Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFYM10A)

• DOT Name: Calpain small subunit 2 (CAPNS2)
• Synonyms: CSS2; Calcium-dependent protease small subunit 2
• Gene Name: CAPNS2
• Related Disease: Depression
• UniProt ID: CPNS2_HUMAN
• Pfam ID: PF13833
• Sequence:
  MFLAKALLEGADRGLGEALGGLFGGGGQRREGGGRNIGGIVGGIVNFISEAAAAQYTPEP
  PPTQQHFTSVEASESEEVRRFRQQFTQLAGPDMEVGATDLMNILNKVLSKHKDLKTDGFS
  LDTCRSIVSVMDSDTTGKLGFEEFKYLWNNIKKWQCVYKQYDRDHSGSLGSSQLRGALQA
  AGFQLNEQLYQMIVRRYANEDGDMDFNNFISCLVRLDAMFRAFKSLDRDRDGLIQVSIKE
  WLQLTMYS
• Function: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. This small subunit may act as a tissue-specific chaperone of the large subunit, possibly by helping it fold into its correct conformation for activity.
• Reactome Pathway:
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Depression	DIS3XJ69	Strong	Biomarker	[1]

4 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 Calpain small subunit 2 (CAPNS2).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calpain small subunit 2 (CAPNS2).	[3]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Calpain small subunit 2 (CAPNS2).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Calpain small subunit 2 (CAPNS2).	[5]

References

• [1] CancerSupportSource: validation of a revised multi-dimensional distress screening program for cancer patients and survivors.Support Care Cancer. 2020 Jan;28(1):55-64. doi: 10.1007/s00520-019-04753-w. Epub 2019 Apr 12.
• [2] 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.
• [3] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [4] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.