{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T03:31:15Z","timestamp":1763436675996,"version":"build-2065373602"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Cephalopods, successful predators, can use a mixture of substances to subdue their prey, becoming interesting sources of bioactive compounds. In addition to neurotoxins and enzymes, the presence of antimicrobial compounds has been reported. Recently, the transcriptome and the whole proteome of the Octopus vulgaris salivary apparatus were released, but the role of some compounds\u2014e.g., histones, antimicrobial peptides (AMPs), and toxins\u2014remains unclear. Herein, we profiled the proteome of the posterior salivary glands (PSGs) of O. vulgaris using two sample preparation protocols combined with a shotgun-proteomics approach. Protein identification was performed against a composite database comprising data from the UniProtKB, all transcriptomes available from the cephalopods\u2019 PSGs, and a comprehensive non-redundant AMPs database. Out of the 10,075 proteins clustered in 1868 protein groups, 90 clusters corresponded to venom protein toxin families. Additionally, we detected putative AMPs clustered with histones previously found as abundant proteins in the saliva of O. vulgaris. Some of these histones, such as H2A and H2B, are involved in systemic inflammatory responses and their antimicrobial effects have been demonstrated. These results not only confirm the production of enzymes and toxins by the O. vulgaris PSGs but also suggest their involvement in the first line of defense against microbes.<\/jats:p>","DOI":"10.3390\/antibiotics9110757","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T09:29:32Z","timestamp":1604050172000},"page":"757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Putative Antimicrobial Peptides of the Posterior Salivary Glands from the Cephalopod Octopus vulgaris Revealed by Exploring a Composite Protein Database"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9874-933X","authenticated-orcid":false,"given":"Daniela","family":"Almeida","sequence":"first","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-972X","authenticated-orcid":false,"given":"Dany","family":"Dom\u00ednguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"}]},{"given":"Ana","family":"Matos","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"},{"name":"Biology Department of the Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9908-2418","authenticated-orcid":false,"given":"Guillermin","family":"Ag\u00fcero-Chapin","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"},{"name":"Biology Department of the Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-8255","authenticated-orcid":false,"given":"Hugo","family":"Os\u00f3rio","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade-i3S, University of Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology of the Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-2417","authenticated-orcid":false,"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"},{"name":"Biology Department of the Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Alexandre","family":"Campos","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1328-1732","authenticated-orcid":false,"given":"Agostinho","family":"Antunes","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal"},{"name":"Biology Department of the Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Almeida, D., Maldonado, E., Vasconcelos, V., and Antunes, A. (2015). Adaptation of the Mitochondrial Genome in Cephalopods: Enhancing Proton Translocation Channels and the Subunit Interactions. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135405"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4056\/sigs.3136559","article-title":"Cephalopod genomics: A plan of strategies and organization","volume":"7","author":"Albertin","year":"2012","journal-title":"Stand. Genom. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/B978-0-12-800287-2.00003-2","article-title":"The Study of Deep-Sea Cephalopods","volume":"Volume 67","author":"Hoving","year":"2014","journal-title":"Advances in Marine Biology"},{"key":"ref_4","unstructured":"Nateewathana, A., Munprasit, A., and Dithachey, P. (1999, January 13\u201315). Systematics and distribution of oceanic cephalopods in the South China Sea, Area III: Western Philippines. Proceedings of the Third Technical Seminar on Marine Fishery Resources Survey in the South China Sea, Area III, Western Philippines, Philippines."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1242\/jeb.201.16.2413","article-title":"Flight of the vampire: Ontogenetic gait-transition in vampyroteuthis infernalis (Cephalopoda: Vampyromorpha)","volume":"201","author":"Seibel","year":"1998","journal-title":"J. Exp. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/j.1096-3642.2010.00656.x","article-title":"What can the mitochondrial genome reveal about higher-level phylogeny of the molluscan class Cephalopoda?","volume":"161","author":"Allcock","year":"2011","journal-title":"Zool. J. Linn. Soc."