Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P24335 (WAG13_TROWA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 63. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Waglerin-3
Alternative name(s):
SL-Waglerin-1
Short name=SL-I

Cleaved into the following chain:

  1. Waglerin-1
    Alternative name(s):
    Lethal peptide I
    Waglerin I
    Wtx-1
OrganismTropidolaemus wagleri (Wagler's pit viper) (Trimeresurus wagleri)
Taxonomic identifier8770 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaViperidaeCrotalinaeTropidolaemus

Protein attributes

Sequence length24 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Waglerin-1 selectively blocks the epsilon subunit of muscle nicotinic acetylcholine receptor (nAChR). Has also effects on rodent ionotropic GABA(A)/GABRA1 receptors, since it potentiates I(GABA) in some neurons and depresses I(GABA) in others. In mice, it elicits tachypnea, ocular proptosis, rapid collapse and spasms, whereas no toxic effects on respiration and blood pressure are observed in rats. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9

Waglerin-3 selectively blocks the epsilon subunit of muscle nicotinic acetylcholine receptor (nAChR). It elicits tachypnea, ocular proptosis, rapid collapse and spasms in mice. It causes death by respiratory failure. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

Waglerin-1 is monomeric. Ref.10

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom gland.

Post-translational modification

Amidation of the waglerin-1 C-terminus increases the affinity by 2-fold.

Toxic dose

LD50 of waglerin-1 is 0.33-0.369 mg/kg by intraperitoneal injection into mice. Ref.1 Ref.2 Ref.5

LD50 of waglerin-3 is 0.22 mg/kg by intraperitoneal injection into mice. Ref.1 Ref.2 Ref.5

Miscellaneous

Exists in two forms, due to cis-trans isomerization at 13-Pro-Pro-14.

Sequence similarities

Belongs to the waglerin family.

Caution

Mutagenesis results from Ref.5 should be interpreted carefully, since the authors found waglerin-2 (AC P58930) as inactive, despite the finding of other groups that found this peptide equipotent in lethality to waglerin-1.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Peptide1 – 2424Waglerin-3
PRO_0000404085
Peptide3 – 2422Waglerin-1 Ref.2
PRO_0000044549

Amino acid modifications

Disulfide bond11 ↔ 15 Ref.1

Experimental info

Mutagenesis3 – 42Missing: No loss of affinity; in Waglerin-1.
Mutagenesis51K → A: No decrease in lethality; in Waglerin-1. Ref.5
Mutagenesis71D → E or N: Slight decrease in lethality; in Waglerin-1. Ref.4
Mutagenesis91R → A: Slight decrease in lethality; in Waglerin-1. Ref.5
Mutagenesis111C → S: 3000-fold decrease in affinity at the alpha-epsilon site of nAChR and 4- to 9-fold decrease at the alpha-gamma and alpha-delta sites, respectively; when associated with S-15 in Waglerin-1. Ref.9
Mutagenesis121H → A: Very important (34-fold) decrease in lethality; in Waglerin-1. Ref.5 Ref.9
Mutagenesis121H → D: 260-fold decrease in affinity; in Waglerin-1. Ref.5 Ref.9
Mutagenesis151C → S: 3000-fold decrease in affinity at the alpha-epsilon site of nAChR and 4- to 9-fold decrease at the alpha-gamma and alpha-delta sites, respectively; when associated with S-11 in Waglerin-1. Ref.9
Mutagenesis161H → A: Important (16-fold) decrease in lethality; in Waglerin-1. Ref.5 Ref.9
Mutagenesis161H → D: 1160-fold decrease in affinity; in Waglerin-1. Ref.5 Ref.9
Mutagenesis201R → A: Slight decrease in lethality; in Waglerin-1. Ref.5
Mutagenesis221K → A: Slight decrease in lethality; in Waglerin-1. Ref.5
Mutagenesis23 – 242Missing: No loss of affinity; in Waglerin-1. Ref.5
Mutagenesis241R → A: Slight decrease in lethality; in Waglerin-1. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P24335 [UniParc].

