Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYNZPC4)

• DOT Name: Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2)
• Synonyms: Centaurin-beta-2; Cnt-b2
• Gene Name: ACAP2
• Related Disease:
  Colon cancer
  Colon carcinoma
  Advanced cancer
  Esophageal cancer
  Lymphoma
• UniProt ID: ACAP2_HUMAN
• PDB ID: 6IF3
• Pfam ID: PF12796 ; PF01412 ; PF16746 ; PF00169
• Sequence:
  MKMTVDFEECLKDSPRFRAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFM
  NGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTILFDQTQRSIKAQLQNFVKEDLRKF
  KDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEATNILTATRKCFRHIALDYVLQINVL
  QSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKDLGAQLDRLVVDAAKEKREMEQ
  KHSTIQQKDFSSDDSKLEYNVDAANGIVMEGYLFKRASNAFKTWNRRWFSIQNNQLVYQK
  KFKDNPTVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCMLQADSEKLRQAWIKAVQTSI
  ATAYREKGDESEKLDKKSSPSTGSLDSGNESKEKLLKGESALQRVQCIPGNASCCDCGLA
  DPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE
  ANVEKMGIKKPQPGQRQEKEAYIRAKYVERKFVDKYSISLSPPEQQKKFVSKSSEEKRLS
  ISKFGPGDQVRASAQSSVRSNDSGIQQSSDDGRESLPSTVSANSLYEPEGERQDSSMFLD
  SKHLNPGLQLYRASYEKNLPKMAEALAHGADVNWANSEENKATPLIQAVLGGSLVTCEFL
  LQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANA
  DIVTLLRLARMNEEMRESEGLYGQPGDETYQDIFRDFSQMASNNPEKLNRFQQDSQKF
• Function: GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).
• Tissue Specificity: Widely expressed. Highest level in lung.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Esophageal cancer	DISGB2VN	Limited	Altered Expression	[2]
Lymphoma	DISN6V4S	Limited	Altered Expression	[2]

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 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[3]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[17]

13 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 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[9]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[12]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (ACAP2).	[16]

References

• [1] The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells.Cell Physiol Biochem. 2018;49(4):1539-1550. doi: 10.1159/000493457. Epub 2018 Sep 13.
• [2] Human ACAP2 is a homolog of C. elegans CNT-1 that promotes apoptosis in cancer cells.Cell Cycle. 2015;14(12):1771-8. doi: 10.1080/15384101.2015.1026518.
• [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] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] 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.