},{"key":"ref_7","unstructured":"Boyle, P., and Rodhouse, P. (2008). Cephalopods: Ecology and Fisheries, Wiley-Blackwell."},{"key":"ref_8","first-page":"199","article-title":"Distribution of recent Cephalopoda and implications for Plio-Pleistocene events","volume":"3","author":"Nesis","year":"2003","journal-title":"Berliner Pal\u00e4obiologische Abhandlungen"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20130273","DOI":"10.1098\/rspb.2013.0273","article-title":"Mitochondrial genome diversity and population structure of the giant squid Architeuthis: Genetics sheds new light on one of the most enigmatic marine species","volume":"280","author":"Winkelmann","year":"2013","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hanlon, R.T., and Messenger, J.B. (2018). Cephalopod Behaviour, Cambridge University Press. [2nd ed.].","DOI":"10.1017\/9780511843600"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wells, M.J. (1978). Octopus: Physiology and Behaviour of an Advanced Invertebrate, Chapman and Hall. [1st ed.].","DOI":"10.1007\/978-94-017-2468-5"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3389\/fphys.2017.00598","article-title":"Cephalopods as Predators: A Short Journey among Behavioral Flexibilities, Adaptions, and Feeding Habits","volume":"8","author":"Villanueva","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cooke, I.R., Whitelaw, B., Norman, M., Caruana, N., and Strugnell, J.M. (2015). Toxicity in Cephalopods. Evolution of Venomous Animals and Their Toxins, Springer.","DOI":"10.1007\/978-94-007-6727-0_7-1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"580","DOI":"10.3389\/fphys.2017.00580","article-title":"Salivary Glands in Predatory Mollusks: Evolutionary Considerations","volume":"8","author":"Ponte","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/1831192b0","article-title":"Cephalotoxin: The Crab-paralysing Agent of the Posterior Salivary Glands of Cephalopods","volume":"183","author":"Ghiretti","year":"1959","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0196-9781(02)00274-7","article-title":"Isolation and characterization of novel tachykinins from the posterior salivary gland of the common octopus Octopus vulgaris","volume":"24","author":"Kanda","year":"2003","journal-title":"Peptides"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.toxicon.2008.07.007","article-title":"Purification and molecular cloning of SE-cephalotoxin, a novel proteinaceous toxin from the posterior salivary gland of cuttlefish Sepia esculenta","volume":"52","author":"Ueda","year":"2008","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s00239-013-9552-5","article-title":"Molecular Phylogeny and Evolution of the Proteins Encoded by Coleoid (Cuttlefish, Octopus, and Squid) Posterior Venom Glands","volume":"76","author":"Ruder","year":"2013","journal-title":"J. Mol. Evol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1021\/acs.jproteome.6b00452","article-title":"Combined Transcriptomic and Proteomic Analysis of the Posterior Salivary Gland from the Southern Blue-Ringed Octopus and the Southern Sand Octopus","volume":"15","author":"Whitelaw","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00239-009-9223-8","article-title":"Tentacles of Venom: Toxic Protein Convergence in the Kingdom Animalia","volume":"68","author":"Fry","year":"2009","journal-title":"J. Mol. Evol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jprot.2014.05.019","article-title":"Dual role of the cuttlefish salivary proteome in defense and predation","volume":"108","author":"Cornet","year":"2014","journal-title":"J. Proteom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1021\/acs.jproteome.8b00525","article-title":"Shotgun Proteomics Analysis of Saliva and Salivary Gland Tissue from the Common Octopus Octopus vulgaris","volume":"17","author":"Fingerhut","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1016\/j.ygeno.2018.11.026","article-title":"The Harderian gland transcriptomes of Caraiba andreae, Cubophis cantherigerus and Tretanorhinus variabilis, three colubroid snakes from Cuba","volume":"111","author":"Durban","year":"2019","journal-title":"Genomics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sunagar, K., Fry, B.G., Jackson, T.N.W., Casewell, N.R., Undheim, E.A.B., Vidal, N., Ali, S.A., King, G.F., Vasudevan, K., and Vasconcelos, V. (2013). Correction: Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf. PLoS ONE, 8.","DOI":"10.1371\/annotation\/accecc73-91b2-45d4-bb33-774b1f394ca1"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ag\u00fcero-Chapin, G., Galpert, D., Molina-Ruiz, R., Ancede-Gallardo, E., P\u00e9rez-Machado, G., De la Riva, G.A., and Antunes, A. (2019). Graph Theory-Based Sequence Descriptors as Remote Homology Predictors. Biomolecules, 10.","DOI":"10.3390\/biom10010026"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1080\/07388551.2017.1331335","article-title":"Beyond the beaten path: Improving natural products bioprospecting using an eco-evolutionary framework\u2014The case of the