Granzyme A (GzmA, EC3.4.21.78, CTLA3, HuTPS, T-cell associated protease 1, cytotoxic T lymphocyte serine protease, TSP-1, T-cell derived serine proteinase) is a tryptase[5][6][7] and is one of the five granzymes encoded in the human genome.[8][9][10] In humans, GzmA is encoded by the GZMAgene 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[11] and lamin B[12] are shared with Granzyme B. Substrates of GzmA include Pro-IL-1β,[13] NDUFS3,[14] SET, APE1, and Ku70 among others. In vitro studies suggest that GzmA may have less cytotoxic capabilities than GzmB.[15][16]
In colorectal cancer, GzmA was associated with promotion of cancer development, which may be due to activation of inflammation-inducing cytokines from macrophages.[17]
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Murphy ME, Moult J, Bleackley RC, et al. (1989). "Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes". Proteins. 4 (3): 190–204. doi:10.1002/prot.340040306. PMID3237717. S2CID35164948.
Inoue M, Hoshino T, Fukuma T, et al. (1994). "Close co-localization of CD4 and a serine esterase tryptase TL2 on the cell-surface of human monocytoid and CD4+ lymphoid cells". Biochem. Biophys. Res. Commun. 201 (3): 1390–5. doi:10.1006/bbrc.1994.1857. PMID7912927.
Fink TM, Lichter P, Wekerle H, et al. (1994). "The human granzyme A (HFSP, CTLA3) gene maps to 5q11-q12 and defines a new locus of the serine protease superfamily". Genomics. 18 (2): 401–3. doi:10.1006/geno.1993.1483. PMID8288245.
Fan Z, Beresford PJ, Zhang D, et al. (2003). "Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A". Nat. Immunol. 4 (2): 145–53. doi:10.1038/ni885. PMID12524539. S2CID29433133.
Bell JK, Goetz DH, Mahrus S, et al. (2003). "The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity". Nat. Struct. Biol. 10 (7): 527–34. doi:10.1038/nsb944. PMID12819769. S2CID9608837.
