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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).

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     

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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