octocorals","volume":"38","author":"Ledoux","year":"2018","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.peptides.2013.07.002","article-title":"Functional characterization on invertebrate and vertebrate tissues of tachykinin peptides from octopus venoms","volume":"47","author":"Ruder","year":"2013","journal-title":"Peptides"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/0003-9861(63)90533-2","article-title":"The isolation and amino acid sequence of eledoisin, the active endecapeptide of the posterior salivary glands of Eledone","volume":"101","author":"Anastasi","year":"1963","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Norman, M.D., and Reid, A.L. (2000). Guide to Squid, Cuttlefish and Octopuses of Australasia, CSIRO Publishing.","DOI":"10.1071\/9780643101098"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/15569543.2016.1220397","article-title":"Toxin synergism in snake venoms","volume":"35","author":"Laustsen","year":"2016","journal-title":"Toxin Rev."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-P\u00e9rez, D., Campos, A., Rodr\u00edguez, A.A., Turkina, M.V., Ribeiro, T., Osorio, H., Vasconcelos, V., and Antunes, A. (2018). Proteomic Analyses of the Unexplored Sea Anemone Bunodactis verrucosa. Mar. Drugs, 16.","DOI":"10.3390\/md16020042"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sutherland, S.K., and Lane, W.R. (1969). Toxins and mode of envenomation of the common ringed or blue-banded octopus. Med. J. Aust., 893\u2013898.","DOI":"10.5694\/j.1326-5377.1969.tb49778.x"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s00726-018-2633-4","article-title":"Design of antimicrobial peptides from a cuttlefish database","volume":"50","author":"Houyvet","year":"2018","journal-title":"Amin. Acids"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Matos, A., Dom\u00ednguez-P\u00e9rez, D., Almeida, D., Ag\u00fcero-Chapin, G., Campos, A., Os\u00f3rio, H., Vasconcelos, V., and Antunes, A. (2020). Shotgun Proteomics of Ascidians Tunic Gives New Insights on Host\u2013Microbe Interactions by Revealing Diverse Antimicrobial Peptides. Mar. Drugs, 18.","DOI":"10.3390\/md18070362"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Maselli, V., Galdiero, E., Salzano, A.M., Scaloni, A., Maione, A., Falanga, A., Naviglio, D., Guida, M., Di Cosmo, A., and Galdiero, S. (2020). OctoPartenopin: Identification and Preliminary Characterization of a Novel Antimicrobial Peptide from the Suckers of Octopus vulgaris. Mar. Drugs, 18.","DOI":"10.3390\/md18080380"},{"key":"ref_37","first-page":"32","article-title":"Cephalopods as a Source of New Antimicrobial Substances","volume":"61","author":"Besednova","year":"2016","journal-title":"Antibiotiki i Khimioterapiia = Antibiot. Chemoterapy [sic]"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1134\/S1063074017020031","article-title":"Cephalopods: The potential for their use in medicine","volume":"43","author":"Besednova","year":"2017","journal-title":"Russ. J. Mar. Biol."},{"key":"ref_39","first-page":"3582","article-title":"Molecular characterization and antimicrobial activity of Octopus aegina and Octopus dolfusii in gulf of Mannar coast","volume":"4","author":"Monolisha","year":"2013","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2217\/fmb.15.151","article-title":"Histones as mediators of host defense, inflammation and thrombosis","volume":"11","author":"Hoeksema","year":"2016","journal-title":"Future Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1038\/s41598-018-20912-1","article-title":"Histone H5 is a potent Antimicrobial Agent and a template for novel Antimicrobial Peptides","volume":"8","author":"Jodoin","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2174\/1871526510808030195","article-title":"Potential Roles of Histones in Host Defense as Antimicrobial Agents","volume":"8","author":"Kawasaki","year":"2008","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.4049\/jimmunol.165.6.3268","article-title":"Pepsin-Mediated Processing of the Cytoplasmic Histone H2A to Strong Antimicrobial Peptide Buforin I","volume":"165","author":"Kim","year":"2000","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1093\/bioinformatics\/btv180","article-title":"Overlap and diversity in antimicrobial peptide databases: Compiling a non-redundant set of sequences","volume":"31","author":"Salgado","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3390\/ph7030265","article-title":"Antimicrobial Peptides from Fish","volume":"7","author":"Diamond","year":"2014","journal-title":"Pharmaceuticals"},{"key":"ref_46","unstructured":"Almeida, D., Dom\u00ednguez-P\u00e9rez, D., Matos, A., Ag\u00fcero-Chapin, G., Casta\u00f1o, Y., Vasconcelos, V., Campos, A., and Antunes, A. Data employed in the construction of a composite protein database for proteogenomic analyses of cephalopods salivary apparatus. Data, submitted."},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0305-0491(93)90186-9","article-title":"Separation and partial characterization of SALIVARY enzymes expressed during prey handling in the octopus eledone cirrhosa","volume":"105","author":"Grisley","year":"1993","journal-title":"Comp. Biochem. Physiol. Part B Comp. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1210\/er.2008-0032","article-title":"The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins\u2014Roles in Reproduction, Cancer, and Immune Defense","volume":"29","author":"Gibbs","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbapap.2011.04.009","article-title":"Snake venom metalloproteinases: Structure, function and relevance to the mammalian ADAM\/ADAMTS family proteins","volume":"1824","author":"Takeda","year":"2012","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.toxicon.2005.02.029","article-title":"Hemorrhage induced by snake venom metalloproteinases: Biochemical and biophysical mechanisms involved in microvessel damage","volume":"45","author":"Rucavado","year":"2005","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1074\/mcp.M112.023143","article-title":"Squeezers and Leaf-cutters: Differential Diversification and Degeneration of the Venom System in Toxicoferan Reptiles","volume":"12","author":"Fry","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1093\/molbev\/msv155","article-title":"Olfactory Receptor Subgenomes Linked with Broad Ecological Adaptations in Sauropsida","volume":"32","author":"Khan","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/sj.cr.7290123","article-title":"Structure, expression, and developmental function of early divergent forms of metalloproteinases in Hydra","volume":"12","author":"Sarras","year":"2002","journal-title":"Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/0305-0491(90)90081-4","article-title":"Chitinase, a new enzyme in octopus saliva","volume":"95","author":"Grisley","year":"1990","journal-title":"Comp. Biochem. Physiol. Part B Comp. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4103\/0975-7406.106559","article-title":"Chitinases: An update","volume":"5","author":"Hamid","year":"2013","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.toxicon.2003.11.002","article-title":"Excitement ahead: Structure, function and mechanism of snake venom phospholipase A2 enzymes","volume":"42","author":"Kini","year":"2003","journal-title":"Toxicon"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.toxicon.2010.06.013","article-title":"Venom on ice: First insights into Antarctic octopus venoms","volume":"56","author":"Undheim","year":"2010","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Prentis, P.J., Pavasovic, A., and Norton, R.S. (2018). Sea Anemones: Quiet Achievers in the Field of Peptide Toxins. Toxins, 10.","DOI":"10.3390\/toxins10010036"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10126-005-5093-2","article-title":"Peptide Toxins in Sea Anemones: Structural and Functional Aspects","volume":"8","author":"Honma","year":"2006","journal-title":"Mar. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"25121","DOI":"10.1074\/jbc.270.42.25121","article-title":"Kalicludines and Kaliseptine: Two different classes of sea anemone toxins for voltage-sensitive K+ channels","volume":"270","author":"Schweitz","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.3390\/md11082873","article-title":"Insights into the Toxicological Properties of a Low Molecular Weight Fraction from Zoanthus sociatus (Cnidaria)","volume":"11","author":"Antunes","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/00001721-200006000-00011","article-title":"Textilinins from Pseudonaja textilis textilis. Characterization of two plasmin inhibitors that reduce bleeding in an animal model","volume":"11","author":"Masci","year":"2000","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1365-2141.2009.07605.x","article-title":"Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss","volume":"145","author":"Flight","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/0014-5793(90)81426-O","article-title":"Purification and characterization of a chymotrypsin Kunitz inhibitor type of polypeptide fro the venom of cobra ( Naja naja naja )","volume":"275","author":"Shafqat","year":"1990","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0014-5793(91)81361-B","article-title":"Purification and characterization of a Kunitz-type trypsin inhibitor from Leaf-nosed viper venom","volume":"294","author":"Siddiqi","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.peptides.2007.11.013","article-title":"A novel serine protease inhibitor from Bungarus fasciatus venom","volume":"29","author":"Lu","year":"2008","journal-title":"Peptides"},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1074\/jbc.274.2.563","article-title":"Thyroglobulin Type-1 Domains in Equistatin Inhibit Both Papain-like Cysteine Proteinases and Cathepsin D","volume":"274","author":"Lenarcic","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13899","DOI":"10.1074\/jbc.272.21.13899","article-title":"Equistatin, a New Inhibitor of Cysteine Proteinases from Actinia equina, Is Structurally Related to Thyroglobulin Type-1 Domain","volume":"272","author":"Ritonja","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S1096-4959(01)00530-9","article-title":"Vanden Structural and functional properties