Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0MMANL)

• DOT Name: Aminopeptidase O (AOPEP)
• Synonyms: AP-O; EC 3.4.11.-
• Gene Name: AOPEP
• Related Disease:
  Juvenile idiopathic arthritis
  Neoplasm
  Polycystic ovarian syndrome
  Atrial fibrillation
  Familial atrial fibrillation
  Precancerous condition
• UniProt ID: AMPO_HUMAN
• EC Number: 3.4.11.-
• Pfam ID: PF09127 ; PF01433
• Sequence:
  MDIQLDPARDDLPLMANTSHILVKHYVLDLDVDFESQVIEGTIVLFLEDGNRFKKQNSSI
  EEACQSESNKACKFGMPEPCHIPVTNARTFSSEMEYNDFAICSKGEKDTSDKDGNHDNQE
  HASGISSSKYCCDTGNHGSEDFLLVLDCCDLSVLKVEEVDVAAVPGLEKFTRSPELTVVS
  EEFRNQIVRELVTLPANRWREQLDYYARCSQAPGCGELLFDTDTWSLQIRKTGAQTATDF
  PHAIRIWYKTKPEGRSVTWTSDQSGRPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRA
  AASFVVLMSGENSAKPTQLWEECSSWYYYVTMPMPASTFTIAVGCWTEMKMETWSSNDLA
  TERPFSPSEANFRHVGVCSHMEYPCRFQNASATTQEIIPHRVFAPVCLTGACQETLLRLI
  PPCLSAAHSVLGAHPFSRLDVLIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTRLCHE
  IAHAWFGLAIGARDWTEEWLSEGFATHLEDVFWATAQQLAPYEAREQQELRACLRWRRLQ
  DEMQCSPEEMQVLRPSKDKTGHTSDSGASVIKHGLNPEKIFMQVHYLKGYFLLRFLAKRL
  GDETYFSFLRKFVHTFHGQLILSQDFLQMLLENIPEEKRLELSVENIYQDWLESSGIPKP
  LQRERRAGAECGLARQVRAEVTKWIGVNRRPRKRKRREKEEVFEKLLPDQLVLLLEHLLE
  QKTLSPRTLQSLQRTYHLQDQDAEVRHRWCELIVKHKFTKAYKSVERFLQEDQAMGVYLY
  GELMVSEDARQQQLARRCFERTKEQMDRSSAQVVAEMLF
• Function: Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
• Reactome Pathway: Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[3]
Atrial fibrillation	DIS15W6U	moderate	Genetic Variation	[4]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[4]
Precancerous condition	DISV06FL	Limited	Biomarker	[5]

12 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 Aminopeptidase O (AOPEP).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aminopeptidase O (AOPEP).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Aminopeptidase O (AOPEP).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aminopeptidase O (AOPEP).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Aminopeptidase O (AOPEP).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Aminopeptidase O (AOPEP).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Aminopeptidase O (AOPEP).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Aminopeptidase O (AOPEP).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Aminopeptidase O (AOPEP).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Aminopeptidase O (AOPEP).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Aminopeptidase O (AOPEP).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Aminopeptidase O (AOPEP).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Aminopeptidase O (AOPEP).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Aminopeptidase O (AOPEP).	[17]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [2] Human papillomavirus type 16 E6 suppresses microRNA-23b expression in human cervical cancer cells through DNA methylation of the host gene C9orf3.Oncotarget. 2017 Feb 14;8(7):12158-12173. doi: 10.18632/oncotarget.14555.
• [3] Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.PLoS Genet. 2018 Dec 19;14(12):e1007813. doi: 10.1371/journal.pgen.1007813. eCollection 2018 Dec.
• [4] 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.
• [5] Hepatocellular carcinoma-associated protein markers investigated by MALDI-TOF MS.Mol Med Rep. 2010 Jul-Aug;3(4):589-96. doi: 10.3892/mmr_00000302.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [13] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [14] 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.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.