Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family.

Abstract

Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the -1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5' regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These rmdings provide genetic evidence that human mast cell tryptases are the products of a multigene family.

Cloning and expression in Escherichia coli of cDNA encoding house dust mite allergen Der f 3, serine protease from Dermatophagoides farinae

“…Tryptase, a trypsin-like serine protease, is produced as a precursor with a N-terminal pro-segment. This precursor is known to be converted to an active form by another protease which cleaves the peptide bond of Gly-Ile at the pro-mature junction [21]. From these observations, we assume that group-3 allergens are converted to an active form from the precursor by the mechanism mediated by some other factors.…”

The mouse mast cell–restricted tetramer‐forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis

“…Our group (1)(2)(3)(4) and many other investigators (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) have obtained data implicating a prominent involvement of mast cells (MCs) and their mediators in RA and some animal models of this autoimmune disorder. On a weight basis, tetramer-forming ␤ tryptases (15)(16)(17)(18)(19) are the most abundant proteins present in the secretory granules of human MCs. Three ␤ tryptase complementary DNAs (designated hTryptase ␤1, ␤2, and ␤3) have been cloned.…”

Characterization of Human γ-Tryptases, Novel Members of the Chromosome 16p Mast Cell Tryptase and Prostasin Gene Families

“…Intron splice junctions were predicted by reference to dog mastin cDNA (27) and patterns of intron phase and placement in known tryptase genes (22,23) by examination of open reading frames and by application of "GT. .…”

“…Human ␤I-tryptase cDNA (22) and gene sequence (23) and Basic Local Alignment Search Tool (www.ncbi.nlm.nih.gov) algorithms were used to query expressed sequence tag (EST) and high throughput genome sequence (HTGS) in GenBank. Predicted novel human cDNAs were used to query GenBank's mouse EST database to identify mouse homologues.…”