Serpins Flex Their Muscle

Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis. Studies using model organisms, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and conformational flexibility are exploited to control proteolysis in molecular pathways associated with cell survival, development, and host defense. In addition, an increasing number of non-inhibitory serpins are emerging as important elements within a diversity of biological systems by serving as chaperones, hormone transporters, or anti-angiogenic factors.

• Publication year

  2010

• Venue

  Journal of Biological Chemistry

• Publication date

  2010-05-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.R110.112771PMID 20498369PMCID PMC2915665
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Serpins Flex Their Muscle

  2010cited by this paper
• Control of granzymes by serpins

  2010cited by this paper
• Arabidopsis AtSerpin1, Crystal Structure and in Vivo Interaction with Its Target Protease RESPONSIVE TO DESICCATION-21 (RD21)*

  2010cited by this paper
• Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses*

  2009cited by this paper
• Identification and analysis of serpin-family genes by homology and synteny across the 12 sequenced Drosophilid genomes

  2009cited by this paper
• Exosite Determinants of Serpin Specificity*

  2009cited by this paper
• Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia

  2009cited by this paper
• Uptake of the Necrotic Serpin in Drosophila melanogaster via the Lipophorin Receptor-1

  2009cited by this paper
• Drosophila Toll Pathway: The New Model

  2009cited by this paper
• The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases

  2009cited by this paper
• A single modular serine protease integrates signals from pattern-recognition receptors upstream of the Drosophila Toll pathway

  2009cited by this paper
• Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll

  2008cited by this paper
• Functional diversification of a protease inhibitor gene in the genus Drosophila and its molecular basis.

  2008cited by this paper
• PEDF-deficient mice exhibit an enhanced rate of retinal vascular expansion and are more sensitive to hyperoxia-mediated vessel obliteration.

  2008cited by this paper
• Mutation-, Aging-, and Gene Dosage-dependent Accumulation of Neuroserpin (G392E) in Endoplasmic Reticula and Lysosomes of Neurons in Transgenic Mice*

  2008cited by this paper
• Serpins in plants and green algae

  2008cited by this paper
• Drosophila Serpin-28D regulates hemolymph phenoloxidase activity and adult pigmentation.

  2008cited by this paper
• The multi‐functional serpin, protein C inhibitor: beyond thrombosis and hemostasis

  2008cited by this paper
• A serpin that regulates immune melanization in the respiratory system of Drosophila.

  2008cited by this paper
• Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity

  2007cited by this paper
• The Spn4 gene from Drosophila melanogaster is a multipurpose defence tool directed against proteases from three different peptidase families.

  2007cited by this paper
• The Plasminogen Activator System and Cancer

  2007cited by this paper
• Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development

  2007cited by this paper
• An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury.

  2007cited by this paper
• SERPINB11 Is a New Noninhibitory Intracellular Serpin

  2007cited by this paper
• An overview of the serpin superfamily

  2006cited by this paper
• X‐ray crystal structure of MENT: evidence for functional loop–sheet polymers in chromatin condensation

  2006cited by this paper
• The Caenorhabditis elegans muscle specific serpin, SRP-3, neutralizes chymotrypsin-like serine peptidases.

  2006cited by this paper
• Hyporesponsiveness to Glucocorticoids in Mice Genetically Deficient for the Corticosteroid Binding Globulin

  2006cited by this paper
• Serpin1 of Arabidopsis thaliana is a suicide inhibitor for metacaspase 9.

  2006cited by this paper
• Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic.

  2006cited by this paper
• Genetic Ablation of Angiotensinogen in the Subfornical Organ of the Brain Prevents the Central Angiotensinergic Pressor Response

  2006cited by this paper
• Cathepsin L Stabilizes the Histone Modification Landscape on the Y Chromosome and Pericentromeric Heterochromatin

  2006cited by this paper
• An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease

  2006cited by this paper
• Molecular gymnastics: serpin structure, folding and misfolding.

  2006cited by this paper
• Shape-shifting serpins--advantages of a mobile mechanism.

  2006cited by this paper
• Tip of another iceberg: Drosophila serpins.

  2005cited by this paper
• Acinar Cell Apoptosis in Serpini2-Deficient Mice Models Pancreatic Insufficiency

  2005cited by this paper
• SRP-2 Is a Cross-class Inhibitor That Participates in Postembryonic Development of the Nematode Caenorhabditis elegans

  2004cited by this paper
• Maspin plays an essential role in early embryonic development

  2004cited by this paper
• Disruption of the murine alpha1-antitrypsin/PI2 gene.

  2004cited by this paper
• Targeted Disruption of SPI3/Serpinb6 Does Not Result in Developmental or Growth Defects, Leukocyte Dysfunction, or Susceptibility to Stroke

  2004cited by this paper
• Absence of mutations in the PCI gene in subfertile men.

