Title : Structure, chromosomal assignment, and deduced amino acid
sequence of a human gene for
mast cell chymase
Abstract :
- A gene encoding human chymase was cloned and sequenced
- The protein-coding exons reveal a prepro enzyme with a 19-amino acid signal peptide , an acidic 2-amino acid propeptide , and a 226-amino acid catalytic domain
- The mature enzyme is predicted to be cationic (net charge of +13) and to be modified by N-glycosylation at two sites
- The amino acid sequence is identical to the 35 residues of NH2-terminal amino acid sequence reported for human skin chymase and is identical to 29 of 31 residues of NH2-terminal and internal amino acid sequence reported for human heart chymase
- The full predicted sequence of the catalytic domain reveals a high level of sequence identity to dog mast cell chymase (83%) and a lower level of identity to the sequences of rodent chymases (58-62%)
- In the phase and placement of introns, the organization of this human chymase gene is similar to that of several other granule-associated leukocyte serine proteases, including rat chymase II , lymphocyte granzymes, and neutrophil cathespin G and elastase
- However, the gene organization differs from that of mast cell tryptase , providing additional evidence that the major mast cell serine proteases are separated by substantial evolutionary distance
- Amplification of chymase gene-specific fragments from hamster/human hybrid cell line DNA suggests localization of the chymase gene to human chromosome 14
- High stringency hybridization of chymase DNA to a human genomic DNA blot suggests the possibility of more than one human chymase gene
- Evidence that the chymase gene is expressed in human tissues was obtained by the amplification of chymase-specific DNA from skin and placental cDNA libraries