Cloning of the gene and cDNA for human heart chymase.
We have recently identified and characterized a chymotrypsin-like serine proteinase in human heart (human heart chymase) that is the most catalytically efficient enzyme described, thus far, for the cleavage of angiotensin I to yield angiotensin II and the dipeptide His-Leu. Compared to other chymases, this enzyme also has an unusually high degree of specificity for the substrate angiotensin I. We report here the molecular cloning and nucleotide sequence of the gene and cDNA encoding human heart chymase, and determination of its entire deduced amino acid sequence. These data indicate that human heart chymase is highly homologous to other members of the chymase subfamily of chymotrypsin-like proteinases and, most likely, all evolved from a common ancestral gene. Potential regulatory elements found in the 5'-untranslated region of other chymases are also found in the human heart chymase gene. However, this gene lacks mast cell-specific sequences found in the 5'- and 3'-untranslated regions of the rat chymase II gene. In addition, human heart chymase contains clusters of unique amino acid sequences located at key positions likely involved in substrate binding, which may contribute to its high substrate specificity. These contrasting features of the human heart chymase gene and cDNA, and the potential determinants of its primary structure that underlie its unique functional characteristics are considered.
Urata
H
H
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio 44195-5069.
Kinoshita
A
A
Perez
D M
DM
Misono
K S
KS
Bumpus
F M
FM
Graham
R M
RM
Husain
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002851:Chromatography, High Pressure Liquid; D053818:Chymases; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D015183:Restriction Mapping; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
D004247:DNA; D012697:Serine Endopeptidases; D053818:Chymases