Serpins: Structure, function and molecular evolution. Int J Biochem Cell Biol

Division of Clinical Chemistry, Institute of Genetics, Queen's Medical Centre, University of Nottingham, NG7 2UH Nottingham, UK.
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.05). 12/2003; 35(11):1536-47. DOI: 10.1016/S1357-2725(03)00134-1
Source: PubMed


The superfamily of serine proteinase inhibitors (serpins) are involved in a number of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression and are expressed in a cell-specific manner. The average protein size of a serpin family member is 350-400 amino acids, but gene structure varies in terms of number and size of exons and introns. Previous studies of all known serpins identified 16 clades and 10 orphan sequences. Vertebrate serpins can be conveniently classified into six sub-groups. We provide additional data that updates the phylogenetic analysis in the context of structural and functional properties of the proteins. From these, we can conclude that the functional classification of serpins relies on their protein structure and not on sequence similarity.

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    • "In rat it has been suggested to play a role in detoxification of electrophilic compounds the small intestine mucus [73] (Fig. 3). Serpins are a homologous family of proteins with diverse functions in processes such as blood coagulation, fibrinolysis , programmed cell death, development and inflammation [74]. Leukocyte elastase inhibitor (LEI) belongs to this family and function to limit and fine tune protease activity to limit host damage (Fig. 3) during inflammation and apoptosis [75] and during pathogen destruction by host through proteolytic activity. "
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    ABSTRACT: Skin mucus is the first barrier of fish defence. Proteins from skin mucus of European sea bass (Dicentrarchus labrax) were identified by 2DE followed by LC-MS/MS. From all the identified proteins in the proteome map, we focus on the proteins associated with several immune pathways in fish. Furthermore, the qPCR transcript levels in skin are shown. Proteins found include apolipoprotein A1, calmodulin, complement C3, fucose-binding lectin, lysozyme and several caspases. To our knowledge, this is the first skin mucus proteome study and further transcriptional profiling of the identified proteins done on this bony fish species. This not only contributes knowledge on the routes involved in mucosal innate immunity, but also establishes a non-invasive technique based on locating immune markers with a potential use for prevention and/or diagnosis of fish diseases.This article is protected by copyright. All rights reserved
    Proteomics 09/2015; DOI:10.1002/pmic.201500120 · 3.81 Impact Factor
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    • "All catfish serpin genes were clustered into distinct families with their respective counterparts from other teleosts. Notably, serpinA8 appears to be significantly different from its family members as it is distantly related to the other genes in the serpinA subfamily, which is consistent with the observation reported in mammals (Atchley et al., 2001; van Gent et al., 2003). The annotation for several catfish serpin genes from serpinA, serpinB and serpinC subfamilies were Table 3 Copy numbers of serpin genes in several representative vertebrate genomes. "
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    ABSTRACT: The superfamily of serine protease inhibitors (serpins) are broadly distributed in all kingdoms of life. Serpins play critical roles in an array of fundamental biological processes. In this study, we identified a complete set of 25 serpin genes from channel catfish genome by comprehensive data mining of existing genomic resources. Phylogenetic analysis verified their identities and supported the classification of serpins into six families as in mammals. Extensive comparative genomic analyses suggested that most serpins were conserved among vertebrates, while some were lineage-specific. Analysis of serpin gene expression in mucosal tissues after bacterial infections indicated that serpin genes were regulated in a tissue-specific and time-dependent manner. Distinct expression patterns between infections of the two pathogens were observed, indicating that much more rapid host responses of serpin expression were initiated after ESC infection than after columnaris infection. These studies set the foundation for future studies of host-pathogen interactions. Copyright © 2014. Published by Elsevier Ltd.
    Developmental & Comparative Immunology 12/2014; 49(2). DOI:10.1016/j.dci.2014.12.006 · 2.82 Impact Factor
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    • "The members of serpin superfamily have instrumental roles in a variety of physiological and cellular functions and are associated with the vertebrate blood coagulation cascade, complement activation, inflammation, programmed cell death, cell development, and fibrinolysis 1-3. Serpins are single domain proteins with an average size: 350-400 amino acids and molecular weights of 40-60 kDa 2-4. These proteins are classified into two functional categories - inhibitory (majority) such as antithrombin III 5, while some of them are non-inhibitory, which adopt other function than inhibitory roles such as angiotensinogen, which lost inhibition during vertebrate evolution 6. Serpins are thought to have evolved through gene duplication and divergence events, giving rise to a large number of serpin genes within an organism, each encoding a protein with a unique reactive center region and physiological function(s) 7. "
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    ABSTRACT: Members of serpins superfamily are involved in wide array of cellular processes to control proteolytic activities of eukaryotic organisms. Vertebrate serpins are extensively studied and reported to be classified into six groups based on gene structures. However, there is no study conducted for serpins in urochordates (the closest living invertebrates related to vertebrates) to date. To unravel further the phylogenetic history of serpin genes, we characterized serpin genes from two urochordates (Ciona intestinalis and Ciona savignyi). There are 11 and 5 serpins in the C. intestinalis and C. savignyi, respectively. The exon/intron structure and genomic locus comparisons together with sequence phylogenetic analysis, suggested that urochordate serpins are classified into six groups (U1-U6), different from six groups (V1-V6) of vertebrate serpins. Human α1-antitrypsin shared lower sequence identities and similarities with urochordates serpins ranged from 14-29% and 30-49%, respectively. Based on protein sequences, genes and genomic architectures, we conclude that these two urochordates do not contain a single copy of genuine ortholog of the vertebrate serpins.
    06/2014; 2:131-140. DOI:10.7150/jgen.9437
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