Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8Y55RY)

• DOT Name: Developmental pluripotency-associated protein 2 (DPPA2)
• Synonyms: Pluripotent embryonic stem cell-related gene 1 protein
• Gene Name: DPPA2
• Related Disease:
  Neoplasm
  Alzheimer disease
  Colorectal carcinoma
  Lung neoplasm
  Embryonal neoplasm
• UniProt ID: DPPA2_HUMAN
• Pfam ID: PF14047 ; PF14049
• Sequence:
  MSDANLDSSKKNFLEGEVDDEESVILTLVPVKDDANMEQMEPSVSSTSDVKLEKPKKYNP
  GHLLQTNEQFTAPQKARCKIPALPLPTILPPINKVCRDTLRDWCQQLGLSTNGKKIEVYL
  RLHRHAYPEQRQDMPEMSQETRLQRCSRKRKAVTKRARLQRSYEMNERAEETNTVEVITS
  APGAMLASWARIAARAVQPKALNSCSIPVSVEAFLMQASGVRWCVVHGRLLSADTKGWVR
  LQFHAGQAWVPTTHRRMISLFLLPACIFPSPGIEDNMLCPDCAKRNKKMMKRLMTVEK
• Function: Binds to target gene promoters, including NKX2-5 and SYCE1, but not GATA4, and may be involved in the maintenance of the active epigenetic status of these genes.
• Tissue Specificity: Expressed in embryonic stem cells. No expression is seen in 5 months embryo, mesenchymal stem cells, embryonic fibrocytes and adult tissues.
• Reactome Pathway: Zygotic genome activation (ZGA) (R-HSA-9819196)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Lung neoplasm	DISVARNB	Strong	Biomarker	[4]
Embryonal neoplasm	DIS5MQSB	moderate	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Developmental pluripotency-associated protein 2 (DPPA2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Developmental pluripotency-associated protein 2 (DPPA2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Developmental pluripotency-associated protein 2 (DPPA2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Developmental pluripotency-associated protein 2 (DPPA2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Developmental pluripotency-associated protein 2 (DPPA2).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Developmental pluripotency-associated protein 2 (DPPA2).	[8]

References

• [1] Zinc ion coordination significantly improved the transfection efficiency of low molecular weight polyethylenimine.Biomater Sci. 2019 Mar 26;7(4):1716-1728. doi: 10.1039/c9bm00039a.
• [2] S100a9 knockdown decreases the memory impairment and the neuropathology in Tg2576 mice, AD animal model.PLoS One. 2010 Jan 21;5(1):e8840. doi: 10.1371/journal.pone.0008840.
• [3] Diagnostic clinical relevance of developmental pluripotency-associated 2 (DPPA2) in colorectal cancer.Int J Surg. 2015 Jan;13:193-197. doi: 10.1016/j.ijsu.2014.11.036. Epub 2014 Dec 12.
• [4] ECSA/DPPA2 is an embryo-cancer antigen that is coexpressed with cancer-testis antigens in non-small cell lung cancer.Clin Cancer Res. 2008 Jun 1;14(11):3291-8. doi: 10.1158/1078-0432.CCR-07-1322.
• [5] Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development.Mol Hum Reprod. 2008 Jun;14(6):347-55. doi: 10.1093/molehr/gan025. Epub 2008 May 8.
• [6] 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.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.