Last modified February 8, 2011. Version 2.
Checksum: D9B533A32692594F

FASTA242,722
        10         20 
SLGGKPDLRP CHPPCHYIPR PKPR 

« Hide

References

[1]"Molecular properties and structure-function relationships of lethal peptides from venom of Wagler's pit viper, Trimeresurus wagleri."
Schmidt J.J., Weinstein S.A., Smith L.A.
Toxicon 30:1027-1036(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (WAGLERIN-3), SYNTHESIS OF 1-24 (WAGLERIN-3) AND 3-24 (WAGLERIN-1), DISULFIDE BOND, LETHAL DOSE.
Tissue: Venom.
[2]"Characterization and amino acid sequences of two lethal peptides isolated from venom of Wagler's pit viper, Trimeresurus wagleri."
Weinstein S.A., Schmidt J.J., Bernheimer A.W., Smith L.A.
Toxicon 29:227-236(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 3-24 (WAGLERIN-1), LETHAL DOSE.
Tissue: Venom.
[3]"A study on the cause of death due to waglerin-I, a toxin from Trimeresurus wagleri."
Lin W.W., Smith L.A., Lee C.Y.
Toxicon 33:111-114(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (WAGLERIN-1).
[4]"Structure-function studies of waglerin I, a lethal peptide from the venom of Wagler's pit viper, Trimeresurus wagleri."
Schmidt J.J., Weinstein S.A.
Toxicon 33:1043-1049(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-7.
[5]"Protein engineering of venom toxins by synthetic approach and NMR dynamic simulation: status of basic amino acid residues in waglerin I."
Hsiao Y.-M., Chuang C.-C., Chuang L.-C., Yu H.-M., Wang K.-T., Chiou S.-H., Wu S.-H.
Biochem. Biophys. Res. Commun. 227:59-63(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: LETHAL DOSE, SYNTHESIS, MUTAGENESIS OF LYS-5; ARG-9; HIS-12; HIS-16; ARG-20; LYS-22 AND ARG-24.
[6]"Waglerin-1 modulates gamma-aminobutyric acid activated current of murine hypothalamic neurons."
Ye J.-H., McArdle J.J.
J. Pharmacol. Exp. Ther. 282:74-80(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOXIN TARGET.
Tissue: Venom.
[7]"Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor."
McArdle J.J., Lentz T.L., Witzemann V., Schwarz H., Weinstein S.A., Schmidt J.J.
J. Pharmacol. Exp. Ther. 289:543-550(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (WAGLERIN-1), TOXIN TARGET.
[8]"Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors."
Molles B.E., Rezai P., Kline E.F., McArdle J.J., Sine S.M., Taylor P.
J. Biol. Chem. 277:5433-5440(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOXIN TARGET.
[9]"Structure and function of the waglerins, peptide toxins from the venom of Wagler's Pit Viper, Tropidolaemus wagleri."
Molles B.E., Taylor P.
J. Toxicol. Toxin Rev. 21:273-292(2002)
Cited for: FUNCTION, TOXIN TARGET, MUTAGENESIS OF 3-GLY-GLY-4; 23-PRO-ARG-24; CYS-11; HIS-12; CYS-15 AND HIS-16, REVIEW.
[10]"Determination of three-dimensional solution structure of waglerin I, a toxin from Trimeresurus wagleri, using 2D-NMR and molecular dynamics simulation."
Chuang L.C., Yu H.M., Chen C., Huang T.H., Wu S.H., Wang K.T.
Biochim. Biophys. Acta 1292:145-155(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 3-24, SYNTHESIS OF 3-24, ISOMERIZATION (WAGLERIN-1).
[11]"Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor."
Sellin L.C., Mattila K., Annila A., Schmidt J.J., McArdle J.J., Hyvonen M., Rantala T.T., Kivisto T.
Biophys. J. 70:3-13(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 3-24.

Cross-references

Sequence databases

PIRB44008.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR012637. Toxin_33.
[Graphical view]
PfamPF08121. Toxin_33. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameWAG13_TROWA
AccessionPrimary (citable) accession number: P24335
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: February 8, 2011
Last modified: April 16, 2014
This is version 63 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families