Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3AA61T)

• DOT Name: Ankyrin repeat and SOCS box protein 9 (ASB9)
• Synonyms: ASB-9
• Gene Name: ASB9
• UniProt ID: ASB9_HUMAN
• PDB ID: 3D9H; 3ZKJ; 3ZNG; 6V9H
• Pfam ID: PF12796 ; PF07525
• Sequence:
  MDGKQGGMDGSKPAGPRDFPGIRLLSNPLMGDAVSDWSPMHEAAIHGHQLSLRNLISQGW
  AVNIITADHVSPLHEACLGGHLSCVKILLKHGAQVNGVTADWHTPLFNACVSGSWDCVNL
  LLQHGASVQPESDLASPIHEAARRGHVECVNSLIAYGGNIDHKISHLGTPLYLACENQQR
  ACVKKLLESGADVNQGKGQDSPLHAVARTASEELACLLMDFGADTQAKNAEGKRPVELVP
  PESPLAQLFLEREGPPSLMQLCRLRIRKCFGIQQHHKITKLVLPEDLKQFLLHL
• Function: Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes at least two forms of creatine kinase, CKB and CKMT1A.
• Tissue Specificity: Predominantly expressed in testis, kidney, and liver.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

16 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 Ankyrin repeat and SOCS box protein 9 (ASB9).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[10]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ankyrin repeat and SOCS box protein 9 (ASB9).	[17]

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 decreases the methylation of Ankyrin repeat and SOCS box protein 9 (ASB9).	[13]

References

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• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] 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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] 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.
• [10] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [11] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.