Alternative titles; symbols
HGNC Approved Gene Symbol: GZMM
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:544,053-549,922 (from NCBI)
Human natural killer (NK) cells and activated lymphocytes express and store a distinct subset of neutral serine proteases together with proteoglycans and other immune effector molecules in large cytoplasmic granules. These serine proteases are collectively termed granzymes and include 4 distinct gene products: granzyme A (140050), granzyme B (123910), granzyme H (116831), and Met-ase, also known as granzyme M (Pilat et al., 1994).
Using a rat cDNA as a probe, Pilat et al. (1994) identified cosmid clones containing the genes for the human and murine granzyme M.
Pilat et al. (1994) found that the human GZMM gene has a size of 7.5 kb and an exon-intron structure identical to that of other serine protease genes.
By fluorescence in situ hybridization, Pilat et al. (1994) mapped the GZMM gene to chromosome 19p13.3. Interphase studies with 2 differentially labeled probes for GZMM and the azurocidin (AZU1; 162815), proteinase-3 (PRTN3; 177020), and elastase-2 (ELA2; 130130) gene cluster indicated that the GZMM gene is 200 to 500 kb from that gene cluster. Using differentially labeled mouse cosmid probes, they also mapped the murine gene to chromosomal band 10C, close to the gene for lamin B2. Thus, these genes fall into an established region of homology between mouse chromosomal band 10C and human 19p13.3.
Pao et al. (2005) generated Gzmm-deficient mice. FACS analysis showed that NK- and T-cell development and homeostasis were normal in these mice. Gzmm was not essential for NK cell-mediated cytotoxicity, but Gzmm-deficient mice had an altered response to murine cytomegalovirus (CMV) infection, with increased number of cells showing cytomegaly and increased frequency of viral inclusions. Responses to ectromelia virus were not distinguishable from those in wildtype mice. Pao et al. (2005) concluded that GZMM is not critical for NK-cell function, but it has a role in host response to CMV infection.
Pao, L. I., Sumaria, N., Kelly, J. M., van Dommelen, S., Cretney, E., Wallace, M. E., Anthony, D. A., Uldrich, A. P., Godfrey, D. I., Papadimitriou, J. M., Mullbacher, A., Degli-Esposti, M. A., Smyth, M. J. Functional analysis of granzyme M and its role in immunity to infection. J. Immun. 175: 3235-3243, 2005. [PubMed: 16116214] [Full Text: https://doi.org/10.4049/jimmunol.175.5.3235]
Pilat, D., Fink, T., Obermaier-Skrobanek, B., Zimmer, M., Wekerle, H., Lichter, P., Jenne, D. E. The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to the serine protease gene cluster on 19p13.3. Genomics 24: 445-450, 1994. [PubMed: 7713495] [Full Text: https://doi.org/10.1006/geno.1994.1651]