{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:35:46Z","timestamp":1782513346991,"version":"3.54.5"},"reference-count":150,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_162564"],"award-info":[{"award-number":["31003A_162564"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Most knowledge of spider venom concerns neurotoxins acting on ion channels, whereas proteins and their significance for the envenomation process are neglected. The here presented comprehensive analysis of the venom gland transcriptome and proteome of Cupiennius salei focusses on proteins and cysteine-containing peptides and offers new insight into the structure and function of spider venom, here described as the dual prey-inactivation strategy. After venom injection, many enzymes and proteins, dominated by \u03b1-amylase, angiotensin-converting enzyme, and cysteine-rich secretory proteins, interact with main metabolic pathways, leading to a major disturbance of the cellular homeostasis. Hyaluronidase and cytolytic peptides destroy tissue and membranes, thus supporting the spread of other venom compounds. We detected 81 transcripts of neurotoxins from 13 peptide families, whereof two families comprise 93.7% of all cysteine-containing peptides. This raises the question of the importance of the other low-expressed peptide families. The identification of a venom gland-specific defensin-like peptide and an aga-toxin-like peptide in the hemocytes offers an important clue on the recruitment and neofunctionalization of body proteins and peptides as the origin of toxins.<\/jats:p>","DOI":"10.3390\/toxins11030167","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T12:12:25Z","timestamp":1552997545000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["The Dual Prey-Inactivation Strategy of Spiders\u2014In-Depth Venomic Analysis of Cupiennius salei"],"prefix":"10.3390","volume":"11","author":[{"given":"Lucia","family":"Kuhn-Nentwig","sequence":"first","affiliation":[{"name":"Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Langenegger","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6364-7325","authenticated-orcid":false,"given":"Manfred","family":"Heller","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Freiburgstrasse 15, CH-3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Koua","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland"},{"name":"Institut National Polytechnique F\u00e9lix Houphouet-Boigny, BP 1093 Yamoussoukro, Cote d\u2019Ivoire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Nentwig","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"ref_1","unstructured":"(2018, September 11). World Spider Catalog. Version 19.5. Available online: http:\/\/wsc.nmbe.ch."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wise, D.H. (1993). Spiders in Ecological Webs, Cambridge University Press.","DOI":"10.1017\/CBO9780511623431"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-387668-3.00001-5","article-title":"Venom composition and strategies in spiders: Is everything possible?","volume":"40","author":"Nentwig","year":"2011","journal-title":"Adv. Insect Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.3390\/toxins2122851","article-title":"Spider-venom peptides as therapeutics","volume":"2","author":"Saez","year":"2010","journal-title":"Toxins"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1007\/s00018-013-1315-3","article-title":"The insecticidal potential of venom peptides","volume":"70","author":"Smith","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"He, Q., Duan, Z., Yu, Y., Liu, Z., Liu, Z., and Liang, S. (2013). The venom gland transcriptome of Latrodectus tredecimguttatus revealed by deep sequencing and cDNA library analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081357"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Oldrati, V., Koua, D., Allard, P.M., Hulo, N., Arrell, M., Nentwig, W., Lisacek, F., Wolfender, J.L., Kuhn-Nentwig, L., and Stocklin, R. (2017). Peptidomic and transcriptomic profiling of four distinct spider venoms. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172966"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Huang, Y., He, Q., Liu, J., Luo, J., Zhu, L., Lu, S., Huang, P., Chen, X., and Zeng, X. (2014). Toxin diversity revealed by a transcriptomic study of Ornithoctonus huwena. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100682"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Biner, O., Trachsel, C., Moser, A., Kopp, L., Langenegger, N., K\u00e4mpfer, U., von Ballmoos, C., Nentwig, W., Sch\u00fcrch, S., and Schaller, J. (2015). Isolation, N-glycosylations and function of a hyaluronidase-like enzyme from the venom of the spider Cupiennius salei. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143963"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pedroso, A., Matioli, S.R., Murakami, M.T., Pidde-Queiroz, G., and Tambourgi, D.V. (2015). Adaptive evolution in the toxicity of a spider\u2019s venom enzymes. BMC Evol. Biol., 15.","DOI":"10.1186\/s12862-015-0561-4"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Diniz, M.R.V., Paiva, A.L.B., Guerra-Duarte, C., Nishiyama, M.Y.J., Mudadu, M.A., Oliveira, U., Borges, M.H., Yates, J.R., and Junqueira-de-Azevedo, I.L. (2018). An overview of Phoneutria nigriventer spider venom using combined transcriptomic and proteomic approaches. