Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUI456H)

• DOT Name: Prostaglandin F2-alpha receptor (PTGFR)
• Synonyms: PGF receptor; PGF2-alpha receptor; Prostanoid FP receptor
• Gene Name: PTGFR
• UniProt ID: PF2R_HUMAN
• PDB ID: 8IUK; 8IUL; 8IUM
• Pfam ID: PF00001
• Sequence:
  MSMNNSKQLVSPAAALLSNTTCQTENRLSVFFSVIFMTVGILSNSLAIAILMKAYQRFRQ
  KSKASFLLLASGLVITDFFGHLINGAIAVFVYASDKEWIRFDQSNVLCSIFGICMVFSGL
  CPLLLGSVMAIERCIGVTKPIFHSTKITSKHVKMMLSGVCLFAVFIALLPILGHRDYKIQ
  ASRTWCFYNTEDIKDWEDRFYLLLFSFLGLLALGVSLLCNAITGITLLRVKFKSQQHRQG
  RSHHLEMVIQLLAIMCVSCICWSPFLVTMANIGINGNHSLETCETTLFALRMATWNQILD
  PWVYILLRKAVLKNLYKLASQCCGVHVISLHIWELSSIKNSLKVAAISESPVAEKSAST
• Function: Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum. Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and isoform 5 are proposed to be a receptor for prostamides including the synthetic analog bimatoprost.
• Tissue Specificity: Eye.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Phospholipase D sig.ling pathway (hsa04072)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Prostanoid ligand receptors (R-HSA-391908)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[4]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Prostaglandin F2-alpha receptor (PTGFR).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prostaglandin F2-alpha receptor (PTGFR).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] 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.