Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2NNFKZ)

• DOT Name: RNA exonuclease 4 (REXO4)
• Synonyms: EC 3.1.-.-; Exonuclease XPMC2; Prevents mitotic catastrophe 2 protein homolog; hPMC2
• Gene Name: REXO4
• Related Disease:
  Breast cancer
  Breast carcinoma
  Lung squamous cell carcinoma
• UniProt ID: REXO4_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF00929
• Sequence:
  MGKAKVPASKRAPSSPVAKPGPVKTLTRKKNKKKKRFWKSKAREVSKKPASGPGAVVRPP
  KAPEDFSQNWKALQEWLLKQKSQAPEKPLVISQMGSKKKPKIIQQNKKETSPQVKGEEMP
  AGKDQEASRGSVPSGSKMDRRAPVPRTKASGTEHNKKGTKERTNGDIVPERGDIEHKKRK
  AKEAAPAPPTEEDIWFDDVDPADIEAAIGPEAAKIARKQLGQSEGSVSLSLVKEQAFGGL
  TRALALDCEMVGVGPKGEESMAARVSIVNQYGKCVYDKYVKPTEPVTDYRTAVSGIRPEN
  LKQGEELEVVQKEVAEMLKGRILVGHALHNDLKVLFLDHPKKKIRDTQKYKPFKSQVKSG
  RPSLRLLSEKILGLQVQQAEHCSIQDAQAAMRLYVMVKKEWESMARDRRPLLTAPDHCSD
  DA

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[2]

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 RNA exonuclease 4 (REXO4).	[3]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of RNA exonuclease 4 (REXO4).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RNA exonuclease 4 (REXO4).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RNA exonuclease 4 (REXO4).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of RNA exonuclease 4 (REXO4).	[6]

References

• [1] Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.Cancer Biol Ther. 2015;16(4):518-27. doi: 10.1080/15384047.2015.1016661. Epub 2015 Apr 7.
• [2] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [3] 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.
• [4] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [5] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.