ID   SCX8_CENSU              Reviewed;          66 AA.
AC   P0DL83;
DT   20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2017, sequence version 1.
DT   03-AUG-2022, entry version 13.
DE   RecName: Full=Toxin Css8 {ECO:0000305};
DE   AltName: Full=Beta-neurotoxin CssVIII {ECO:0000303|PubMed:21329715};
DE            Short=Css VIII {ECO:0000305};
OS   Centruroides suffusus (Durango bark scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX   NCBI_TaxID=6880;
RN   [1]
RP   PROTEIN SEQUENCE OF 1-46 AND 73-79, MASS SPECTROMETRY, SUBCELLULAR
RP   LOCATION, AND TOXIC DOSE.
RC   TISSUE=Venom;
RX   PubMed=21329715; DOI=10.1016/j.toxicon.2011.02.006;
RA   Espino-Solis G.P., Estrada G., Olamendi-Portugal T., Villegas E.,
RA   Zamudio F., Cestele S., Possani L.D., Corzo G.;
RT   "Isolation and molecular cloning of beta-neurotoxins from the venom of the
RT   scorpion Centruroides suffusus suffusus.";
RL   Toxicon 57:739-746(2011).
CC   -!- FUNCTION: Beta toxins bind voltage-independently at site-4 of sodium
CC       channels (Nav) and shift the voltage of activation toward more negative
CC       potentials thereby affecting sodium channel activation and promoting
CC       spontaneous and repetitive firing. This toxin compete with high
CC       affinity with 125I-Css4 bound on rat brain synaptosome and may bind
CC       with high affinity to Nav1.1/SCN1A, Nav1.2/SCN2A and Nav1.6/SCN8A.
CC       {ECO:0000269|PubMed:21329715}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21329715}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:21329715}.
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=7588.6; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:21329715};
CC   -!- TOXIC DOSE: LD(100) is 3 ug/kg by intracranial injection into mice.
CC       {ECO:0000269|PubMed:21329715}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
CC   -!- CAUTION: Authors of PubMed:21329715 describe the nucleotide sequencing
CC       of this toxin. Unfortunately, the nucleotide sequence submitted
CC       (accession number HQ262493) corresponds to Css4 (AC P60266). As a
CC       consequence, we choose to show the mature sequence of Css8, since it
CC       has been partially directly sequenced. As the authors propose that Css4
CC       and Css8 differ by only two residues (table 2 and 3), the missing
CC       residues in Css8 are propagated from Css4 and indicated as 'unsure' in
CC       the feature table. {ECO:0000305|PubMed:21329715}.
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DR   AlphaFoldDB; P0DL83; -.
DR   SMR; P0DL83; -.
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; Neurotoxin; Secreted;
KW   Toxin.
FT   CHAIN           1..66
FT                   /note="Toxin Css8"
FT                   /evidence="ECO:0000305|PubMed:21329715"
FT                   /id="PRO_5003266498"
FT   DOMAIN          1..66
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   MOD_RES         66
FT                   /note="Asparagine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P60266"
FT   DISULFID        12..65
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        16..41
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        25..46
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        29..48
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   UNSURE          47..53
FT                   /evidence="ECO:0000305|PubMed:21329715"
FT   UNSURE          61..66
FT                   /evidence="ECO:0000305|PubMed:21329715"
SQ   SEQUENCE   66 AA;  7598 MW;  76B98C5C6B0CE751 CRC64;
     KEGYLVNSYT GCKFECFKLG DNDYCKRECK QQYGKGSGGY CYAFGCWCTH LYEQAVVWPL
     PNKTCN