Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT00YSWZ)

• DOT Name: ADP-ribosylation factor-like protein 15 (ARL15)
• Synonyms: ADP-ribosylation factor-related protein 2; ARF-related protein 2
• Gene Name: ARL15
• Related Disease:
  Alcohol dependence
  Cardiovascular disease
  Coronary atherosclerosis
  Coronary heart disease
  Lipodystrophy
  Non-insulin dependent diabetes
  Alcohol-induced disorders
  Alcohol-related disorders
  Obesity
  Rheumatoid arthritis
  Neoplasm
  Type-1/2 diabetes
• UniProt ID: ARL15_HUMAN
• PDB ID: 8F6D
• Pfam ID: PF00025
• Sequence:
  MSDLRITEAFLYMDYLCFRALCCKGPPPARPEYDLVCIGLTGSGKTSLLSKLCSESPDNV
  VSTTGFSIKAVPFQNAILNVKELGGADNIRKYWSRYYQGSQGVIFVLDSASSEDDLEAAR
  NELHSALQHPQLCTLPFLILANHQDKPAARSVQEIKKYFELEPLARGKRWILQPCSLDDM
  DALKDSFSQLINLLEEKDHEAVRM

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[3]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[4]
Lipodystrophy	DIS3SGVD	Strong	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[1]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[1]
Obesity	DIS47Y1K	moderate	Biomarker	[6]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[7]
Neoplasm	DISZKGEW	Disputed	Biomarker	[8]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[9]

2 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 ADP-ribosylation factor-like protein 15 (ARL15).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ADP-ribosylation factor-like protein 15 (ARL15).	[16]

7 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 ADP-ribosylation factor-like protein 15 (ARL15).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ADP-ribosylation factor-like protein 15 (ARL15).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor-like protein 15 (ARL15).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of ADP-ribosylation factor-like protein 15 (ARL15).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ADP-ribosylation factor-like protein 15 (ARL15).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ADP-ribosylation factor-like protein 15 (ARL15).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ADP-ribosylation factor-like protein 15 (ARL15).	[17]

References

• [1] Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families.Drug Alcohol Depend. 2014 Sep 1;142:56-62. doi: 10.1016/j.drugalcdep.2014.05.023. Epub 2014 Jun 11.
• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] ARL15 overexpression attenuates high glucose-induced impairment of insulin signaling and oxidative stress in human umbilical vein endothelial cells.Life Sci. 2019 Mar 1;220:127-135. doi: 10.1016/j.lfs.2019.01.030. Epub 2019 Jan 22.
• [4] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [5] The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion.Sci Rep. 2017 Dec 14;7(1):17593. doi: 10.1038/s41598-017-17746-8.
• [6] A Proteomics-Based Approach Reveals Differential Regulation of Urine Proteins between Metabolically Healthy and Unhealthy Obese Patients.Int J Mol Sci. 2019 Oct 3;20(19):4905. doi: 10.3390/ijms20194905.
• [7] Functional characterisation of ADP ribosylation factor-like protein 15 in rheumatoid arthritis synovial fibroblasts.Clin Exp Rheumatol. 2018 Jul-Aug;36(4):581-588. Epub 2018 Feb 14.
• [8] Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks.Cell. 2008 May 16;133(4):727-41. doi: 10.1016/j.cell.2008.03.021.
• [9] ADP-ribosylation factor-like GTPase 15 enhances insulin-induced AKT phosphorylation in the IR/IRS1/AKT pathway by interacting with ASAP2 and regulating PDPK1 activity.Biochem Biophys Res Commun. 2017 May 13;486(4):865-871. doi: 10.1016/j.bbrc.2017.03.079. Epub 2017 Mar 18.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] 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.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] 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.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.