{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P24335","uniProtkbId":"WAG13_TROWA","entryAudit":{"firstPublicDate":"1992-03-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2011-02-08","entryVersion":81,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Tropidolaemus wagleri","commonName":"Wagler's pit viper","synonyms":["Trimeresurus wagleri"],"taxonId":8770,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Lepidosauria","Squamata","Bifurcata","Unidentata","Episquamata","Toxicofera","Serpentes","Colubroidea","Viperidae","Crotalinae","Tropidolaemus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Waglerin-3"}},"alternativeNames":[{"fullName":{"value":"SL-Waglerin-1"},"shortNames":[{"value":"SL-I"}]}],"contains":[{"recommendedName":{"fullName":{"value":"Waglerin-1"}},"alternativeNames":[{"fullName":{"value":"Lethal peptide I"}},{"fullName":{"value":"Waglerin I"}},{"fullName":{"value":"Wtx-1"}}]}]},"comments":[{"texts":[{"value":"Waglerin-1 selectively blocks the epsilon subunit of muscle nicotinic acetylcholine receptor (nAChR). Also has effects on rodent ionotropic GABA(A) receptors (GABR), 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"}],"commentType":"FUNCTION"},{"texts":[{"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"value":"Waglerin-1 is monomeric"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"value":"Expressed by the venom gland"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"value":"Amidation of the waglerin-1 C-terminus increases the affinity by 2-fold"}],"commentType":"PTM"},{"texts":[{"value":"LD(50) of waglerin-1 is 0.33-0.369 mg/kg by intraperitoneal injection into mice"}],"commentType":"TOXIC DOSE"},{"texts":[{"value":"LD(50) of waglerin-3 is 0.22 mg/kg by intraperitoneal injection into mice"}],"commentType":"TOXIC DOSE"},{"texts":[{"value":"Exists in two forms, due to cis-trans isomerization at 13-Pro-Pro-14"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the waglerin family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"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"}],"commentType":"CAUTION"}],"features":[{"type":"Peptide","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"Waglerin-3","featureId":"PRO_0000404085"},{"type":"Peptide","location":{"start":{"value":3,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"Waglerin-1","featureId":"PRO_0000044549"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":10,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Disulfide bond","location":{"start":{"value":11,"modifier":"EXACT"},"end":{"value":15,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1440639"}]},{"type":"Mutagenesis","location":{"start":{"value":3,"modifier":"EXACT"},"end":{"value":4,"modifier":"EXACT"}},"description":"No loss of affinity; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{}},{"type":"Mutagenesis","location":{"start":{"value":5,"modifier":"EXACT"},"end":{"value":5,"modifier":"EXACT"}},"description":"No decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":7,"modifier":"EXACT"},"end":{"value":7,"modifier":"EXACT"}},"description":"Slight decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8533138"}],"alternativeSequence":{"originalSequence":"D","alternativeSequences":["E","N"]}},{"type":"Mutagenesis","location":{"start":{"value":9,"modifier":"EXACT"},"end":{"value":9,"modifier":"EXACT"}},"description":"Slight decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":11,"modifier":"EXACT"},"end":{"value":11,"modifier":"EXACT"}},"description":"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.","evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":12,"modifier":"EXACT"}},"description":"Very important (34-fold) decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":12,"modifier":"EXACT"}},"description":"260-fold decrease in affinity; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["D"]}},{"type":"Mutagenesis","location":{"start":{"value":15,"modifier":"EXACT"},"end":{"value":15,"modifier":"EXACT"}},"description":"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.","evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":16,"modifier":"EXACT"},"end":{"value":16,"modifier":"EXACT"}},"description":"Important (16-fold) decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":16,"modifier":"EXACT"},"end":{"value":16,"modifier":"EXACT"}},"description":"1160-fold decrease in