Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOFAQ2Z)

• DOT Name: Translin (TSN)
• Synonyms: EC 3.1.-.-; Component 3 of promoter of RISC; C3PO
• Gene Name: TSN
• Related Disease:
  Fatty liver disease
  Hepatocellular carcinoma
  Liposarcoma
  Lymphoma
  Neoplasm
  Non-small-cell lung cancer
  Pancytopenia
  T-cell acute lymphoblastic leukaemia
• UniProt ID: TSN_HUMAN
• PDB ID: 1J1J; 3PJA; 3QB5; 4WYV
• EC Number: 3.1.-.-
• Pfam ID: PF01997
• Sequence:
  MSVSEIFVELQGFLAAEQDIREEIRKVVQSLEQTAREILTLLQGVHQGAGFQDIPKRCLK
  AREHFGTVKTHLTSLKTKFPAEQYYRFHEHWRFVLQRLVFLAAFVVYLETETLVTREAVT
  EILGIEPDREKGFHLDVEDYLSGVLILASELSRLSVNSVTAGDYSRPLHISTFINELDSG
  FRLLNLKNDSLRKRYDGLKYDVKKVEEVVYDLSIRGFNKETAAACVEK
• Function: DNA-binding protein that specifically recognizes consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. Seems to recognize single-stranded DNA ends generated by staggered breaks occurring at recombination hot spots.; Exhibits both single-stranded and double-stranded endoribonuclease activity. May act as an activator of RNA-induced silencing complex (RISC) by facilitating endonucleolytic cleavage of the siRNA passenger strand.
• Reactome Pathway: Small interfering RNA (siRNA) biogenesis (R-HSA-426486)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fatty liver disease	DIS485QZ	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Liposarcoma	DIS8IZVM	Strong	Biomarker	[3]
Lymphoma	DISN6V4S	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Pancytopenia	DISVKEHV	Strong	Biomarker	[5]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Translin (TSN).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Translin (TSN).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Translin (TSN).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Translin (TSN).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Translin (TSN).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Translin (TSN).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Translin (TSN).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Translin (TSN).	[14]

References

• [1] Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance.Int J Obes (Lond). 2020 Jan;44(1):254-266. doi: 10.1038/s41366-018-0315-7. Epub 2019 Jan 15.
• [2] Interaction between hepatitis C virus core protein and translin protein--a possible molecular mechanism for hepatocellular carcinoma and lymphoma caused by hepatitis C virus.World J Gastroenterol. 2003 Feb;9(2):300-3. doi: 10.3748/wjg.v9.i2.300.
• [3] Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;6).Oncogene. 2000 Nov 23;19(50):5821-5. doi: 10.1038/sj.onc.1203943.
• [4] Tudor staphylococcal nuclease drives chemoresistance of non-small cell lung carcinoma cells by regulating S100A11. Oncotarget. 2015 May 20;6(14):12156-73. doi: 10.18632/oncotarget.3495.
• [5] Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins.Ann N Y Acad Sci. 2018 Jun;1421(1):37-45. doi: 10.1111/nyas.13690. Epub 2018 May 8.
• [6] Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11).Int Immunol. 1994 Jul;6(7):1017-25. doi: 10.1093/intimm/6.7.1017.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Resveratrol-induced gene expression profiles in human prostate cancer cells. Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):596-604. doi: 10.1158/1055-9965.EPI-04-0398.
• [12] Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.