Details of Drug Off-Target (DOT)

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

• DOT Name: Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1)
• Synonyms: Elongation factor 1A-binding protein
• Gene Name: ABTB1
• Related Disease:
  Advanced cancer
  Uveal Melanoma
• UniProt ID: ABTB1_HUMAN
• Pfam ID: PF12796 ; PF00651
• Sequence:
  MDTSDLFASCRKGDVGRVRYLLEQRDVEVNVRDKWDSTPLYYACLCGHEELVLYLLANGA
  RCEANTFDGERCLYGALSDPIRRALRDYKQVTASCRRRDYYDDFLQRLLEQGIHSDVVFV
  VHGKPFRVHRCVLGARSAYFANMLDTKWKGKSVVVLRHPLINPVAFGALLQYLYTGRLDI
  GVEHVSDCERLAKQCQLWDLLSDLEAKCEKVSEFVASKPGTCVKVLTIEPPPADPRLRED
  MALLADCALPPELRGDLWELPFPCPDGFNSCPDICFRVAGCSFLCHKAFFCGRSDYFRAL
  LDDHFRESEEPATSGGPPAVTLHGISPDVFTHVLYYMYSDHTELSPEAAYDVLSVADMYL
  LPGLKRLCGRSLAQMLDEDTVVGVWRVAKLFRLARLEDQCTEYMAKVIEKLVEREDFVEA
  VKEEAAAVAARQETDSIPLVDDIRFHVASTVQTYSAIEEAQQRLRALEDLLVSIGLDC
• Function: May act as a mediator of the PTEN growth-suppressive signaling pathway. May play a role in developmental processes.
• Tissue Specificity: Ubiquitously expressed in all fetal tissues examined including heart, brain, liver, and kidney. Also expressed at lower levels in both adult heart and hypertrophic heart.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[2]

10 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 BTB/POZ domain-containing protein 1 (ABTB1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1).	[10]

References

• [1] Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.Oncogene. 2001 Jul 27;20(33):4457-65. doi: 10.1038/sj.onc.1204608.
• [2] Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.Exp Eye Res. 2018 Jan;166:13-20. doi: 10.1016/j.exer.2017.10.007. Epub 2017 Oct 12.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.