proteolysis involved in cellular protein catabolic process
negative regulation of endodeoxyribonuclease activity
cytolysis
negative regulation of oxidoreductase activity
immune response
proteolysis
apoptotic process
response to bacterium
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
3001
14938
Ensembl
ENSG00000145649
ENSMUSG00000023132
UniProt
P12544
P11032
RefSeq (mRNA)
NM_006144
NM_010370
RefSeq (protein)
NP_006135
NP_034500
Location (UCSC)
Chr 5: 55.1 – 55.11 Mb
Chr 13: 113.23 – 113.24 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
Granzyme A (GzmA, EC 3.4.21.78, 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 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[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]
^ abcGRCh38: Ensembl release 89: ENSG00000145649 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000023132 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Simon MM, Hoschützky H, Fruth U, Simon HG, Kramer MD (December 1986). "Purification and characterization of a T cell specific serine proteinase (TSP-1) from cloned cytolytic T lymphocytes". The EMBO Journal. 5 (12): 3267–74. doi:10.1002/j.1460-2075.1986.tb04638.x. PMC 1167321. PMID 3545816.
^Gershenfeld HK, Hershberger RJ, Shows TB, Weissman IL (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. 85 (4): 1184–8. Bibcode:1988PNAS...85.1184G. doi:10.1073/pnas.85.4.1184. PMC 279731. PMID 3257574.
^Odake S, Kam CM, Narasimhan L, Poe M, Blake JT, Krahenbuhl O, Tschopp J, Powers JC (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. 30 (8): 2217–27. doi:10.1021/bi00222a027. PMID 1998680.
^Hameed A, Lowrey DM, Lichtenheld M, Podack ER (Nov 1988). "Characterization of three serine esterases isolated from human IL-2 activated killer cells". J Immunol. 141 (9): 3142–7. doi:10.4049/jimmunol.141.9.3142. PMID 3262682.
^Masson D, Zamai M, Tschopp J (Dec 1986). "Identification of granzyme A isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes". FEBS Lett. 208 (1): 84–8. doi:10.1016/0014-5793(86)81537-X. PMID 3533635. S2CID 10670230.
^Zhu P, Martinvalet D, Chowdhury D, Zhang D, Schlesinger A, Lieberman J (2009-08-06). "The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5'-diphosphate-ribose) polymerase-1". Blood. 114 (6): 1205–1216. doi:10.1182/blood-2008-12-195768. ISSN 1528-0020. PMC 2723016. PMID 19506301.
^Zhang D, Beresford PJ, Greenberg AH, Lieberman J (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. 98 (10): 5746–5751. Bibcode:2001PNAS...98.5746Z. doi:10.1073/pnas.101329598. ISSN 0027-8424. PMC 33284. PMID 11331782.
^Irmler M, Hertig S, MacDonald HR, Sadoul R, Becherer JD, Proudfoot A, Solari R, Tschopp J (1995-05-01). "Granzyme A is an interleukin 1 beta-converting enzyme". The Journal of Experimental Medicine. 181 (5): 1917–1922. doi:10.1084/jem.181.5.1917. ISSN 0022-1007. PMC 2191995. PMID 7722467.
^Martinvalet D, Dykxhoorn DM, Ferrini R, Lieberman J (2008-05-16). "Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death". Cell. 133 (4): 681–692. doi:10.1016/j.cell.2008.03.032. ISSN 1097-4172. PMC 2840390. PMID 18485875.
^Metkar SS, Menaa C, Pardo J, Wang B, Wallich R, Freudenberg M, Kim S, Raja SM, Shi L, Simon MM, Froelich CJ (2008-11-14). "Human and mouse granzyme A induce a proinflammatory cytokine response". Immunity. 29 (5): 720–733. doi:10.1016/j.immuni.2008.08.014. ISSN 1097-4180. PMID 18951048.
^Santiago L, Castro M, Sanz-Pamplona R, Garzón M, Ramirez-Labrada A, Tapia E, Moreno V, Layunta E, Gil-Gómez G, Garrido M, Peña R, Lanuza PM, Comas L, Jaime-Sanchez P, Uranga-Murillo I (2020-07-07). "Extracellular Granzyme A Promotes Colorectal Cancer Development by Enhancing Gut Inflammation". Cell Reports. 32 (1): 107847. doi:10.1016/j.celrep.2020.107847. hdl:10230/45276. ISSN 2211-1247. PMID 32640217.
Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death...
Granzyme B (GrB) is one of the serine protease granzymes most commonly found in the granules of natural killer cells (NK cells) and cytotoxic T cells....
Granzyme B is a serine protease that in humans is encoded by the GZMB gene. Granzyme B is expressed by cytotoxic T lymphocytes (CTL) and natural killer...
Granzyme K (GrK) is a protein that is encoded by the GZMK gene on chromosome 5 in humans. Granzymes are a family of serine proteases which have various...
aortic aneurysm. Other recent research identified Granzyme B (GZMB) (a protein-degrading enzyme) to be a potential target in the treatment of abdominal aortic...
Granzyme H is a protein that in humans is encoded by the GZMH gene. GRCh38: Ensembl release 89: ENSG00000100450 – Ensembl, May 2017 GRCm38: Ensembl release...
associated with the macromolecular complex of granzymes and perforin, and serves as a scaffold for the granzyme and perforin in granule-mediated apoptosis...
Todd DJ, Anolik JH, McDavid A, Wei K, Rao DA, Raychaudhuri S, Brenner MB (June 2022). "Granzyme K+ CD8 T cells form a core population in inflamed human...
(IP-10, lymphotactin), trigger cytolysis of target cells (perforins, granzymes...), and interact with other cells, such as epithelial cells, monocytes...
which are antigenic. Normally, a cytotoxic T cell will immediately come to "inject" lymphotoxins, such as perforin or granzyme, that will kill the infected...
membrane attack complex. Clusterin, a soluble molecule with functions similar to CD59, forms a complex with Granzyme B and inhibits activation of apoptosis...
triggered by activated T cells – which secrete toxic granzymes and perforin – or indirectly as a result of reduced blood flow or the generation of reactive...
latter's Fc regions interact with their Fc receptors, releasing perforin and granzyme B to kill the tumor cell. Examples include rituximab, ofatumumab, elotuzumab...
"Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction"...
mediate keratinocyte cell death through release of a number of molecules, including perforin, granzyme B, and granulysin. Other agents, including tumor...
cell, and causing it to burst or lyse. CTL release granzyme, a serine protease encapsulated in a granule that enters cells via pores to induce apoptosis...
collectively termed granzymes and include 4 distinct gene products: granzymeA, granzyme B, granzyme H, and Met-ase, also known as granzyme M. GRCh38: Ensembl...
as perforin and granzyme B. Flow cytometry is also commonly used. Bone marrow involvement in this disease is often present, but to a variable extent....
American television production company Gamma-ray burst, an astronomical event Granzyme B (GrB), serine protease most commonly found in the granules of NK cells...
and mice IELs express higher levels of CD103, activation marker CD69, granzyme B and perforin cytolytic granules. CD25 expression is lower in comparison...
cytokine responses, antibody specific secreting cells, tumor antigens, granzyme B and Perforin release by T cells, vaccine efficacy, epitope mapping, cytotoxic...
with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzymeA". Molecular and Cellular Biology. 22 (8): 2810–20...
activity due to impaired expression of associated molecules such as IFN-γ, granzyme B or perforin impaired proliferation in response to antigenic stimulation...
Bird PI (November 1996). "A cytosolic granzyme B inhibitor related to the viral apoptotic regulator cytokine response modifier A is present in cytotoxic...
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