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GZMA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1OP8, 1ORF
Identifiers
Aliases	GZMA, CTLA3, HFSP, granzyme A
External IDs	OMIM: 140050; MGI: 109266; HomoloGene: 21237; GeneCards: GZMA; OMA:GZMA - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q11.2 Start 55,102,646 bp End 55,110,252 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13 D2.2|13 63.93 cM Start 113,230,359 bp End 113,237,515 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte blood spleen jejunal mucosa lymph node mucosa of transverse colon duodenum testicle palpebral conjunctiva rectum Top expressed in gastrula jejunum thymus duodenum blood right lung lobe spleen ankle joint decidua mesenteric lymph nodes More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity serine-type peptidase activity serine-type endopeptidase activity hydrolase activity protein binding protein homodimerization activity Cellular component immunological synapse extracellular region nucleus Biological process positive regulation of apoptotic process negative regulation of DNA binding 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
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 and is one of the five granzymes encoded in the human genome. 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 and lamin B are shared with Granzyme B. Substrates of GzmA include Pro-IL-1β, NDUFS3, SET, APE1, and Ku70 among others. In vitro studies suggest that GzmA may have less cytotoxic capabilities than GzmB.

In colorectal cancer, GzmA was associated with promotion of cancer development, which may be due to activation of inflammation-inducing cytokines from macrophages.

See also

• GZMA
• GZMK
• GZMB
• GZMH

References

1. ^ GRCh38: Ensembl release 89: ENSG00000145649 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000023132 – Ensembl, 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

• Pasternack MS, Bleier KJ, McInerney TN (1991). "Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro". J. Biol. Chem. 266 (22): 14703–8. doi:10.1016/S0021-9258(18)98743-0. PMID 1860869.
• Poe M, Bennett CD, Biddison WE, et al. (1988). "Human cytotoxic lymphocyte tryptase. Its purification from granules and the characterization of inhibitor and substrate specificity". J. Biol. Chem. 263 (26): 13215–22. doi:10.1016/S0021-9258(18)37694-4. PMID 3047119.
• 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. PMID 3237717. S2CID 35164948.
• Gershenfeld HK, Hershberger RJ, Shows TB, Weissman IL (1988). "Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease". Proc. Natl. Acad. Sci. U.S.A. 85 (4): 1184–8. Bibcode:1988PNAS...85.1184G. doi:10.1073/pnas.85.4.1184. PMC 279731. PMID 3257574.
• Krähenbühl O, Rey C, Jenne D, et al. (1988). "Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes". J. Immunol. 141 (10): 3471–7. doi:10.4049/jimmunol.141.10.3471. PMID 3263427.
• Baetz K, Isaaz S, Griffiths GM (1995). "Loss of cytotoxic T lymphocyte function in Chediak-Higashi syndrome arises from a secretory defect that prevents lytic granule exocytosis". J. Immunol. 154 (11): 6122–31. doi:10.4049/jimmunol.154.11.6122. PMID 7751653.
• 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. PMID 7912927.
• 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. PMID 8288245.
• Beresford PJ, Kam CM, Powers JC, Lieberman J (1997). "Recombinant human granzyme A binds to two putative HLA-associated proteins and cleaves one of them". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9285–90. Bibcode:1997PNAS...94.9285B. doi:10.1073/pnas.94.17.9285. PMC 23158. PMID 9256474.
• Spaeny-Dekking EH, Hanna WL, Wolbink AM, et al. (1998). "Extracellular granzymes A and B in humans: detection of native species during CTL responses in vitro and in vivo". J. Immunol. 160 (7): 3610–6. doi:10.4049/jimmunol.160.7.3610. PMID 9531325.
• Zhang D, Beresford PJ, Greenberg AH, Lieberman J (2001). "Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis". Proc. Natl. Acad. Sci. U.S.A. 98 (10): 5746–51. Bibcode:2001PNAS...98.5746Z. doi:10.1073/pnas.101329598. PMC 33284. PMID 11331782.
• Beresford PJ, Zhang D, Oh DY, et al. (2001). "Granzyme A activates an endoplasmic reticulum-associated caspase-independent nuclease to induce single-stranded DNA nicks". J. Biol. Chem. 276 (46): 43285–93. doi:10.1074/jbc.M108137200. PMID 11555662.
• Fan Z, Beresford PJ, Zhang D, Lieberman J (2002). "HMG2 Interacts with the Nucleosome Assembly Protein SET and Is a Target of the Cytotoxic T-Lymphocyte Protease Granzyme A". Mol. Cell. Biol. 22 (8): 2810–20. doi:10.1128/MCB.22.8.2810-2820.2002. PMC 133744. PMID 11909973.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• 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. PMID 12524539. S2CID 29433133.
• Pinkoski MJ, Green DR (2003). "Granzyme A: the road less traveled". Nat. Immunol. 4 (2): 106–8. doi:10.1038/ni0203-106. PMID 12555094. S2CID 38687759.
• Saito S, Iida A, Sekine A, et al. (2003). "Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population". J. Hum. Genet. 48 (5): 249–70. doi:10.1007/s10038-003-0021-7. PMID 12721789.
• 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. PMID 12819769. S2CID 9608837.

External links

• Granzyme+A at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

• Biology

• Genes on human chromosome 5
• EC 3.4.21