title: Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families.
abstract: 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 alpha1H Ca2+ channel gene (CACNA1H) and a betaII- or betaIII-tryptase gene and is approximately 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 gammaI- and gammaII-tryptases are alleles at the same site. betaII- and betaIII-tryptases appear to be alleles at a neighboring site, and alphaII- and betaI-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 approximately 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.
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco 94143, USA. ghc@itsa.ucsf.edu
authors.forename: G H
authors.initials: GH
authors.lastname: Caughey
authors.forename: W W
authors.initials: WW
authors.lastname: Raymond
authors.forename: J L
authors.initials: JL
authors.lastname: Blount
authors.forename: L W
authors.initials: LW
authors.lastname: Hau
authors.forename: M
authors.initials: M
authors.lastname: Pallaoro
authors.forename: P J
authors.initials: PJ
authors.lastname: Wolters
authors.forename: G M
authors.initials: GM
authors.lastname: Verghese
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002885:Chromosomes, Human, Pair 16 / Q000201:enzymology* / Q000235:genetics; D053818:Chymases; D018076:DNA, Complementary / Q000302:isolation & purification; D004285:Dogs; D005091:Exons; D006801:Humans; D007438:Introns; D008407:Mast Cells / Q000201:enzymology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity / Q000235:genetics; D011544:Pseudogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D053802:Tryptases; D000099271:Prostasin
chemical_list: D053818:Chymases; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D053802:Tryptases; D000099271:Prostasin; C509190:Tpsb2 protein, mouse; C083294:chymase 2; C509222:Tpsab1 protein, mouse