Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR0RNB1)

• DOT Name: N-acylneuraminate-9-phosphatase (NANP)
• Synonyms: EC 3.1.3.29; Haloacid dehalogenase-like hydrolase domain-containing protein 4; Neu5Ac-9-Pase
• Gene Name: NANP
• Related Disease:
  Colorectal neoplasm
  Esophageal cancer
  Neoplasm
  Malaria
• UniProt ID: NANP_HUMAN
• PDB ID: 2W4M; 4KNV; 4KNW
• EC Number: 3.1.3.29
• Pfam ID: PF00702
• Sequence:
  MGLSRVRAVFFDLDNTLIDTAGASRRGMLEVIKLLQSKYHYKEEAEIICDKVQVKLSKEC
  FHPYNTCITDLRTSHWEEAIQETKGGAANRKLAEECYFLWKSTRLQHMTLAEDVKAMLTE
  LRKEVRLLLLTNGDRQTQREKIEACACQSYFDAVVVGGEQREEKPAPSIFYYCCNLLGVQ
  PGDCVMVGDTLETDIQGGLNAGLKATVWINKNGIVPLKSSPVPHYMVSSVLELPALLQSI
  DCKVSMST
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway: Sialic acid metabolism (R-HSA-4085001)
• BioCyc Pathway: MetaCyc:HS10082-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[1]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Malaria	DISQ9Y50	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of N-acylneuraminate-9-phosphatase (NANP).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-acylneuraminate-9-phosphatase (NANP).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of N-acylneuraminate-9-phosphatase (NANP).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of N-acylneuraminate-9-phosphatase (NANP).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of N-acylneuraminate-9-phosphatase (NANP).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of N-acylneuraminate-9-phosphatase (NANP).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of N-acylneuraminate-9-phosphatase (NANP).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of N-acylneuraminate-9-phosphatase (NANP).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of N-acylneuraminate-9-phosphatase (NANP).	[12]

References

• [1] Pan-cancer analysis of the metabolic reaction network.Metab Eng. 2020 Jan;57:51-62. doi: 10.1016/j.ymben.2019.09.006. Epub 2019 Sep 14.
• [2] Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations.Nat Genet. 2011 Jun 5;43(7):679-84. doi: 10.1038/ng.849.
• [3] Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies.Immunity. 2017 Dec 19;47(6):1197-1209.e10. doi: 10.1016/j.immuni.2017.11.007. Epub 2017 Nov 29.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] 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.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.