Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYMBK3Q)

• DOT Name: Nucleoside diphosphate kinase homolog 7 (NME7)
• Synonyms: NDK 7; NDP kinase homolog 7; 3'-5' exonuclease NME7; EC 3.1.-.-; Protein kinase NME7; EC 2.7.-.-; nm23-H7
• Gene Name: NME7
• Related Disease:
  Colon cancer
  Colon carcinoma
  Congenital hydrocephalus
  Drug dependence
  Gastrointestinal stromal tumour
  Hydrocephalus
  Substance abuse
  Substance dependence
  Coronary heart disease
  Venous thromboembolism
  Situs inversus
  Type-1/2 diabetes
• UniProt ID: NDK7_HUMAN
• PDB ID: 7UNG; 8J07
• EC Number: 2.7.-.-; 3.1.-.-
• Pfam ID: PF00334
• Sequence:
  MNHSERFVFIAEWYDPNASLLRRYELLFYPGDGSVEMHDVKNHRTFLKRTKYDNLHLEDL
  FIGNKVNVFSRQLVLIDYGDQYTARQLGSRKEKTLALIKPDAISKAGEIIEIINKAGFTI
  TKLKMMMLSRKEALDFHVDHQSRPFFNELIQFITTGPIIAMEILRDDAICEWKRLLGPAN
  SGVARTDASESIRALFGTDGIRNAAHGPDSFASAAREMELFFPSSGGCGPANTAKFTNCT
  CCIVKPHAVSEGLLGKILMAIRDAGFEISAMQMFNMDRVNVEEFYEVYKGVVTEYHDMVT
  EMYSGPCVAMEIQQNNATKTFREFCGPADPEIARHLRPGTLRAIFGKTKIQNAVHCTDLP
  EDGLLEVQYFFKILDN
• Function: Possesses an intrinsic kinase activity. Displays 3'-5' exonuclease activity with a preference for single-stranded DNA. Does not seem to have nucleoside diphosphate kinase activity. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Functional component of the gamma-tubulin ring complex, implicated in the regulation of the microtubule-nucleating activity of the gamma-tubulin ring complex in centrosomes, in a kinase activity-dependent manner.
• Tissue Specificity: Expressed in airway epithelial cells.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway:
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Congenital hydrocephalus	DIS7O6UL	Strong	Biomarker	[2]
Drug dependence	DIS9IXRC	Strong	Biomarker	[3]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[4]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[5]
Substance abuse	DIS327VW	Strong	Biomarker	[3]
Substance dependence	DISDRAAR	Strong	Biomarker	[3]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[6]
Venous thromboembolism	DISUR7CR	moderate	Genetic Variation	[7]
Situs inversus	DISFA7AJ	Supportive	Autosomal dominant	[2]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Nucleoside diphosphate kinase homolog 7 (NME7) decreases the response to substance of Afimoxifene.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Nucleoside diphosphate kinase homolog 7 (NME7).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Nucleoside diphosphate kinase homolog 7 (NME7).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nucleoside diphosphate kinase homolog 7 (NME7).	[21]

References

• [1] Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer.J Pathol. 2005 Apr;205(5):623-32. doi: 10.1002/path.1724.
• [2] A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis. Hum Mutat. 2016 Aug;37(8):727-31. doi: 10.1002/humu.22998. Epub 2016 May 9.
• [3] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [4] Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. Oncotarget. 2016 Nov 29;7(48):78226-78241. doi: 10.18632/oncotarget.12909.
• [5] Congenital hydrocephalus in genetically engineered mice.Vet Pathol. 2012 Jan;49(1):166-81. doi: 10.1177/0300985811415708. Epub 2011 Jul 11.
• [6] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [7] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [8] Expression profiling of Nme7 interactome in experimental models of metabolic syndrome.Physiol Res. 2018 Nov 28;67(Suppl 3):S543-S550. doi: 10.33549/physiolres.934021.
• [9] 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.
• [10] 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.
• [11] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] 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.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [18] 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.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.