Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8OLFN)

• DOT Name: Nucleoside diphosphate kinase homolog 5 (NME5)
• Synonyms: NDK-H 5; NDP kinase homolog 5; 3'-5' exonuclease NME5; EC 3.1.-.-; Inhibitor of p53-induced apoptosis-beta; IPIA-beta; Testis-specific nm23 homolog; nm23-H5
• Gene Name: NME5
• Related Disease:
  Advanced cancer
  Hydrocephalus
  Pancreatic cancer
  Transitional cell carcinoma
  Urothelial carcinoma
  Ciliary dyskinesia, primary, 48, without situs inversus
• UniProt ID: NDK5_HUMAN
• PDB ID: 8J07
• EC Number: 3.1.-.-
• Pfam ID: PF05186 ; PF00334
• Sequence:
  MEISMPPPQIYVEKTLAIIKPDIVDKEEEIQDIILRSGFTIVQRRKLRLSPEQCSNFYVE
  KYGKMFFPNLTAYMSSGPLVAMILARHKAISYWLELLGPNNSLVAKETHPDSLRAIYGTD
  DLRNALHGSNDFAAAEREIRFMFPEVIVEPIPIGQAAKDYLNLHIMPTLLEGLTELCKQK
  PADPLIWLADWLLKNNPNKPKLCHHPIVEEPY
• Function: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. Does not seem to have nucleoside diphosphate kinase (NDPK) activity. Confers protection from cell death by BAX and alters the cellular levels of several antioxidant enzymes including GPX5. May play a role in spermiogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species. Exhibits a 3'-5' exonuclease activity with a preference for single-stranded DNA, suggesting roles in DNA proofreading and repair.
• Tissue Specificity: Specifically expressed in testis germinal cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[3]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[3]
Ciliary dyskinesia, primary, 48, without situs inversus	DISBUKYU	Moderate	Autosomal recessive	[4]

7 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 Nucleoside diphosphate kinase homolog 5 (NME5).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleoside diphosphate kinase homolog 5 (NME5).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Nucleoside diphosphate kinase homolog 5 (NME5).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Nucleoside diphosphate kinase homolog 5 (NME5).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nucleoside diphosphate kinase homolog 5 (NME5).	[9]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Nucleoside diphosphate kinase homolog 5 (NME5).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleoside diphosphate kinase homolog 5 (NME5).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleoside diphosphate kinase homolog 5 (NME5).	[11]

References

• [1] Transactivation of the human NME5 gene by Sp1 in pancreatic cancer cells.Gene. 2012 Jul 25;503(2):200-7. doi: 10.1016/j.gene.2012.04.088. Epub 2012 May 4.
• [2] NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia.PLoS Genet. 2019 Sep 3;15(9):e1008378. doi: 10.1371/journal.pgen.1008378. eCollection 2019 Sep.
• [3] Genes involved in differentiation, stem cell renewal, and tumorigenesis are modulated in telomerase-immortalized human urothelial cells.Mol Cancer Res. 2008 Jul;6(7):1154-68. doi: 10.1158/1541-7786.MCR-07-2168.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] 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.