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P24335

- WAG13_TROWA

UniProt

P24335 - WAG13_TROWA

Protein

Waglerin-3

Gene
N/A
Organism
Tropidolaemus wagleri (Wagler's pit viper) (Trimeresurus wagleri)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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.
    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.

    GO - Molecular functioni

    1. acetylcholine receptor inhibitor activity Source: InterPro
    2. chloride channel inhibitor activity Source: UniProtKB-KW

    Keywords - Molecular functioni

    Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Waglerin-3
    Alternative name(s):
    SL-Waglerin-1
    Short name:
    SL-I
    Cleaved into the following chain:
    Alternative name(s):
    Lethal peptide I
    Waglerin I
    Wtx-1
    OrganismiTropidolaemus wagleri (Wagler's pit viper) (Trimeresurus wagleri)
    Taxonomic identifieri8770 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaViperidaeCrotalinaeTropidolaemus

    Subcellular locationi

    GO - Cellular componenti

    1. other organism postsynaptic membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Toxic dosei

    LD50 of waglerin-1 is 0.33-0.369 mg/kg by intraperitoneal injection into mice.
    LD50 of waglerin-3 is 0.22 mg/kg by intraperitoneal injection into mice.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi3 – 42Missing: No loss of affinity; in Waglerin-1.
    Mutagenesisi5 – 51K → A: No decrease in lethality; in Waglerin-1. 1 Publication
    Mutagenesisi7 – 71D → E or N: Slight decrease in lethality; in Waglerin-1. 1 Publication
    Mutagenesisi9 – 91R → A: Slight decrease in lethality; in Waglerin-1. 1 Publication
    Mutagenesisi11 – 111C → 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. 1 Publication
    Mutagenesisi12 – 121H → A: Very important (34-fold) decrease in lethality; in Waglerin-1. 2 Publications
    Mutagenesisi12 – 121H → D: 260-fold decrease in affinity; in Waglerin-1. 2 Publications
    Mutagenesisi15 – 151C → 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. 1 Publication
    Mutagenesisi16 – 161H → A: Important (16-fold) decrease in lethality; in Waglerin-1. 2 Publications
    Mutagenesisi16 – 161H → D: 1160-fold decrease in affinity; in Waglerin-1. 2 Publications
    Mutagenesisi20 – 201R → A: Slight decrease in lethality; in Waglerin-1. 1 Publication
    Mutagenesisi22 – 221K → A: Slight decrease in lethality; in Waglerin-1. 1 Publication
    Mutagenesisi23 – 242Missing: No loss of affinity; in Waglerin-1.
    Mutagenesisi24 – 241R → A: Slight decrease in lethality; in Waglerin-1. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Peptidei1 – 2424Waglerin-3PRO_0000404085Add
    BLAST
    Peptidei3 – 2422Waglerin-1PRO_0000044549Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi11 ↔ 151 Publication

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond

    Expressioni

    Tissue specificityi

    Expressed by the venom gland.

    Interactioni

    Subunit structurei

    Waglerin-1 is monomeric.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the waglerin family.Curated

    Family and domain databases

    InterProiIPR012637. Toxin_33.
    [Graphical view]
    PfamiPF08121. Toxin_33. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P24335-1 [UniParc]FASTAAdd to Basket

    « Hide

    SLGGKPDLRP CHPPCHYIPR PKPR                               24
    Length:24
    Mass (Da):2,722
    Last modified:February 8, 2011 - v2
    Checksum:iD9B533A32692594F
    GO

    Sequence databases

    PIRiB44008.

    Cross-referencesi

    Sequence databases

    PIRi B44008.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    InterProi IPR012637. Toxin_33.
    [Graphical view ]
    Pfami PF08121. Toxin_33. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiWAG13_TROWA
    AccessioniPrimary (citable) accession number: P24335
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 1992
    Last sequence update: February 8, 2011
    Last modified: October 1, 2014
    This is version 64 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programAnimal Toxin Annotation Program
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

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

    Caution

    Mutagenesis results from PubMed:8858103 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.Curated

    Keywords - Technical termi

    Direct protein sequencing

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3