ID   TX1A_AUGEZ              Reviewed;          39 AA.
AC   P0DPG5;
DT   23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT   23-MAY-2018, sequence version 1.
DT   25-MAY-2022, entry version 10.
DE   RecName: Full=Mu-theraphotoxin-Ae1a {ECO:0000303|PubMed:27383378};
DE            Short=Mu-TRTX-Ae1a {ECO:0000303|PubMed:27383378};
OS   Augacephalus ezendami (Mozambique baboon spider) (Ceratogyrus ezendami).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Augacephalus.
OX   NCBI_TaxID=2053131;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, AMIDATION AT PHE-39, MASS SPECTROMETRY,
RP   SUBCELLULAR LOCATION, AND TOXIC DOSE.
RC   TISSUE=Venom;
RX   PubMed=27383378; DOI=10.1038/srep29538;
RA   Herzig V., Ikonomopoulou M., Smith J.J., Dziemborowicz S., Gilchrist J.,
RA   Kuhn-Nentwig L., Rezende F.O., Moreira L.A., Nicholson G.M., Bosmans F.,
RA   King G.F.;
RT   "Molecular basis of the remarkable species selectivity of an insecticidal
RT   sodium channel toxin from the African spider Augacephalus ezendami.";
RL   Sci. Rep. 6:29538-29538(2016).
CC   -!- FUNCTION: Insecticidal toxin that acts, at least partially, by
CC       inhibiting insect voltage-gated sodium (NaV) channels of several insect
CC       species. The toxin binds to the voltage sensor in NaV channel domain II
CC       and inhibits channel opening by shifting the threshold for channel
CC       activation to more positive voltages. The toxin binding is sensitive to
CC       residues in the S1-S2 loop of the domain II voltage sensor. In vivo,
CC       the recombinant toxin causes paralysis and/or death to two dipteran
CC       species (Lucilia cuprina and Drosophila melanogaster). In contrast, the
CC       toxin does not show paralytic or lethal effect on the cotton bollworm
CC       Helicoverpa armigera and the triatomine bug Rhodinius prolixus.
CC       {ECO:0000269|PubMed:27383378}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27383378}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:27383378}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P56855}.
CC   -!- MASS SPECTROMETRY: Mass=4257.11; Method=MALDI; Note=Monoisotopic mass.;
CC       Evidence={ECO:0000269|PubMed:27383378};
CC   -!- TOXIC DOSE: PD(50) is 0.96 nmol/g in Lucilia cuprina (at 0.5-1 hour
CC       post-injection). No paralytic or lethal effects are observed 24 hours
CC       post-injection. {ECO:0000269|PubMed:27383378}.
CC   -!- TOXIC DOSE: Injection of recombinant toxin into Drosophila melanogaster
CC       induces irreversible paralysis leading to death. PD(50) is 0.285 nmol/g
CC       (at 3 hours post-injection). PD(50) is 1.9 nmol/g (at 24 hours post-
CC       injection). LD(50) is 4.3 nmol/g (at 24 hours post-injection).
CC       {ECO:0000269|PubMed:27383378}.
CC   -!- MISCELLANEOUS: The recombinant toxin has no effect on american
CC       cockroach Nav channels and on the human voltage-gated sodium channel
CC       Nav1.5/SCN5A. {ECO:0000269|PubMed:27383378}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 47 subfamily.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; P0DPG5; -.
DR   SMR; P0DPG5; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR011696; Huwentoxin-1.
DR   Pfam; PF07740; Toxin_12; 1.
PE   1: Evidence at protein level;
KW   Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..39
FT                   /note="Mu-theraphotoxin-Ae1a"
FT                   /evidence="ECO:0000269|PubMed:27383378"
FT                   /id="PRO_0000444200"
FT   MOD_RES         39
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:27383378"
FT   DISULFID        7..21
FT                   /evidence="ECO:0000250|UniProtKB:P56855"
FT   DISULFID        14..26
FT                   /evidence="ECO:0000250|UniProtKB:P56855"
FT   DISULFID        20..33
FT                   /evidence="ECO:0000250|UniProtKB:P56855"
SQ   SEQUENCE   39 AA;  4268 MW;  149B6FB9B60EC73D CRC64;
     GVDKEGCRYL LGACTIDDDC CLHLGCNKKY GHCGWDGTF