ID   NTXA_DENEC              Reviewed;          73 AA.
AC   P0DQP3; A0A7G9XV73;
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=Excelsatoxin A {ECO:0000303|PubMed:32938666};
DE            Short=ExTxA {ECO:0000303|PubMed:32938666};
DE   Flags: Precursor;
OS   Dendrocnide excelsa (Giant stinging tree) (Urera excelsa).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; fabids; Rosales; Urticaceae; Dendrocnide.
OX   NCBI_TaxID=647263;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 58-73, FUNCTION, TISSUE
RP   SPECIFICITY, SYNTHESIS OF 38-73, STRUCTURE BY NMR OF 38-73, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
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)=58 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 (PubMed:32938666).
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 (PubMed:32938666). In vivo, it
CC       causes nocifensive behavior in mice (licking or biting and shaking or
CC       lifting of the affected paw) lasting for approximately 1 hour
CC       (PubMed:32938666). {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 (PubMed:32938666).
CC       Not expressed in other aerial parts (PubMed:32938666).
CC       {ECO:0000269|PubMed:32938666}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000305|PubMed:32938666}.
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; MN784116; QNO39340.1; -; mRNA.
DR   PDB; 6VH8; NMR; -; A=38-73.
DR   PDBsum; 6VH8; -.
DR   AlphaFoldDB; P0DQP3; -.
DR   SMR; P0DQP3; -.
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   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..37
FT                   /evidence="ECO:0000305|PubMed:32938666"
FT                   /id="PRO_0000452285"
FT   CHAIN           38..73
FT                   /note="Excelsatoxin A"
FT                   /evidence="ECO:0000305|PubMed:32938666"
FT                   /id="PRO_0000452286"
FT   DISULFID        41..58
FT                   /evidence="ECO:0000269|PubMed:32938666,
FT                   ECO:0007744|PDB:6VH8"
FT   DISULFID        46..60
FT                   /evidence="ECO:0000269|PubMed:32938666,
FT                   ECO:0007744|PDB:6VH8"
FT   DISULFID        54..69
FT                   /evidence="ECO:0000269|PubMed:32938666,
FT                   ECO:0007744|PDB:6VH8"
SQ   SEQUENCE   73 AA;  7740 MW;  2ABD98614A95F10A CRC64;
     MRFALVAAIT IALLVAGSVA DESSEDIDNI VIKTPLDLPR CDSPFCSLFR IGLCGDKCTC
     VPLPIFGLCV PDV