  2004cited by this paper
• Comparative genomic analysis of the clade B serpin cluster at human chromosome 18q21: amplification within the mouse squamous cell carcinoma antigen gene locus.

  2004cited by this paper
• Human clade B serpins (ov-serpins) belong to a cohort of evolutionarily dispersed intracellular proteinase inhibitor clades that protect cells from promiscuous proteolysis

  2004cited by this paper
• Disruption of the Murine α1-Antitrypsin/PI2 Gene

  2004cited by this paper
• Spatial regulation of developmental signaling by a serpin.

  2003cited by this paper
• The Intracellular Granzyme B Inhibitor, Proteinase Inhibitor 9, Is Up-Regulated During Accessory Cell Maturation and Effector Cell Degranulation, and Its Overexpression Enhances CTL Potency1

  2003cited by this paper
• A serpin regulates dorsal-ventral axis formation in the Drosophila embryo.

  2003cited by this paper
• An immune-responsive Serpin regulates the melanization cascade in Drosophila.

  2002cited by this paper
• Comparison of human chromosome 6p25 with mouse chromosome 13 reveals a greatly expanded ov-serpin gene repertoire in the mouse.

  2002cited by this paper
• Activation of Drosophila Toll During Fungal Infection by a Blood Serine Protease

  2002cited by this paper
• Drosophila innate immunity: an evolutionary perspective

  2002cited by this paper
• A serpin mutant links Toll activation to melanization in the host defence of Drosophila

  2002cited by this paper
• Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1

  2001cited by this paper
• SERPINB12 Is a Novel Member of the Human ov-serpin Family That Is Widely Expressed and Inhibits Trypsin-like Serine Proteinases*

  2001cited by this paper
• The Serpins Are an Expanding Superfamily of Structurally Similar but Functionally Diverse Proteins

  2001cited by this paper
• Embryonic Lethality of Molecular Chaperone Hsp47 Knockout Mice Is Associated with Defects in Collagen Biosynthesis

  2000cited by this paper
• Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function.

  2000cited by this paper
• MENT, a Heterochromatin Protein That Mediates Higher Order Chromatin Folding, Is a New Serpin Family Member*

  1999cited by this paper
• Regulation of pro‐apoptotic leucocyte granule serine proteinases by intracellular serpins

  1999cited by this paper
• Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila.

  1999cited by this paper
• A New Family of 10 Murine Ovalbumin Serpins Includes Two Homologs of Proteinase Inhibitor 8 and Two Homologs of the Granzyme B Inhibitor (Proteinase Inhibitor 9)*

  1997cited by this paper
• Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by homologous recombination and characterization.

  1993cited by this paper
• Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis.

  1993cited by this paper

• The serine Protease-Serine protease inhibitor regulatory network in inflammatory bowel Disease: From molecular mechanisms to novel therapeutic Horizons.

  2026cites this paper
• Morphotype-Specific Antifungal Defense in Cacopsylla chinensis Arises from Metabolic and Immune Network Restructuring

  2025cites this paper
• Ai-Assisted Discovery of a Direct Physical Interaction Between a Venom Serpin from the Parasitoid Wasp Liragathis javana and a Host Serine Carboxypeptidase

  2025cites this paper
• Transcriptome analyses of mRNA and circular RNAs reveal dietary supplementation with freeze-dried Lactiplantibacillus plantarum primes immune memory of White leg shrimp (Penaeus vannamei) against pathogens.

  2024cites this paper
• Regulation of epidermal barrier function and pathogenesis of psoriasis by serine protease inhibitors

  2024cites this paper
• The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation.

  2024cites this paper
• The identification of a serpin with immune defense role in oriental river prawn Macrobrachium nipponense.

  2024cites this paper
• Conformational transition of the Ixodes ricinus salivary serpin Iripin-4

  2023cites this paper
• Plant Serpins: Potential Inhibitors of Serine and Cysteine Proteases with Multiple Functions

  2023cites this paper
• Proteolytic and Antiproteolytic Activity in the Skin: Gluing the Pieces Together.

  2023cites this paper
• Serpins in Tick Physiology and Tick-Host Interaction

  2022cites this paper
• Serpin–4 Facilitates Baculovirus Infection by Inhibiting Melanization in Asian Corn Borer, Ostrinia furnacalis (Guenée)

  2022cites this paper
• Sodium Accumulation and Blood Capillary Rarefaction in the Skin Predispose Spontaneously Hypertensive Rats to Salt Sensitive Hypertension

  2022cites this paper
• Editorial: The Serpin Family in the Cardiovascular System

  2022cites this paper
• Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins

  2022cites this paper
• Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

  2021cites this paper
• COVID-19 and Progesterone: Part 1. SARS-CoV-2, Progesterone and its potential clinical use

  2021cites this paper
• C1-Inhibitor: Structure, Functional Diversity and Therapeutic Development.

