Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP051G2)

• DOT Name: PiggyBac transposable element-derived protein 5 (PGBD5)
• Synonyms: EC 3.1.-.-; PiggyBac domain-related protein 5; PiggyBac transposase 5
• Gene Name: PGBD5
• Related Disease:
  Malignant rhabdoid tumour
  Leukemia
• UniProt ID: PGBD5_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF13843
• Sequence:
  MAEGGGGARRRAPALLEAARARYESLHISDDVFGESGPDSGGNPFYSTSAASRSSSAASS
  DDEREPPGPPGAAPPPPRAPDAQEPEEDEAGAGWSAALRDRPPPRFEDTGGPTRKMPPSA
  SAVDFFQLFVPDNVLKNMVVQTNMYAKKFQERFGSDGAWVEVTLTEMKAFLGYMISTSIS
  HCESVLSIWSGGFYSNRSLALVMSQARFEKILKYFHVVAFRSSQTTHGLYKVQPFLDSLQ
  NSFDSAFRPSQTQVLHEPLIDEDPVFIATCTERELRKRKKRKFSLWVRQCSSTGFIIQIY
  VHLKEGGGPDGLDALKNKPQLHSMVARSLCRNAAGKNYIIFTGPSITSLTLFEEFEKQGI
  YCCGLLRARKSDCTGLPLSMLTNPATPPARGQYQIKMKGNMSLICWYNKGHFRFLTNAYS
  PVQQGVIIKRKSGEIPCPLAVEAFAAHLSYICRYDDKYSKYFISHKPNKTWQQVFWFAIS
  IAINNAYILYKMSDAYHVKRYSRAQFGERLVRELLGLEDASPTH
• Function: Transposase that mediates sequence-specific genomic rearrangements. Can induce genomic rearrangements that inactivate the HPRT1 gene.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant rhabdoid tumour	DIS46HZU	Strong	Biomarker	[1]
Leukemia	DISNAKFL	moderate	Genetic Variation	[2]

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 PiggyBac transposable element-derived protein 5 (PGBD5).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PiggyBac transposable element-derived protein 5 (PGBD5).	[10]

8 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 PiggyBac transposable element-derived protein 5 (PGBD5).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of PiggyBac transposable element-derived protein 5 (PGBD5).	[12]

References

• [1] PGBD5 promotes site-specific oncogenic mutations in human tumors.Nat Genet. 2017 Jul;49(7):1005-1014. doi: 10.1038/ng.3866. Epub 2017 May 15.
• [2] Emerging functions of DNA transposases and oncogenic mutators in childhood cancer development.JCI Insight. 2018 Oct 18;3(20):e123172. doi: 10.1172/jci.insight.123172.
• [3] 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.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] 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.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.