WAG13_TROWA
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 Waglerin-
FT 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 alpha-
FT epsilon site of nAChR and 4- to 9-fold decrease at the
FT 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 alpha-
FT epsilon site of nAChR and 4- to 9-fold decrease at the
FT 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 Waglerin-
FT 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
