Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE4MKOZ)

• DOT Name: ADP-ribosylation factor-like protein 14 (ARL14)
• Synonyms: ADP-ribosylation factor 7
• Gene Name: ARL14
• Related Disease: Lung adenocarcinoma
• UniProt ID: ARL14_HUMAN
• Pfam ID: PF00025
• Sequence:
  MGSLGSKNPQTKQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELERNLSL
  TVWDVGGQEKMRTVWGCYCENTDGLVYVVDSTDKQRLEESQRQFEHILKNEHIKNVPVVL
  LANKQDMPGALTAEDITRMFKVKKLCSDRNWYVQPCCALTGEGLAQGFRKLTGFVKSHMK
  SRGDTLAFFKQN
• Function: GTPase that recruits MYO1E to MHC class II-containing vesicles via the effector protein ARL14EP and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells.
• Tissue Specificity: Expressed in immature dendritic cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]

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 14 (ARL14).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ADP-ribosylation factor-like protein 14 (ARL14).	[9]

9 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 14 (ARL14).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of ADP-ribosylation factor-like protein 14 (ARL14).	[12]

References

• [1] Silencing of ARL14 Gene Induces Lung Adenocarcinoma Cells to a Dormant State.Front Cell Dev Biol. 2019 Oct 15;7:238. doi: 10.3389/fcell.2019.00238. eCollection 2019.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.