ID   WAG13_TROWA             Reviewed;          24 AA.
AC   P24335;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   08-FEB-2011, sequence version 2.
DT   25-MAY-2022, entry version 77.
DE   RecName: Full=Waglerin-3;
DE   AltName: Full=SL-Waglerin-1;
DE            Short=SL-I;
DE   Contains:
DE     RecName: Full=Waglerin-1;
DE     AltName: Full=Lethal peptide I;
DE     AltName: Full=Waglerin I;
DE     AltName: Full=Wtx-1;
OS   Tropidolaemus wagleri (Wagler's pit viper) (Trimeresurus wagleri).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Tropidolaemus.
OX   NCBI_TaxID=8770;
RN   [1]
RP   PROTEIN SEQUENCE (WAGLERIN-3), SYNTHESIS OF 1-24 (WAGLERIN-3) AND 3-24
RP   (WAGLERIN-1), DISULFIDE BOND, AND TOXIC DOSE.
RC   TISSUE=Venom;
RX   PubMed=1440639; DOI=10.1016/0041-0101(92)90047-9;
RA   Schmidt J.J., Weinstein S.A., Smith L.A.;
RT   "Molecular properties and structure-function relationships of lethal
RT   peptides from venom of Wagler's pit viper, Trimeresurus wagleri.";
RL   Toxicon 30:1027-1036(1992).
RN   [2]
RP   PROTEIN SEQUENCE OF 3-24 (WAGLERIN-1), AND TOXIC DOSE.
RC   TISSUE=Venom;
RX   PubMed=2048140; DOI=10.1016/0041-0101(91)90107-3;
RA   Weinstein S.A., Schmidt J.J., Bernheimer A.W., Smith L.A.;
RT   "Characterization and amino acid sequences of two lethal peptides isolated
RT   from venom of Wagler's pit viper, Trimeresurus wagleri.";
RL   Toxicon 29:227-236(1991).
RN   [3]
RP   FUNCTION (WAGLERIN-1).
RX   PubMed=7778124; DOI=10.1016/0041-0101(94)00134-t;
RA   Lin W.W., Smith L.A., Lee C.Y.;
RT   "A study on the cause of death due to waglerin-I, a toxin from Trimeresurus
RT   wagleri.";
RL   Toxicon 33:111-114(1995).
RN   [4]
RP   MUTAGENESIS OF ASP-7.
RX   PubMed=8533138; DOI=10.1016/0041-0101(95)00043-l;
RA   Schmidt J.J., Weinstein S.A.;
RT   "Structure-function studies of waglerin I, a lethal peptide from the venom
RT   of Wagler's pit viper, Trimeresurus wagleri.";
RL   Toxicon 33:1043-1049(1995).
RN   [5]
RP   TOXIC DOSE, SYNTHESIS, AND MUTAGENESIS OF LYS-5; ARG-9; HIS-12; HIS-16;
RP   ARG-20; LYS-22 AND ARG-24.
RX   PubMed=8858103; DOI=10.1006/bbrc.1996.1467;
RA   Hsiao Y.-M., Chuang C.-C., Chuang L.-C., Yu H.-M., Wang K.-T., Chiou S.-H.,
RA   Wu S.-H.;
RT   "Protein engineering of venom toxins by synthetic approach and NMR dynamic
RT   simulation: status of basic amino acid residues in waglerin I.";
RL   Biochem. Biophys. Res. Commun. 227:59-63(1996).
RN   [6]
RP   FUNCTION, AND TOXIN TARGET.
RC   TISSUE=Venom;
RX   PubMed=9223541;
RA   Ye J.-H., McArdle J.J.;
RT   "Waglerin-1 modulates gamma-aminobutyric acid activated current of murine
RT   hypothalamic neurons.";
RL   J. Pharmacol. Exp. Ther. 282:74-80(1997).
RN   [7]
RP   FUNCTION (WAGLERIN-1), AND TOXIN TARGET.
RX   PubMed=10087048;
RA   McArdle J.J., Lentz T.L., Witzemann V., Schwarz H., Weinstein S.A.,
RA   Schmidt J.J.;
RT   "Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic
RT   acetylcholine receptor.";
RL   J. Pharmacol. Exp. Ther. 289:543-550(1999).
RN   [8]
RP   FUNCTION, AND TOXIN TARGET.
RX   PubMed=11724791; DOI=10.1074/jbc.m109232200;
RA   Molles B.E., Rezai P., Kline E.F., McArdle J.J., Sine S.M., Taylor P.;
RT   "Identification of residues at the alpha and epsilon subunit interfaces
RT   mediating species selectivity of Waglerin-1 for nicotinic acetylcholine
RT   receptors.";
RL   J. Biol. Chem. 277:5433-5440(2002).
RN   [9]
RP   FUNCTION, TOXIN TARGET, MUTAGENESIS OF 3-GLY-GLY-4; 23-PRO-ARG-24; CYS-11;
RP   HIS-12; CYS-15 AND HIS-16, AND REVIEW.
RX   DOI=10.1081/TXR-120014406;
RA   Molles B.E., Taylor P.;
RT   "Structure and function of the waglerins, peptide toxins from the venom of
RT   Wagler's Pit Viper, Tropidolaemus wagleri.";
RL   J. Toxicol. Toxin Rev. 21:273-292(2002).
RN   [10]
RP   STRUCTURE BY NMR OF 3-24, SYNTHESIS OF 3-24, AND ISOMERIZATION
RP   (WAGLERIN-1).
