Table 6.1.
Prominent granule protease of mouse and human MCs
| Mouse MC granule proteases | Human MC granule proteases | ||||
|---|---|---|---|---|---|
| Protease | Gene symbol | GenBank GeneID | Protease | Gene symbol | GenBank GeneID |
| mMCP-1a | Mcpt1 | 17224 | – | – | – |
| mMCP-2a | Mcpt2 | 17225 | – | – | – |
| mMCP-3/ mMCP-La | Mcptl | 17233 | – | – | – |
| mMCP-4a | Mcpt4 | 17227 | – | – | – |
| mMCP-5 | Cma1 | 17228 | Chymase-1 | CMA1 | 1215 |
| mMCP-6b | Tpsb2 | 17229 | hTryptase-βb | TPSB2 | 64499 |
| mMCP-7b | Tpsab1 | 100503895 | hTryptase-βb | TPSAB1 | 7177 |
| – | – | – | hTryptase-δb | TPSD1 | 23430 |
| mMCP-8a | Mcpt8 | 17231 | – | – | – |
| mMCP-9a | Mcpt9 | 17232 | – | – | – |
| mMCP-10a | Cma2 | 545055 | – | – | – |
| Prss31 | Tpsg1 | 26945 | PRSS31 | TPSG1 | 25823 |
| Carboxypeptidase A3 | Cpa3 | 12873 | Carboxypeptidase A3 | CPA3 | 1359 |
| Cathepsin G | Ctsg | 13035 | Cathepsin G | CTSG | 1511 |
| Granzyme B | Gzmb | 14939 | Granzyme B | GZMB | 3002 |
| Neuropsin/ Prss19c | Klk8 | 259277 | Kallikrein-related protease-8c | KLK8 | 11202 |
Mouse MCs store varied combinations of 16 proteases in their granules, some of which do not have human orthologs (namely the genes that encode mMCP-1, mMCP-2, mMCP-3/L, mMCP-8, mMCP-9, and mMCP-10). The heparin+ MCs that reside in the mouse’s skin and other connective tissues express both mMCP-4 and mMCP-5. Although the Human and Mouse Genome Consortiums concluded that mMCP-5 is the mouse ortholog of CMA1, mMCP-4 has a more similar substrate preference in terms of its ability to cleave low molecular weight peptide substrates. Thus, there is some debate as to whether mMCP-4 or mMCP-5 is the true ortholog of human CMA1.
Mouse MCs store two tetramer-forming tryptases in their granules that originate from the mMCP-6/ Tpsb2 and mMCP-7/Tpsab1 genes. It was initially thought that human MCs have only one gene that encodes functional tetramer-forming tryptases. It is now know that the corresponding TPSB2 and TPSAB1 genes in the human genome give rise to similar enzymes that regrettably have been called hTryptase-β even though the translated proteins originate from two genes. Complicating the situation, the transcripts that originate from the TPSB2 and TPSAB1 genes can give rise to functionally different proteases due to variable splicing of the precursor transcripts. Thus, studies carried out in the 1980s and 1990s using “hTryptase-β” preparations purified from pooled human lung or skin biopsies actually were a complex mixture of enzymes, some of which likely differed in their substrate preferences. Human MCs also express hTryptase-δ whose TPSD1 gene is closely related to the human TPSAB1 and TPSB2 genes. However, this tryptase has reduced enzymatic activity due to a premature translation–termination codon that causes loss of one of the seven loops that form the enzyme’s substrate-binding site.
Some mouse MCs express neuropsin/Prss18/Klk8. Although there is a corresponding KLK8 gene in the human genome, it remains to be shown that this kallikrein is expressed in any population of human MCs.