodium ion binding
GO:0005248 F:voltage-gated sodium channel activity
GO:0071236 P:cellular response to antibiotic
GO:0007399 P:nervous system development
GO:0019228 P:regulation of action potential in neuron
GO:0046684 P:response to pyrethroid
GO:0009611 P:response to wounding
GO:0019233 P:sensory perception of pain
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport

References (1)

[1] “Primary structure of rat brain sodium channel III deduced from the cDNA sequence.”  Kayano T.et.al.   2449363
Structure:
1QG9     

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAQALLVPPG PESFRLFTRE SLAAIEKRAA EEKAKKPKKE QDIDDENKPK PNSDLEAGKN 
61:	LPFIYGDIPP EMVSEPLEDL DPYYVSKKTF VVLNKGKAIF RFSATSALYI LTPLNPVRKI 
121:	AIKILVHSLF SMLIMCTILT NCVFMTLSNP PDWTKNVEYT FTGIYTFESL IKILARGFCL 
181:	EDFTFLRDPW NWLDFSVIVM AYVTEFVDLG NVSALRTFRV LRALKTISVI PGLKTIVGAL 
241:	IQSVKKLSDV MILTVFCLSV FALIGLQLFM GNLRNKCSQW PPSDSAFETN TTSYFNGTMD 
301:	SNGTFVNVTM STFNWKDYIA DDSHFYVLDG QKDPLLCGNG SDAGQCPEGY ICVKAGRNPN 
361:	YGYTSFDTFS WAFLSLFRLM TQDYWENLYQ LTLRAAGKTY MIFFVLVIFL GSFYLVNLIL 
421:	AVVAMAYEEQ NQATLEEAEQ KEAEFQQMLE QLKKQQEEAQ AVAAASAASR DFSGIGGLGE 
481:	LLESSSEASK LSSKSAKEWR NRRKKRRQRE HLEGNHRADG DRFPKSESED SVKRRSFLLS 
541:	LDGNPLTGDK KLCSPHQSLL SIRGSLFSPR RNSKTSIFSF RGRAKDVGSE NDFADDEHST 
601:	FEDSESRRDS LFVPHRPGER RNSNGTTTET EVRKRRLSSY QISMEMLEDS SGRQRSMSIA 
661:	SILTNTMEEL EESRQKCPPC WYRFANVFLI WDCCDAWLKV KHLVNLIVMD PFVDLAITIC 
721:	IVLNTLFMAM EHYPMTQQFS SVLTVGNLVF TGIFTAEMVL KIIAMDPYYY FQEGWNIFDG 
781:	IIVSLSLMEL GLANVEGLSV LRSFRLLRVF KLAKSWPTLN MLIKIIGNSV GALGNLTLVL 
841:	AIIVFIFAVV GMQLFGKSYK ECVCKINVDC KLPRWHMNDF FHSFLIVFRV LCGEWIETMW 
901:	DCMEVAGQTM CLIVFMLVMV IGNLVVLNLF LALLLSSFSS DNLAATDDDN EMNNLQIAVG 
961:	RMQKGIDFVK NKIRECFRKA FFRKPKVIEI QEGNKIDSCM SNNTGIEISK ELNYLKDGNG 
1021:	TTSGVGTGSS VEKYVIDEND YMSFINNPSL TVTVPIAVGE SDFENLNTEE FSSESELEES 
1081:	KEKLNATSSS EGSTVDVAPP REGEQAEIEP EEDLKPEACF TEGCIKKFPF CQVSTEEGKG 
1141:	KIWWNLRKTC YSIVEHNWFE TFIVFMILLS SGALAFEDIY IEQRKTIKTM LEYADKVFTY 
1201:	IFILEMLLKW VAYGFQTYFT NAWCWLDFLI VDVSLVSLVA NALGYSELGA IKSLRTLRAL 
1261:	RPLRALSRFE GMRVVVNALV GAIPSIMNVL LVCLIFWLIF SIMGVNLFAG KFYHCVNTTT 
1321:	GNMFEIKEVN NFSDCQALGK QARWKNVKVN FDNVGAGYLA LLQVATFKGW MDIMYAAVDS 
1381:	RDVKLQPIYE ENLYMYLYFV IFIIFGSFFT LNLFIGVIID NFNQQKKKFG GQDIFMTEEQ 
1441:	KKYYNAMKKL GSKKPQKPIP RPANKFQGMV FDFVTRQVFD ISIMILICLN MVTMMVETDD 
1501:	QSKYMTLVLS RINLVFIVLF TGEFLLKLIS LRYYYFTIGW NIFDFVVVIL SIVGMFLAEL 
1561:	IEKYFVSPTL FRVIRLARIG RILRLIKGAK GIRTLLFALM MSLPALFNIG LLLFLVMFIY 
1621:	AIFGMSNFAY VKKEAGIDDM FNFETFGNSM ICLFQITTSA GWDGLLAPIL NSAPPDCDPD 
1681:	AIHPGSSVKG DCGNPSVGIF FFVSYIIISF LVVVNMYIAV ILENFSVATE ESAEPLSEDD 
1741:	FEMFYEVWEK FDPDATQFIE FCKLSDFAAA LDPPLLIAKP NKVQLIAMDL PMVSGDRIHC 
1801:	LDILFAFTKR VLGESGEMDA LRIQMEDRFM ASNPSKVSYE PITTTLKRKQ EEVSAAIIQR 
1861:	NYRCYLLKQR LKNISSKYDK ETIKGRIDLP IKGDMVIDKL NGNSTPEKTD GSSSTTSPPS 
1921:	YDSVTKPDKE KFEKDKPEKE IKGKEVRENQ K