Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAH2GFA)

• DOT Name: ADP-ribosylation factor-like protein 4A (ARL4A)
• Gene Name: ARL4A
• Related Disease:
  Glioma
  Carcinoma
• UniProt ID: ARL4A_HUMAN
• Pfam ID: PF00025
• Sequence:
  MGNGLSDQTSILSNLPSFQSFHIVILGLDCAGKTTVLYRLQFNEFVNTVPTKGFNTEKIK
  VTLGNSKTVTFHFWDVGGQEKLRPLWKSYTRCTDGIVFVVDSVDVERMEEAKTELHKITR
  ISENQGVPVLIVANKQDLRNSLSLSEIEKLLAMGELSSSTPWHLQPTCAIIGDGLKEGLE
  KLHDMIIKRRKMLRQQKKKR
• Function: Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Recruits CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane in GDP-bound form.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Carcinoma	DISH9F1N	Limited	Biomarker	[2]

11 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 ADP-ribosylation factor-like protein 4A (ARL4A).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide affects the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of ADP-ribosylation factor-like protein 4A (ARL4A).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ADP-ribosylation factor-like protein 4A (ARL4A).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ADP-ribosylation factor-like protein 4A (ARL4A).	[13]

References

• [1] Increased expression of the glioma-associated antigen ARF4L after loss of the tumor suppressor PTEN. Laboratory investigation.J Neurosurg. 2008 Feb;108(2):299-303. doi: 10.3171/JNS/2008/108/2/0299.
• [2] High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.J Neuropathol Exp Neurol. 2015 Feb;74(2):110-20. doi: 10.1097/NEN.0000000000000154.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.