affinity; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["D"]}},{"type":"Mutagenesis","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":20,"modifier":"EXACT"}},"description":"Slight decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":22,"modifier":"EXACT"},"end":{"value":22,"modifier":"EXACT"}},"description":"Slight decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":23,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"No loss of affinity; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.9"}],"alternativeSequence":{}},{"type":"Mutagenesis","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"Slight decrease in lethality; in Waglerin-1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8858103"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}}],"keywords":[{"id":"KW-0008","category":"Molecular function","name":"Acetylcholine receptor inhibiting toxin"},{"id":"KW-0903","category":"Technical term","name":"Direct protein sequencing"},{"id":"KW-1015","category":"PTM","name":"Disulfide bond"},{"id":"KW-0872","category":"Molecular function","name":"Ion channel impairing toxin"},{"id":"KW-0528","category":"Molecular function","name":"Neurotoxin"},{"id":"KW-0629","category":"Molecular function","name":"Postsynaptic neurotoxin"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"},{"id":"KW-0800","category":"Molecular function","name":"Toxin"}],"references":[{"referenceNumber":1,"citation":{"id":"1440639","citationType":"journal article","authors":["Schmidt J.J.","Weinstein S.A.","Smith L.A."],"citationCrossReferences":[{"database":"PubMed","id":"1440639"},{"database":"DOI","id":"10.1016/0041-0101(92)90047-9"}],"title":"Molecular properties and structure-function relationships of lethal peptides from venom of Wagler's pit viper, Trimeresurus wagleri.","publicationDate":"1992","journal":"Toxicon","firstPage":"1027","lastPage":"1036","volume":"30"},"referencePositions":["PROTEIN SEQUENCE (WAGLERIN-3)","SYNTHESIS OF 1-24 (WAGLERIN-3) AND 3-24 (WAGLERIN-1)","DISULFIDE BOND","TOXIC DOSE"],"referenceComments":[{"value":"Venom","type":"TISSUE"}]},{"referenceNumber":2,"citation":{"id":"2048140","citationType":"journal article","authors":["Weinstein S.A.","Schmidt J.J.","Bernheimer A.W.","Smith L.A."],"citationCrossReferences":[{"database":"PubMed","id":"2048140"},{"database":"DOI","id":"10.1016/0041-0101(91)90107-3"}],"title":"Characterization and amino acid sequences of two lethal peptides isolated from venom of Wagler's pit viper, Trimeresurus wagleri.","publicationDate":"1991","journal":"Toxicon","firstPage":"227","lastPage":"236","volume":"29"},"referencePositions":["PROTEIN SEQUENCE OF 3-24 (WAGLERIN-1)","TOXIC DOSE"],"referenceComments":[{"value":"Venom","type":"TISSUE"}]},{"referenceNumber":3,"citation":{"id":"7778124","citationType":"journal article","authors":["Lin W.W.","Smith L.A.","Lee C.Y."],"citationCrossReferences":[{"database":"PubMed","id":"7778124"},{"database":"DOI","id":"10.1016/0041-0101(94)00134-t"}],"title":"A study on the cause of death due to waglerin-I, a toxin from Trimeresurus wagleri.","publicationDate":"1995","journal":"Toxicon","firstPage":"111","lastPage":"114","volume":"33"},"referencePositions":["FUNCTION (WAGLERIN-1)"]},{"referenceNumber":4,"citation":{"id":"8533138","citationType":"journal article","authors":["Schmidt J.J.","Weinstein S.A."],"citationCrossReferences":[{"database":"PubMed","id":"8533138"},{"database":"DOI","id":"10.1016/0041-0101(95)00043-l"}],"title":"Structure-function studies of waglerin I, a lethal peptide from the venom of Wagler's pit viper, Trimeresurus wagleri.","publicationDate":"1995","journal":"Toxicon","firstPage":"1043","lastPage":"1049","volume":"33"},"referencePositions":["MUTAGENESIS OF ASP-7"]},{"referenceNumber":5,"citation":{"id":"8858103","citationType":"journal article","authors":["Hsiao Y.-M.","Chuang C.-C.","Chuang L.-C.","Yu H.-M.","Wang K.-T.","Chiou S.-H.","Wu S.-H."],"citationCrossReferences":[{"database":"PubMed","id":"8858103"},{"database":"DOI","id":"10.1006/bbrc.1996.1467"}],"title":"Protein engineering of venom toxins by synthetic approach and NMR dynamic simulation: status of basic amino acid residues in waglerin I.","publicationDate":"1996","journal":"Biochem. Biophys. Res. Commun.","firstPage":"59","lastPage":"63","volume":"227"},"referencePositions":["TOXIC DOSE","SYNTHESIS","MUTAGENESIS OF LYS-5; ARG-9; HIS-12; HIS-16; ARG-20; LYS-22 AND ARG-24"]},{"referenceNumber":6,"citation":{"id":"9223541","citationType":"journal article","authors":["Ye J.