Target Information

General Information of This Target
Target ID
BTDT00025
Target Name
Sodium channel protein type 8 subunit alpha (Scn8a)
Target Bioclass
Transporter and channel
Uniprot ID
O88420
3D Structure
Download
2D Sequence
3D Structure
Source
Predict by Alphafold2
?
Alphafold Parameters: msa_mode: mmseqs2_uniref_env model_type: auto num_recycles: auto
Gene Name
Scn8a
Gene ID
29710
Synonym
Peripheral nerve protein type 4; Sodium channel 6; Sodium channel protein type VIII subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.6
Sequence
MAARLLAPPGPDSFKPFTPESLANIERRIAESKLKKPPKADGSHREDDEDSKPKPNSDLE
AGKSLPFIYGDIPQGLVAVPLEDFDPYYLTQKTFVVLNRGKTLFRFSATPALYILSPFNL
IRRIAIKILIHSVFSMIIMCTILTNCVFMTFSNPPEWSKNVEYTFTGIYTFESLVKIIAR
GFCIDGFTFLRDPWNWLDFSVIMMAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTI
VGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCVVWPINFNESYLENGTRGF
DWEEYINNKTNFYMVPGMLEPLLCGNSSDAGQCPEGFQCMKAGRNPNYGYTSFDTFSWAF
LALFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFVGSFYLVNLILAVVAMAYEEQNQA
TLEEAEQKEAEFKAMLEQLKKQQEEAQAAAMATSAGTVSEDAIEEEGEDGVGSPRSSSEL
SKLSSKSAKERRNRRKKRKQKELSEGEEKGDPEKVFKSESEDGMRRKAFRLPDNRIGRKF
SIMNQSLLSIPGSPFLSRHNSKSSIFSFRGPGRFRDPGSENEFADDEHSTVEESEGRRDS
LFIPIRARERRSSYSGYSGYSQCSRSSRIFPSLRRSVKRNSTVDCNGVVSLIGPGSHIGR
LLPEATTEVEIKKKGPGSLLVSMDQLASYGRKDRINSIMSVVTNTLVEELEESQRKCPPC
WYKFANTFLIWECHPYWIKLKEIVNLIVMDPFVDLAITICIVLNTLFMAMEHHPMTPQFE
HVLAVGNLVFTGIFTAEMFLKLIAMDPYYYFQEGWNIFDGFIVSLSLMELSLADVEGLSV
LRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYK
ECVCKINQECKLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVFMMVMV
IGNLVVLNLFLALLLSSFSADNLAATDDDGEMNNLQISVIRIKKGVAWTKVKVHAFMQAH
FKQREADEVKPLDELYEKKANCIANHTGVDIHRNGDFQKNGNGTTSGIGSSVEKYIIDED
HMSFINNPNLTVRVPIAVGESDFENLNTEDVSSESDPEGSKDKLDDTSSSEGSTIDIKPE
VEEVPVEQPEEYLDPDACFTEGCVQRFKCCQVNIEEGLGKSWWILRKTCFLIVEHNWFET
FIIFMILLSSGALAFEDIYIEQRKTIRTILEYADKVFTYIFILEMLLKWTAYGFVKFFTN
AWCWLDFLIVAVSLVSLIANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALVG
AIPSIMNVLLVCLIFWLIFSIMGVNLFAGKYHYCFNETSEIRFEIDIVNNKTDCEKLMEG
NSTEIRWKNVKINFDNVGAGYLALLQVATFKGWMDIMYAAVDSRKPDEQPDYEGNIYMYI
YFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNAMKKLGSKKPQK
PIPRPLNKIQGIVFDFVTQQAFDIVIMMLICLNMVTMMVETDTQSKQMENILYWINLVFV
IFFTCECVLKMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVSPTLFRVIRLA
RIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIFSIFGMSNFAYVKHEAGI
DDMFNFETFGNSMICLFQITTSAGWDGLLLPILNRPPDCSLDKEHPGSGFKGDCGNPSVG
IFFFVSYIIISFLIVVNMYIAIILENFSVATEESADPLSEDDFETFYEIWEKFDPDATQF
IEYCKLADFADALEHPLRVPKPNTIELIAMDLPMVSGDRIHCLDILFAFTKRVLGDSGEL
DILRQQMEERFVASNPSKVSYEPITTTLRRKQEEVSAVVLQRAYRGHLARRGFICRKMAS
NKLENGGTHRDKKESTPSTASLPSYDSVTKPDKEKQQRAEEGRRERAKRQKEVRESKC

    Click to Show/Hide
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.

