Details of Drug Off-Target (DOT)

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

• DOT Name: Cathepsin W (CTSW)
• Synonyms: EC 3.4.22.-; Lymphopain
• Gene Name: CTSW
• Related Disease:
  Gastroesophageal reflux disease
  Extrapulmonary tuberculosis
  Tuberculosis
• UniProt ID: CATW_HUMAN
• EC Number: 3.4.22.-
• Pfam ID: PF08246 ; PF00112
• Sequence:
  MALTAHPSCLLALLVAGLAQGIRGPLRAQDLGPQPLELKEAFKLFQIQFNRSYLSPEEHA
  HRLDIFAHNLAQAQRLQEEDLGTAEFGVTPFSDLTEEEFGQLYGYRRAAGGVPSMGREIR
  SEEPEESVPFSCDWRKVASAISPIKDQKNCNCCWAMAAAGNIETLWRISFWDFVDVSVQE
  LLDCGRCGDGCHGGFVWDAFITVLNNSGLASEKDYPFQGKVRAHRCHPKKYQKVAWIQDF
  IMLQNNEHRIAQYLATYGPITVTINMKPLQLYRKGVIKATPTTCDPQLVDHSVLLVGFGS
  VKSEEGIWAETVSSQSQPQPPHPTPYWILKNSWGAQWGEKGYFRLHRGSNTCGITKFPLT
  ARVQKPDMKPRVSCPP
• Function: May have a specific function in the mechanism or regulation of T-cell cytolytic activity.; (Microbial infection) Plays a role during influenza virus infection in lungs cells ex vivo. Acts at the level of virus entering host cytoplasm from late endosome.
• Tissue Specificity: Expressed predominantly in natural killer cells, and in cytotoxic T cells.
• KEGG Pathway:
  Lysosome (hsa04142)
  Apoptosis (hsa04210)
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastroesophageal reflux disease	DISQ8G5S	Strong	Altered Expression	[1]
Extrapulmonary tuberculosis	DIS6KM28	Limited	Biomarker	[2]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[2]

1 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 Cathepsin W (CTSW).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cathepsin W (CTSW).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cathepsin W (CTSW).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cathepsin W (CTSW).	[6]

References

• [1] Expression pattern of cathepsin W isoforms in peripheral blood and gastroesophageal mucosa of patients with gastroesophageal reflux disease.Biol Chem. 2011 Dec;392(12):1167-72. doi: 10.1515/BC.2011.192.
• [2] Microarray analysis of gene expression associated with extrapulmonary dissemination of tuberculosis.Respirology. 2006 Sep;11(5):557-65. doi: 10.1111/j.1440-1843.2006.00896.x.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.