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Serpins can modulate immune responses by negatively regulating serine protease activities strictly and precisely. The codling moth, Cydia pomonella (L.), a major invasive pest in China, can cause serious economic losses. However, knowledge of serpin genes in this insect remain largely unknown. In this study, we performed a systematic analysis of the serpin genes in C. pomonella, obtaining 26 serpins from the C. pomonella genome. Subsequently, their sequence features, evolutionary relationship, and expression pattern were characterized. Comparative analysis revealed the evolution of a number of serpin genes in Lepidoptera. Importantly, the evolutionary relationship and putative roles of serpin genes in C. pomonella were revealed. Additionally, selective pressure analysis found amino acid sites with strong evidence of positive selection. Interestingly, the serpin1 gene possessed at least six splicing isoforms with distinct reactive-center loops, and these isoforms were experimentally validated. Furthermore, we observed a subclade expansion of serpins, and these genes showed high expression in multiple tissues, suggesting their important roles in C. pomonella. Overall, this study will enrich our knowledge of the immunity of C. pomonella and help to elucidate the role of serpins in the immune response.<\/jats:p>","DOI":"10.3390\/ijms242216349","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:51:37Z","timestamp":1700045497000},"page":"16349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Genome-Wide Analysis of Serine Protease Inhibitors in Cydia pomonella Provides Insights into Their Evolution and Expression Pattern"],"prefix":"10.3390","volume":"24","author":[{"given":"Qiang","family":"Wu","sequence":"first","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longsheng","family":"Xing","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei Basic Science Center for Biotic Interactions, Institute of Life Sciences and Green Development, Hebei University, Baoding 071000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Du","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory for Integrated Control of Plant Diseases and Insect Pests, Sino-Australian Joint Research Institute of Agriculture and Environmental Health, College of Plant Health & Medicine, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-9450","authenticated-orcid":false,"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory for Integrated Control of Plant Diseases and Insect Pests, Sino-Australian Joint Research Institute of Agriculture and Environmental Health, College of Plant Health & Medicine, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxue","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-8632","authenticated-orcid":false,"given":"Fanghao","family":"Wan","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqiang","family":"Qian","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1538-7836.2011.04360.x","article-title":"Serpin structure, function and dysfunction","volume":"9","author":"Huntington","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.semcdb.2016.09.001","article-title":"Serpins in arthropod biology","volume":"62","author":"Meekins","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shakeel, M., Xu, X., De Mandal, S., and Jin, F. (2019). Role of serine protease inhibitors in insect-host-pathogen interactions. Arch. Insect Biochem., 102.","DOI":"10.1002\/arch.21556"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0022-2836(73)90448-8","article-title":"Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. Crystal structure determination and stereochemistry of the contact region","volume":"77","author":"Kukla","year":"1973","journal-title":"J. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1101\/gr.147800","article-title":"Phylogeny of the serpin superfamily: Implications of patterns of amino acid conservation for structure and function","volume":"10","author":"Irving","year":"2000","journal-title":"Genome Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Law, R.H., Zhang, Q., McGowan, S., Buckle, A.M., Silverman, G.A., Wong, W., Rosado, C.J., Langendorf, C.G., Pike, R.N., and Bird, P.I. (2006). An overview of the serpin superfamily. Genome Biol., 7.","DOI":"10.1186\/gb-2006-7-5-216"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1038\/s41598-019-40432-w","article-title":"Reactive centre loop dynamics and serpin specificity","volume":"9","author":"Marijanovic","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/2211-5463.12825","article-title":"Serpin7 controls egg diapause of migratory locust (Locusta migratoria) by regulating polyphenol oxidase","volume":"10","author":"Chen","year":"2020","journal-title":"FEBS Open Bio"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0969-2126(99)80013-6","article-title":"The structure of active serpin 1K from Manduca sexta","volume":"7","author":"Li","year":"1999","journal-title":"Structure"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4751","DOI":"10.1021\/cr010170+","article-title":"Serpin structure, mechanism, and function","volume":"102","author":"Gettins","year":"2002","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.bi.49.070180.003113","article-title":"Protein inhibitors of proteinases","volume":"49","author":"Laskowski","year":"1980","journal-title":"Annu. Rev. