Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB6N6BR)

• DOT Name: ADP-ribosylation factor-like protein 1 (ARL1)
• Gene Name: ARL1
• UniProt ID: ARL1_HUMAN
• PDB ID: 1UPT; 4DCN; 5EE5; 5J5C
• Pfam ID: PF00025
• Sequence:
  MGGFFSSIFSSLFGTREMRILILGLDGAGKTTILYRLQVGEVVTTIPTIGFNVETVTYKN
  LKFQVWDLGGQTSIRPYWRCYYSNTDAVIYVVDSCDRDRIGISKSELVAMLEEEELRKAI
  LVVFANKQDMEQAMTSSEMANSLGLPALKDRKWQIFKTSATKGTGLDEAMEWLVETLKSR
  Q
• Function: GTP-binding protein that recruits several effectors, such as golgins, arfaptins and Arf-GEFs to the trans-Golgi network, and modulates their functions at the Golgi complex. Plays thereby a role in a wide range of fundamental cellular processes, including cell polarity, innate immunity, or protein secretion mediated by arfaptins, which were shown to play a role in maintaining insulin secretion from pancreatic beta cells.
• Tissue Specificity: Detected in heart, liver, lung and liver (at protein level). Detected in fetal heart, lung, liver and kidney. Detected in adult heart, placenta, lung, liver, skeletal muscle, kidney and pancreas.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[5]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[6]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[10]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of ADP-ribosylation factor-like protein 1 (ARL1).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of ADP-ribosylation factor-like protein 1 (ARL1).	[8]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 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.
• [4] 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.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [7] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [8] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.