Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXBB7R3)

• DOT Name: Aurora kinase A- and ninein-interacting protein (AUNIP)
• Synonyms: AIBp
• Gene Name: AUNIP
• Related Disease:
  Atherosclerosis
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: AUNIP_HUMAN
• Pfam ID: PF15334
• Sequence:
  MRRTGPEEEACGVWLDAAALKRRKVQTHLIKPGTKMLTLLPGERKANIYFTQRRAPSTGI
  HQRSIASFFTLQPGKTNGSDQKSVSSHTESQINKESKKNATQLDHLIPGLAHDCMASPLA
  TSTTADIQEAGLSPQSLQTSGHHRMKTPFSTELSLLQPDTPDCAGDSHTPLAFSFTEDLE
  SSCLLDRKEEKGDSARKWEWLHESKKNYQSMEKHTKLPGDKCCQPLGKTKLERKVSAKEN
  RQAPVLLQTYRESWNGENIESVKQSRSPVSVFSWDNEKNDKDSWSQLFTEDSQGQRVIAH
  NTRAPFQDVTNNWNWDLGPFPNSPWAQCQEDGPTQNLKPDLLFTQDSEGNQVIRHQF
• Function: DNA-binding protein that accumulates at DNA double-strand breaks (DSBs) following DNA damage and promotes DNA resection and homologous recombination. Serves as a sensor of DNA damage: binds DNA with a strong preference for DNA substrates that mimic structures generated at stalled replication forks, and anchors RBBP8/CtIP to DSB sites to promote DNA end resection and ensuing homologous recombination repair. Inhibits non-homologous end joining (NHEJ). Required for the dynamic movement of AURKA at the centrosomes and spindle apparatus during the cell cycle.
• Tissue Specificity: Expressed in heart, skeletal muscles, placenta and testis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[10]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Aurora kinase A- and ninein-interacting protein (AUNIP).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Aurora kinase A- and ninein-interacting protein (AUNIP).	[14]

References

• [1] AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate.Science. 2019 Mar 8;363(6431):1085-1088. doi: 10.1126/science.aav1749. Epub 2019 Jan 31.
• [2] Identification of AUNIP as a candidate diagnostic and prognostic biomarker for oral squamous cell carcinoma.EBioMedicine. 2019 Sep;47:44-57. doi: 10.1016/j.ebiom.2019.08.013. Epub 2019 Aug 10.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] 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.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] 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.
• [14] 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.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.