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200628"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gopalakrishnakone, P. (2016). Venom of Cupiennius salei. Spider Venoms, Springer Science + Business Media.","DOI":"10.1007\/978-94-007-6389-0"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1111\/j.1742-4658.2012.08650.x","article-title":"Multicomponent venom of the spider Cupiennius salei: A bioanalytical investigation applying different strategies","volume":"279","author":"Trachsel","year":"2012","journal-title":"FEBS J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Barth, F. (2002). A Spider\u2019s World, Springer.","DOI":"10.1007\/978-3-662-04899-3"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25640","DOI":"10.1074\/jbc.M112.339051","article-title":"A Venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits cytolytic activities","volume":"287","author":"Fedorova","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D279","DOI":"10.1093\/nar\/gkv1344","article-title":"The Pfam protein families database: Towards a more sustainable future","volume":"44","author":"Finn","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s004410050040","article-title":"Immunocytochemical localization and secretion process of the toxin CSTX-1 in the venom gland of the wandering spider Cupiennius salei (Araneae: Ctenidae)","volume":"299","author":"Malli","year":"2000","journal-title":"Cell Tissue Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.ibmb.2011.08.003","article-title":"Purification, cDNA structure and biological significance of a single insulin-like growth factor-binding domain protein (SIBD-1) identified in the hemocytes of the spider Cupiennius salei","volume":"41","author":"Largiader","year":"2011","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/pro.757","article-title":"Signal peptidase I: Cleaving the way to mature proteins","volume":"21","author":"Auclair","year":"2012","journal-title":"Protein Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"D343","DOI":"10.1093\/nar\/gkv1118","article-title":"Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors","volume":"44","author":"Rawlings","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_21","first-page":"70","article-title":"Protein disulfide isomerase a multifunctional protein with multiple physiological roles","volume":"2","author":"Mutus","year":"2014","journal-title":"Front. Chem."},{"key":"ref_22","first-page":"163","article-title":"A new species of the genus Alopecosa Simon, 1885 (Araneae, Lycosidae) from south-east Kazakhstan","volume":"22","author":"Logunov","year":"2015","journal-title":"Arthropoda Selecta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/(SICI)1520-6327(200002)43:2<49::AID-ARCH1>3.0.CO;2-M","article-title":"Mono- and dibasic proteolytic cleavage sites in insect neuroendocrine peptide precursors","volume":"43","author":"Veenstra","year":"2000","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.toxicon.2006.11.007","article-title":"The universal algorithm of maturation for secretory and excretory protein precursors","volume":"49","author":"Kozlov","year":"2007","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1074\/jbc.M117.810911","article-title":"Identification of a precursor processing protease from the spider Cupiennius salei essential for venom neurotoxin maturation","volume":"293","author":"Langenegger","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11251","DOI":"10.1073\/pnas.0402226101","article-title":"CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the spider Cupiennius salei (Ctenidae)","volume":"101","author":"Wullschleger","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/1520-6327(200007)44:3<101::AID-ARCH1>3.0.CO;2-S","article-title":"A lysine rich C-terminal tail is directly involved in the toxocity of CSTX-1, a neurotoxic peptide from the venom of the spider Cupiennius salei","volume":"44","author":"Schaller","year":"2000","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20983","DOI":"10.1074\/jbc.M602168200","article-title":"Latarcins, antimicrobial and cytolytic peptides from the venom of the spider Lachesana tarabaevi (Zodariidae) that exemplify biomolecular diversity","volume":"281","author":"Kozlov","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_29","first-page":"1571","article-title":"The multifunctional peptidylglycine alpha-amidating monooxygenase gene: Exon\/intron organization of catalytic, processing, and routing domains","volume":"6","author":"Ouafik","year":"1992","journal-title":"Mol. