Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGQ8UH7)

• DOT Name: Arf-GAP with dual PH domain-containing protein 2 (ADAP2)
• Synonyms: Centaurin-alpha-2; Cnt-a2
• Gene Name: ADAP2
• Related Disease:
  Advanced cancer
  Malignant peripheral nerve sheath tumor
  Neurofibroma
  Neurofibromatosis type 1
• UniProt ID: ADAP2_HUMAN
• Pfam ID: PF01412 ; PF00169
• Sequence:
  MGDRERNKKRLLELLRAPDTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISR
  VKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKYERR
  EFMADGETISLPGNREGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVISI
  KDLNATFQTEKIGHPHGLQITYRRDGHTRNLFVYHESGKEIVDWFNALRAARLQYLKMAF
  PELPESELVPFLTRNYLKQGFMEKTGPKQKEPFKKRWFALDCHERRLLYYKNPLDAFEQG
  QVFLGNKEQGYEAYEDLPKGIRGNRWKAGLTIVTPERRFVLTCPSEKEQQEWLESLRGVL
  SSPLTPLNRLTASTESGRSSR
• Function: GTPase-activating protein for the ADP ribosylation factor family (Potential). Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). Possesses a stoichiometry of two binding sites for InsP4 with identical affinity.
• Tissue Specificity: Highly expressed in placenta, spleen, kidney, skeletal muscle and adrenal gland. Weakly expressed in thyroid, liver, heart, lung, small intestine, peripheral blood leukocytes. Not detected in spinal cord, brain, stomach, trachea, colon, lymph node and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[1]
Neurofibroma	DISIJJMH	Strong	Biomarker	[2]
Neurofibromatosis type 1	DIS53JH9	moderate	Genetic Variation	[3]

12 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 Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[14]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of Arf-GAP with dual PH domain-containing protein 2 (ADAP2).	[15]

References

• [1] Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients.Mol Med. 2011 Jan-Feb;17(1-2):79-87. doi: 10.2119/molmed.2010.00079. Epub 2010 Sep 10.
• [2] Expression analysis of genes lying in the NF1 microdeletion interval points to four candidate modifiers for neurofibroma formation.Neurogenetics. 2009 Feb;10(1):79-85. doi: 10.1007/s10048-008-0154-0. Epub 2008 Oct 11.
• [3] Identification of gene structure and subcellular localization of human centaurin alpha 2, and p42IP4, a family of two highly homologous, Ins 1,3,4,5-P4-/PtdIns 3,4,5-P3-binding, adapter proteins.J Neurochem. 2004 Jan;88(2):326-36. doi: 10.1046/j.1471-4159.2003.02143.x.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood. Toxicol Appl Pharmacol. 2017 Apr 15;321:57-66. doi: 10.1016/j.taap.2017.02.019. Epub 2017 Feb 24.
• [10] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [11] 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.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [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] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.