Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3ECS6P)

• DOT Name: Angiogenin (ANG)
• Synonyms: EC 3.1.27.-; Ribonuclease 5; RNase 5
• Gene Name: ANG
• Related Disease:
  Amyotrophic lateral sclerosis type 9
  Amyotrophic lateral sclerosis
• UniProt ID: ANGI_HUMAN
• PDB ID: 1A4Y ; 1ANG ; 1AWZ ; 1B1E ; 1B1I ; 1B1J ; 1GV7 ; 1H0D ; 1H52 ; 1H53 ; 1HBY ; 1K58 ; 1K59 ; 1K5A ; 1K5B ; 1UN3 ; 1UN4 ; 1UN5 ; 2ANG ; 4AHD ; 4AHE ; 4AHF ; 4AHG ; 4AHH ; 4AHI ; 4AHJ ; 4AHK ; 4AHL ; 4AHM ; 4AHN ; 4AOH ; 4B36 ; 5EOP ; 5EPZ ; 5EQO ; 5M9A ; 5M9C ; 5M9G ; 5M9J ; 5M9M ; 5M9P ; 5M9Q ; 5M9R ; 5M9S ; 5M9T ; 5M9V ; 7NPM ; 7PNJ ; 7PNP ; 7PNR ; 8AF0
• EC Number: 3.1.27.-
• Pfam ID: PF00074
• Sequence:
  MVMGLGVLLLVFVLGLGLTPPTLAQDNSRYTHFLTQHYDAKPQGRDDRYCESIMRRRGLT
  SPCKDINTFIHGNKRSIKAICENKNGNPHRENLRISKSSFQVTTCKLHGGSPWPPCQYRA
  TAGFRNVVVACENGLPVHLDQSIFRRP
• Function: Ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.
• Tissue Specificity: Expressed predominantly in the liver. Also detected in endothelial cells and spinal cord neurons.
• KEGG Pathway: Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis (R-HSA-9708296)
  Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 9	DISPPL4H	Definitive	Autosomal dominant	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Angiogenin (ANG) affects the response to substance of Fluorouracil.	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Angiogenin (ANG).	[3]

29 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 Angiogenin (ANG).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Angiogenin (ANG).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Angiogenin (ANG).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Angiogenin (ANG).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Angiogenin (ANG).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Angiogenin (ANG).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Angiogenin (ANG).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Angiogenin (ANG).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Angiogenin (ANG).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Angiogenin (ANG).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Angiogenin (ANG).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Angiogenin (ANG).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Angiogenin (ANG).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Angiogenin (ANG).	[17]
Valsartan	DMREUQ6	Approved	Valsartan decreases the expression of Angiogenin (ANG).	[18]
Enalapril	DMNFUZR	Approved	Enalapril decreases the expression of Angiogenin (ANG).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Angiogenin (ANG).	[20]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Angiogenin (ANG).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Angiogenin (ANG).	[22]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Angiogenin (ANG).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Angiogenin (ANG).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Angiogenin (ANG).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Angiogenin (ANG).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Angiogenin (ANG).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Angiogenin (ANG).	[27]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Angiogenin (ANG).	[24]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Angiogenin (ANG).	[24]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Angiogenin (ANG).	[28]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion decreases the expression of Angiogenin (ANG).	[24]

References

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• [16] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [17] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [18] Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial. PLoS One. 2012;7(6):e39930. doi: 10.1371/journal.pone.0039930. Epub 2012 Jun 29.
• [19] Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension. Clin Ther. 1987;9(4):390-9.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [22] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [23] 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.
• [24] Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.
• [25] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [26] 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.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [28] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
• [29] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.