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.str.2015.05.003","article-title":"Weaponization of a hormone: Convergent recruitment of hyperglycemic hormone into the venom of arthropod predators","volume":"23","author":"Undheim","year":"2015","journal-title":"Structure"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.genom.9.081307.164356","article-title":"The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms","volume":"10","author":"Fry","year":"2009","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5090","DOI":"10.1038\/s41598-018-23108-9","article-title":"Transcriptome profiles reveal the crucial roles of hormone and sugar in the bud dormancy of Prunus mume","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.3389\/fmicb.2016.01129","article-title":"Bacterial and archaeal alpha-amylases: Diversity and amelioration of the desirable characteristics for industrial applications","volume":"7","author":"Mehta","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_34","first-page":"35","article-title":"Isolation, identification and in silico analysis of alpha-amylase gene of Aspergillus niger strain CSA35 obtained from cassava undergoing spoilage","volume":"14","author":"Avwioroko","year":"2018","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.archoralbio.2015.05.008","article-title":"Salivary amylase\u2014The enzyme of unspecialized euryphagous animals","volume":"60","author":"Boehlke","year":"2015","journal-title":"Arch. Oral Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.jinsphys.2012.10.002","article-title":"Transcriptome analysis of the salivary glands of potato leafhopper, Empoasca fabae","volume":"58","author":"DeLay","year":"2012","journal-title":"J. Insect Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF00738421","article-title":"Comparison of digestive \u03b1-amylases from two species of spiders (Tegenaria atrica and Cupiennius salei)","volume":"127","author":"Mommsen","year":"1978","journal-title":"J. Comp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Fuzita, F.J., Pinkse, M.W., Patane, J.S., Verhaert, P.D., and Lopes, A.R. (2016). High throughput techniques to reveal the molecular physiology and evolution of digestion in spiders. BMC Genom., 17.","DOI":"10.1186\/s12864-016-3048-9"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.asd.2014.12.002","article-title":"Changes in the midgut diverticula in the harvestmen Amilenus aurantiacus (Phalangiidae, Opiliones) during winter diapause","volume":"44","author":"Lipovsek","year":"2015","journal-title":"Arthropod Struct. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Smrz, J., Kovac, L., Mikes, J., and Lukesova, A. (2013). Microwhip scorpions (Palpigradi) feed on heterotrophic cyanobacteria in Slovak caves\u2014A curiosity among Arachnida. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075989"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fphys.2018.00030","article-title":"Invertebrate trehalose-6-phosphate synthase gene: Genetic architecture, biochemistry, physiological function, and potential applications","volume":"9","author":"Tang","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gronke, S., Clarke, D.F., Broughton, S., Andrews, T.D., and Partridge, L. (2010). Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000857"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ibmb.2014.04.002","article-title":"Functional analysis of the glycogen binding subunit CG9238\/Gbs-70E of protein phosphatase 1 in Drosophila melanogaster","volume":"49","author":"Kerekes","year":"2014","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bbagen.2013.08.015","article-title":"FoxO is required for the activation of hypertrehalosemic hormone expression in cockroaches","volume":"1840","author":"Abrisqueta","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3389\/fendo.2018.00245","article-title":"Drosophila insulin-like peptides DILP2 and DILP5 differentially stimulate cell signaling and glycogen phosphorylase to regulate longevity","volume":"9","author":"Post","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/bs.ctdb.2016.07.011","article-title":"Drosophila as a model for diabetes and diseases of insulin resistance","volume":"121","author":"Graham","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31105","DOI":"10.1074\/jbc.M304843200","article-title":"Isolation and characterization of a cone snail protease with homology to CRISP proteins of the pathogenesis-related protein superfamily","volume":"278","author":"Milne","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12828","DOI":"10.1021\/bi061311a","article-title":"A single gamma-carboxyglutamic acid residue in a novel cysteine-rich secretory protein without propeptide","volume":"45","author":"Hansson","year":"2006","journal-title":"Biochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1745-7270.2008.00385.x","article-title":"Cloning and isolation of a Conus cysteine-rich protein homologous to Tex31 but without proteolytic activity","volume":"40","author":"Qian","year":"2008","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14341","DOI":"10.1074\/jbc.M113.466995","article-title":"Salivary antigen-5\/CAP family members are Cu2+-dependent antioxidant enzymes that scavenge O(2)(-). and inhibit collagen-induced platelet aggregation and neutrophil oxidative burst","volume":"288","author":"Assumpcao","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cajado-Carvalho, D., Kuniyoshi, A.K., Duzzi, B., Iwai, L.K., Oliveira, U.C., Junqueira de Azevedo, I.L., Kodama, R.T., and Portaro, F.V. (2016). Insights into the hypertensive effects of Tityus serrulatus scorpion venom: Purification of an angiotensin-converting enzyme-like peptidase. Toxins, 8.","DOI":"10.3390\/toxins8120348"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"de Oliveira, U.C., Nishiyama, M.Y.J., Dos Santos, M.B.V., Santos-da-Silva, A.P., Chalkidis, H.M., Souza-Imberg, A., Candido, D.M., Yamanouye, N., Dorce, V.A.C., and Junqueira-de-Azevedo, I.L.M. (2018). Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193739"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jprot.2017.04.022","article-title":"Proteomic and transcriptomic analysis of saliva components from the hematophagous reduviid Triatoma pallidipennis","volume":"162","author":"Gil","year":"2017","journal-title":"J. Proteom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.gene.2017.01.017","article-title":"The angiotensin-converting enzyme (ACE) gene family of Bombyx mori","volume":"608","author":"Yan","year":"2017","journal-title":"Gene"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.peptides.2018.06.004","article-title":"Glucose, some amino acids and a plant secondary metabolite, chlorogenic acid induce the secretion of a regulatory hormone, tachykinin-related peptide, from the silkworm midgut","volume":"106","author":"Yamagishi","year":"2018","journal-title":"Peptides"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1126\/science.2274788","article-title":"Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue","volume":"250","author":"Scott","year":"1990","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1432-1033.1974.tb03787.x","article-title":"The amino-acid sequence and carbohydrate content of phospholipase A2 from bee venom","volume":"48","author":"Shipolini","year":"1974","journal-title":"Eur. J. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.gene.2007.03.007","article-title":"Sequence analysis and phylogenetic relationship of genes encoding heterodimeric phospholipases A2 from the venom of the scorpion Anuroctonus phaiodactylus","volume":"396","author":"Segovia","year":"2007","journal-title":"Gene"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kordis, D., and Turk, V. (2009). Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes. BMC Evol. Biol., 9.","DOI":"10.1186\/1471-2148-9-266"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e3142","DOI":"10.7717\/peerj.3142","article-title":"Comparative venom gland transcriptomics of Naja kaouthia (monocled cobra) from Malaysia and Thailand: Elucidating geographical venom variation and insights into sequence novelty","volume":"5","author":"Tan","year":"2017","journal-title":"PeerJ"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.2741\/3089","article-title":"Cystatins: Biochemical and structural properties, and medical relevance","volume":"13","author":"Turk","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1042\/BJ20100280","article-title":"Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata","volume":"429","author":"Salat","year":"2010","journal-title":"Biochem. J."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Choo, Y.M., Lee, K.S., Yoon, H.J., Qiu, Y., Wan, H., Sohn, M.R., Sohn, H.D., and Jin, B.R. (2012). Antifibrinolytic role of a bee venom serine protease inhibitor that acts as a plasmin inhibitor. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032269"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhao, R., Dai, H., Qiu, S., Li, T., He, Y., Ma, Y., Chen, Z., Wu, Y., Li, W., and Cao, Z. (2011). SdPI, the first functionally characterized Kunitz-type trypsin inhibitor from scorpion venom. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027548"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Santibanez-Lopez, C.E., Ontano, A.Z., Harvey, M.S., and Sharma, P.P. (2018). Transcriptomic analysis of pseudoscorpion venom reveals a unique cocktail dominated by enzymes and protease inhibitors. Toxins, 10.","DOI":"10.3390\/toxins10050207"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wan, H., Lee, K.S., Kim, B.Y., Zou, F.M., Yoon, H.J., Je, Y.H., Li, J., and Jin, B.R. (2013). A spider-derived Kunitz-type serine protease inhibitor that acts as a plasmin inhibitor and an elastase inhibitor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053343"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.vetpar.2012.01.027","article-title":"Expression and functional characterization of boophilin, a thrombin inhibitor from Rhipicephalus (Boophilus) microplus midgut","volume":"187","author":"Soares","year":"2012","journal-title":"Vet. Parasitol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Tsujimoto, H., Kotsyfakis, M., Francischetti, I.M., Eum, J.H., Strand, M.R., and Champagne, D.E. (2012). Simukunin from the salivary glands of the black fly Simulium vittatum inhibits enzymes that regulate clotting and inflammatory responses. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029964"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.ibmb.2009.07.003","article-title":"Tick-derived Kunitz-type inhibitors as antihemostatic factors","volume":"39","year":"2009","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bcp.2011.03.023","article-title":"A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties","volume":"82","author":"Peigneur","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Santibanez-Lopez, C.E., Cid-Uribe, J.I., Batista, C.V., Ortiz, E., and Possani, L.D. (2016). Venom gland transcriptomic and proteomic analyses of the enigmatic scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with insights on the evolution of its venom components. Toxins, 8.","DOI":"10.3390\/toxins8120367"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Anatriello, E., Ribeiro, J.M., de Miranda-Santos, I.K., Brandao, L.G., Anderson, J.M., Valenzuela, J.G., Maruyama, S.R., Silva, J.S., and Ferreira, B.R. (2010). An insight into the sialotranscriptome of the brown dog tick, Rhipicephalus sanguineus. BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-450"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1515\/BC.2007.155","article-title":"Two decades of thyroglobulin type-1 domain research","volume":"388","author":"Mihelic","year":"2007","journal-title":"Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chandler, J.C., Gandhi, N.S., Mancera, R.L., Smith, G., Elizur, A., and Ventura, T. (2017). Understanding insulin endocrinology in decapod Crustacea: Molecular modelling characterization of an insulin-binding protein and insulin-like peptides in the eastern spiny lobster, Sagmariasus verreauxi. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091832"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10493-007-9064-3","article-title":"The molecular basis of the Amblyomma americanum tick attachment phase","volume":"41","author":"Mulenga","year":"2007","journal-title":"Exp. Appl. Acarol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10086","DOI":"10.1073\/pnas.96.18.10086","article-title":"Horseshoe crab acetyl group-recognizing lectins involved in innate immunity are structurally related to fibrinogen","volume":"96","author":"Gokudan","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-4615-1291-2_18","article-title":"Role of tachylectins in host defense of the Japanese horseshoe crab Tachypleus tridentatus","volume":"484","author":"Kawabata","year":"2001","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1007\/s00436-015-4365-7","article-title":"Identification of the Babesia-responsive leucine-rich repeat domain-containing protein from the hard tick Haemaphysalis longicornis","volume":"114","author":"Maeda","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Koua, D., and Kuhn-Nentwig, L. (2017). Spider neurotoxins, short linear cationic peptides and venom protein classification improved by an automated competition between exhaustive profile HMM classifiers. Toxins, 9.","DOI":"10.3390\/toxins9080245"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.toxicon.2008.05.020","article-title":"A rational nomenclature for naming peptide toxins from spiders and other venomous animals","volume":"52","author":"King","year":"2008","journal-title":"Toxicon"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/S0041-0101(98)00149-4","article-title":"The cystine knot structure of ion channel toxins and related polypeptides","volume":"36","author":"Norton","year":"1998","journal-title":"Toxicon"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/75921","article-title":"Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge","volume":"7","author":"Wang","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/molbev\/msu038","article-title":"Experimental conversion of a defensin into a neurotoxin: Implications for origin of toxic function","volume":"31","author":"Zhu","year":"2014","journal-title":"Mol. Biol. Evol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"King, G.F. (2015). The structural universe of disulfide-rich venom peptides. Venoms to Drugs, The Royal Society of Chemistry.","DOI":"10.1039\/9781849737876"},{"key":"ref_85","unstructured":"Kopp, L. (2013). Biochemical and Mass Spectrometric Analysis of Venom Components, Venom Gland, and Hemocytes of the Spider Cupiennius salei. [Ph.D. Thesis, The University of Bern]."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1016\/j.peptides.2005.05.012","article-title":"Discovery of an MIT-like atracotoxin family: Spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins","volume":"26","author":"Wen","year":"2005","journal-title":"Peptides"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5608","DOI":"10.1021\/bi0360915","article-title":"How C-terminal carboxyamidation alters the biological activity of peptides from the venom of the eumenine solitary wasp","volume":"43","author":"Sforca","year":"2004","journal-title":"Biochemistry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.neuropharm.2007.03.012","article-title":"CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons","volume":"52","author":"Kubista","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"32293","DOI":"10.1074\/jbc.M110.104265","article-title":"Novel class of spider toxin: Active principle from the yellow sac spider Cheiracanthium