Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT95HCMO)

• DOT Name: PiggyBac transposable element-derived protein 4 (PGBD4)
• Gene Name: PGBD4
• Related Disease: Major depressive disorder
• UniProt ID: PGBD4_HUMAN
• Pfam ID: PF13843 ; PF13842
• Sequence:
  MSNPRKRSIPMRDSNTGLEQLLAEDSFDESDFSEIDDSDNFSDSALEADKIRPLSHLESD
  GKSSTSSDSGRSMKWSARAMIPRQRYDFTGTPGRKVDVSDITDPLQYFELFFTEELVSKI
  TRETNAQAALLASKPPGPKGFSRMDKWKDTDNDELKVFFAVMLLQGIVQKPELEMFWSTR
  PLLDTPYLRQIMTGERFLLLFRCLHFVNNSSISAGQSKAQISLQKIKPVFDFLVNKFSTV
  YTPNRNIAVDESLMLFKGPLAMKQYLPTKRVRFGLKLYVLCESQSGYVWNALVHTGPGMN
  LKDSADGLKSSRIVLTLVNDLLGQGYCVFLDNFNISPMLFRELHQNRTDAVGTARLNRKQ
  IPNDLKKRIAKGTTVARFCGELMALKWCDGKEVTMLSTFHNDTVIEVNNRNGKKTKRPRV
  IVDYNENMGAVDSADQMLTSYPSERKRHKVWYKKFFHHLLHITVLNSYILFKKDNPEHTM
  SHINFRLALIERMLEKHHKPGQQHLRGRPCSDDVTPLRLSGRHFPKSIPATSGKQNPTGR
  CKICCSQYDKDGKKIRKETRYFCAECDVPLCVVPCFEIYHTKKNY

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of PiggyBac transposable element-derived protein 4 (PGBD4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PiggyBac transposable element-derived protein 4 (PGBD4).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PiggyBac transposable element-derived protein 4 (PGBD4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PiggyBac transposable element-derived protein 4 (PGBD4).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PiggyBac transposable element-derived protein 4 (PGBD4).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PiggyBac transposable element-derived protein 4 (PGBD4).	[7]

References

• [1] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.