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"606797","DOI":"10.4061\/2011\/606797","article-title":"Serpin inhibition mechanism: A delicate balance between native metastable state and polymerization","volume":"2011","author":"Khan","year":"2011","journal-title":"J. Amino Acids"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/35038119","article-title":"Structure of a serpin-protease complex shows inhibition by deformation","volume":"407","author":"Huntington","year":"2000","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.tibs.2010.04.006","article-title":"Proteolytic cascades and their involvement in invertebrate immunity","volume":"35","author":"Cerenius","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.aspen.2015.06.004","article-title":"A serine protease inhibitor from the hornfaced bee, Osmia cornifrons, exhibits antimicrobial activities","volume":"18","author":"Lee","year":"2015","journal-title":"J. Asia-Pac. Entomol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.dci.2017.05.017","article-title":"Serpin-14 negatively regulates prophenoloxidase activation and expression of antimicrobial peptides in Chinese oak silkworm Antheraea pernyi","volume":"76","author":"Kausar","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Garrett, M., Fullaondo, A., Troxler, L., Micklem, G., and Gubb, D. (2009). Identification and analysis of serpin-family genes by homology and synteny across the 12 sequenced Drosophilid genomes. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-489"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zou, Z., Evans, J.D., Lu, Z., Zhao, P., Williams, M., Sumathipala, N., Hetru, C., Hultmark, D., and Jiang, H. (2007). Comparative genomic analysis of the Tribolium immune system. Genome Biol., 8.","DOI":"10.1186\/gb-2007-8-8-r177"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1365-2583.2006.00682.x","article-title":"Immune pathways and defence mechanisms in honey bees Apis mellifera","volume":"15","author":"Evans","year":"2006","journal-title":"Insect Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Xiong, G.H., Xing, L.S., Lin, Z., Saha, T.T., Wang, C., Jiang, H., and Zou, Z. (2015). High throughput profiling of the cotton bollworm Helicoverpa armigera immunotranscriptome during the fungal and bacterial infections. BMC Genom., 16.","DOI":"10.1186\/s12864-015-1509-1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ygeno.2008.12.010","article-title":"A comparative analysis of serpin genes in the silkworm genome","volume":"93","author":"Zou","year":"2009","journal-title":"Genomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1534-5807(02)00267-8","article-title":"An immune-responsive Serpin regulates the melanization cascade in Drosophila","volume":"3","author":"Han","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.1093\/emboj\/cdf661","article-title":"A serpin mutant links Toll activation to melanization in the host defence of Drosophila","volume":"21","author":"Ligoxygakis","year":"2002","journal-title":"EMBO J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.285.5435.1917","article-title":"Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila","volume":"285","author":"Levashina","year":"1999","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/genetics\/156.3.1117","article-title":"The necrotic gene in Drosophila corresponds to one of a cluster of three serpin transcripts mapping at 43A1.2","volume":"156","author":"Green","year":"2000","journal-title":"Genetics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev.biochem.78.082107.133320","article-title":"Conformational pathology of the serpins: Themes, variations, and therapeutic strategies","volume":"78","author":"Gooptu","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhao, P., Dong, Z., Duan, J., Wang, G., Wang, L., Li, Y., Xiang, Z., and Xia, Q. (2012). Genome-wide identification and immune response analysis of serine protease inhibitor genes in the silkworm, Bombyx mori. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031168"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.gene.2017.02.011","article-title":"Bombyx mori Serpin6 regulates prophenoloxidase activity and the expression of antimicrobial proteins","volume":"610","author":"Li","year":"2017","journal-title":"Gene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ibmb.2018.09.008","article-title":"The Manduca sexta serpinome: Analysis of serpin genes and proteins in the tobacco hornworm","volume":"102","author":"Li","year":"2018","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.gene.2008.03.015","article-title":"Differential expansion and evolution of the exon family encoding the Serpin-1 reactive centre loop has resulted in divergent serpin repertoires among the Lepidoptera","volume":"418","author":"Hegedus","year":"2008","journal-title":"Gene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0965-1748(01)00034-0","article-title":"A