-H.","McArdle J.J."],"citationCrossReferences":[{"database":"PubMed","id":"9223541"}],"title":"Waglerin-1 modulates gamma-aminobutyric acid activated current of murine hypothalamic neurons.","publicationDate":"1997","journal":"J. Pharmacol. Exp. Ther.","firstPage":"74","lastPage":"80","volume":"282"},"referencePositions":["FUNCTION","TOXIN TARGET"],"referenceComments":[{"value":"Venom","type":"TISSUE"}]},{"referenceNumber":7,"citation":{"id":"10087048","citationType":"journal article","authors":["McArdle J.J.","Lentz T.L.","Witzemann V.","Schwarz H.","Weinstein S.A.","Schmidt J.J."],"citationCrossReferences":[{"database":"PubMed","id":"10087048"},{"database":"DOI","id":"10.1016/s0022-3565(24)38167-4"}],"title":"Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor.","publicationDate":"1999","journal":"J. Pharmacol. Exp. Ther.","firstPage":"543","lastPage":"550","volume":"289"},"referencePositions":["FUNCTION (WAGLERIN-1)","TOXIN TARGET"]},{"referenceNumber":8,"citation":{"id":"11724791","citationType":"journal article","authors":["Molles B.E.","Rezai P.","Kline E.F.","McArdle J.J.","Sine S.M.","Taylor P."],"citationCrossReferences":[{"database":"PubMed","id":"11724791"},{"database":"DOI","id":"10.1074/jbc.m109232200"}],"title":"Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors.","publicationDate":"2002","journal":"J. Biol. Chem.","firstPage":"5433","lastPage":"5440","volume":"277"},"referencePositions":["FUNCTION","TOXIN TARGET"]},{"referenceNumber":9,"citation":{"id":"CI-CMO460R5BUCTD","citationType":"journal article","authors":["Molles B.E.","Taylor P."],"citationCrossReferences":[{"database":"DOI","id":"10.1081/TXR-120014406"}],"title":"Structure and function of the waglerins, peptide toxins from the venom of Wagler's Pit Viper, Tropidolaemus wagleri.","publicationDate":"2002","journal":"J. Toxicol. Toxin Rev.","firstPage":"273","lastPage":"292","volume":"21"},"referencePositions":["FUNCTION","TOXIN TARGET","MUTAGENESIS OF 3-GLY-GLY-4; 23-PRO-ARG-24; CYS-11; HIS-12; CYS-15 AND HIS-16","REVIEW"]},{"referenceNumber":10,"citation":{"id":"8547337","citationType":"journal article","authors":["Chuang L.C.","Yu H.M.","Chen C.","Huang T.H.","Wu S.H.","Wang K.T."],"citationCrossReferences":[{"database":"PubMed","id":"8547337"},{"database":"DOI","id":"10.1016/0167-4838(95)00181-6"}],"title":"Determination of three-dimensional solution structure of waglerin I, a toxin from Trimeresurus wagleri, using 2D-NMR and molecular dynamics simulation.","publicationDate":"1996","journal":"Biochim. Biophys. Acta","firstPage":"145","lastPage":"155","volume":"1292"},"referencePositions":["STRUCTURE BY NMR OF 3-24","SYNTHESIS OF 3-24","ISOMERIZATION (WAGLERIN-1)"]},{"referenceNumber":11,"citation":{"id":"8770182","citationType":"journal article","authors":["Sellin L.C.","Mattila K.","Annila A.","Schmidt J.J.","McArdle J.J.","Hyvonen M.","Rantala T.T.","Kivisto T."],"citationCrossReferences":[{"database":"PubMed","id":"8770182"},{"database":"DOI","id":"10.1016/s0006-3495(96)79559-0"}],"title":"Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor.","publicationDate":"1996","journal":"Biophys. J.","firstPage":"3","lastPage":"13","volume":"70"},"referencePositions":["STRUCTURE BY NMR OF 3-24"]}],"uniProtKBCrossReferences":[{"database":"PIR","id":"B44008","properties":[{"key":"EntryName","value":"B44008"}]},{"database":"AlphaFoldDB","id":"P24335","properties":[{"key":"Description","value":"-"}]},{"database":"GO","id":"GO:0005576","properties":[{"key":"GoTerm","value":"C:extracellular region"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0030550","properties":[{"key":"GoTerm","value":"F:acetylcholine receptor inhibitor activity"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"InterPro","id":"IPR012637","properties":[{"key":"EntryName","value":"Toxin_33"}]},{"database":"Pfam","id":"PF08121","properties":[{"key":"EntryName","value":"Toxin_33"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"SLGGKPDLRPCHPPCHYIPRPKPR","length":24,"molWeight":2722,"crc64":"D9B533A32692594F","md5":"C4E8436C695CD8DA26EF01B898FAF4DB"},"extraAttributes":{"countByCommentType":{"FUNCTION":2,"SUBUNIT":1,"SUBCELLULAR LOCATION":1,"TISSUE SPECIFICITY":1,"PTM":1,"TOXIC DOSE":2,"MISCELLANEOUS":1,"SIMILARITY":1,"CAUTION":1},"countByFeatureType":{"Peptide":2,"Region":1,"Compositional bias":1,"Disulfide bond":1,"Mutagenesis":14},"uniParcId":"UPI000017BFC9"}}