Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN769MT)

• DOT Name: Tryptase beta-2 (TPSB2)
• Synonyms: Tryptase-2; EC 3.4.21.59; Tryptase II
• Gene Name: TPSB2
• Related Disease:
  Neoplasm
  Keloid
  Mastocytosis
  46,XY sex reversal 2
  Charcot-Marie-Tooth disease type 3
• UniProt ID: TRYB2_HUMAN
• PDB ID: 1A0L; 2BM2; 2FPZ; 2FS8; 2FS9; 2FWW; 2FXR; 2GDD; 2ZA5; 3V7T
• EC Number: 3.4.21.59
• Pfam ID: PF00089
• Sequence:
  MLNLLLLALPVLASRAYAAPAPGQALQRVGIVGGQEAPRSKWPWQVSLRVRDRYWMHFCG
  GSLIHPQWVLTAAHCVGPDVKDLAALRVQLREQHLYYQDQLLPVSRIIVHPQFYTAQIGA
  DIALLELEEPVNVSSHVHTVTLPPASETFPPGMPCWVTGWGDVDNDERLPPPFPLKQVKV
  PIMENHICDAKYHLGAYTGDDVRIVRDDMLCAGNTRRDSCQGDSGGPLVCKVNGTWLQAG
  VVSWGEGCAQPNRPGIYTRVTYYLDWIHHYVPKKP
• Function: Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. May play a role in innate immunity.
• KEGG Pathway: Influenza A (hsa05164)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Keloid	DISV09JY	Strong	Biomarker	[2]
Mastocytosis	DIS1TEE0	Strong	Genetic Variation	[3]
46,XY sex reversal 2	DIS0USUN	Limited	Genetic Variation	[4]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Genetic Variation	[4]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tryptase beta-2 (TPSB2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tryptase beta-2 (TPSB2).	[9]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Tryptase beta-2 (TPSB2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tryptase beta-2 (TPSB2).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Tryptase beta-2 (TPSB2).	[8]

References

• [1] Programmed death ligand 1 expression in early stage, resectable non-small cell lung cancer.Oncotarget. 2019 Jan 15;10(5):561-572. doi: 10.18632/oncotarget.26529. eCollection 2019 Jan 15.
• [2] Comparative proteomic analysis between normal skin and keloid scar.Br J Dermatol. 2010 Jun;162(6):1302-15. doi: 10.1111/j.1365-2133.2010.09660.x. Epub 2010 Feb 1.
• [3] Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels.Clin Immunol. 2007 Jun;123(3):268-71. doi: 10.1016/j.clim.2007.02.007. Epub 2007 Apr 20.
• [4] Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines.Hum Immunol. 2015 May;76(5):318-23. doi: 10.1016/j.humimm.2015.03.009. Epub 2015 Mar 20.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.