ID   DEL2A_HOTJU             Reviewed;          64 AA.
AC   P0DQN9;
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-Hj2a {ECO:0000303|PubMed:32259093};
DE            Short=Delta-BUTX-Hj2a {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, AMIDATION AT
RP   ARG-64, AND PHARMACEUTICAL.
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 non-amidated recombinant toxin slows fast inactivation
CC       on Nav1.1/SCN1A (EC(50)=52.8 nM), Nav1.4/SN4A (EC(50)=32 nM),
CC       Nav1.5/SCN5A (EC(50)=116.7 nM), Nav1.6/SCN8A (EC(50)=46.3 nM), and
CC       Nav1.7/SCN9A (EC(50)=147.4 nM) voltage-gated sodium channels
CC       (PubMed:32259093). On Nav1.1/SCN1A channel, acts as an agonist by
CC       inducing a shift in both the voltage dependence of channel inactivation
CC       (alpha-toxin activity) and activation (beta-toxin activity)
CC       (PubMed:32259093). {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:0000250|UniProtKB:P0DQN8}.
CC   -!- MASS SPECTROMETRY: Mass=7112.20; Method=Electrospray; Note=Monoisotopic
CC       mass.; Evidence={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: Does not show effects on Nav1.2/SCN2A, and Nav1.3/SCN3A
CC       voltage-gated sodium channels (PubMed:32259093). Does not show
CC       insecticidal activity (PubMed:32259093). {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   AlphaFoldDB; P0DQN9; -.
DR   SMR; P0DQN9; -.
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   Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Pharmaceutical; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..64
FT                   /note="Delta-buthitoxin-Hj2a"
FT                   /evidence="ECO:0000269|PubMed:32259093"
FT                   /id="PRO_0000451605"
FT   MOD_RES         64
FT                   /note="Arginine amide"
FT                   /evidence="ECO:0000269|PubMed:32259093"
FT   DISULFID        12..63
FT                   /evidence="ECO:0000250|UniProtKB:P0DQN8"
FT   DISULFID        16..36
FT                   /evidence="ECO:0000250|UniProtKB:P0DQN8"
FT   DISULFID        22..46
FT                   /evidence="ECO:0000250|UniProtKB:P0DQN8"
FT   DISULFID        26..48
FT                   /evidence="ECO:0000250|UniProtKB:P0DQN8"
FT   CONFLICT        24
FT                   /note="N -> D (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   64 AA;  7127 MW;  FA4A06880F1B922D CRC64;
     GRDAYIADDK NCVYTCAKNS YCNNECTKNG AESGYCQWLG KYGNGCWCKN LPDKVPIRIP
     GPCR