punctorium venom is a unique two-domain polypeptide","volume":"285","author":"Vassilevski","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.zool.2009.04.001","article-title":"Transcriptome analysis of the venom glands of the Chinese wolf spider Lycosa singoriensis","volume":"113","author":"Zhang","year":"2010","journal-title":"Zoology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1042\/BCJ20160573","article-title":"Structure of purotoxin-2 from wolf spider: Modular design and membrane-assisted mode of action in arachnid toxins","volume":"473","author":"Oparin","year":"2016","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Nentwig, W. (2013). The cytotoxic mode of action of the venom of Cupiennius salei (Ctenidae). Spider Ecophysiology, Springer.","DOI":"10.1007\/978-3-642-33989-9_16"},{"key":"ref_93","unstructured":"de Lima, M.E. (2009). Structural and functional diversity in the venom of spiders of the genus Phoneutria. Animal Toxins: State of the Art, Editora UFMG."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0041-0101(93)90354-L","article-title":"Purification and amino acid sequences of six Tx3 type neurotoxins from the venom of the Brazilian \u2018armed\u2019 spider Phoneutria nigriventer (Keys)","volume":"31","author":"Diniz","year":"1993","journal-title":"Toxicon"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.toxicon.2007.07.004","article-title":"Omega-Lsp-IA, a novel modulator of P-type Ca2+ channels","volume":"50","author":"Pluzhnikov","year":"2007","journal-title":"Toxicon"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0304-3940(94)90572-X","article-title":"Omega aga-toxin IVA blocks high-voltage-activated calcium channel currents in cultured pars intercerebralis neurosecretory cells of adult Locusta migratoria","volume":"181","author":"Bickmeyer","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_97","first-page":"681","article-title":"Structure and properties of omega-agatoxin IVB, a new antagonist of P-type calcium channels","volume":"44","author":"Adams","year":"1993","journal-title":"Mol. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jprot.2015.11.021","article-title":"Agatoxin-like peptides in the neuroendocrine system of the honey bee and other insects","volume":"132","author":"Sturm","year":"2016","journal-title":"J. Proteom."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/molbev\/mst199","article-title":"The first venomous crustacean revealed by transcriptomics and functional morphology: Remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin","volume":"31","author":"Blanke","year":"2014","journal-title":"Mol. Biol. Evol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/prot.20390","article-title":"A novel strategy for the identification of toxinlike structures in spider venom","volume":"59","author":"Kozlov","year":"2005","journal-title":"Proteins"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1124\/mol.105.021147","article-title":"Phoneutria nigriventer toxin 1: A novel, state-dependent inhibitor of neuronal sodium channels that interacts with micro conotoxin binding sites","volume":"69","author":"Mansuelle","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s004240050670","article-title":"Omega-phonetoxin-IIA: A calcium channel blocker from the spider Phoneutria nigriventer","volume":"436","author":"Cassola","year":"1998","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"13856","DOI":"10.1074\/jbc.M112348200","article-title":"Phoneutria nigriventer omega-phonetoxin IIA blocks the Cav2 family of calcium channels and interacts with omega-conotoxin-binding sites","volume":"277","author":"Mansuelle","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"140023","DOI":"10.1038\/sdata.2014.23","article-title":"Comprehensive analysis of the venom gland transcriptome of the spider Dolomedes fimbriatus","volume":"1","author":"Kozlov","year":"2014","journal-title":"Sci. Data"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1016\/S0021-9258(18)45925-X","article-title":"Antagonism of synaptosomal calcium channels by subtypes of omega-agatoxins","volume":"267","author":"Venema","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1016\/j.bbamem.2012.07.016","article-title":"Modulation of P2X3 receptors by spider toxins","volume":"1818","author":"Kabanova","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.3390\/toxins5122488","article-title":"A proteomics and transcriptomics investigation of the venom from the barychelid spider Trittame loki (brush-foot trapdoor)","volume":"5","author":"Undheim","year":"2013","journal-title":"Toxins"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/1744-7917.12305","article-title":"Identification and characterization of toxins in the venom gland of the Chinese bird spider, Haplopelma hainanum, by transcriptomic analysis","volume":"23","author":"Cheng","year":"2016","journal-title":"Insect Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"26471","DOI":"10.1074\/jbc.A114.635458","article-title":"Structural and functional diversity of peptide toxins from tarantula Haplopelma hainanum (Ornithoctonus hainana) venom revealed by