Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT86I3WH)

• DOT Name: Phospholipase D2 (PLD2)
• Synonyms: PLD 2; hPLD2; EC 3.1.4.4; Choline phosphatase 2; PLD1C; Phosphatidylcholine-hydrolyzing phospholipase D2
• Gene Name: PLD2
• UniProt ID: PLD2_HUMAN
• PDB ID: 6OHM; 6OHO; 6OHP; 6OHQ; 6OHS; 7SVP
• EC Number: 3.1.4.4
• Pfam ID: PF00614 ; PF13091 ; PF00787
• Sequence:
  MTATPESLFPTGDELDSSQLQMESDEVDTLKEGEDPADRMHPFLAIYELQSLKVHPLVFA
  PGVPVTAQVVGTERYTSGSKVGTCTLYSVRLTHGDFSWTTKKKYRHFQELHRDLLRHKVL
  MSLLPLARFAVAYSPARDAGNREMPSLPRAGPEGSTRHAASKQKYLENYLNRLLTMSFYR
  NYHAMTEFLEVSQLSFIPDLGRKGLEGMIRKRSGGHRVPGLTCCGRDQVCYRWSKRWLVV
  KDSFLLYMCLETGAISFVQLFDPGFEVQVGKRSTEARHGVRIDTSHRSLILKCSSYRQAR
  WWAQEITELAQGPGRDFLQLHRHDSYAPPRPGTLARWFVNGAGYFAAVADAILRAQEEIF
  ITDWWLSPEVYLKRPAHSDDWRLDIMLKRKAEEGVRVSILLFKEVELALGINSGYSKRAL
  MLLHPNIKVMRHPDQVTLWAHHEKLLVVDQVVAFLGGLDLAYGRWDDLHYRLTDLGDSSE
  SAASQPPTPRPDSPATPDLSHNQFFWLGKDYSNLITKDWVQLDRPFEDFIDRETTPRMPW
  RDVGVVVHGLPARDLARHFIQRWNFTKTTKAKYKTPTYPYLLPKSTSTANQLPFTLPGGQ
  CTTVQVLRSVDRWSAGTLENSILNAYLHTIRESQHFLYIENQFFISCSDGRTVLNKVGDE
  IVDRILKAHKQGWCYRVYVLLPLLPGFEGDISTGGGNSIQAILHFTYRTLCRGEYSILHR
  LKAAMGTAWRDYISICGLRTHGELGGHPVSELIYIHSKVLIADDRTVIIGSANINDRSLL
  GKRDSELAVLIEDTETEPSLMNGAEYQAGRFALSLRKHCFGVILGANTRPDLDLRDPICD
  DFFQLWQDMAESNANIYEQIFRCLPSNATRSLRTLREYVAVEPLATVSPPLARSELTQVQ
  GHLVHFPLKFLEDESLLPPLGSKEGMIPLEVWT
• Function: Function as phospholipase selective for phosphatidylcholine. May have a role in signal-induced cytoskeletal regulation and/or endocytosis.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
  Ras sig.ling pathway (hsa04014)
  cAMP sig.ling pathway (hsa04024)
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Endocytosis (hsa04144)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Glutamatergic sy.pse (hsa04724)
  GnRH sig.ling pathway (hsa04912)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Pancreatic cancer (hsa05212)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Synthesis of PA (R-HSA-1483166)
  Role of phospholipids in phagocytosis (R-HSA-2029485)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  Synthesis of PG (R-HSA-1483148)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phospholipase D2 (PLD2).	[1]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phospholipase D2 (PLD2).	[1]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Phospholipase D2 (PLD2).	[2]
Methadone	DMTW6IU	Approved	Methadone increases the activity of Phospholipase D2 (PLD2).	[3]
Fentanyl	DM8WAHT	Approved	Fentanyl increases the activity of Phospholipase D2 (PLD2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phospholipase D2 (PLD2).	[2]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Phospholipase D2 (PLD2).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phospholipase D2 (PLD2).	[5]

References

• [1] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [2] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [3] opioid receptor agonist-selective regulation of interleukin-4 in T lymphocytes. J Neuroimmunol. 2013 Oct 15;263(1-2):35-42. doi: 10.1016/j.jneuroim.2013.07.012. Epub 2013 Jul 25.
• [4] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [5] 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.