Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4ACZPJ)

• DOT Name: Pleckstrin homology domain-containing family N member 1 (PLEKHN1)
• Synonyms: PH domain-containing family N member 1; Cardiolipin and phosphatidic acid-binding protein
• Gene Name: PLEKHN1
• UniProt ID: PKHN1_HUMAN
• Sequence:
  MGNSHCVPQAPRRLRASFSRKPSLKGNREDSARMSAGLPGPEAARSGDAAANKLFHYIPG
  TDILDLENQRENLEQPFLSVFKKGRRRVPVRNLGKVVHYAKVQLRFQHSQDVSDCYLELF
  PAHLYFQAHGSEGLTFQGLLPLTELSVCPLEGSREHAFQITGPLPAPLLVLCPSRAELDR
  WLYHLEKQTALLGGPRRCHSAPPQRRLTRLRTASGHEPGGSAVCASRVKLQHLPAQEQWD
  RLLVLYPTSLAIFSEELDGLCFKGELPLRAVHINLEEKEKQIRSFLIEGPLINTIRVVCA
  SYEDYGHWLLCLRAVTHREGAPPLPGAESFPGSQVMGSGRGSLSSGGQTSWDSGCLAPPS
  TRTSHSLPESSVPSTVGCSSQHTPDQANSDRASIGRRRTELRRSGSSRSPGSKARAEGRG
  PVTPLHLDLTQLHRLSLESSPDAPDHTSETSHSPLYADPYTPPATSHRRVTDVRGLEEFL
  SAMQSARGPTPSSPLPSVPVSVPASDPRSCSSGPAGPYLLSKKGALQSRAAQRHRGSAKD
  GGPQPPDAPQLVSSAREGSPEPWLPLTDGRSPRRSRDPGYDHLWDETLSSSHQKCPQLGG
  PEASGGLVQWI
• Function: Controls the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR, in cooperation with the RNA stabilizer ELAVL1. Decreases the stability of the leptin mRNA by antagonizing the function of ELAVL1 by inducing its atypical recruitment from the nucleus to the cytosol. Binds to cardiolipin (CL), phosphatidic acid (PA), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidylserine (PS). Promotes apoptosis by enhancing BAX-BAK hetero-oligomerization via interaction with BID in colon cancer cells.
• Tissue Specificity: Ubiquitous . Epressed in several cancer cell lines of differing origin .

Molecular Interaction Atlas (MIA) of This DOT

1 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 Pleckstrin homology domain-containing family N member 1 (PLEKHN1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pleckstrin homology domain-containing family N member 1 (PLEKHN1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Pleckstrin homology domain-containing family N member 1 (PLEKHN1).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pleckstrin homology domain-containing family N member 1 (PLEKHN1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Pleckstrin homology domain-containing family N member 1 (PLEKHN1).	[5]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.