From Wikipedia, the free encyclopedia
Granzyme A
Identifiers
EC no. 3.4.21.78
CAS no. 143180-73-8
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Search
PMC articles
PubMed articles
NCBI proteins
GZMA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases GZMA, CTLA3, HFSP, granzyme A
External IDs OMIM: 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 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]

See also

References

  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

External links

From Wikipedia, the free encyclopedia
Granzyme A
Identifiers
EC no. 3.4.21.78
CAS no. 143180-73-8
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Search
PMC articles
PubMed articles
NCBI proteins
GZMA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases GZMA, CTLA3, HFSP, granzyme A
External IDs OMIM: 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 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]

See also

References

  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

External links


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