SCXN1_MESEU
ID SCXN1_MESEU Reviewed; 85 AA.
AC P86408; E4VP24; E7CZY7;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2019, sequence version 2.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Sodium channel neurotoxin MeuNaTxalpha-1 {ECO:0000303|PubMed:21969612, ECO:0000303|Ref.2};
DE Flags: Precursor;
OS Mesobuthus eupeus (Lesser Asian scorpion) (Buthus eupeus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34648;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 20-24,
RP FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND AMIDATION AT ASN-83.
RC TISSUE=Venom, and Venom gland;
RX PubMed=21969612; DOI=10.1074/mcp.m111.012054;
RA Zhu S., Peigneur S., Gao B., Lu X., Cao C., Tytgat J.;
RT "Evolutionary diversification of Mesobuthus alpha-scorpion toxins affecting
RT sodium channels.";
RL Mol. Cell. Proteomics 11:M111.012054-M111.012054(2012).
RN [2]
RP PROTEIN SEQUENCE OF 20-83, FUNCTION, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND AMIDATION AT ASN-83.
RC TISSUE=Venom;
RA Zhu S.Y., Gao B.;
RT "Characterization of an alpha-sodium neurotoxin from the scorpion
RT Mesobuthus eupeus venom.";
RL Submitted (NOV-2009) to UniProtKB.
RN [3]
RP PROTEIN SEQUENCE OF 20-34, FUNCTION, RECOMBINANT EXPRESSION WITHOUT
RP C-TERMINAL AMIDATION, TOXIC DOSE, AND BIOASSAY.
RX PubMed=33051988; DOI=10.1111/febs.15593;
RA van Cann M., Kuzmenkov A., Isensee J., Andreev-Andrievskiy A., Peigneur S.,
RA Khusainov G., Berkut A., Tytgat J., Vassilevski A., Hucho T.;
RT "Scorpion toxin MeuNaTxalpha-1 sensitizes primary nociceptors by selective
RT modulation of voltage-gated sodium channels.";
RL FEBS J. 288:2418-2435(2021).
RN [4]
RP STRUCTURE BY NMR OF 20-83, DISULFIDE BONDS, AND RECOMBINANT EXPRESSION
RP WITHOUT C-TERMINAL AMIDATION.
RX PubMed=33713480; DOI=10.1002/prot.26074;
RA Mineev K.S., Kuzmenkov A.I., Arseniev A.S., Vassilevski A.A.;
RT "Structure of MeuNaTxalpha-1 toxin from scorpion venom highlights the
RT importance of the nest motif.";
RL Proteins 89:1055-1060(2021).
CC -!- FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium
CC channels (Nav) and inhibit the inactivation of the activated channels,
CC thereby blocking neuronal transmission. This toxin inhibits
CC inactivation of Nav1.6/SCN8A (EC(50)=3.1 uM) and drosophila DmNav1
CC (EC(50)=1.17 uM) (PubMed:21969612, Ref.2, PubMed:33051988). It also
CC shows a weak inhibition of inactivation on Nav1.2/SCN2A Nav1.3/SCN3A,
CC and Nav1.7/SCN9A (PubMed:21969612, PubMed:33051988). The toxin (1 uM)
CC does not significantly shift the midpoint of activation at the two
CC channels, but induces a significant depolarizing shift in the V(1/2) of
CC inactivation of the channels (PubMed:21969612). The toxin has also been
CC shown to dose-dependently stimulates intracellular signaling in DRG
CC neurons through activation of two kinases (type II protein kinase A
CC (PKA-II) and MAP kinases 1/3 (MAPK1/MAPK3)) (PubMed:33051988).
CC Nav1.2/SCN2A is strongly suggested to be the target channel
CC predominantly involved in this activation (PubMed:33051988). In vivo,
CC the toxin induces a dose-dependent thermal hyperalgesia lasting 30-45
CC minutes (PubMed:33051988). {ECO:0000269|PubMed:21969612,
CC ECO:0000269|Ref.2}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21969612}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:21969612}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC {ECO:0000305}.
