Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOOQL35)

• DOT Name: Kinetochore protein Nuf2 (NUF2)
• Synonyms: hNuf2; hNuf2R; hsNuf2; Cell division cycle-associated protein 1
• Gene Name: NUF2
• UniProt ID: NUF2_HUMAN
• PDB ID: 2VE7; 3IZ0; 8G0P
• Pfam ID: PF03800
• Sequence:
  METLSFPRYNVAEIVIHIRNKILTGADGKNLTKNDLYPNPKPEVLHMIYMRALQIVYGIR
  LEHFYMMPVNSEVMYPHLMEGFLPFSNLVTHLDSFLPICRVNDFETADILCPKAKRTSRF
  LSGIINFIHFREACRETYMEFLWQYKSSADKMQQLNAAHQEALMKLERLDSVPVEEQEEF
  KQLSDGIQELQQSLNQDFHQKTIVLQEGNSQKKSNISEKTKRLNELKLSVVSLKEIQESL
  KTKIVDSPEKLKNYKEKMKDTVQKLKNARQEVVEKYEIYGDSVDCLPSCQLEVQLYQKKI
  QDLSDNREKLASILKESLNLEDQIESDESELKKLKTEENSFKRLMIVKKEKLATAQFKIN
  KKHEDVKQYKRTVIEDCNKVQEKRGAVYERVTTINQEIQKIKLGIQQLKDAAEREKLKSQ
  EIFLNLKTALEKYHDGIEKAAEDSYAKIDEKTAELKRKMFKMST
• Function: Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules.
• 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)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kinetochore protein Nuf2 (NUF2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kinetochore protein Nuf2 (NUF2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kinetochore protein Nuf2 (NUF2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kinetochore protein Nuf2 (NUF2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Kinetochore protein Nuf2 (NUF2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Kinetochore protein Nuf2 (NUF2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Kinetochore protein Nuf2 (NUF2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Kinetochore protein Nuf2 (NUF2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Kinetochore protein Nuf2 (NUF2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Kinetochore protein Nuf2 (NUF2).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Kinetochore protein Nuf2 (NUF2).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Kinetochore protein Nuf2 (NUF2).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Kinetochore protein Nuf2 (NUF2).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Kinetochore protein Nuf2 (NUF2).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Kinetochore protein Nuf2 (NUF2).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Kinetochore protein Nuf2 (NUF2).	[15]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Kinetochore protein Nuf2 (NUF2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kinetochore protein Nuf2 (NUF2).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Kinetochore protein Nuf2 (NUF2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kinetochore protein Nuf2 (NUF2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Kinetochore protein Nuf2 (NUF2).	[20]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Kinetochore protein Nuf2 (NUF2).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Kinetochore protein Nuf2 (NUF2).	[22]

References

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• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer. 2008 Mar;15(1):161-73.
• [7] 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.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [12] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [13] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [14] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] 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.
• [20] 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.
• [21] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [22] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.