Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DIWA0)

• DOT Name: Aminopeptidase B (RNPEP)
• Synonyms: AP-B; EC 3.4.11.6; Arginine aminopeptidase; Arginyl aminopeptidase
• Gene Name: RNPEP
• UniProt ID: AMPB_HUMAN
• EC Number: 3.4.11.6
• Pfam ID: PF09127 ; PF01433 ; PF17900
• Sequence:
  MASGEHSPGSGAARRPLHSAQAVDVASASNFRAFELLHLHLDLRAEFGPPGPGAGSRGLS
  GTAVLDLRCLEPEGAAELRLDSHPCLEVTAAALRRERPGSEEPPAEPVSFYTQPFSHYGQ
  ALCVSFPQPCRAAERLQVLLTYRVGEGPGVCWLAPEQTAGKKKPFVYTQGQAVLNRAFFP
  CFDTPAVKYKYSALIEVPDGFTAVMSASTWEKRGPNKFFFQMCQPIPSYLIALAIGDLVS
  AEVGPRSRVWAEPCLIDAAKEEYNGVIEEFLATGEKLFGPYVWGRYDLLFMPPSFPFGGM
  ENPCLTFVTPCLLAGDRSLADVIIHEISHSWFGNLVTNANWGEFWLNEGFTMYAQRRIST
  ILFGAAYTCLEAATGRALLRQHMDITGEENPLNKLRVKIEPGVDPDDTYNETPYEKGFCF
  VSYLAHLVGDQDQFDSFLKAYVHEFKFRSILADDFLDFYLEYFPELKKKRVDIIPGFEFD
  RWLNTPGWPPYLPDLSPGDSLMKPAEELAQLWAAEELDMKAIEAVAISPWKTYQLVYFLD
  KILQKSPLPPGNVKKLGDTYPSISNARNAELRLRWGQIVLKNDHQEDFWKVKEFLHNQGK
  QKYTLPLYHAMMGGSEVAQTLAKETFASTASQLHSNVVNYVQQIVAPKGS
• Function: Exopeptidase which selectively removes arginine and/or lysine residues from the N-terminus of several peptide substrates including Arg(0)-Leu-enkephalin, Arg(0)-Met-enkephalin and Arg(-1)-Lys(0)-somatostatin-14. Can hydrolyze leukotriene A4 (LTA-4) into leukotriene B4 (LTB-4).

Molecular Interaction Atlas (MIA) of This DOT

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 Aminopeptidase B (RNPEP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aminopeptidase B (RNPEP).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Aminopeptidase B (RNPEP).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Aminopeptidase B (RNPEP).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Aminopeptidase B (RNPEP).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aminopeptidase B (RNPEP).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Aminopeptidase B (RNPEP).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Aminopeptidase B (RNPEP).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Aminopeptidase B (RNPEP).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Aminopeptidase B (RNPEP).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Aminopeptidase B (RNPEP).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Aminopeptidase B (RNPEP).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Aminopeptidase B (RNPEP).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Aminopeptidase B (RNPEP).	[13]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] 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.
• [8] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [9] 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.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] 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.
• [12] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [13] 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.
• [14] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.