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Title
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Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase.
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Authors
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G.H.Caughey,
E.H.Zerweck,
P.Vanderslice.
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Ref.
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J Biol Chem, 1991,
266,
12956-12963.
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PubMed id
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Abstract
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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.
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