Nowadays, Granzyme A has become a topic of great interest and relevance in today's society. Whether on a personal, professional or academic level, Granzyme A has aroused the interest of many people due to its impact and repercussion in different areas of daily life. This is why it is essential to analyze and understand all aspects related to Granzyme A, from its origins to its short- and long-term consequences. In this article, we will delve into the fascinating world of Granzyme A, exploring its many facets and unraveling its mysteries to obtain a more complete and in-depth view of this phenomenon.
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.