Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase.
A gene encoding human chymase was cloned and sequenced. The protein-coding exons reveal a preproenzyme 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.
Caughey
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GH
Cardiovascular Research Institute, University of California, San Francisco 94143-0911.
Zerweck
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EH
Vanderslice
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D053818:Chymases; D003001:Cloning, Molecular; D004285:Dogs; D005260:Female; D005796:Genes; D015698:Genomic Library; D006801:Humans; D008407:Mast Cells / Q000201:enzymology*; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics*
D012697:Serine Endopeptidases; D053818:Chymases