Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIP5ZJ7)

• DOT Name: ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2)
• Synonyms: ARF GAP 2; GTPase-activating protein ZNF289; Zinc finger protein 289
• Gene Name: ARFGAP2
• Related Disease:
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Major depressive disorder
  Mood disorder
• UniProt ID: ARFG2_HUMAN
• PDB ID: 2P57
• Pfam ID: PF01412
• Sequence:
  MAAEPNKTEIQTLFKRLRAVPTNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHL
  SFIRSTELDSNWNWFQLRCMQVGGNANATAFFRQHGCTANDANTKYNSRAAQMYREKIRQ
  LGSAALARHGTDLWIDNMSSAVPNHSPEKKDSDFFTEHTQPPAWDAPATEPSGTQQPAPS
  TESSGLAQPEHGPNTDLLGTSPKASLELKSSIIGKKKPAAAKKGLGAKKGLGAQKVSSQS
  FSEIERQAQVAEKLREQQAADAKKQAEESMVASMRLAYQELQIDRKKEEKKLQNLEGKKR
  EQAERLGMGLVSRSSVSHSVLSEMQVIEQETPVSAKSSRSQLDLFDDVGTFASGPPKYKD
  NPFSLGESFGSRWDTDAAWGMDRVEEKEPEVTISSIRPISERATNRREVESRSSGLESSE
  ARQKFAGAKAISSDMFFGREVDAEYEARSRLQQLSGSSAISSSDLFGDMDGAHGAGSVSL
  GNVLPTADIAQFKQGVKSVAGKMAVLANGVMNSLQDRYGSY
• Function: GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  CDC42 GTPase cycle (R-HSA-9013148)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[1]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[2]

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 2 (ARFGAP2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of ADP-ribosylation factor GTPase-activating protein 2 (ARFGAP2).	[8]

References

• [1] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [2] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [3] 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.
• [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] 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.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] 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.
• [9] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.