ID   TX30_ANDCR              Reviewed;          84 AA.
AC   E7BLC7;
DT   03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT   08-MAR-2011, sequence version 1.
DT   03-AUG-2022, entry version 32.
DE   RecName: Full=Toxin Acra3;
DE   Flags: Precursor;
OS   Androctonus crassicauda (Arabian fat-tailed scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Androctonus.
OX   NCBI_TaxID=122909;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-40, FUNCTION, BIOASSAY,
RP   MASS SPECTROMETRY, AMIDATION AT SER-83, SUBCELLULAR LOCATION, AND TOXIC
RP   DOSE.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=22819772; DOI=10.1016/j.peptides.2012.07.009;
RA   Caliskan F., Garcia B.I., Coronas F.I., Restano-Cassulini R., Korkmaz F.,
RA   Sahin Y., Corzo G., Possani L.D.;
RT   "Purification and cDNA cloning of a novel neurotoxic peptide (Acra3) from
RT   the scorpion Androctonus crassicauda.";
RL   Peptides 37:106-112(2012).
RN   [2]
RP   FUNCTION.
RC   TISSUE=Venom;
RX   PubMed=24055552; DOI=10.1016/j.toxicon.2013.09.009;
RA   Caliskan F., Ergene E., Sogut I., Hatipoglu I., Basalp A., Sivas H.,
RA   Kanbak G.;
RT   "Biological assays on the effects of Acra3 peptide from Turkish scorpion
RT   Androctonus crassicauda venom on a mouse brain tumor cell line (BC3H1) and
RT   production of specific monoclonal antibodies.";
RL   Toxicon 76:350-361(2013).
CC   -!- FUNCTION: The molecular target of Acra3 remains undiscovered. In vivo,
CC       induces severe neurotoxic events in mice such as excitability and
CC       convulsions, leading to the death of the animals within a few minutes
CC       after injection. Does not show toxicity in insects and crustaceans
CC       (PubMed:22819772). Exerts very strong cytotoxic effect on a mouse brain
CC       tumor cell line (BC3H1) with an IC(50) value of 5 mg/ml. It exerts its
CC       effects by inducing a stronger necrosis than apoptosis in BC3H1 cells
CC       (PubMed:24055552). {ECO:0000269|PubMed:22819772,
CC       ECO:0000269|PubMed:24055552}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22819772}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
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   -!- MASS SPECTROMETRY: Mass=7620.3; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:22819772};
CC   -!- TOXIC DOSE: LD(50) is less than 25 ug/kg in mouse by intracranial
CC       injection. {ECO:0000269|PubMed:22819772}.
CC   -!- MISCELLANEOUS: Does not inhibit Nav1.1/SCN1A, Nav1.2/SCN2A,
CC       Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, and Nav1.6/SCN8A voltage-
CC       gated sodium channels. {ECO:0000305|PubMed:22819772}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
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DR   EMBL; GQ454796; ADK12684.1; -; mRNA.
DR   AlphaFoldDB; E7BLC7; -.
DR   SMR; E7BLC7; -.
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   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; Neurotoxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000269|PubMed:22819772"
FT   CHAIN           18..83
FT                   /note="Toxin Acra3"
FT                   /id="PRO_0000421898"
FT   DOMAIN          19..82
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   MOD_RES         83
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000269|PubMed:22819772"
FT   DISULFID        30..81
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        34..57
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        43..62
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        47..64
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
SQ   SEQUENCE   84 AA;  9698 MW;  D3388189F8C25B1B CRC64;
     MKIIFLVLMM ILSEVYSDRD GYPVHDGTNC KYSCDIREKW EYCTPLCKRR NAKTGYCYAF
     ACWCIGLPDE VKVYGDDGIF CKSG