Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT073JKX)

• DOT Name: Nuclear migration protein nudC (NUDC)
• Synonyms: Nuclear distribution protein C homolog
• Gene Name: NUDC
• Related Disease:
  Prostate neoplasm
  Acute erythroid leukemia
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Childhood acute lymphoblastic leukemia
  leukaemia
  Leukemia
• UniProt ID: NUDC_HUMAN
• PDB ID: 3QOR; 7NDX
• Pfam ID: PF04969 ; PF16273 ; PF14050
• Sequence:
  MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKLITQTFS
  HHNQLAQKTRREKRARQEAERREKAERAARLAKEAKSETSGPQIKELTDEEAERLQLEID
  QKKDAENHEAQLKNGSLDSPGKQDTEEDEEEDEKDKGKLKPNLGNGADLPNYRWTQTLSE
  LDLAVPFCVNFRLKGKDMVVDIQRRHLRVGLKGQPAIIDGELYNEVKVEESSWLIEDGKV
  VTVHLEKINKMEWWSRLVSSDPEINTKKINPENSKLSDLDSETRSMVEKMMYDQRQKSMG
  LPTSDEQKKQEILKKFMDQHPEMDFSKAKFN
• Function: Plays a role in neurogenesis and neuronal migration. Necessary for correct formation of mitotic spindles and chromosome separation during mitosis. Necessary for cytokinesis and cell proliferation.
• Tissue Specificity: Ubiquitous. Highly expressed in fetal liver, kidney, lung and brain. Highly expressed in adult pancreas, kidney, skeletal muscle, liver, lung, placenta, prostate, brain and heart.
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  RND2 GTPase cycle (R-HSA-9696270)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[1]
Acute erythroid leukemia	DISZFC1O	Limited	Altered Expression	[2]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Biomarker	[2]
leukaemia	DISS7D1V	Limited	Altered Expression	[2]
Leukemia	DISNAKFL	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Nuclear migration protein nudC (NUDC) affects the binding of PEITC.	[13]

9 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 Nuclear migration protein nudC (NUDC).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear migration protein nudC (NUDC).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear migration protein nudC (NUDC).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear migration protein nudC (NUDC).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Nuclear migration protein nudC (NUDC).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Nuclear migration protein nudC (NUDC).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear migration protein nudC (NUDC).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear migration protein nudC (NUDC).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Nuclear migration protein nudC (NUDC).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Nuclear migration protein nudC (NUDC).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Nuclear migration protein nudC (NUDC).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nuclear migration protein nudC (NUDC).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nuclear migration protein nudC (NUDC).	[7]

References

• [1] Inhibition of prostate tumor growth by overexpression of NudC, a microtubule motor-associated protein.Oncogene. 2004 Apr 1;23(14):2499-506. doi: 10.1038/sj.onc.1207343.
• [2] The nuclear migration gene NudC and human hematopoiesis.Leuk Lymphoma. 2000 Nov;39(5-6):447-54. doi: 10.3109/10428190009113375.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [11] 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.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [13] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.