Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7REEDA)

• DOT Name: ADP-ribosylation factor-like protein 2-binding protein (ARL2BP)
• Synonyms: ARF-like 2-binding protein; ARL2-binding protein; Binder of ARF2 protein 1
• Gene Name: ARL2BP
• Related Disease:
  Bartonellosis
  Ciliopathy
  Epstein barr virus infection
  Gastroesophageal reflux disease
  Male infertility
  Nasopharyngeal carcinoma
  Retinitis pigmentosa with or without situs inversus
  Carcinoma
  Cardiovascular disease
  Coronary atherosclerosis
  Coronary heart disease
  Niemann-Pick disease type C
  Pancreatic cancer
  Stomach cancer
  Retinitis pigmentosa
  Gastric cancer
  Metastatic malignant neoplasm
• UniProt ID: AR2BP_HUMAN
• PDB ID: 2K9A; 3DOE; 3DOF
• Pfam ID: PF11527
• Sequence:
  MDALEGESFALSFSSASDAEFDAVVGYLEDIIMDDEFQLLQRNFMDKYYLEFEDTEENKL
  IYTPIFNEYISLVEKYIEEQLLQRIPEFNMAAFTTTLQHHKDEVAGDIFDMLLTFTDFLA
  FKEMFLDYRAEKEGRGLDLSSGLVVTSLCKSSSLPASQNNLRH
• Function: Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2.
• Tissue Specificity: Expressed in retina pigment epithelial cells (at protein level). Widely expressed.
• Reactome Pathway: Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane (R-HSA-83936)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bartonellosis	DISMKP1N	Strong	Biomarker	[1]
Ciliopathy	DIS10G4I	Strong	Biomarker	[2]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[3]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[4]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[5]
Retinitis pigmentosa with or without situs inversus	DISQFLN0	Strong	Autosomal recessive	[6]
Carcinoma	DISH9F1N	moderate	Altered Expression	[7]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[8]
Coronary atherosclerosis	DISKNDYU	moderate	Genetic Variation	[8]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[8]
Niemann-Pick disease type C	DIS492ZO	moderate	Altered Expression	[9]
Pancreatic cancer	DISJC981	moderate	Biomarker	[10]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[11]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[6]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[11]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[12]

6 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 ADP-ribosylation factor-like protein 2-binding protein (ARL2BP).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ADP-ribosylation factor-like protein 2-binding protein (ARL2BP).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ADP-ribosylation factor-like protein 2-binding protein (ARL2BP).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ADP-ribosylation factor-like protein 2-binding protein (ARL2BP).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribosylation factor-like protein 2-binding protein (ARL2BP).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ADP-ribosylation factor-like protein 2-binding protein (ARL2BP).	[18]

References

• [1] Detection of Bartonella in cat scratch disease using a single-step PCR assay kit.J Med Microbiol. 2017 Nov;66(11):1596-1601. doi: 10.1099/jmm.0.000626. Epub 2017 Oct 25.
• [2] Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice.PLoS Genet. 2019 Aug 19;15(8):e1008315. doi: 10.1371/journal.pgen.1008315. eCollection 2019 Aug.
• [3] Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells.Virol J. 2013 Oct 26;10:314. doi: 10.1186/1743-422X-10-314.
• [4] Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review.Expert Rev Clin Pharmacol. 2018 Dec;11(12):1195-1208. doi: 10.1080/17512433.2018.1540298. Epub 2018 Dec 6.
• [5] Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-B pathway.Cancer Lett. 2019 Apr 10;447:33-40. doi: 10.1016/j.canlet.2019.01.022. Epub 2019 Jan 23.
• [6] Mutations in ARL2BP, encoding ADP-ribosylation-factor-like 2 binding protein, cause autosomal-recessive retinitis pigmentosa. Am J Hum Genet. 2013 Aug 8;93(2):321-9. doi: 10.1016/j.ajhg.2013.06.003. Epub 2013 Jul 11.
• [7] Dissecting the regulation of EBV's BART miRNAs in carcinomas.Virology. 2017 May;505:148-154. doi: 10.1016/j.virol.2017.02.013. Epub 2017 Mar 1.
• [8] Detection of Left Ventricular Hypertrophy Using Bayesian Additive Regression Trees: The MESA.J Am Heart Assoc. 2019 Mar 5;8(5):e009959. doi: 10.1161/JAHA.118.009959.
• [9] Interplay of Viral Infection, Host Cell Factors and Tumor Microenvironment in the Pathogenesis of Nasopharyngeal Carcinoma.Cancers (Basel). 2018 Apr 4;10(4):106. doi: 10.3390/cancers10040106.
• [10] BART inhibits pancreatic cancer cell invasion by PKC inactivation through binding to ANX7.PLoS One. 2012;7(4):e35674. doi: 10.1371/journal.pone.0035674. Epub 2012 Apr 19.
• [11] Key elements involved in Epstein-Barr virus-associated gastric cancer and their network regulation.Cancer Cell Int. 2018 Sep 21;18:146. doi: 10.1186/s12935-018-0637-5. eCollection 2018.
• [12] Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.Nat Commun. 2015 Jul 2;6:7353. doi: 10.1038/ncomms8353.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [17] 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.
• [18] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.