Target Information

General Information of This Target
Target ID
BTDT00035
Target Name
Sodium channel protein type 1 subunit alpha (Scn1a)
Target Bioclass
Transporter and channel
Uniprot ID
P04774
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
Scn1a
Gene ID
81574
Synonym
Sodium channel protein brain I subunit alpha; Sodium channel protein type I subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.1
Sequence
MEQTVLVPPGPDSFNFFTRESLAAIERRIAEEKAKNPKPDKKDDDENGPKPNSDLEAGKN
LPFIYGDIPPEMVSEPLEDLDPYYINKKTFIVLNKGKAIFRFSATSALYILTPFNPLRKI
AIKILVHSLFSMLIMCTILTNCVFMTMSNPPDWTKNVEYTFTGIYTFESLIKIIARGFCL
EDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGAL
IQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCVQWPPTNASLEEHSIEKNVTTDY
NGTLVNETVFEFDWKSYIQDSRYHYFLEGVLDALLCGNSSDAGQCPEGYMCVKAGRNPNY
GYTSFDTFSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILA
VVAMAYEEQNQATLEEAEQKEAEFQQMLEQLKKQQEAAQQAAAATASEHSREPSAAGRLS
DSSSEASKLSSKSAKERRNRRKKRKQKEQSGGEEKDDDEFHKSESEDSIRRKGFRFSIEG
NRLTYEKRYSSPHQSLLSIRGSLFSPRRNSRTSLFSFRGRAKDVGSENDFADDEHSTFED
NESRRDSLFVPRRHGERRNSNLSQTSRSSRMLAGLPANGKMHSTVDCNGVVSLVGGPSVP
TSPVGQLLPEVIIDKPATDDNGTTTETEMRKRRSSSFHVSMDFLEDPSQRQRAMSIASIL
TNTVEELEESRQKCPPCWYKFSNIFLIWDCSPYWLKVKHIVNLVVMDPFVDLAITICIVL
NTLFMAMEHYPMTEHFNHVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIV
TLSLVELGLANVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAII
VFIFAVVGMQLFGKSYKDCVCKIATDCKLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCM
EVAGQAMCLTVFMMVMVIRNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMH
KGVAYVKRKIYEFIQQSFVRKQKILDEIKPLDDLNNRKDNCTSNHTTEIGKDLDCLKDVN
GTTSGIGTGSSVEKYIIDESDYMSFINNPSLTVTVPIAVGESDFENLNTEDFSSESDLEE
SKEKLNESSSSSEGSTVDIGAPAEEQPVMEPEETLEPEACFTEGCVQRFKCCQISVEEGR
GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFT
YIFILEMLLKWVAYGYQTYFTNAWCWLDFLIVDVSLVSLTANALGYSELGAIKSLRTLRA
LRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCVNTT
TGDTFEITEVNNHSDCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYA
AVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFM
TEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMV
ETDDQSDYVTSILSRINLVFIVLFTGECVLKLISLRHYYFTIGWNIFDFVVVILSIVGMF
LAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLV
MFIYAIFGMSNFAYVKREVGIDDMFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPD
CDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPL
SEDDFEMFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGD
RIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTTLKRKQEEVSAV
IIQRAYRRHLLKRTVKQASFTYNKNKLKGGANLLVKEDMIIDRINENSITEKTDLTMSTA
ACPPSYDRVTKPIVEKHEQEGKDEKAKGK

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Family
the sodium channel (TC 1.A.1.10) family
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. Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons. Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli.

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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    Mu-conotoxin SmIIIA Dissociation constant
3.8 nM
 [1- 5]
 Toxin Info    Mu-conotoxin BuIIIB Dissociation constant
360 nM
 [2- 9]
 Toxin Info    Mu-conotoxin PIIIA IC50
120 nM
 [2- 14]
 Toxin Info    Mu-conotoxin GIIIA IC50
260 nM
 [2- 25]
 Toxin Info    Mu-conotoxin SxIIIA IC50
370 nM
 [2- 26]
References
Ref 1 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 2 -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 3 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 4 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 5 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 6 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 7 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 8 - 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 9 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.
Ref 10 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 11 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 12 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 13 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 14 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 15 Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014 Mar 24;5:3521. doi: 10.1038/ncomms4521.
Ref 16 Conus geographus toxins that discriminate between neuronal and muscle sodium channels. J Biol Chem. 1985 Aug 5;260(16):9280-8.
Ref 17 The amino acid sequences of homologous hydroxyproline-containing myotoxins from the marine snail Conus geographus venom. FEBS Lett. 1983 May 8;155(2):277-80. doi: 10.1016/0014-5793(82)80620-0.
Ref 18 Disulfide pairings in geographutoxin I, a peptide neurotoxin from Conus geographus. FEBS Lett. 1990 May 7;264(1):29-32. doi: 10.1016/0014-5793(90)80756-9.
Ref 19 Active site of mu-conotoxin GIIIA, a peptide blocker of muscle sodium channels. J Biol Chem. 1991 Sep 15;266(26):16989-91.
Ref 20 Action of derivatives of mu-conotoxin GIIIA on sodium channels. Single amino acid substitutions in the toxin separately affect association and dissociation rates. Biochemistry. 1992 Sep 8;31(35):8229-38. doi: 10.1021/bi00150a016.
Ref 21 Role of hydroxyprolines in the in vitro oxidative folding and biological activity of conotoxins. Biochemistry. 2008 Feb 12;47(6):1741-51. doi: 10.1021/bi701934m. Epub 2008 Jan 12.
Ref 22 NMR Structure of -Conotoxin GIIIC: Leucine 18 Induces Local Repacking of the N-Terminus Resulting in Reduced Na(V) Channel Potency. Molecules. 2018 Oct 22;23(10):2715. doi: 10.3390/molecules23102715.
Ref 23 Solution structure of mu-conotoxin GIIIA analysed by 2D-NMR and distance geometry calculations. FEBS Lett. 1991 Jan 28;278(2):160-6. doi: 10.1016/0014-5793(91)80107-e.
Ref 24 Tertiary structure of conotoxin GIIIA in aqueous solution. Biochemistry. 1991 Jul 16;30(28):6908-16. doi: 10.1021/bi00242a014.
Ref 25 Structure-activity relationships of mu-conotoxin GIIIA: structure determination of active and inactive sodium channel blocker peptides by NMR and simulated annealing calculations. Biochemistry. 1992 Dec 22;31(50):12577-84. doi: 10.1021/bi00165a006.
Ref 26 NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA. J Am Chem Soc. 2008 Oct 29;130(43):14280-6. doi: 10.1021/ja804303p. Epub 2008 Oct 3.
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