TPSB2 explained

Tryptase beta-2, also known as tryptase II, is a proteolytic enzyme that in humans is encoded by the TPSB2 gene.^[1]

Formerly, the enzyme was known as Tryptase Clara.

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, beta II and beta III.

Beta tryptases appear to be the main isoenzymes expressed in mast cells and club cells, whereas in basophils, alpha-tryptases predominate.

Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. In particular, influenza A virus is activated by TPSB2-mediated proteolytic cleavage in the upper respiratory tract.^[2]

Further reading

• Miller JS, Moxley G, Schwartz LB . Cloning and characterization of a second complementary DNA for human tryptase . The Journal of Clinical Investigation . 86 . 3 . 864–870 . September 1990 . 2203827 . 296804 . 10.1172/JCI114786 .
• Hallgren J, Lindahl S, Pejler G . Structural requirements and mechanism for heparin-dependent activation and tetramerization of human betaI- and betaII-tryptase . Journal of Molecular Biology . 345 . 1 . 129–139 . January 2005 . 15567416 . 10.1016/j.jmb.2004.10.029 .
• Sommerhoff CP, Bode W, Matschiner G, Bergner A, Fritz H . The human mast cell tryptase tetramer: a fascinating riddle solved by structure . Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology . 1477 . 1–2 . 75–89 . March 2000 . 10708850 . 10.1016/s0167-4838(99)00265-4 .
• Huang C, Li L, Krilis SA, Chanasyk K, Tang Y, Li Z, Hunt JE, Stevens RL . 6 . 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 . The Journal of Biological Chemistry . 274 . 28 . 19670–19676 . July 1999 . 10391906 . 10.1074/jbc.274.28.19670 . free .
• Caughey GH, Raymond WW, Blount JL, Hau LW, Pallaoro M, Wolters PJ, Verghese GM . Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families . Journal of Immunology . 164 . 12 . 6566–6575 . June 2000 . 10843716 . 10.4049/jimmunol.164.12.6566 . free .
• Vanderslice P, Ballinger SM, Tam EK, Goldstein SM, Craik CS, Caughey GH . Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family . Proceedings of the National Academy of Sciences of the United States of America . 87 . 10 . 3811–3815 . May 1990 . 2187193 . 53993 . 10.1073/pnas.87.10.3811 . free . 1990PNAS...87.3811V .
• Guida M, Riedy M, Lee D, Hall J . Characterization of two highly polymorphic human tryptase loci and comparison with a newly discovered monkey tryptase ortholog . Pharmacogenetics . 10 . 5 . 389–396 . July 2000 . 10898108 . 10.1097/00008571-200007000-00002 .
• Blom T, Hellman L . Characterization of a tryptase mRNA expressed in the human basophil cell line KU812 . Scandinavian Journal of Immunology . 37 . 2 . 203–208 . February 1993 . 8434231 . 10.1111/j.1365-3083.1993.tb01757.x . 22041090 .
• 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 . The Journal of Biological Chemistry . 274 . 6 . 3355–3362 . February 1999 . 9920877 . 10.1074/jbc.274.6.3355 . free .
• Caughey GH . New developments in the genetics and activation of mast cell proteases . Molecular Immunology . 38 . 16–18 . 1353–1357 . September 2002 . 12217407 . 10.1016/S0161-5890(02)00087-1 .
• Akin C, Soto D, Brittain E, Chhabra A, Schwartz LB, Caughey GH, Metcalfe DD . Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels . Clinical Immunology . 123 . 3 . 268–271 . June 2007 . 17449330 . 1949411 . 10.1016/j.clim.2007.02.007 .
• Sommerhoff CP, Bode W, Pereira PJ, Stubbs MT, Stürzebecher J, Piechottka GP, Matschiner G, Bergner A . 6 . The structure of the human betaII-tryptase tetramer: fo(u)r better or worse . Proceedings of the National Academy of Sciences of the United States of America . 96 . 20 . 10984–10991 . September 1999 . 10500112 . 34230 . 10.1073/pnas.96.20.10984 . free . 1999PNAS...9610984S .
• Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR . 6 . Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16 . Human Molecular Genetics . 10 . 4 . 339–352 . February 2001 . 11157797 . 10.1093/hmg/10.4.339 . free .
• Trivedi NN, Tamraz B, Chu C, Kwok PY, Caughey GH . Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations . The Journal of Allergy and Clinical Immunology . 124 . 5 . 1099–1105.e4 . November 2009 . 19748655 . 2783561 . 10.1016/j.jaci.2009.07.026 .
• Pereira PJ, Bergner A, Macedo-Ribeiro S, Huber R, Matschiner G, Fritz H, Sommerhoff CP, Bode W . 6 . Human beta-tryptase is a ring-like tetramer with active sites facing a central pore . Nature . 392 . 6673 . 306–311 . March 1998 . 9521329 . 10.1038/32703 . 4421972 . 1998Natur.392..306P .
• Wu C, Ma MH, Brown KR, Geisler M, Li L, Tzeng E, Jia CY, Jurisica I, Li SS . 6 . Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening . Proteomics . 7 . 11 . 1775–1785 . June 2007 . 17474147 . 10.1002/pmic.200601006 . 22474278 .

Notes and References

1. Web site: Entrez Gene: tryptase beta 2 (gene/pseudogene).
2. Kido H, Yokogoshi Y, Sakai K, Tashiro M, Kishino Y, Fukutomi A, Katunuma N . Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein . The Journal of Biological Chemistry . 267 . 19 . 13573–13579 . July 1992 . 10.1016/S0021-9258(18)42250-8 . 1618859 . free .