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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    • "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.
    Full-text · Article · Dec 2014 · Developmental & Comparative Immunology
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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.
    Full-text · Article · Jun 2014
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    • "Malfunction of serpins results in a number of diseases including emphysema, thrombosis, cirrhosis, dementia, tissue self-destruction, and hypersensitivity of the immune system (Irving et al. 2000; van Gent et al. 2003). Serpins are classified into 16 clades (A-P) based on their phylogenetic relationships (Silverman and Lomas 2004). "
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    ABSTRACT: PC12 cells are used to study the signaling mechanisms underlying the neurotrophic and neuroprotective activities of pituitary adenylate cyclase-activating polypeptide (PACAP) and nerve growth factor (NGF). Previous microarray experiments indicated that serpinb1a was the most induced gene after 6 h of treatment with PACAP or NGF. The present study confirmed that serpinb1a is strongly activated by PACAP and NGF in a time-dependent manner with a maximum induction (~50-fold over control) observed after 6 h of treatment. Co-incubation with PACAP and NGF resulted in a synergistic up-regulation of serpinb1a expression (200-fold over control), suggesting that PACAP and NGF act through complementary mechanisms. Consistently, PACAP-induced serpinb1a expression was not blocked by TrkA receptor inhibition. Nevertheless, the stimulation of serpinb1a expression by PACAP and NGF was significantly reduced in the presence of ERK, calcineurin, PKA, p38 and PI3K inhibitors, indicating that the two trophic factors share some common pathways in the regulation of serpinb1a. Finally, functional investigations conducted with siRNA revealed that serpinb1a is not involved in the effects of PACAP and NGF on PC12 cell neuritogenesis, proliferation or body volume but mediates their ability to block caspase-3/7 activity and to promote PC12 cell survival. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2014 · Journal of Neurochemistry
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