Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL4VJC5)

• DOT Name: Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1)
• Synonyms: P1
• Gene Name: NUCKS1
• Related Disease:
  Alzheimer disease
  Androgen insensitivity syndrome
  Atrial fibrillation
  Epithelial ovarian cancer
  Gastric cancer
  Hepatocellular carcinoma
  Myocardial infarction
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Schizophrenia
  Stomach cancer
  Ulcerative colitis
  Colorectal carcinoma
  Familial atrial fibrillation
  Breast cancer
  Breast carcinoma
  Obesity
• UniProt ID: NUCKS_HUMAN
• Sequence:
  MSRPVRNRKVVDYSQFQESDDADEDYGRDSGPPTKKIRSSPREAKNKRRSGKNSQEDSED
  SEDKDVKTKKDDSHSAEDSEDEKEDHKNVRQQRQAASKAASKQREMLMEDVGSEEEQEEE
  DEAPFQEKDSGSDEDFLMEDDDDSDYGSSKKKNKKMVKKSKPERKEKKMPKPRLKATVTP
  SPVKGKGKVGRPTASKASKEKTPSPKEEDEEPESPPEKKTSTSPPPEKSGDEGSEDEAPS
  GED
• Function: Chromatin-associated protein involved in DNA repair by promoting homologous recombination (HR). Binds double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures, but with less affinity than RAD51AP1.
• Tissue Specificity: Widely expressed, with highest levels in thyroid gland, prostate and uterus and in fetal liver, thymus and lung.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Androgen insensitivity syndrome	DISUZBBO	Strong	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[4]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Myocardial infarction	DIS655KI	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[4]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[8]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[5]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[9]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[3]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Obesity	DIS47Y1K	Limited	Altered Expression	[10]

5 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 Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[23]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[23]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[15]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[16]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[18]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[19]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[20]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[21]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[28]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1).	[30]

References

• [1] Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese.Mol Neurobiol. 2017 Jan;54(1):308-318. doi: 10.1007/s12035-015-9649-5. Epub 2016 Jan 6.
• [2] Genetic Polymorphism of NUCKS1 Is Associated With the Susceptibility of Adolescent Idiopathic Scoliosis.Spine (Phila Pa 1976). 2017 Nov 1;42(21):1629-1634. doi: 10.1097/BRS.0000000000002167.
• [3] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [4] NUCKS nuclear elevated expression indicates progression and prognosis of ovarian cancer.Tumour Biol. 2017 Sep;39(9):1010428317714631. doi: 10.1177/1010428317714631.
• [5] NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway.Carcinogenesis. 2019 Apr 29;40(2):370-379. doi: 10.1093/carcin/bgy142.
• [6] Identification of NUCKS1 as a putative oncogene and immunodiagnostic marker of hepatocellular carcinoma.Gene. 2016 Jun 10;584(1):47-53. doi: 10.1016/j.gene.2016.03.006. Epub 2016 Mar 9.
• [7] Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated cardiac protection.Exp Cell Res. 2017 Jul 1;356(1):74-84. doi: 10.1016/j.yexcr.2017.04.012. Epub 2017 Apr 12.
• [8] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [9] Nondysplastic Ulcerative Colitis Has High Levels of the Homologous Recombination Repair Protein NUCKS1 and Low Levels of the DNA Damage Marker Gamma-H2AX.Inflamm Bowel Dis. 2018 Feb 15;24(3):593-600. doi: 10.1093/ibd/izx071.
• [10] Effect of NUCKS-1 overexpression on cytokine profiling in obese women with breast cancer.Asian Pac J Cancer Prev. 2014;15(2):837-45. doi: 10.7314/apjcp.2014.15.2.837.
• [11] 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.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [15] 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.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Proteomic analysis of antiproliferative effects by treatment of 5-fluorouracil in cervical cancer cells. DNA Cell Biol. 2004 Nov;23(11):769-76.
• [18] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [19] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [20] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [21] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [22] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [23] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [24] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [25] 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.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [28] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [29] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [30] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.