ID   DEL1A_HOTJU             Reviewed;          66 AA.
AC   P0DQN8;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 1.
DT   03-AUG-2022, entry version 7.
DE   RecName: Full=Delta-buthitoxin-Hj1a {ECO:0000303|PubMed:32259093};
DE            Short=Delta-BUTX-Hj1a {ECO:0000305|PubMed:32259093};
OS   Hottentotta judaicus (Black scorpion) (Buthotus judaicus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Hottentotta.
OX   NCBI_TaxID=6863;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, RECOMBINANT EXPRESSION,
RP   SUBCELLULAR LOCATION, STRUCTURE BY NMR, DISULFIDE BOND, TOXIC DOSE, AND
RP   BIOASSAY.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=32259093; DOI=10.1021/acsptsci.9b00079;
RA   Chow C.Y., Chin Y.K., Walker A.A., Guo S., Blomster L.V., Ward M.J.,
RA   Herzig V., Rokyta D.R., King G.F.;
RT   "Venom peptides with dual modulatory activity on the voltage-gated sodium
RT   channel Nav1.1 provide novel leads for development of antiepileptic
RT   drugs.";
RL   ACS Pharmacol. Transl. Sci. 3:119-134(2020).
CC   -!- FUNCTION: This recombinant toxin slows fast inactivation on
CC       Nav1.1/SCN1A (EC(50)=17 nM), Nav1.4/SN4A (EC(50)=7.5 nM), Nav1.5/SCN5A
CC       (EC(50)=9.2 nM) and Nav1.6/SCN8A (EC(50)=37.3 nM) voltage-gated sodium
CC       channels (PubMed:32259093). On Nav1.1/SCN1A channel, it acts as an
CC       agonist by inducing a shift in both the voltage dependence of channel
CC       inactivation (alpha-toxin activity) and activation (beta-toxin
CC       activity) (PubMed:32259093). In vivo, shows moderate insecticidal
CC       activities (PubMed:32259093). It induces irreversible paralysis in
CC       blowflies and lethal effects in D.melanogaster (PubMed:32259093).
CC       {ECO:0000269|PubMed:32259093}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32259093}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:32259093}.
CC   -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC       antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC       {ECO:0000269|PubMed:32259093}.
CC   -!- MASS SPECTROMETRY: Mass=7476.30; Method=Electrospray; Note=Monoisotopic
CC       mass.; Evidence={ECO:0000269|PubMed:32259093};
CC   -!- TOXIC DOSE: LD(50) of the recombinant toxin is 745 +- 108 pmol/g on
CC       D.melanogaster. {ECO:0000269|PubMed:32259093}.
CC   -!- TOXIC DOSE: LD(50) of the native toxin is 914 +- 138 pmol/g on
CC       D.melanogaster. {ECO:0000269|PubMed:32259093}.
CC   -!- PHARMACEUTICAL: Lead molecule for the development of selective
CC       Nav1.1/SCN1A agonists for the treatment of Dravet syndrome epilepsy.
CC       {ECO:0000305|PubMed:32259093}.
CC   -!- MISCELLANEOUS: Shows very weak activity on Nav1.2/SCN2A, Nav1.3/SCN3A,
CC       and Nav1.7/SCN9A voltage-gated sodium channels.
CC       {ECO:0000269|PubMed:32259093}.
CC   -!- MISCELLANEOUS: The complete amino acid sequence was obtained by
CC       combining proteomic and transcriptomic techniques.
CC       {ECO:0000305|PubMed:32259093}.
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   PDB; 6OHX; NMR; -; A=1-66.
DR   PDBsum; 6OHX; -.
DR   AlphaFoldDB; P0DQN8; -.
DR   SMR; P0DQN8; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
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; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Pharmaceutical; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..66
FT                   /note="Delta-buthitoxin-Hj1a"
FT                   /evidence="ECO:0000269|PubMed:32259093"
FT                   /id="PRO_0000451604"
FT   DOMAIN          4..66
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        14..65
FT                   /evidence="ECO:0000269|PubMed:32259093"
FT   DISULFID        18..38
FT                   /evidence="ECO:0000269|PubMed:32259093"
FT   DISULFID        24..48
FT                   /evidence="ECO:0000269|PubMed:32259093"
FT   DISULFID        28..50
FT                   /evidence="ECO:0000269|PubMed:32259093"
SQ   SEQUENCE   66 AA;  7491 MW;  BB00DC7EBCE2D7DC CRC64;
     EEVRDAYIAQ PHNCVYHCFR DSYCNDLCIK HGAESGECKW FTSSGNACWC VKLPKSEPIK
     VPGKCH