Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2G3KCG)

• DOT Name: ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3)
• Synonyms: ARF GAP 3
• Gene Name: ARFGAP3
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: ARFG3_HUMAN
• PDB ID: 2CRW
• Pfam ID: PF01412
• Sequence:
  MGDPSKQDILTIFKRLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGSHRSLGVHLS
  FIRSTELDSNWSWFQLRCMQVGGNASASSFFHQHGCSTNDTNAKYNSRAAQLYREKIKSL
  ASQATRKHGTDLWLDSCVVPPLSPPPKEEDFFASHVSPEVSDTAWASAIAEPSSLTSRPV
  ETTLENNEGGQEQGPSVEGLNVPTKATLEVSSIIKKKPNQAKKGLGAKKGSLGAQKLANT
  CFNEIEKQAQAADKMKEQEDLAKVVSKEESIVSSLRLAYKDLEIQMKKDEKMNISGKKNV
  DSDRLGMGFGNCRSVISHSVTSDMQTIEQESPIMAKPRKKYNDDSDDSYFTSSSSYFDEP
  VELRSSSFSSWDDSSDSYWKKETSKDTETVLKTTGYSDRPTARRKPDYEPVENTDEAQKK
  FGNVKAISSDMYFGRQSQADYETRARLERLSASSSISSADLFEEPRKQPAGNYSLSSVLP
  NAPDMAQFKQGVRSVAGKLSVFANGVVTSIQDRYGS
• Function: GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes.
• Tissue Specificity: Widely expressed. Highest expression in endocrine glands (pancreas, pituitary gland, salivary gland, and prostate) and testis with a much higher expression in the testis than in the ovary.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOG GTPase cycle (R-HSA-9013408)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Genetic Variation	[1]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[1]

7 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 GTPase-activating protein 3 (ARFGAP3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[10]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3).	[9]

References

• [1] Lentiviral vector-mediated insertional mutagenesis screen identifies genes that influence androgen independent prostate cancer progression and predict clinical outcome.Mol Carcinog. 2016 Nov;55(11):1761-1771. doi: 10.1002/mc.22425. Epub 2015 Oct 29.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] 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.
• [7] 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.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [9] 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.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.