CC -!- DOMAIN: A labile and variable specificity module composed of 3 loops
CC determines the selectivity of scorpion Nav alpha-toxins. In this toxin,
CC the specificity module consists of: an N-terminal loop following beta-1
CC and up to the first cysteine residue (residues 27-31), the tip of the
CC beta-2-beta-3 hairpin (58-62), and a C-terminal region (75-83).
CC {ECO:0000305|PubMed:33713480}.
CC -!- PTM: C-terminal amidation does not appear to play an important role in
CC activity, since the non-amidated recombinant toxin and the native toxin
CC (which is amidated) show similar activities on all sodium channels
CC tested. {ECO:0000269|PubMed:33051988}.
CC -!- MASS SPECTROMETRY: Mass=7181; Method=MALDI;
CC Evidence={ECO:0000269|Ref.2};
CC -!- MASS SPECTROMETRY: Mass=7178.27; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21969612};
CC -!- TOXIC DOSE: LD(50) is 5.8 mg/kg by subcutaneous administration into
CC mice. {ECO:0000269|PubMed:33051988}.
CC -!- MISCELLANEOUS: Shows no effect on Nav1.4/SCN4A, Nav1.5/SCN5A and
CC Nav1.8/SCN10A (PubMed:21969612, PubMed:33051988).
CC {ECO:0000269|PubMed:21969612}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
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DR EMBL; EF445066; ABR21041.1; -; Genomic_DNA.
DR EMBL; HM989910; ADT82850.1; -; mRNA.
DR PDB; 6THI; NMR; -; A=20-83.
DR PDBsum; 6THI; -.
DR AlphaFoldDB; P86408; -.
DR SMR; P86408; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006952; P:defense response; IEA:InterPro.
DR CDD; cd00107; Knot1; 1.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR InterPro; IPR003614; Scorpion_toxin-like.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR018218; Scorpion_toxinL.
DR InterPro; IPR002061; Scorpion_toxinL/defensin.
DR Pfam; PF00537; Toxin_3; 1.
DR PRINTS; PR00285; SCORPNTOXIN.
DR SMART; SM00505; Knot1; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51863; LCN_CSAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:21969612,
FT ECO:0000269|PubMed:33051988, ECO:0000269|Ref.2"
FT CHAIN 20..83
FT /note="Sodium channel neurotoxin MeuNaTxalpha-1"
FT /evidence="ECO:0000269|Ref.2"
FT /id="PRO_0000401119"
FT DOMAIN 21..83
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT REGION 27..31
FT /note="Specificity module, loop 1"
FT /evidence="ECO:0000305|PubMed:33713480"
FT REGION 58..62
FT /note="Specificity module, loop 2"
FT /evidence="ECO:0000305|PubMed:33713480"
FT REGION 75..83
FT /note="Specificity module, loop 3"
FT /evidence="ECO:0000305|PubMed:33713480"
FT MOD_RES 83
FT /note="Asparagine amide"
FT /evidence="ECO:0000269|PubMed:21969612, ECO:0000269|Ref.2"
FT DISULFID 31..82
FT /evidence="ECO:0000269|PubMed:33713480,
FT ECO:0007744|PDB:6THI"
FT DISULFID 35..55
FT /evidence="ECO:0000269|PubMed:33713480"
FT DISULFID 41..65
FT /evidence="ECO:0000269|PubMed:33713480"
FT DISULFID 45..67
FT /evidence="ECO:0000269|PubMed:33713480,
FT ECO:0007744|PDB:6THI"
FT STRAND 21..26
FT /evidence="ECO:0007829|PDB:6THI"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:6THI"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:6THI"
FT STRAND 62..70
FT /evidence="ECO:0007829|PDB:6THI"
SQ SEQUENCE 85 AA; 9390 MW; 3A2504D5D2733EBA CRC64;
MNSLVMISLA LLVMTGVESV RDGYIADDKN CAYFCGRNAY CDEECKKKGA ESGYCQWAGQ
YGNACWCYKL PDKVPIKVSG KCNGR
