Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJYI4WV)

• DOT Name: Tryptase alpha/beta-1 (TPSAB1)
• Synonyms: Tryptase-1; EC 3.4.21.59; Tryptase I; Tryptase alpha-1
• Gene Name: TPSAB1
• UniProt ID: TRYB1_HUMAN
• PDB ID: 1LTO; 2F9N; 2F9O; 2F9P; 2ZEB; 2ZEC; 4A6L; 4MPU; 4MPV; 4MPW; 4MPX; 4MQA; 5F03; 5WI6; 6O1F; 6P0P; 6VVU
• EC Number: 3.4.21.59
• Pfam ID: PF00089
• Sequence:
  MLNLLLLALPVLASRAYAAPAPGQALQRVGIVGGQEAPRSKWPWQVSLRVHGPYWMHFCG
  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. Isoform 2 cleaves large substrates, such as fibronectin, more efficiently than isoform 1, but seems less efficient toward small substrates.
• Tissue Specificity: Isoform 1 and isoform 2 are expressed in lung, stomach, spleen, heart and skin; in these tissues, isoform 1 is predominant. Isoform 2 is expressed in aorta, spleen, and breast tumor, with highest levels in the endothelial cells of some blood vessels surrounding the aorta, as well as those surrounding the tumor and low levels, if any, in mast cells (at protein level).
• KEGG Pathway: Influenza A (hsa05164)
• Reactome Pathway: Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DOT

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 alpha/beta-1 (TPSAB1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tryptase alpha/beta-1 (TPSAB1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tryptase alpha/beta-1 (TPSAB1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tryptase alpha/beta-1 (TPSAB1).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tryptase alpha/beta-1 (TPSAB1).	[4]

References

• [1] 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.
• [2] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] 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.