Characterization of human γ-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families

Previously, this laboratory identified clusters of alpha-, beta-, and mast cell protease-7-like tryptase genes on human chromosome 16p13.3. The present work characterizes adjacent genes encoding novel serine proteases, termed gamma-tryptases, and generates a refined map of the multitryptase locus, Each gamma gene lies between an alpha 1H Ca2+ channel gene (CACNA1H) and a beta II- or beta III-tryptase gene and is similar to 30 kb from polymorphic minisatellite MS205, The tryptase locus also contains at least four tryptase-like pseudogenes, including mastin, a gene expressed in dogs but not in humans. Genomic DNA blotting results suggest that gamma I- and gamma II-tryptases are alleles at the same site, beta II- and beta III-tryptases appear to be alleles at a neighboring site, and alpha II- and beta I-tryptases appear to be alleles at a third site. gamma-Tryptases are transcribed in lung, intestine, and in several other tissues and in a mast cell line (HMC-1) that also expresses gamma-tryptase protein. Immunohistochemical analysis suggests that gamma-tryptase is expressed by airway mast cells. gamma-Tryptase catalytic domains are similar to 48% identical with those of known mast cell tryptases and possess mouse homologues. We predict that gamma-tryptases are glycosylated oligomers with tryptic substrate specificity and a distinct mode of activation. A feature not found in described tryptases is a C-terminal hydrophobic domain, which may be a membrane anchor, Although the catalytic domains contain tryptase-like features, the hydrophobic segment and intron exon organization are more closely related to another recently described protease, prostasin, In summary, this work describes gamma-tryptases, which are novel members of chromosome 16p tryptase/prostasin gene families. Their unique features suggest possibly novel functions.