ID   TX1A_PARCV              Reviewed;          26 AA.
AC   P41736;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2024, sequence version 2.
DT   02-SEP-2026, entry version 95.
DE   RecName: Full=Glycyl-poneratoxin {ECO:0000303|PubMed:27266841};
DE            Short=Glycyl-PoTx {ECO:0000303|PubMed:27266841};
DE   Contains:
DE     RecName: Full=Delta-paraponeritoxin-Pc1a {ECO:0000305|PubMed:26805882};
DE              Short=Delta-PPOTX-Pc1a {ECO:0000305|PubMed:26805882};
DE     AltName: Full=Pac-TX;
DE     AltName: Full=Poneratoxin {ECO:0000303|PubMed:12097919, ECO:0000303|PubMed:1317947, ECO:0000303|PubMed:15153103, ECO:0000303|PubMed:1685424, ECO:0000303|PubMed:1685425};
DE              Short=PoTX {ECO:0000303|PubMed:1685424, ECO:0000303|PubMed:1685425};
DE     AltName: Full=Poneritoxin {ECO:0000305};
OS   Paraponera clavata (Bullet ant) (Formica clavata).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida;
OC   Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota;
OC   Hymenoptera; Apocrita; Aculeata; Formicoidea; Formicidae; Paraponerinae;
OC   Paraponera.
OX   NCBI_TaxID=55425;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, AMIDATION AT ARG-25, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=1685424; DOI=10.1016/0742-8413(91)90275-x;
RA   Piek T., Hue B., Mantel P., Nakajima T., Schmidt J.O.;
RT   "Pharmacological characterization and chemical fractionation of the venom
RT   of the ponerine ant, Paraponera clavata (F.).";
RL   Comp. Biochem. Physiol. 99C:481-486(1991).
RN   [2]
RP   PROTEIN SEQUENCE, AND SYNTHESIS.
RC   TISSUE=Venom;
RA   Konopinska D., Lombarska-Sliwinska D., Plech A., Rosinski G., Lisowski M.;
RT   "Poneratoxin, neurotoxic pentacosapeptide from ant venom: synthetic,
RT   biological and conformational studies.";
RL   (In) Schneider C.H., Eberles A.N. (eds.);
RL   Peptides 1992, pp.759-760, Escom Science Publishers, Leiden (1993).
RN   [3]
RP   FUNCTION, AND SYNTHESIS.
RC   TISSUE=Venom;
RX   PubMed=1685425; DOI=10.1016/0742-8413(91)90276-y;
RA   Piek T., Duval A., Hue B., Karst H., Lapied B., Mantel P., Nakajima T.,
RA   Pelhate M., Schmidt J.O.;
RT   "Poneratoxin, a novel peptide neurotoxin from the venom of the ant,
RT   Paraponera clavata.";
RL   Comp. Biochem. Physiol. 99C:487-495(1991).
RN   [4]
RP   FUNCTION.
RC   TISSUE=Venom;
RX   PubMed=1317947; DOI=10.1007/bf00374453;
RA   Duval A., Malecot C.O., Pelhate M., Piek T.;
RT   "Poneratoxin, a new toxin from an ant venom, reveals an interconversion
RT   between two gating modes of the Na channels in frog skeletal muscle
RT   fibres.";
RL   Pflugers Arch. 420:239-247(1992).
RN   [5]
RP   FUNCTION.
RX   PubMed=12097919;
RA   Hendrich A.B., Mozrzymas J.W., Konopinska D., Scuka M.;
RT   "The effect of poneratoxin on neuromuscular transmission in the rat
RT   diaphragm.";
RL   Cell. Mol. Biol. Lett. 7:195-202(2002).
RN   [6]
RP   FUNCTION, VARIANTS 22-ASP-ALA-23 DELINS ASN-VAL AND GLU-23, AND SYNTHESIS.
RX   PubMed=27266841; DOI=10.1016/j.peptides.2016.05.012;
RA   Johnson S.R., Rikli H.G., Schmidt J.O., Evans M.S.;
RT   "A reexamination of poneratoxin from the venom of the bullet ant Paraponera
RT   clavata.";
RL   Peptides 98:51-62(2017).
RN   [7]
RP   FUNCTION, BIOASSAY, TOXIC DOSE, AND SYNTHESIS.
RX   PubMed=37221205; DOI=10.1038/s41467-023-38839-1;
RA   Robinson S.D., Deuis J.R., Touchard A., Keramidas A., Mueller A.,
RA   Schroeder C.I., Barasse V., Walker A.A., Brinkwirth N., Jami S.,
RA   Bonnafe E., Treilhou M., Undheim E.A.B., Schmidt J.O., King G.F.,
RA   Vetter I.;
RT   "Ant venoms contain vertebrate-selective pain-causing sodium channel
RT   toxins.";
RL   Nat. Commun. 14:2977-2977(2023).
RN   [8]
RP   REVIEW, AND NOMENCLATURE.
RX   PubMed=26805882; DOI=10.3390/toxins8010030;
RA   Touchard A., Aili S.R., Fox E.G., Escoubas P., Orivel J., Nicholson G.M.,
RA   Dejean A.;
RT   "The biochemical toxin arsenal from ant venoms.";
RL   Toxins 8:1-28(2016).
RN   [9]
RP   STRUCTURE BY NMR, AND SYNTHESIS.
