Details of Drug Off-Target (DOT)

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

• DOT Name: Developmental pluripotency-associated protein 4 (DPPA4)
• Gene Name: DPPA4
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Head-neck squamous cell carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Seminoma
• UniProt ID: DPPA4_HUMAN
• Pfam ID: PF14047 ; PF14049
• Sequence:
  MLRGSASSTSMEKAKGKEWTSTEKSREEDQQASNQPNSIALPGTSAKRTKEKMSIKGSKV
  LCPKKKAEHTDNPRPQKKIPIPPLPSKLPPVNLIHRDILRAWCQQLKLSSKGQKLDAYKR
  LCAFAYPNQKDFPSTAKEAKIRKSLQKKLKVEKGETSLQSSETHPPEVALPPVGEPPALE
  NSTALLEGVNTVVVTTSAPEALLASWARISARARTPEAVESPQEASGVRWCVVHGKSLPA
  DTDGWVHLQFHAGQAWVPEKQEGRVSALFLLPASNFPPPHLEDNMLCPKCVHRNKVLIKS
  LQWE
• Function: May be involved in the maintenance of active epigenetic status of target genes. May inhibit differentiation of embryonic cells into a primitive ectoderm lineage.
• Reactome Pathway:
  Zygotic genome activation (ZGA) (R-HSA-9819196)
  POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (R-HSA-2892247)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[5]

5 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 Developmental pluripotency-associated protein 4 (DPPA4).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Developmental pluripotency-associated protein 4 (DPPA4).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Developmental pluripotency-associated protein 4 (DPPA4).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Developmental pluripotency-associated protein 4 (DPPA4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Developmental pluripotency-associated protein 4 (DPPA4).	[11]

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 affects the methylation of Developmental pluripotency-associated protein 4 (DPPA4).	[9]

References

• [1] Genomic functions of developmental pluripotency associated factor 4 (Dppa4) in pluripotent stem cells and cancer.Stem Cell Res. 2018 Aug;31:83-94. doi: 10.1016/j.scr.2018.07.009. Epub 2018 Jul 19.
• [2] Developmental pluripotency-associated 4: a novel predictor for prognosis and a potential therapeutic target for colon cancer.J Exp Clin Cancer Res. 2015 Jun 11;34(1):60. doi: 10.1186/s13046-015-0176-z.
• [3] Copy number increase of oncoprotein CIP2A is associated with poor patient survival in human head and neck squamous cell carcinoma.J Oral Pathol Med. 2016 May;45(5):329-37. doi: 10.1111/jop.12372. Epub 2015 Oct 5.
• [4] High developmental pluripotencyassociated 4 expression promotes cell proliferation and glycolysis, and predicts poor prognosis in nonsmallcell lung cancer.Mol Med Rep. 2019 Jul;20(1):445-454. doi: 10.3892/mmr.2019.10272. Epub 2019 May 22.
• [5] Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures.Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17763-8. doi: 10.1073/pnas.0509082102. Epub 2005 Nov 23.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.