Serpin
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A Review and Database of Snake Venom Proteomes Open
Advances in the last decade combining transcriptomics with established proteomics methods have made possible rapid identification and quantification of protein families in snake venoms. Although over 100 studies have been published, the va…
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A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation Open
Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on ear…
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Design and characterization of an APC-specific serpin for the treatment of hemophilia Open
Key Points The endogenous inhibitors of APC also inhibit other coagulation proteases rendering them unacceptable for treatment of hemophilia. Rationally designed APC-specific serpins rescue thrombin generation in vitro and restore hemostas…
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PEDF and its roles in physiological and pathological conditions: implication in diabetic and hypoxia-induced angiogenic diseases Open
Pigment epithelium-derived factor (PEDF) is a broadly expressed multifunctional member of the serine proteinase inhibitor (serpin) family. This widely studied protein plays critical roles in many physiological and pathophysiological proces…
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Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition Open
Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily with antiprotease activity, is the main physiological inhibitor of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators …
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A Serpin With a Finger in Many PAIs: PAI-1's Central Function in Thromboinflammation and Cardiovascular Disease Open
Plasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA), and urokinase-type plasminogen…
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SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes Open
C1 inhibitor (C1Inh) deficiency is responsible for hereditary angioedema (C1-INH-HAE) and caused by variants of the SERPING1/C1INH/C1NH gene. C1Inh is the major control of kallikrein-kinin system. C1Inh deficiency leads to its uncontrolled…
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Inhibition of melanization by serpin-5 and serpin-9 promotes baculovirus infection in cotton bollworm Helicoverpa armigera Open
Melanization, an important insect defense mechanism, is mediated by clip-domain serine protease (cSP) cascades and is regulated by serpins. Here we show that proteolytic activation of prophenoloxidase (PPO) and PO-catalyzed melanization ki…
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The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases Open
Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. In COPD, the relationship between the …
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Anti-tumor effects of pigment epithelium-derived factor (PEDF): implication for cancer therapy. A mini-review Open
Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein and a non-inhibitory member of the serine protease inhibitor (serpin) family. It is widely expressed in human fetal and adult tissues but its expression decreases with age…
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Past, Present, and Future Perspectives of Plasminogen Activator Inhibitor 1 (PAI-1) Open
Plasminogen activator inhibitor 1 (PAI-1), a SERPIN inhibitor, is primarily known for its regulation of fibrinolysis. However, it is now known that this inhibitor functions and contributes to many (patho)physiological processes including i…
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SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and Complement System Leading to Platelet Aggregation Open
Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 to infect and replicate in endothelial cell…
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Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance Open
Serpins are a widely distributed family of high molecular mass protein proteinase inhibitors that can inhibit both serine and cysteine proteinases by a remarkable mechanism-based kinetic trapping of an acyl or thioacyl enzyme intermediate …
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The complex world of plant protease inhibitors: Insights into a Kunitz-type cysteine protease inhibitor of<i>Arabidopsis thaliana</i> Open
Plants have evolved an intricate regulatory network of proteases and corresponding protease inhibitors (PI), which operate in various biological pathways and serve diverse spatiotemporal functions during the sedentary life of a plant. Intr…
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Recognition of Plasminogen Activator Inhibitor Type 1 as the Primary Regulator of Fibrinolysis Open
The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that diffe…
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Serpin functions in host-pathogen interactions Open
Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potent ser ine p roteases in hibitors. Early studies of serpins focused o…
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A Comprehensive Phylogenetic Analysis of the Serpin Superfamily Open
Serine protease inhibitors (serpins) are found in all kingdoms of life and play essential roles in multiple physiological processes. Owing to the diversity of the superfamily, phylogenetic analysis is challenging and prokaryotic serpins ha…
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Polyphosphate is a novel cofactor for regulation of complement by a serpin, C1 inhibitor Open
Key Points PolyP, like heparin, is a physiologic cofactor for the C1-INH:C1s interaction, and thus a key negative regulator of complement. Colocalization of polyP with C1-INH in activated platelets suggests that its cofactor function is ph…
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A Hexasaccharide Containing Rare 2‐<i>O</i>‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II Open
Glycosaminoglycan (GAG) sequences that selectively target heparin cofactor II (HCII), a key serpin present in human plasma, remain unknown. Using a computational strategy on a library of 46 656 heparan sulfate hexasaccharides we identified…
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Squamous Cell Carcinoma Antigen 2 (SCCA2, SERPINB4): An Emerging Biomarker for Skin Inflammatory Diseases Open
Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4), members of the ovalbumin serpin (ov-serpin)/clade B serpin family, were originally discovered as tumor-specific antigens and are used as tumor markers for various ki…
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At<span>SERPIN</span>1 is an inhibitor of the metacaspase At<span>MC</span>1‐mediated cell death and autocatalytic processing <i>in planta</i> Open
Summary The hypersensitive response ( HR ) is a localized programmed cell death phenomenon that occurs in response to pathogen recognition at the site of attempted invasion. Despite more than a century of research on HR , little is known a…
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Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein Open
Alpha-1-antitrypsin (AAT), an acute-phase protein encoded by the SERPINA1 gene, is a member of the serine protease inhibitor (SERPIN) superfamily. Its primary function is to protect tissues from enzymes released during inflammation, such a…
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Distinct structures of the α-fucose branches in fucosylated chondroitin sulfates do not affect their anticoagulant activity Open
Fucosylated chondroitin sulfate (FCS) is a glycosaminoglycan found in sea cucumbers. It has a backbone like that of mammalian chondroitin sulfate (4-β-d-GlcA-1→3-β-d-GalNAc-1)n but substituted at the 3rd position of the β-d-glururonic acid…
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Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19 Open
No definitive treatment for COVID-19 exists although promising results have been reported with remdesivir and glucocorticoids. Short of a truly effective preventive or curative vaccine against SARS-CoV-2, it is becoming increasingly clear …
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Singlet Oxygen-Induced Membrane Disruption and Serpin-Protease Balance in Vacuolar-Driven Cell Death Open
Singlet oxygen plays a role in cellular stress either by providing direct toxicity or through signaling to initiate death programs. It was therefore of interest to examine cell death, as occurs in Arabidopsis, due to differentially localiz…
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The Effects of Rare <i>SERPINA1</i> Variants on Lung Function and Emphysema in SPIROMICS Open
Rationale: The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, SERPINA1 (serpin peptidase inhibitor, clade A, member 1), in determining chronic obstructiv…
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Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis Open
Appropriate activation of coagulation requires a balance between procoagulant and anticoagulant proteins in blood. Loss in this balance leads to hemorrhage and thrombosis. A number of endogenous anticoagulant proteins, such as antithrombin…
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Identification of potential protein biomarkers for early detection of pregnancy in cow urine using 2D DIGE and label free quantitation Open
This is first report on differentially expressed protein during various time points of pregnancy in cow to our best knowledge. In our work, we identified few proteins such MBP, SERPIN, IGF which were differentially expressed and actively i…
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Serpins in Tick Physiology and Tick-Host Interaction Open
Tick saliva has been extensively studied in the context of tick-host interactions because it is involved in host homeostasis modulation and microbial pathogen transmission to the host. Accumulated knowledge about the tick saliva compositio…
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Matrix metalloproteinase‐13 is fully activated by neutrophil elastase and inactivates its serpin inhibitor, alpha‐1 antitrypsin: Implications for osteoarthritis Open
Matrix metalloproteinase‐13 (MMP‐13) is a uniquely important collagenase that promotes the irreversible destruction of cartilage collagen in osteoarthritis (OA). Collagenase activation is a key control point for cartilage breakdown to occu…