Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0NZGEI)

• DOT Name: Ankyrin repeat and SOCS box protein 1 (ASB1)
• Synonyms: ASB-1
• Gene Name: ASB1
• Related Disease:
  Anxiety
  Anxiety disorder
• UniProt ID: ASB1_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF07525
• Sequence:
  MAEGGSPDGRAGPGSAGRNLKEWLREQFCDHPLEHCEDTRLHDAAYVGDLQTLRSLLQEE
  SYRSRINEKSVWCCGWLPCTPLRIAATAGHGSCVDFLIRKGAEVDLVDVKGQTALYVAVV
  NGHLESTQILLEAGADPNGSRHHRSTPVYHASRVGRADILKALIRYGADVDVNHHLTPDV
  QPRFSRRLTSLVVCPLYISAAYHNLQCFRLLLLAGANPDFNCNGPVNTQGFYRGSPGCVM
  DAVLRHGCEAAFVSLLVEFGANLNLVKWESLGPESRGRRKVDPEALQVFKEARSVPRTLL
  CLCRVAVRRALGKHRLHLIPSLPLPDPIKKFLLHE
• Function: Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Mediates Notch-induced ubiquitination and degradation of TCF3/E2A and JAK2. May play a role in testis development.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Disputed	Genetic Variation	[1]
Anxiety disorder	DISBI2BT	Disputed	Genetic Variation	[1]

11 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 Ankyrin repeat and SOCS box protein 1 (ASB1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[6]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Ankyrin repeat and SOCS box protein 1 (ASB1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[9]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Ankyrin repeat and SOCS box protein 1 (ASB1).	[10]

References

• [1] Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.Neuropsychopharmacology. 2018 Jan;43(2):342-353. doi: 10.1038/npp.2017.102. Epub 2017 May 25.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [5] 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.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [8] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [9] 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.
• [10] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.