Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZTE1PG)

• DOT Name: Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1)
• Synonyms: hDAPP1; B lymphocyte adapter protein Bam32; B-cell adapter molecule of 32 kDa
• Gene Name: DAPP1
• Related Disease: Osteoarthritis
• UniProt ID: DAPP1_HUMAN
• PDB ID: 1FAO; 1FB8
• Pfam ID: PF00169 ; PF00017
• Sequence:
  MGRAELLEGKMSTQDPSDLWSRSDGEAELLQDLGWYHGNLTRHAAEALLLSNGCDGSYLL
  RDSNETTGLYSLSVRAKDSVKHFHVEYTGYSFKFGFNEFSSLKDFVKHFANQPLIGSETG
  TLMVLKHPYPRKVEEPSIYESVRVHTAMQTGRTEDDLVPTAPSLGTKEGYLTKQGGLVKT
  WKTRWFTLHRNELKYFKDQMSPEPIRILDLTECSAVQFDYSQERVNCFCLVFPFRTFYLC
  AKTGVEADEWIKILRWKLSQIRKQLNQGEGTIRSRSFIFK
• Function: May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.
• Tissue Specificity: Highly expressed in placenta and lung, followed by brain, heart, kidney, liver, pancreas and skeletal muscle. Expressed by B-lymphocytes, but not T-lymphocytes or nonhematopoietic cells.
• KEGG Pathway: B cell receptor sig.ling pathway (hsa04662)
• Reactome Pathway: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteoarthritis	DIS05URM	Limited	Biomarker	[1]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[12]

1 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 Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (DAPP1).	[10]

References

• [1] Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
• [2] 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.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] 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.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] 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.
• [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] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [12] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.