transcriptomic, peptidomic, and patch clamp approaches","volume":"290","author":"Zhang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.toxicon.2004.05.012","article-title":"Rapid and efficient identification of cysteine-rich peptides by random screening of a venom gland cDNA library from the hexathelid spider Macrothele gigas","volume":"44","author":"Satake","year":"2004","journal-title":"Toxicon"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bcp.2007.05.017","article-title":"The omega-atracotoxins: Selective blockers of insect M-LVA and HVA calcium channels","volume":"74","author":"Chong","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1021\/pr1000016","article-title":"Molecular diversification of peptide toxins from the tarantula Haplopelma hainanum (Ornithoctonus hainana) venom based on transcriptomic, peptidomic, and genomic analyses","volume":"9","author":"Tang","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0197-0186(92)90176-R","article-title":"Omega-agatoxins differentially block calcium channels in locust, chick and rat synaptosomes","volume":"20","author":"Pocock","year":"1992","journal-title":"Neurochem. Int."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"20701","DOI":"10.1016\/S0021-9258(19)36742-0","article-title":"Heterodimeric structure of the spider toxin omega-agatoxin IA revealed by precursor analysis and mass spectrometry","volume":"267","author":"Santos","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1093\/bioinformatics\/btx661","article-title":"ArachnoServer 3.0: An online resource for automated discovery, analysis and annotation of spider toxins","volume":"34","author":"Pineda","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.1998.2057","article-title":"A structural homologue of colipase in black mamba venom revealed by NMR floating disulphide bridge analysis","volume":"283","author":"Boisbouvier","year":"1998","journal-title":"J. Mol. Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1002\/cbic.201000330","article-title":"Chemical synthesis and structure of the prokineticin Bv8","volume":"11","author":"Morales","year":"2010","journal-title":"Chembiochem"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0041-0101(99)00174-9","article-title":"Isolation of a funnel-web spider polypeptide with homology to mamba intestinal toxin 1 and the embryonic head inducer Dickkopf-1","volume":"38","author":"Szeto","year":"2000","journal-title":"Toxicon"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxicon.2017.01.014","article-title":"Venom-gland transcriptomics and venom proteomics of the black-back scorpion (Hadrurus spadix) reveal detectability challenges and an unexplored realm of animal toxin diversity","volume":"128","author":"Rokyta","year":"2017","journal-title":"Toxicon"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/1756-3305-7-430","article-title":"The sialotranscriptome of Amblyomma triste, Amblyomma parvum and Amblyomma cajennense ticks, uncovered by 454-based RNA-seq","volume":"7","author":"Garcia","year":"2014","journal-title":"Parasit Vectors"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1007\/s00018-010-0354-2","article-title":"Expression of defensins in non-infected araneomorph spiders","volume":"67","author":"Baumann","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7097","DOI":"10.1074\/jbc.M115.680611","article-title":"Scorpion potassium channel-blocking defensin highlights a functional link with neurotoxin","volume":"291","author":"Meng","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.toxicon.2017.12.042","article-title":"Venom-gland transcriptomics and venom proteomics of the Hentz striped scorpion (Centruroides hentzi; Buthidae) reveal high toxin diversity in a harmless member of a lethal family","volume":"142","author":"Ward","year":"2018","journal-title":"Toxicon"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jprot.2015.07.030","article-title":"Unique diversity of the venom peptides from the scorpion Androctonus bicolor revealed by transcriptomic and proteomic analysis","volume":"128","author":"Zhang","year":"2015","journal-title":"J. Proteom."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"9103","DOI":"10.1038\/srep09103","article-title":"Tissue- and time-dependent transcription in Ixodes ricinus salivary glands and midguts when blood feeding on the vertebrate host","volume":"5","author":"Kotsyfakis","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1242\/jeb.01594","article-title":"Spider venom: Enhancement of venom efficacy mediated by different synergistic strategies in Cupiennius salei","volume":"208","author":"Wullschleger","year":"2005","journal-title":"J. Exp. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"11208","DOI":"10.1074\/jbc.M111099200","article-title":"Cupiennin 1, a new family of highly basic antimicrobial peptides in the venom of the spider Cupiennius salei (Ctenidae)","volume":"277","author":"Schaller","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00726-009-0471-0","article-title":"Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells","volume":"40","author":"Willems","year":"2011","journal-title":"Amino Acids"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1111\/j.1742-4658.2007.05726.x","article-title":"Cupiennin1a, an antimicrobial peptide from the venom of the neotropical wandering spider Cupiennius salei, also inhibits the formation of nitric oxide by neuronal nitric oxide synthase","volume":"274","author":"Pukala","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.tree.2012.10.020","article-title":"Complex cocktails: The evolutionary novelty of venoms","volume":"28","author":"Casewell","year":"2013","journal-title":"Trends Ecol. Evol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.toxicon.2017.05.002","article-title":"Venom gland transcriptomic and venom proteomic analyses of the scorpion Megacormus gertschi Diaz-Najera, 1966 (Scorpiones: Euscorpiidae: Megacorminae)","volume":"133","author":"Zamudio","year":"2017","journal-title":"Toxicon"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0041-0101(94)90082-5","article-title":"Purification of toxic peptides and the amino acid sequence of CSTX-1 from the multicomponent venom of Cupiennius salei (Araneae: Ctenidae)","volume":"32","author":"Schaller","year":"1994","journal-title":"Toxicon"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1093\/bioinformatics\/btu031","article-title":"InterProScan 5: Genome-scale protein function classification","volume":"30","author":"Jones","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0968-0004(99)01540-6","article-title":"NPS@: Network protein sequence analysis","volume":"25","author":"Combet","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s12064-012-0162-3","article-title":"Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples","volume":"131","author":"Wagner","year":"2012","journal-title":"Theory Biosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nmeth.1701","article-title":"SignalP 4.0: Discriminating signal peptides from transmembrane regions","volume":"8","author":"Petersen","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1074\/mcp.M116.060491","article-title":"Robust label-free, quantitative profiling of circulating plasma microparticle (MP) associated proteins","volume":"15","author":"Buchs","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1093\/bioinformatics\/btw398","article-title":"TopPIC: A software tool for top-down mass spectrometry-based proteoform identification and characterization","volume":"32","author":"Kou","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/nbt.2377","article-title":"A cross-platform toolkit for mass spectrometry and proteomics","volume":"30","author":"Chambers","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s13361-015-1179-x","article-title":"A deeper look into Comet\u2014Implementation and features","volume":"26","author":"Eng","year":"2015","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1002\/rcm.1198","article-title":"A method for reducing the time required to match protein sequences with tandem mass spectra","volume":"17","author":"Craig","year":"2003","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1038\/ncomms6277","article-title":"MS-GF+ makes progress towards a universal database search tool for proteomics","volume":"5","author":"Kim","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1021\/pr0604054","article-title":"MyriMatch: Highly accurate tandem mass spectral peptide identification by multivariate hypergeometric analysis","volume":"6","author":"Tabb","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1021\/pr7006818","article-title":"Statistical validation of peptide identifications in large-scale proteomics using the target-decoy database search strategy and flexible mixture modeling","volume":"7","author":"Choi","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/pmic.200900375","article-title":"A guided tour of the trans-proteomic pipeline","volume":"10","author":"Deutsch","year":"2010","journal-title":"Proteomics"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"M111.007690","DOI":"10.1074\/mcp.M111.007690","article-title":"iProphet: Multi-level integrative analysis of shotgun proteomic data improves peptide and protein identification rates and error estimates","volume":"10","author":"Shteynberg","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.1021\/ac0341261","article-title":"A statistical model for identifying proteins by tandem mass spectrometry","volume":"75","author":"Nesvizhskii","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/sysbio\/sys029","article-title":"MrBayes 3.2: Efficient Bayesian phylogenetic inference and model choice across a large model space","volume":"61","author":"Ronquist","year":"2012","journal-title":"Syst. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/3\/167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:54Z","timestamp":1760186334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/3\/167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,19]]},"references-count":150,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["toxins11030167"],"URL":"https:\/\/doi.org\/10.3390\/toxins11030167","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,19]]}}}