RX   PubMed=15153103; DOI=10.1111/j.1432-1033.2004.04128.x;
RA   Szolajska E., Poznanski J., Ferber M.L., Michalik J., Gout E., Fender P.,
RA   Bailly I., Dublet B., Chroboczek J.;
RT   "Poneratoxin, a neurotoxin from ant venom. Structure and expression in
RT   insect cells and construction of a bio-insecticide.";
RL   Eur. J. Biochem. 271:2127-2136(2004).
CC   -!- FUNCTION: [Delta-paraponeritoxin-Pc1a]: Toxin that causes pain in
CC       vertebrates by targeting tetrodotoxin (TTX)-sensitive sodium channels
CC       in peripheral sensory neurons (PubMed:37221205). Also blocks synaptic
CC       transmission and stimulates smooth muscle contraction (PubMed:12097919,
CC       PubMed:1685424, PubMed:1685425). Converts the normally rapidly
CC       activating and inactivating sodium channel current into one that does
CC       not inactivate (PubMed:27266841, PubMed:37221205). Is active on both
CC       Nav1.6/SCN8A and Nav1.7/SCN9A sodium channels, with a much potent
CC       activity on Nav1.6/SCN8A (EC(50)=97 nM on human channels) than on
CC       Nav1.7/SCN9A (EC(50)=2.3 uM on human and EC(50)=1.8 uM on mouse
CC       channels) (PubMed:27266841, PubMed:37221205). On these channels, causes
CC       a sustained current, a reduction in peak current amplitude and a
CC       hyperpolarising shift (PubMed:27266841, PubMed:37221205). Modulates
CC       Nav1.7/SCN9A in a non-competitive manner with TTX or tetracaine
CC       (Probable). Toxin-induced persistant current is very slowly reversible
CC       with repeated wash steps over 30 minutes (PubMed:37221205). In vivo,
CC       shallow intraplantar injection in mice causes immediate, long-lasting
CC       and near-maximal nocifensive behaviors, which decrease with coinjection
CC       of TTX (PubMed:37221205). When tested on insects, causes paralysis but
CC       not mortality at high doses (PubMed:37221205).
CC       {ECO:0000269|PubMed:12097919, ECO:0000269|PubMed:1685424,
CC       ECO:0000269|PubMed:1685425, ECO:0000269|PubMed:27266841,
CC       ECO:0000269|PubMed:37221205, ECO:0000305|PubMed:27266841}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1685424}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:1685424}.
CC   -!- PTM: The glycine-PoTx is a non-amidated form of poneratoxin, with an
CC       extra-Gly at C-terminus. This loss of amidation does not alter toxin
CC       activity on Nav1.7/SCN9A. {ECO:0000269|PubMed:27266841}.
CC   -!- TOXIC DOSE: PD(50) (measured at 1 hour) is 74.3 nmol/g by intrathoracic
CC       injection into blowflies (Lucilia caesar). Is not lethal by
CC       intrathoracic injection to blowflies at the highest dose tested (123
CC       nmol/g). {ECO:0000269|PubMed:37221205}.
CC   -!- MISCELLANEOUS: The variant A23E has an 8-fold reduction in potency
CC       compared to delta-paraponeritoxin-Pc1a. {ECO:0000269|PubMed:27266841}.
CC   -!- MISCELLANEOUS: The variant D22N/A23V, has an ~5-fold increase in
CC       potency compared to delta-paraponeritoxin-Pc1a.
CC       {ECO:0000269|PubMed:27266841}.
CC   -!- MISCELLANEOUS: Negative results: does not show activity on human
CC       Nav1.8/SCN10A channels (EC(50)>10 uM). At 1 uM, also very weakly
CC       inhibits hNav1.9/SCN11A inactivation. {ECO:0000269|PubMed:37221205}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Princess Bala's sting
CC       - Issue 14 of September 2001;
CC       URL="https://www.proteinspotlight.org/back_issues/014";
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DR   PDB; 1G92; NMR; -; A=1-25.
DR   AlphaFoldDB; P41736; -.
DR   BMRB; P41736; -.
DR   SMR; P41736; -.
DR   EvolutionaryTrace; P41736; -.
DR   GO; GO:0005576; C:extracellular region; EXP:UniProtKB.
DR   PDBsum; 1G92; -.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Direct protein sequencing;
KW   Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin;
KW   Presynaptic neurotoxin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..26
FT                   /note="Glycyl-poneratoxin"
FT                   /evidence="ECO:0000269|PubMed:27266841"
FT                   /id="PRO_0000459135"
FT   PEPTIDE         1..25
FT                   /note="Delta-paraponeritoxin-Pc1a"
FT                   /evidence="ECO:0000269|PubMed:1685424,
FT                   ECO:0000269|PubMed:27266841"
FT                   /id="PRO_0000044538"
FT   MOD_RES         25
FT                   /note="Arginine amide; in delta-paraponeritoxin-Pc1a"
FT                   /evidence="ECO:0000269|PubMed:1685424"
FT   VARIANT         22..23
FT                   /note="DA -> NV"
FT                   /evidence="ECO:0000269|PubMed:27266841"
FT   VARIANT         23
FT                   /note="A -> E"
FT                   /evidence="ECO:0000269|PubMed:27266841"
FT   HELIX           2..8
FT                   /evidence="ECO:0007829|PDB:1G92"
FT   STRAND          11..13
FT                   /evidence="ECO:0007829|PDB:1G92"
FT   TURN            16..18
FT                   /evidence="ECO:0007829|PDB:1G92"
FT   HELIX           19..24
FT                   /evidence="ECO:0007829|PDB:1G92"
SQ   SEQUENCE   26 AA;  2814 MW;  9DFEA403CC125E7B CRC64;
     FLPLLILGSL LMTPPVIQAI HDAQRG
//