ID   SCX1A_TITFA             Reviewed;          84 AA.
AC   P0DQH5;
DT   05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Beta-toxin Tf1a {ECO:0000303|PubMed:30131471};
DE   Flags: Precursor;
OS   Tityus fasciolatus (Central Brazilian scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX   NCBI_TaxID=203543;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-46 AND 59-73, FUNCTION,
RP   SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND AMIDATION AT CYS-81.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=30131471; DOI=10.3390/toxins10090339;
RA   Mata D.O.D., Tibery D.V., Campos L.A., Camargos T.S., Peigneur S.,
RA   Tytgat J., Schwartz E.F.;
RT   "Subtype specificity of beta-toxin Tf1a from Tityus fasciolatus in voltage
RT   gated sodium channels.";
RL   Toxins 10:1-17(2018).
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. The toxin induces a leftward shift,
CC       on all channels tested (including Blattella germanica and Varroa
CC       destructor Nav1), displacing a change in voltage dependence activation
CC       to more hyperpolarized potentials (PubMed:30131471). In addition, the
CC       toxin mostly inhibits peak current of hNav1.4/SCN4A (53% inhibition of
CC       peak current at 100 nM) and hNav1.5/SCN5A (71% inhibition)
CC       (PubMed:30131471). {ECO:0000269|PubMed:30131471}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30131471}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:30131471}.
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=6927.5; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:30131471};
CC   -!- MISCELLANEOUS: The toxin shows a weak peak current inhibition of
CC       Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.6/SCN8A, Nav1.7/SCN9A
CC       (17-30% inhibition of peak current at 100 nM). It does not inhibit peak
CC       current on insect (BgNaV1 from Blattella germanica) and arachnidan
CC       (VdNaV1 from Varroa destructor) sodium channel subtypes (tested at 100
CC       nM) (PubMed:30131471). {ECO:0000269|PubMed:30131471}.
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   AlphaFoldDB; P0DQH5; -.
DR   SMR; P0DQH5; -.
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; Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..81
FT                   /note="Beta-toxin Tf1a"
FT                   /evidence="ECO:0000305|PubMed:30131471"
FT                   /id="PRO_0000447418"
FT   DOMAIN          21..82
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   MOD_RES         81
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000269|PubMed:30131471"
FT   DISULFID        31..81
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        35..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;  9426 MW;  A24B6FCA68468136 CRC64;
     MKGMILFISC LLLIGIVVEC KEGYLMDHEG CKLSCFIRPS GYCGSECKIK KGSSGYCAWP
     ACYCYGLPNW VKVWERATNR CGKK