Granzyme A

Granzyme A (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 an enzyme.[5][6][7] that in humans is encoded by the GZMA gene, and is one of the five granzymes encoded in the human genome .[8][9][10] This enzyme is present in cytotoxic T lymphocyte granules.

Granzyme A
Identifiers
EC number	3.4.21.78
CAS number	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 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
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q11.2 Start 55,102,646 bp[1] End 55,110,252 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 D2.2|13 63.93 cM Start 113,093,825 bp[2] End 113,100,981 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • peptidase activity • serine-type peptidase activity • serine-type endopeptidase activity • hydrolase activity • GO:0001948 protein binding • protein homodimerization activity Cellular component • immunological synapse • extracellular region • cell 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: 113.09 – 113.1 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here is a T cell- and natural killer cell-specific serine protease that may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells.[10]

This enzyme catalyses the following chemical reaction:

Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg-, -Lys- >> -Phe- in small molecule substrates.

Human Granzyme Genes

• GZMA
• GZMB
• GZMH
• GZMK
• GZMM

See also

• GZMA

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. 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. 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. 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.
10. "Entrez Gene: GZMA granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)".

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. 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. 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.
• 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. 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. 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. 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. 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. 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. 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. 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.
• Pinkoski MJ, Green DR (2003). "Granzyme A: the road less traveled". Nat. Immunol. 4 (2): 106–8. doi:10.1038/ni0203-106. PMID 12555094.
• 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.

External links

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