Abstract
GASPIDs (granule associated serine protease of immune defence) are a family of serine proteases intimately involved with the function of the vertebrate immune system. With the availability of a large and growing set of assembled genomes, we undertook an evolutionary analysis to plot the development of this protein family from a single precursor to the modern mammalian cohort of 12 genes, in an attempt to define and systematically classify subgroups or clades within this family, which are implied by the conventional gene designations. We identified a primordial GASPID gene as either GzmA or GzmK in cartilaginous fish and reconstructed an evolutionary path through to humans. Apart from historic value, the current sub-designations (granzymes, mast cell proteases and neutrophil serine proteases) serve no useful purpose and are increasingly misleading. We therefore used our phylogenetic and point mutation analyses to separate GASPIDs into three clades. These could form the basis of a simple nomenclature that allows effective classification of GASPIDs without implying functional roles.
Acknowledgments
This work was supported by the National Health and Medical Research Council (Australia) and by a scholarship from the University of Peshawar to JA.
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©2014 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: The protease web
- Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence
- Non-B HIV-1 subtypes in sub-Saharan Africa: impact of subtype on protease inhibitor efficacy
- Inflammatory outcomes of apoptosis, necrosis and necroptosis
- Angiotensin-converting enzyme overexpression in myelocytes enhances the immune response
- The leader proteinase of foot-and-mouth disease virus: structure-function relationships in a proteolytic virulence factor
- Immune-modulating effects of alpha-1 antitrypsin
- Mammalian gamete fusion depends on the inhibition of ovastacin by fetuin-B
- The activity and localization patterns of cathepsins B and X in cells of the mouse gastrointestinal tract differ along its length
- Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/ CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium
- Homology model of human prothrombinase based on the crystal structure of Pseutarin C
- Specific targeting of human caspases using designed ankyrin repeat proteins
- Analysis of the evolution of granule associated serine proteases of immune defence (GASPIDs) suggests a revised nomenclature
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: The protease web
- Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence
- Non-B HIV-1 subtypes in sub-Saharan Africa: impact of subtype on protease inhibitor efficacy
- Inflammatory outcomes of apoptosis, necrosis and necroptosis
- Angiotensin-converting enzyme overexpression in myelocytes enhances the immune response
- The leader proteinase of foot-and-mouth disease virus: structure-function relationships in a proteolytic virulence factor
- Immune-modulating effects of alpha-1 antitrypsin
- Mammalian gamete fusion depends on the inhibition of ovastacin by fetuin-B
- The activity and localization patterns of cathepsins B and X in cells of the mouse gastrointestinal tract differ along its length
- Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/ CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium
- Homology model of human prothrombinase based on the crystal structure of Pseutarin C
- Specific targeting of human caspases using designed ankyrin repeat proteins
- Analysis of the evolution of granule associated serine proteases of immune defence (GASPIDs) suggests a revised nomenclature