    Click to Show/Hide
Taxonomy ID
10116
        Click to Show/Hide the Complete Species Lineage
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
69 nM
 [1- 5]
 Toxin Info    Mu-conotoxin SrVA Inhibition rate
14 %
 [6], [7], [8]
 Toxin Info    APETx2 Inhibition rate
17 %
 [9- 18]
 Toxin Info    Mu-conotoxin SmIIIA IC50
160 nM
 [1- 5]
 Toxin Info    Mu-conotoxin BuIIIB IC50
>30 μM
 [2- 22]
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 Identification, by RT-PCR, of four novel T-1-superfamily conotoxins from the vermivorous snail Conus spurius from the Gulf of Mexico. Peptides. 2009 Aug;30(8):1396-404. doi: 10.1016/j.peptides.2009.05.003. Epub 2009 May 15.
Ref 7 A biologically active hydrophobic T-1-conotoxin from the venom of Conus spurius. Peptides. 2006 Mar;27(3):500-5. doi: 10.1016/j.peptides.2005.07.020. Epub 2005 Nov 16.
Ref 8 The T-1 conotoxin -SrVA from the worm hunting marine snail Conus spurius preferentially blocks the human Na(V)1.5 channel. Peptides. 2022 Oct;156:170859. doi: 10.1016/j.peptides.2022.170859. Epub 2022 Aug 5.
Ref 9 A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J. 2004 Apr 7;23(7):1516-25. doi: 10.1038/sj.emboj.7600177. Epub 2004 Mar 25.
Ref 10 ASIC3, a sensor of acidic and primary inflammatory pain. EMBO J. 2008 Nov 19;27(22):3047-55. doi: 10.1038/emboj.2008.213. Epub 2008 Oct 16.
Ref 11 Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3. Toxicon. 2009 Jul;54(1):56-61. doi: 10.1016/j.toxicon.2009.03.014. Epub 2009 Mar 21.
Ref 12 Expression in Pichia pastoris and characterization of APETx2, a specific inhibitor of acid sensing ion channel 3. Toxicon. 2010 Dec;56(8):1388-97. doi: 10.1016/j.toxicon.2010.08.004. Epub 2010 Sep 9.
Ref 13 Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2. Br J Pharmacol. 2012 Apr;165(7):2167-77. doi: 10.1111/j.1476-5381.2011.01674.x.
Ref 14 A natural point mutation changes both target selectivity and mechanism of action of sea anemone toxins. FASEB J. 2012 Dec;26(12):5141-51. doi: 10.1096/fj.12-218479. Epub 2012 Sep 12.
Ref 15 Cyclisation increases the stability of the sea anemone peptide APETx2 but decreases its activity at acid-sensing ion channel 3. Mar Drugs. 2012 Jul;10(7):1511-1527. doi: 10.3390/md10071511. Epub 2012 Jul 16.
Ref 16 Functional expression in Escherichia coli of the disulfide-rich sea anemone peptide APETx2, a potent blocker of acid-sensing ion channel 3. Mar Drugs. 2012 Jul;10(7):1605-1618. doi: 10.3390/md10071605. Epub 2012 Jul 23.
Ref 17 Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels. Protein Sci. 2005 Aug;14(8):2003-10. doi: 10.1110/ps.051378905. Epub 2005 Jun 29.
Ref 18 Understanding the molecular basis of toxin promiscuity: the analgesic sea anemone peptide APETx2 interacts with acid-sensing ion channel 3 and hERG channels via overlapping pharmacophores. J Med Chem. 2014 Nov 13;57(21):9195-203. doi: 10.1021/jm501400p. Epub 2014 Nov 4.
Ref 19 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 20 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 21 - 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 22 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.
Data Quality & Feedback

Help us maintain data quality by reporting any errors or inaccuracies you may find.

samedaypayday.com visits since 2024

If you find any error in data or bug in web service, please kindly report it to biodb_contact@163.com et al.