bacteria-induced, intracellular serpin in granular hemocytes of Manduca sexta","volume":"31","author":"Gan","year":"2001","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ibmb.2013.03.015","article-title":"Manduca sexta serpin-7, a putative regulator of hemolymph prophenoloxidase activation","volume":"43","author":"Suwanchaichinda","year":"2013","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1074\/jbc.272.2.1082","article-title":"Characterization and functional analysis of 12 naturally occurring reactive site variants of serpin-1 from Manduca sexta","volume":"272","author":"Jiang","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/S0965-1748(03)00123-1","article-title":"Prophenoloxidase-activating proteinase-3 (PAP-3) from Manduca sexta hemolymph: A clip-domain serine proteinase regulated by serpin-1J and serine proteinase homologs","volume":"33","author":"Jiang","year":"2003","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"46556","DOI":"10.1074\/jbc.M309682200","article-title":"Manduca sexta serpin-3 regulates prophenoloxidase activation in response to infection by inhibiting prophenoloxidase-activating proteinases","volume":"278","author":"Zhu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ibmb.2003.12.005","article-title":"Purification and characterization of Manduca sexta serpin-6: A serine proteinase inhibitor that selectively inhibits prophenoloxidase-activating proteinase-3","volume":"34","author":"Wang","year":"2004","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14923","DOI":"10.1074\/jbc.M500531200","article-title":"Manduca sexta serpin-4 and serpin-5 inhibit the prophenol oxidase activation pathway: cDNA cloning, protein expression, and characterization","volume":"280","author":"Tong","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.gene.2009.04.013","article-title":"The serpin gene family in Anopheles gambiae","volume":"442","author":"Suwanchaichinda","year":"2009","journal-title":"Gene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.ibmb.2010.07.001","article-title":"Manduca sexta serpin-5 regulates prophenoloxidase activation and the Toll signaling pathway by inhibiting hemolymph proteinase HP6","volume":"40","author":"An","year":"2010","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.dci.2010.09.004","article-title":"Serpin-1 splicing isoform J inhibits the proSp\u00e4tzle-activating proteinase HP8 to regulate expression of antimicrobial hemolymph proteins in Manduca sexta","volume":"35","author":"An","year":"2011","journal-title":"Dev. Comp. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.ibmb.2012.09.008","article-title":"Identification of plasma proteinase complexes with serpin-3 in Manduca sexta","volume":"42","author":"Christen","year":"2012","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ibmb.2016.04.003","article-title":"Serpin-5 regulates prophenoloxidase activation and antimicrobial peptide pathways in the silkworm, Bombyx mori","volume":"73","author":"Li","year":"2016","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.micpath.2019.02.035","article-title":"Effects of Bombyx mori nuclear polyhedrosis virus on serpin and antibacterial peptide expression in B. mori","volume":"130","author":"Dong","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yuan, C., Xing, L., Wang, M., Wang, X., Yin, M., Wang, Q., Hu, Z., and Zou, Z. (2017). Inhibition of melanization by serpin-5 and serpin-9 promotes baculovirus infection in cotton bollworm Helicoverpa armigera. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006645"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"671","DOI":"10.18388\/abp.2009_2501","article-title":"Molecular cloning, expression and characterization of Bmserpin-2 gene from Bombyx mori","volume":"56","author":"Pan","year":"2009","journal-title":"Acta Biochim. Pol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1021\/pr800383r","article-title":"Comparative proteomic analysis between the domesticated silkworm (Bombyx mori) reared on fresh mulberry leaves and on artificial diet","volume":"7","author":"Zhou","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/B978-0-12-386471-0.00011-0","article-title":"The Drosophila serpins: Multiple functions in immunity and morphogenesis","volume":"499","author":"Reichhart","year":"2011","journal-title":"Methods Enzymol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S1534-5807(03)00338-1","article-title":"Spatial regulation of developmental signaling by a serpin","volume":"5","author":"Hashimoto","year":"2003","journal-title":"Dev. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1016\/j.cub.2003.10.062","article-title":"A serpin regulates dorsal-ventral axis formation in the Drosophila embryo","volume":"13","author":"Ligoxygakis","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1038\/s41467-019-12175-9","article-title":"A chromosome-level genome assembly of Cydia pomonella provides insights into chemical ecology and insecticide resistance","volume":"10","author":"Wan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1093\/molbev\/msi157","article-title":"Networks of coevolving sites in structural and functional domains of serpin proteins","volume":"22","author":"Buck","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/S1357-2725(03)00134-1","article-title":"Serpins: Structure, function and molecular evolution","volume":"35","author":"Sharp","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lin, H., Lin, X., Zhu, J., Yu, X.Q., Xia, X., Yao, F., Yang, G., and You, M. (2017). Characterization and expression profiling of serine protease inhibitors in the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae). BMC Genom., 18.","DOI":"10.1186\/s12864-017-3583-z"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.tcb.2005.10.001","article-title":"Tip of another iceberg: Drosophila serpins","volume":"15","author":"Reichhart","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16858","DOI":"10.1073\/pnas.0608033103","article-title":"Increased melanizing activity in Anopheles gambiae does not affect development of Plasmodium falciparum","volume":"103","author":"Michel","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.dci.2018.10.006","article-title":"Silkworm serpin32 functions as a negative-regulator in prophenoloxidase activation","volume":"91","author":"Wang","year":"2019","journal-title":"Dev. Comp. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14341","DOI":"10.1074\/jbc.M500570200","article-title":"Manduca sexta serpin-6 regulates immune serine proteinases PAP-3 and HP8. cDNA cloning, protein expression, inhibition kinetics, and function elucidation","volume":"280","author":"Zou","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jinsphys.2012.08.015","article-title":"The roles of serpins in mosquito immunology and physiology","volume":"59","author":"Gulley","year":"2013","journal-title":"J. Insect Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"An, C., Hiromasa, Y., Zhang, X., Lovell, S., Zolkiewski, M., Tomich, J.M., and Michel, K. (2012). Biochemical characterization of Anopheles gambiae SRPN6, a malaria parasite invasion marker in mosquitoes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048689"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ibmb.2018.05.004","article-title":"Manduca sexta serpin-12 controls the prophenoloxidase activation system in larval hemolymph","volume":"99","author":"Yang","year":"2018","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Yan, Z., Fang, Q., Song, J., Yang, L., Xiao, S., Wang, J., and Ye, G. (2023). A serpin gene from a parasitoid wasp disrupts host immunity and exhibits adaptive alternative splicing. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011649"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Han, P., Fan, J., Liu, Y., Cuthbertson, A.G., Yan, S., Qiu, B.L., and Ren, S. (2014). RNAi-mediated knockdown of serine protease inhibitor genes increases the mortality of Plutella xylostella challenged by destruxin A. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097863"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1007\/s11033-010-0424-4","article-title":"Alternative splicing of the antitrypsin gene in the silkworm, Bombyx mori","volume":"38","author":"Liu","year":"2011","journal-title":"Mol. Biol. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/arch.20179","article-title":"Differential protein expression in the honey bee head after a bacterial challenge","volume":"65","author":"Scharlaken","year":"2007","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1365-2583.2006.00684.x","article-title":"Comparative analysis of serine protease-related genes in the honey bee genome: Possible involvement in embryonic development and innate immunity","volume":"15","author":"Zou","year":"2006","journal-title":"Insect Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jinsphys.2019.04.009","article-title":"A trypsin inhibitor-like protein secreted by Cotesia vestalis teratocytes inhibits hemolymph prophenoloxidase activation of Plutella xylostella","volume":"116","author":"Gu","year":"2019","journal-title":"J. Insect Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.ijpara.2021.05.002","article-title":"The trypsin inhibitor-like domain is required for a serine protease inhibitor of Haemonchus contortus to inhibit host coagulation","volume":"51","author":"Wu","year":"2021","journal-title":"Int. J. Parasitol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"900129","DOI":"10.3389\/fimmu.2022.900129","article-title":"A TIL-type serine protease inhibitor involved in humoral immune response of Asian corn borer Ostrinia furnaculis","volume":"13","author":"Guan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tikhe, C.V., Cardoso-Jaime, V., Dong, S., Rutkowski, N., and Dimopoulos, G. (2022). Trypsin-like inhibitor domain (TIL)-harboring protein is essential for Aedes aegypti reproduction. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147736"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"11018","DOI":"10.1073\/pnas.1502026112","article-title":"Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3)","volume":"112","author":"Koymans","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1159\/000479100","article-title":"The TLR2 antagonist staphylococcal superantigen-like protein 3 acts as a virulence factor to promote bacterial pathogenicity in vivo","volume":"9","author":"Koymans","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ab.2018.01.026","article-title":"Characterization of fatty acid amide hydrolase activity by a fluorescence-based assay","volume":"546","author":"Dato","year":"2018","journal-title":"Anal. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"15047","DOI":"10.18632\/oncotarget.7592","article-title":"Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells","volume":"7","author":"Winkler","year":"2016","journal-title":"Oncotarget"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/ijc.23674","article-title":"Expression and function of fatty acid amide hydrolase in prostate cancer","volume":"123","author":"Endsley","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"R1409","DOI":"10.1152\/ajpregu.90484.2008","article-title":"Inhibiting parabrachial fatty acid amide hydrolase activity selectively increases the intake of palatable food via cannabinoid CB1 receptors","volume":"295","author":"Dipatrizio","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15872","DOI":"10.1021\/bi00048a033","article-title":"The contribution of the conserved hinge region residues of alpha1-antitrypsin to its reaction with elastase","volume":"34","author":"Hopkins","year":"1995","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: A new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1101\/gr.10.4.516","article-title":"Ab initio gene finding in Drosophila genomic DNA","volume":"10","author":"Salamov","year":"2000","journal-title":"Genome Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1101\/gr.1865504","article-title":"GeneWise and Genomewise","volume":"14","author":"Birney","year":"2004","journal-title":"Genome Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"D427","DOI":"10.1093\/nar\/gky995","article-title":"The Pfam protein families database in 2019","volume":"47","author":"Mistry","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"D302","DOI":"10.1093\/nar\/gkr931","article-title":"SMART 7: Recent updates to the protein domain annotation resource","volume":"40","author":"Letunic","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Eddy, S.R. (2011). Accelerated Profile HMM Searches. PLoS Comput. Biol., 7.","DOI":"10.1371\/journal.pcbi.1002195"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: The proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"Gasteiger","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_84","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_85","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_86","first-page":"406","article-title":"The neighbor-joining method: A new method for reconstructing phylogenetic trees","volume":"4","author":"Saitou","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_87","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":"2015","journal-title":"Mol. Biol. Evol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"W293","DOI":"10.1093\/nar\/gkab301","article-title":"Interactive Tree Of Life (iTOL) v5: An online tool for phylogenetic tree display and annotation","volume":"49","author":"Letunic","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1093\/bioinformatics\/btl097","article-title":"CAFE: A computational tool for the study of gene family evolution","volume":"22","author":"Cristianini","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","article-title":"RAxML version 8: A tool for phylogenetic analysis and post-analysis of large phylogenies","volume":"30","author":"Stamatakis","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Emms, D.M., and Kelly, S. (2019). OrthoFinder: Phylogenetic orthology inference for comparative genomics. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1832-y"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/bioinformatics\/19.2.301","article-title":"r8s: Inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock","volume":"19","author":"Sanderson","year":"2003","journal-title":"Bioinformatics"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"W609","DOI":"10.1093\/nar\/gkl315","article-title":"PAL2NAL: Robust conversion of protein sequence alignments into the corresponding codon alignments","volume":"34","author":"Suyama","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1672-0229(10)60008-3","article-title":"KaKs_Calculator 2.0: A toolkit incorporating gamma-series methods and sliding window strategies","volume":"8","author":"Wang","year":"2010","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1093\/molbev\/msm088","article-title":"PAML 4: Phylogenetic analysis by maximum likelihood","volume":"24","author":"Yang","year":"2007","journal-title":"Mol. Biol. Evol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16349\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:25Z","timestamp":1760131405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":98,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216349"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216349","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}