Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4FLFT4)

• DOT Name: Deoxycytidylate deaminase (DCTD)
• Synonyms: EC 3.5.4.12; dCMP deaminase
• Gene Name: DCTD
• UniProt ID: DCTD_HUMAN
• PDB ID: 2W4L
• EC Number: 3.5.4.12
• Pfam ID: PF00383
• Sequence:
  MSEVSCKKRDDYLEWPEYFMAVAFLSAQRSKDPNSQVGACIVNSENKIVGIGYNGMPNGC
  SDDVLPWRRTAENKLDTKYPYVCHAELNAIMNKNSTDVKGCSMYVALFPCNECAKLIIQA
  GIKEVIFMSDKYHDSDEATAARLLFNMAGVTFRKFIPKCSKIVIDFDSINSRPSQKLQ
• Function: Catalyzes the deamination of dCMP to dUMP, providing the nucleoside monophosphate substrate for the thymidylate synthase/TYMS. Also, part of a nucleotide salvage pathway that eliminates epigenetically modified 5-hydroxymethyl-dCMP (hmdCMP) in a two-step process entailing deamination to cytotoxic 5-hydroxymethyl-dUMP (hmdUMP), followed by its hydrolysis into 5-hydroxymethyluracil (hmU) and 2-deoxy-D-ribose 5-phosphate (deoxyribosephosphate). Catalyzes the first step in that pathway, the deamination of 5-hydroxymethyl-dCMP (hmdCMP).
• KEGG Pathway:
  Pyrimidine metabolism (hsa00240)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway: Interconversion of nucleotide di- and triphosphates (R-HSA-499943)
• BioCyc Pathway: MetaCyc:HS05252-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Deoxycytidylate deaminase (DCTD) affects the response to substance of Paclitaxel.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Deoxycytidylate deaminase (DCTD).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Deoxycytidylate deaminase (DCTD).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Deoxycytidylate deaminase (DCTD).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deoxycytidylate deaminase (DCTD).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Deoxycytidylate deaminase (DCTD).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Deoxycytidylate deaminase (DCTD).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Deoxycytidylate deaminase (DCTD).	[7]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Deoxycytidylate deaminase (DCTD).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] 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.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [8] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.