Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3004C1)

• DOT Name: NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13)
• Synonyms: EC 3.6.1.22; Nucleoside diphosphate-linked moiety X motif 13; Nudix motif 13; Protein KiSS-16
• Gene Name: NUDT13
• Related Disease:
  Gastric cancer
  Stomach cancer
• UniProt ID: NUD13_HUMAN
• EC Number: 3.6.1.22
• Pfam ID: PF00293 ; PF09296 ; PF09297
• Sequence:
  MSLYCGIACRRKFFWCYRLLSTYVTKTRYLFELKEDDDACKKAQQTGAFYLFHSLAPLLQ
  TSAHQYLAPRHSLLELERLLGKFGQDAQRIEDSVLIGCSEQQEAWFALDLGLDSSFSISA
  SLHKPEMETELKGSFIELRKALFQLNARDASLLSTAQALLRWHDAHQFCSRSGQPTKKNV
  AGSKRVCPSNNIIYYPQMAPVAITLVSDGTRCLLARQSSFPKGMYSALAGFCDIGESVEE
  TIRREVAEEVGLEVESLQYYASQHWPFPSGSLMIACHATVKPGQTEIQVNLRELETAAWF
  SHDEVATALKRKGPYTQQQNGTFPFWLPPKLAISHQLIKEWVEKQTCSSLPA
• Function: NAD(P)H pyrophosphatase that hydrolyzes NADH into NMNH and AMP, and NADPH into NMNH and 2',5'-ADP. Has a marked preference for the reduced pyridine nucleotides. Does not show activity toward NAD-capped RNAs; the NAD-cap is an atypical cap present at the 5'-end of some RNAs.
• Tissue Specificity: Highly expressed in metastasis-suppressed chromosome 6 melanoma hybrids.
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Peroxisome (hsa04146)
• Reactome Pathway: Interconversion of nucleotide di- and triphosphates (R-HSA-499943)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of NAD(P)H pyrophosphatase NUDT13, mitochondrial (NUDT13).	[9]

References

• [1] Metastatic pathway-specific transcriptome analysis identifies MFSD4 as a putative tumor suppressor and biomarker for hepatic metastasis in patients with gastric cancer.Oncotarget. 2016 Mar 22;7(12):13667-79. doi: 10.18632/oncotarget.7269.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.