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Title: Granzymes: a variety of serine protease specificities encoded by genetically distinct subfamilies.
Austin Authors: Smyth, Mark J;O'Connor, M D;Trapani, Joseph A
Affiliation: Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Nov-1996
Publication information: Journal of Leukocyte Biology; 60(5): 555-62
Abstract: Granzymes are a family of granule serine proteases found specifically in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells. Granzymes have features that are strongly conserved including: consensus sequences at their N-termini and around the three catalytic residues, activation from zymogenic forms, and conserved disulphide bridges. However, there is good genetic evidence to suggest that three distinct subfamilies of granzymes have coevolved. These subfamilies are most strikingly depicted by their distinct chromosomal loci and gene organization, dividing the granzyme family into subfamilies of the following: tryptases (human chromosome 5); chymotrypsin-like proteases (human chromosome 14); and a Metase amongst a cluster of elastase-like proteases (human chromosome 19). Modeling and mutational analysis has revealed that each subfamily of granzymes displays special sequence and structural features and a proteolytic specificity determined by subtle modifications to substrate binding pocket residues. It now remains of great interest to determine whether these subfamilies also possess distinct biological functions. Granzyme B has been shown to play an important role in lymphocyte-mediated target cell apoptosis and the tryptase, granzyme A, has been demonstrated to regulate the clearance of some pox virus infections. The future creation of other granzyme gene knockout mice should elucidate whether other chymotrypsin-like granzymes (C-H) also contribute to target cell apoptosis and whether the third subfamily member, natural killer cell-specific Metase, has a distinct biological function.
Gov't Doc #: 8929545
Type: Journal Article
Subjects: Amino Acid Sequence
Consensus Sequence
Cytoplasmic Granules.enzymology
Evolution, Molecular
Killer Cells, Natural.enzymology.secretion
Molecular Sequence Data
Sequence Alignment
Sequence Homology, Amino Acid
Serine Endopeptidases.classification.genetics.metabolism.secretion
Serine Proteinase Inhibitors.pharmacology
Substrate Specificity.genetics
T-Lymphocytes, Cytotoxic.enzymology.secretion
Appears in Collections:Journal articles

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