  2021cites this paper
• Gut Serpinome: Emerging Evidence in IBD

  2021cites this paper
• Stepwise Reversion of Multiply Mutated Recombinant Antitrypsin Reveals a Selective Inhibitor of Coagulation Factor XIa as Active as the M358R Variant

  2021cites this paper
• Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement

  2021cites this paper
• In‐bone protein digestion followed by LC‐MS/MS peptide analysis as a new way towards the routine proteomic characterization of human maxillary and mandibular bone tissue in oral surgery

  2021cites this paper
• Engineered EVs for Oxidative Stress Protection

  2021cites this paper
• Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury

  2021cites this paper
• Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases

  2021cites this paper
• Identification of an alpha-1 antitrypsin variant with enhanced specificity for factor XIa by phage display, bacterial expression, and combinatorial mutagenesis

  2021cites this paper
• Serine protease SP7 cleaves prophenoloxidase and is regulated by two serpins in Ostrinia furnacalis melanization.

  2021cites this paper
• Lymphedema Fluid

  2021cites this paper
• Serpin7 controls egg diapause of migratory locust (Locusta migratoria) by regulating polyphenol oxidase

  2020cites this paper
• Dual Host-Intracellular Parasite Transcriptome of Enucleated Cells Hosting Leishmania amazonensis: Control of Half-Life of Host Cell Transcripts by the Parasite

  2020cites this paper
• Rhipicephalus microplus serpins interfere with host immune responses by specifically modulating mast cells and lymphocytes.

  2020cites this paper
• Protease Inhibitors and Their Applications: An Overview

  2019cites this paper
• Genome-Wide Identification and Expression Analysis of the Protease Inhibitor Gene Families in Tomato

  2019cites this paper
• Transcriptome Sequencing to Detect the Potential Role of Long Noncoding RNAs in Salt-Sensitive Hypertensive Rats

  2019cites this paper
• Tissue and exosomal serine protease inhibitors are significantly overexpressed in chronic rhinosinusitis with nasal polyps

  2019cites this paper
• Radioresistance of Serpinb3a-/- Mice and Derived Hematopoietic and Marrow Stromal Cell Lines.

  2019cites this paper
• The Use of Tick Salivary Proteins as Novel Therapeutics

  2019cites this paper
• Serine protease inhibitors and human wellbeing interplay: new insights for old friends

  2019cites this paper
• Engineering the serpin α1‐antitrypsin: A diversity of goals and techniques

  2019cites this paper
• AtSERPIN1 is an inhibitor of the metacaspase AtMC1-mediated cell death and autocatalytic processing in planta.

  2018cites this paper
• Serpin Facilitates Tumor-Suppressive Cell Competition by Blocking Toll-Mediated Yki Activation in Drosophila.

  2018cites this paper
• Basic Characteristics of Muse Cells.

  2018cites this paper
• SERPINB3 Delays Glomerulonephritis and Attenuates the Lupus-Like Disease in Lupus Murine Models by Inducing a More Tolerogenic Immune Phenotype

  2018cites this paper
• Serpin Phage Display: The Use of a T7 System to Probe Reactive Center Loop Libraries with Different Serine Proteinases.

  2018cites this paper
• Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation

  2018cites this paper
• Resolving distinct molecular origins for copper effects on PAI-1

  2017cites this paper
• The Melanization Response in Insect Immunity

  2017cites this paper
• Serum Immune Proteins in Limb Lymphedema Reflecting Tissue Processes Caused by Lymph Stasis and Chronic Dermato-lymphangio-adenitis (Cellulitis)

  2017cites this paper
• Buserelin alleviates chloride transport defect in human cystic fibrosis nasal epithelial cells

  2017cites this paper
• Serine protease SP105 activates prophenoloxidase in Asian corn borer melanization, and is regulated by serpin-3

  2017cites this paper
• Transcriptome profiling of ontogeny in the acridid grasshopper Chorthippus biguttulus

  2017cites this paper
• Role of protease and protease inhibitors in cancer pathogenesis and treatment.

  2017cites this paper
• Cell penetrating SERPINA5 (ProteinC inhibitor, PCI): More questions than answers.

  2017cites this paper
• Comparison of two neurotrophic serpins reveals a small fragment with cell survival activity

  2017cites this paper
• Protease Inhibitors in Tick Saliva: The Role of Serpins and Cystatins in Tick-host-Pathogen Interaction

  2017cites this paper
• A pro‐survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection

  2017cites this paper
• l -Arginine, Pancreatic Beta Cell Function, and Diabetes: Mechanisms of Stimulated Insulin Release and Pathways of Metabolism

  2017cites this paper
• Serine Protease Inhibitors as Good Predictors of Meat Tenderness: Which Are They and What Are Their Functions?

