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.

Granzyme A
Identifiers
EC no.3.4.21.78
CAS no.143180-73-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins
GZMA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGZMA, CTLA3, HFSP, granzyme A
External IDsOMIM: 140050; MGI: 109266; HomoloGene: 21237; GeneCards: GZMA; OMA:GZMA - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006144

NM_010370

RefSeq (protein)

NP_006135

NP_034500

Location (UCSC)Chr 5: 55.1 – 55.11 MbChr 13: 113.23 – 113.24 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145649Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023132Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ "Entrez Gene: GZMA granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)".
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ Martinvalet D, Walch M, Jensen D, Thiery J, Lieberman J (Oct 29, 2009). "Response: Granzyme A: cell death–inducing protease, proinflammatory agent, or both?". Blood. 114 (8): 3969–3970. doi:10.1182/blood-2009-08-233577. PMC 2773496.
  16. ^ 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.
  17. ^ 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.

Further reading

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