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Granzyme A

Class of enzymes

Field	Value
Name	Granzyme A
EC_number	3.4.21.78
CAS_number	143180-73-8

Granzyme A (GzmA, , CTLA3, HuTPS, T-cell associated protease 1, cytotoxic T lymphocyte serine protease, TSP-1, T-cell derived serine proteinase) is a tryptase and is one of the five granzymes encoded in the human genome. In humans, GzmA is encoded by the GZMA gene in proximity to the GZMK gene on chromosome 5. 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.

References

(December 1986). "Purification and characterization of a T cell specific serine proteinase (TSP-1) from cloned cytolytic T lymphocytes". The EMBO Journal.
(February 1988). "Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease". Proceedings of the National Academy of Sciences of the United States of America.
(February 1991). "Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins". Biochemistry.
(Nov 1988). "Characterization of three serine esterases isolated from human IL-2 activated killer cells". J Immunol.
(Dec 1986). "Identification of granzyme A isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes". FEBS Lett.
"Entrez Gene: GZMA granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)".
(2009-08-06). "The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5'-diphosphate-ribose) polymerase-1". Blood.
(2001-05-08). "Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis". Proceedings of the National Academy of Sciences of the United States of America.
(1995-05-01). "Granzyme A is an interleukin 1 beta-converting enzyme". The Journal of Experimental Medicine.
(2008-05-16). "Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death". Cell.
(Oct 29, 2009). "Response: Granzyme A: cell death–inducing protease, proinflammatory agent, or both?". Blood.
(2008-11-14). "Human and mouse granzyme A induce a proinflammatory cytokine response". Immunity.
(2020-07-07). "Extracellular Granzyme A Promotes Colorectal Cancer Development by Enhancing Gut Inflammation". Cell Reports.

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ec-3.4.21

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