  2016cites this paper
• Role of heparin and non heparin binding serpins in coagulation and angiogenesis: A complex interplay.

  2016cites this paper
• 1.45 Å resolution structure of SRPN18 from the malaria vector Anopheles gambiae.

  2016cites this paper
• The circadian Clock gene regulates acrosin activity of sperm through serine protease inhibitor A3K

  2016cites this paper
• Developmental biology: Females have a lot of guts

  2016cites this paper
• Mast cell glycosaminoglycans

  2016cites this paper
• Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1)

  2016cites this paper
• Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation.

  2016cites this paper
• Human T cell activation induces synaptic translocation and alters expression of the serine protease inhibitor neuroserpin and its target protease

  2015cites this paper
• HIV and mucosal barrier interactions: consequences for transmission and pathogenesis.

  2015cites this paper
• Ostrinia furnacalis serpin-3 regulates melanization cascade by inhibiting a prophenoloxidase-activating protease.

  2015cites this paper
• ANISERP: a new serpin from the parasite Anisakis simplex

  2015cites this paper
• Recombinant expression and characterization of a serine protease inhibitor (Lvserpin7) from the Pacific white shrimp, Litopenaeus vannamei.

  2015cites this paper
• Psoriasis pathogenesis – Pso p27 constitutes a compact structure forming large aggregates

  2015cites this paper
• A Novel Serpin Regulatory Mechanism

  2015cites this paper
• Human SERPINB12 Is an Abundant Intracellular Serpin Expressed in Most Surface and Glandular Epithelia

  2015cites this paper
• Enzyme Inhibitors in Regulating Enzyme Processing of Food and Beverages

  2015cites this paper
• Charakterystyka proteazy i serpiny Tannerella forsythia

  2015cites this paper
• SERPINB12 Is a Slow-Binding Inhibitor of Granzyme A and Hepsin.

  2015cites this paper
• The Aggregation-Prone Intracellular Serpin SRP-2 Fails to Transit the ER in Caenorhabditis elegans

  2015cites this paper
• A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency.

  2014cites this paper
• A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting.

  2014cites this paper
• High resolution structure of cleaved Serpin 42 Da from Drosophila melanogaster

  2014cites this paper
• SERPINB3 is associated with TGF-β1 and cytoplasmic β-catenin expression in hepatocellular carcinomas with poor prognosis

  2014cites this paper
• The Role of Serpin and Cystatin Antiproteases in Mucosal Innate Immunity and their Defense against HIV

  2014cites this paper
• Phage Display of the Serpin Alpha-1 Proteinase Inhibitor Randomized at Consecutive Residues in the Reactive Centre Loop and Biopanned with or without Thrombin

  2014cites this paper
• Identification of Immunity-Related Genes in Ostrinia furnacalis against Entomopathogenic Fungi by RNA-Seq Analysis

  2014cites this paper
• Structure-Function Relationship of SW-AT-1, a Serpin-Type Protease Inhibitor in Silkworm

  2014cites this paper
• TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.

  2014cites this paper
• Miropin, a Novel Bacterial Serpin from the Periodontopathogen Tannerella forsythia, Inhibits a Broad Range of Proteases by Using Different Peptide Bonds within the Reactive Center Loop*

  2014cites this paper
• Inhibition of the serine proteases of the complement system.

  2013cites this paper
• Isolation purification characterization and application of proteinaceous protease inhibitor from marine bacterium Pseudomonas mendocina BTMW 301

  2013cites this paper
• Genome scan for meat quality traits in Nelore beef cattle.

  2013cites this paper
• Splicing Variants of SERPINA1 Gene in Ovine Milk: Characterization of cDNA and Identification of Polymorphisms

  2013cites this paper
• Fusion of the C-terminal triskaidecapeptide of hirudin variant 3 to alpha1-proteinase inhibitor M358R increases the serpin-mediated rate of thrombin inhibition

  2013cites this paper
• Tomato cystatin SlCYS8 as a stabilizing fusion partner for human serpin expression in plants.

  2013cites this paper
• C1-Esterase Inhibitor: Biological Activities and Therapeutic Applications

  2013cites this paper
• OMICS OF SERPIND1 FROM HOMO SAPIENS

  2013cites this paper
• Functional Analysis of a Cross-tick Species Conserved Amblyomma americanum Serine Protease Inhibitor 39

  2013cites this paper
• The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential

  2013cites this paper
• Kinetic Intermediates en Route to the Final Serpin-Protease Complex

  2013cites this paper
• SERPINB3 protects from oxidative damage by chemotherapeutics through inhibition of mitochondrial respiratory complex I

  2013cites this paper
• Proteomic identification of protease cleavage sites: cell-biological and biomedical applications

  2013cites this paper