General Information of This Target
Target ID
BTDT00054
Target Name
Sodium channel protein type 5 subunit alpha (Scn5a)
Target Bioclass
Transporter and channel
Uniprot ID
P15389
3D Structure
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2D Sequence
3D Structure
Source
Predict by Alphafold2
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Alphafold Parameters: msa_mode: mmseqs2_uniref_env model_type: auto num_recycles: auto
Gene Name
Scn5a
Gene ID
25665
Synonym
Sodium channel protein cardiac muscle subunit alpha; Sodium channel protein type V subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.5
Sequence
MANLLLPRGTSSFRRFTRESLAAIEKRMAEKQARGGSATSQESREGLQEEEAPRPQLDLQ
ASKKLPDLYGNPPRELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHP
VRRAAVKILVHSLFSMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILAR
GFCLHAFTFLRDPWNWLDFSVIVMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTI
VGALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTELNGTNGSVEADGL
VWNSLDVYLNDPANYLLKNGTTDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFA
WAFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQ
NQATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVTNHERKSKRR
KRLSSGTEDGGDDRLPKSDSEDGPRALNQLSLTHGLSRTSMRPRSSRGSIFTFRRRDQGS
EADFADDENSTAGESESHRTSLLVPWPLRHPSAQGQPGPGASAPGYVLNGKRNSTVDCNG
VVSLLGAGDAEATSPGSYLLRPMVLDRPPDTTTPSEEPGGPQMLTPQAPCADGFEEPGAR
QRALSAVSVLTSALEELEESHRKCPPCWNRFAQHYLIWECCPLWMSIKQKVKFVVMDPFA
DLTITMCIVLNTLFMALEHYNMTAEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQ
GWNIFDSIIVILSLMELGLSRMGNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGAL
GNLTLVLAIIVFIFAVVGMQLFGKNYSELRHRISDSGLLPRWHMMDFFHAFLIIFRILCG
EWIETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDGEMN
NLQLALARIQRGLRFVKRTTWDFCCGILRRRPKKPAALATHSQLPSCITAPRSPPPPEVE
KVPPARKETRFEEDKRPGQGTPGDSEPVCVPIAVAESDTEDQEEDEENSLGTEEESSKQE
SQVVSGGHEPYQEPRAWSQVSETTSSEAGASTSQADWQQEQKTEPQAPGCGETPEDSYSE
GSTADMTNTADLLEQIPDLGEDVKDPEDCFTEGCVRRCPCCMVDTTQSPGKVWWRLRKTC
YRIVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKW
VAYGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFE
GMRVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIV
NNKSECESFNVTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQP
QWEDNLYMYIYFVVFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAM
KKLGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKVN
ILAKINLLFVAIFTGECIVKMAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFS
PTLFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMAN
FAYVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPNLPNSNGS
RGNCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIW
EKFDPEATQFIEYLALSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFT
KRVLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSATVIQRAFRRHLLQ
RSVKHASFLFRQQAGGSGLSDEDAPEREGLIAYMMNGNFSRRSAPLSSSSISSTSFPPSY
DSVTRATSDNLPVRASDYSRSEDLADFPPSPDRDRESIV

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Family
the sodium channel (TC 1.A.1.10) family
Function
This protein 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. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.

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Taxonomy ID
10116
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Rattus
Species: Rattus norvegicus
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    HWTX-IV IC50
>10 μM
[1]
 Toxin Info    Mu-conotoxin SmIIIA IC50
1.3 μM
[2- 6]
 Toxin Info    Mu-conotoxin PIIIA IC50
3.1 - 6.2 μM
[3- 12]
 Toxin Info    Mu-conotoxin BuIIIB IC50
9 μM
[3- 15]
References
Ref 1 Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena. Peptides. 2013 Jun;44:40-6. doi: 10.1016/j.peptides.2013.03.011. Epub 2013 Mar 19.
Ref 2 Mu-conotoxin SmIIIA, a potent inhibitor of tetrodotoxin-resistant sodium channels in amphibian sympathetic and sensory neurons. Biochemistry. 2002 Dec 24;41(51):15388-93. doi: 10.1021/bi0265628.
Ref 3 -Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10302-7. doi: 10.1073/pnas.1107027108. Epub 2011 Jun 7.
Ref 4 A novel -conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors. Br J Pharmacol. 2012 Jul;166(5):1654-68. doi: 10.1111/j.1476-5381.2012.01837.x.
Ref 5 Co-expression of Na(V) subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking -conotoxins. Br J Pharmacol. 2013 Apr;168(7):1597-610. doi: 10.1111/bph.12051.
Ref 6 Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA. J Biol Chem. 2003 Nov 21;278(47):46805-13. doi: 10.1074/jbc.M309222200. Epub 2003 Sep 10.
Ref 7 Definition of the M-conotoxin superfamily: characterization of novel peptides from molluscivorous Conus venoms. Biochemistry. 2005 Jun 7;44(22):8176-86. doi: 10.1021/bi047541b.
Ref 8 mu-Conotoxin PIIIA, a new peptide for discriminating among tetrodotoxin-sensitive Na channel subtypes. J Neurosci. 1998 Jun 15;18(12):4473-81. doi: 10.1523/JNEUROSCI.18-12-04473.1998.
Ref 9 Distinction among neuronal subtypes of voltage-activated sodium channels by mu-conotoxin PIIIA. J Neurosci. 2000 Jan 1;20(1):76-80. doi: 10.1523/JNEUROSCI.20-01-00076.2000.
Ref 10 Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus. Toxicon. 2009 Jan;53(1):90-8. doi: 10.1016/j.toxicon.2008.10.017. Epub 2008 Nov 20.
Ref 11 Structurally diverse -conotoxin PIIIA isomers block sodium channel NaV 1.4. Angew Chem Int Ed Engl. 2012 Apr 23;51(17):4058-61. doi: 10.1002/anie.201107011. Epub 2012 Mar 12.
Ref 12 Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels. J Biol Chem. 2002 Jul 26;277(30):27247-55. doi: 10.1074/jbc.M201611200. Epub 2002 May 2.
Ref 13 Characterization of the Conus bullatus genome and its venom-duct transcriptome. BMC Genomics. 2011 Jan 25;12:60. doi: 10.1186/1471-2164-12-60.
Ref 14 - and -subunit composition of voltage-gated sodium channels investigated with -conotoxins and the recently discovered O-conotoxin GVIIJ. J Neurophysiol. 2015 Apr 1;113(7):2289-301. doi: 10.1152/jn.01004.2014. Epub 2015 Jan 28.
Ref 15 Mammalian neuronal sodium channel blocker -conotoxin BuIIIB has a structured N-terminus that influences potency. ACS Chem Biol. 2013;8(6):1344-51. doi: 10.1021/cb300674x. Epub 2013 Apr 16.
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