Granzyme A is a tryptase and is one of the five granzymes encoded in the human genome. This enzyme is present in cytotoxic T lymphocyte (CTL) granules. GzmA cleaves proteins after arginine or lysine basic residues. In CTL-targeted cells, it activates caspase-independent programmed cell death pathways that are unique and parallel to that of Granzyme B, although some substrates such as PARP-1 and lamin B are shared with Granzyme B. Substrates of GzmA include Pro-IL-1β, NDUFS3, SET, APE1, and Ku70 among others. In vitro studies suggest that GzmA may have less cytotoxic capabilities than GzmB. In colorectal cancer, GzmA was associated with promotion of cancer development, which may be due to activation of inflammation-inducing cytokines from macrophages.
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