RX   PubMed=8547337; DOI=10.1016/0167-4838(95)00181-6;
RA   Chuang L.C., Yu H.M., Chen C., Huang T.H., Wu S.H., Wang K.T.;
RT   "Determination of three-dimensional solution structure of waglerin I, a
RT   toxin from Trimeresurus wagleri, using 2D-NMR and molecular dynamics
RT   simulation.";
RL   Biochim. Biophys. Acta 1292:145-155(1996).
RN   [11]
RP   STRUCTURE BY NMR OF 3-24.
RX   PubMed=8770182; DOI=10.1016/s0006-3495(96)79559-0;
RA   Sellin L.C., Mattila K., Annila A., Schmidt J.J., McArdle J.J., Hyvonen M.,
RA   Rantala T.T., Kivisto T.;
RT   "Conformational analysis of a toxic peptide from Trimeresurus wagleri which
RT   blocks the nicotinic acetylcholine receptor.";
RL   Biophys. J. 70:3-13(1996).
CC   -!- FUNCTION: Waglerin-1 selectively blocks the epsilon subunit of muscle
CC       nicotinic acetylcholine receptor (nAChR). Has also effects on rodent
CC       ionotropic GABA(A) receptors (GABR), since it potentiates I(GABA) in
CC       some neurons and depresses I(GABA) in others. In mice, it elicits
CC       tachypnea, ocular proptosis, rapid collapse and spasms, whereas no
CC       toxic effects on respiration and blood pressure are observed in rats.
CC   -!- FUNCTION: Waglerin-3 selectively blocks the epsilon subunit of muscle
CC       nicotinic acetylcholine receptor (nAChR). It elicits tachypnea, ocular
CC       proptosis, rapid collapse and spasms in mice. It causes death by
CC       respiratory failure.
CC   -!- SUBUNIT: Waglerin-1 is monomeric.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- PTM: Amidation of the waglerin-1 C-terminus increases the affinity by
CC       2-fold.
CC   -!- TOXIC DOSE: LD(50) of waglerin-1 is 0.33-0.369 mg/kg by intraperitoneal
CC       injection into mice.
CC   -!- TOXIC DOSE: LD(50) of waglerin-3 is 0.22 mg/kg by intraperitoneal
CC       injection into mice.
CC   -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC       13-Pro-Pro-14.
CC   -!- SIMILARITY: Belongs to the waglerin family. {ECO:0000305}.
CC   -!- CAUTION: Mutagenesis results from PubMed:8858103 should be interpreted
CC       carefully, since the authors found waglerin-2 (AC P58930) as inactive,
CC       despite the finding of other groups that found this peptide equipotent
CC       in lethality to waglerin-1. {ECO:0000305}.
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DR   PIR; B44008; B44008.
DR   AlphaFoldDB; P24335; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR012637; Toxin_33.
DR   Pfam; PF08121; Toxin_33; 1.
PE   1: Evidence at protein level;
KW   Acetylcholine receptor inhibiting toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW   Postsynaptic neurotoxin; Secreted; Toxin.
FT   PEPTIDE         1..24
FT                   /note="Waglerin-3"
FT                   /id="PRO_0000404085"
FT   PEPTIDE         3..24
FT                   /note="Waglerin-1"
FT                   /id="PRO_0000044549"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        11..15
FT                   /evidence="ECO:0000269|PubMed:1440639"
FT   MUTAGEN         3..4
FT                   /note="Missing: No loss of affinity; in Waglerin-1."
FT                   /evidence="ECO:0000269|Ref.9"
FT   MUTAGEN         5
FT                   /note="K->A: No decrease in lethality; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103"
FT   MUTAGEN         7
FT                   /note="D->E,N: Slight decrease in lethality; in
FT                   Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8533138"
FT   MUTAGEN         9
FT                   /note="R->A: Slight decrease in lethality; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103"
FT   MUTAGEN         11
FT                   /note="C->S: 3000-fold decrease in affinity at the
FT                   alpha-epsilon site of nAChR and 4- to 9-fold decrease at
FT                   the alpha-gamma and alpha-delta sites, respectively; when
FT                   associated with S-15 in Waglerin-1."
FT                   /evidence="ECO:0000269|Ref.9"
FT   MUTAGEN         12
FT                   /note="H->A: Very important (34-fold) decrease in
FT                   lethality; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103, ECO:0000269|Ref.9"
FT   MUTAGEN         12
FT                   /note="H->D: 260-fold decrease in affinity; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103, ECO:0000269|Ref.9"
FT   MUTAGEN         15
FT                   /note="C->S: 3000-fold decrease in affinity at the
FT                   alpha-epsilon site of nAChR and 4- to 9-fold decrease at
FT                   the alpha-gamma and alpha-delta sites, respectively; when
FT                   associated with S-11 in Waglerin-1."
FT                   /evidence="ECO:0000269|Ref.9"
FT   MUTAGEN         16
FT                   /note="H->A: Important (16-fold) decrease in lethality; in
FT                   Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103, ECO:0000269|Ref.9"
FT   MUTAGEN         16
FT                   /note="H->D: 1160-fold decrease in affinity; in
FT                   Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103, ECO:0000269|Ref.9"
FT   MUTAGEN         20
FT                   /note="R->A: Slight decrease in lethality; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103"
FT   MUTAGEN         22
FT                   /note="K->A: Slight decrease in lethality; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103"
FT   MUTAGEN         23..24
FT                   /note="Missing: No loss of affinity; in Waglerin-1."
FT                   /evidence="ECO:0000269|Ref.9"
FT   MUTAGEN         24
FT                   /note="R->A: Slight decrease in lethality; in Waglerin-1."
FT                   /evidence="ECO:0000269|PubMed:8858103"
SQ   SEQUENCE   24 AA;  2722 MW;  D9B533A32692594F CRC64;
     SLGGKPDLRP CHPPCHYIPR PKPR
//