Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS7N4Q9)

• DOT Name: Developmental pluripotency-associated protein 3 (DPPA3)
• Synonyms: Stella-related protein
• Gene Name: DPPA3
• Related Disease:
  Embryonal neoplasm
  Erythema multiforme
  Germ cell tumor
  Non-insulin dependent diabetes
  Neoplasm
• UniProt ID: DPPA3_HUMAN
• Pfam ID: PF15549
• Sequence:
  MDPSQFNPTYIPGSPQMLTEENSRDDSGASQISSETLIKNLSNLTINASSESVSPLSEAL
  LRRESVGAAVLREIEDEWLYSRRGVRTLLSVQREKMARLRYMLLGGVRTHERRPTNKEPK
  GVKKESRPFKCPCSFCVSNGWDPSENARIGNQDTKPLQP
• Function: Primordial germ cell (PGCs)-specific protein involved in epigenetic chromatin reprogramming in the zygote following fertilization. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in protection of DNA methylation in the maternal pronucleus by preventing conversion of 5mC to 5hmC: specifically recognizes and binds histone H3 dimethylated at 'Lys-9' (H3K9me2) on maternal genome, and protects maternal genome from TET3-mediated conversion to 5hmC and subsequent DNA demethylation. Does not bind paternal chromatin, which is mainly packed into protamine and does not contain much H3K9me2 mark. Also protects imprinted loci that are marked with H3K9me2 in mature sperm from DNA demethylation in early embryogenesis. May be important for the totipotent/pluripotent states continuing through preimplantation development. Also involved in chromatin condensation in oocytogenesis.
• Tissue Specificity: Low expression in testis, ovary and thymus. Expressed in embryonic stem and carcinoma cells. Highly expressed in testicular germ cell tumors.
• Reactome Pathway: Chromatin modifications during the maternal to zygotic transition (MZT) (R-HSA-9821002)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Embryonal neoplasm	DIS5MQSB	Strong	Biomarker	[1]
Erythema multiforme	DISKCLM1	Strong	Genetic Variation	[2]
Germ cell tumor	DIS62070	Strong	Posttranslational Modification	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]

2 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 3 (DPPA3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Developmental pluripotency-associated protein 3 (DPPA3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Developmental pluripotency-associated protein 3 (DPPA3).	[1]

References

• [1] Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
• [2] Bare Metal Versus Paclitaxel-Eluting Stents for Long Femoropopliteal Lesions: Prospective Cohorts Comparison Using a Propensity Score-Matched Analysis.Ann Vasc Surg. 2017 Aug;43:166-175. doi: 10.1016/j.avsg.2016.10.058. Epub 2017 Mar 11.
• [3] Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors.Genome Res. 2016 Nov;26(11):1490-1504. doi: 10.1101/gr.201293.115. Epub 2016 Oct 20.
• [4] Safety and Effectiveness of Ipragliflozin for Type 2 Diabetes in Japan: 12-Month Interim Results of the STELLA-LONG TERM Post-Marketing Surveillance Study.Adv Ther. 2019 Apr;36(4):923-949. doi: 10.1007/s12325-019-0895-1. Epub 2019 Feb 14.
• [5] Dppa3 is a marker of pluripotency and has a human homologue that is expressed in germ cell tumours.Cytogenet Genome Res. 2003;101(3-4):261-5. doi: 10.1159/000074346.
• [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] Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
• [8] 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.