Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSJX9UU)

• DOT Name: PiggyBac transposable element-derived protein 1 (PGBD1)
• Synonyms: Cerebral protein 4
• Gene Name: PGBD1
• Related Disease:
  Psychotic disorder
  Rheumatoid arthritis
  Lung cancer
  Lung squamous cell carcinoma
  Systemic lupus erythematosus
• UniProt ID: PGBD1_HUMAN
• Pfam ID: PF13843 ; PF02023
• Sequence:
  MYEALPGPAPENEDGLVKVKEEDPTWEQVCNSQEGSSHTQEICRLRFRHFCYQEAHGPQE
  ALAQLRELCHQWLRPEMHTKEQIMELLVLEQFLTILPKELQPCVKTYPLESGEEAVTVLE
  NLETGSGDTGQQASVYIQGQDMHPMVAEYQGVSLECQSLQLLPGITTLKCEPPQRPQGNP
  QEVSGPVPHGSAHLQEKNPRDKAVVPVFNPVRSQTLVKTEEETAQAVAAEKWSHLSLTRR
  NLCGNSAQETVMSLSPMTEEIVTKDRLFKAKQETSEEMEQSGEASGKPNRECAPQIPCST
  PIATERTVAHLNTLKDRHPGDLWARMHISSLEYAAGDITRKGRKKDKARVSELLQGLSFS
  GDSDVEKDNEPEIQPAQKKLKVSCFPEKSWTKRDIKPNFPSWSALDSGLLNLKSEKLNPV
  ELFELFFDDETFNLIVNETNNYASQKNVSLEVTVQEMRCVFGVLLLSGFMRHPRREMYWE
  VSDTDQNLVRDAIRRDRFELIFSNLHFADNGHLDQKDKFTKLRPLIKQMNKNFLLYAPLE
  EYYCFDKSMCECFDSDQFLNGKPIRIGYKIWCGTTTQGYLVWFEPYQEESTMKVDEDPDL
  GLGGNLVMNFADVLLERGQYPYHLCFDSFFTSVKLLSALKKKGVRATGTIRENRTEKCPL
  MNVEHMKKMKRGYFDFRIEENNEIILCRWYGDGIISLCSNAVGIEPVNEVSCCDADNEEI
  PQISQPSIVKVYDECKEGVAKMDQIISKYRVRIRSKKWYSILVSYMIDVAMNNAWQLHRA
  CNPGASLDPLDFRRFVAHFYLEHNAHLSD

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psychotic disorder	DIS4UQOT	Strong	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[3]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[4]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of PiggyBac transposable element-derived protein 1 (PGBD1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of PiggyBac transposable element-derived protein 1 (PGBD1).	[15]

References

• [1] Common variant at 16p11.2 conferring risk of psychosis.Mol Psychiatry. 2014 Jan;19(1):108-14. doi: 10.1038/mp.2012.157. Epub 2012 Nov 20.
• [2] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [3] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [4] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [5] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.