ID   SCX9_ANDCR              Reviewed;          64 AA.
AC   C0HLG5;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 1.
DT   03-AUG-2022, entry version 7.
DE   RecName: Full=Alpha-mammal toxin AnCra1 {ECO:0000303|PubMed:34379289, ECO:0000303|Ref.1};
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   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP   TOXIC DOSE.
RC   TISSUE=Venom;
RX   DOI=10.2478/s11756-019-00400-1;
RA   Bayatzadeh M.A., Mirakabadi A.Z., Babaei N., Doulah A.H., Doosti A.;
RT   "Characterization, molecular modeling and phylogenetic analysis of a long
RT   mammalian neurotoxin from the venom of the Iranian scorpion Androctonus
RT   crassicauda.";
RL   Biologia 75:1029-1041(2020).
RN   [2]
RP   FUNCTION, RECOMBINANT EXPRESSION, TOXIC DOSE, AND 3D-STRUCTURE MODELING.
RX   PubMed=34379289; DOI=10.1007/s11033-021-06624-2;
RA   Bayatzadeh M.A., Zare Mirakabadi A., Babaei N., Doulah A., Doosti A.;
RT   "Expression and purification of recombinant alpha-toxin AnCra1 from the
RT   scorpion Androctonus crassicauda and its functional characterization on
RT   mammalian sodium channels.";
RL   Mol. Biol. Rep. 48:6303-6312(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 is active against
CC       mammals (Ref.1). The recombinant toxin selectively inhibits the fast
CC       inactivation of hNav1.7/SCN9A channel (EC(50)=136.7 nM)
CC       (PubMed:34379289). Is potent in inhibiting the fast inactivation of
CC       hNav1.7 and has little effect on the steady-state inactivation
CC       (PubMed:34379289). In vivo, intravenous injection into mice induces
CC       muscle contraction, leading to severe paralysis and death (Ref.1).
CC       {ECO:0000269|PubMed:34379289, ECO:0000269|Ref.1}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
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=7255.23; Method=MALDI;
CC       Evidence={ECO:0000269|Ref.1};
CC   -!- TOXIC DOSE: LD(50) of native toxin is 29.5 ug/kg by intravenous
CC       injection into mice. LD(100) is 39 ug/kg by intravenous injection into
CC       mice. {ECO:0000269|Ref.1}.
CC   -!- TOXIC DOSE: LD(50) of recombinant toxin is 167 ug/kg by intravenous
CC       injection into mice. {ECO:0000269|PubMed:34379289}.
CC   -!- MISCELLANEOUS: Has very weak activity on hNav1.5/SCN5A sodium channels
CC       (EC(50)=31.9 uM). {ECO:0000269|PubMed:34379289}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   AlphaFoldDB; C0HLG5; -.
DR   SMR; C0HLG5; -.
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; IDA:UniProtKB.
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   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..64
FT                   /note="Alpha-mammal toxin AnCra1"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000451148"
FT   DOMAIN          2..64
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        12..63
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        16..36
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        22..46
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        26..48
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
SQ   SEQUENCE   64 AA;  7255 MW;  5E10CF2D59A73F94 CRC64;
     LKDGYIVDDV NCTYFCGRNA YCNEECIKLK GESGYCQWAS PYGNACYCYK LPDHVRTKGP
     GRCN