of a novel serine protease inhibiting peptide family in arthropods","volume":"132","author":"Simonet","year":"2002","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15397","DOI":"10.1021\/bi00255a021","article-title":"Solution Structure of PMP-D2, a 35-Residue Peptide Isolated from the Insect Locusta migratoria","volume":"33","author":"Mer","year":"1994","journal-title":"Biochemistry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0028-3908(97)83783-5","article-title":"Inhibition of Neuronal High Voltage-activated Calcium Channels by Insect Peptides: A Comparison with the Actions of $\u03c9$-Conotoxin GVIA","volume":"36","author":"Scott","year":"1997","journal-title":"Neuropharmacology"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ghosh, S. (2020). Sialic acid and biology of life: An introduction. Sialic Acids and Sialoglycoconjugates in the Biology of Life, Health and Disease, Elsevier.","DOI":"10.1016\/B978-0-12-816126-5.00001-9"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Margres, M.J., Aronow, K., Loyacano, J., and Rokyta, D.R. (2013). The venom-gland transcriptome of the eastern coral snake (Micrurus fulvius) reveals high venom complexity in the intragenomic evolution of venoms. BMC Genom.oS On, 14.","DOI":"10.1186\/1471-2164-14-531"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.1073\/pnas.88.15.6829","article-title":"Histone contributions to the structure of DNA in the nucleosome","volume":"88","author":"Hayes","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jb\/mvm214","article-title":"Packaging the Genome: The Structure of Mitotic Chromosomes","volume":"143","author":"Maeshima","year":"2008","journal-title":"J. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(00)81958-3","article-title":"Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome","volume":"98","author":"Kornberg","year":"1999","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Alex, A., Silva, V., Vasconcelos, V., and Antunes, A. (2013). Evidence of Unique and Generalist Microbes in Distantly Related Sympatric Intertidal Marine Sponges (Porifera: Demospongiae). PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080653"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Alex, A., and Antunes, A. (2015). Pyrosequencing Characterization of the Microbiota from Atlantic Intertidal Marine Sponges Reveals High Microbial Diversity and the Lack of Co-Occurrence Patterns. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127455"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"R14","DOI":"10.1016\/j.cub.2015.11.017","article-title":"Antimicrobial peptides","volume":"26","author":"Zhang","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0051834","article-title":"Unusual Symbiotic Cyanobacteria Association in the Genetically Diverse Intertidal Marine Sponge Hymeniacidon perlevis (Demospongiae, Halichondrida)","volume":"7","author":"Alex","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrd3591","article-title":"Designing antimicrobial peptides: Form follows function","volume":"11","author":"Fjell","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.febslet.2013.01.026","article-title":"Effect of amino acid distribution of amphipathic helical peptide derived from human apolipoprotein A-I on membrane curvature sensing","volume":"587","author":"Tanaka","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1006\/bbrc.1996.0071","article-title":"A novel antimicrobial peptide from Bufo bufo gargarizans","volume":"218","author":"Park","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1006\/bbrc.1998.8159","article-title":"Mechanism of Action of the Antimicrobial Peptide Buforin II: Buforin II Kills Microorganisms by Penetrating the Cell Membrane and Inhibiting Cellular Functions","volume":"244","author":"Park","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4161\/viru.1.5.12983","article-title":"Antimicrobial peptides: The ancient arm of the human immune system","volume":"1","author":"Wiesner","year":"2010","journal-title":"Virulence"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molimm.2012.07.003","article-title":"Purification and antimicrobial function of ubiquitin isolated from the gill of Pacific oyster, Crassostrea gigas","volume":"53","author":"Seo","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1073\/pnas.72.1.11","article-title":"Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells","volume":"72","author":"Goldstein","year":"1975","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.pneurobio.2004.05.005","article-title":"Ubiquitin-proteasome-mediated local protein degradation and synaptic plasticity","volume":"73","author":"Hegde","year":"2004","journal-title":"Prog. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1021\/bi00681a026","article-title":"The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells","volume":"14","author":"Schlesinger","year":"1975","journal-title":"Biochemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/0076-6879(84)06025-0","article-title":"[23] Ubiquitination of Proteins","volume":"Volume 106","author":"Busch","year":"1984","journal-title":"Methods Enzymol"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.3003913","article-title":"Cell surface molecule associated with lymphocyte homing is a ubiquitinated branched-chain glycoprotein","volume":"231","author":"Siegelman","year":"1986","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0076-6879(85)16022-2","article-title":"Thymopoietin and ubiquitin","volume":"Volume 116","author":"Audhya","year":"1985","journal-title":"Methods Enzymol"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1073\/pnas.0700036104","article-title":"Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy","volume":"104","author":"Alonso","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.fsi.2015.02.040","article-title":"The new insights into the oyster antimicrobial defense: Cellular, molecular and genetic view","volume":"46","author":"Rosa","year":"2015","journal-title":"Fish Shellfish Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1046\/j.0014-2956.2001.02675.x","article-title":"Antibacterial peptides in stimulated human granulocytes","volume":"269","author":"Wang","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ag\u00fcero-Chapin, G., Molina-Ruiz, R., Maldonado, E., de la Riva, G., S\u00e1nchez-Rodr\u00edguez, A., Vasconcelos, V., and Antunes, A. (2013). Exploring the Adenylation Domain Repertoire of Nonribosomal Peptide Synthetases Using an Ensemble of Sequence-Search Methods. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065926"},{"key":"ref_99","first-page":"127","article-title":"[Rat bladder ubiquitin-like molecule: Isolation, purification and N-terminal sequencing]","volume":"24","author":"Wang","year":"1993","journal-title":"J. West China Univ. Med. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1096\/fj.02-0699fje","article-title":"The N- and C-terminal fragments of ubiquitin are important for the antimicrobial activities","volume":"17","author":"Kieffer","year":"2003","journal-title":"FASEB J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.bbapap.2007.06.013","article-title":"Purification and antimicrobial activity studies of the N-terminal fragment of ubiquitin from human amniotic fluid","volume":"1774","author":"Kim","year":"2007","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/mmi.12621","article-title":"Bovine pancreatic trypsin inhibitor is a new antifungal peptide that inhibits cellular magnesium uptake","volume":"92","author":"Bleackley","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1006\/bbrc.2000.4052","article-title":"A Protease Inhibitor of the Kunitz Family from Skin Secretions of the Tomato Frog, Dyscophus guineti (Microhylidae)","volume":"279","author":"Conlon","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1073\/pnas.84.15.5449","article-title":"Magainins, a class of antimicrobial peptides from Xenopus skin: Isolation, characterization of two active forms, and partial cDNA sequence of a precursor","volume":"84","author":"Zasloff","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.peptides.2010.03.002","article-title":"Orthologs of magainin, PGLa, procaerulein-derived, and proxenopsin-derived peptides from skin secretions of the octoploid frog Xenopus amieti (Pipidae)","volume":"31","author":"Conlon","year":"2010","journal-title":"Peptides"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1093\/gbe\/evw041","article-title":"Whole-Genome Identification, Phylogeny, and Evolution of the Cytochrome P450 Family 2 (CYP2) Subfamilies in Birds","volume":"8","author":"Almeida","year":"2016","journal-title":"Genome Biol. Evol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Zougman","year":"2009","journal-title":"Nat. Meth."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"UniProt: A worldwide hub of protein knowledge","volume":"47","author":"UniProt","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.toxicon.2012.03.010","article-title":"The UniProtKB\/Swiss-Prot Tox-Prot program: A central hub of integrated venom protein data","volume":"60","author":"Jungo","year":"2012","journal-title":"Toxicon"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","article-title":"SignalP 5.0 improves signal peptide predictions using deep neural networks","volume":"37","author":"Tsirigos","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1093\/bioinformatics\/btx431","article-title":"DeepLoc: Prediction of protein subcellular localization using deep learning","volume":"33","author":"Nielsen","year":"2017","journal-title":"Bioinformatics"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/11\/757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:26:50Z","timestamp":1760178410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/11\/757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,30]]},"references-count":113,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["antibiotics9110757"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics9110757","relation":{},"ISSN":["2079-6382"],"issn-type":[{"type":"electronic","value":"2079-6382"}],"subject":[],"published":{"date-parts":[[2020,10,30]]}}}