TPSAB1 explained

Tryptase alpha-1 and tryptase beta-1 are enzymes that in humans are encoded by the same TPSAB1 gene.^{[1] [2]} Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha tryptases predominate.

Function

Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. These genes are characterized by several distinct features. They have a highly conserved 3' UTR and contain tandem repeat sequences at the 5' flank and 3' UTR which are thought to play a role in regulation of the mRNA stability. These genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. The alleles of this gene exhibit an unusual amount of sequence variation, such that the alleles were once thought to represent two separate genes, alpha and beta 1.Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders.^[3]

Further reading

• Sommerhoff CP, Bode W, Matschiner G, etal . The human mast cell tryptase tetramer: a fascinating riddle solved by structure. . Biochim. Biophys. Acta . 1477 . 1–2 . 75–89 . 2000 . 10708850 . 10.1016/s0167-4838(99)00265-4.
• Kam CM, Hudig D, Powers JC . Granzymes (lymphocyte serine proteases): characterization with natural and synthetic substrates and inhibitors . Biochim. Biophys. Acta . 1477 . 1–2 . 307–23 . 2000 . 10708866 . 10.1016/s0167-4838(99)00282-4.
• Caughey GH . New developments in the genetics and activation of mast cell proteases . Mol. Immunol. . 38 . 16–18 . 1353–7 . 2003 . 12217407 . 10.1016/S0161-5890(02)00087-1 .
• Vanderslice P, Ballinger SM, Tam EK, etal . Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family . Proc. Natl. Acad. Sci. U.S.A. . 87 . 10 . 3811–5 . 1990 . 2187193 . 10.1073/pnas.87.10.3811 . 53993 . 1990PNAS...87.3811V . free .
• Miller JS, Westin EH, Schwartz LB . Cloning and characterization of complementary DNA for human tryptase . J. Clin. Invest. . 84 . 4 . 1188–95 . 1989 . 2677049 . 10.1172/JCI114284 . 329777 .
• Schwartz LB, Bradford TR, Littman BH, Wintroub BU . The fibrinogenolytic activity of purified tryptase from human lung mast cells . J. Immunol. . 135 . 4 . 2762–7 . 1985 . 10.4049/jimmunol.135.4.2762 . 3161948 . free .
• Schwartz LB, Lewis RA, Seldin D, Austen KF . Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells . J. Immunol. . 126 . 4 . 1290–4 . 1981 . 10.4049/jimmunol.126.4.1290 . 7009736 . free .
• Xia HZ, Kepley CL, Sakai K, etal . Quantitation of tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNAs in human mast cells and basophils by competitive reverse transcription-polymerase chain reaction . J. Immunol. . 154 . 10 . 5472–80 . 1995 . 10.4049/jimmunol.154.10.5472 . 7730649 . free .
• Blom T, Hellman L . Characterization of a tryptase mRNA expressed in the human basophil cell line KU812 . Scand. J. Immunol. . 37 . 2 . 203–8 . 1993 . 8434231 . 10.1111/j.1365-3083.1993.tb01757.x . 22041090 .
• Cairns JA, Walls AF . Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression . J. Immunol. . 156 . 1 . 275–83 . 1996 . 10.4049/jimmunol.156.1.275 . 8598474 . free .
• Schwartz LB, Sakai K, Bradford TR, etal . The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis . J. Clin. Invest. . 96 . 6 . 2702–10 . 1996 . 8675637 . 10.1172/JCI118337 . 185977 .
• Cairns JA, Walls AF . Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts . J. Clin. Invest. . 99 . 6 . 1313–21 . 1997 . 9077541 . 10.1172/JCI119290 . 507947 .
• Xia HZ, Du Z, Craig S, etal . Effect of recombinant human IL-4 on tryptase, chymase, and Fc epsilon receptor type I expression in recombinant human stem cell factor-dependent fetal liver-derived human mast cells . J. Immunol. . 159 . 6 . 2911–21 . 1997 . 10.4049/jimmunol.159.6.2911 . 9300715 . 45026410 .
• Thomas VA, Wheeless CJ, Stack MS, Johnson DA . Human mast cell tryptase fibrinogenolysis: kinetics, anticoagulation mechanism, and cell adhesion disruption . Biochemistry . 37 . 8 . 2291–8 . 1998 . 9485375 . 10.1021/bi972119z .
• Pereira PJ, Bergner A, Macedo-Ribeiro S, etal . Human beta-tryptase is a ring-like tetramer with active sites facing a central pore . Nature . 392 . 6673 . 306–11 . 1998 . 9521329 . 10.1038/32703 . 1998Natur.392..306P . 4421972 .
• Huang C, Li L, Krilis SA, etal . Human tryptases alpha and beta/II are functionally distinct due, in part, to a single amino acid difference in one of the surface loops that forms the substrate-binding cleft . J. Biol. Chem. . 274 . 28 . 19670–6 . 1999 . 10391906 . 10.1074/jbc.274.28.19670 . free .
• Sommerhoff CP, Bode W, Pereira PJ, etal . The structure of the human betaII-tryptase tetramer: fo(u)r better or worse . Proc. Natl. Acad. Sci. U.S.A. . 96 . 20 . 10984–91 . 1999 . 10500112 . 10.1073/pnas.96.20.10984 . 34230 . 1999PNAS...9610984S . free .
• Romagnani P, De Paulis A, Beltrame C, etal . Tryptase-chymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines . Am. J. Pathol. . 155 . 4 . 1195–204 . 1999 . 10514402 . 10.1016/S0002-9440(10)65222-4. 1867029 .

Notes and References

1. Miller JS, Moxley G, Schwartz LB . Cloning and characterization of a second complementary DNA for human tryptase . J Clin Invest . 86 . 3 . 864–70 . Oct 1990 . 2203827 . 296804 . 10.1172/JCI114786 .
2. Pallaoro M, Fejzo MS, Shayesteh L, Blount JL, Caughey GH . Characterization of genes encoding known and novel human mast cell tryptases on chromosome 16p13.3 . J Biol Chem . 274 . 6 . 3355–62 . Feb 1999 . 9920877 . 10.1074/jbc.274.6.3355 . free .
3. Web site: Entrez Gene: TPSAB1 tryptase alpha/beta 1.