ID   NTXA_DENMD              Reviewed;          80 AA.
AC   P0DQP4; A0A7G9XV75;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   07-APR-2021, sequence version 1.
DT   25-MAY-2022, entry version 4.
DE   RecName: Full=Moroidotoxin A {ECO:0000303|PubMed:32938666};
DE            Short=MoTxA {ECO:0000303|PubMed:32938666};
DE   Flags: Precursor;
OS   Dendrocnide moroides (Gympie stinging tree) (Laportea moroides).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; fabids; Rosales; Urticaceae; Dendrocnide.
OX   NCBI_TaxID=1842752;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SYNTHESIS OF 45-80, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=32938666; DOI=10.1126/sciadv.abb8828;
RA   Gilding E.K., Jami S., Deuis J.R., Israel M.R., Harvey P.J., Poth A.G.,
RA   Rehm F.B.H., Stow J.L., Robinson S.D., Yap K., Brown D.L., Hamilton B.R.,
RA   Andersson D., Craik D.J., Vetter I., Durek T.;
RT   "Neurotoxic peptides from the venom of the giant Australian stinging
RT   tree.";
RL   Sci. Adv. 6:0-0(2020).
CC   -!- FUNCTION: Neurotoxin certainly responsible of defensive persistent and
CC       painful stings of the giant stinging tree, since it provokes similar
CC       effects (PubMed:32938666). Acts by potently delaying voltage-gated
CC       sodium channel (Nav) inactivation in a concentration-dependent manner
CC       (EC(50)=4 nM) (PubMed:32938666). Mainly targets Nav1.7/SCN9A channels,
CC       since the two Nav1.7/SCN9A inhibitors tetrodotoxin and the spider toxin
CC       Pn3a potently reduce nocifensive behaviors it causes (By similarity).
CC       On the Nav1.7/SCN9A channel, this toxin causes a significant
CC       hyperpolarizing shift in the voltage dependence of activation, but has
CC       no significant effect on the voltage dependence of steady-state fast
CC       inactivation (PubMed:32938666). Its effects on Nav currents are
CC       irreversible, with no apparent reduction in activity even after
CC       repeated wash steps over 30 minutes (By similarity). In vivo, it causes
CC       nocifensive behavior in mice (licking or biting and shaking or lifting
CC       of the affected paw) lasting for approximately 1 hour
CC       (PubMed:32938666). {ECO:0000250|UniProtKB:P0DQP3,
CC       ECO:0000269|PubMed:32938666}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:32938666}.
CC   -!- TISSUE SPECIFICITY: Expressed in trichomes, that are stiff epidermal
CC       hairs located on the surface of petioles and leaves. Not expressed in
CC       other aerial parts. {ECO:0000250|UniProtKB:P0DQP3}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P0DQP3}.
CC   -!- MISCELLANEOUS: The name 'gympietide' is derived from the name in the
CC       Gubbi-Gubbi language for the stinging trees (gympie-gympie).
CC       {ECO:0000305|PubMed:32938666}.
CC   -!- SIMILARITY: Belongs to the gympietide family. {ECO:0000305}.
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DR   EMBL; MN784118; QNO39342.1; -; mRNA.
DR   AlphaFoldDB; P0DQP4; -.
DR   SMR; P0DQP4; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   3: Inferred from homology;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW   Signal; Toxin; Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   PROPEP          28..44
FT                   /evidence="ECO:0000305|PubMed:32938666"
FT                   /id="PRO_0000452287"
FT   CHAIN           45..80
FT                   /note="Moroidotoxin A"
FT                   /evidence="ECO:0000305|PubMed:32938666"
FT                   /id="PRO_0000452288"
FT   DISULFID        48..65
FT                   /evidence="ECO:0000250|UniProtKB:P0DQP3"
FT   DISULFID        53..67
FT                   /evidence="ECO:0000250|UniProtKB:P0DQP3"
FT   DISULFID        61..76
FT                   /evidence="ECO:0000250|UniProtKB:P0DQP3"
SQ   SEQUENCE   80 AA;  8424 MW;  51CBCF60B36709DE CRC64;
     MAAVKKHLRF ALVAAITIAL LVAGSVADES SEDIDNIVIK TPLDIPRCDS PLCSLFRIGL
     CGDKCFCVPL PIVGICVPSV